Volume 91 No. 7 July 2008 Lyme Disease Medicine Health UNDER THE JOINT VOLUME 91 NO. 7 July 2008 EDITORIAL SPONSORSHIP OF: The Warren Alpert Medical School of Brown University Edward J. Wing, MD, Dean of Medicine & Biological Science RHODE ISLAND PUBLICATION OF THE RHODE ISLAND MEDICAL SOCIETY Rhode Island Department of Health David R. Gifford, MD, MPH, Director Quality Partners of Rhode Island Richard W. Besdine, MD, Chief Medical Officer COMMENTARIES Rhode Island Medical Society Nick Tsiongas, MD, MPH, President 206 When Is a Somatic Disorder Psychiatric? Joseph H. Friedman, MD EDITORIAL STAFF Joseph H. Friedman, MD 207 The Awkward Birth Pangs of Bolero Editor-in-Chief Stanley M. Aronson, MD Joan M. Retsinas, PhD Managing Editor CONTRIBUTIONS Stanley M. Aronson, MD, MPH SPECIAL ISSUE: Lyme Disease Editor Emeritus Guest Editors: Jerome Larkin, MD, and Jennifer Mitty, MD, MPH EDITORIAL BOARD 208 Introduction: Lyme Disease Stanley M. Aronson, MD, MPH Jerome Larkin, MD, and Jennifer Mitty, MD, MPH Jay S. Buechner, PhD John J. Cronan, MD 209 Ticks and Tick-Related Illness James P. Crowley, MD Jerome M. Larkin, MD Edward R. Feller, MD 212 Lyme Disease In Children and Pregnant Women John P. Fulton, PhD Peter A. Hollmann, MD Jerome M. Larkin, MD Sharon L. Marable, MD, MPH 213 Musculoskeletal Manifestations of Lyme Disease Anthony E. Mega, MD Imad Bitar, MD, and Edward V. Lally, MD Marguerite A. Neill, MD Frank J. Schaberg, Jr., MD 216 Neurological Complications of Lyme Disease Lawrence W. Vernaglia, JD, MPH Syed Rizvi, MD, and Amanda Diamond, MD Newell E. Warde, PhD 219 Updates and Controversy In the Treatment of Lyme Disease OFFICERS Jennifer Mitty, MD, MPH, and David Margolius Nick Tsiongas, MD, MPH President COLUMNS Diane R. Siedlecki, MD 224 GERIATRICS FOR THE PRACTICING P HYSICIAN – Dementia Screening: Should President-Elect We Screen Asymptomatic Older Adults? Vera A. DePalo, MD Ana Tuya Fulton, MD Vice President Margaret A. Sun, MD 226 THE CREATIVE CLINICIAN – Rituximab In Treating Refractory Thrombotic Secretary Thrombocytopenic Purpura: Three Case Reports Mark S. Ridlen, MD Samir Dalia, MD, Brendan McNulty, MD, and Gerald A. Colvin, DO Treasurer 229 HEALTH BY NUMBERS – Estimating the Incidence of New Onset Lyme Barry Wall, MD Disease in Rhode Island Immediate Past President John P. Fulton, PhD DISTRICT & COUNTY PRESIDENTS 232 PUBLIC HEALTH BRIEFING – The RI Board of Medical Licensure and Geoffrey R. Hamilton, MD Discipline, 2007 Year Summary Bristol County Medical Society Robert Crausman, MD, Mary E. Salerno, MA, Linda Julian, Lauren Dixon, Herbert J. Brennan, DO and Bruce McIntyre, JD Kent County Medical Society Rafael E. Padilla, MD 235 PHYSICIAN ’S LEXICON – The Eight Little Wrist Bones Pawtucket Medical Association Stanley M. Aronson, MD Patrick J. Sweeney, MD, MPH, PhD Providence Medical Association 235 Vital Statistics Nitin S. Damle, MD 236 July Heritage Washington County Medical Society Jacques L. Bonnet-Eymard, MD Woonsocket District Medical Society Cover: “What Makes Lyme Disease Tick?” oil. The artist is an itinerant New England physician. Medicine and Health/Rhode Island (USPS 464-820), a monthly publication, is owned and published by the Rhode Island Medical Society, 235 Promenade St., Suite 500, Providence, RI 02908, Phone: (401) 331-3207. Single copies $5.00, individual subscriptions $50.00 per year, and $100 per year for institutional subscriptions. Published articles represent opinions of the authors and do not necessarily reflect the official policy of the Rhode Island Medical Society, unless clearly specified. Advertisements do not imply sponsorship or endorsement by the Rhode Island Medical Society. Periodicals postage paid at Providence, Rhode Island. ISSN 1086-5462. POSTMASTER: Send address changes to Medicine and Health/Rhode Island, 235 Promenade St., Suite 500, Providence, RI 02908. Classified Information: RI Medical Journal Marketing Department, P.O. Box 91055, Johnston, RI 02919, phone: (401) 383-4711, fax: (401) 383-4477, e-mail: firstname.lastname@example.org. Production/Layout Design: John T eehan, e-mail: email@example.com. 205 VOLUME 91 NO. 7 JULY 2008 Commentaries When Is a Somatic Disorder Psychiatric? This issue is devoted to Lyme disease, column in the last few decades. Undoubt- confront him, the father then falling an important illness in our state, which edly many more will. Restless legs syn- helplessly to the ground because of cata- boasts, on Prudence Island, the highest drome was described about 30 years ago plexy. seropositive region in the world. It is a but didn’t “catch on” until recently, get- In the 1800s the term “neurosis” disease with interesting clinical phenom- ting a big boost from drug companies described neurological syndromes that ena, similar to, but less devastating than that market drugs that treat the disorder. had no known pathological basis. Char- its spirochete cousin, syphilis. Like syphi- Most doctors, who didn’t suffer from cot, the great French neurologist, who lis, it may cause a chronic illness, quite RLS, considered it a non-entity. After all, renamed “Paralysis agitans” Parkinson’s different than the acute illness. Unlike everyone gets restless sometime. But then disease (PD), classified that disease as a syphilis, which may have been the final as polysomnography became popular, it neurosis. The term was then hijacked by common answer for sporadic dementias turned out that 60% of people who re- Freud and colleagues, although it should and behavioral disorders 100 years ago, ported RLS had a peculiar kicking move- be pointed out that Freud studied with Lyme is being used to explain a large num- ment during sleep, obviously something Charcot. Affixing the term neurosis did ber of fairly nebulous symptoms that oc- that was organic and not emotionally not imply that a pathology wouldn’t be cur in the general American population. based. This year two genes have been found, just that it wasn’t known. Inter- It may be the only illness in which an of- found to explain RLS, and more are likely estingly however, some psychoanalysts in ficial medical group has been sued by a to be found. the mid-20th century published papers state government (Connecticut) for issu- Writer’s cramp had been considered blaming childhood conflicts for the ing evidenced-based guidelines that con- a psychiatric syndrome until recently. It tremors, and rigid personalities for tradict non-scientific beliefs embraced by is very clear how one might divine an muscle rigidity, in PD, misunderstand- a politically influential voting block. unconscious urge to twist one’s hand, ing, perhaps, the difference between Medicine by democracy, as it were. when it occurred only when writing, but Charcot’s neurosis and Freud’s. There are two fascinating aspects to not doing anything else, an explanation In this issue the authors grapple with this issue. One is the problem that clini- that makes a lot more intuitive sense than the battle between the infectious disease cal physicians (in contrast to test-based an organic physiological one. There is no experts who base recommendations on physicians like radiologists, more evidence today that these are or- evidence-based medicine, and self pro- interventionalists and pathologists) face ganic than there was before, but we’ve claimed Lyme experts who base opinions ever yday, of discriminating the “psy- developed a greater reliance on psychi- on their common experience, without chogenic” from the organic, a topic I atric experience to exclude a psychody- addressing the pathophysiology of “post never tire of. The other is political. namic formulation rather than found an treatment Lyme disease”. Post treatment There is no doubt that political be- objective measure of organicity. This is an Lyme disease is an entity, perhaps based liefs influence medicine. It is hard to unusual form of nosology. We often do on an organic etiology, probably, like imagine that cultural change rather than tests to exclude certain diagnoses, and, neurasthenia, a disorder that is so diffuse scientific evidence alone altered the psy- like Sherlock Holmes, conclude that that it includes a large overlap between chiatric classification of homosexuality. when all the various possibilities one can the organic and the psychological, mak- How did “neurasthenia” develop into think of have been eliminated, what is left ing it a daunting challenge to figure out. chronic fatigue syndrome? Why is must be the truth. Yet one can never be The fact is that long term antibiotic treat- Chronic Fatigue Syndrome not in DSM “sure” in excluding psychiatric etiologies. ment hasn’t worked and causes compli- IV, but classified by the Centers for Dis- Another organic disorder that pro- cations. Yet a lay organization has sued ease Control and Prevention? Why is vided fuel for psychoanalysis is cataplexy, an organization of bone fida experts to fibromyalgia or Irritable Bowel Syn- the sudden loss of body tone, causing claim that double blind placebo con- drome not in DSM? Where does mul- people with narcolepsy to fall to the trolled trials have been inadequate, not tiple chemical sensitivity syndrome be- ground when experiencing a sudden because of study design but because their long? When is a physiologically inexpli- emotion. I will never forget, in the early results fly in the face of the organization’s cable syndrome a somatoform disorder, days of sleep medicine, hearing a lecture common experience. or a conversion disorder rather than a from a sleep doctor pioneer, who de- If blood letting didn’t work, why specific organ system disorder? scribed a teenage boy who would delib- would we use it, asked our predecessors Many disorders have moved from erately provoke his father to the point of two hundred years ago, or steroids a mere the psychological column to the organic getting him to jump out of his chair to 20 years ago? I think there is a rationale 206 MEDICINE & HEALTH /RHODE ISLAND for a democratic process for disease clas- Disclosure of Financial Interests Ingelheim, Sepracor, Glaxo; Speakers’ Bureau: sification, limiting voting to experts, but Joseph Friedman, MD, Consultant: Acarta AstraZeneca,Teva,Novartis,Boehringer-Ingelheim, surely not for disease treatment. Pharmacy, Ovation, Transoral; Grant Research GlaxoAcadia, Sepracor, Glaxo Smith Kline eva, Support: Cephalon, T Novartis, Boehringer- – JOSEPH H. FRIEDMAN, MD The Awkward Birth Pangs of Bolero Creative genius in the arts, as portrayed in our current mythology, leagues noted then subtle changes in Ravel’s behavior and personal- is allegedly born in travail, matures in unyielding poverty and ulti- ity. He exhibited a gradual loss of empathy, showing an increasing mately enriches the world despite rampant tuberculosis. Survival indifference to the illnesses and travails of others. His remarks be- is typically brief – Keats is given only 26 years, Mozart 35 years come increasingly inappropriate, tactless, annoyingly repetitive, even and Schubert a mere 31 years. And disease is always there, an embarrassing, with evidence of a loss of inhibitions. Even his eating insistent impediment to be overcome in some unheated attic. became both repetitive and indiscriminately excessive. When assembling the biography of many an artist, the word, In the next year Ravel withdrew from the public eye, be- despite, seems to be an essential element of this bohemian scenario. came apathetic, increasingly incommunicative and only belat- [For example, we read: “The artist managed to write three slim edly, losing his sense of memory, orientation and capacity to books of immortal poetry despite his lung disease.”] It therefore compose – or even understand - music. A diagnosis of fronto- becomes an act of shear perversity, outright blasphemy, to suggest temporal dementia [Pick’s disease] was offered. In 1937 an ill- that some great work of art might never have been created were it considered neurosurgical intervention was attempted, but not for the accompanying burden of some disease. Yet, as the cre- Ravel died without regaining consciousness. ative forces underlying art are evaluated, three possibilities emerge. Frontotemporal dementia is not as common as Alzheimer’s The disease and the concerto are causally unrelated; or the vir- disease. It differs not only in frequency but in its manifestations of tuoso writes an immortal concerto despite the weight of his illness; behavioral and judgmental deterioration long before there is loss or this same virtuoso writes an immortal concerto because of the of orientation or memory. The mean duration of frontotemporal weight of his illness, with the inescapable implication that this con- dementia tends to be somewhat longer and the disease tends to be certo might never have been born were it not for the malign ill- hereditary in about 40% of cases. Patients frequently exhibit re- ness. The third possibility, however, seems implausible. Yet the life petitive, compulsive behavior associated with outbursts of chagrin of Joseph-Maurice Ravel, one of France’s greatest musical geniuses, and decay of social graces, a loss of cognitive skills in planning and might say otherwise. organizing - yet with relative preservation of memory. Ravel, of Swiss-Basque heritage, was born in the French vil- Ravel’s works have been characterized by musicologists as lage of Ciboure near Biarritz, on March 7, 1875. The family moved graceful, intricately nuanced, impressionistic, subtle, highly inven- to Paris when Ravel was seven. He began piano lessons then and tive, discriminating, ingeniously contrived and delicate. But then within a few years was enrolled in Conservatoire de Paris. His co- there is Bolero, admittedly Ravel’s most famous, most financially hort of students described him as slight and delicate of build, re- successful venture [and the title for at least two motion pictures, mote in behavior, a perfectionist in his musical efforts, suspicious the first, starring George Raft and Carole Lombard in 1934, and of others, a fractious personality easily given to argument and per- the second, starring Bo Derek in 1984.] haps slightly paranoid toward his colleagues and teachers. He was Bolero, one of Ravel’s last compositions, differs appreciably from not known to enter into any intimate relationships with either men his other works and does not seem to be the culmination of his or women; and rumors of a labile sexuality followed him through- genius. Instead of intricate orchestration, it is a somewhat primitive, out his life. iterative and erotic enterprise that emphasizes insistence and crude The legendary impresario, Sergei Diaghilev, was impressed with rhythmicity rather than subtle tonalities or musical development. Ravel’s musical genius; and in 1920 the two collaborated in staging And so, some neurologists have quietly speculated that this late or- Ravel’s “Daphnis et Chloe,” danced by the immortal Valsav Nijinsky. chestral effort, thought banal by many, is more a consequence of By 1925 Ravel and Diaghilev were no longer on speaking terms; Ravel’s organic dementia than his innate musical genius. They ex- only the intervention of mutual friends prevented a mortal duel. press these tentative speculations in whispers, knowing that Bolero is Ravel was invited to the United States in 1928 where his con- one of the world’s most played, most popular pieces of music. certs were uniformly successful. He met George Gershwin in one of his California performances and the two shared their musical – STANLEY M. ARONSON, MD thoughts on jazz, altered tonality and Afro-Caribbean folk music. For the remainder of Ravel’s life, less than a decade, he felt that Disclosure of Financial Interests only America understood and appreciated his music. Stanley M. Aronson, MD, has no financial interests to disclose. In a motor accident in 1932, Ravel sustained a mild head in- jury. His behavior from this point on visibly deteriorated although CORRESPONDENCE many colleagues dated his neurological deficits back to 1928. Col- e-mail: SMAMD@cox.net 207 VOLUME 91 NO. 7 JULY 2008 Introduction: Lyme Disease Jerome Larkin, MD, and Jennifer Mitty, MD, MPH Lyme disease is named for a small town on the southeast and should not be used to rule out acute infection but may be help- coast of Connecticut. In 1977, Steere et al described a cluster- ful if positive or if seroconversion can be demonstrated with later ing of 51 patients (39 children and 12 adults) in three contigu- testing. Most if not all illness, when diagnosed acutely and even for ous towns with recurrent attacks of arthritis of the large joints. weeks to months after the initial manifestations, responds promptly Approximately 25% of patients had developed a preceding to oral antibiotics. Central nervous system involvement, however, erythemetous annular rash. Arthritic attacks typically lasted one should be treated parenterally. Later manifestations of illness, in week. Although originally thought to be juvenile rheumatoid particular heart block, arthritis and neurologic symptoms may war- arthritis, diagnostic testing did not support this hypothesis; and rant judicious use of antibiotics but should be limited to patients seasonal and geographic clustering suggested transmission by an with serologic evidence of infection and rarely if ever should be ex- arthropod vector.1 Over the next few years effective antibiotic tended beyond a month of treatment. There is no scientific evi- regimens were developed, and in 1982 Willy Burgdorfer cul- dence that long term (months to years) of antimicrobial therapy is tured a spirochete (subsequently named Borrelia burgdorferi and ever indicated.6 demonstrated to be the cause of Lyme disease) from the mid-gut In October, 2006 the Infectious Diseases Society of of ixodes (hard-bodied) ticks.2 Ixodes damini (formerly scapularis) America published guidelines for the assessment, treatment and was eventually shown to be the vector for Lyme disease (borreliosis) prevention of Lyme disease. The Centers for Disease Control as well as for babesiosis and erhlichiosis (anaplasmosis). It is also and Prevention (CDC) have endorsed those guidelines. Like now apparent that human disease attributable to B. burgdorferi other such tools, it is a concensus document based on the best has been described in the medical literature, particularly in Eu- available scientific evidence and meant to assist physicians in in- rope, since at least 1909 and likely as early as 1883.3 Since 1977, dividualizing patient care in a scientifically and medically appro- other aspects of the disease have also been described, in particu- priate manner. In November, 2006, Connecticut Attorney lar the involvement of the central nervous and cardiovascular General Richard Blumenthal launched an investigation into systems in addition to the more typical skin and musculoskeletal possible violation of antitrust laws on the part of the IDSA in manifestations of illness. formulating the guidelines, stating they “may severely constrict A unique aspect of Lyme disease and its history since 1977 is choices and legitimate diagnosis and treatment options for pa- advocacy. The original investigation of the outbreak was in part tients.”7 The absurdity of his proposition almost does not war- spurred by two parents who contacted the Connecticut State Health rant comment. How will the story end? It certainly will not be Department and physicians at Yale University School of Medicine, with Mr. Blumenthal’s investigation and perhaps not with the questioning the seemingly too frequent incidence of JRA in their latest iteration of the IDSA guidelines. In an agreement an- community. This has, in a sense, set the tone for the public medical nounced in April 2008, Mr. Blumenthal agreed to end the in- and political debate over Lyme disease. As with many previously vestigation. In exchange, the IDSA will convene a special review unrecognized illnesses, the period following its original description panel to “conduct a comprehensive and up-to-date evaluation was characterized by an expanding body of knowledge regarding of the scientific literature, in order to determine whether the pathophysiology, diagnosis and treatment. However, concurrent 2006 guidelines should be revised or updated. As part of the with this progress came a growing tendency on the part of some review process, interested individuals will be invited to submit clinicians and patients to attribute a wide variety of often subjective relevant information, and a public hearing will be held. The and nonspecific symptoms, persisting at times for decades, to Lyme review panel will consider all the evidence and make recommen- disease. Unfortunately, the debate has reached a level such that dations regarding whether the Lyme disease guidelines should clinicians are intimidated and threatened for withholding antibiot- be revised. If the panel recommends revisions, they will be car- ics despite the scientific validity of this position, and patients are ried out in accordance with our normal procedures overseen by therefore exposed to the toxicity of long courses of antimicrobial the IDSA Standards and Practice Guidelines Committee.”8 The agents of no proven benefit.4 Misinformation abounds on the agreement by the IDSA was explicitly to avoid the considerable internet and even such lay publications as Yankee Magazine, usually costs of litigation, and to protect the volunteer authors of the confining itself to serious topics such as country inns and flower guidelines, with every expectation that the guidelines will stand arrangements, have joined in the fray.5 It is a free for all. as written after the review. That the Society would have been The diagnosis of Lyme disease relies on three principal find- vindicated if the matter had gone to court was never in question. ings: epidemiologic exposure, appropriate clinical manifestations and Research continues and our knowledge and experience serology. All residents of the mid-Atlantic states and coastal New increase. Ultimately these are matters of biology and medicine England are at risk of infections regardless of occupation or habits. and we have every confidence that science will prevail. To- Typical symptoms include headache, myalgias, arthralgias and fa- ward that end, this edition of Medicine & Health/ Rhode Island tigue. Frank meningitis may be present as part of the acute illness. is intended to provide insight into the diagnosis and treatment Physical findings include erythema migrans, arthritis and Bell’s Palsy. of Lyme disease and other tick-related illnesses and assist the Other cranial nerves may be involved and transverse myelitis is a clinician in negotiating the thicket of controversy and misin- rare but reported manifestation. Serology may be negative initially formation while attempting to help afflicted patients. 208 MEDICINE & HEALTH /RHODE ISLAND REFERENCES Disclosure of Financial Interests 1. Steere AC, et al. Lyme arthritis. Arthritis Rheum 1977; 20:7 The authors have no financial interests to disclose. 2. Burgdorfer W, et al. Lyme Disease. Science 1982; 216:1317. 3. Sternbach G, Dibble CL. Willy Burgdorfer. J Emerg Med 1996; 14:631. 4. Grann D. Stalking Dr. Steer over Lyme disease. NYTimes Magazine June 17, 2001. CORRESPONDENCE: 5. Clark E. Lyme Disease. Yankee Magazine July/August 2007. Jerome M. Larkin, MD 6. Wormser GP, Dattwyler RJ, Shapiro ED. The clinical assessment, treatment Rhode Island Hospital and prevention of lyme disease, human granulocytic anaplasmosis, and babe- 593 Eddy St. siosis. Clin Infect Dis 2006; 43: 1089. 7. Hamilton E. Lyme Disease Guidelines Focus of Antitrust Probe. Hartford Providence, RI 02903 Courant, November 17, 2006. Phone: (401 444-8130 8. Electronic communication to the membership of The Infectious Diseases So- e-mail: JLarkin@lifespan.org ciety of America, May 1, 2008. Jennifer A. Mitty, MD, MPH Jerome M. Larkin, MD, is Assistant Professor of Medicine, The Miriam Hospital Division of Infectious Diseases, The Warren Alpert Medical School 164 Summit Avenue of Brown University. Providence, RI 02906 Jennifer Mitty, MD, MPH, is Assisstant Professor of Medi- phone: (401) 793-4851 cine, The Warren Alpert Medical School of Brown University and e-mail: JMitty@Lifespan.org the Director of the Lyme Clinic at Rhode Island Hospital. Ticks and Tick-Related Illness Jerome M. Larkin, MD There are over 800 described species of a febrile illness in the spring, summer or throughout most of the rest of the year. ticks all of which share the characteristic of fall months, and physicians in endemic Disease activity drops off after the first hard requiring blood meals during their life cycle. areas should be familiar with their presen- frost in the fall or early winter. However They are often adapted to specific seasons tation, diagnosis and treatment. 2 ticks may still be active in areas which expe- and environments and feed on a specific rience less severe cold weather, such as animal or group of animals. Their bites tend ERHLICHIOSIS coastal areas, or in years of relatively little to be painless and feeding lasts for hours to Ehrlichiosis is caused by three distinct freezing weather. 2963 cases of HGA have days. Affinity for humans is variable. Ix- species: Ehrlichia chaffeensis, Ehrlichia been reported since 1994 with over 700 odes damini, the vector of Lyme disease, ewingii and Anaplasma phagocytophilum. in 2005 alone. Although a reportable dis- belongs to the group of hard-bodied or The three species have the capacity to in- ease, most surveillance is passive and so the damini ticks. I. damini has three distinct fect a number of mammals other than true incidence of infection and or disease is life cycles, larva, nymph and adult, and humans including deer, dogs, coyotes, likely underreported. The highest preva- must take a blood meal once during each mice and other rodents. A. lence is reported in Minnesota, Connecti- cycle. A single nest may harbor as many as phagocytophilum can also infect I. cut and Rhode Island, the last with 36.5 10,000 insects. The tick must itself be in- damini. Accordingly it is typically the cases/million. Infection and disease are fected with the bacterial pathogen in or- pathogen of ehrlichiosis in the northeast- more likely to occur in males and in those der to transmit infection to humans. In- ern United States while E. chaffeensis is over the age of 50. As with infection with fection in the tick persists across the stages more common in the southern United Borrelia burgdorferi, the majority of pa- of its life cycle and can be transmitted to States. Human granulocytic anaplasmo- tients do not recall a tick bite. A lack of offspring. sis and human granulocytic erhlichiosis are outdoor exposure does not reliably exclude Two infections other than Lyme dis- synonymous terms. All three pathogens the diagnosis. In one study approximately ease, ehrlichiosis and babesiosis, are of con- are small, gram negative intracellular bac- 1% of Connecticut residents were serop- cern in Lyme-endemic areas. The patho- teria. They exhibit a trophism for white ositive with no current or past history of gens of both diseases can be transmitted blood cells; A. phagocytophilum for the disease. Other studies have reported by the tick Ixodes scapularis and ticks and granulocyte. As a result, infection may be seroprevalence rates as high as 36%. people can be dually or triply infected.1 evident by the observation of clusters of Incubation is two to three weeks al- Infection can be asymptomatic for both bacteria in cytoplasmic vacuoles known as though shorter periods have been de- microorganisms. Presentation, as with a morula. This is, however, a relatively rare scribed. The typical patient with Lyme disease, can be non-specific with fe- finding.3 ehrlichiosis caused by any of the three ver, malaise and an otherwise flu-like syn- Human granulocytic anaplasmosis pathogens is likely to present with fever drome. Similarly, patients often do not (HGA) follows a seasonal pattern reflect- and malaise. The fever is often persistent recall a tick bite at presentation. Accord- ing the activity of the I. damini tick. Peaks and out of proportion to the typical viral ingly, ehrlichiosis and babesiosis are in the of clinical illness occur in July and Novem- illness and usually striking for its presenta- differential for any patient presenting with ber with a low level of endemic activity tion during the summer months. Head- 209 VOLUME 91 NO. 7 JULY 2008 ache is very common, myalgias and gas- patients intolerant of or allergic to doxy- Babesia microti is the more typical trointestinal symptoms frequent. Other cycline. Children should be treated with pathogen in the United States and many reported symptoms include rash, cough doxycycline at 3-4 mg/kg/day divided bid. infections are clinically silent. An epide- and confusion. No single symptom is spe- Successful treatment of children with miologic study in blood donors in Con- cific for ehrlichiosis. Physical exam is simi- rifampin has been reported but should be necticut found a seroprevalence rate of larly nonfocal. The classic laboratory find- reserved for those under the age of eight 1.4%.8 Fifty-three percent of seroposi- ing is leukopenia with thrombocytopenia. years and who are judged to be only mildly tive patients were parasitemic. Other Transaminitis is relatively common. Mild ill. Beta-lactams, cephalosporins, studies in highly endemic areas indicate anemia may also be present. macrolides, quinolones and chloram- a relatively high incidence of asymptom- More fulminant disease is possible phenicol are all ineffective therapy. atic infection. The parasite can also in- and appears to be relatively more common fect white-footed mice and white-tailed from infections with E. chaffeensis and in deer which serve as a reservoir of infec- the immunosuppressed, the latter includ- The majority of tion in the environment. Infection of ing those with HIV infection and solid patients do not ticks is endemic in southern New En- organ transplant recipients . Manifesta- gland and its coastal islands and New tions of more severe disease include men- recall a tick bite. York. Cases have also been described in ingoencephalitis, adult respiratory distress the mid-Atlantic states, the midwest and syndrome, acute renal insufficiency and A recent report describes treatment on the west coast. Several transfusion re- sepsis. Opportunistic infections with fun- of nine woman diagnosed with HGA dur- lated cases have been reported in Rhode gal and viral pathogens are possible. Pe- ing pregnancy from 1997 to 2006. Ges- Island. Distinct species, designated MO- ripheral neuropathies including an isolated tational age at time of diagnosis ranged 1 and WA-1 have been described as caus- facial palsy are also possible. from 10 to 39 weeks. Four women re- ing disease in Missouri and Washington Diagnosis relies on clinical suspicion in ceived therapy with doxycycline and five respiectively. Asymptomatic parasitemia an appropriate epidemiologic setting be- received therapy with rifampin. One can persist for months. Treatment of as- cause no single symptom, physical finding woman was not treated. None of the ymptomatic but parasitemic patients re- or laboratory value is specific. The spec- woman presented with fulminant disease sults in more rapid clearance and is indi- trum of fever, a nonfocal exam and find- and all those treated responded promptly cated if the patient remains parasitemic ings of leukpenia and thrombocytopenia to antimicrobial therapy. One perinatal for more than three months. Treatment during the summer in an endemic area infection occurred. All pregnancies went of a seropositive but not parasitemic, as- warrant therapy. More difficult is the pa- to term and no adverse outcomes were ymptomatic patient is not indicated. tient with fever alone. Cautious observa- observed in the children at 21 months of Babesia species infect the red blood tion for 48 to 72 hours is reasonable. Treat- follow-up. 4 cell of humans and other species where ment should be initiated in the face of any Overall prognosis is generally good they undergo asexual reproduction. This worsening or if the fever persists and no with the exceptions described above. results in the classic tetramer or “maltese other diagnosis, such as enterovirus, is ap- There is no known chronic syndrome as- cross” inclusion seen on examination of the parent. Approximately 25% of patients sociated with ehrlichiosis. Reinfections peripheral blood smear. The diagnosis of have positive serologic evidence of infection have been reported.5,6,7 malaria should be considered in a patient at the time of presentation; 95-100% of with anemia, red blood cell inclusions and patients are positive within two weeks of the BABESIOSIS an appropriate epidemiologic risk profile. onset of symptoms. Polymerase chain reac- Babesiosis is a parasitic infection Eventually hemolysis occurs with subse- tion is highly specific but has a sensitivity of caused by one of many different species quent infection of uninfected cells. Pa- only 60 to 85%. The presence of morula of Babesia. The genus is names for tients typically present with non-specific, on peripheral smear is variable, reported as Viktor Babes who first described disease “flu-like” symptoms: fever, headache, mal- approximately 7% in infections with E. in cattle in 1888. The first case of hu- aise, anorexia. Rash is distinctly unusual. chaffeensis and 20-80% in infections with man disease was described in an asplenic The typical finding on laboratory testing A. phagocytophylum. Culture is difficult and farmer from Yugoslavia in 1957 and the is anemia and thrombocytopenia. It is not currently used only in research. first case in the United States in a resi- unusual for the diagnosis to be made when All forms of ehrlichiosis respond to dent of Nantucket in 1969. There are and automated blood counter mandates treatment with tetracycline. Doxycycline more than 100 known species of Babe- review of a smear as a result of thromb- at a dose of 100 mg twice daily for seven sia infecting many different vertebrates. ocytopenia. Red blood cell inclusions are to ten days is the therapeutic regimen of The two most common species to infect then noted by the laboratory technician choice. The use of doxycycline has the humans are Babesia microti and Babe- as consistent with either babesiosis or ma- advantage of potent activity against B. sia divergens. Babesia divergens is pri- laria. In suspected cases in which initial burgdorferi and so is effective treatment marily seen in Europe, usually results in smears are negative repeating the smear for dually infected patients. Treatment, symptomatic disease, often in asplenic several times over the course of days or however, should be extended to 21 days individuals, and typically presents as a PCR testing may be helpful.5, 9 in this instance. Rifampin is an alterna- more fulminant disease with a high Patients with significant tive agent at 300 mg bid for 7-10 days for mortality. immunocompromise such as HIV infec- 210 MEDICINE & HEALTH /RHODE ISLAND tion, asplenia, chronic steroid dependence CONCLUSION REFERENCES and solid organ transplantation are at risk Ticks are ubiquitous arthropods 1. Nadelman RB, Horowitz HW, et al. Simulta- neous human granulocytic ehrlichiosis and Lyme for more fulminant disease. This can present which are highly adapted to specific envi- borreliosis. NEJM 1997; 337:27. as rapidly progressive sepsis with multisys- ronments and seasons. They are the vec- 2. Parola P, Raoult D. Ticks and tickborne bacterial tem organ failure, particularly acute renal tors of a multitude of human diseases. Ix- disease in humans. Clin Infect Dis 2201; 32:897. failure and pulmonary edema with respi- odes damini is endemic to the coastal north- 3. Bakken JS, Krueth J, et al. Clinical and laboratory characteristics of human granulocytic ehrlichiosis. ratory failure. Review of the peripheral eastern United States, including Rhode Is- JAMA 1996; 275:199. smear is critical to diagnosis in this instance. land. It requires a single blood meal dur- 4. Dhand A, Nadelman R, et al. Human granulo- Increased age also appears to be a risk fac- ing each of its three life stages. During cytic anaplasmosis during pregnancy. Clin Infect tor for more fulminant disease. 9,10 feeding it can transmit infection with Bor- Dis 2007 45:589. 5. Gakken JS, Dumler JS. Human granulocytic Treatment is with one of two differ- relia burgdorferi, Anaplasma ehrlichiosis. Clin Infect Dis 2000; 31:554. ent antibiotic combinations. Effective phagocytophilum and Babesia microti. Pa- , 6. Wormser GP Dattwyler RJ, Shapiro ED, The clini- therapy was first achieved with tients with dual and even triple infection cal assessment, treatment and prevention of lyme clindamycin 600 mg three times daily and have been described. Ehrlichiosis (ana- disease, human granulocytic anaplasmosis, and babesiosis. Clin Infect Dis 2006; 43: quinine 650 mg both three times daily for plasmosis) and babesiosis typically present 7. Dumler JS, Madigan JE, et al. Ehrlichioses in 7 to 10 days. More recently, a combina- with non-specific, “flu-like” symptoms humans. Clin Infect Dis 2007; 45:S45. tion of atovaquone 750 mg twice daily and during the spring, summer and fall. The 8. Krause PJ, Telford SR, et al. Babesiosis. Pediatrics azithromycin 500 mg on day one and majority of patients do not recall a tick bite 1992; 89:1045. 9. Krause PJ. Babesiosis. Med Clin North Am 2002; then either 250 mg or 500 mg thereafter, and all residents of endemic areas are at 86:361. both for 7 to 10 days have been shown to some degree of risk of infection regardless 10. Sun T, et al. Morphologic and clinical observa- be equally effective. The combination of of lifestyle and habits. Diagnosis rests on tions in human infection with Babesia microti. J Infect Dis 1983; 148:239. atovaquone and azithromycin is better tol- clinical suspicion and the finding of ab- 11. Krause PJ, Lepore T, et al. Atovaquone and erated with fewer side effects than normalities on blood count and smear. azithromycin for the treatment of babesiosis. clindamycin and quinine. Quinine has Ehrlichiosis is suggested by leukopenia and NEJM 2000; 343:1454. the advantage of offering treatment for thrombocytopenia, babesiosis by anemia, 12. Bonoan JT, Johnson DH, Cunha BA. Life-threat- ening babesiosis in an asplenic patient treated with malaria in instances where this diagnosis thrombocytopenia and intraerythrocytic exchange transfusion, azithromycin and may be of concern. Additionally, quinine parasites on peripheral smear. Ehrlichiosis atovaquone. Heart Lung 1998; 27: 424. appears to result in a more rapid drop in is effectively treated by doxycycline and parasite burden.11 so is covered when treating with typical Jerome M. Larkin, MD, is Assistant Patients presenting with fulminant regimens of this drug for Lyme disease. Ba- Professor of Medicine, Division of Infec- disease should be treated in an intensive besia infection while quite common is as- tious Diseases, The Warren Alpert Medical care unit (ICU). Parasite burden can be ymptomatic in more than 95% of cases in School of Brown University. as high as 85%. Exchange transfusion is otherwise healthy individuals. Symptom- indicated for high levels of parasitemia atic disease is effectively treated in most Disclosure of Financial Interests (>10%), severe hemolysis or evidence of cases by a combination of clindamycin and The author has no financial inter- liver, kidney or pulmonary involvement. quinine or atovaquone and azithromycin. ests to disclose. In such patient, antimicrobial therapy Fulminant disease in the immune-com- should continue at least until the parasite promised requires hospitalization, often CORRESPONDENCE: level is less than .04% or for 10 days, which- admission to the ICU and potentially ex- Jerome M. Larkin, MD ever is longer. Repeat exchange transfu- change transfusion. Rhode Island Hospital sion should be considered for patients with 593 Eddy St. a parasitemia persisting over 5% after an Providence, RI 02903 initial exchange. Patients who are immune Phone: (401) 444-8130 compromised and/or present with fulmi- e-mail: JLarkin@lifespan.org nant illness should be rechecked for para- sites both by smear and PCR at one and three months. Retreatment is indicated for positive results.12 211 VOLUME 91 NO. 7 JULY 2008 Lyme Disease In Children and Pregnant Women Jerome M. Larkin, MD Two populations, pregnant women and daily. Azithromycin 500 mg daily and REFERENCES children under the age of eight, warrant clarithromycin 500 mg twice daily also 1. Committee on Infectious Diseases American Academy of Pediatrics, Red Book: 2006 Report special mention as therapy with the drug have activity but are inferior to amoxicillin of the Committee on Infectious Diseases, The of choice for Lyme disease, doxycycline, and cefuroxime. Doxycycline may be American Academy of Pediatrics, 2006:428. is contraindicated for both. used safely in children over the age of , 2. Wormser GP Dattwyler RJ, Shapiro ED. The clini- eight. Patients should be advised regard- cal assessment, treatment and prevention of lyme CHILDREN ing simultaneous calcium consumption disease, human granulocytic anaplasmosis, and babesiosis. Clin Infect Dis 2006; 43. The epidemiology, presentation and and photosensitivity when taking doxy- 3. Schlesinger PA, Duray PH, , et al. Maternal-fetal clinical course of Lyme disease in children cycline. Central nervous system involve- transmission of the Lyme disease spirochete. Ann is similar to that in adults. Children be- ment and third degree heart block should Intern Med 1985; 103:67. 4. Strobino BA, Williams CL, et al. Lyme disease tween the ages of five and nine years com- be treated with ceftriaxone 75-100 mg/ and pregnancy outcome. Am J Obstet Gynecol prise one of the peaks of incidence in re- day daily up to 2 grams total dose for 21- 1993; 169:367. gard to age. An intriguing notion is the 28 days. Isolated cranial nerve palsies and 5. Williams CL, Strobino B, et al. Maternal Lyme possibility that children under the age of lower degrees of heart block are treated disease and congenital malformations. Paediatric Perinatal Epidemiol 1995; 9:320. five may have less incidence of disease de- as for early disseminated disease although 6. Gerber MA, Zalneratis EL. Childhood neuro- spite exposure because children in this age for longer periods of time i.e. 28 days. logic disorders and Lyme disease during pregnancy. group are often treated with courses of Frank arthritis (warmth, redness, swell- Peaditric Neurol 1994; 11:41. amoxicillin and second and third genera- ing, pain, and as opposed to arthralgia) tion cephalosporins for presumed otitis should likewise be treated with a 28 day Jerome M. Larkin, MD, is Assistant media. These antibiotics in the doses and course of therapy.2 Professor of Medicine, Division of Infec- courses they are commonly prescribed tious Diseases, The Warren Alpert Medical would constitute effective therapy for early PREGNANCY School of Brown University. localized and disseminated disease. The epidemiology, presentation and As with adults, children may present diagnosis of Lyme disease in pregnant Disclosure of Financial Interests with erythema migrans in around 15% of women is the same as for non-pregnant The author has no financial inter- cases. Other manifestations of disease in- adults. Doxycycline, however, is absolutely ests to disclose. clude fever, headache, arthritis, arthralgia, contraindicated as therapy. The most ap- myalgia, cranial nerve palsies and menin- propriate alternatives are amoxicillin 500 CORRESPONDENCE: gitis. Approximately 50% of children who mg three times daily or cefuroxime 500mg Jerome M. Larkin, MD do not receive appropriate antimicrobial twice daily for 14 to 21 days.2 Rhode Island Hospital therapy will develop arthritis. Abnormali- In 1985 Schlesinger et al published 593 Eddy St. ties of the cardiac conduction system are possible evidence of maternal fetal trans- Providence, RI 02903 possible later. Diagnosis is based on clini- mission of B. burgdorgeri. Concerns were Phone: (401) 444-8130 cal signs and symptoms, appropriate epi- raised regarding the possibility of fetal e-mail: JLarkin@lifespan.org demiologic exposure and serologic testing. malformations and stillbirth.3 Several large Antibody testing in early disease may be studies have not, however, borne these negative and should not preclude treat- concerns out. A prospective study of 2000 ment in the appropriate setting. Demon- pregnancies and outcomes in an endemic stration of seroconversion by repeated test- area did not find an increased risk of preg- ing may be helpful in selected cases.1 nancy loss or congenital malformation.4,5 For children under the age of eight, A survey of pediatric neurologists in an amoxicillin at a dose of 50 mg/kg divided endemic area did not detect a clinical syn- three times a day for 14 to 21 days is the drome or pattern of abnormalities which drug choice for early localized and dis- could be attributed to Lyme disease.6 Fi- seminated disease. Alternatives include nally, there is no evidence that infection is cefuroxime 30 mg/kg day divided twice transmitted via breast milk. 212 MEDICINE & HEALTH /RHODE ISLAND Musculoskeletal Manifestations of Lyme Disease Imad Bitar, MD, and Edward V. Lally, MD In 1977, Dr. Allen Steere and colleagues and synovial effusions are not evident. At ease compared to more chronic illness. reported an outbreak of arthritis in chil- this stage, the patient’s illness resembled Between the episodes of joint inflamma- dren and adults in three small Connecti- a typical viral syndrome. tion, the patients typically do not have cut comminutes: Lyme, Old Lyme and any joint symptoms. East Haddam.1 These cases were first LYME ARTHRITIS noted in this small geographic region Frank arthritis develops months to Chronic Arthritis beginning in about 1972 and several of a few years following the tick bite in un- About 10% of untreated patients the children were diagnosed with juve- treated or inadequately treated patients with recurrent attacks of arthritis lose the nile rheumatoid arthritis (now called ju- and Lyme arthritis is considered a mani- typical periodicity of flares and develop venile idiopathic arthritis). Steere and festation of late Lyme disease (previously chronic arthritis in one to three large colleagues described this syndrome as a referred to as Stage 3 Lyme disease). This joints. This does not resemble the pat- previously unrecognized disorder and arthritis affects one or a few joints in two tern of rheumatoid arthritis, and Lyme coined the term “Lyme Arthritis.” There distinctive patterns, intermittent arthri- arthritis should not be considered in the was a strong suspicion that the syndrome tis and chronic arthritis.4 differential diagnosis of chronic inflam- was caused by an infectious agent, trans- matory polyarthritis, especially if the small mitted by an arthropod vector. Intermittent Arthritis joints of the fingers and toes are involved. Subsequently, Lyme arthritis was Intermittent arthritis develops in at Chronic Lyme arthritis clinically causes found to be a major feature of a larger least 60% of patients with Lyme disease unremitting joint swelling and pain for multi-systemic illness, Lyme disease, who are not treated during the early at least one year and one or both knees caused by the spirochete Borrelia stages. The presence of prodromal symp- are almost always involved.4 Due to the Burgdorferi transmitted by a bite from toms of polyarthralgia does not predict the increased awareness of EM in endemic the deer tick Ixodes damini. Following the development of future arthritis. Patients areas and the development of clearer tick bite, the syndrome may involve mul- develop episodes of severe joint inflamma- treatment guidelines, the proportion of tiple organs. Musculoskeletal symptoms tion that are variable in frequency. The patients with Lyme arthritis who do not and findings are noted in the majority of usual pattern of joint involvement is ei- have a history of EM is increasing and patients with Lyme disease. ther an asymmetric oligoarthritis or a the lack of EM should not exclude pa- Arthritis was, and is, a dominant fea- monoarthritis primarily affecting large tients with characteristic arthritis in en- ture in most patients with Lyme disease; joints. The knee is the most common joint demic areas from being tested for Lyme however, the pattern of arthritis varies involved and is almost always affected at disease. during different stages of this syndrome. some point during the illness; the ankle In fact, the pathogenesis of Lyme arthri- and the wrist are the next most common Synovial Pathology tis is initially related directly to the spiro- sites for arthritis.5 Unlike other forms of bacterial in- chete infection and later, it is postulated, During episodes of arthritis the af- fections affecting the joint, Lyme arthri- to immunologic abnormalities. This is fected joint may become very swollen and tis is indolent and damage is delayed for particularly true in patients with chronic warm although the patient usually com- months or even years. The Borrelia spi- Lyme arthritis. Lyme disease is said to be plains only of mild pain. Patients with epi- rochete lacks the enzymatic activity of an infectious disease that behaves like a sodes of arthritis that are severely painful other bacterial pathogens that may affect rheumatic disease.2 or associated with fever should be evalu- the joints and it is believed that joint dam- ated for other causes of joint inflammation age occurs largely due to an exuberant PRODROME including crystal disease or even septic ar- inflammatory response. Erythema migrans (EM), the classic thritis; this is true even in patients that have The synovial pathology of patients skin manifestation of Lyme disease, is noted previously proven Lyme arthritis. with Lyme arthritis is similar to that seen in approximately 90% of patients, usually The presence of effusions in one or in other types of non-bacterial inflamma- within one month of the tick bite .3 Syn- both knee joints is typical of the inter- tory arthritis. This includes synovial hy- chronously with, or subsequently to, the mittent arthritis of Lyme disease. Very pertrophy, vascular proliferation, and skin rash, a prodrome develops consist- large knee effusions, and Baker cysts for- infiltration of the synovial membrane ing of flu-like symptoms, fever, fatigue, mation and spontaneous rupture in these with mononuclear cells. However, it may malaise, myalgias and polyarthralgias. settings have been described.6 be distinguished from the synovial pa- Joint pain is typically polyarticular, involv- The exacerbations of arthritis usu- thology of rheumatoid arthritis in that ing both large and small joints as well as ally last weeks to months and typically germinal centers and follicular hyperpla- occasionally the back and neck. During resolve spontaneously. In general the fre- sia are not typically seen. this early localized phase of Lyme disease, quency and duration of arthritis attacks Synovial fluid analysis shows only patients rarely developed frank arthritis are greater in the early years of the dis- mild elevations of white blood cells in the 213 VOLUME 91 NO. 7 JULY 2008 low inflammatory range. The synovial (doxycycline or amoxicillin) are usually Methotrexate and even tumor ne- fluid white blood cell count is usually less given for 30 to 60 days; this is effective in crosis factor a inhibitors have been con- than 50,000 cells/cubic millimeter. about 90% of patients. Other recommen- sidered for patients in this category.13. dations are that patients who did not re- A treatment strategy which is usually Laboratory spond to 30-60 day course of oral antibi- effective in patients with persistent arthri- Virtually all patients with Lyme ar- otics should be treated with a 30 day tis is arthroscopic synovectomy. Although thritis have serum immunoglobulin G course of intravenous ceftriaxone.9 These it is difficult to achieve a complete synovec- (IgG) antibodies to Borrelia burgdorferi strategies are generally extremely effective tomy with arthroscopy this should still be by Western blotting,7 but the presence of in treating chronic Lyme arthritis. considered as a treatment option. anti Borrelia antibodies within the synovial It should be further emphasized fluid by ELISA or Western blot is an ac- that although chronic Lyme arthritis may curate and reliable method of proving that Lyme arthritis, be associated with joint erosions and car- arthritis is truly related to Lyme disease. whether tilage loss, the arthritis resolves eventu- In patients with chronic Lyme ar- ally in all patients. thritis cultures of the synovial fluid for intermittent or the causative organism are usually nega- chronic, is a POST-LYME DISEASE SYNDROME tive but the genomic DNA of B. Lyme disease at any stage may have burgdorferi can be identified in the syn- hallmark of late associated nonspecific symptoms of fa- ovial fluid by Polymerase chain reaction Lyme disease. tigue, myalgas, malaise, and wide spread (PCR) with sensitivity about 85%. The body pain. A fibromyalgia-like symp- conversion of a positive PCR to a nega- tom is well described in some of these pa- tive PCR after antibiotic therapy is used Antibiotic-Refractor y Lyme tients even in those who received ad- to confirm successful treatment. PCR Arthritis equate antibiotic therapy for Lyme dis- analysis of synovial tissue has a higher yield Approximately 5-10% of patients ease.14 These patients have been referred than that of synovial fluid for the pres- with Lyme arthritis do not respond to to as having post-Lyme disease syndrome. ence of B. burgdorferi DNA. either oral or intravenous antibiotic Additional symptoms include not only therapy according to the prescribed rec- fatigue, arthralgias, myalgias, and malaise Radiology ommendations. These patients are felt but symptoms of cognitive dysfunction In a study of 25 patients with Lyme to have antibiotic-refractory (or slowly including difficulty concentrating, poor arthritis8 who had active arthritis in the resolving) arthritis. This condition is de- attention and memory deficit. Head- knees for a median of 9 months (range 2 fined by persistent joint swelling for 3 aches, poor sleep and irritability also com- to 24 months), 20 patients (80%) were or more months after the start of at least prise this syndrome in many patients. found with radiographic abnormalities. 4 weeks of IV antibiotic therapy or at Although those patients have signifi- The most frequent findings were: soft tis- least 8 weeks of oral antibiotic therapy cant symptoms and functional disability, sue changes including knee effusions, syn- or both. This condition could, theoreti- they lack the objective findings of active ovial hypertrophy, edema of the cally, result from persistent infection, inflammation, such as synovitis, on physi- infrapatellar fat pad and enthesitis. Other but the identification of either spiro- cal examination. findings included symmetrical articular chetes or spirochetal DNA in these pa- The etiology of this syndrome is still cartilage loss, juxta-articular osteoporosis tients is rare.10,11 unclear and the actual incidence is very and erosions at bare areas at the margins It is believed that persistent arthritis variable. However, it does not seem to of the cartilage. However, radiographs of in these patients results from immuno- represent chronic active infection and it involved joints in the early stages of Lyme logic abnormalities. Patients with this does not benefit from prolonged courses arthritis are typically normal. No studies condition have a higher incidence of of antibiotics, whether orally or intrave- specifically evaluate the role of magnetic HLA-DRB1 alleles (similar to the alleles nously.15 resonance imaging in Lyme arthritis. associated with rheumatoid arthritis) and are thought to have greater immune re- OTHER MANIFESTATIONS Treatment of Lyme Arthritis activity to Borrelia burgdorferi Outer-Sur- Based on case reports, Lyme disease Antibiotic treatment early in the face Protein A (OspA).12 could be associated with myositis, osteo- course of Lyme disease is very effective in Once the patients in this category have myelitis, and panniculitis. 14,16 Patients preventing arthritis, and when started af- a negative PCR for Borrelia Burgdorferi, the with myositis may develop weakness and ter the presence of arthritis, shortens the general recommendation is to treat these muscle pain. The patients in this category duration of attacks with resolution of ar- patients with oral non-steroidal anti-inflam- have been found to have elevated muscle thritis within weeks to months. Oral anti- matory drugs, hydroxychloroquine, enzymes and other inflammatory mark- biotic therapy is preferred over intrave- sulfasalazine or intraarticular steroids. ers in their serum. In one report 16 a nous antibiotic therapy because both treat- Intraarticular steroids should not be used muscle biopsy showed tissue invasion with ments are equally effective, but oral treat- for Lyme arthritis if the patient has not pre- B. burgdorferi and an immune response ment is cheaper and probably associated viously been treated with adequate antibi- to this organism. with fewer side effects. Oral antibiotics otic therapy. 214 MEDICINE & HEALTH /RHODE ISLAND SUMMARY REFERENCES Web references: Musculoskeletal symptoms in Lyme 1. Steere AC, et al. 1977. Lyme arthritis. Arthritis Centers for Disease Control and Preven- Rheum 1977; 20:7–17. disease are very common at all stages of tion: http://www.cdc.gov. 2. Stephen E. Malawista. Resolution of Lyme ar- the disease. Lyme arthritis, whether in- thritis, acute or prolonged. Inflammation 2000; National Institute of Allergy and Infec- termittent or chronic, is a hallmark of late 24 (6). tious Diseases (NIAID): http:// Lyme disease. This may cause severe joint 3. Linden Hu, MD. Lyme arthritis. Infect Dis Clin www3.niaid.nih.gov. N Am 2005;19: 947–61. pain and swelling especially confined to 4. Steere AC. Chronic Lyme arthritis. Ann Intern one or a few joints, most notably the knee. Med 1979; 90:896-901. Edward V. Lally, MD, is Director, Antibiotic therapy is very effective in 5. Steere AC, et al. The clinical evolution of Lyme Division of Rheumatology, Rhode Island treating Lyme arthritis in the majority of arthritis. Ann Intern Med 1987; 107:725. Hospital and the Warren Alpert Medical 6. Massarotti EM. Lyme arthritis. Med Clin North cases. However, a small proportion of Am 2002 86:297-309. School, and Professor of Medicine, The individuals will develop persistent 7. Weinstein, Britchkov. Lyme arthritis and post- Warren Alpert Medical School at Brown chronic arthritis which is likely mediated Lyme disease syndrome. Curr Opin Rheumatol University. through immunologic mechanisms. In 2002, 14:383-7. Imad Bitar, MD, is a Rheumatology 8. Lawson JP, Steere AC. Lyme arthritis. Radiol 1985; these patients treatment strategies should 154:37. Fellow, Roger Williams Medical Center. include anti-inflammatory medications 9. Steere AC, Angelis SM. Therapy for Lyme arthri- and possibly immunosuppressive treat- tis. Arthritis Rheum 2006; 54: 3079–86. Disclosure of Financial Interests ments. Arthroscopic synovectomy ma 10. Sigal LH. Lyme arthritis. Arthritis & Rheumatism The authors have no financial inter- 1999; 42: 1809–12. ybe very helpful in some of these patients. 11. Steere AC, Gibofsky A, et al. Chronic Lyme ar- ests to disclose. Post Lyme disease syndrome and Lyme thritis. Ann Intern Med 1979; 90:896. myositis are two other sequelae that are 12. Steere AC. Medical progress. NEJM 2001;345 CORRESPONDENCE: associated with Lyme disease. (2): July 12. Edward V. Lally, MD 13. Steere AC, et al. Therapy for Lyme arthritis. Arthritis & Rheumatism 2006;54 (10). Rhode Island Hospital 14. Steere AC. Musculoskeletal manifestations of Lyme 2 Dudley St. Suite # 370 disease. Am J Med 1995; 95 (suppl 4 A). Providence, RI 02905 15. Sigal LH. Musculoskeletal manifestations of Lyme Phone: (401) 444-2248 arthritis. Rheum Dis Clin North Am 1998;24:323- 51. e-mail: ELally@lifespan.org 16. Holmgren AR, Matteson EL. Lyme myositis. Arthritis Rheum 2006;54:2697-700. 215 VOLUME 91 NO. 7 JULY 2008 Neurological Complications of Lyme Disease Syed Rizvi, MD, and Amanda Diamond, MD A tick-bite associated rash with later Radiculoneuropathy. Painful radicu- The same patients have been discovered neurological manifestations, including pa- litis is one of the most common early neu- to develop an axonal neuropathy* in the ralysis and meningitis, had been docu- rologic symptoms of Lyme disease in Eu- affected limb.9, In the case of chronic mented in Europe for several years before rope. Incidentally, it was also part of the infection, it has been estimated that one Lyme arthritis was recognized in the symptom-complex described in the first in four patients may have peripheral 1970s.1-4 The illness was later understood patient reported with the syndrome.1 Usu- nerve involvement. These patients may to be part of a multisystem disease caused ally occurring within the first weeks to present with mainly sensory symptoms. 10, 11 by spirochetae and transmitted by Ixodes months in the infection, the ticks.5, 6 Borrelia burgdorferi, although radiculoneuropathies of Lyme disease have initially thought to be a single species, has included motor, sensory and mixed symp- NEUROBORRELIOSIS OF THE been found to have several sub-species. toms. They are usually self-limited and may CENTRAL NERVOUS SYSTEM These subgroups may be responsible for be easily mistaken for nerve-impingement Meningitis. Although many syn- the variation in clinical symptoms observed syndromes, with segmental symptoms of dromes involving the central nervous sys- in different parts of the world.7 weakness, sensory or reflex changes.9 The tem remain controversial, several have The pathophysiology of neuro- symptoms may not occur in the region of been well-defined. Certainly, the early borreliosis is difficult to demonstrate, but the tick bit. Electrodiagnostic testing usu- appearance of lymphocytic meningitis mimics other spirochetal infections. In- ally shows multifocal mild sensorimotor in- is well recognized. Mildly increased fection is local with subsequent dissemi- volvement.10, 11 CSF pressure with headache and nation. During this time spirochete num- Cranial neuropathies. Involvement of papiledema may occur. The lympho- bers are high. B. burgdorferi components cranial nerves, particularly the seventh cytic pleocytosis usually includes tens to that induce cytokine production by T nerve, may be present in up to 50%-75% hundreds of lymphocytic cells per mL. and B cells produce immune activation of all patients experiencing neurologic A mild elevation of protein may also be and indirect cell damage. Central ner- symptoms.4 Multiple cranial nerves may seen, with CSF glucose usually remain- vous system involvement is common and be involved simultaneously.9 Reports in- ing within a normal range to minimally clinical syndromes tend to occur in clude symptoms of every cranial nerve ex- decreased. 12 The ‘typical’ symptoms stages.7 cept the olfactory nerve. The facial nerve that usually occur with ‘aseptic’ menin- Lyme disease has been implicated in involvement is reported to be bilateral in gitis, such as photophobia, headache a variety of peripheral and central ner- up to one third of cases.11 Facial nerve and neck stiffness, are extremely variable vous system disorders. The neurological symptoms may not affect taste or hearing, with Lyme meningitis.11, 12 syndromes are often accompanied by indicating that involvement may be outside Intracranial hypertension syn- more general complaints (arthralgias, fa- the subarachnoid space. Additionally, CSF drome. A rare complication of Lyme dis- tigue, myalgias). Earlier neurological analysis in isolated Lyme disease facial palsy ease resulting in headache and potential symptoms, or those occurring during dis- may be normal. Complete recovery occurs papilledema, this syndrome seems to be semination within weeks to months, tend in 80-90% of patients within weeks to associated more often with children and to be more clinically obvious and develop months. adolescents. CSF abnormalities may oc- in an estimated 15% to 20% of patients.4 “Guillain Barré-like” syndrome. cur. There does not appear to be a cor- Several late syndromes seem to follow a Although rare, an acute and severe syn- relation with female sex or obesity, as with more insidious course.8 For purposes of drome of diffuse polyneuropathy, includ- pseudotumor cerebri. 11, 13 simplification, disorders of the peripheral ing bifacial weakness, may mimic the Encephalomyelitis. A chronic and central nervous systems will be re- symptoms of Guillan Barré. A CSF lym- manifestation of Lyme disease, encepha- viewed separately. phocytic pleocytosis and/or neurophysi- litis is rare in North American (nearly all ologic testing may help differentiate be- cases have been reported in Europe). On NEUROBORRELIOSIS OF THE tween the syndromes.7 MRI there is evidence of parenchymal PERIPHERAL NERVOUS SYSTEM Peripheral neuropathy. Symptoms involvement. This can include hemi- The most common peripheral mani- of peripheral neuropathies in patients spheric or brainstem abnormalities and festations of Lyme disease are cranial neu- with Lyme disease tend to be primarily is usually nonspecific, although may ropathies, peripheral neuropathies and sensory, occurring in a stocking-glove fash- mimic ischemic patterns.11 radicultis. However, many other syn- ion, although patchy paresthesias may Myelopathy. Patients may present dromes, including a “Guillian Barré-like” also be noted. In some European pa- with symptoms of transverse myelitis so syndrome, motor neuron disease, tients, a dermatologic manifestation is that Lyme disease should be considered axonopathies, brachial and lumbar often associated with the neuropathy. in the diagnosis of these patients.11, 14 plexopathies, mononeuropathy multiplex Labeled acrodermatitis atrophicans, the Rarely, a transverse myelopathy may ac- and even myositis have been described. 7 skin becomes tissue-thin and discolored. company Lyme radiculoneuritis. This 216 MEDICINE & HEALTH /RHODE ISLAND typically occurs at the same level as radicu- testing. Spinal fluid can, however, be Given the high incidence of B. lar involvement and may be preceeded tested for the presence of anti-B. burgdorferi antibody in the CSF of pa- by a leptomeningitis.12 burgdorferi antibodies.19 tients who are seropostive but without Lyme encephalopathy. This may be The American Academy of Neurol- neuroborreliosis, other tests for the di- the most common late neurologic mani- ogy (AAN) guidelines for the diagnosis agnosis of central nervous system disease festation of Lyme disease. Patients express of neurologic Lyme disease include the have been evaluated. A recent study by difficulties with concentration, sleep dis- consideration of exposure to ticks in an Blanc, et.al.22 suggested the use of an turbance, emotional lability, memory and endemic region, clinical abnormalities anti-Borrelia antibody index (AI). The attention.11, 15, 16 Despite studies includ- other than those affecting the nervous AI is the ratio of anti-Borrelia IgG in ing requirements for CSF abnormalities system (including cardiac, rheumatologic CSF to anti-Borrelia IgG in the serum and SPECT imaging, the definitive di- and dermatologic symptoms), and ad- and is considered positive if greater than agnosis of Lyme encephalopathy remains equate laboratory support (proof of the or equal to two. The study noted 74 pa- elusive.16 In the consideration of acute presence of B. burgdorferi or immuno- tients with diagnoses of other neurologic encephalopathy, one should note that logic evidence of exposure) in addition diseases all had positive CSF Lyme anti- persons with Lyme-induced cognitive to the causally-related neurologic disease bodies; only two of those patients had a changes likely have a mild encephalitis; or syndrome.20 positive AI (specificity of 97%). The sen- these patients should not be confused sitivity of positive AI was determined to with mental status changes associated …prolonged courses be 75%. The authors suggested the fol- with systemic symptoms.17 Such patients lowing criteria for diagnosis of are likely to have objective findings on of antibiotics do not neuroborreliosis: presence of four of the neuropsychiatric testing and such a di- improve outcomes following five items. 1) no past history agnosis should only be made in the pres- of neuroborreliosis, 2) positive CSF anti- ence of appropriate findings after test- and are not Borrelia antibodies, 3) positive anti-Bor- ing has been performed by a qualified recommended. relia antibody index, 4) favorable out- professional. This is distinct from the come after specific antibiotic treatment, more subjective symptoms patients often 5) no other etiologic diagnosis.22 experience for weeks to months follow- Additionally, the US Centers for Researchers have also described a ing an episode of acute infection with B. Disease Control and Prevention (CDC) B-cell-tropic chemokine, CXCL13, burgdorferi (discussed below). has recommended a two-tier system to test which appears abnormally elevated in Post-Lyme disease. Several patients for anti-B. burgdorferi antibodies. Sero- CSF of patients with Lyme who have had Lyme disease have been logic testing starts with enzyme-linked neuroborreliosis. If confirmed, this noted to have other psychiatric and cog- immunosorbent assay (ELISA), with cytokine might serve as a marker to as- nitive symptoms, such as fatigue, cogni- usually high sensitivity depending on sist in the confirmation of the diagnosis tive slowing and depression. These pa- acuity of infection and organ systems in- of neuroborreliosis.23 tients are sometimes diagnosed with post- volved, and low specificity due to cross- Lyme disease. It is unlikely that these reacting antigens.21 Seropositivity may TREATMENT OF NEUROBORRELIOSIS symptoms indicate persistent neurologic remain for years and can occur in up to Although the general recommen- infection, and studies have not shown 10% of the asymptomatic population in dation in the US is to use parenteral an- that antimicrobial therapy is helpful in endemic areas. The antibody may not tibiotics whenever the nervous system is these patients.18 be detected within the first 2 to 6 weeks involved, there is considerable evidence after exposure, so retesting (or treatment in the European literature suggesting DIAGNOSIS OF NEUROLOGIC LYME without testing in cases with Erythema oral doxycycline (200-400mg/day) may DISEASE migricans) may be important in cases of be equally effective in most patients. At The crucial element for the consid- high clinical suspicion. Borderline or the recommended doses it appears that eration of neurologic Lyme disease is the positive results are then confirmed by the CSF concentrations of doxycycline presence of an indicative neurologic Western blot. IgM testing is recom- exceed minimum inhibitory concentra- symptom. Laboratory data should be mended only acutely in disease, when tion for most strains. Although there are complimentary and supportive of clini- clinical history is limited to 1 to 2 months, strain differences between United States cal findings. In evaluating response to and requires 2 of 3 possible bands (sensi- and Europe, there probably is not a sig- therapy, the clinician must remember tivity 32%). Confirmatory testing of IgG nificant difference in antimicrobial sus- that many neurologic illnesses improve presence requires 5 of 10 possible bands ceptibility. 24 Also, prolonged courses of with time, regardless of treatent.17 Un- (sensitivity 83%). Given lower sensitivi- antibiotics do not improve outcomes and fortunately, sensitivity of culture in ner- ties, clinical judgment should in used in are not recommended. The duration of vous system infections is low (only about patients with positive ELISA whom do parenteral treatment suggested is 2 to 4 10% in CSF in Lyme meningitis). The not meet Western blot criteria. Also, weeks, with no data showing any definite sensitivity of PCR testing appears to be positive Western blot performed without advantage of prolonged treatment. 25, 26 low as well. Confirmation of the diagno- ELISA may be deceptive and should not Oral regimens are generally given for 30 sis, therefore, relies largely on serologic be used.19, 20, 21 days. 217 VOLUME 91 NO. 7 JULY 2008 22. Blanc F, Jaulhac B, , et.al. Neurol 2007;69: Table 1. Antimicrobial regimens for the treatment of 953-8. nervous system Lyme disease 23. Rupprecht TA, Pfister HW, et.al. Neurol 2005;65:448-50. 24. KarlssonM, Hammers S, et al. Antimicrobial agents Medication Chemother 1996; 40:1104-7. Oral regimens Adult dose Pediatric dose 25. Klempner M, Hu L. et al. NEJM 2001;345:85- Doxycycline 100 (-200) mg BID Aged = 8 years: 92. 4 mg/kg/day in 26. Krupp LB, Hymann LG, et al. Neurol 2003; 2 divided doses; 60:1923-60. max 200mg/dose Amoxicillin (when 500 mg TID 50 mg/kg/day in Syed Rizvi, MD, is Director, Rhode doxycycline 3 divided doses; Island Hospital Multiple Sclerosis Center, contraindicated) max 500 mg/dose and Assistant Professor of Clinical Neuro- Cefuroxime (when 500 mg BID 30 mg/kg/day in sciences. Warren Alpert Medical School of doxycycline 2 divided doses; Brown University. contraindicated) max 500 mg/dose Amanda Diamond, MD, is a Neu- rolog y Fellow, Warren Alpert Medical Parenteral regimens School of Brown University. Ceftriaxone 2 g IV daily 50-75 mg/kd/d in single dose, max 2 g Disclosure of Financial Cefotaxime 2 g IV Q8H 150-200 mg/kg/day in Interests 3-4 divided doses; Syed Rizvi, MD, has no financial max 6 g/day interests to disclose. Penicillin G 18-24 MU/day, 200-400,000 U/kg/day Amanda Diamond, MD. Consult- divided doses Q4H divided Q4H, max 18-24 ant: Guidant, Teva, Berlex (Bayer), MU/day Genentech, Cordis. The AAN published practice pa- REFERENCES Discussion of drug used off- rameters for the treatment of nervous sys- 1. Garin B. J Med Lyon 1922;71:765-7. label or under investigation: 2. Bannwarth A. Arch Psychiatr Nervenkr Doxycycline, amoxicillin, ceftriaxone, tem Lyme disease in March, 2007. It rec- 1944;117:161-85. ommended: 3. Steere, AC, Malawista SE, et .al. Arthritis Rheum ceftriaxime and penicillin are not FDA- 1977;20:7-17. approved for the treatment of Lyme dis- 1) Parenteral penicillin, ceftriaxone, 4. Said, G. Neurol Clinics 2007;25:115-37. ease, but all have been shown either effec- 5. Burgdorfer W, Barbour AG, et .al. Science tive or have evidence indicating efficacy. and cefotaxime are probably safe 1982;216:1317-9. and effective treatments for periph- 6. Steere, AC, Grodzidki, RL, et.al. NEJM eral nervous system Lyme disease 1983;308:733-40. CORRESPONDENCE: and for CNS Lyme disease with or 7. Halperin, JJ. J Neurol Sci 1998;153:182-91. Syed Rizvi, MD 8. Halperin, JJ, Luft, BJ, et.al. Neurol 1989;39: 2 Dudley Street, suite 555 without parenchymal involvement 753-9. (Level B recommendation). 9. Halperin, JJ. Muscle Nerve 2003;28:133-43. Providence RI 02903 2) Oral doxycycline is probably a safe 10. Halperin, JJ, Luft, B, et.al. Brain Phone: (401) 444-3799 and effective treatment for periph- 1990;113;1207-21. e-mail: SRizvi@lifespan.org 11. Coyle, PK. Lyme disease. Curr Neurol Neurosci eral nervous system Lyme disease Rep 2002;2:479-87. and for CNS Lyme disease without 12. Pachner, AR, Steere, AC. Neurol 1985;35:47- parenchymal involvement (Level B 53. recommendation). Amoxicillin and 13. Kan, L, Sood, SK, Maytal, J Pediatr Neurol 1998;18:439-41. cefuroxime axetil may provide alter- 14. Mantienne, C, Albucher, JF, et.al. Neuroradiol natives but supporting data are 2001;43:485-8. lacking. 15. Logigian EL, Kaplan RF, Steere, AC.. J Infect Dis 1999;180:377-83. 3) Prolonged courses of antibiotics do 16. Logigian EL, Johnson KA, et.al. Neurol not improve the outcome of post- 1997;49:1661-70. Lyme syndrome, are potentially as- 17. Halperin, JJ. Vector Borne Zoonotic Dis sociated with adverse events, and are 2002;2:241-7. 18. Halperin JJ, Shapiro ED, Logigian E, et.al. Neurol therefore not recommended (Level 2007;69: 91-102. A recommendation). 19. Halperin, JJ. Curr Treat Options Neurol 2007;9:93- 100. Treatment regimens are listed in 20. Halperin JJ, Logigian EL, et al. Neurol 1996;46:619-27. Table 1. 21. Aguero-Rosenfeld ME, Wang G, et.al. Clin Microbiol Rev 2005;18:484-509. 218 MEDICINE & HEALTH /RHODE ISLAND Updates and Controversies In the Treatment of Lyme Disease Jennifer Mitty, MD, MPH, and David Margolius Lyme disease is the most commonly have published treatment guidelines for ing the diagnosis. 3 Conversely, the reported vector-borne disease in the Lyme disease. The guidelines, which dif- ILADS guidelines rely on physician United States, with approximately 20,000 fer significantly, can be confusing to pa- judgement coupled with a list of symp- cases diagnosed each year.1 A majority of tients and providers. The IDSA guide- toms, of which most, if not all, can be these cases occur in the Northeast and lines have generally been derived from present in other infectious and non-in- upper Midwest, with a significant num- controlled clinical trials especially with fectious disease states. Per the ILADS ber of cases each year in Rhode Island.2 regard to choice of antibiotic and dura- guidelines, antibody assays are not sensi- According to the Rhode Island Depart- tion of treatment. Conversely, the ILADS tive enough to be used clinically and ment of Health, 736 cases were reported guidelines are largely symptom-based Lyme disease is a suspected diagnosis in in 2003, the last year for which it has pub- and eschew the use of diagnostic testing many circumstances. This is especially lished data. Because patients with Lyme to confirm cases, relying on physician true when there are both musculoskel- disease can present to primary care pro- judgement on when, with what and how etal and neuropsychiatric symptoms, and viders, subspecialists or providers in urgent long to treat a given patient. when there is no evidence to indicate care centers and emergency departments, another illness.5 Accordingly, many pa- all Rhode Island physicians should under- DIAGNOSIS tients may be treated with antibiotics stand the diagnosis and management of Both the IDSA and ILADS guide- without clear lab-based or objective Lyme disease. Similarly, they should have lines agree that the presence of an physical evidence of a specific disease. knowledge of the controversies surround- erythema migrans type rash is highly sug- This can lead to overuse of antibiotics and ing diagnosis and the use of antimicrobial gestive of Lyme disease and, when the resulting complications of drug reac- therapy. present, constitutes sufficient evidence tions and the development of resistant Lyme borreliosis is caused by a spi- to make a diagnosis of acute infection. bacteria, with the attendant negative im- rochete, Borrelia burgdorferi, which is Yet such a rash is not present in all pact on both the patient and the com- transmitted by the Ixodes scapularis tick, cases.3,5 Accordingly, the IDSA guide- munity. commonly known as the deer tick. The lines maintain that in the absence of disease consists of three stages. The first erythema migrans, a positive serologic LABORATORY TESTING stage is usually localized, and presents as test is necessary to make a diagnosis of IDSA and Centers for Disease Con- erythema migrans (EM), the character- Lyme disease. The joint and other sys- trol and Prevention (CDC) recommen- istic “bullseye rash.” This rash is an ex- temic symptoms of infection are too dations consist of a two-test approach us- panding skin lesion that appears at the nonspecific, and overlap with other ing a sensitive ELISA or immunofluores- site of the tick bite, presents within 7-14 types of, usually viral, infections..3 Ad- cent assay (IFA) followed by a confirma- days after removing the engorged tick, ditionally, the majority of patients pre- tory Western blot test.3,6 If the ELISA or and is usually at least 5cm in largest di- senting with systemic symptoms, i.e. early IFA is negative, these guidelines state that ameter.3 Although helpful for diagnosis disseminated disease, are seropositive at a Western blot should not be performed. when present, not all patients develop a the time of presentation. Those patients The need for confirmatory Western blot rash. Additionally, some patients may who still may not have seroconverted is supported by the results of a study by have an atypical rash; i.e., smaller and may be reasonably treated empirically, Engstrom et al. where 29% of positive without central clearing. Relatively few especially if the case is highly suggestive ELISA tests were recorded in persons with patients recall a tick bite. Stage 2 or dis- and in an area of high endemicity, with illnesses other than Lyme disease.7 Al- seminated infection may begin several follow-up testing used to demonstrate though the western blot is highly specific, days or weeks after the rash, as the spiro- seroconversion and confirm the diagno- false positives do exist, particularly in the chete spreads hematogenously. Manifes- sis. The ILADS guidelines, in contrast, IgM immunoblot.8,9 The one exception tations of disseminated infection include hold that clinical judgment alone stands to this algorithm is in the acute phase of multiple erythema migrans, meningitis, as the only alternative basis for the diag- infection. Most of the current tests are too cranial or peripheral neuritis, carditis, nosis of Lyme disease. insensitive to be helpful diagnostically, atrioventricular nodal block, or migra- In terms of late stage Lyme, where given the time lapse in developing an im- tory musculoskeletal pain.4 Stage 3, the the time from initial bite to presentation mune response to the spirochete antigens. late stage disease, may present as chronic is relatively long, a diagnosis per the IDSA The ILADS guidelines state that a arthritis or chronic neurologic distur- guidelines requires a positive blood en- seronegative patient may present with bances. zyme-linked immunosorbent assay Lyme disease, especially if evidence does Two national organizations, the In- (ELISA) confirmed with a Western blot. not indicate another disease. 5 Citing fectious Diseases Society of America A lumbar puncture or joint aspiration unpublished surveillance data, the (IDSA) and the International Lyme and yielding a positive polymerose chain re- ILADS guidelines state that laboratory Associated Diseases Society (ILADS), action (PCR) may be helpful in confirm- testing advocated by the CDC fails to 219 VOLUME 91 NO. 7 JULY 2008 180 MEDICINE & HEALTH /RHODE ISLAND THE IMAGING INSTITUTE OPEN MRI • MEDICAL IMAGING • Offering both 1.5T High Field & Higher Field OPEN MRI Systems • Advanced CT with multi-slice technology, 3D reconstruction High Field MRI MRA • Digital Ultrasound with enhanced 3D/4D technology • Digital Mammography with CAD (computer assisted diagnosis) CT • 3D CT CTA 3D Ultrasound Digital Mammography Digital X-Ray & DEXA • Preauthorization Department for obtaining all insurance preauthorizations • Fellowship, sub-specialty trained radiologists • Friendly, efficient staff and convenient, beautiful office settings • Transportation Service for patients Higher Field OPEN MRI WARWICK CRANSTON CRANSTON N. PROVIDENCE E. PROVIDENCE 250 Toll Gate Rd. 1301 Reservoir Ave. 1500 Pontiac Ave. 1500 Mineral Spring 450 Vets. Mem. Pkwy. #8 TEL 401.921.2900 TEL 401.490.0040 TEL 401.228.7901 TEL 401.533.9300 TEL 401.431.0080 181 VOLUME 91 NO. 6 JUNE 2008 A Clearer Vision of Health ™ theimaginginstitute.com identify up to 90% of cases of Lyme dis- even without objective values. To sup- months, or even years. Chronic Lyme ease.10 ILADS proposes to increase sen- port their recommendations, the authors and Post-Treatment Lyme Disease Syn- sitivity of the test by registering a serop- cite 2 non randomized studies: one in- drome refer to a set of non-specific symp- ositive case when only 2 of the volves 43 acute psychiatric patients with toms that can occur after initial treatment immunoblot bands are positive rather a positive Lyme serology who improved for Lyme disease. The real question is than the CDC recommended 5 IgG after 90 or more days of concurrent an- whether these symptoms are due to ac- bands. ILADS maintains that other tests, tibiotic and antipsychotic pharmacologic tive spirochetal infection, or a post-infec- including antigen capture, urine antigen, therapy;15 and another, where 18/23 pa- tious disease state. and PCR on fluids other than CSF and tients previously treated for Lyme had ILADS describes Chronic Lyme as synovial remain options for Lyme diag- better outcomes in cognition, but simi- a set of permanent symptoms that include nosis. Although the ILADS guidelines lar improvement in depression and anxi- fatigue, cognitive dysfunction, headaches, acknowledge that these tests have not ety as compared to the 5 who were not sleep disturbance, demyelinating disease, been standardized,5 the CDC has taken retreated with antibiotics.16 neuropsychiatric presentations, cardiac this a step further and put out an advi- presentations, and musculoskeletal prob- lems that seems to be a growing epidemic. sory warning against the use of these tests, as the accuracy and clinical usefulness of …at this time there ILADS maintains that chronic Lyme and these assays have not been adequately es- are no randomized its symptoms may continue despite a 30 day treatment course (persistent), may re- tablished.11 controlled studies lapse in the absence of a new tick bite TREATMENT that show a (recurrent), and may be poorly respon- sive to antibiotic therapy (refractory).5 In The IDSA guidelines recommend doxycycline, amoxicillin, or cefuroxime sustained benefit these cases, ILADS guidelines state that axetil for 14 days for adult patients with of long term the Lyme disease is often resistant to treat- ment and may require higher and longer early Lyme disease associated with an EM, and state that macrolides should only be antibiotics. doses of antibiotics to produce clear evi- used when the patient has contraindications dence of improvement. for all of the medications listed above. These To summarize, IDSA proposes a In an exhaustive review of the litera- recommendations are based on the re- fixed treatment course for each stage of ture, the authors of the IIDSA guidelines sults of randomized controlled trials.12,13 Lyme disease based on the results of con- found no convincing biologic evidence Late Lyme disease should be treated with trolled studies, while ILADS avoids spe- of the persistence of the spirochete in a full 28 days of the oral antibiotics listed cific recommendations, arguing to treat humans following recommended treat- or parenteral therapy with ceftriaxone, the patient, often with long courses of ment regimens for Lyme disease. 3 In- cefotaxime, or penicillin G for 14-28 antibiotics, based on clinical response. stead, they propose that the symptoms fol- days. In cases where symptoms such as Given the growing concern of antibiotic lowing treatment of Lyme be entitled arthritis persist, a second cycle of antibi- resistance, and the substantial morbidity Post-Treatment Lyme Disease Syn- otics may be given. However, clinicians and even mortality16 associated with per- drome. Chronic symptoms following are advised by the IDSA to wait several sistent antibiotic usage, physicians and Lyme disease most likely represent either months to allow for the slow resolution patients should understand that at this an autoimmune phenomenon or stem of inflammation associated with this dis- time there are no randomized controlled from the slow resolution of the initial ease. As a general rule, these guidelines studies that show a sustained benefit of immune response to the infection. They state that response to treatment is slow, long term antibiotics. also note that there are a high rate of simi- and re-treatment in most cases is not rec- lar complaints in the general population, ommended unless objective measures in- LATE STAGE VS. CHRONIC VS. as is supported by population-based sur- dicate relapse.3,14 POST-LYME DISEASE SYNDROME veillance data.3, 18 In contrast, ILADS states that giv- Often the terms late stage, chronic, The concept of a post- infectious ing antibiotics for a fixed amount of time and post-treatment Lyme disease are used state is supported by a landmark study based on recommendations is “arbitrary”. interchangeably; however, it is important that randomized individuals with a his- Instead, the patient’s symptoms and clini- to note that they describe very different tory of Lyme disease and persistent symp- cal response should guide the duration disease states, and that there is disagree- toms to placebo or an additional 90 days of the treatment. ILADS defends this ment regarding the presence of chronic of antibiotic therapy; in this study, ex- ambiguity by stating that in an ideal situ- lyme disease. Late stage Lyme disease is tended antibiotic therapy showed no ad- ation treatment would be halted when generally a point of consensus between ditional benefits but did have slightly in- the Lyme spirochete is cleared from the IDSA and ILADS and is defined as the creased adverse events over the placebo body; however, without such a test clini- late manifestations of the disease such as group.14 Two recent studies, published cians must rely on symptom based diag- arthritis, encephalopathy, encephalomy- since the IDSA guidelines in November nosis and treatment.5 The ILADS panel elitis, and peripheral neuropathy.3,5 This 2007, also argue against the use of long writes that treatment should be initiated stage of Lyme can arise from a spirochete term antibiotics. A randomized, placebo- at once upon suspicion of a diagnosis, infection that has gone untreated for controlled trial of 10 weeks of IV 222 MEDICINE & HEALTH /RHODE ISLAND Jennifer Mitty, MD,MP H, is Table 1. Web Sites That Provide Information for Patients and Assisstant Professor of Medicine at the War- Clinicians on Lyme Disease ren Alpert Medical School of Brown Uni- versity and the Director of the Lyme Clinic • www.cdc.gov • www.nih.gov at Rhode Island Hospital. • www.idsociety.org • www.familydoctor.org David Margolius, is a student in the Warren Alpert Medical School of Brown • www.tickencounter.org University. ceftriaxone,19 showed slight cognitive at this time that support their use. Disclosure of Financial Interests improvement in patients on intravenous Through education, patients can under- The authors have no financial inter- antibiotics versus the intravenous placebo stand the risks of prolonged antibiotics, ests to disclose. at 12 weeks, but this difference was not and through such understanding, can maintained at 24 weeks post treatment; embrace alternative forms of treatment CORRESPONDENCE: and more than one quarter of the patients for symptoms that can often be quite dis- Jennifer A. Mitty, MD, MPH experienced adverse effects attributed to abling. Physicians in Lyme endemic ar- The Miriam Hospital IV ceftriaxone. Another double-blind, eas can play a central role helping pa- 164 Summit Avenue randomized, placebo controlled study, tients negotiate the controversies and Providence, RI 02906 from Finland, demonstrated that an ad- choose safe and studied treatments. phone: (401) 793-4851? ditional 100 days of oral amoxicillin e-mail: JMitty@Lifespan.org showed no benefit over placebo after REFERENCES both groups were treated with 3 weeks 1. CDC. MMWR 2007; 56: 573-6. 2. Health RID.o. Lyme Disease. 2008 [cited 2008 of IV ceftriaxone.20 Based on the results January 16]; http://www.health.state.ri.us/dis- of these studies, physicians should explore ease/communicable/lyme/index.php. other treatment modalities, similar to . 3. Wormser GP et al. Clin Infect Dis 2006; 43:1089- those used for patients with fibromyalgia, 134. 4. Harrison TR, Kasper KL, ebrary Inc., Harrison’s such as increased physical activity, anti- principles of internal medicine. 2005, McGraw- depressants and alternative/complimen- Hill, Medical Pub. Division: New York. p. xxvii, tary medicine. 2754 p. 5. Cameron D., et al., Expert Rev Anti Infect Ther CONCLUSION 2004. 2(1 Suppl): p. S1-13. 6. CDC. MMWR 1995;44: 590-1. The nature of the spirochete that 7. Engstrom SM., Shoop E, Johnson RC. J Clin causes Lyme disease has to date prevented Microbiol 1995; 33: 419-27. the development of laboratory testing 8. Dressler F, et al. J Infect Dis 1993; 167:392-400. 9. Aguero-Rosenfeld ME., et al.. Clin Microbiol Rev that would allow us to accurately moni- 2005; 18(3): 484-509. tor disease activity. Controversy stems 10. Cameron D. Monitoring Lyme disease in the com- from differing interpretations of the avail- munity in 12th Annual International Scientific able data. Whereas the ILADS guide- Conference on Lyme Disease and Other Spiro- chetal and Tick-Borne Disorders. 1999. lines rely primarily on small, clinically 11. CDC. MMWR 2005; 54: 125. based studies, the IDSA guidelines were 12. Luft BJ, et al. Ann Intern Med 1996; 124:785- evidence-based, using data from random- 91. 13. Wormser, GP. Ramanathan R, et al. Ann Intern ized, controlled, and open-label trials. Med 2003;138;697-704. Given the non-specific symptoms of 14. Klempner MS, et al. NEMJ 2001l 345: 85-92. many patients, following the ILADS rec- 15. Battaglia, H, et al. J Spirochetal and Tick-Borne ommendations could lead to a rise in the Dis 2000;7:22-5. 16. Fallon B., et al. J Spirochetal and Tick-Borne Dis misdiagnosis of Lyme disease with a re- 1999; 6:94-102. sultant overuse of antibiotics. Therefore, 17. Patel R, et al. Clin Infect Dis 2000; 31: 1107-9. it is important that we educate our pa- 18. Zahran HS, et al. MMWR Surveill Summ 2005; tients (Table 1) regarding the significant 54:1-35. 19. Fallon BA, et al. Neurol 2008; 70:992-1003 negative effects of prolonged antibiotics, 20. Oksi, J., et al., Eur J Clin Microbiol Infect Dis 2007; and the lack of convincing scientific data 26: 571-81. 223 VOLUME 91 NO. 7 JULY 2008 THE WARREN ALPERT MEDICAL SCHOOL OF BROWN UNIVERSITY GERIATRICS FOR THE Division of Geriatrics Department of Medicine PRACTICING PHYSICIAN Quality Partners of RI EDITED BY ANA T UYA FULTON, MD Dementia Screening: Should We Screen Asymptomatic Older Adults? Ana Tuya Fulton, MD A 76-year-old woman comes to your office for her routine improvements in cognition as measured by several rating scales annual visit. She’s been doing well since you last saw her, has (Alzheimer’s disease Assessment scale and Clinician’s global rat- no complaints, and is in her usual state of health. She has a ings)3. There was no effect on quality of life scores. A second history of hypertension that has been well controlled on hy- placebo controlled trial, AD2000, showed a small but signifi- drochlorothiazide. She attends the local senior center weekly, cant improvement in cognition (Mini Mental Status Exam score participates in Tai Chi every morning and volunteers at the up by an average of 0.8 points).3 These effects are consistent local elementary school on weekdays. You have seen her regu- with several other studies.3 However, the study did not dem- larly and she is up to date with influenza and pneumococcal onstrate a delay in institutionalization.3 Other studies have vaccines, had a normal colonoscopy 4 years ago, and normal demonstrated delays in the decline of performance of activities yearly mammograms, which she has decided to continue as daily living. More consistently demonstrated is that cholinest- long as she is active and independent. Today, she asks you about erase inhibitors have a positive effect on the behavioral compli- dementia screening, because her best friend was just diagnosed cations of dementia. with Alzheimer’s and is now on donepezil. You ask her tar- An additional argument in favor of dementia screening is geted questions about her memory, functional status and ask that there are conditions, albeit rare, that cause dementia but whether she or her family have noted any deficits or problems; are not due to underlying neurodegeneration or stroke. These she reports none. rare situations result from an array of metabolic disorders, CNS Dementia is a major cause of morbidity and mortality in infections, nutritional deficiencies, drug toxicities and even the older patient population, as well as in younger, more active psychiatric conditions. But even if these “reversible dementias” adults, who are just beginning their “leisure years”. It is esti- are rare, the more common circumstance is that the dementia mated that about 8% of adults over 65 years old have demen- due to neurodegeneration or stroke is made worse by the ef- tia; for those over 85 years old, the number jumps to 30-40%.1 fects of the superimposed comorbidity. This translates to more than 4 million people.1 The question to the patient then becomes a personal one: Dementia care is estimated to exceed $100 billion per year.2 “when would you want to know”? As discussed above, the ar- The per person, per year cost for formal health care (long term gument for screening is colored by the fact that we cannot care, medications, acute care and emergency visits) is estimated alter the outcome, only delay it at best. However, allowing at $27,672, and the cost of informal care (caregiver and pri- patients and families to do advance care and estate planning in vate home care) ranges from $10,400 to $34,5172. These fig- the earlier, more functional stages is often argued as a large ures do not include the social costs of a debilitating disease that benefit of earlier detection. There are people who prefer to can ravage a family, and almost always results in permanent know, regardless of the answer, and who would worry more nursing home placement and loss of independence, personal- about the chance of the disease than the disease itself. But ity and the most basic of functional activities. Due to dementia’s some might be crippled by the knowledge and lose day-to-day dramatic impact, many are considering instituting screening enjoyment and quality of life due to their anxiety about the programs. Screening programs would involve asking asymp- future. No studies demonstrate psychosocial benefits to patients tomatic patients questions about their memory and functional or their caregivers through earlier detection.4 status, and performing cognitive assessment tests (e.g, Mini A good screening test is evaluated by its sensitivity and Mental Status Exam, 7 minute screen, Mini-Cog). specificity for the disease or condition. Many of the cognitive The discussion of screening is difficult, because the treat- tests that are routinely used to evaluate for cognitive impair- ments we can offer are not curative. The purpose of a screen- ment have met the desired sensitivity and specificity cut offs. ing test is early identification to permit early initiation of therapy However, a valuable screening test must also have a high posi- that will improve outcomes. Data indicate that cholinesterase tive predictive value4 to be sure that patients are correctly iden- inhibitors at best temporarily slow or delay progression of dis- tified as having the disease. The positive predictive value should ease and improve measures of cognition on some scales. Most be higher than the disease prevalence, a criterion on which experts describe a delay in progression of approximately 6 to12 many cognitive tests for dementia fail. In addition, there must months with use of cholinesterase inhibitors. Studies of follow a discussion of cost-effectiveness. A screening study donepezil, for example, have demonstrated mixed results. A should, thinking pragmatically, not only impact mortality and 24-week, placebo controlled trial demonstrated significant morbidity, but also the financial and resource burden on the 224 MEDICINE & HEALTH /RHODE ISLAND health care system. No evidence supports the hypothesis that Further reading and practice guidelines: earlier diagnosis will ameliorate costs to our health care system. In fact, many speculate that early detection will increase costs American Geriatrics Society Position Statement: due to increased physician and support staff time, longer du- h t t p : / / w w w. a m e r i c a n g e r i a t r i c s . o r g / p r o d u c t s / ration of use of medications (6 month cost of Aricept is almost positionpapers/stopscreening.shtml $1000 5), and longer use of community and health care re- sources.4 For many of the reasons discussed, the current rec- American Academy of Neurology Guidelines: ommendation by the US Preventative Services Task Force is an http://www.aan.com/pr ofessionals/practice/pdfs/ “I” recommendation, indicating insufficient evidence to rec- dementia_guideline.pdf ommend for or against dementia screening.6 “Rationale: The USPSTF found good evidence that some USPSTF rationale: screening tests have good sensitivity but only fair specificity in http://www.ahrq.go v/clinic/3rduspstf/dementia/ detecting cognitive impairment and dementia. There is fair to dementrr.htm good evidence that several drug therapies have a beneficial ef- fect on cognitive function (equivalent to delaying the natural REFERENCES progression of Alzheimer’s disease from 2 to 7 months), but 1. NIA Alzheimer’s Disease Fact Sheet: http://www.nia.nih.gov/Alzheimers/Pub- lications/adfact.htm. Accessed May 13, 2008. the evidence of their beneficial effects on instrumental activi- 2. Rice DP, Fillit HM, et. al. Prevalence, costs, and treatment of Alzheimer’s ties of daily living is mixed, with the benefit being small, at Disease and related dementia. Am J Manag Care 2001; 7: 809-18. best. There is insufficient evidence to determine whether the 3. Press D, Alexander M. Cholinesterase inhibitors in dementia. In DeKosky ST, benefits observed in drug trials are generalizable to patients Schmader KE, Wilterdink J: UpToDate Online 16.1. Updated January 2008. Accessed May 13, 2008. whose disease would be detected by screening in primary care 4. Brayne C, Fox C, Boustani M. Dementia screening in primary care. JAMA settings. The accuracy of diagnosis, the feasibility of screening 2007; 298: 2409-11. and treatment in routine clinical practice, and the potential 5. Drugstore: http://www.drugstore.com. Accessed May 18, 2008 harms of screening (e.g., labeling effects) are also unknown. 6. Boustani M, Peterson B, et al. Screening for dementia. Systematic evidence review. http://www.ahrq.gov/. Accessed May 13, 2008. The Task Force therefore could not determine whether the benefits of screening for dementia outweigh the harms. “ http:/ Ana Tuya Fulton, MD, is Assistant Professor, Division of /www.ahrq.gov/clinic/3rduspstf/dementia/dementrr.htm Geriatrics, Warren Alpert Medical School of Brown University. Using objective criteria to evaluate a screening test, de- mentia screening does not pass the bar. However, many pro- Disclosure of Financial Interests fessional organizations recommend screening and early inter- The author has no financial interests to disclose. vention. As better treatments emerge, a concerted screening effort will follow. For now, individualized conversations with 8SOWRI-GERIATRICS-072008 patients, discussing the evidence for screening, the likely re- sults of treatment and the impact on quality of life are the best THE ANALYSES UPON WHICH THIS PUBLICATION IS BASED were course of action. performed under Contract Number 500-02-RI02, funded by the Centers for Medicare & Medicaid Services, an agency of What to do with our patient? She has no symptoms of the U.S. Department of Health and Human Services. The con- cognitive impairment, and is high functioning and active. tent of this publication does not necessarily reflect the views Reassurance with a discussion of the rationale above, and plans or policies of the Department of Health and Human Services, to follow closely with screening if she strongly desires, or devel- nor does mention of trade names, commercial products, or ops any symptoms or concerns would be a reasonable approach. organizations imply endorsement by the U.S. Government. The author assumes full responsibility for the accuracy and completeness of the ideas presented. 225 VOLUME 91 NO. 7 JULY 2008 The Creative Clinican Rituximab In Treating Refractory Thrombotic Thrombocytopenic Purpura: Three Case Reports Samir Dalia, MD, Brendan McNulty, MD, Gerald A. Colvin, DO Thrombotic thrombocytopenic purpura (TTP), previ- twice daily PE on hospital day five with subsequent improve- ously often fatal, today is managed effectively with corticoster- ment in platelet count. After one week of twice daily PE, her oids and plasma exchange (PE); but a subset of patients will platelet count fell again, and a rituximab course of four weekly require further treatment. Though the classic pentad charac- doses of 375mg/m2 was initiated in addition to a prednisone teristic of TTP includes microangiopathic hemolytic anemia, taper. Her platelet count normalized within a week. On hos- thrombocytopenia, neurological deficits, fever, and renal im- pital day twenty-one she was discharged home following her pairment, only one sixth of cases have all these features. 1 Treat- third dose of rituximab with close follow-up and a weaning ment is often initiated based on the findings of microangiopathic course of PE. After twelve months, she had no signs of relapse hemolytic anemia, including significant schistocytes on periph- without any medications. eral blood smear, in combination with thrombocytopenia un- explained by disseminated intravascular coagulation or other CASE 2 processes. A 23 year-old woman with history of hydrocephalus, The additional therapy may include immunosuppressive treated at age 8 with a VP shunt, presented to the emergency agents, including vincristine, cyclophosphamide, and department with a week of progressive spontaneous bruising, cyclosporine, which have been used with variable success.2 dizziness, blurry vision, headache, and intermittent numbness Rituximab, a chimeric monoclonal antibody against CD20, a on the right side of her body. Her roommate noticed a right- phosphoprotein that is expressed on the surface of all mature sided facial droop on the day prior to her admission. On ad- B-cells, has increasingly been shown to induce remission in re- mission, the patient’s physical exam was notable for diffuse trun- fractory TTP.2,3 In fact, a retrospective review of TTP cases cal petechiae with multiple ecchymoses on the legs. Her neu- treated with rituximab demonstrated a decrease in the titer of rologic exam was normal. A CT scan of the head revealed no antibodies of ADAMTS13, a metalloproteinase that regulates acute abnormalities, as did a subsequent MRI. She had an the biological breakdown of Von Willebran factor (vWF), a initial hemoglobin of 9.2 g/dL, a platelet count of 16,000/µL, platelet aggregation regulator.4 haptoglobin was <5.83 mg/dL and normal renal function. We report three cases of refractory TTP in which the early Coagulation studies and fibrogen level were within normal lim- use of rituximab, combined with PE and corticosteroids, led to its. An assay of ADAMTS13 was <5% with an inhibitor unit favorable outcomes. level of 1.0. Review of the peripheral blood smear revealed multiple schistocytes. CASE 1 Daily PE with prednisone 100mg daily was started, and A 28 year-old woman with no significant medical his- her platelet count rapidly improved along with her symptoms. tory presented with a two-week history of worsening, sponta- She was weaned to every other day PE when her platelet count neous bruising of her limbs and left breast. She reported reached 173,000 on hospital day four. However, her platelet malaise and generalized abdominal pain with nausea, but count decreased again and daily PE was restarted. Her disease denied any history of fever, diarrhea, or numbness. She had became refractory to once daily exchange, and the patient was mild diffuse abdominal tenderness, truncal petechiae, and then transferred to the intensive care unit for twice-daily PE ecchymoses on the extremities and left breast. She was alert, on hospital day nine because of falling platelet counts. By hos- oriented and had no neurologic deficits. Imaging of the ab- pital day fifteen her platelet count response remained poor so domen by CT revealed no abnormal findings. Initial labora- weekly rituximab was initiated with a prednisone taper. Her tory studies showed a hemoglobin of 10.5 g/dL, a platelet platelet count increased to the low normal range within the count of 11,000/µL, and normal renal function, PT/PTT, first week of treatment with rituximab and this trend contin- and fibrinogen levels. Hemolysis studies were notable for an ued after the second dose. She was discharged home for out- LDH of 892 IU/L, an undetectable haptoglobin, and an el- patient PE three times per week, and two further doses of evated indirect bilirubin of 1.6. Review of a peripheral blood weekly rituximab therapy. PE was weaned slowly and after six smear revealed numerous schistocytes supporting the diag- months of follow-up, she remained relapse-free on no medica- nosis of TTP. An assay for ADAMTS13 was at <5% (refer- tions. ence range > or = 67%) with a protease inhibitor level >8.0 inhibitor units. CASE 3 The patient was transferred to the medical intensive care A 25 year-old man with a history of schizophrenia,, hy- unit where once daily PE was initiated with prednisone 100mg. pertension and pancreatitis secondary to hypertriglyceridemia Due to suboptimal platelet response the patient was started on presented initially to an outside hospital with renal failure and 226 MEDICINE & HEALTH /RHODE ISLAND slight improvement in his renal function Patie nt 1- Plate le t Count Rituximab and on post hospital day six rituximab 210 Rituximab therapy was started for continued renal fail- Rituximab ure thought to be from the TTP. After four Platelet Count x 1000/µL 180 150 doses of weekly rituximab therapy the 120 2xdPE patient’s creatinine improved to 1.3 mg/dl 90 from a high of 5.0 mg/dl with a stable plate- 60 let count. He has been disease free for four 30 months on no medications. 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Hospital C ourse (D ays) 14 15 16 17 18 19 20 21 DISCUSSION Treatment of TTP with PE has been accepted since PE was compared with Patie nt 2- Plate le t Count plasma infusion for treatment in 1991.5 In 270 Rituximab refractory cases immunosuprpression is of- 240 ten utilized based on the rationale that TTP Platelet Count x 1000/µL 210 Rituximab may be caused by autoantibodies that in- 180 150 2xdPE hibit ADAMTS13 activity. Several differ- 120 ent immunosuppressant medications have 90 been tried but none seem as promising and 60 safe as rituximab. Rituximab’s efficacy as 30 an adjunct to plasma exchange and corti- 0 costeroids in the treatment of TTP is de- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 scribed in multiple case reports.3-4,6-13 One Hospi tal C ou rse (D ays ) case study demonstrated the use of Patie nt 3- Plate le t Count rituximab as a first line treatment in TTP.8 350 2xdPE Another study demonstrated that prophy- 300 Rituximab laxis with rituximab in patients with previ- Platelet Count x 1000/µL 250 ous TTP was beneficial.3 Unlike other im- 200 munosuppressants, rituximab is generally 1xd PE 150 3xW safe and well tolerated though it does have 100 a common adverse effect of infusion reac- 50 tions. 0 Discharge Our case reports illustrate that early 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 21 22 25 27 30 60 Hos pital Cours e (Days ) intervention with rituximab may provide rapid improvement of refractory TTP. In Figure 1: Platelet Count of Patients while in the hospital. 1xd PE: Once daily plasma these cases use of rituximab may have con- exchange. 2xd PE: Twice daily plasma exchange, 3xW: Three times a week plasma exchange. tributed to a decrease in length of hospital stay as well as the associated morbidity and mortality of refractory TTP. The benefits hyperkalemia requiring emergent dialysis. The patient had a of early rituximab therapy in TTP management will need to be hemoglobin of 9.1 g/dL, platelet count of 8,000/µL and mul- established through a prospective clinical trial. The Transfu- tiple shistocytes on peripheral smear. He was transferred to our sion Medicine and Hemostatis Clinical Trials Network, spon- institution for management of TTP. An assay of ADAMTS13, sored by the National Heart, Lung and Blood Institute drawn during PE therapy, revealed proteases activity level (NHLBI), has initiated a multi-center, randomized clinical trial, >67%. designed to determine whether rituximab, in addition to stan- The patient received twice daily PE with Solu-Medrol dard treatment of PE and corticosteroids, decreases initial treat- 125mg intravenous every 6 hours for one week. The patient ment failure rates as well as subsequent relapses of TTP over was tapered to once daily PE and the Solu-Medrol was changed three years. Data from this study will establish rituximab’s role to a prednisone taper. The patient’s hospital course was com- in the first line treatment in TTP. plicated by an intra-abdominal infection and continued wors- Data are mounting in regard to the efficacy of rituximab ening of his renal function. The week prior to discharge the in TTP management. In our experience rituximab has pro- patient was tapered to prednisone 10mg once a day receiving vided considerable benefit for patients with refractory TTP by thrice weekly PE. On hospital day nineteen the patient had a facilitating the rapid wean of PE and systemic corticosteroid platelet count of 175,000/µL and was discharged with outpa- therapy. It shows promise for reducing the morbidity and tient dialysis and thrice weekly PE. mortality of this dangerous immune-mediated disorder. His platelets stayed between 160,000-190,000/µL with 227 VOLUME 91 NO. 7 JULY 2008 REFERENCES Samir Dalia, MD, is a resident in Internal Medicine, Rhode 1. Eldor A. Thrombotic thrombocytopenic purpura. Baillieres Clin Haematol Island Hospital/ Warren Alpert Medical School of Brown Uni- 1998;11:475-95. versity. 2. George JN. Clinical practice. Thrombotic thrombocytopenic purpura. NEJM 2006; 354:1927-35. Brendan McNulty, MD, is a Clinical Fellow in Hematol- 3. Fakhorui F, Vernat JP, et al. Efficiency of curative and prophylactic treatment ogy/Oncology Brown University Hematology/Oncology Fellowship with rituximab in ADAMTS13-deficient thrombotic thrombocytopenic pur- Program. pura.. Blood 2005;106:1932-7. Gerald A. Colvin, DO, is Associate Professor of Medicine, 4. Scully M, Cohen H, et al. Remission in acute refractory and relapsing throm- botic thrombocytopenic purpura following rituximab. Br J Haematol Warren Alpert Medical School of Brown University. 2007;136:451-61. 5. Rock GA, Shumak KH, et al. Comparison of plasma exchange with plasma Disclosure of Financial Interests infusion in the treatment of thrombotic thrombocytopenic purpura. NEJM 1991;325:393-7. The authors have no financial interests to disclose. 6. Millward PM, Bandarenko N, et al. Cardiogenic shock complicates successful treatment of refractory thrombotic thrombocytopenia purpura with rituximab. Discussion of use of off-label or investigational Transfusion 2005; 45:1481-6. product: 7. Scott SM, Szczepiorkowski ZM. Rituximab for TTP. Am J Hematol 2005;80:87-8. Rituximab 8. Patino W, Sarode R. Successful repeat therapy with rituximab for relapsed thrombotic thrombocytopenic purpura. J Clin Apheresis 2007;22:17-20. 9. George JN, Woodson RD, et al. Rituximab therapy for thrombotic thromb- ocytopenic purpura. J Clin Apheresis 2006;21:49-56. 10. Chow KV, Carroll R, et al. Anti-CD20 antibody in thrombotic thrombocy- CORRESPONDENCE: topenic purpura refractory to plasma exchange. Intern Med J 2007;37:329- Samir Dalia, MD 32. Rhode Island Hospital 11. Basquiera AL, Damonte JC, et al. Long-term remission in a patient with 593 Eddy Street refractory thrombotic thrombocytopenic purpura treated with rituximab and plasma exchange. Ann Hematol 2007 Set 27 (Epub ahead of print). George Building, 3rd floor 12. Darabi K. Berg AH. Rituximab can be combined with daily plasma ex- Providence, RI 02903 change to achieve effective B-cell depletion and clinical improvement in acute Phone: (401) 444-4000 autoimmune TTP. Am J Clin Pathol 2006;125:592-7. e-mail: firstname.lastname@example.org 13. Koulova L, Alexandrescu D, et al. Rituximab for the treatment of refractory idiopathic thrombocytopenic purpura (ITP) and thrombotic thrombocy- topenic purpura (TTP). Am J Hematol 2005;78:49-54. 228 MEDICINE & HEALTH /RHODE ISLAND RHODE ISLAND DEPARTMENT OF HEALTH • DAVID GIFFORD, MD, MPH, DIRECTOR OF HEALTH E DITED BY JAY S. BUECHNER, PHD Estimating the Incidence of New Onset Lyme Disease in Rhode Island John P. Fulton, PhD Lyme disease (LD), a tick-borne illness caused by the bac- lance. Between 2002 and 2006 (inclusive), the New Jersey terium Borrelia burgdorferi, is prevalent along the northeast- Department of Health (NJDH) mandated electronic report- ern seaboard of the US and in Wisconsin and Minnesota.1 It is ing of all positive laboratory tests for LD among New Jersey reported with much less frequency in other parts of the nation. residents.6 Compared to the year preceding mandated labora- (Figures 1 and 2.1,2) According to the Centers for Disease tory reporting (2001), the average annual number of LD re- Control and Prevention (CDC): ports quintupled in 2002-2006, creating a significant strain on human resources in local health departments. Nonetheless, Typical symptoms include fever, headache, fatigue, and the results of this natural experiment are quite instructive, and a characteristic skin rash called erythema migrans. If left may be compared—albeit roughly—with Connecticut’s expe- untreated, infection can spread to joints, the heart, and rience. Laboratory reporting increased the average annual in- the nervous system. Lyme disease is diagnosed based cidence of confirmed LD in New Jersey by 18%, less than on symptoms, physical findings (e.g., rash), and the Connecticut’s increase (~50%). About 29% of New Jersey’s possibility of exposure to infected ticks; laboratory test- laboratory reports yielded confirmed LD cases, slightly less than ing is helpful in the later stages of disease.3 Connecticut’s yield (36%).4,6 Thus, even though the net yield of confirmed LD cases from laboratory-initiated reports (the Because laboratory tests are not definitive for the diagno- yield over and above physician-initiated reports) was lower in sis of LD, public health agencies must rely on reports from New Jersey than Connecticut—18% versus ~50%—the gross clinicians containing detailed information “on symptoms, physi- yield was roughly the same—29% versus 36%. Ultimately, cal findings (e.g., rash), and the possibility of exposure to in- New Jersey changed its surveillance practices to conserve hu- fected ticks”3 in order to establish the burden of LD in a de- man resources. It now follows up only on those laboratory fined population. Obtaining timely, accurate, and complete reports that are linked to physician-initiated reports.6 reporting of LD is labor intensive for both clinician reporters Like its neighbors in the northeastern United States, Rhode and public health agencies; and the result, to no one’s surprise, Island has struggled to muster sufficient resources to follow up has been significant under-reporting of new onset LD. 4-8 on mandated laboratory reports for LD. In common with vir- Connecticut is a case in point, as revealed in the results of tually all jurisdictions in which LD is prevalent, cases of new a study undertaken by the Connecticut Department of Public onset disease are known to be undercounted and under-re- Health (CDPH) from 1998 through 2002.4 By means of la- ported to the CDC. Nonetheless, from 1992-1998, Rhode bor-intensive investigation during those five years, the CDPH Island had the second highest state LD incidence rate in the identified an average of 3755 new onset cases of LD per year, of which only about half (approximately Figure 1. Number* of newly reported Lyme disease cases by 1830 per year) were identified through “physician county** – United States, 2006 initiated” reporting. The rest of the cases were iden- tified by following up on every positive laboratory test for LD reported to the CDPH. Of more than 10,000 positive tests per year reported to the CDPH by man- date, “only 36% of reports received through required laboratory surveillance resulted in identification that met the national surveillance case definition [as de- fined by the CDC] for LD.” 4 The CDPH could not sustain this intensity of effort for the long term, and dropped mandatory laboratory reporting for LD in 2003. The number of cases reported to the CDC from Connecticut dropped from a high of about 4600 in 2002, the last year of intense case finding, to an average of about 1500 per year in 2003, 2004, and 2005.4 New Jersey provides another documented illus- *N=23,174; county not available for 131 other cases. **One dot placed tration of the difficulties associated with LD surveil- randomly within the county of patient residence for each reported case. 229 VOLUME 91 NO. 7 JULY 2008 Figure 2. Number of reported cases of Lyme disease by LD counts recorded for Rhode Island in previous years county – United States, 1982-1998* – 789 cases in 1998, 852 cases in 2002, and 736 cases in 2003.1,2 As well, the estimated Rhode Island rate of 96 per 100,000 population (computed from Connecticut’s yield) compares favorably with Connecticut’s rate for the 1998-2002 period, 109 per 100,000 persons (an average of 3730 confirmed LD cases per year, with a mid-period population of 3,409,549).4 On the basis of all LD surveillance in- formation collected to date, it is reasonable to expect similar LD rates in the two states, with Connecticut having a marginally higher rate than Rhode Island. If the high-end estimate for Rhode Island is roughly correct – 96 LD cases per 100,000 per year in 2005 (the estimate computed from Connecticut’s 1998-2002 experience) – then at best (e.g., in 2002, when Rhode Island confirmed 852 cases) Rhode Is- land has been able to confirm and report about 83% of LD cases meeting CDC’s case definition. *Includes Pennsylvania cases for 1994-1998 and Oregon cases for 1993-1998. DISCUSSION Surveillance for LD is costly, because it is neces- nation, 44.8 per 100,000 population,2 and by 2004, had sur- sary to obtain clinical information on signs and symptoms passed all other states in new onset cases of LD per capita: 68.39 from clinician’s records, and because so many clinicians are per 100,000 population.1 involved. In Rhode Island, more than 400 physicians were Just how high is the actual LD incidence rate in Rhode responsible for generating the 2881 LD laboratory reports Island? Can it be estimated? It can, because Rhode Island transmitted to HEALTH in 2005. Connecticut, New Jersey, mandates reporting of positive LD laboratory tests, and be- and Rhode Island all tried to enhance surveillance by man- cause two of Rhode Island’s sister states (Connecticut and New dating LD laboratory reporting, and found it too labor-in- Jersey) have evaluated the yield of confirmed LD cases from tensive to sustain the follow-up necessary to identify LD cases positive laboratory reports. It is reasonable to employ the find- meeting the CDC’s case definition. In the recently published ings of Connecticut’s and New Jersey’s LD reporting evalua- evaluation of its LD surveillance system, New Jersey public tions to Rhode Island because the three states share similar geo- health officials reported that “LD investigations required a graphic features and LD history (Figures 1 and 2), and be- median of 2 months to complete follow-up and classify the cause the LD case yields from positive LD laboratory tests were report… representing approximately 1 hour of active infor- roughly similar in Connecticut and New Jersey.4,6 mation collection per case.” 6 This experience closely paral- lels informal observations of the same activity as undertaken METHODS in Rhode Island. Applying New Jersey’s “1 hour of active Positive LD laboratory reports transmitted to the Rhode Is- information collection per case” finding to Rhode Island, land Department of Health (HEALTH) in 2005 were carefully 835-1037 cases would consume one well-trained, full-time evaluated for address (of the patient, or, lacking that, of the or- employee for the entire year – for just one of many report- dering clinician), test (several tests for other tick-borne illnesses able diseases. Furthermore, because LD activity is much more were discovered in this manner and removed), and positivity of common in the warmer months, it would actually require more result. 2881 contained an authentic Rhode Island address and than one full-time employee to keep pace with clinical prac- at least one of several positive test results for LD. tice. Keeping pace with receipt of laboratory tests is an im- The number of positive test results was multiplied by pro- portant time-saver for clinicians, especially the many who see portions of yield (for confirmed LD) as reported by the States one or two possible LD cases per year, so that they may re- of Connecticut (for the 1998-2002 reporting years) and New spond to public health requests for case information without Jersey (for the 2002-2006 reporting years) to estimate the num- having to search through old records. Keeping pace also as- ber of new onset LD cases meeting the CDC’s case definition, sures timely reporting of confirmed cases to the CDC. Every as used in the 1998-2002 and 2002-2006 periods. year, public health agencies have a window of opportunity to report calendar year cases to the CDC. Cases that are con- RESULTS firmed outside the window are never counted in national sta- In 2005, an estimated 835-1037 cases of new onset LD (meet- tistics. From its evaluation of LD surveillance activities in ing CDC’s case definition for that year) occurred in Rhode Island, 2001-2006, New Jersey concluded that 24% of its LD cases yielding crude incidence rates of 78-96 per 100,000 population. were confirmed outside the window of opportunity for re- The estimates have good face validity. The number of porting, and therefore were omitted from statistics published estimated cases approximates (or exceeds) the highest annual by the CDC.6 230 MEDICINE & HEALTH /RHODE ISLAND The CDC has recently attempted to address the costliness Additional information on LD is available on HEALTH’s of LD surveillance by permitting public health agencies to re- website. (http://www.health.ri.gov /disease/communicable/ port LD cases in several categories: lyme/index.php) REFERENCES Case classification 9 1. Bacon RM, Kugeler KJ, et al. Lyme disease — United States, 2003—2005. MMWR (Weekly) June 15, 2007 / 56(23);573-6. • Confirmed: a) a case of EM [erythema migrans] with 2. Orloski KA, Hayes EB, Campbell GL. Surveillance for Lyme disease — United a known exposure, or b) a case of EM with laboratory States, 1992—1998. MMWR (Surveillance Summaries) April 28, 2000 / evidence of infection* and without a known exposure 49(SS03);1-11. or c) a case with at least one late manifestation that 3. Centers for Disease Control and Prevention, Division of Vector-Borne Infec- has laboratory evidence of infection.* tious Diseases. Lyme Disease. http://www.cdc.gov/ncidod/dvbid/lyme/ index.htm • Probable: any other case of physician-diagnosed 4. Cartter ML, Mshar P, Hadler JL. The epidemiology of Lyme disease in Con- Lyme disease that has laboratory evidence of infec- necticut. Conn Med 1989;53:320-3. tion.* 5. Coyle BS, et al. The public health impact of Lyme disease in Maryland. J Infect • Suspected: a) a case of EM where there is no known Dis 1996;173:1260-2. exposure and no laboratory evidence of infection,* or 6. McHugh LA, Semple S, et al. Effect of electronic laboratory reporting on the b) a case with laboratory evidence of infection but no burden of Lyme disease surveillance — New Jersey, 2001—2006. MMWR clinical information available (e.g. a laboratory report). (Weekly) January 18, 2008 / 57;42-5. 7. Meek JI, et al. Underreporting of Lyme disease by Connecticut physicians, [Lyme disease reports will not be considered cases if the medi- 1992. J Public Health Management Practice 1996;2:61-5. 8. Naleway AL, Belongia EA, et al. Lyme disease incidence in Wisconsin. Am J cal provider specifically states this is not a case of Lyme dis- Epidemiol 2002;155:1120-7. ease, or the only symptom listed is “tick bite” or “insect bite.”] 9. Centers for Disease Control and Prevention, Division of Vector-Borne Infec- tious Diseases. Lyme Disease 2008 Case Definition. http://www.cdc.gov/ncphi/ * For a definition of “laboratory evidence of infection,” please see disss/nndss/ casedef/lyme_disease_2008.htm criteria as established in: Centers for Disease Control and Pre- vention. Recommendations for test performance and interpreta- John P. Fulton, PhD, is Chief Health Program Evaluator, tion from the Second National Conference on Serologic Diagno- sis of Lyme Disease. MMWR (Weekly) 1995; 44:590-1. http:// Center for Epidemiology and Infectious Diseases, Rhode Island www.cdc.gov/mmwr/preview/mmwrhtml/00038469.htm Department of Health, and Clinical Associate Professor of Com- munity Health, The Warren Alpert Medical School of Brown University. Using this convention (the 2008 Case Definition) allows public health agencies to report all information to CDC with- Disclosure of Financial Interests out having to confirm each individual case. This, in turn, will The author has no financial interests to disclose. allow the CDC to estimate the true burden of Lyme disease incidence, much as Rhode Island has done by applying esti- mates of LD yield (and other measures) to numbers of positive LD laboratory reports. Nonetheless, individual clinician re- porting of LD cases remains the backbone of LD surveillance. Therefore, health care providers in Rhode Island are strongly urged to report all new onset LD to the Center for Epidemiol- ogy and Infectious Diseases on the standard reporting form. (http://www.health.ri.gov/disease/communicable/lyme/ LymeReportForm2005.pdf ) 231 VOLUME 91 NO. 7 JULY 2008 DAVID GIFFORD, MD, MPH, DIRECTOR OF HEALTH RHODE ISLAND DEPARTMENT OF HEALTH EDITED BY J OHN P. FULTON, PHD The RI Board of Medical Licensure and Discipline, 2007 Year Summary Robert S. Crausman, MD, Mary E. Salerno, MA, Linda Julian, Lauren Dixon, and Bruce McIntyre, JD Few professions involve the unique privileges and responsibilities In 2007 a total of 332 completed applications were pro- that medicine and osteopathy require of practitioners in mod- cessed: 320 MD and 11 DO licenses granted with 1 rejection. ern American society. So extraordinary is this role and so nec- essary is this commitment, that every state operates a govern- Complaints and discipline mental agency to monitor and enforce the professional con- The Board serves as a clearinghouse for written complaints duct of physicians. These Boards of Medicine in turn have the regarding unprofessional conduct. Complaints may come from obligation to be open to performance review by the physician individuals, institutions, public officers, other physicians, community and society at large. healthcare professionals or anyone who has contact with medi- cal professionals—including the Board itself. All complaints and THE RHODE ISLAND BOARD OF MEDICAL LICENSURE investigations remain confidential prior to final Board action.1 AND DISCIPLINE The Board reviews all complaints and refers those meriting The Board is an agency of state government established, by further investigation to a three-member subcommittee. The sub- law, to protect the public and to assure high practice and profes- committee—including at least one physician and one layper- sional standards in the nearly 4000-member physician commu- son—investigates and makes a recommendation to the full Board. nity.1 The Board discharges these responsibilities primarily through Written Board decisions include findings of fact and law. A ma- the licensing process, receiving and investigating complaints, and jority of Board members must concur for an individual to be serving as a disciplinary body. Chapter 5-37 of the RI General found guilty of unprofessional conduct. A variety of sanctions Laws describes the Board’s composition, the appointment of mem- may be administered, including: a reprimand; a suspension, limi- bers, its mandate, powers and functions. The 12-member Board tation or restriction to practice medicine; probation subject to includes equal appointment of physicians and public members. conditions and requirements; indefinite revocation of the medi- The Governor appoints members with input from the medical or cal license; mandatory participation in a remedial continuing osteopathic societies and the Health Department. medical education program; compelled submission to care, coun- The Director of the RI Department of Health (HEALTH) seling or treatment; and assessment of fees to cover the adminis- serves as Chair. The Board’s Physician Chief Administrator and trative costs of proceedings. Appeals receive judicial review by Legal Counsel serve in vital support roles. the RI Superior Court. In cases of egregious misconduct consti- tuting an immediate danger to the public, the Director of Health BOARD ACTIVITIES may immediately suspend the individual’s license. Licensing The law speaks in terms of negative examples, i.e. behav- A license to practice medicine in the State of Rhode Is- iors or activities that constitute “unprofessional conduct.” Ex- land is considered a privilege, not a right. The essential require- amples include: conviction of a crime arising from the practice ments include: graduation from a school of medicine, success- of medicine; patient abandonment; medical practice while ful completion of no less then two years of postgraduate train- under the influence of alcohol or illicit drugs; volitional falsifi- ing or three years of postgraduate training for ECFMG (Edu- cation or misrepresentation of medical reports records or treat- cation Commission for Foreign Medical Graduates) certified ments; fee splitting; willful overcharging for professional ser- international graduates, successful completion of the USMLE vices; deceptive billing practices or collection of fees for ser- licensing examination (no greater than 3 attempts per section, vices not rendered; malpractice or incompetence; negligent or all complete in 7 years), evidence of a high moral and ethical willful misconduct in the practice of medicine; sexual contact standard and payment of the application fee. The Board en- in the context of a physician/patient relationship; and failure deavors to render a decision on a complete license application to comply with requests from the Board or its agents.1-4 within 30-90 days. The national advocacy group Public Citizen ranks State In 2006 the Board adopted electronic licensing renewal. Medical Boards according to the number of sanctions made In 2008 the Board plans to adopt web-based licensing with a per 1000 licensed physicians. For years 2004-2006, RI ranked common application recognized by other states and linked with 38 out of 51 jurisdictions with a serious action rate of 2.75. nationally accepted credentials verification via FCVS (Federa- The range for jurisdictions was Alaska at 7.30 through Missis- tion Credentials Verification Service), testing, USMLE and sippi at 1.41. [http://www.citizen.org/publications/ ECFMG certification to further speed processing. release.cfm?ID=7525] In 2007 the State legislature increased the licensing fee struc- In 2007, 279 new complaints were received and reviewed; ture to: $570 for initial license, $650 for the two-year renewal, 182 were opened for investigation; 126 investigations were and $140 for the RI controlled substances registration. closed, with an average time-to-close of 117 days. 232 MEDICINE & HEALTH /RHODE ISLAND In 2007 the Board issued 23 public orders regarding phy- - A physician involved with the Physician’s Health Com- sicians. Six orders related to medical negligence, 4 to drugs or mittee received a reprimand for willfully making a false alcohol, 3 to reciprocal actions recognizing unprofessional con- report when applying for hospital privileges. duct findings in another State on a RI licensed physician, 2 to - A physician received a reprimand and was placed on pro- medical/psychiatric illness rendering a physician unable to prac- bation for prescribing a medication for one family mem- tice safely, 2 to Boundary violations (e.g. inappropriate rela- ber using the insurance member identification number tionship with a patient or key third party), 3 to crime in the of another. No physician-patient relationship existed. practice of medicine, 3 to falsification of records, 2 to inappro- priate prescribing – 1 via the internet, and 1 to facilitating the - A physician received a reprimand and was directed to medical practice of an unlicensed physician.* complete an ethics program for facilitating the unlicensed Below are short summaries. These orders are public docu- practice of another physician who had previously had his ments. [http://www.health.state.ri.us/hsr/bmld/disciplinary.php] license revoked by the Board. - Two physicians were relicensed on probation and required - Three physicians were issued reciprocal actions to reflect to comply with a treatment and monitoring program. sanctions and findings of unprofessional conduct by other They are each required to have a chaperone present for State medical boards for their practice outside of RI. all examinations of female patients. - An immediate compliance order was issued to a physician to - A physician voluntarily surrendered his medical license prohibit the prescription of sublingual midazolam as treatment while under investigation for inappropriately purchasing for agitation in unmonitored nursing home patients. This was approximately 50,000 Vicodin tablets, not for patient use. not associated with any sanction against the physician. - A physician voluntarily surrendered his license while un- - An immediate compliance order was issued to a physi- der investigation by the RI Attorney General. cian to discontinue the operation of an illegal physician operatory. The physician was subsequently sanctioned - A physician voluntarily surrendered his medical license with a 3-month suspension and reinstated on probation. owing to medical illness. It was found that his continued practice posed a significant risk to his patients.** * Total greater than the 23 orders issued due to several re- - A physician voluntarily surrendered his license due to lating to multiple categories health-related problems. He was subsequently reinstated ** N.B. physicians are not generally required to surrender with a 5-year treatment and monitoring contract with their medical license upon retirement or infirmity. Un- the Physician’s Health Committee. fortunately the nature of some illness occasionally forces the Board to intervene with a public order for the pro- - A physician previously suspended by the Director of tection of both the physician and the public. Health for failing to comply with a Board Consent Or- der settled the outstanding case with a revocation retro- Policy Statements active to 1998. Of note, a physician who has been re- The Board is empowered by statute to identify the Standard voked may reapply after 5 years. of Care in the practice of medicine. In the course of case investiga- - A physician previously revoked by the State of Massa- tion the Board occasionally finds areas of practice where there is a chusetts, who had also been imprisoned for crimes re- perceived need for clear articulation of the Standard. The Board lated to healthcare fraud, was suspended for one year by issues ‘policy statements’ to disseminate this standard. Statements order of a hearing committee for moral unfitness, inap- are on the web [ http://www.health.state.ri.us/hsr/bmld/ propriate prescribing, making false statements to the positions.php]. RI licensed physicians are expected to review these Board, and falsification of a medical record. statements at least biannually with their license renewal. - A physician first voluntarily consented to cease all surgical In 2007 the Board articulated 3 new statements. cases while under investigation for his role in a wrong-site 12/12/2007 - Physician or Advanced Practice Clinician Pa- surgery. He subsequently consented to a retroactive sus- tient Visits in a Hospital Setting – In general, when caring pension of surgical privileges to the date of the initial order for inpatients in an acute general medicine/surgical hospi- and was allowed to resume full and unrestricted practice. tal, at least daily visits by either the attending physician, his/ - A physician was placed on probation for three years and her physician cross-coverage, or advanced practice clinician required to undergo a skills and competency assessment should occur and be documented in the medical record. in his area of specialty surgery. He was required to dis- 12/12/2007 - The Physician/Patient Relationship – “It is continue all surgery in the interim. Conditions were inappropriate to prescribe medications via the Internet or placed upon his supervision of physician assistants and similar venue without an appropriate physician/patient re- nurse practitioners. lationship that would typically include: 1) patient history, - A physician with undergraduate training as a pharmacist 2) physical and/or mental health assessment, 3) legitimate received a reprimand for approving prescriptions for an records kept, 4) licensed and trained practitioners, 5) ele- Internet pharmacy. 233 VOLUME 91 NO. 7 JULY 2008 ments of informed consent wherever appropriate and rea- REFERENCES sonable, and 6) AMA/AOA code of ethics followed.” 1. Crausman RS. Protecting the public and assuring high practice and profes- sional standards in the physician community. Med Health RI 2003:279-81 12/12/2007 - Physician Self-Treatment or Treatment of 2. Crausman RS, Savoretti A, Conroy J. Disruptive physician behaviors. Med Immediate Family MembersThe Board endorses the Health RI 2007:48-9 3. Crausman RS. Sexual boundary violations in the physician-patient relation- AMA Statement E-8.19 [ http://www.ama-assn.org/ama/ ship. Med Health RI 2004:255-6 pub/category/8510.html]. Specifically, the Board em- 4. Crausman RS, Baruch JM. Abandonment in the physician-patient relation- phasizes that, “Except in emergencies, it is not appropri- ship. Med Health RI 2004:154-6 ate for physicians to write prescriptions for controlled sub- 5. RI BMLD website http://www.health.state.ri.us/hsr/bmld/positions.php stances for themselves or immediate family members.” Robert S. Crausman, MD, is Chief Administrative Officer, CONCLUSION RI Board of Medical Licensure and Discipline, Interim Direc- The Board of Medical Licensure and Discipline contin- tor, Center for Epidemiology and Infectious Disease, and Associ- ues to protect the high standards of professionalism and ethics ate Professor of Medicine, Warren Alpert Medical School of Brown that characterize medical practice, to safeguard the public wel- University. fare, to provide an efficient yet thorough licensing process, and Mary E. Salerno, MA, is Associate Administrator, RI Board to provide balanced review and investigation of complaints. of Medical Licensure and Discipline. The challenges associated with new technologies, telemedicine, Linda Julian is a Complaint Investigator, RI Department of emergency preparedness and an increasingly international Health. physician workforce have fostered improved collaboration Lauren Dixon is a Medical License Coordinator, RI De- across State jurisdictions and led to recognition that there are partment of Health. national standards for practice and licensure. The Board’s role Bruce McIntyre, JD, is Deputy Legal Counsel, Rhode Island in patient safety continues to evolve. Department of Health. Disclosure of Financial Interests The authors have no financial interests to disclose. CORRESPONDENCE: Robert S. Crausman, MD, MMS RI Board of Medical Licensure and Discipline 3 Capitol Hill, Room 205 Providence, RI 02908 Phone: (401) 222-7888 e-mail: RSCrausman@aol.com 234 MEDICINE & HEALTH /RHODE ISLAND Physician’s Lexicon The Eight Little Wrist Bones In an era where gene deletions, neu- Capitate: From the Latin, capitatus, “Open Sesame !” unlocks the cave hold- rotransmitters and folding proteins domi- meaning headlike in shape; cognate ing the treasures of the forty thieves. nate the content of newer medical text- words include capitation, decapitation, Trapezium: From the Latin mean- books, the study of the morphology of capital and Capitol [originally, Jupiter’s ing a four-sided plane figure with no two the eight wrist bones seems at best ar- Temple in Rome.] sides parallel. Earlier from a Greek word, chaic. Since wiser heads have fashioned Hamate: From the Latin, hamatus, trapezion, meaning a table with four legs. the curricula of yesteryear, perhaps this meaning hook-shaped. Cognate words include trapeze and the exercise in memorization, if nothing else, Pisiform: From the Latin, pisum, voluntary muscle, trapezius. taught us something about patience, for- meaning pea-like. Trapezoid: Shaped like a trapezium. bearance and discipline. Scaphoid: From the Greek, scaphos, Tr iquetrum: From the Latin, Yes, there were eight of them; and meaning boat-like [an older term for a triquestris, meaning having three corners other than some orthopedic surgeons per- submarine is a bathyscaphe]; and from or angles. forming hand repair and a cadre of an older Greek term, scaphoi, meaning The other bones of the hand and rheumatologists, it is unlikely that many shaped like a shovel [which led to the wrist employ such terms as phalanx [From physicians remember their names, con- anatomic name, scapula and the name of the Greek, meaning a trunk or log; and tours or juxtapositions let alone evolution. a short cloak, scapulary.] the Latin describing an infantry unit]; Nor is it likely that these eight names will Sesamoid: Shaped like a sesame seed. and metacarpal [meta- from the Greek arise in casual conversation except, per- Derived from the Aramaic, shimshim. meaning after or beyond or above; and haps, in recounting the details of a night- Why a street has also been named Sesame carpus, meaning wrist.] mare. In no order other than alphabetic, is unclear, but perhaps related to the Ali these eight carpal bones are: Baba tale wherein the secret message, – STANLEY M. ARONSON, MD RHODE ISLAND DEPARTMENT OF HEALTH DAVID G IFFORD, MD, MPH V I TA L S TAT I S T I C S DIRECTOR OF HEALTH EDITED BY COLLEEN FONTANA, STATE REGISTRAR Underlying Reporting Period Rhode Island Monthly Cause of Death July 12 Months Ending with July 2007 2007 Vital Statistics Report Number (a) Number (a) Rates (b) YPLL (c) Provisional Occurrence Diseases of the Heart 216 2,768 258.8 3,764.0 Malignant Neoplasms 213 2,279 213.0 5,792.5 Data from the Cerebrovascular Diseases 25 388 36.3 619.5 Division of Vital Records Injuries (Accidents/Suicide/Homicde) 48 559 52.3 9,015.5 COPD 31 436 40.8 375.0 Reporting Period (a) Cause of death statistics were derived from Vital Events the underlying cause of death reported by January 12 Months Ending with physicians on death certificates. 2008 January 2008 (b) Rates per 100,000 estimated population of Number Number Rates 1,067,610 Live Births 1,112 13,219 12.4* Deaths 870 9,880 9.3* (c) Years of Potential Life Lost (YPLL) Infant Deaths (2) (96) 7.3 # Neonatal Deaths (1) (76) 5.7 # Note: Totals represent vital events which occurred in Rhode Marriages 200 6,771 6.3* Island for the reporting periods listed above. Monthly pro- Divorces 265 2,966 2.8* visional totals should be analyzed with caution because the numbers may be small and subject to seasonal variation. Induced Terminations 458 5,087 384.8 # Spontaneous Fetal Deaths 39 920 69.6 # * Rates per 1,000 estimated population Under 20 weeks gestation (35) (842) 63.7 # # Rates per 1,000 live births 20+ weeks gestation (4) (78) 5.9 # 235 VOLUME 91 NO. 7 JULY 2008 The Official Organ of the Rhode Island Medical Society Issued Monthly under the direction of the Publications Committee VOLUME 1 PER YEAR $2.00 NUMBER 1 PROVIDENCE, R.I., JANUARY, 1917 SINGLE COPY, 25 CENTS NINETY YEARS AGO, JULY 1918 ground radiation compared to which radioactive fallout is of John Champlin, MD, in the President’s Annual Address, very minor significance.” briefly discussed Society business, then turned “to the consid- The Honorable John D. Pastore, in “The Atom – Its Ulti- eration of patriotic and medical questions concerning the war.” mate Promise,” reflected: “We know that all power God shares The usual agenda was not appropriate, “when we have been with man is power for good. We know that the power and the participants in the most destructive war the world has ever promise of the atom is – peace.” known, when our country is calling for more and still more Johannes Virks, MD, and Baruth B. Motola, MD, in medical men for its service.” In 1918 the Medical Society had “Megimide and Daptazole in Treatment of Barbituate Poison- 460 members (dues: $10.00); the total number of physicians ing,” reviewed 4 cases: all recovered, with no serious side ef- in Rhode Island came to 751; 18.2% of physicians in the state fects from the treatment. accepted military commissions. W. Louis Chapman, MD, in “Roentgen Method of Gas- TWENTY-FIVE YEARS AGO, JULY 1983 trointestinal Investigation,” cautioned that patients’ histories Thomas C. McOsker, in “Subdural Hematomas in Sub- were often unreliable: “The patient’s story should be elicited teens,” declared: “A subteen child with mild to moderate with as little coaching as possible. It should be verified by ques- trauma to the head is unlikely to develop a subdural collec- tions on succeeding days and will often be found to change tion.” He drew his conclusion from chart review of 64 cases of with surprising frequency.” The Roentgen examination was children, aged up to 12, admitted with intracranial bleeding essential to understanding the patient’s complaint. He suggested at Rhode Island Hospital, 1973-82. For 47 cases, the cause clinicians begin investigating gastrointestinal concerns with was not trauma. One 11 year-old child, an “exceptional case,” mouth x-rays: “The first step ought to be a study of the mouth, had struck his head on frozen ground, but not lost conscious- and in any case that is at all obscure this should be an x-ray ness. For five weeks he had no symptoms, then he developed study…if one takes a set of x-rays of the teeth in…cases of ar- headaches, which was attributed to migraines (his family had thritis and gastric ulcer the results may be surprising.” He had migraines). A CT scan, though, showed a “large left fronto- judged subjective symptoms “misleading.” temporal mass which proved at craniotomy to be hygroma.” An Editorial, “The Surgeon General of the Army,” praised After the operation, the CT scan still showed subdural collec- General Gorgas, who was nearing retirement age. “No one re- tion, but it finally was reabsorbed. alizes that he is old, for in reality he is young in body as well as Duane Golomb, MD, in “Attitudes toward Pelvic Exami- in mind.” The Editorial urged physicians “as a patriotic mea- nations in Two Primary Care Settings,” found that the exams sure” to lobby the President, their Congressional representa- “…are tolerated, but not with enthusiasm.” tives, and their state legislators to urge the reappointment of Joseph Chazan, MD, contributed a Commentary: “Insti- General Gorgas. tutional Prerogatives and the Private Practicing Physician: A Changing Partnership or the Development of Adversarial FIFTY YEARS AGO, JULY 1958 Roles?” Shields Warren, MD, Professor of Pathology, Harvard Norman A. Baxter, PhD, Executive Director, RI Medical Medical School, delivered the 17th Charles Value Chapin Ora- Society, in Special Report: “The RIMS Federation: A Neces- tion: “The Prevention of Somatic and Genetic Radiation In- sary Step Forward,” explained the decision of the Medical So- jury.” He stressed the persistence of radiation in normal life. ciety (a 501c6 organization) to create a separate 501c3 organi- Providence had 4.5r per generation “at least since the days of zation focused on education. the Narragansett Indians. Radioactive fallout to date is adding about 1/40 of that amount. The amount added by industrial utilization of atomic energy…is at present insignificant, and appears likely to be adequately controlled.” As for why deaths from radiation still occurred, he cited “ignorance.” For instance, he cited a professor who carried in his vest pocket a piece of radium. As for bomb testing, he reassured readers: “…radio- active fallout at the present time is not likely to cause harm from continued bomb testing, because it is less significant than the changes in background radiation that are produced from changes in altitude alone. Thus the move from Providence to Denver involves the receipt of an increased amount of back- 236 MEDICINE & HEALTH /RHODE ISLAND integrity whatdrivesyou? Whatever it is that sustains you through the daily challenges of your profession, know that you have an ally in NORCAL. (800) 652-1051 ● www.norcalmutual.com Call RIMS Insurance Brokerage Corporation at (401) 272-1050 to purchase NORCAL coverage.
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