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					              Complications of Chlamydia and Gonorrhea




                                                                                                 Chlamydia and GC Complications                                                                              Case 1
    Complications of Chlamydia and                                                                 • Upper Genital Tract Infection                                                                         History
              Gonorrhea                                                                               – PID in women                                        • 26yo heterosexual male has increasing pain and swelling
                                                                                                      – Epididymitis and prostatitis in men                   of his right scrotum for 2 days. Denies urethral discharge,
                                                                                                   • Complications from Upper Genital Tract Infection         dysuria, or urinary urgency or frequency. Has had
                                                                                                      – Infertility                                           unprotected intercourse with 3 partners in the last 6
                                                                                                      – Ectopic pregnancy                                     months, with his last sexual contact 2 weeks ago. He got
                                                                                                   • Other Complications                                      kicked 2 days ago in the groin during a fight.
            William M. Geisler M.D., M.P.H.                                                           – Reiter’s syndrome
             University of Alabama at Birmingham                                                      – Disseminated gonorrhea
                                                                                                      – Increase in HIV transmission/acquisition risk
                                                                                                                                                            • A genital examination was performed
                                                                                                                                                            • Urethral specimens were collected for chlamydia and
                                                                                                                                                              gonorrhea tests and a urethral Gram Stain was done




                                                                                                           Epididymitis                                                       Epididymis Anatomy
                                                                                                  Epidemiology and Clinical Findings                                          NORMAL                                    EPIDIDYMITIS

                                                                                                • Epididymitis: inflammation of epididymis usually due
                                                                                                  to infection
                                                                                                • Believed to occur in 1 to 4 per 1000 men per year
                                   http://www.siamhealth.net/Disease/infectious/std/Epidi.htm
                                                                                                • May be accompanied by urethritis (may be
                                                                                                  asymptomatic)
                                                                                                • Symptoms: unilateral testicular pain and tenderness
•Ceftriaxone 250mg IM x 1 and Doxycycline 100mg BID x 10days
•Pt sent to urgent care for ultrasound to rule out torsion                                      • Signs: tender/swollen testicle and/or scrotum, palpable
•Scheduled for follow-up in 72 hours                                                              swelling and tenderness of the epididymis, urethral               Galejs LE, Kass EJ. Am Fam Physician 1999;59
                                                                                                                                                                                                                      Junnila J, Lassen P. Am Fam Physician 1998;57


•Requested to refer sexual partners for evaluation and treatment                                  discharge or hydrocele may be present                     ÆEpididymis receives sperm and seminal fluid from the efferent
                                                                                                                                                            ducts, and here sperm mature becoming motile and fertile




                                                                                                                                                                                                                                        1
            Complications of Chlamydia and Gonorrhea




              Epididymitis Etiology                                         Etiologies of Epididymitis
                                                                                                                                         Etiologies of Epididymitis
Heterosexual men < 35 (and MSM)
• Usual etiology
   – C. trachomatis 60-80%                                          Associated with Urethritis                                 • Associated with Systemic Infection
   – N. gonorrhoeae 5-20%                                                                                                                    Æ
                                                                                                                                 – BacterialÆ TB, MOTT, Brucellosis, Haemophilus
                                                                            Gonorrhea, Chlamydia, Trichomoniasis
• Predisposing factors                                                                                                             influenzue, Listeria, Streptococcus
   – Sexually transmitted urethritis                                Associated with Bacteriuria                                  – FungalÆ Histoplasmosis, Coccidioidomycosis,
Older men (and MSM)                                                                                                                Blastomycosis, Cryptococcosis
                                                                            Coliform bacteria (e.g. E. coli),
• Usual etiology                                                            Pseudomonas aeruginosa                               – ViralÆ Mumps, Cytomegalovirus
   – Coliforms (esp. E. coli) account for more cases
                                                                                                                                 – ParasiticÆ Schistosomiasis, Sparganosis,
• Predisposing factors                                              Associated with Funguria
                                                                                                                                   Bancroftian filariasis
   – Underlying genitourinary pathology or bacterial prostatitis
                                                                            Candida spp.
   – Sexually transmitted in MSM




                                                                                      Epididymitis                                     Epididymitis Evaluation
            Etiologies of Epididymitis                                          Differential Diagnosis                           • History
• Associated with Drugs                                                                                                          • Examination of the external genitalia
   – Amiodarone                                                    –   Varicocele                                                • Palpation of scrotum and its contents
• Associated with a Systemic Vasculitis or                         –   Inguinal hernia                                           • Prostate exam if indicated by history
  Inflammatory Diseases                                            –   Spermatocele                                              • Gram stain of urethral exudate
   – Behcet’s, Henoch-Schõnlein purpura,                                                                                         • Gram stain of 1st void and midstream urine for
     Polyarteritis nodosa, Wegener’s granulomatosis,               –   Injury (Trauma)
                                                                   –   Torsion                                                     WBCs or bacterial if urethral Gram stain
     sarcoidosis                                                                                                                   unremarkable or indicated by history
• Associated with a Post-Infectious Etiology                                                                                     • Test for chlamydia and gonorrhea and/or urine
   – Upper respiratory tract infections (viral and                 – Ureteral obstruction from nephrolithiasis (renal colic)       culture
     atypical bacterial)                                           – Tumor                                                       • Rule out testicular torsion if indicated
• Associated with Trauma




                                                                                                                                                                           2
               Complications of Chlamydia and Gonorrhea




           Epididymitis Management                                                      Epididymitis Complications                                                                      Case 2
 • Likely cause is N. gonorrhoeae or C. trachomatis:                         • Infertility or Decreased fertility                                                                       History
    – Ceftriaxone 250mg IM x 1 + Doxycycline 100mg PO x 10 days
                                                                                – More common in bilateral disease                                          • 18 yo female presents with 5 days of vaginal
 • Likely cause is enteric bacteria:                                                                                                                          discharge, pelvic pain, nausea, and low grade fever.
    – Ofloxacin 300mg PO BID OR Levofloxacin 500mg PO QD x 10                   – Inflammation of the epididymis leads to epididymal and
                                                                                  efferent ductule obstruction                                                She douches frequently and has a history of gonorrhea
      days                                                                                                                                                    2 years ago. She had unprotected intercourse with a
 • Bed rest, scrotal elevation, and analgesics                                  – Occasionally spontaneously reversible                                       new partner 2 weeks ago
 • Hospitalize                                                               • Chronic epididymitis with chronic pain (15% of cases)
    – Severe pain suggesting complications or other diagnoses                   – Generally considered idiopathic                                           • A genital examination was performed
    – Fever                                                                     – Often unresponsive to antibiotics
    – Noncompliant
                                                                                                                                                            • Endocervical specimens were collected for chlamydia
                                                                             • Abscess formation and infarction of the testicle                               and gonorrhea tests
 • Sexual partner referral for evaluation and treatment
                                                                                – Inflammation of vas leads to vascular compromise                          • A wet mount revealed 20 WBCs per 400x and a
 • Schedule follow-up appointment in 72 hours                                                                                                                 pH<4.5, otherwise unremarkable
                                                                                – Less common since the use of antibiotics
                        CDC 2006 STD Treatment Guidelines                       – Surgical drainage and possibly orchiectomy




                                                                                         Female Pelvis Anatomy                                                                               PID
                                                                                         Normal                                                       PID




                    http://www.brooksidepress.org/Products/Military_OBGYN/
                    Textbook/Discharge/Discharge.htm




•Cervical motion tenderness and right adnexal tenderness were
       noted
                                                                                                                                                                           http://www.endo-resolved.com/images/adhesions.jpg
•Ceftriaxone 250mg IM x 1 and doxycycline 100mg PO BID x
       14d
•Scheduled for follow-up in 72 hours
                                                                                          http://iuhs-isa.org/USMLE/Reproduction/FemaleReproduction1.htm
•Requested to refer sexual partners for evaluation and treatment



                                                                                                                                                                                                                               3
               Complications of Chlamydia and Gonorrhea



                 PID                                                                     PID Etiology                                                PID Risk Factors
   Epidemiology and Clinical Findings
                                                                   STD
• Occurs in 1 million women in the US annually                     • More common (around 40-50%)                                  • Increased Risk
                                                                      – C. trachomatis                                               –   Douching
• Significant associated morbidity
                                                                      – N. gonorrhoeae                                               –   IUD
• Broad spectrum of symptoms:
                                                                   • Less common or frequency unknown (other 50-60%)                 –   Demographics (younger, lower SES, nonwhite)
   –   Asymptomatic
                                                                      –   Mycoplasma genitalium and M. hominis                       –   Prior PID and prior GC
   –   Painful intercourse, vaginal bleeding, vaginal discharge
                                                                      –   Ureaplasma urealyticum                                     –   Menses (loss of mucus plug, introduction of vaginal bacteria)
   –   Fever
                                                                      –   Anaerobes: Bacteroides fragilis, peptostreptococci         –   Bacterial vaginosis
   –   Abdominal pain, pelvic pain, adnexal pain
                                                                      –   H. influenzae                                           • Decreased Risk
• Proportion of clinical manifestations
                                                                   Puerperal, Post-abortion, Post-instrumentation                    – Pregnancy
   – Subclinical/silent 60%, Mild-Moderate 36%, Severe 4%
                                                                   Polymicrobial (Staphylococcus, Streptococcus, Coliforms,          – Oral contraceptives (for Chlamydia trachomatis only)
• Recent trends suggest a decrease in hospitalized cases             Clostridium perfringens, etc.                                   – Depo provera or Norplant (thicker cervical mucus)
  and outpatient visits




                                                                     PID: Indications for Hospitalization                          2006 CDC STD Treatment Guidelines
                      PID Evaluation
                                                                                                                                                     PID Hospitalized
                                                                  • Inability to exclude surgical emergency (ectopic            Recommended Parenteral:
       • Vital signs
                                                                    pregnancy or appendicitis)                                  • Clindamycin 900mg Q8 + Gent 2 mg/kg load then 1.5 mg/kg Q8
       • Speculum evaluation                                                                                                    • Cefotetan 2 g q12 or Cefoxitin 2 g q6 + Doxycycline 100mg
                                                                  • Pelvic abscess                                                po/iv q12
       • Gram stain of cervical swab low sensitivity and
         specificity and now not routinely done in women          • Pregnancy
                                                                                                                                Alternative Parenteral:
       • Test for chlamydia and gonorrhea                         • Inability to reliably take oral meds                        • Ampicillin/Sulbactam + Doxycycline 100mg po/iv q12
       • Bimanual and abdominal examination                       • Outpatient treatment failure                                ÆQuinolones are no longer recommended for empiric PID
          – Finding of cervical motion tenderness or adnexal or   • Clinical follow-up in 72 hours can not be arranged           treatment due to resistance in gonorrhea (updated in Apr 13,
                                                                                                                                 2007 MMWR)
            fundal tenderness sufficient for empific therapy      • Consider in HIV+                                            ÆAfter 24h improvement, change to Clindamycin 450mg po qid or
       • Determine need for hospitalization                          – more often: fail therapy, need change in therapy, need    Doxycycline 100mg po bid to complete total 14 days
                                                                       surgery, hospitalized longer (Cohen et al. JID 1998)
                                                                                                                                                         * New recommendation compared
                                                                                                                                                             to 1998 CDC guidelines




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             Complications of Chlamydia and Gonorrhea




   2006 CDC STD Treatment Guidelines                                                                                                            PID Complications: Infertility
                                                                        Other PID Management Issues
                  PID Outpatient
                                                                                                                                             • Inflammation and associated tissue repair from PID
                                                                  • Schedule outpatient PID for follow-up visit in 72 hours                    leads to tubal occlusion and tubal adhesion
• Ceftriaxone 250mg IM (or other 3rd gen cephalosporin) or
  Cefoxitin 2 g IM (plus 1 g oral Probenecid) + Doxycycline 100   • Refer sexual partners for evaluation and treatment                         (intraluminal and extraluminal)
  mg po bid to complete for 14 days w/ or w/o Metronidazole       • Some experts recommend rescreening for chlamydia                         • Of all infertile women, >15% are infertile due to
  500 mg BID for 14 days                                                                                                                       tubal damage from PID
                                                                    and gonorrhea 4-6 weeks after therapy completion if
                                                                    these pathogens are identified                                           • Infertility development by # of PID episodes
                                                                                                                                                – One episode: 8%
Æ Quinolones are no longer recommended for empiric PID
treatment due to resistance in gonorrhea (updated in Apr 13,                                                                                    – Two episode: 20%
2007 MMWR)                                                                                                                                      – Three episodes: 40%
                                                                                                                                             • Overall, estimated 20% of women with PID will
                                                                                                                                               become infertile
                     * New recommendation compared
                         to 1998 CDC guidelines
                                                                                                                                                                             Westrom et al. Sex Transm Dis 1992;19




                PID Complications                                                    PID Complications                                                Other PID Complications
                Ectopic Pregnancy                                                    Ectopic Pregnancy
                                                                                                                                             • Chronic pelvic pain
   • Implantation occurs at a site other than the                                                                                               – Overall occurs in 18% following PID
                                                                     • Diagnosis: standard is laparoscopy, but this is being
     endometrium                                                       replaced by algorithms incorporating ß-HCG, pelvic                       – Range 12 to >50% with one to multiple PID episodes
      – Tubal location 96%: rare ovary, cervical,                      ultrasonography, and uterine curettage                                   – Etiology for pain not clear, but likely related to pelvic
                                                                     • Treatment:                                                                 adhesions versus chronic tubular inflammation
        abdomen
                                                                        – Surgical: salpingectomy (partial or complete) via                  • Bowel obstruction secondary to adhesions
   • Abdominal pain and irregular vaginal bleeding are
     the most common presenting symptoms                                  laparotomy versus laparoscopy                                      • Perihepatitis (“Fitz-Hugh-Curtis Syndrome”)
   • Risk for ectopic pregnancy after PID increased 6-                  – Medical: methotrexate (folate antagonist that                         – Inflammation of liver capsule and adjacent peritoneum
                                                                          interferes with DNA synthesis and cell multiplication                 – Dense adhesions form between liver capsule and
     10 fold                                                              in actively proliferating trophoblasts: indicated if                    abdominal wall
   • Recent trends suggest a decrease in hospitalized                     mass (sac) unruptured and <4cm and patient                            – Usually due to chlamydia or gonnorhea
     cases in the US                                                      hemodynamically stable                                                – Importance in excluding other disease and revealing
                                                                                Gabbe: Obstetrics - Normal and Problem Pregnancies, 4th ed
                                                                                                                                                  underlying salpingitis
                                                                                                                                                                            Holmes et al. Sexually Transmitted Diseases, 3rd ed




                                                                                                                                                                                                       5
             Complications of Chlamydia and Gonorrhea




                           Case 3                                                                                                                                      Reiter’s Syndrome
                           History                                                                                                                     • Aseptic inflammatory polyarthritis that usually follows:
       22yo heterosexual male construction worker                                                                                                         – nongonococcal genitourinary infection (mainly Chlamydia,
   presents with worsening pain in his left ankle and right                                                                                                 possibly GC)
   second toe for 3 days. He recalls mild painful urination                                                                                               – infectious dysentery (Salmonella, Shigella, Campylobacter,
                                                                                                                                                            Yersinia, etc)
   and small amount of clear urethral discharge 3 weeks
   prior, which he attributed to “rough sex” after heavy                                                                                               • Linked to expression of HLA-B27 antigen in many but not
   alcohol intake. He complains of watery, itchy eyes, but                                                                                               all cases
   denies a rash.                                                http://www.immunologyclinic.com/jpg/30
                                                                 0_96dpi/NS10_300.jpg
                                                                                                           http://www.aafp.org/afp/990800ap/499.html
                                                                                                                                                       • Initial manifestations and natural course more aggressive
                                                                                                                                                         in HLA-B27 haplotypes
                                                                                                                                                       • Male predominance M > F 2:1




                                                                                             Reiter’s Syndrome                                                           Reiter’s Syndrome
                Reiter’s Syndrome
                                                                                           Clinical Manifestations
              Clinical Manifestations
                                                                 Other clinical findings
• Classic triad of findings (not in all patients)                   – mucocutaneous disease
   – associated trigger infection: urethritis or cervicitis or         • Eye: uveitis
     enteritis                                                         • Skin (dermatitis): keratoderma blennorrhagica, balanitis
   – rheumatoid factor-negative asymmetric polyarthritis                 circinata
      • knee, ankle, digits, sacroiliac, enthesitis (esp.              • Oral: painless mucosal ulcers
        achilles)                                                   – cardiac (uncommon)
   – conjunctivitis                                                    • heart block, myocarditis, pericarditis, aortitis
                                                                    – neurologic (rare)
                                                                       • peripheral neuropathy, meningoencephalitis
                                                                                                                                                                             www.emedicine.com/derm/topic207.htm




                                                                                                                                                                                                                   6
           Complications of Chlamydia and Gonorrhea




                  Reiter’s Syndrome                                          Reiter’s Syndrome Management
                                                                                                                                          Reiter’s Syndrome Management

                                                                         • Antibiotics                                                  • Anti-inflammatory agents
                                                                           – conflicting data on whether antibiotics alter natural            – indomethacin or NSAIDs (ASA and po steroids
                                                                             course of initial Reiter’s episode once it develops, but           usually ineffective)
                                                                             data suggest antibiotics may decrease recurrences                – intra-articular steroid injection
                                                                           – Antibiotics more efficacious when caused by STD                  – methotrexate, sulfasalazine, or immuran in
                                                                             rather than enteritis                                              severe cases
                                                                           – ideal length of therapy unknown, some treat for patients
                                                                             with arthritis for up to 3 months (STD etiology)
             http://www.rad.washington.edu/mskbook/axialarthritis.html




                          Case 4

    18 year old female developed pain in her left
shoulder and left elbow 3 days prior to admission
(PTA). This pain resolved a day later, but she then
developed pain in her left hip, left knee, right ankle and
right achilles tendon. This same day she developed
fever and about 15 skin lesions involving both hands
and feet. One day prior to admission, her right ankle
become hot and swollen. She denies any vaginal
discharge or pelvic pain. Her last menstrual period
                                                                            http://www.brooksidepress.org/Products/Military_OBGYN/
ended 5 days PTA.                                                           Textbook/Discharge/Discharge.htm                            http://www.dph.sf.ca.us/sfcityclinic/stdbasics/gonorrhea.asp
                                                                                                                                                                                                       www.aafp.org/afp/20050201/photo.html




                                                                                                                                                                                                                       7
               Complications of Chlamydia and Gonorrhea




                    DGI Epidemiology                                                    DGI Clinical Manifestations
                                                                                                                                                                       DGI Treatment
                                                                           • Most commonly present as “arthritis-dermatitis” syndrome
 • Disseminated infection from gonococcal bacteremia                       • Clinical features
 • Occurs in 0.5 to 3% of infected patients and                               – Fever                                                                   • Hospitalization is recommended initially
   prevalence decreasing                                                      – Migratory polyarthritis (monoarticular uncommon)                        • Recommended treatment
 • Certain GC strains possess biological properties                               • Wrists, knees, and small joints common                                 – Ceftriaxone 250mg IV/IM q24h
   facilitating dissemination                                                 – Septic arthritis in 1 or 2 joints
                                                                                                                                                        • Alternative treatment
 • Risk factors                                                               – Tenosynovitis
                                                                                                                                                           – Spectinomycin 2g IM q12h
    –    female                                                               – Rash: 5- 40 papules and pustules with hemmorhagic base, mostly
    –    complement defect(s): C5-C9 pathway (13% of patients)                  on distal extremities
    –    menstruation: pH and hormonal changes                                – GC culture positive up 80% from urogenital site, <50% from blood
                                                                                or synovium                                                           ÆQuinolones are no longer recommended for empiric DGI
    –    Pregnancy                                                                                                                                    treatment due to resistance in gonorrhea
                                                                              – RARE: meningitis, endocarditis, osteomyelitis, sepsis, ARDS
    –    ?initial site of infection: pharynx                                                                                                          Æ(updated in Apr 13, 2007 MMWR)
                                                                                                                                                                        CDC 2006 STD Treatment Guidelines




                         DGI Treatment                                                               Summary                                                                    Summary

• Inpatient regimens should be continued for 24 to 48
  hours after improvement begins, after which therapy                     • Epididymitis and PID usually occur when chlamydia,                     • Epididymitis and PID usually occur when chlamydia,
  may be switched to one of the following PO meds if                        gonorrhea, or other pathogens spread to the upper genital tract          gonorrhea, or other pathogens spread to the upper genital tract
  septic arthritis or complications are absent:                           • Compliance and follow-up in 72 hours must be ensured for               • Compliance and follow-up in 72 hours must be ensured for
   – Cefixime 400mg daily                                                   epididymitis and PID                                                     epididymitis and PID
   – Cefpodoxime 400mg twice daily                                        • Consider the need to rule out testicular torsion in patients           • Consider the need to rule out testicular torsion in patients
                                                                            evaluated for epididymitis                                               evaluated for epididymitis
   – Cefuroxime 500mg twice daily
                                                                          • Infertility and ectopic pregnancy are long-term sequelae of PID        • Infertility and ectopic pregnancy are long-term sequelae of PID
                                                                          • Reiter’s syndrome is a reactive arthritis following urethritis,        • Reiter’s syndrome is a reactive arthritis following urethritis,
• Oral therapy is continued until one week of antibiotic                    cervicitis, or enteritis that affects multiple organ systems and         cervicitis, or enteritis that affects multiple organ systems and
  therapy has been completed                                                requires antibiotics and anti-inflammatory medications                   requires antibiotics and anti-inflammatory medications
        CDC 2006 STD Treatment Guidelines (Update in Apr 13, 2007 MMWR)
                                                                          • Disseminated gonorrhea requires hospitalization initially              • Disseminated gonorrhea requires hospitalization initially




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