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					NOTES: 5/23/08
          Anti-cyclic citrullinated peptide is useful in the early diagnosis of rheumatoid arthritis and is equally
sensitive (@ 67%) but much more specific (95%) than rheumatoid factor (85%) (Nishimura K. Ann Int Med
2007;146:797) and predicts progression of undifferentiated arthritis to rheumatoid arthritis (van Gaalen FA, 2004).
          The earliest lesion in rheumatoid arthritis is an increase in the number of synovial lining cells with
microvascular injury.
          Complications of RA: Hammer toe, swan neck deformity, ulnar deviation, and Boutonniere deformity.
          Eye manifestations of rheumatoid arthritis include sicca complex syndrome, with decreased tear formation
as a result of secondary Sjogren's syndrome, and "corneal melt" with linear ulcerations usually at the limbus, leading
to corneal perforation.
          In RA, DIP joint involvement is distinctly unusual.
The most commonly involved joints in the rheumatoid hand are the PIPs, MCPs, and wrist.
Path: Microvascular injury with increased number of synovial lining cells is the earliest lesion.
RF is IgM gainst Fc portion of IgG. Not pathogenic. RF level is predictive of disease severity.
Anti-cyclic citrullinated peptide antibody detected by ELISA has a S & S of 62 & 92%.
RA has highest incidence of infective arthritis (more than Osteoarthritis, renal failure, or DM).
The first treatment is NSAIDs. If these fail, use methotrexate, which is the 1 st choice because of relatively rapid
onset. However, gold, pencillamine, antimalarials, sulfasalazine, low dose prednisone, and TNF blockers
(infliximab, etanercept, adalimumab) are also effective.
For methotrexate: frequent non-life threatening side effects: GI sx's. Less common: alopecia and stomatitis. Potential
effect on sperm: men should discontinue methotrexate 3 to 4 months before attempting conception. Serious adverse
effects (rare): hepato-toxicity, marrow suppression and interstitial lung disease: v WBC, v Platelets, pneumonitis,
and cirrhosis.
Lab monitoring: pregnancy test at baseline and CBC, platelet count, alkaline phosphatase, and AST. Repeat

Patients with adult Still's disease are RA negative.
In RA, RA antibodies are specific for Fc portion of human IgG.
Sensitivity: 75%.
RF is an IgM antibody recognizing Fc determinants of autologous IgG. It is not pathogenic.
Specificity low: sarcoid, Sjogren's, SBE, and vasculitic syndromes.
RA extra-articular CMs: vasculitis, RA nodule of aortic valve, cacchexia, pleuritis, and pericarditis.
Pleural effusions is often asymptomatic, exudative, WBC < 5,000 /mm3, very low glucose.

RA course at 10 years:
80%+ have residual disability or joint destruction.
50% have work disability.
Predictors of poor prognosis:
20+ inflammed joints.
^^ ESR
^^ Rheumatoid factor
Rheumatoid nodules
^ Age at onset
Sustained disease for more than 1 year
White females versus white males.
The median life expectancy of patients with RA is shortened by 3 to 7 years.
Contributors to decreased mortality are RA itself, increased CV risk, steroid use.

For early aggressive disease, treat with a combination of MTX and Anti-TNF alpha druge (e.g., etanercept).

MTX induced lung disease usually has fever and abrupt onset (Q 59, p 80).

Anti-TNF alpha has 6 side effects: Serious infections including disseminated TB, pancytopenia,
demyelinating disorders, exacerbations of congestive heart failure (hence contraindication to anti-TNF alpha in those
with EF < 50%), hypersensitivity to the
infusion or injection, and the development of drug-induced systemic lupus erythematosus.

Use capsaicin cream to control pain of arthritis, particularly hands & wrists.

NSAIDs are contraindicated in renal insufficiency.

NSAIDs should be taken 2 hours after ASA in ASH or CVA patients on ASA because they block the ASA-
antiplatelet effect.

Inhibitors of tumor necrosis factor alpha are effective in rheumatic diseases but infrequently cause infections, CHF,
lymphoma, and demyelinating syndromes (PMFLE). Infection: extra-pulmonary TB (e.g., renal TB) is the most
common form of TB. PPD positivity is set at 5 mm, and patients given INH for 9 months as indicated.
Pneumococcal and influenza vaccines are given to all patients. Patients with fever on anti-TNF-alpha drugs are
diagnosed and treated aggressively as if splenectomized. Afebrile patients are given oral drugs to be given at the
sign of first infection.

Lymphoma: There was a suggestive but not established increase in lymphoma in patients on adalimumab in a clinical

Celecoxib (Celebrex) has not been withdrawn (as of 2005) from the market, unlike other COX 2
inhibitors, but should be avoided in high risk cardiovascular patients, though it can be used in
patients on anti-coagulants (e.g., ASA).

The treatment of anti-phospholipid antibody syndrome in pregnancy with prior fetal loss criteria
(more than 3 prior to the 10th week, one spontaneous abortion of a normal fetus at or after the
10th week, or one premature birth of a normal fetus at or prior to the 34th week) should be treated
with ASA + LMWH (MKSAP 13 update).

Both SLE and Rheumatoid arthritis patients are at increased risk for CAD (MKSAP 13 update).

Gout: Cyclosporine, treatment of malignancy, meats, diuretics (HCTZ), obesity, beer, and
hypothyroidism are risk factors for gouty attacks and appropriate steps should be taken. All of
these decrease uric acid secretion with the exception of malignancy under treatment and meats.

30 yo man. Intermittent painful swelling of right great toe, left ankle, and left knee every month
relieved by ibuprofen.
Also, he has HPT and Crohn’s disease and takes azathioprine and prednisone 5 mg/day.
He drinks alcohol on weekends.
PE: Joint exam is normal.
Uric acid, CBC, creatinine, RF, LFTs, and electrolytes are normal. ESR=40.
What is the correct management: Watchful waiting, allopurinol, low dose colchicine,
indomethacin, or increase prednisone to 10 mg/day?
Ddx: Gout versus arthritis associated with IBD.
Watchful waiting and confirm gout with joint aspiration.
If confirmed, allopurinol is given.
Along with this give a prophylactic anti-inflammatory drug such as colchicine (low dose: 0.6 mg
BID), prednisone, or indomethacin. However, in this patient both indomethacin and colchicine
are contraindicated because of the IBD.

In under excreters (85% of gout patients; defined as less than 800 mg uric acid/day), no renal
insufficiency, no history of renal stones, and no problem with TID compliance, give probenecid.

If all of those criteria are not met, give allopurinol (which is QD). However, adverse effects are
>in 3% to 5%: rash, fever, diarhea, v WBC, and v platelets,
>rarely: a potentially fatal (25%) rash, fever, hepatitis, and renal failure, particularly when
given in standard dose allopurinol with renal insufficiency with diuretics.

What advice do you give patients who are taking allopurinol?
Answer: If a rash occurs, stop the drug and never restart it, else it may precipitate fatal TEN or
hypersensitivity syndrome with hepatitis and renal failure (25% fatality rate).
Tophi can occur on heart valves and spinal canal causing a parapersis.

Foods to eat: cheese, eggs and fruit. Foods to avoid: Diuretics, beer, and meats. Treat ^ TSH.

Pseudogout can be prevented by colchicine.

55 yo man
cc: intermittent attacks of joint pain lasting 1 week for past 10 years
PE: Hallux valgus deformity of both 1st MT joints.
PIP joints: left 1st and 4th and right 2nd and 3rd joints.
HARD NODULES OVER OLECRANON BURSA, swollen, not tender or warm.
X-ray: 1st MP bony erosion and 1st MT joint soft tissue density.
Dx: Is this RA, gout, pseudogout, osteroarthritis, or tenosynovitis universalis (?)
Ans: Gout. NOT RA.
Tophaceous deposits of monosodium urate over olecranon. Also can be found over the ear and
achilles tendon.
        Prednisone (to 30+ mg/d) is associated with alleviating symptoms of an acute gouty
flare within a few days and could be tapered during inter-critical periods.
        Allopurinol can cause TEN, hepatitis, agranulocytosis, and hypersensitivity syndrome
(erythematous rash, fever, hepatitis, eosinophilia and renal failure).

       Rheumatologic emergencies:
*In RA, loss of PIP or MP Joint Extension. >>>>> Tendon Rupture.
*Acute pain, swelling of single joint + fever. >>>>>>> Septic arthritis
*Tender spinous process.      >>>>>>>> Mets to vertebra. OR Vertebral Abscess.
*Sudden blindness w/HA or jaw claudication in elderly patient >>>>>> Giant cell arteritis.
*Bladder or bowel dysfunction with back pain >>>>> S.C. Compression, transverse myelitis,
cauda equina syndrome, or mets.
*Asymmetric lower leg swelling >>>>> DVT.
Arthritis & skeletal disease can antedate the clinical onset of IBD.

SLE (and RA) are major risk factors for coronary artery disease.

When starting a female pre-menopausal patient on warfarin, always remember to get a pregnancy
Beta blockers are contraindicated in Scleroderma and in Raynaud’s.
Prednisone is contraindicated in Scleroderma as it may facilitate scleroderma renal crisis.
ACEIs must be given in scleroderma to prevent renal failure.

In inflammatory myopathies, a muscle biopsy must be preceded by an MRI to identify the best
site for biopsy.

5 pulmonary renal syndromes:
1) Goodpasture’s syndrome: anti-glomerular basement membrane antibody.
2) Five Pulmonary-renal vasculitides:
        Wegener’s (C-ANCA/antiproteinase-3),
        Microscopic Polyangiitis, and
        Churg-Strauss (last two are P-ANCA/antimyeloperoxidase). (alveolar hem, ^ eos, FSGN,
mono-neuritis multiplex, subcu nodules.

Increased ESR is caused by :
1. Anemia
2. Neutralization of negatively charged sialic acid residues on RBC surfaces >> decreased RBC
repulsion, congregation of RBCs, and more rapid sedimentation. Causes of neutralization are:
a) Increase in fibrinogen (often from synthetic response of liver to inflammation or infection, or
drugs such as OCPs)
b) Increase in the ratio of total protein/albumen (e.g., myeloma)
A DECREASE IN THE ALBUMEN (e.g., from nephrotic syndrome) CAUSES AN INCREASE

                             joints                                            Other
                             MP joints (2nd & 3rd digits) & wrists
                             Symmetric, large joints, sacroiliitis.            Tophyrema Whippelii
Whipple’s Disease
                             Carpal tunnel syndrome, polyarthropy of large
                             limb joints with subchondral bone cysts &
                             erosions. Destructive arthropy of the C-spine
                             SBE can present as excruciating back pain or as
                             a peripheral non-septic arthritis.
                             Peripheral or Sacral                              Can Present With Oral Ulcers !!
Inflammatory Bowel disease

Lymphoma                                                                       Without MTX: Increased risk.
                                                                               With MTX: EBV + B cell lymphoma.
                             Ankles bilaterally
                             Hands, wrists, knees, ankles, shoulder            Unlike IBD, GI symptoms are painless
Celiac Sprue
       JOINT PATTERNS OF ARTHRITIS                          August 30, 2004
Rheumatoid Arthritis              Wrist, MP, PIP, Elbow, Shoulder (late),
                                  MT joint of foot, Tarsus, retrocalcineal bursitis, Tibio-talar joint
                                  Hip (late)
                                  Cervical Spine (watch for long tract findings)
                                  Cryco-aretynoid joint (laryngeal stridor) 30%

Parvo virus B19                   15% of new onset poly arthritis. Joint pattern is identical to RA. Lab Dx: IgM & IgG serology.

Osteoarthritis                    Knee, Hip, Base of Thumb (squaring), PIP (Heberden’s) & DIP (Bouchard’s–most
                                  1st Meta-Tarsal joint (Hallus Valgus & Rigidus)
                                  Shoulder (acromioclavicular joint)

Gout                              1st MT joint, knee, ankle, instep( 80% of all attacks in lower extremity)
                                  Wrist, finger, shoulder, hip, sternoclavicular joint, and even spine.

Pseudo-gout =                     Knee, Ankle, 1st MT joint (i.e., weight bearing joints), wrist.
calcium pyrophosphate             Hypothyroidism, hemochromatosis, hyperparathyroidism, hypomagnesemia, hypothyroidism
deposition disease (CPPD)         Chondrocalcinosis refers to finding calcification on x-ray.

Hemochromatosis                   MCP joints, 2nd & 3rd digits; Pseudo gout (particularly the knees)

Arthritis with inflammatory       Central: Spondylitis & sacroiliitis.
bowel disease                     Peripheral: Knee, MCP (ankle, elbow, shoulder, wrist, PIP)

Arthritis with psoriasis          Several types:
(= psoriatic arthritis)           *DIP (Distal type) (nails have pitting)
                                  *Oligoarticular asymmetric, Small & large type.
                                  *Symmetric poylarthritis (rheumatoid like)
                                  *Dactylitis (arthritis mutilans)
                                  *Spondylo-arthropathy (sacroiliitis & spondylitis)

Infectious arthritis              *Site of prosthetic surgery.
(monoarticular)                   *Site of Adjacent surgery (e.g., GYN operation can lead to pubic symphysis infection)
                                  *Site of prior non-infectious arthritis (e.g., RA [most common] or OA)
                                  *Overall, the knee is the site in 50%, then the wrist, ankles & hips.
                                  *Gonoccocal arthritis: Knee, wrist & ankle. (May have multiply infected joints.)

SLE                               Symmetric: PIP, MCP, wrists, knees. (Like RA) Effusions are common, deformities unusual
                                  (10% develop swan neck at MCP joints), and erosions are rare.
                                  HIP: aseptic necrosis if receiving steroids (also in shoulder & knee)

Reactive arthritis                MTP, PIP, DIP (sausage digits), wrists, sacro-iliitis, knee, achilles tendon.

Sarcoid                           Ankles & knees (less so: PIP joints, wrists, elbows). Acute onset.

Subacute bacterial endocarditis   can present as excruciating back pain or as a peripheral non-septic arthritis.

       Criteria for RA: (4+ of 7):
       1. Morning stiffness
       2. Symmetric arthritis
       3. Typical joint distribution (PIP, MP,
       4. Multiple joints
       5. Subcutaneous nodules
       6. Radiographic erosions
       7. +ve Rheumatoid factor or Anti-CCP

       Remember to check for Hepatitis C, which
       can give a positive rheumatoid factor and
       joint pain!!!
CLASSIFICATION OF SCLERODERMA                                   August 30, 2004
                    Skin involvement with      Pulmonary HPT           Internal Organs               AB
                    Raynaud’s & dilated
                    nailfold capillary loops

Diffuse Cutaneous   YES.                       No                      Early:                        ANA in 98%
Scleroderma         Truncal & acral skin                               Interstitial Lung disease.    Anti-Scl-70
                    involvement                                        Renal disease (ACEI block)    (Anti-
                    Puffy, hidebound skin.                             Wide mouth diverticulae of    topoisomerase
                    Tendon friction rubs.                              Colon.                        I) in 30%
                                                                       Late:Ca of lung increased.

Limited Cutaneous   YES.                       YES but late in 15%.    Late, if at all:              Anti-
Scleroderma.        Limited to hands, face,                            GI disease or                 Centromere Ab
                    feet & forearms.                                   Interstitial Lung Disease.    in 70%.
                    CREST* in some.
                    YES. With evidence of                                                            Any of the
                    digital ischemia.                                                                above.
                    NO, except may have                                Early: Interstitial Lung      Any of above
Scleroderma sine
                    Raynaud’s                                          Disease, Renal disease, GI
                                                                       disease, myocardial disease
                    Either Diffuse or          SLE, RA,
Overlap syndromes
                    Limited.                   dermatomyositis,
                                               vasculitis, Sjogren’s
*CREST= Calcinosis, Raynaud’s, Esophogeal dysmotility, Sclerodactyly, Telangiectasia. This
occurs in some, but not all, patients with Limited Cutaneous Scleroderma.

Polyarteritis Nodosa:
Hypertension and/or renal insufficiency                    60%
Arthritis, arthralgias or myalgias                         64%
Peripheral neuropathy                                 51%
Abdominal pain, GI bleed, or ischemia or
infarctions of bowel, liver or pancreas                    44%
Rash, purpura, livido reticularis, uclers or Raynaud’s     43%
CHF, MI, or pericarditis 36%
CVA or seizures                                            23%.
Hepatitis B                                                25%
Hepatitis C                                                5%
Best dx for PAN is by biopsy of affected nerve which will show vasculitis.

(Hepatitis C is associated with essential cryoglobulinemia.)

Four or more are required. There are 11 which can be thought of as:

Skin-mucous mb - 4
Arthritis-Serositis - 2
Hem, cns, kidney - 3
Autoimmune & ana - 2

1. Malar rash
2. Discoid rash: PASTE: Plugging, Atrophy, Scarring, Telangiectasias, Erythema
3. Photosensitivity – UVA and UVB so get sun screen that blocks both. Coppertone Spectra 3.
4. Ulcers (painless)
5. Arthritis: HAM: Knees & Hands, Asymmetric, Migratory, Usually Non-Deforming. If
deforming in the hands, they are reducible.
6. Serositis – pericarditis and pleuritis
7. Hematologic – hemolytic anemia (warm autoimmune, Anti-IgG and Anti-C3),
thrombocytopenia, lymphopenia.
8. CNS: Seizures & Psychosis.
9. Glomerulonephritis (proteinuria, RBCs, RBC casts): I. None, II. Mesangial proliferative, III
Focal proliferative, IV Diffuse proliferative GN, V Membranous GN.
10. Autoimmune: Anti-DS DNA, APLA, LAC, False + VDRL, Anti-Smith AB.
11. Positive ANA (usually peripheral pattern).

Other symptoms AND signs:
fatigue 95%
Increased AST and ALT (10 x nlormal) (Liver inflammation; hence increase in fibrinogen and
increase in ESR!!)
vasculitis (bleeding or perforation of GI tract in 5%)
conjunctivitis or sicca syndrome in 15%
Venous thrombosis in 10%
Cerebrovascular disease in 10%
SLE causes a transverse myelitis manifest by cauda equina syndrome (difficulty urinating,
incontinence, decreased sphincter tone, erectile dysfunciton) and lower extremity weakness (Q
64, p81, Q 27, p y70).

In general, the alopecia associated with active lupus may improve with treatment of the disease,
except with discoid lesions, in which there is follicular plugging and scarring that may result in
permanent alopecia.

SLE eye involvement: retinal vascular disease, cotton-wool spots (cytoid bodies) or retinal
exudates from distended and disrupted axons resulting from anoxia.
Hemorrhage is commonly observed in the retina.

Renal biopsy is not necessary in SLE patients whose renal function is rapidly deteriorating when
they have an active sediment.
Indications for biopsy: a) failure to respond to glucocorticoid therapy and b) patients with mild
clinical disease (to determine if they have active, severe, inflammatory lesions, which might
respond to therapy).

In Antiphospholipid antibody syndrome, keep the INR at 3.0 (Q53, p79)

Athralgias of wrist and clubbing of digits may be hypertrophic osteoarthropathy with periosteal
new bone formation, due to lung cancer, suppurative lung disease, congenital heart disease; relief
of the feet with elevating the legs is said to be pathognomonic. Glucosamine relieves OA pain.
To diagnose sarcoid, obtain transbronchial lung biopsy, showing a mononuclear granulomatous

This is dermatomyositis: heliotrope                          This is Pemphigus Vulgaris
Serum aldolase is elevated in dermatomyositis.


Jaw claudication due to ischemia to the lingual arteries <> temporal arteritis.

43 yo man
right hand weakness x 2 days (unable to extend right wrist), HPT x 2 months, weight loss, HA,
post prandial abdominal pain. H/o IVDU.
Lab: ESR 88, AST 154, ALT 176.
Dx: Polyarteritis nodosa + Hepatitis B (the latter in 30% of PN; hepatitis C is NOT in PN)
Test: Biopsy the affected nerve.
The pathology of polyarteritis consists of fibrinoid necrosis within medium and small sized
vessels with a variable cellular infiltration, primarily neutrophils.

55 y.o. man
CMs: fever, ^ BP, renal failure, abdominal pain (bleeding or bowel infarction), Livedo
reticularis, digital gangrene.
*Invasive arterial studies, such as cardiac catheterization (days)
*Anticoagulant therapy (weeks).
Lab: ^ESR, Creatinine, CK, WBC, Eos, vHgb, proteinuria, eosinophiliuria.
Dx: Cholesterol emboli. DDX: Polyarteritis nodosa.
(Most cholesterol emboli originate in the abdominal aorta or iliofemoral arteries, but cardiac and
thoracic aorta sources have been described. )
Rx with observation. Steroids and cytotoxic agents are futile.

63 yo woman
hempotysis, SOB, fatigue,10 lb wt loss, RR 44, P 120, BP 170/110, O2 sat 78%
Hgb 10, Creat 3.2 U/A 1+protein, 30 RBCs, occ RBC casts
CT: diffuse alveolar infiltrates
P-ANCA + (antimyeloperoxidase titer is 126 U/ml.)
Dx: microscopic polyangiitis. However, this patient could easily have Goodpastures syndrome
because P-ANCA and systemic symptoms occur in a minority of Goodpastures patients;
however, they are less likely to have P-ANCA and systemic symptoms than patients with
microscopic polyangiitis. DDx: Goodpastures (usually has no systemic symptoms), Wegeners,
PAN, cryoglobulinemia.
Pathology: no granulomatous inflammation (unlike Wegener’s), pauci-immune (unlike
Rx: prednisone and cyclophosphamide

A 65-year-old man admitted for cholecystitis and undergoes cholecystectomy.
Post op: low-grade fever, intermittent severe crampy abdominal pain, and purpuric lower
extremity skin lesions.
On the 10th hospital day, he experiences a right footdrop and diplopia.
Dx: Possible necrotizing vasculitis.
Confirmatory tests: arteriography of celiac and mesenteric arteries. Also, biopsy of skin or sural

Palpable purpura (multi-organ involvement may occur but usually just skin).
Bx: small vessel leukocytoclastic vasculitis. = Hypersensitivity vasculitis.
20 y.o. man
URI (Q 18, Rheum, MKSAP 12)
Fever, symmetric polyarthritis of wrists, elbows & ankles
Palpable purpura on hands and feet.
Severe abdominal pain with hematemesis.
Increased LFTs, Normal platelet count.
On biopsy this is a leukocytoclastic vasculitis. IgA may be found.
DX: Henoch-Schoenlein purpura (NEJM 2004;351:278..
Self-limited illness with prolonged renal insufficiency; death is an uncommon outcome.

Infiltrates consisting of atypical lymphoid and plasmacytoid cells are characteristic of
lymphomatoid granulomatosis, not Wegener's granulomatosis.

62 man
Rt knee pain, swelling. Obesity, DM2 and HPT.
Moderate effusion in right knee, minimal warmth, and no redness. Effusion is pale yellow color,
good viscosity, a WBC count < 2,000, and normal glucose.
x-ray: osteophytes and joint space narrowing.
Dx: Osteoarthritis 2nd to obesity.

60 y.o. man
With H/O Sjogren’s syndrome
Develops night sweats, parotid gland enlargement, v WBC, v C4, and cryglobulinemia.
Dx: Low grade B cell lymphoma.

In Sjogren’s, what medication can be used for dryness?
Ans: Pilocarpine.

Which exam is most specific for lumbar disk hernation?
Ans: Cross straight leg raise sign. This maneuver produces pain in the opposite leg or buttock.
Stretches L5, S1 and the sciatic nerve.
 Back disease      Worse With             Better With                   Other

 Herniated disc    Lumbar flexion,        Leg extension, lying down     tends to be localized, unilateral
                   standing, sitting
 Spinal stenosis   Leg extension,         leg flexion, sitting, or      Tends to be diffuse, bilateral. Surgery is cost
                   walking                stooping                      effective (Otsteson AnnIntMed2008;149:845).

Relapsing polychondiritis can be complicated by CVA (from vasculitis), respiratory failure, glomerulonephritis, and
aortic regurgitation. Rx: Prednisone 50 mg/day.

In low back pain, what are the risk factors for serious cases of spine pathology, such as infection, malignant disease,
and trauma? Ans:
Intravenous drug use or chronic infection >> osteomyelitis
Bed rest without relief
Duration of pain of more than 1 month
Urinary incontinence or nocturia >> Cauda equina
Pain that increases with standing and is relieved by sitting >> spinal stenosis (surgery is more likely to be
Chronic steroid use.>> aseptic necrosis

45 y.o. Saudi Arabian, Turkish, Japanese, Korean, Chinese man.
Painful oral ulcers, genital ulcers, erythema nodosum, CNS changes, anterior uveitis, retinitis (causing blindness),
Dx: Bechet’s disease.
Ddx: IBD, Herpes simplex, Sweet’s syndrome (neutrophilic infiltration of dermis)
Uveitis can progress to blindness rapidly. Rx is with steroids and azothiaprine.
Rx: prednisone and azathioprine.

ILD. (ILD occurs in association with Antibody to histdyl transfer RNA synthetase or anti-Jo-1.)
44 y.o. woman from Middle East.
Intermittent Pleuritic chest and abdominal pain, accompanied by fever. Occ. Pain and swelling of knees. Renal
failure. Cr. 3.4. 4+ Proteinuria.
Negative ANA and other serologies.
Renal biopsy: congo red stain gives apple green birefringence.
Dx: FMF.
Rx: Colchicine.
Has AA amyloid (unlike myeloma which has AL amyloid).

Wegener’s can have 8th nerve involvement with tinnitus.
The highest yield in diagnosis of Wegener’s is lung biopsy. The upper airway shows granulomatous involvement
without vasculitis. C-ANCA is not considered sufficient for Dx when lung pathology is present.

23 y.o. man. (Median age; 3 x more likely to be a man than woman)
Back and buttock pain, morning stiffness decreasing with activity, recurring after resting.
Cauda equina syndrome (late). 25% will have work disability.
25% mono or aligo arthritis.
Schoeber's test: decreased LS flexion.
Anterior uveitis (the most common extra-articular manifestation and occurs in 30%; can progress to blindness),
apical lung fibrosis, conduction disturbances, and aortic insufficiency.
CT (note: MRI not necessary and is more expensive): Areas of edema at entheses in the inter-osseus ligaments and
joint capsule. Sacroiliac sclerosis and/or erosions (widening).
Sacral-illiitis is one of the earliest CMs of AS.
Late: Fusion.
Dx: Ankylosing spondylitis
Criterion for DX:
Sacroiliitis by radiography and
1. H/o inflammatory back pain
2. Limitation of LS motion sagitally and frontally.
3. Limitation of chest expansion.
Rx: After NSAIDs, the most effective treatment is infliximab (Remicade) and etanercept (Enbrel), TNF blocking
agents, even in long-standing disease. Sulfasalzine and methotrexate have modest benefit.

Psoriatic arthritis has 5 joint patterns: 1) DIP arthritis, 2) arthritis mutilans with pencil in cup deformity on
radiology, 3) asymmetric oligoarthritis, 4) RA-like symmetric polyarthritis, and 5) sacroiliitis (axial involvement).
Nail changes are prominent in 90% of psoriatic arthritis.

CDC criteria for chronic fatigue syndrome:
1. Fatigue: unexplained, persistent, relapsing, not alleviated by rest, and disabling.
4+ of the following over 6 months (not necessarily continuous): Memory impairment, ST, HA, tender cervical or
axillary adenopathy, muscle pain, multiple arthralgias, unrefreshed sleep, post exertional malaise lasting 24 hours.

64 y.o. AA man
CHF, renal failure, poly neuropathy.
Raised waxy papules in axilla and groin.
TP 9.0 albumin 3.2, HCT 24%, 3+proteinuria, US showing thick left ventricle with normal EF.
Dx: MM.
Test: Bone marrow biopsy for plasma cells.
AL amyloid on Congo red staining with apple-green birefringence in heart, kidneys, liver and CNS.

45 y.o. man in ICU x 3 weeks.
Painful elbow, with swelling, fluctuance, and warmth.
Dx: Olecranon bursitis.
Test: Aspiration for bacteria and crystals.

A 32-year-old homosexual man
Painless oral ulcers.
Left ankle pain with tenderness, swelling, and marked limitation of motion.
Achilles tendonitis.
Painful swelling of the left second and third MTP, PIP, and DIP joints.
A clear mucoid penile discharge
Hyperkeratosis of the soles and palms ("keratoderma blenorrhgica")
Multiple erythematous plaque lesions with scaling over the trunk, arms, and legs
Dx: Reactive arthritis. DDx is GC.

In long-term follow-up of reactive arthritis:
*About 45% of patients develop chronic joint symptoms with episodes of acute recurrence.
*Up to 25% will no longer work or are forced to change jobs.
*Chronic heel pain is the most common symptom.
*Predictors of increased likelihood of symptoms: HLA-B27-positivity and Shigella reactivity.

26 y.o. woman with new sexual partner.
It has NOT been shown related to GC, but is related to Chlamydia, Salmonella, Shigella, Yersinia, Campylobacter,
and HIV.
Painful red eye resolving spontaneously. Uveitis or iritis. The latter can lead to blindness if not treated.
T 100.8.
Right knee: warm with large effusion.
Wrist extensors: tenderness at insertion sites.
Achilles tendonitis.
Clear vesicles on an erythematous base on palms and soles (Keratoderma blenorrhagica). Indistinguishable from
HCT 35%. ESR 36.
Possible Proteinuria 2nd to AA amyloidosis.
Dx: Reactive arthritis.
DDx: RA, GC, psoriatic arthritis.
Test urine for Chlamydia and test serum for HIV.
Rx: refer to ophthalmologist for slit lamp exam. Iritis does not parallel other symptoms. Treat with mydriatics and
local steroids.

58 y.o. woman.
Right shoulder pain.
Tender to touch.
Limited passive and active ROM.
Causalgia may co-exist.
Dx: Adhesive capsulitis.
Rx: NSAIDs, steroid inections, PT, early mobilization.
Resolves spontaneously in 1 – 3 years.

                Setting    location               lesion                                  Other

 Pemphigus      elderly    oral mucosa(>50%),     flaccid blisters,      Intra-           Mortality 75% before
 vulgaris                  face, scalp, trunk,    normal or red base,    epidermal IgG    prednisone 70mg/day.
                           axilla                 mild pressure          against
                                                  causes new blisters    desmogleins
 Bulllus        elderly   Lower abdomen,        Tense blisters           IgG against      Multiple exacerbations &
 pemphigoid     *         groin,                                         subepidermal     remissions. Also,
                          flexor surfaces.                               basement         prednisone.
                          Oral lesions in 30%                            membrane
*Bullous pemphigoid is the most common blistering disease.

In SLE, patients with mild renal manifestations should have a kidney biopsy to determine if they have active severe
inflammatory lesions that might respond to therapy.

50 y.o. woman
Raynaud’s. Arthralgias, arthritis, dysphagia for solid foods.
Anti-centromere antibodies in high titers. No antiribonucleoprotein antibodies.
Dx: Limited scleroderma.

In SLE and pregnancy, exacerbations occur in 1st trimester and immediate post partum.
30% end in spontaneous abortion.
37 y.o. woman
Raynaud’s syndrome (systemic sclerosis)
Proximal muscle weakness (DM/PM)
Sausage like fingers
Alopecia (SLE)
Red patches on knuckles (DM)
Facial telangiectasias (SLE)
Crackles on lung exam (Systemic sclerosis)
CK is 270.
Anti-U1-RNP (AKA: Extractable nuclear antigen) (seen in 100%) RF+ at 1:1600; ANA + at 1:1500 with speckled
High titer to ribonuclease-sensitive ribonucleoprotein component of extractable nuclear antigen.
Dx: MCTD. This is the overlap of SLE, polymyositis, RA, and diffuse scleroderma.

51 yo woman
raised 2 x 2 cm rash on trunk
pain in her shoulders
prior erythema nodosum
elevated serum calcium
Dx: sarcoidosis

Sarcoid CMs: Organ involvement: Lung (95%), lymph nodes (15%), skin (16%) or eyes (12%)..
Skin: violaceous plaques on cheek and nose. = lupus pernio
Eyes: Anterior uveitis
Neuro: Cranial 7 or other cranial nerve palsy (Cr. 8… hearing loss)
Liver: ^ transaminases in 10%.... even hepatic failure.
Lytes: Hypercalcuria in 40% of sarcoid patients (obtain 24 hour urine in all patients)
Hypercalcemia in 10%
(Macrophage enzyme converts 25OH D to 1,25 HOD.)
Cardiac: Complete heart block & sudden death!!!

40 y.o. Scandinavian, Irish, or Puerto Rican woman
Erythema nodosum, arthralgias, and bilateral hilar adenopathy.
Dx: Lofgren’s syndrome of sarcoidosis.

Case 40 y.o.
Fever, parotid enlargment, anterior uveitis, and facial nerve palsy.
Heerfordt-Waldenstrom syndrome of sarcoidosis.

5% of patients with sarcoid have cardiac abnormalities with arrhythmias including heart block, syncope, and sudden

Asthma, allergic rhinitis, FSGN, mononeuritis multiplex, subcutaneous nodules, pulmonary hemorrhage, eosinophilia
< > ChurgStrauss syndrome (a systemic necrotizing vasculitis)

Latex allergy: diagnosis requires RAST IgE testing to natural rubber latex or a patch test using part of a latex glove.
Latex-fruit cross-reactivity may occur with banana, avocado, passion fruit, kiwi, and chestnut, but not celery. Warn
the patient.

Child with only urticaria and angioedema in response to sting. Management: Low probability of
Adult with only urticaria or angioedema in response to sting. Management is venom testing and
prophylaxis and anaphylaxis kit. See ch 298, Harrison's

Treatment of anaphylaxis:
Airway, epinephrine 1:1,000 i.m.(repeat Q 15 minutes x 3), epi drip 1:10,000 at 5 mcg/min (1-10) OR
norepinephrine (levophed) 5 mcg/min (0.5-30), diphenhydramine 25 mg i.v. Q 4 hours, cimetidine 300 mg Q 8 hrs,
hydrocortisone 100 mg i.v. Q 6 hours.
42 yo man, cc: knee and hand pain and swelling x 18 months
Exam: 2nd and 3rd MP joint swelling
Osteophytes (hooked projections) from the 2nd and 3rd MP joints.
Dx:CPPDD r/o hemochromatosis and hyperparathyroidism.

Arthritis of wrist, MTP joint, or knee.
Joint effusion: cloudy and watery joint fluid. WBC 4,800/L, crystals that are rhomboidal and weakly positively bi-
Radiologic manifestations: 1) cystic changes in bones of the wrist, with triangular cartilage calcification, 2)
periarticular calcification of the 1st MTP joint, 3) in the knee, severe degenerative changes and subarticular cysts,
4) linear calcification of hyaline knee cartilage.
DX CPPDD (pseudogout).
Correlates: hyperparathyroidism, hemochromatosis, hypothyroidism, hypomagnesemia, and hypophosphatasia. Also
gout, familial hypocalciuric hypercalcemia
RX of these does not regress the calcinosis.

Colchicine 0.6 mg BID has been shown to reduce the frequency of pseudogout attacks in CPPD.
NSAIDs or colchicine may be used in acute attacks.

Rupture of the long head of the biceps: Indications for surgery:
*Heavy manual labor.
Otherwise, surgery is not required because the short head of the biceps and brachioradialis remain intact and provide
most of the power for elbow flexion.

Collagens are the most abundant protein in the human body and constitute approximately 30% of
the total protein. They serve diverse functions. Defects of type I collagen, the most abundant
collagen type, have been associated with genetic syndromes, including Ehlers-Danlos syndrome
and osteogenesis imperfecta. In the formation of specialized collagens, collagen interacts with
other components to make functional basement membranes. Type II collagen is the major
fibrillar component of hyaline articular cartilage, and proteoglycans are the major noncollagenous
structural proteins associated with elastic resistance to compression of this tissue

NSAIDs inhbits cyclooxygenase, the enzyme that catalyzes the conversion of arachidonic acid to prostaglandins,
prostacyclin, and thromboxanes, leading to vasoconstriction.

Mononeuritis multiplex: wrist and foot drop (radial and peroneal (or sciatic) nerves) and/or cranial nerve
abnormalities <> polyarteritis nodosa (also seen in SLE or Wegener's).
Case: 55 y.o. woman.
Stiffness and soreness in the shoulder and hip girdle.
NO weakness.
v Hgb. ^ESR. Normal CK and normal electromyogram.
Dx: PMR.
Weakness suggests a proximal myopathy such as polymyositis.

B cells directly secrete antibodies and require a variety of cytokines for activation, proliferation, and differentiation.
Within their surface membranes, B cells have receptors, allowing them to recognize foreign antigenic determinants.
These receptors are membrane immunoglobulins of unique specificity.
Antigenic determinants are located on chromosomes 2, 14, and 22.

Radiography of lumbosacral spine films may show the following:
*In myeloma, focal or generalized decrease in bone density.
*In osteomyelitis, the earliest change is localized rarefaction of the vertebral end plate.
*In metastatic disease, involvement is the vertebral body but sparing the intervening disk space.

Collagens are the most abundant protein in the human body and (30% of the total protein).
Type I collagen <> Ehlers-Danlos syndrome and osteogenesis imperfecta.
Basement alterations are frequently found in diabetes mellitus.
Phagocytes may function to clear circulating immune complexes.
Activation of both complement terminal components C6, C7, C8, and C9, attaches to the membrane and induce the
formation of pores, with ultimate cell lysis.
Recurrent sepsis with Neisseria species <> deficiencies of C5-8 (terminal components).

Low CH50 and C2 deficiency is by far the most common complement deficiency State <> Several rheumatic
diseases, SLE, vasculitis, and polymyositis.

IL1 and IL2 produces fever, prostaglandin release, and bone resorption.
T cells produce IL2 which stimulates proliferation of T and Natural Killer Cells.
TNF alpha produces fever, macrophage activation and bone resorption.
IL6 induces antibody secretion.

Vasculitic skin lesions are common and do not portend CNS vasculitis.
Pleural fluid is usually transudative.
Alopecia associated with active lupus may improve with treatment of SLE, except with discoid lesions, in which
follicular plugging and scarring may cause permanent alopecia.
A number of patients with end-stage renal disease caused by lupus have successfully received
kidney transplants.
IgG anti-SS-A (Ro) antibody <> congenital heart block.

Corneal melt (linear ulcerations at the limbus and corneal perforation secondary to decreased tear
formation)- rheumatoid arthritis.
Ischemic optic atrophy (posterior ciliary and pial artery networks)- temporal arteritis.
Retinal vascular disease (cotton wool spots and hemorrhage) - SLE.

Destruction of the tufts of the terminal phalanges is commonly seen in scleroderma, vinyl chloride disease, and
secondary hyperparathyroidism.
Premature or exaggerated osteoarthritis, including osteophyte formation - acromegaly.
Punched-out erosions, overhanging bone around deposits of monosodium urate <>gout.
Multiple foci of metaplastic hyaline cartilage within the synovium - Osteochondromatosis.

Patients on long-term (8-10 years) chronic dialysis:
** ^PSO4 > ^ PTH > osteolysis of the pharyngeal tufts, demineralization of the bones of the appendicular and axial
skeleton, and pathologic fractures.
** Deposition of á2-microglobulin amyloid within the carpal tunnel is associated with carpal tunnel syndrome and
deposition in the bone with subchondral cysts.
** Deposits of calcium salts (^ PO4xCa) in the skin and joints may lead to pruritus and periarthritis. .

In rheumatic fever, erythema marginatum occurs in 10 to 20% of children and rarely in adults.

Pattern: first MTP joint, first interphalangeal joint, ankle and instep area <> Gout.
Ankles, instep and knees <> Reactive arthritis.
Digital clubbing, periostitis, and painful swelling of bones and joints (hypertropic osteoarthropathy) -- lung
malignancies and pulmonary infections.

Acute arthritis of ankles and knees and less frequently the PIP joints of the
hands, wrists, and elbows -- Sarcoidosis.

In hemodialysis, motor weakness and atrophy of the muscles of the thenar eminence <>
Deposits of á2-microglobulin in the carpal tunnel.

Proximal Myopathy with an elevated creatine kinase level: Hypothyroidism vs. polymyositis.
Transient Raynaud's phenomenon-like illness -- acromegaly.
Painless limitation of joint mobility in PIP and DIP joints <> diabetic cheiropathy-DM 1 & 2.

Low CH50 & C2 deficiency<> SLE-like syndrome, vasculitis and polymyositis-like syndromes.
Antibody to 29-kD serine protease <> Wegener's granulomatosis (correlates with severity).

25 y.o. man.
Unaccustomed strenuous exercise OR initiation of dialysis OR B. burgdorferi infection OR spontaneous onset >>
tender, symmetric induration of the skin with retraction of subcutaneous tissue (scleroderma-like).
Lab: eosinophilia, ^ ESR, ^ gammaglobulin (polyclonal).
Dx: eosinophilic fasciitis.

Intense and incapacitating generalized myalgia, fatigue, memory loss, leukocytosis, eosinophilia (early), and history
of ingestion of l-tryptophan
Dx: Eosinophilia-myalgia syndrome. Ddx: toxic oil syndrome (rapseed oil), Trichinosis.

59 yo well controlled diabetic woman
cc: Painless triggering and locking of her right index and left ring finger.
18 months ago a painful shoulder improved with PT.
Right carpal tunnel 6 months ago
Asymmetric Heberden’s nodes
Sclerodactyly with thick tight waxy skin
Positive prayer sign
Thickening of some flexor tendon’s (early dupuytren’s contractures)
Dx: Cheiro-arthropathy or (Diabetic) limited joint mobility syndrome. The sclerodactyly is “pseudo-scleroderma of
Buschke” and is part of the syndrome. Differential diagnosis includes carpal tunnel syndrome, osteoarthritis,
dupuytren’s contractures, flexor tenosynovitis, reflex sympathetic dystrophy. Prevalence of cheiro-arthropathy in
diabetics occurs in 4% to up to 3/4 of type 2 diabetics and up to ½ of type 1 diabetics. The prevalence in the general
population is 4% to 14%.
Cheiroarthropathy is correlated with micro-vascular complications of diabetes and may be caused by local ischemia.
It is also associated with restrictive lung disease.
Treatment is physical therapy.
(Aljahlen M, Post Grad Med 1999).

47 yo man on omeprazole (GERD), erythromycin (acne), terazosin (prostatitis) and ciprofloxacin (prostatis)
develops acute tendonitis. Eventually, it ruptures. What is the etiology?
Ans: cipro. Tendonitis and tendon rupture have been well documented with the quinolones.

40 yo man
Cough, fever, rash with subcutaneous nodules, and ataxia (or cranial nerve abnormalities)
CXR: Nodules in Mid and lower lung fields.
Serology: EBV positive
Biopsy: Polymorphic lymphoid infiltrates of tissue, lymphoid infiltrates of arteries and veins, areas of central
Dx: Lymphomatoid granulomatosis, a B cell lymphoma.
Rx: Steroids and cyclophosphamide.
Survival is 1 to 6 years. Neurologic involvement has a worse outcome.
Condition     Spondyl Sacroi Other joints Extra-articular Eyes GI                                  GU         pulm Vascu        Rx
              itis    liitis              Skin                                                                onar lar
Ankylosing         4+          4+       hips & knees                           Uveitis    +        +          Apic    aortiti   Exercise
spondylitis                                                                                                   al      s         NSAIDs
                                                                                                              fibro             Sulfasalazin
                                                                                                              sis               e
Reactive         None          1+       fingers            circumate           Conjun     Gastroe urethriti                     NSAIDs
arthritis                               (dactylitis)       balanitis           ctivitis   nteritis s                            Sulfasalazin
(Reiter’s syndr)                                                               uveitis    (1)                                   e
                                        Oligoarthritis     keratoderma                                                          MTX
                                        of lower           blenorrhagicum

Psoriatic          1+          1+       Arthritis         Psoriasis            +                                                NSAIDs
arthritis                               mutilans &                                                                              Exercise
                                        pencil-in-cup                                                                           MTX
                                        on x-ray.                                                                               Leflunomid
                                        Rheumatoid                                                                              e
                                        like distribution                                                                       Etanercept
Enteropathic       1+          1+       Dactylitis.        Keratoderma         Uveitis    ++++     +                            NSAIDs
arthritis                               Polyarthritis of   blennorrhagicum                                                      Sulfasalazin
                                        medium &                                                                                e
                                        small joints:      Pyoderma                                                             MTX
                                        Celiac,            gangrenosum                                                          Exercise
                                        of large joints:
                                        IBD. (Q8,
                                        MKSAP 12)
            Common features of these seronegative spondylo arthropathies are enthesitis, infectious triggers and extra articular
            Dactylitis occurs with reactive arthritis and psoriatic arthritis.
            Pencil in cup occurs with psoriatic arthritis.

            Rheumatic diseases with uveitis: , ankylosing spondylitis, reactive arthritis, enteropathic arthritis.

            SHOULDER-ARM-HAND syndromes:
            Syringomyelia (symmetric bilateral symptoms),
            Cervical entrapment,
            Thoracic outlet syndrome (cervical rib),
            Pancoast tumor,
            Radial nerve palsy (Saturday night palsy with wrist drop), and
            Carpal tunnel syndrome.

            40 yo man cc shoulder pain following carrying of a platter of lunch items.
            PE: He has pain on passive abduction to 90 degrees. At 45 degrees, he resists abduction against force but
            minimal pain. No pain on adduction.
            Dx: Impingement syndrome.
            DDX: rotator cuff tear, subacromial bursitis, thoracic outlet syndrome, osteoarthritis of the shoulder.
            Greater pain on active abduction than on passive abduction would point to subacromial bursitis or rotator
            cuff tear. Pain from the base of the neck over the top of the shoulder and down the arm would point to
            thoracic outlet syndrome. Osteoarthritis of the shoulder is rare.
55 yo diabetic woman cc: stiffness in right shoulder. Can not put on her coat. Can’t reach overhead in
coat closet.
Patient had a fracture with a sling and since has lost rom in shoulder. There is minimal pain.
On passive abduction, the arm can be moved only to 75 degrees. Inability to scratch the back at T 10.
NFL touchdown side on right. There is mild pain.
Dx: Frozen shoulder syndrome. This may co-exist with rotator cuff tendonitis or bicipital tendonitis.
Rx: PT: Swinging pendulum of 5-10lbs. External and internal band pull with elbow flexed at 90 degrees.
Injection of the subacromial bursa with steroid when there is co-existing rotator cuff or bicipital

Case: 54-year-old woman
Sudden, severe, non-trauma-related right shoulder pain localized at midhumerus but also diffusely
around the anterolateral shoulder.
PE: limited abduction with point tenderness over the subacromial bursa and the greater
tuberosity of the humerus.
x-ray: linear calcific density in the supraspinatus tendon.
Dx: calcific hydroxyl apatite crystal tendonitis of supraspinatus tendon (less commonly infraspinatus and
Conservative Rx is successful in the vast majority of cases.

Case 42 y.o. obese man.
Color change, sense of fullness, and pain of arm in the ulnar distribution of right hand in 4th and 5th digits
with mild wasting.
Glucose 148.
Dx: C8-T1 root impingement at the level of 1st rib and the scapula, thoracic outlet, lower brachial plexus.
Ddx: DM (usually symmetric), cervical radiculopathy (see below), cervical spondylosis (C2 and C4
nerve roots… pain in neck radiating to back of head, shoulders, and arms).
Test: EMG and MRI.
 Cervical       Root Pain and sensory loss                       Motor                                    Reflex
 C6 - C7                   C7         Medial scapula, triceps, 3rd finger                            Triceps, wrist flexors, finger* extensors                  Triceps

                           C6         Thumb and index finger                                         Biceps, Wrist extensors,                                   Biceps
 C5 - C6

*Examination tests to confirm the diagnosis: 1) Examiner tilts head with 15 pounds of pressure toward the effected side.. Provoking symptoms. 2) Patient places hand
on side of symptoms on head.. Reduces symptoms. 3) With patient supine, examiner gently places traction on occiput and reduces symptoms.
C8 is least common of these and involves the 4th
                                                   and 5th digits, as does the thoracic outlet syndrome.

Pruritis. Joint pain
Etiology: ^ Ca x Phosphate product.

Latex-fruit cross-reactivity may occur with certain foods: banana, avocado, passion fruit, kiwi, and chestnut

77 yo man: cc: morning stiffness, pains in shoulders, hips, knees, and severe pain with swelling in his hands and
PE: Pitting edema of hands & fingers. No warmth or redness.
RSSSPE: Relapsing and remitting symmetric seronegative synovitis with pitting edema.
Rx: Prednisone 10 mg QD. (Q 40, rheum, MKSAP 12).

The following require TB testing prior to administration:
*High Dose steroids.
*Any anti-TNF-alpha agent: Infliximab, etanercept, etc.
Supraspinatus testing: Abduct at shoulder, forward flexion, thumbs down. Resist downward force.

Infraspinatus testing: external rotation against resistance.
Neer’s sign for impingement of the rotator cuff under the coraco-acromial arch
Fully pronated arm; then place in forward flexion.

Hawkin’s test for subacromial impingement
Forward elevate the arm to 90 degrees then forcibly internally rotated.
This reveals supraspinatus tendon impingement.

Cross arm test for acromioclavicular joint disorder. Elevate the arm to 90 degrees then actively adduct.
Apprehension test for anterior instability. Patient abducts arm to 90 degrees. Examiner externally rotates
the arm and applies anterior pressure to the humerus.

Sulcus test for glenohumeral instability: Apply downward traction to the humerus and watch for a
depression lateral or inferior to the acromion.

Sperling’s test for cervical root disorder: Extend the neck and rotate toward the effected shoulder while an
axial load is placed on the spine.
  SHOULDER SYNDROMES                              August 1, 2008 See:NEJM 2008;358:2138.
Symptoms           PE Hallmark.                              Dx                     Rx

Pain on reaching,               Pain on Resistance            Rotator cuff                Acute: Ice. NSAID. Limit
pushing, or pulling.            Empty can, external           tendonitis or minor         movement. Pendulum.
Pain when lying on              rotation, & lift off(1)       tear (Impingement           Ongoing: Pendulum. Ext
shoulder.                                                     syndrome co-exists.)        and int band
                                                              Possibly linear             strengthening. No sling.
Overhead reaching.              Passively performed           Impingement                 Acute: Ice. NSAID.
                                painful arc                   syndrome                    Pendulum. Limit
                                maneuvers(2).                                             movement.
                                Biceps tenderness.            Biceps tendonitis           Ongoing: Pendulum. Ext
                                No pain on resisted                                       and int band exercise. No
                                abduction.                                                sling.
Progressive onset of pain an    Limited ROM. Bone-on-         Joint-space narrowing,      Surgical intervention.
stiffness                       bone crepitance               osteophytes, sclerosis

Pain 4 inches down outer        Crepitance on arm             Subacromial bursitis        NSAIDs. If no relief, methyl
arm at insertion of deltoid.    rotation.                     Pain is referred and is     prednisolone is injected into
                                                              complication of             the bursa. (May be seen with
                                                              supraspinatus tendonitis.   RA, PMR, or pseudo-gout.)

Dramatic loss of weakness ...   Weakness on mid arc           Rotator cuff full thickness Surgery
inability to lift overhead      abduction or external         tear (5)
                                rotation Positive “drop
                                arm test” (ratchet effect.)

Patient notes sudden            “Popeye” deformity in         Rupture of the biceps       Surgery
weakness and lump just          the ante-cubital fossa        tendon
above elbow flexor.

Loss of ROM. Can’t put on       Inability to scratch back.    Frozen shoulder             PT: hanging pendulum with 5
coat. Can’t reach top shelf.    Loss of external rotation                                 to 10 lb weight. External and
                                and abduction                                             internal rotation.

Young; history of trauma,       Sulcus sign with down-        subluxation of shoulder.
pain over the A-C joint         ward traction at elbow

   Rotator cuff: Posteriorly: Supraspinatus (at supraspinous fossa of scapula), infraspinatus (at infraspinous fossa), teres
   minor (at the most inferior part of the scapula) , and on the anterior scapula: subscapularis (at the subscapular fossa).
   The supraspinatus abducts. The infraspinatus and teres minor externally rotate arm and hold the humeral head in the
   glenoid cavity. The subscapularis medially rotates and also holds the humeral head in the glenoid cavity.
   INSPECTION: Disrobe, visualize both shoulders; look for deformity, atrophy, winging, asymmetry.
   PALPATION: AC and SC joint; cervical spine; biceps tendon. Anterior glenohumeral joint, coracoid process,
   acromion & scapula.
   RANGE OF MOTION: Assess active ROM by the Aply scratch test of the scapula from above and from below.
   (1) Supraspinatus: Empty can test: Shoulders abducted to 90 degrees in forward flexion and thumbs down; Dr.
   attempts to push down: Pain & weak. Infraspinatus & teres minor: Elbow at side with hand forward; patient
   externally rotates against resistance. Subscapularis: Lift off test: Dorsum of hand on lumbar region and lift off.
   (2) Neer’s sign: Standing behind the sore shoulder, the clinician places one hand on the acromion to keep the patient
   from shrugging; put the hand a the side and fully internally rotate the arm (full pronation) and then slowly raise the
   arm forward and above the shoulder. Hawkin’s test: Place elbow forward at shoulder height with hand upward and
   then internally rotate the biceps.
   (3) A variant is supraspinatus tendonitis from calcific hydroxy apatite crystals, manifest by linear calcific density in
   the tendon. Treatment is conservative.
   (4) Or degenerative rotator-cuff failure (Normal or narrowed space beteween the humeral head and acromion), OR
   anter-superior excape (superior displacement of humeral head).
   AC Joint dysfunction: Cross Arm Test Arm at 90 degrees; active adduction
   Glenohumeral instability: Apprehension test: Should with 90 decree abduction, examiner applies anterior pressure to
    Condition          WBC count          Diff                 Crystals

    Osteoarthritis, traumatic   < 2,000                      monos, lymphs               negative

    RA                          5,000 - 10,000               PMNs                        negative

    Gout                        5,000 - 75,000               PMNs                        negative bi-refringence

    CPPD                        ditto                        PMNs                        weakly pos. bi-refringence

    Septic arthritis            > 50,000                     PMNs                        Negative

Drug              v WBCs    Renal tox                Pneumonitis     hepatotoxic     retinopathy     diarrhea

Methotrexate             Y                Y          Y                Y

Gold                     Y                Y          Y                                                Y

Penicillamine            Y                Y          Y


Azathioprine (6 MP)      Y**

sulfasalzine*            Y

   **Azathioprine (or 6 mercaptopurine) + Allopurinol can cause fatal bone marrow failure.

   Monitor: LFTS + CBC.
   Azathiprine + MTX can cause severe febrile episodes.

   Disorders causing decreased complement: Active SLE, vasculitis, post infectious and membrano-proliferative GN.

   If a patient has a prolonged PTT uncorrected by mixing with normal serum and a positive VDRL, does he have
   Ans: No. He has APL Antibody syndrome.

   Antibody tests positive in Sjogren’s: RF 90%, ANA 70%, 60% Anti-La, and 45% Anti-Ro

   ^CK, Irritability on EMG, biopsy with T cell infiltrates in muscle fascicles.
   Dx: PM
   Do MRI to find best place for biopsy.

   In polymyositis, what abnormalities are seen on barium swallow?
   Ans: Nasal regurgitation, dysphagia, poor initiation of swallowing, aspiration, dysfunction of the
   distal 1/3 of the esophagus and loss of lower esophogeal tone, or zencker’s diverticulum.
   What are the most common abnormalities?
   Ans: distal 1/3 dysfunction and loss of LES tone occurs in the majority of patients. The proximal
   symptoms of the esophagus can also commonly occurs. There is rarely a zencker’s diverticulum.
   Increase in AST & ALT ocurs in 10% of those with polymyositis (Q51, MKSAP 12, Rheumatology)

   Four criteria for Polymyositis:
   1. Proximal muscle weakness (and myalgias)
   2. Abnormal EMG: Myopathic type.
   3. Increased CPK.
   5. (Abnormal MRI to show site for Muscle Biuopsy showing cytotoxic T-cell infiltration with myonecrosis.
As the disease progresses, dysphagia and EKG changes also occur.

CC: chest pain relieved by bending, abdominal pain, and right foot drop.
Dx: PAN.

Causes of false positive Lyme serology: SLE, RA, RMSF, syphilis, and leptospirosis.

There is concordance of 15 - 30% in monozygotic twins for auto-immune conditions: type 1 diabetes, multiple
sclerosis, and systemic lupus erythematosus. Endogenous mechanisms of auto-immunity may be altered antigen
presentation, increased T cell help, increased B cell function, apoptotic defects, cytokine imbalance, and altered
immunoregulation. Exogenous factors may be molecular mimicry, superantigen stimulation, and microbial

Idiopathic midline granuloma is usually localized to the midline nasopharynx and is most
appropriately treated with a combination of prednisone, cyclophosphamide, and radiation.

64-year-old African-American male presents with congestive heart failure, renal failure, and polyneuropathy.
PE: There are also raised waxy papules in the axilla and inguinal region.
Lab: BUN 90, creatinine 6.3 mg/dL, Total protein 9.0 g/dL, albumin of 3.2 g/dL. HCT 24%
U/A: 3+ proteinuria
Echo: thickened left ventricle and preserved systolic function.
What condition reflects the raised waxy papules in body folds?
Amyloidosis: waxy papules in body folds are classic.
Work up:
R/O Myeloma. If negative do fat pad biopsy which has 70% sensitivity for amyloid

Recurrent sepsis with Neisseria species has been demonstrated in patients with deficiencies of the terminal
C2 deficiency, detected by low CH50.
C4 and C2 deficiencies occur in SLE-like syndrome, vasculitis, and polymyositis.

40 y.o. alcoholic male presents with left hip and groin pain. Has pain in the groin on internal rotation.
X-ray: flattening of humoral head.
Dx: Avascular necresis. This occurs in 2 - 5% of alcoholics.

Destruction of the tufts of the terminal phalanges is commonly seen in scleroderma, vinyl
chloride disease, and secondary hyperparathyroidism.

35 y.o. woman
Recurrent urticaria with residual discoloration.
ESR 85.
Dx: Cutaneous necrotizing vasculitis
W/U: Skin biopsy.

Vasculitis (like serum sickness): Antigen excess >> blood borne immune complexes >> deposition in vessel walls >>
tissue damage >> activation of complement, particularly C5a >>
chemoattractant for neutrophils>> further propagation >> damage to vessel wall >> thrombosis >> tissue ischemia.
A similar process occurs in body tissues.
Cryoglobulinemia (from UpToDate)

                              Type I                        Type II (“Essential mixed     Type III

 Type of globulin             Monoclonal IgG or IgM         Monoclonal Ig +               polyclonal
                                                            polyclonal Ig

 Typical correlate            MM or Waldenstrom’s           hepatitis C or HIV            CTD

 Essential (72%)              30 %                          70%                           57%

 Secondary (28%)              70%                           30%                           43%
                              LPD >>> Essential             LPD > CLD > CTD               Essential >>
                              CTD, CLD                                                    CLD>>CTD>> LPD

 Symptoms & Signs

 Purpura                      Sometime                      Often                         Often

 Gangrene/acrocyanosis        Frequent                      Frequent                      Rare

 Arthralgias > arthritis      Occurs                        prominent                     prominent

 Renal                        Occurs                        Occurs                        Occurs

 Neurologic                   Occurs                        Occurs                        Occurs

 Liver                        Rare                          Occurs                        Frequent

CLD: chronic liver disease. CTD: connective tissue disease. LPD: lympho or plasma proliferative disease.

To detect cryoglobulins: 1) Draw blood fasting. 2) Keep at body temperature. 3) Centrifuge at 37degrees. 4) Put in
Freezer at 4 degrees for 3 days. 5) Look for precipitants.

Cryoglobulinemia is present in 40% of patients with chronic hepatitis C, but vasculitis is seen in only 2% of these,
consisting of palpable purpura (80%, nerve involvement in 50%, and renal involvement (Type I
membranoproliferative glomulronephritis.. 30%). NEJM 2006;355:2468.

Cryoglobulinemic vasculitis is one of the pulmonary renal syndromes.

Locking of the knee indicates a meniscal tear. Arthroscopy can be diagnostic and therapeutic.

Anti-ribonuclear component of extractable nuclear antigen indicates MCTD.

Anti-Jo1 antibody indicates polymyositis.

           OA of the hip can be referred to the knee

Differential diagnosis of myopathy:
Viral           hypothyroidism      hyperthyroidism                               Alchol abuse
Cocaine         steroids            Cushings syndrome                             PMR
Polymyositis statins                Fibromyalgia

Strategies to reduce statin induced myopathy: Fluvastatin/ low dose rosuvastatin/ Ezetimibe
Lung: CXR patterns: 1: bilat HLA without infiltration. 2: bilat HLA with infiltration. 3:infiltration alone; 4: fibrotic
bands, bullae, hilar retraction, bronchiectasis & diaphragmatic tenting. PFTs: Restrictive disease. (decreased FVC.
50% with concurrent obstructive disease: decreased FEV1/FVC. Airway hyper-reactivity in 5 – 83%. Pulmonary
hypertension (23%).
         Skin (25 – 35%): Macules, papules, plaques. Neck, upper back, extremities, turnk. AA: Scars, pits, and
pale de-pigmented areas. Lupus pernio: Nose, cheeks, lips, ears, indurated lumpy purplish. Erythema nodosum in
10% (biopsy of these is not helpful… paniculitis).
         Eyes and adnexa: 25% to 80%. Slit lamp exam. Anterior uveitis.
         CNS symptoms: 10%. Cranial nerve palsies, HA, ataxia, cognitive dysfunction, weakness, seizures.
Central DI, hypothalamic hypopituitarism. Of these, neurologic involvement precedes the diagnosis in 74%. CSF:
lymphocytic. MRI can guide therapy.
         Cardiac sarcoid in 5%. Left ventricle. Use EP studies to detect conduction delays.
         Urinary: Hypercalcuria in 40%; Hypercalcemia (11%). Renal stones: 10%. Measure 24 hour urinary
excretion for calcium. (Sarcoid macrophages convert 205 HO vit D to 1,25 vit D.)

2. DIAGNOSIS: (This is a diagnosis of exclusion).
         *Diagnosis is established when there are 1. clinical and radiologic findings and histologic evidence in 1 or
more organs of 2. noncaseating epithelioid-cell granulomas. 3. exclusion of other diseases, organisms or particles.
Sarcoidal granulomas are not unique.
         *Differential Dx: hypersensitivity pneumonitis, eosinophilic granuloma, common
variable immunodeficiency, CT dis, pneumoconiosis, berylliois, TB & histoplasmosis.
         *18 FDGPET scanning for pinpointing candidates for biopsy
         *Biopsy specimens: skin, peripheral lymph nodes, lacrimal glands or conjunctiva.
         *Transbronchial biopsy via bronchoscopy has a diagnostic yield of 85%+ when multiple lung segments are
sampled. (If negative and no other organs are involved, then biopsy intra-thoracic lymph nodes … often enlarged in
         *Endoscopic ultrasound-guided FNA of intra-thoracic lymph nodes is reported to provide a diagnostic yield
of 82% and may obviate the need for mediastinoscopy.
         *Diagnosis is “reasonably certain” without biopsy in patients who present with Lofgren’s syndrome (in
women: migratory poly arthritis, erythema nodosum, bilateral hilar adenopathy & fever). (Also note: Uveoparotid
         Other points: Sarcoid granulomas produce angiotensin converting enzyme (ACE). In one study, Positive
and negative predictive values were 84% and 74% respectively. Response to steroids does not establish the

Reference: Iannuzzi MC et al. Sarcoidosis. NEJM 2007; 357:2153-65. UptoDate
     Urticaria:    Superficial dermis. Pruritic or painful. Mast cell mediated.
     Angioedema. Deep Dermis.
              Mast cell mediated.
              Non-mast cell mediated.
                       Kinin pathway: ACEI or ARB etiology.
                       Complement Pathway: Low C1 inh.
                            Inherited: Normal C1q
                            Acquired: Low C1q: Malignancy, lymphoproliferative disorder, or auto-antibody.

Darier’s sign=urticaria upon rubbing or scratching the      skin >> mastocystosis.

URTICARIA (= “HIVES”... mast cell mediated):
>Raised, circumscribed, central pallor (may simulate        erythema migrans), and pruritic (but painful in physical
                            >Involves the superficial       dermis
                            >May have associated            ANGIOEDEMA (deep dermis) in 50% and/or
                            ANAPHYLAXIS (also               mast cell mediated).
                            >Acute(2/3 of cases)= less than 6 weeks; Chronic(1/3 of cases).
                            >May have thyroid disease, but there is no correlation to thyroid status.
                            >Progesterone containing OCPs are correlated with this.
                            >Foods: fruits & nuts cross react with trees, grass, weeds.
                            >Viral infections: hepatitis A,B,C; HIV; Coxsackie.
                            >Schistosoma and                Blastocystis hominis.
                            >Lab studies: CBC               (possible anemia or eosinophilia), ESR, ANA, thyroid
                            peroxidase Abs,                 Cryoglobulins, complement profile (but not C1 inhibitor
                            deficiency, which is not        associated with hives), hep B & C.
                            Biopsy lesion (diagnose         vasculitis) if lesion persists beyond 1 day and is painful rather
                            than pruritic, or if ^ ESR or systemic symptoms or if ? Of mastocytosis.
                            RX: 1) H1 blockers              (antihistamines, e.g., loratidine), H2 blockers (e.g., ranitidine),
                            H1 & H2 blocker                 (doxepin).
                            2) Steroids (or                 cyclosporine) in chronic recurrent urticaria when the above
                            fail. 3) Epi pen if there is associated laryngeal angio-edema or anaphylaxis. In auto-
                            immune induced urticaria when the above fail, add leukotriene inhibitor (zafirleukast).
                            >Swelling in the deep dermis. >Rapid onset.
                            >Lips, larynx, bowel.
                            >due to inflammatory mediators that dilate venules and increase their permeability.
                            >Angio-edema can be viewed as an extension of urticaria from the superficial dermis into
                            the deep dermis.
                            >The pathway may involve mast cells (as for urticaria) or non-mast cell mediated.

                              1. MAST CELL MEDIATED angioedema: Causes are same as for urticaria, except no
                              physical causes and no mastocytosis. Though rare and not suggested in the table, life
                              threatening angioedema does occur in SLE.
                              ANAPHYLAXIS (with bronchospasm and hypotension), mediated by histamines and
                              prostaglandins from mast cells and basophils, may accompany the laryngeal edema of

                              2. NON-MAST CELL MEDIATED angioedema:
a) Kinin pathway angioedema is effected by ACE inhibition. ACEIs decrease angiotensin II and increase bradykinin
which causes angioedema. ACEIs cause angioedema in 0.3% of patients. Usually this occurs in days to weeks but may
occur as late as several years. This is NOT related to ACEI cough, which is much more common.
>ARBs may also cause angioedema in about 8% of patients with ACE inhibitor angioedema. Thus, ARBs should be
used cautiously in ACEI-sensitive patients.
b) Complement pathway angioedema: Deficiency or dysfunction of C1 inhibitor protein (C1 inh) causes an increase in
levels of edema-producing bradykinin and complement C2b.
>Inherited form (AD) is due to very low C1 inh (2/3) or dysfunction of C1 inh (1/3). Patients present as adolescents or
young adults and may have bowel swelling with severe abdominal pain, vomiting, and life-threatening laryngeal edema.
>Acquired forms have a deficiency of C1 inh (usually), C1 and its substrates, C4 and C2. Causes are
          >lymphoproliferative disorders and malignancies
          >Autoantibody production, including SLE.

DIAGNOSIS AND TREATMENT: 1. MAST CELL TYPE (urticaria and/or anaphylaxis). Lab studies are the same as
for urticaria: CBC (possible eosinophilia), ESR, ANA, thyroid peroxidase Abs, Cryoglobulins, complement profile (but
not C1 inhibitor deficiency, which is not associated with hives), hep B & C. RX: As above for urticaria.
For laryngeal edema, give EPINEPHRINE (1:1,000) 0.4 ml subcu Q 15 min. (This is also part of anaphylaxis Rx.)

a) Kinin mediated. Take history for ACEI or ARB! Treat a life-threatening acute attack with FFP.

b) Complement mediated: (Negative ACEI or ARB Hx):
Consider malignancy.
Obtain ANA, C1 inh, C1q, C4, and C2 to distinguish hereditary and acquired angioedema.

Treat any angioedema of the larynx acutely with the ANDROGEN, stanazolol 4mg Q4H x 4. Continue 4 mg/day and
follow LFTs and C4 levels. Taper as C4 levels rise. Prophylaxis is effective in >90% of patients with hereditary

SOURCE: Uptodate, MKSAP 13, and selected references (Thong, 2001; Cacoub, 2001).