DIAGNOSIS & TREATMENT - PART 4 potx

Systemic Lupus Erythematosus■ Essentials of Diagnosis • Predominantly in young women • Multisystem inflammatory autoimmune disorder with periods ofexacerbation and remission • Four or mo

Systemic Lupus Erythematosus

■ Essentials of Diagnosis

• Predominantly in young women

• Multisystem inflammatory autoimmune disorder with periods ofexacerbation and remission

• Four or more of the following 11 criteria must be present: malar(“butterfly”) rash, discoid rash, photosensitivity, oral ulcers, ar-thritis, serositis, renal disease, neurologic disease, hematologicdisorders, positive antinuclear antibody (ANA), and immuno-logic abnormalities (eg, antibody to native double stranded DNA

or to Sm, or false-positive serologic test for syphilis)

• Also associated with fever, myositis, alopecia, myocarditis, carditis, vasculitis, lymphadenopathy, conjunctivitis, anti-phospholipid antibodies with hypercoagulability and miscarriages,thrombocytopenia, glomerulonephritis (focal, membranoprolifer-ative, or membranous), sicca complex

peri-• Syndrome may be drug-induced (eg, procainamide, lazine), in which case brain and kidney usually spared

• Withdraw offending agent if drug-induced lupus suspected

• Avoid sun exposure

Systemic Sclerosis (Scleroderma)

intesti-• Limited disease (80% of patients) or CREST syndrome nosis cutis, Raynaud’s phenomenon, esophageal hypomotility,sclerodactyly, and telangiectasia): skin tightening limited to thedistal extremities and feet, with lower risk of renal disease, lateronset of pulmonary hypertension and biliary cirrhosis, and anoverall better prognosis

(calci-• ANA frequently useful in systemic sclerosis; anticentromere body positive in 1% of patients with diffuse scleroderma and 50%

anti-of those with CREST syndrome; antitopoisomerase I (Scl-70) inone-third of patients with diffuse systemic sclerosis and 20% ofthose with CREST syndrome, and a poor prognostic factor

• Corticosteroids not helpful; penicillamine may be

• Warm clothing, smoking cessation, and extended-release calciumchannel blockers for Raynaud’s phenomenon; intravenous ilo-prost may be helpful for digital ulcers

• H2receptor antagonists or omeprazole for esophageal reflux

■ Pearl

Malabsorption in systemic sclerosis is due not to intestinal fibrosis but

to bacterial overgrowth from hypomotility.

Reference

Clements PJ: Systemic sclerosis (scleroderma) and related disorders: clinicalaspects Baillieres Best Pract Res Clin Rheumatol 2000;14:1 [PMID:10882211]

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Overlap Syndromes (Mixed Connective Tissue Disease & Undifferentiated Connective

myosi-• Presence of a specific antibody to ribonuclear protein

• Suggested clinical criteria include three of the following: edema

of the hands, synovitis, myositis, Raynaud’s phenomenon, andacrosclerosis

• Associated with pulmonary fibrosis, pericarditis, myocarditis,esophageal hypomotility, glomerulonephritis

• May evolve to one predominant phenotype over time

■ Essentials of Diagnosis

• Bilateral proximal muscle weakness

• Periorbital edema and a purplish (heliotrope) rash over the uppereyelids in many

• Violaceous, occasionally scaly papules overlying the dorsal face of the interphalangeal joints of the hands (Gottron’s papules)

sur-• Serum CK elevated; ANA only uncommonly positive save inoverlap syndromes; anti-Jo-1 antibodies in the subset of patientswho have associated interstitial lung disease; anti-Mi-2 is morespecific for dermatomyositis but is insensitive

• Muscle biopsy and characteristic electromyographic pattern arediagnostic

• May be associated with rheumatoid arthritis, SLE, scleroderma,mixed connective tissue disease; increased incidence of malig-nancy, especially in older patients

• Methotrexate or azathioprine spares steroids

• Intravenous immune globulin for some cases of dermatomyositis

• Search for malignancy unwarranted unless historical or nation findings indicate it

• Occasionally associated with glomerulonephritis, renal tubularacidosis, biliary cirrhosis, pancreatitis, neuropsychiatric dysfunc-tion, polyneuropathy, interstitial pneumonitis, thyroiditis, cardiacconduction defects

• Over 50% have cytoplasmic antibodies, Ro (SS-A), and

■ Differential Diagnosis

• Sicca complex associated with other autoimmune diseases such

as sarcoidosis, rheumatoid arthritis, SLE, and systemic sclerosis

• Cholinergic drugs such as pilocarpine

• Meticulous care of teeth and avoidance of sugar-containing candies

• Corticosteroids or azathioprine; cyclophosphamide for peripheralneuropathy, interstitial pneumonitis, glomerulonephritis, and vas-culitis

Polyarteritis Nodosa

■ Essentials of Diagnosis

• Fever, hypertension, abdominal pain, arthralgias, myalgias

• Cotton-wool spots and microaneurysms in fundus; pericarditis,myocarditis, palpable purpura, mononeuritis multiplex, livedoreticularis

• Acceleration of sedimentation rate in most; serologic evidence ofhepatitis B or hepatitis C in 30–50%

• ANCA positive in most

• Diagnosis confirmed by biopsy or visceral angiography

• Renal or pulmonary involvement in variant microscopic arteritis

• Essential mixed cryoglobulinemia

• Cholesterol atheroembolic disease

■ Treatment

• Corticosteroids with cyclophosphamide for systemic vasculitis;azathioprine is used as a maintenance immunosuppressant

■ Pearl

Treat polyarteritis nodosa with immunosuppressives at your own risk

if endocarditis has not been definitively excluded.

Reference

Savage C et al: ABC of arterial and vascular disease: vasculitis BMJ 2000;320:1325 [PMID: 10807632]

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Polymyalgia Rheumatica & Giant Cell Arteritis

■ Essentials of Diagnosis

• Patients usually over age 50

• Polymyalgia rheumatica characterized by pain and stiffness, notweakness, of the shoulder and pelvic girdle lasting 1 month ormore without evidence of infection or malignancy

• Associated with fever, little if any joint swelling, sedimentationrate > 40mm/h, and rapid response to prednisone 15 mg/d

• Giant cell (temporal) arteritis frequently coexists with gia rheumatica; headache, transient or permanent blindness, jawclaudication, or temporal artery tenderness; lingual Raynaud’sphenomenon, scalp necrosis

polymyal-• Diagnosis confirmation by 5 cm temporal artery biopsy remainsreliable for 1–2 weeks after starting steroids

• Carotid plaque with embolic amaurosis fugax

• Carotid Takayasu’s arteritis

■ Treatment

• Prednisone 10–20 mg/d for polymyalgia rheumatica

• Prednisone 60 mg/d immediately on suspicion of temporalarteritis; treat for at least 4 months depending on response ofsymptoms—not sedimentation rate

• Methotrexate or azathioprine spares steroids in some patientswith side effects on high doses

■ Pearl

Instruct patients with polymyalgia rheumatica to keep 60 mg of nisone with them at all times and to take it and come in if there are any visual symptoms.

pred-Reference

Epperly TD et al: Polymyalgia rheumatica and temporal arthritis Am FamPhysician 2000;62:789 [PMID: 10969858]

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Churg-Strauss Vasculitis (Allergic Granulomatosis & Angiitis)

■ Essentials of Diagnosis

• Granulomatous vasculitis of small- and medium-sized arteries

• Four of the following have a sensitivity of 85% and specificity of100% for diagnosis: asthma; allergic rhinitis; transient pulmonaryinfiltrates; palpable purpura or extravascular eosinophils; mono-neuritis multiplex; and eosinophilia

Hypersensitivity Vasculitis

■ Essentials of Diagnosis

• Leukocytoclastic vasculitis of small blood vessels

• Palpable purpura of lower extremities the predominant feature

• Secondary to numerous drugs, neoplasms, connective tissue orders, congenital complement deficiency, serum sickness, viral

dis-or bacterial infection

• On occasion associated with fever, arthralgias, abdominal painwith or without gastrointestinal bleeding, pulmonary infiltrates,kidney involvement with hematuria

• Treat underlying disease if present

• Discontinue offending drug

• Corticosteroids in severe cases

symp-• Proptosis, scleritis, arthritis, purpura, or neuropathy (mononeuritismultiplex) may also be present

• cANCA in 90%; sinus, lung, or renal biopsy makes the sis, though the latter is seldom specific, showing focal glomeru-lonephritis; eosinophilia not a feature

diagno-• Chest film may reveal large nodular densities; urinalysis mayshow hematuria, red cell casts; CT scans of sinuses often revealbony erosion

• Increased risk of bladder cancer and lymphoma

• Primarily oral cyclophosphamide or methotrexate in addition

• Trimethoprim-sulfamethoxazole effective in mild disease; given

to all patients not allergic to sulfonamides

■ Essentials of Diagnosis

• Refers to any globulin precipitable at lower than body temperature

• Any elevation of globulin may be associated

• Monoclonal gammopathies, reactive hypergammaglobulinemia,cryoprecipitable immune complexes are the main causes; firsttwo have acral cold symptoms because of higher titers of cryo-proteins

• Symptoms and signs depend upon type

• Low erythrocyte sedimentation rate; correctable by doing 37 °CESR

■ Differential Diagnosis

• Multiple myeloma, Waldenström’s macroglobulinemia

• Chronic inflammatory diseases such as endocarditis, sarcoidosis,rheumatoid arthritis

• Essential mixed cryoglobulinemia: palpable purpura and lonephritis in patients serologically positive for hepatitis C

Takayasu’s Arteritis (“Pulseless Disease”)

■ Essentials of Diagnosis

• Large-vessel vasculitis involving the aortic arch and its majorbranches

• A disease of Asian women under 40

• Associated with myalgias, arthralgias, headaches, angina, dication, erythema nodosum-like lesions; hypertension, bruits,absent pulses, cerebrovascular insufficiency, aortic insufficiency

clau-• Angiography reveals narrowing, stenosis, and aneurysms of theaortic arch and its major branches

• Bruits may be heard over the subclavian arteries or aorta in up to40% of patients; additionally, there may be a > 10 mm Hg dif-ference in systolic blood pressure in the two arms

• Rich collateral flow visible in the shoulder, chest, and neck areas

• Cyclophosphamide or methotrexate added for severe disease

• Surgical bypass or reconstruction of affected vessels

Thromboangiitis Obliterans (Buerger’s Disease)

• Associated with migratory superficial segmental thrombophlebitis

of superficial veins, absent peripheral pulses, claudication, ness, paresthesias, Raynaud’s phenomenon, ulceration and gan-grene of fingertips and toes

numb-• Angiography reveals multiple occluded segments in the small- andmedium-sized arteries of the arms and legs

■ Differential Diagnosis

• Atherosclerosis

• Raynaud’s disease

• Livedo reticularis due to other cause

• Antiphospholipid antibody syndrome

• Cholesterol atheroembolic disease

■ Treatment

• Smoking cessation is essential

• Warm clothing, nifedipine for Raynaud’s phenomenon

• Surgical sympathectomy of some value

• Amputation required in some

Behçet’s Syndrome

■ Essentials of Diagnosis

• Usually occurs in young adults from Mediterranean countries orJapan; incidence decreases if patient’s descendants emigrate else-where

• Most common: recurrent oral aphthous ulcerations (99%), genitalulcers (80%), ocular lesions in half (uveitis, hypopyon, iritis, ker-atitis, optic neuritis), and skin lesions (erythema nodosum, super-ficial thrombophlebitis, cutaneous hypersensitivity, folliculitis)

• Less common: gastrointestinal erosions, epididymitis, lonephritis, cranial nerve palsies, aseptic meningitis, and focalneurologic lesions

glomeru-• Pathergy test—a papule or a pustule forms 24–48 hours aftersimple trauma such as a needle prick

• Diagnosis is clinical

• HLA-B5 histocompatibility antigen often present

■ Differential Diagnosis

• HLA-B27 spondyloarthropathies

• Oral aphthous ulcers

• Herpes simplex infection

• Colchicine (for erythema nodosum and arthralgia)

• Azathioprine, cyclosporine in some

lor-• Peripheral arteritis and anterior uveitis in many

• Aortic insufficiency with cardiac conduction defects in some

• Cauda equina syndrome, apical pulmonary fibrosis are late plications

com-• HLA-B27 histocompatibility antigen present in over 90% ofpatients; rheumatoid factor absent

• Radiographic evidence of sacroiliac joint sclerosis; ization and squaring of the vertebral bodies with calcification ofthe anterior and lateral spinal ligaments (bamboo spine)

• Diffuse idiopathic skeletal hyperostosis (DISH)

• Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) drome

syn-■ Treatment

• Physical therapy to maintain posture and mobility

• NSAIDs (eg, indomethacin 50 mg three times daily) often ginally effective

mar-• Sulfasalazine reported effective in some patients

• Intra-articular corticosteroids for synovitis; ophthalmic steroids for uveitis

cortico-• Surgery for severely affected joints; anti-TNF agents may beeffective but are toxic

■ Pearl

In a patient with burned-out ankylosing spondylitis and symptomatic

“benign prostatic hyperplasia,” test the cauda equina distribution neurologically before undertaking prostatectomy.

Reference

Koehler L et al: Managing seronegative spondarthritides Rheumatology 2000;39:360 [PMID: 10817767]

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Psoriatic Arthritis

■ Essentials of Diagnosis

• Classically a destructive arthritis of distal interphalangeal joints;many patients also have peripheral arthritis involving shoulders,elbows, wrists, knees, and ankles, often asymmetrically

• Sacroiliitis in B27-positive patients

• Occurs in 15–20% of patients with psoriasis

• Psoriatic arthritis associated with nail pitting, onycholysis,sausage digits, arthritis mutilans (severe deforming arthritis)

• Rheumatoid factor negative; serum uric acid may be elevated

• Radiographs may reveal irregular destruction of joint spaces andbone, pencil-in-cup deformity of the phalanges, sacroiliitis

• Gold salts, methotrexate

• Sulfasalazine reportedly effective in patients with symmetric arthritis

poly-• Treatment of psoriasis helpful in many but not in sacroiliitis

Reactive Arthritis

■ Essentials of Diagnosis

• Predominantly found in young men

• Triad of urethritis, conjunctivitis (or uveitis), and arthritis whichmay occur within a month of another sign or symptom; conjunc-tivitis may be subtle and evanescent

• Follows dysenteric infection (with shigella, salmonella, yersinia,campylobacter) or sexually transmitted infection (with chlamydia)

• Asymmetric, oligoarticular arthritis typically involving the kneesand ankles

• Associated with fever, mucocutaneous lesions, stomatitis, aorticregurgitation, optic neuritis, circinate balanitis, prostatitis, kerato-derma blennorrhagicum, pericarditis

• HLA-B27 histocompatibility antigen in most

in-• Tetracycline for associated Chlamydia trachomatis infection;

obtain VDRL, consider HIV testing

• Azathioprine, methotrexate in severe cases

• Sulfasalazine may help in some patients

• Intra-articular corticosteroids for arthritis, ophthalmic steroids for uveitis

cortico-■ Pearl

Synovial fluid occasionally shows characteristic cells: large clear cell with ingested polymorphonuclear leukocytes which may have inclusion bodies.

mononu-Reference

Barth WF et al: Reactive arthritis (Reiter’s syndrome) Am Fam Physician1999;60:499 [PMID: 10465225]

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Arthritis Associated with Inflammatory

Bowel Disease

■ Essentials of Diagnosis

• Peripheral arthritis: asymmetric oligoarthritis that typically volves the knees, ankles, and occasionally the upper extremities,usually parallels bowel disease in activity

in-• Spondylitis: clinically identical to ankylosing spondylitis; B27 antigen present in most patients in a male:female ratio of 41

HLA-• Articular features may precede intestinal symptoms, especially inCrohn’s disease

• Extra-articular manifestations may also occur in Crohn’s ease (erythema nodosum) and in ulcerative colitis (pyodermagangrenosum)

• Treat underlying intestinal inflammation

• Aspirin, other NSAIDs (eg, indomethacin, 50 mg three timesdaily)

• Physical therapy for spondylitis

■ Pearl

The younger the patient, the less the gastrointestinal complaints; thus, arthritis in adolescence should prompt a search for inflammatory bowel disease despite absence of symptoms.

Reference

De Keyser F et al: Bowel inflammation and the spondyloarthropathies RheumDis Clin North Am 1998;24:785 [PMID: 9891711]

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Septic Arthritis (Nongonococcal Acute

sy-• Previous joint damage and intravenous drug abuse predispose

• Most common organisms: Staphylococcus aureus, group A tococci, Escherichia coli, and Pseudomonas aeruginosa; Haemo- philus influenzae in children under 5; Staphylococcus epidermidis

strep-following arthroscopy or joint surgery

• White cell count in synovial fluid > 100,000/µL; synovial fluidculture positive in 50–75%, blood culture in 50%

• Intravenous antibiotics should be administered empirically

• Surgical evaluation for drainage and irrigation of the knee

• Affected hip joint usually requires surgical drainage

• Rest, immobilization, and elevation

• Removal of prosthetic joint

Gonococcal Arthritis

■ Essentials of Diagnosis

• Most common in young women during menses or pregnancy

• Tenosynovitis in many joints followed by monarticular arthritis

• Characteristic purpuric skin lesions on the distal extremities

• White cell count in synovial fluid 50,000/µL; synovial fluid Gramstain and culture uncommonly positive; likewise blood cultures

• Urethral, cervical, throat, skin lesion and rectal cultures on

choco-late or Thayer-Martin agar for Neisseria gonorrhoeae have higher

yield, may be positive in the absence of symptoms

• Recurrent disseminated gonococcal infection seen with ital complement component deficiencies

• Obtain VDRL, consider HIV testing

• Intravenous ceftriaxone or ceftizoxime for 7 days followed byoral cefixime or ciprofloxacin

• Daily reaspiration of the synovial fluid if it reaccumulates

• Organisms include Staphylococcus aureus, coagulase-negative

staphylococci, group A streptococci, gram-negative rods, obic and polymicrobial infections, tuberculosis, brucellosis, histoplasmosis, coccidioidomycosis, blastomycosis

anaer-• Blood cultures may be positive; aspiration or biopsy of bone isdiagnostic

• Radiographs early in the course are often negative, but ular demineralization, erosion of bone, and periostitis may occurlater

periartic-• Radionuclide bone scan is 90% sensitive and may be positivewithin 2 days after onset of symptoms

• Debridement if response to antibiotics is poor

Eosinophilic Fasciitis

■ Essentials of Diagnosis

• Occurs predominantly in men

• Pain, swelling, stiffness, and tenderness of the hands, forearms,feet, or legs evolving to woody induration and retraction of sub-cutaneous tissue within days to weeks

• Associated with peripheral eosinophilia, polyarthralgias, arthritis,carpal tunnel syndrome; no Raynaud’s phenomenon

• Biopsy of deep fascia is diagnostic

• Association with aplastic anemia, thrombocytopenia

Fibrositis (Fibromyalgia)

■ Essentials of Diagnosis

• Most frequent in women ages 20 –50

• Chronic aching pain and stiffness of trunk and extremities, cially around the neck, shoulder, low back, and hips

espe-• Must have 11 of 18 bilateral tender points: occiput, low cervical,trapezius, supraspinatus, second rib at costochondral junction,lateral epicondyle, gluteal region, greater trochanter, and medialfat pad of the knee

• Associated with fatigue, headaches, subjective numbness, sleepdisorders, irritable bowel symptoms, and history of sexual ordomestic abuse

• Absence of objective signs of inflammation; normal laboratorystudies, including erythrocyte sedimentation rate

• Patient education, supportive care, exercise programs

• Aspirin, other NSAIDs

• Tricyclics, cyclobenzaprine, chlorpromazine

• Injection of trigger points with corticosteroids

• May be primary (idiopathic or myeloma-associated), familial,localized, or secondary to familial Mediterranean fever, chronicinfectious or inflammatory disease, aging, hemodialysis; in each,

a different protein is responsible

• Distribution depends on type of amyloid; most systemic, butlocalized amyloid found in Alzheimer’s plaques, islet cells in dia-betics, carpal ligaments in dialysis patients

• Associated variably and unpredictably with peripheral athy, postural hypotension, nephrotic syndrome, cardiomyopa-thy, arrhythmias, esophageal hypomotility, hepatosplenomegaly,gastrointestinal malabsorption and obstruction, carpal tunnel syn-drome, macroglossia, arthropathy, endocrine gland insufficiency,respiratory failure, cutaneous lesions, and ecchymoses

neurop-• M-spike in primary amyloidosis

• Melphalan, prednisone if myeloma-associated

• Treat underlying disease if present

■ Pearl

The combination of nephrotic syndrome and hepatosplenomegaly in a middle-aged patient is amyloidosis; only rarely can other single pro- cesses do it.

Reference

Gertz MA et al: Amyloidosis Hematol Oncol Clin North Am 1999;13:1211.PMID: 10626146]

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Reflex Sympathetic Dystrophy

• Shoulder-hand variant with restricted ipsilateral shoulder ment common after neck or shoulder injuries or following myo-cardial infarction

move-• Characteristic disparity between degree of injury (usually est) and degree of pain (debilitating)

mod-• Triple phase bone scan reveals increased uptake in the early phases

of the disease; radiographs show severe osteopenia (Sudeck’s phy) late in the course

• Active and passive exercises combined with benzodiazepines

• Stellate ganglion or lumbar sympathetic block

• Short course of corticosteroids given early in course

Carpal Tunnel Syndrome

■ Essentials of Diagnosis

• The most common entrapment neuropathy, caused by sion of median nerve (which innervates the flexor muscles of thewrist and fingers)

compres-• Middle aged women and those with a history of repetitive use ofthe hands commonly affected

• Pain classically worse at night and exacerbated by hand movement

• Initial symptoms of pain or paresthesias in thumb, index, middle,and lateral part of ring finger; progression to thenar eminencewasting

• Pain radiation to forearm, shoulder, neck, chest, or other fingers

of the hand not uncommon

• Positive Tinel sign

• Usually idiopathic; common secondary causes include toid arthritis, amyloidosis involving carpal ligament, sarcoidosis,hypothyroidism, diabetes, pregnancy, acromegaly, gout

rheuma-• Diagnosis is primarily clinical; electrodiagnostic testing ing nerve conduction velocity) helpful in some

• Steroid injection into the carpal tunnel occasionally

• Surgical decompression in a few; best done prior to development

of thenar atrophy

■ Pearl

When obtaining a history of arm pain, remember that carpal tunnel drome affects the radial three and one-half fingers and myocardial ischemia the ulnar one and one-half—and hope it’s the right arm.

syn-Reference

Whitley JM et al: Carpal tunnel syndrome A guide to prompt intervention grad Med 1995;97:89 [PMID: 7816719]

Post-6

• Sexual dysfunction, weakness, easy fatigability; poor resistance

to stress, cold, or fasting; axillary and pubic hair loss

• Hypotension, often orthostatic; visual field defects if pituitarytumor present

• Deficient cortisol response to ACTH; low serum T4with low orlow-normal TSH; serum prolactin level may be elevated

• Low serum testosterone in men; amenorrhea; FSH and LH arelow or low-normal

• MRI may reveal a pituitary or hypothalamic lesion

■ Differential Diagnosis

• Anorexia nervosa or severe malnutrition

• Hypothyroidism

• Addison’s disease

• Cachexia due to other causes (eg, carcinoma or tuberculosis)

• Empty sella syndrome