Clin Med - Rheumatology Part I .pdf

Rheumatology I Christopher W. Stewart, M.D. Medical Director and Associate Professor Rheumatology Questions to ask: questions to ask to help determine the pathology – What is the joint pattern? how many joints involved? which joints involved? Symmetrical? One joint? Multiple joints? Large joints? Sm...

Rheumatology I Christopher W. Stewart, M.D. Medical Director and Associate Professor Rheumatology Questions to ask: questions to ask to help determine the pathology – What is the joint pattern? how many joints involved? which joints involved? Symmetrical? One joint? Multiple joints? Large joints? Small joints? – Extra-articular manifestations? (fever, rash, nodules, neuropathy, fatigue) Systemic symptoms present? – Inflammation? (erythema, warmth, swelling) Rheumatology Examination of joint fluid: – never pass a needle through area of cellulitis or plaque (risk of infection) – cell count: noninflammatory, inflammatory, purulent (guess where most specimens fall?) either non-inflammatory, inflammatory or purulent based on WBC Most fall between noninflammatory and inflammatory Use clinical judgment in deciding for all those in between – glucose and protein not helpful – microscopic: polarized light-monosodium urate (gout, birefringent urate crystals) vs. Ca2+ pyrophosphate (pseudogout, + birefringent rhomboid crystals) – can send fluid for cx. – Tables in book are good study guides Cell counts, organisms, etc. Osteoarthritis (OA) Most common joint disease Disease of aging Cartilage degeneration and bony hypertrophy at articular margins (wear-and-tear, bone-on-bone)inflammation is minimal Risk factors: Heredity, mechanical factors-also obesity, contact sports, occupational – not recreational running though Primary vs. Secondary not shoulders! mostly on weight baring joints (and hands/thumb) – primary: DIP, PIP joints, thumb, hip, knee, C- and L-spine – secondary: sites of old injury (trauma, overuse) primary is more wear and tear and secondary is sites of old injury OA is NOT systemic inflammation - it is WEAR and TEAR OA Clinical presentation: – Insidious, stiffness less than 15 min (not biggest complaint), pain worse with activity & better with rest – Heberden (DIP) nodes and Bouchard (PIP) nodes – Minimal signs of inflammation, no systemic s/s these nodes are hypertrophy joints from wear and tear If systemic symptoms are present, think something else Labs/Imaging – ESR is normal, synovial fluid noninflammatory Erythrocyte sedimentation rate: if RBC loaded down with lots of fibrin & inflammatory markers, more will settle faster = ESR ESR is non-specific – X-rays: joint space narrowing, osteophytes, thickened subchondral bone, cysts OA DDx.: – Don’t overlook metastatic bone dz. – Multiple myeloma (anemia, hypercalcemia, renal failure also present) – Osteoporosis – Shouldn’t be confused with RA Tx.: weight loss, physical activity, acetaminophen, NSAIDS (careful with elderly and those at risk for GI and renal side effects)-don’t use high doses – steroid injections (up to 4 x per year) – hip and knee replacements are very effective Gout Etiology acute onset of red, hot swollen joint can also be painful! – Metabolic, often familial, acute and monoarticular, can be chronic and deforming – overproduction or underexcretion of uric acid Primary vs. Secondary – primary (hereditary) – secondary (acquired)-table in book-medication, malignancy, chemo, ETOH, chronic kidney disease, lead poisoning etc. Epidemiology – often a challenging problem in transplant pts. – 90% of primary gout is men over 30 yo tophi-deposits of uric acid crystals (develop years later) Gout can occur with normal serum uric acid levels, and everyone with hyperuricemia doesn’t have gout chronic gout Gout Clinical Presentation – sudden onset, often nocturnal, often MTP joint of great toe (“podagra”)-also feet, ankles, knees-rarely hips and shouldersusu. monoarticular – exquisitely tender, swollen, erythematous-can be febrile – asymptomatic periods usu follow the initial attack-can progress to chronic, deforming polyarthritis – uric acid kidney stones in 5-10% – can be associated with progressive chronic kidney disease usually only in ONE joint Polyarticular more common with long-standing disease Gout Labs/Imaging: – serial uric acid levels are elevated in 95%-a single uric acid level is normal in 25% – leukocytosis is common – joint fluid analysis shows uric acid crystals (needlelike, - birefringent urate crystals) – X-ray: later in course-punched-out erosions with overhanging bone (“rat-bite”) must do SERIAL levels!!! DDx.: cellulitis, septic arthritis, pseudogout – chronic tophaceous gout may resemble RA Gout Treatment – asymptomatic hyperuricemia does not need treatment – for acute attack: NSAIDS (indomethacin), colchicine, steroids (provide rapid relief)-NOT a XO inhibitor! – between attacks: -when to start chronic meds? – low purine diet, weight loss, no ETOH, avoid certain meds – colchicine (careful with renal impairment) Gout Treatment (continued) – serum uric acid reducers (uricosurics and xanthine oxidase (XO) inhibitors)-use for frequent attacks, tophi, renal damage-NOT used in acute attacks – 24 hr urine uric acid level: < 800 mg/d, undersecretor, use uricosuric-> 800 mg/d, overproducer, use allopurinol – uricosurics-block tubular reabsorption of uric acidnot very useful with impaired renal function Gout Treatment (continued) – probenecid commonly used – must maintain relatively high urine output and urine alkalinization to prevent uric acid precipitation in urinary tract-don’t use if h/o uric acid stones – XO inhibitors: allopurinol and febuxostat-can precipitate an acute gout attack (can give colchicine)-never start during an acute attack – allopurinol-small but serious chance of toxic epidermal necrolysis (TEN) or Stevens-Johnson syndrome-also have to adjust for impaired renal fxn. Gout Treatment (continued) – febuxostat (Uloric)-less concern for hypersensitivity and easier to use with renal impairment – XO inhibitors can shrink tophi over time if pt. is compliant Chondrocalcinosis/Pseudogout Chondrocalcinosis: Ca2+ salts in articular cartilage – radiographic dx.-often familial-assoc. with many diseases (hemochromatosis, hyperpara., DM, hypothy., Wilson dz., pseudogout) Pseudogout: also called Ca2+ pyrophosphate dihydrate (CPPD) deposition dz.-rhomboid shaped, + birefringent crystals on joint fluid analysis are diagnostic – rarely chronic, often affects large joints, normal uric acid levels Fibromyalgia Similar to “chronic fatigue syndrome” Epidemiology – 3-10% of general population, cause unknown – Women 20-50 yo, absence of objective findings or diagnostic tests DIAGNOSIS OF EXCLUSION People usually get all of these objective tests anyway b/c dx of exclusion (must R/O other disease processes) Clinical Presentation – chronic pain and stiffness of entire body, esp. neck, shoulders, low back and hips – fatigue, sleep disturbance, HA, IBS sx. Theory that sleep disturbance may be involved in etiology of dz – “trigger points”-trapezius, knee, elbow Places that are exquisitely tender to the touch Fibromyalgia Must find at least 11 of these 18 tender points Fibromyalgia Diagnosis of exclusion – must r/o RA, SLE, hypothy., polymyositis, PMR (polymyalgia rheumatica) – unremarkable labs in fibromyalgia Any objective signs (fever, wt. loss, etc.) should prompt further investigation-also in pts. over 50 yo – Remember, these people should have unremarkable exams with the exception of trigger points Treatment: cognitive therapy, meds (anti-dep., gabapentin, pregabalin, muscle relaxers etc.), good sleep hygeine, exercise – NOT opiates Rheumatoid Arthritis (RA) Chronic systemic inflammatory disease – synovitis/arthritis of multiple joints – Very different from OA (limited dz that lacks inflammation) Epidemiology/Etiology – Predominately women, 4th-5th decade – Cause unknown, genetic component – Inflammatory response causes erosion of cartilage, bones, ligaments and tendons Clinical Presentation – joint sx. predominate-insidious onset of pain and stiffness -symmetric swelling of multiple joints Hot, swollen, tender, red joints – morning stiffness > 30 min. Gets better with activity – MCP, PIP, MTP, wrist, knee, ankle - not DIP – carpal tunnel, C-spine Disease attacks the body’s tissues because does not recognize them (sees them as foreign) RA Because this is an inflammatory/systemic disease, symptoms can present anywhere in the body! -multiple complaints -multiple PE findings Clinical Presentation (continued) – rheumatoid nodules: over bony prominences, also lungs, sclera-correlate with + RF Inflammatory nodules, common over shins and extensor surfaces or arms (consider erythema nodosum, sarcoidosis, gout, etc.) – ocular: dryness, scleritis, episcleritis – other: ILD (rheumatoid lung), pericarditis, pleuritis, small vessel vasculitis, aortitis, Felty syndrome, palmar erythema RA Labs/Imaging – anti-CCP antibodies and rheumatoid factor (RF)+ in 70-80% – can have false + RF (aging, Hep. C, syphilis, SBE, TB) Can have sero-negative rheumatoid arthritis Consider other disease processes as well – Elevated ESR and CRP, normocytic anemia (MCV normal, anemia of chronic dz., H&H usually not too low), leukopenia, thrombocytosis ESR and CRP elevated d/t inflammation – Synovial joint fluid is inflammatory Beware of septic arthritis (patients with RA at increased risk) – X-ray: 1st 6 mos. usu. normal-later, joint space narrowing and erosions, C1-2 subluxation x-ray can be used to monitor progress so it is important to get initial and early on x-rays RA DDx.: OA (easy to distinguish), chronic tophaceous gout, spondyloarthropathies, Hep. C, SLE, PMR, rheumatic fever, paraneoplastic synd. Treatment: – NSAIDS (GI and renal side effects) – steroids (usu. 5-10 mg/d of prednisone) – DMARDS (disease-modifying antirheumatic drugs) RA NBDMARDs: – Should be started as soon as possible (the earlier they are started, the better – 1. Methotrexate (MTX) Risk of: GI irritation, stomatitis, cytopenia, hepatotoxicity) – 2. sulfasalazine (cytopenia, G6PD deficiency) – 3. leflunomide – 4. antimalarials-hydroxychloroquine-can cause retinitis so needs yearly eye exams 5. minocycline-has anti-inflammatory properties Biologic Response Modifiers (DMARDs) – 6. TNF inhibitors (etanercept etc.)-work well, risk for bacterial infections and reactivation of latent TB – 7. monoclonal antibodies (-mabs) RA Complications: – chronic deformities: ulnar deviation, boutonniere and swanneck deformities of PIP and DIP joints – higher mortality due to CV disease as a result of chronic systemic inflammation Systemic Lupus Erythematosus (SLE) Autoimmune D/O –autoantibodies to nuclear antigens Affects multiple organ systems, clinical course and severity varies-spontaneous relapses and remissions – Can do anything anywhere (one of the great imitators) Epidemiology/Etiology – influenced by gender (85% female), race (blacks), and inheritance – drug-induced lupus (table in book) men = women, no nephritis or CNS features, no low complement or anti-ds DNA ab, normalize after drug is D/C’d Always suspect SLE in multisystem dz. with positive antinuclear antibody (ANA) – ANA is very sensitive for lupus (if negative, likely r/o lupus) In SLE, body relentlessly attacks its own tissue! SLE Clinical Presentation – fever, anorexia, malaise/fatigue, wt. loss These patients feel terrible – skin lesions (malar “butterfly” rash), discoid lesions, alopecia, mucocutaneous (oral ulcers), Raynaud phenomenon etc. – joint sx. in over 90% – ocular: conjunctivitis, photophobia, transient blindness – cardiac: myocarditis, pericarditis, arrhythmias, mitral regurg. due to Libman-Sacks (fibrinous vegetation), endocarditis – vasculitis: mesenteric, aneurysms SLE Various presentations of discoid lesions Alopecia Libman-Sacks endocarditis SLE Clinical Presentation (continued) CNS and renal manifestations are usually the worst symptoms of lupus – neurologic: psychosis, cognitive deficits, depression, seizures, neuropathy, stroke, myelitis – renal: glomerulonephritis, interstitial nephritis often ends in end-stage renal dz. – pulmonary: pleurisy, effusions, pneumonitis, restrictive lung dz., alveolar hemorrhage (rare) SLE Labs: – See tables in book-useful reference – + ANA is present in virtually all SLE pts. (very sensitive but not as specific) + ANA helps you if you suspect lupus (but there are a lot of things that have + ANA) – ANA really helps you (if negative, usually no lupus) – anti-ds DNA and anti-Sm are specific but not sensitive – APLA can be + – U/A: hematuria, proteinuria, casts SLE DDx. is broad-RA, vasculitis, scleroderma, viral hepatitis etc. Dx.: 4 out of 11 criteria in table in book (learn this table) Treatment: – limit sun exposure, topical steroids for skin lesions – antimalarials (hydroxychloroquine) Requires yearly eye exam – systemic steroids for more troubling sx. (nephritis, pericarditis, CNS dz. etc.) Always use lowest dose for shortest amount of time possible – immunosuppressive drugs (cyclophosphamide, mycophenolate, azathioprine) – if APLA syndrome need anticoagulation SLE Course/Prognosis/Complications – – – – relapsing and remitting course 10 yr survival is 85% early mortality usu. from infection, renal or CNS dz. later mortality due to atherosclerosis from chronic inflammation-risk of MI is 5 x higher in SLE ALL of these disorders that result in chronic inflammation increase risk of CVD Control CV risk factors! – avascular necrosis is a long-term problem – ? Increased risk of malignancy Antiphospholipid Antibody Syndrome (APLA) Definition: body making antibodies to certain phospholipids & causing problems – Recurrent venous/arterial occlusions, recurrent fetal loss, thrombocytopenia with + APLA If making this diagnosis in isolation, no other SLE criteria should be present Clinical Presentation – Often found after multiple miscarriages – DVT, P.E., CVA-less commonly MI or digital infarctions, cerebral sinus vein thrombosis, Budd-Chiari syndrome – mental status changes, livedo reticularis (predictor of arterial events) APLA 3 types of APLA: – anti-cardiolipin ab – lupus anticoagulant Probably most common Lupus anticoag. causes prolonged PTT – antibody assoc. with false + syphilis test (RPR) DDx.: other autoimmune diseases, hypercoagulable states (protein C & S, Factor V Leiden, antithrombin III def.) Treatment: lifelong anticoagulation Pregnancy: heparin and ASA Raynaud’s Phenomenon Definition: paroxysmal digital ischemia (usu. fingers) caused by cold or emotional stress Presentation: – Vasoconstriction followed by vasodilation – Pale, cold, ischemic, white digits that subsequently turn red as blood flow returns Primary vs. Secondary – Primary: 2-6% of population, young women, symmetric involvement of bilat. fingers-no threat – Secondary: (Table 20-12)-assoc. with rheumatic dz. (scleroderma), can cause ulceration or gangrene-nailfold capillary abnormalities DDx.: Buerger dz., type 1 cryoglobulinemia, erythromelalgia RP Treatment: – gloves/mittens – stay warm – avoid hand injury – no smoking – avoid certain drugs (decongestants) – Ca2+ blockers for refractory disease – sympathectomy (digital or cervical) Usually no necessary Scleroderma (Systemic Sclerosis) Relatively rare disorder characterized by diffuse fibrosis of skin and internal organs Epidemiology: 3rd-5th decade, women 3x as often as men Limited vs. Diffuse – Limited (20%) CREST syndrome (calcinosis of skin, RP, esophageal dysmotility, sclerodactyly-thickened, elongated fingers, telangiectasia) skin changes in face and hands only better outcomes but more digital ischemia and pulm HTN – Diffuse (80%) skin changes in trunk and proximal ext.-renal, pulmonary and cardiac complications Renal and pulmonary are major problems Most diet from end-stage pulmonary HTN Scleroderma Clinical Presentation: – RP, polyarthralgia, wt. loss, malaise – skin: thick and hide-like, fingertip ulceration, depigmentation, calcification cutaneous sx. usu. occur before visceral – GI: dysphagia, reflux, hypomotility, malabsorption, pseudoobstruction – pulm: restrictive lung dz., pulm fibrosis  pulm HTN – cardiac: pericarditis, heart block, R sided CHF due to pulm HTN (cor pulmonale) – renal: scleroderma renal crisis with severe HTN Scleroderma Scleroderma Labs: + ANA, anemia, anti-SCL 70, anticentromere ab DDx.: other autoimmune diseases (SLE) Treatment – no effective treatment for underlying disease – Ca2+ blockers for RP, PPI’s for reflux, abx for malabs/bact. overgrowth – ACE-inh. for renal crisis – sildenafil or prostaglandins for pulm HTN Scleroderma Prognosis – 9 yr survival is 40% worse in blacks, males, older pts – Most die from lung dz. (pulm HTN or fibrosis), also from CHF or renal dz. Polymyositis/Dermatomyositis Etiology/Epidemiology – cause unknown-main sx. is muscle weakness – 5th-6th decades, women 2x more than men, more often in blacks Clinical Presentation: – gradual, progressive weakness of proximal muscle groups of upper and lower ext. – difficulty rising from chair or climbing stairs, combing hair, reaching into cabinet overhead – no facial or ocular muscle weakness – muscle pain and dysphagia in ¼ of cases Muscle pain usually not the main complaint – severe dz.-respiratory muscle weakness (mech. ventilation) Poly/Dermato Clinical Presentation (continued) – rash of dermato. is red and can be malar – also rash to face, neck, shoulders, upper chest and back (“shawl sign”) – periorbital edema and purplish heliotrope rash over eyelids – Gottron sign-scaly rash over dorsal MCP and PIP joints Labs – elevated CK and aldolase, + ANA – anti-Jo-1 ab seen in pts with ILD – EMG can aid in diagnosis but muscle biopsy is only specific diagnostic test Poly/Dermato Poly/Dermato Complications: –  risk of malignancy with dermatomyositis (not poly) associated malignancies (dermato-): ovarian, lung, pancreatic, stomach, colorectal, NHL DDx.: SLE, scleroderma, Sjogren synd., inclusion body myositis, thyroid dz., drugs, HIV, vasculitis, MS, myasthenia gravis, ALS etc. Treatment: – steroids, often long-term – steroid resistant: MTX or azathioprine – limit sun exposure with dermato. MCTD and Overlap Syndromes MCTD: mixed connective tissue disease many pts. have signs and sx suggestive of more than one type of rheumatic or autoimmune disease – Do not fit in one specific disease -treat based on organ system involvement -there can be lots of overlap