(1)
Division of Rheumatology, Department of Medicine, University of Alberta, Edmonton, AB, Canada
Septic Arthritis
Differential Diagnosis of Monoarthritis
★ICU RN★
I nfections
BACTERIAL—Gonococci, Staphylococcus aureus, Streptococcus, Enterobacteriaceae, Borrelia burgdorferi, Syphilis, TB
VIRAL—HIV, HBV, Parvovirus, rubella, mumps, enterovirus, adenovirus
FUNGAL—Cryptococcus, Blastococcus
OSTEOMYELITIS/OSTEONECROSIS EXTENDING TO JOINT
C rystal—gout, pseudogout, hydroxyapatite, basic calcium phosphate
U nclassified
TRAUMA
OSTEOARTHRITIS
HEMARTHROSIS—coagulopathy, thrombocytopenia, pigmented villonodular synovitis, trauma
NON–ARTHRITIS
BONE—osteomyelitis, avascular necrosis, fracture
SOFT TISSUE—tendonitis, ligament tear, bursitis, myositis, meniscus tear
R heumatologic (early stage, unusual presentation as monoarthritis)
SEROPOSITIVE★PSSR★—Polymyositis, Palindromic rheumatism, SLE, Scleroderma, Rheumatoid arthritis
SERONEGATIVE★PEAR★—Psoriatic arthritis, Enteric arthritis, Ankylosing spondylitis, Reactive arthritis
SARCOIDOSIS, POLYMYALGIA RHEUMATICA
N eoplastic—chondrosarcoma, osteoid osteoma, metastasis
Pathophysiology
RISK FACTORS
—50% of sexually active adults with septic arthritis are due to gonococcal infections, while most patients with risk factors for septic arthritis listed below are due to non-gonococcal infections (S. aureus, Streptococci, Gram-negative bacilli)
COMORBIDITIES—diabetes, chronic kidney disease, rheumatologic disease, cancer, advanced disability
TREATMENT RELATED—immunosuppressive therapy (glucocorticoids, cytotoxic agents), prosthetic joint
SPECIFICS—IDU (more axial joints with MRSA, Gram negative especially Pseudomonas), endocarditis (sterile fluid as autoimmune process)
GONOCOCCAL ARTHRITIS
—more common in women. Less destructive and has better outcome than non-gonococcal arthritis. The synovial fluid Gram stain is only positive in <10%, and culture is often negative in gonococcal arthritis
COMPLICATIONS
—osteomyelitis (30%), permanent joint damage, sepsis
Clinical Features
HISTORY
—arthritis (location, duration, pain, range of motion, function), adenopathy, fever, rash, oral ulcers, alopecia, Raynaud’s, photosensitivity, sicca, trauma, recent infections, cervical/urethral discharge, sexual encounters, diarrhea, recent travel, past medical history (pre-existing joint disease, gout, rheumatoid arthritis, SLE, IBD, psoriasis, diabetes, IDU), medications (anticoagulants)
PHYSICAL
—vitals (fever), joint examination (tenderness, swelling, range of motion). Look for nail pitting, onycholysis, tophi, rheumatoid nodules, track marks, psoriasis, keratoconjunctivitis sicca, uveitis, conjunctivitis, episcleritis, murmurs, urethral discharge, and penile ulcers. Examine all joints and pay particular attention to the affected one. Soft tissue injuries (bursitis, tendonitis, muscles) usually have decreased active range of motion but normal passive range of motion, while both active and passive range of motion would be affected in joint diseases. Pelvic examination to inspect the cervix and to look for pelvic inflammatory disease
RATIONAL CLINICAL EXAMINATION SERIES: DOES THIS ADULT PATIENT HAVE SEPTIC ARTHRITIS?
Sens (%) | Spc (%) | LR+ | LR− | |
---|---|---|---|---|
History | ||||
Age >80 | 19 | 95 | 3.5 | 0.86 |
Diabetes | 12 | 96 | 2.7 | 0.93 |
Rheumatoid arthritis | 68 | 73 | 2.5 | 0.45 |
Recent joint surgery | 24 | 96 | 6.9 | 0.78 |
Hip/knee prosthesis | 35 | 89 | 3.1 | |
Skin infection | 32 | 88 | 2.8 | 0.73 |
HIV infection | 79 | 50 | 1.7 | 0.47 |
Joint pain | 85 | |||
Joint edema | 78 | |||
Fever | 57 | |||
Sweats | 27 | |||
Rigors | 19 | |||
Physical | ||||
Fever | 46 | 31 | 0.67 | 1.7 |
Investigations | ||||
Elevated WBC | 90 | 36 | 1.4 | 0.28 |
Elevated ESR | 95 | 29 | 1.3 | 0.17 |
Elevated CRP | 77 | 53 | 1.6 | 0.44 |
Synovial fluid analysis | ||||
WBC >100,000/mL | 29 | 99 | 28 | 0.71 |
WBC >50,000/mL | 62 | 92 | 7.7 | 0.42 |
WBC >25,000/mL | 77 | 73 | 2.9 | 0.32 |
PMN ≥90% | 73 | 79 | 3.4 | 0.34 |
APPROACH—“when evaluating a patient with a painful, peripheral, swollen joint, the underlying pathology of a monoarthritis may be difficult to diagnose by clinical history and examination alone due to nonspecific symptoms and signs. Identifiable risk factors and arthrocentesis are most helpful in predicting septic arthritis. In particular, synovial WBC count and percentage of polymorphonuclear cells provide the best utility in identifying septic arthritis while waiting for Gram stain and culture test results. There is no evidence that a patient’s symptoms or the physical examination are useful for predicting non-gonococcal bacterial arthritis”
JAMA 2007 297:13
Investigations
BASIC
LABS—CBCD, lytes, urea, Cr, uric acid, ANA, RF, ESR, CRP, INR, PTT
IMAGING—joint XR (chondrocalcinosis in pseudogout; the presence of crystals does not rule out sepsis)
ARTHROCENTESIS—★3C★ (Cell count with diff, Culture and Gram stain, Crystals)
SPECIAL
INFECTIOUS WORKUP—urethral/rectal swabs, blood C&S
Diagnostic Issues
GOLDEN RULE
—patients with monoarthritis have septic arthritis until proven otherwise. Joint infection is a rheumatologic emergency as permanent damage can occur. Presence of crystal does not rule out infection. In up to 75% of patients with septic arthritis, a focus of infection may be found
ARTHROCENTESIS FLUID ANALYSIS
Normal | Non-Infectious | Infectious | Septic | |
---|---|---|---|---|
WBC (/mm3) | <200 | 200–2000 | 2000–50,000 | >50,000 |
PMNs | <25% | <25% | 25–50% | >50% |
JOINT ASPIRATIONS/INJECTIONS
—for diagnostic and sometimes therapeutic reasons. Absolute contraindication is infection overlying site of injection. Relative contraindications include significant hemostasis defects and bacteremia (NEJM 2006 354:e19)
KNEE—flex 10–15°, enter either medially or laterally immediately beneath the undersurface of the patella slightly above midway
ANKLE—foot perpendicular to leg, medial approach immediately medial to the extensor hallucis longus tendon. Lateral approach just distal to fibula
WRISTS—flex slightly. Medial approach at dorsal surface between the distal ulna and the carpal bones. Lateral approach at dorsum just distal to the end of the radius, between the extensor tendons of the thumb
ADVERSE EFFECTS OF ASPIRATIONS/INJECTIONS—hypersensitivity to anesthetic, pain, infection, tendon rupture, subcutaneous atrophy, post-injection flare, systemic steroid absorption, hemorrhage, steroid arthropathy
Management
REMEMBER TO ALWAYS ASPIRATE BEFORE PROCEEDING TO TREATMENT
SYMPTOM CONTROL
—NSAIDs/opioids for pain
TREAT UNDERLYING CAUSE
—empiric (if not at risk for sexually transmitted disease, nafcillin 2 g IV q4h or vancomycin 1 g IV q12h, plus ceftriaxone 2 g IV q24h or cefotaxime 2 g IV q8h. If at risk of sexually transmitted disease, nafcillin 2 g IV q4h for Gram positive organisms on Gram stain; otherwise, give ceftriaxone 2 g IV q24h or cefotaxime 2 g IV q8h if organisms not identifiable yet). Gonococcal (ceftriaxone 1 g IV q24h). Lyme arthritis (amoxicillin 500 mg PO TID, doxycycline 100 mg PO BID, or ceftriaxone 2 g IV daily × 4 weeks). Therapeutic arthrocentesis. Arthroscopic or surgical drainage (if joint inaccessible to needle drainage, organism resistant to antibiotics, or no clinical response in 3–4 days)
Gout
NEJM 2003 349:17
Causes
DECREASED URATE EXCRETION (90%)
RENAL DISEASE
DRUGS ★CAN’T LEAP★—Cyclosporine, Alcohol, Nicotinic Acid, Thiazides, Loop diuretics, Ethambutol, ASA (low dose), Pyrazinamide
INCREASED URATE PRODUCTION (10%)
METABOLIC SYNDROME—obesity, hyperlipidemia, hypertension
INCREASED METABOLISM—alcohol, hemolytic anemia, psoriasis, Lesch–Nyhan syndrome
NEOPLASTIC—myeloproliferative disease, lymphoproliferative disease, chemotherapy
Pathophysiology
IMBALANCE
—decreased urate excretion and/or increased urate production → uric acid crystals deposited in joints, skin, and kidneys → arthritis, tophi, and renal failure. Gout almost never occurs in pre-menopausal women (estrogen promotes higher urinary fractional excretion of urate)
PRECIPITANTS
—surgery, dehydration, fasting, binge eating, binge drinking, exercise, trauma
Clinical Features
SYMPTOMS
ARTHRITIS—mono/oligo and asymmetric, especially first MTP joint. Podagra, inflammation of the first MTP joint, is the presenting symptom in 75% of gout patients. However, the first MTP is also commonly affected in pseudogout, psoriatic arthritis, sarcoidosis, osteoarthritis, and trauma
TOPHI—yellowish-white nodular urate crystals collection in subcutaneous tissues (particularly colder extremities such as ear, fingers, olecranon bursa, ulnar aspect of forearm), bone, tendons (Achilles), cartilage, and joints. Generally painless but may lead to erosions
KIDNEYS—urolithiasis (radiolucent), uric acid nephropathy (reversible acute renal failure secondary to acute lysis), urate nephropathy (chronic renal failure secondary to interstitial deposits)
Investigations
BASIC
LABS—CBCD, lytes, urea, Cr, uric acid (sens 75%), AST, ALT, ALP, bilirubin, TSH, urinalysis, 24-h urine uric acid collection (<800 mg/day suggests ↓ excretion)
IMAGING—joint XR, dual energy CT
ARTHROCENTESIS—★3C★ (Cell count with diff, Culture and Gram stain, Crystal, for gout, sens 85%, spc 100%)
SPECIAL
TOPHI ASPIRATION
Diagnostic Issues
SERUM URIC ACID LEVELS
—may be falsely lowered in an acute attack
JOINT X-RAY
—soft tissue swelling, normal joint space, erosions (“punched out” and sclerotic lesions with overhanging edge)
JOINT FLUID
—ALWAYS confirm diagnosis with a synovial fluid tap if possible. Microscopy shows predominantly neutrophilic infiltrate with some intracellular monosodium urate crystals (needle shaped, negative birefringence, i.e. yellow when parallel to plane of polarized light)
Management
ACUTE
—NSAIDs (first line, avoid if renal/hepatic failure; naproxen 375–500 mg PO BID × 3 days, then 250–375 mg PO BID × 4–7 days; sulindac 150–200 mg PO BID × 7–10 days; indomethacin 25–50 mg PO TID × 3 days, then 100 mg PO div BID–QID × 4–7 days; celecoxib 200 mg PO BID × 1 day, then 100 mg PO BID × 6–10 days). Systemic corticosteroids (avoid if joint sepsis not excluded; prednisone 30–60 mg PO daily × 3 days, then ↓ 10–15 mg daily × 3 days until discontinuation, triamcinolone 50 mg IM × 1 dose). Intra–articular corticosteroids (for mono- and oligoarthritis only. Methylprednisolone 40–80 mg intra-articularly once). Colchicine 0.6 mg PO daily-BID during acute attack (avoid the approach of giving colchicine q1h until development of diarrhea). Low dose colchicine regimens (≤1.8 g daily) appear as effective and are better tolerated than higher dose regimens
LONG-TERM MANAGEMENT
—purine-restricted diet (↓ red meats, ↓ seafood, ↑ low-fat dairy products, ↑ fruit and veggies) have limited supportive evidence. Avoidance of beer and sugar-laden beverages is beneficial. Allopurinol 50–300 mg PO daily (first line, xanthine oxidase inhibitor, renal dose adjustment required, urate-lowering therapy generally not started in acute attack; however, continue allopurinol if already on it prior to acute attack). Febuxostat 80 mg PO daily is a newer xanthine oxidase inhibitor that can be used in patients intolerant of allopurinol or in those with mild-to-moderate renal failure. Probenecid 250–1000 mg PO BID (first line, ↓ renal urate reabsorption. Ensure normal renal function). Sulfinpyrazone 50–200 mg PO BID. Colchicine 0.6 mg PO BID × 6 months (for prophylaxis against recurrent attacks only. Do not give colchicine IV)
Treatment Issues
LONG-TERM THERAPY
—consider if patients have frequent attacks (≥3/year, tophaceous deposits, overproduction of uric acid, or continued cyclosporine treatment)
ALLOPURINOL OR FEBUXOSTAT TREATMENT
—remember to start colchicine or NSAIDs prior to allopurinol and to overlap therapy to prevent precipitating flare. Allopurinol alone can cause an abrupt decrease in serum uric acid → breakdown and release of synovial urate crystal deposits → inflammation. Aim to decrease serum uric acid level below 362 μmol/L [5.1 mg/dL]. Do not start or stop allopurinol during an acute attack
Specific Entities
CALCIUM PYROPHOSPHATE DEPOSITION DISEASE (CPPD, pseudogout)
—associated with normal urate levels and chondrocalcinosis that may be visible radiographically. Crystals appear rhomboid and have positive birefringence (blue when parallel to polarized light, yellow when perpendicular). Risk factors include old age, advanced osteoarthritis, neuropathic joint, gout, hyperparathyroidism, hemochromatosis, diabetes, hypothyroidism, hypomagnesemia, trauma, and symptoms
BASIC CALCIUM PHOSPHATE CRYSTALS
(BCPC)—crystals appear snowball-like with Alizarin red S stain. Implicated in bursitis, inflammation superimposed on osteoarthritis, and calcinosis cutis in systemic sclerosis and CREST
DIALYSIS PATIENTS
—develop destructive arthritis and tendonitis from calcium oxalate, monosodium urate, calcium pyrophosphate, and basic calcium phosphate crystals. Amyloidosis may also contribute to arthritis
Polyarticular Joint Pain and Fever
NEJM 1994 330:11
Differential Diagnosis
★RICE★
R heumatologic
SEROPOSITIVE—SLE, rheumatoid arthritis
SERONEGATIVE—psoriatic arthritis, enteric arthritis, reactive arthritis, ankylosing spondylitis
VASCULITIS—polymyalgia rheumatica, granulomatosis with polyangiitis, Behcet’s disease, Still’s disease
I nfections
BACTERIAL—septic (Gonococci), meningococci, endocarditis, Lyme disease, Whipple’s disease, mycobacteria
VIRAL—Parvovirus, rubella, HBV, HCV, HIV, EBV
FUNGAL
POST–INFECTIOUS/REACTIVE—enteric infections (Salmonella, Shigella, Campylobacter, Yersinia), genitourinary infections (Chlamydia), rheumatic fever, inflammatory bowel disease
C rystal – induced—gout, pseudogout
E tc
MALIGNANCIES—acute leukemia
SARCOIDOSIS—Lofgren’s syndrome
F AMILIAL M EDITERRANEAN FEVER
POLYMYALGIA RHEUMATICA
MUCOCUTANEOUS DISORDERS—dermatomyositis, erythema nodosum, erythema multiforme, pyoderma gangrenosum, pustular psoriasis
Clinical Features
DISTINGUISHING FEATURES
TEMPERATURE >40 °C [>104 °F]—Still’s disease, bacterial arthritis, SLE
FEVER PRECEDING ARTHRITIS—viral arthritis, Lyme disease, reactive arthritis, Still’s disease, bacterial endocarditis
MORNING STIFFNESS—RA, polymyalgia rheumatica, Still’s disease, some viral/reactive arthritis
MIGRATORY ARTHRITIS—rheumatic fever, gonococcemia, meningococcemia, viral arthritis, SLE, acute leukemia, Whipple’s disease
EPISODIC RECURRENCE—palindromic rheumatism, Lyme disease, crystal-induced arthritis, IBD, Whipple’s disease, Familial Mediterranean fever, Still’s disease, SLE
PAIN DISPROPORTIONATELY GREATER THAN EFFUSION—rheumatic fever, Familial Mediterranean fever, acute leukemia, AIDS
EFFUSION DISPROPORTIONATELY GREATER THAN PAIN—tuberculosis arthritis, bacterial endocarditis, IBD, giant cell arteritis, Lyme disease
SYMMETRIC SMALL JOINT SYNOVITIS—RA, SLE, viral arthritis
LEUKOCYTOSIS (>15 × 109/L)—bacterial arthritis, bacterial endocarditis, Still’s disease, systemic vasculitis, acute leukemia
LEUKOPENIA—SLE, viral arthritis
POSITIVE RHEUMATOID FACTOR—RA (sens 70%, spc 70%), viral arthritis, tuberculosis arthritis, bacterial endocarditis, SLE, sarcoidosis, systemic vasculitis
POSITIVE ANTI – CYCLIC CITRULLINATED PEPTIDE ANTIBODIES ( ACPA )—RA (not sensitive but highly spc 95%)
Investigations
BASIC
LABS—CBCD, lytes, urea, Cr, AST, ALT, ALP, bilirubin, uric acid, TSH, ESR, CRP, RF, anti-CCP, ANA, serologies (Borrelia burgdorferi, Streptococci, Parvovirus, HBV, HCV, HIV), c-ANCA, urinalysis
IMAGING—CXR, X-rays of affected joints
SPECIAL
ARTHROCENTESIS—★3C★ (Cell count with diff [>2000 WBC/mm3], Culture and Gram stain, Crystal)
Management
TREAT UNDERLYING CAUSE
SYMPTOM CONTROL
Specific Entities
STILL’S DISEASE
PATHOPHYSIOLOGY—unknown. Most consider this as a diagnosis of exclusion
DIAGNOSIS—major criteria include fever ≥39 °C [≥102.2 °F] (quotidian vs. diquotidian), salmon color maculopapular rash, arthralgia/arthritis ≥2 weeks, leukocytosis. Minor criteria include pharyngitis, lymphadenopathy, abnormal liver enzymes, hepatomegaly/splenomegaly, negative ANA, and RF. Need at least 2 major criteria and 3 minor criteria to make diagnosis (sens 93%). Important to exclude infections, malignancy, and acute rheumatologic disease. Significantly elevated serum ferritin
TREATMENTS—NSAIDs, corticosteroids, methotrexate, recombinant IL-1 receptor antagonist (anakinra)
Rheumatoid Arthritis
Differential Diagnosis of Polyarthritis
★RICE★
R heumatologic (>6 weeks)
SEROPOSITIVE ★PSSR★—Polymyositis, Palindromic rheumatism, SLE, Scleroderma, Sjogren’s syndrome, Rheumatoid arthritis
SERONEGATIVE ★PEAR★—Psoriatic arthritis, Enteric arthritis, Ankylosing spondylitis, Reactive arthritis, undifferentiated
VASCULITIS—polymyalgia rheumatica, granulomatosis with polyangiitis, Behcet’s disease, Still’s disease
I nfections (<6 weeks)
BACTERIAL—sepsis, endocarditis, Lyme disease, Whipple’s disease, mycobacteria
VIRAL—Parvovirus, rubella, HBV, HCV, HIV
FUNGAL
POST–INFECTIOUS/REACTIVE—enteric infections, genitourinary infections, rheumatic fever, inflammatory bowel disease
C rystal—gout, pseudogout, hydroxyapatite, basic calcium phosphate
E tc
MALIGNANCIES—leukemia
SARCOIDOSIS—Lofgren’s syndrome
F AMILIAL M EDITERRANEAN FEVER
MUCOCUTANEOUS DISORDERS—dermatomyositis, erythema nodosum, erythema multiforme, pyoderma gangrenosum, pustular psoriasis, polymyalgia rheumatica
Pathophysiology
CLASSIFICATION OF ARTHRITIS
MONOARTHRITIS—1 joint involved
OLIGOARTHRITIS—2–4 joints involved
POLYARTHRITIS— ≥ 5 joints involved
DESTRUCTION OF CARTILAGE
—T-helper 1 mediated process → proteases produced by synovial cells destroy proteoglycans in the articular cartilage → irreversible damage 6 months to 1 year from disease onset
POSSIBLE TRIGGERS
—viruses (Parvovirus, EBV, HTLV), super-antigens (from bacteria/viruses), autoantigens (QKRAA)
RISK FACTORS
—age >50, female (3:1), first-degree relative with rheumatoid arthritis, smoking, low level of education
Clinical Features
JOINT SYMPTOMS
—symmetric polyarthritis with joint pain, swelling, redness, morning stiffness (>1 h), and dysfunction
HANDS—MCP, PIP, and wrist joints most commonly involved. Deformities include Boutonniere, swan neck, Z (thumb), ulnar deviation at MCP joint, volar subluxation of proximal phalanx from MCP head, radial deviation of carpus, compression of the carpal bones, subluxation at the wrist
FEET—MTP joint involved. Deformities include valgus of the ankle and hindfoot, pes planus, forefoot varus and hallux valgus, cock-up toes
LEGS—knees (80%), ankles (80%), hips (50%)
ARMS—shoulders (60%), elbows (50%), acromioclavicular (50%)
ATLANTOAXIAL—subluxation may lead to spinal cord compression (cervical myelopathy with hand weakness/numbness)
TEMPOROMANDIBULAR (30%)
OTHERS—related disorders include Baker cyst, tenosynovitis, carpal tunnel syndrome
Related Topics
Gout (p. 311)
Inflammatory Myositis (p. 319)
Lupus (p. 317)
Scleroderma (p. 318)
EXTRA-ARTICULAR MANIFESTATIONS
—only in seropositive patients
RHEUMATOID NODULES (20%)
PULMONARY—pleural effusion (exudates, low glucose), pulmonary nodules (Caplan’s syndrome), acute interstitial pneumonitis, bronchiolitis obliterans
CARDIAC—valvular abnormalities, myocarditis, pericardial effusion, constrictive pericarditis
GI—elevated transaminases (especially ALP), nodular hyperplasia (portal hypertension, hypersplenism)
HEMATOLOGIC—anemia of chronic disease, Felty syndrome (triad of seropositive rheumatoid arthritis, neutropenia often associated with anemia and thrombocytopenia and splenomegaly. Patients at risk of life-threatening bacterial infections). Large granular lymphocyte leukemia, lymphoma
NEUROLOGIC—peripheral sensory neuropathy (not motor), myelopathy from cervical vertebral subluxation
OPHTHALMIC—keratoconjunctivitis sicca (Sjogren’s syndrome), scleritis, episcleritis
DERMATOLOGIC—vasculitis (digital arteritis, cutaneous ulceration, visceral arteritis)
OTHERS—amyloidosis
CONSTITUTIONAL SYMPTOMS
—fatigue (40%), fever (low grade), sweats, weight loss, myalgia
DISTINGUISHING FEATURES BETWEEN INFLAMMATORY AND NON-NFLAMMATORY ARTHRITIS
Inflammatory | Non-inflammatory | |
---|---|---|
Classic example | RA | OA |
Morning stiffness | >1 h | +/− |
Resting | Worsens | Improves |
Activity | Improves | Worsens |
Synovitis, redness | + | – |
Fever, weight loss | + | – |
ESR, CRP, platelets | ↑ | No change |
Investigations
BASIC
LABS—CBCD, lytes, urea, Cr, AST, ALT, ALP, bilirubin, ESR, CRP, RF (IgM), anti-CCP (more specific), ANA, urinalysis
IMAGING—X-rays of affected joints (particularly hands, knees, and ankles; soft tissue swelling, periarticular osteopenia, narrowing of joint space, marginal bony erosions, subluxation, joint destruction, bony ankylosis)
SPECIAL
INFECTIOUS WORKUP—serologies (Parvovirus, HBV, HCV, EBV, CMV, Borrelia burgdorferi)
ARTHROCENTESIS—★3C★ (Cell count with diff [>2000 WBC/mm3], Culture and Gram stain, Crystal. Cannot make definite diagnosis of rheumatoid arthritis from arthrocentesis)
Diagnostic and Prognostic Issues
ACR DIAGNOSTIC CRITERIA FOR RHEUMATOID ARTHRITIS
—add score of categories A to D, with a score of ≥6/10 classified as definite RA
A.
Joint involvement —one large joint (0), 2–10 large joints (1), 1–3 small joints with or without involvement of large joints (2), 4–10 small joints with or without involvement of large joints (3), >10 joints with at least 1 small joint (5);
B.
Serology —negative RF and negative anti-citrullinated protein antibodies (ACPA) (0), low-positive RF or low-positive ACPA (2), high-positive RF or high-positive ACPA (3);
C.
Acute phase reactants —normal CRP and normal ESR (0), abnormal CRP or abnormal ESR (1);
D.
Duration of symptoms — < 6 weeks (0), ≥6 weeks (1)
PROGNOSIS
—increased number of joints involved, presence of rheumatoid nodules, erosions, elevated inflammatory markers and seropositivity all suggest more severe disease
Management
SYMPTOM CONTROL
—physical therapy, diet (Ω-3 fatty acids). Joint protection (range of motion exercises, orthotics, splints). NSAIDs (antiinflammatory dose). Intraarticular steroid injections (if severe pain). Patient education
DISEASE-MODIFYING AGENTS OF RHEUMATOID DISEASE (DMARDs)
—single agent (methotrexate with folic acid, sulfasalazine, hydroxychloroquine, cyclosporine, gold). Combination triple therapy (methotrexate plus sulfasalazine plus hydroxychloroquine). Selective pyrimidine synthesis inhibitor (leflunomide). TNFα inhibitors (infliximab, etanercept, adalimumab, golimumab). B–cell inhibitor (rituximab, an anti-CD20 monoclonal antibody). T–lymphocyte activation inhibitor (abatacept), IL-6 inhibition (tocilizumab). Surgical intervention
Specific Entities
PALINDROMIC RHEUMATISM
—episodic arthritis with one or more joints being affected sequentially for hours to days, and symptom-free periods in between for days to months. May be anti-CCP positive and occasionally progresses to other rheumatic disorders (RA, SLE). Treatment with hydroxychloroquine can be useful
SJOGREN’S SYNDROME (KERATOCONJUNCTIVITIS SICCA)
PATHOPHYSIOLOGY—CD4 lymphocytic infiltration of salivary and lacrimal glands
CAUSES—primary (sicca plus episodic, non-deforming polyarthritis), secondary (RA, SLE, scleroderma, polyarteritis nodosa, polymyositis, HIV)
CLINICAL FEATURES—sicca (dry eyes and dry mouth, along with impaired taste, parotid gland enlargement, dental caries), dyspareunia, arthralgia, arthritis, and constitutional symptoms. May be associated with Raynaud’s phenomenon, cutaneous vasculitis, cerebritis, CNS vasculitis, stroke, and peripheral neuropathy
INVESTIGATIONS—quantitative Ig (polyclonal IgG), RF, ANA, ENA (SS-A, SS-B). Check for secondary causes
TREATMENTS—symptomatic (artificial tears, pilocarpine 5 mg PO QID), hydroxychloroquine, rituximab may have a role
LOFGREN’S SYNDROME
—a benign self-limited form of sarcoidosis. Tetrad of erythema nodosum, hilar lymphadenopathy, arthritis (ankles and sometimes knees), and fever
RESPIRATORY DISEASES IN RHEUMATOID ARTHRITIS
AIRWAY—cricoarytenoid arthritis with central airway obstruction, bronchiectasis, obliterative bronchiolitis, chronic small airway obstruction
PARENCHYMA—pneumonia (particularly with immunosuppression), interstitial fibrosis, bronchiolitis obliterans with organizing pneumonia, rheumatoid nodules, rheumatoid pneumoconiosis, apical fibrobullous disease, drug-related pneumonitis and fibrosis (methotrexate, gold, penicillamine, NSAIDs, cyclophosphamide, azathioprine, sulfasalazine)
VASCULAR—pulmonary hypertension, vasculitis
PLEURAL—pleuritis, pleural effusion, pleural thickening
UNDIFFERENTIATED CONNECTIVE TISSUE DISEASE
—overlap syndrome with clinical features of two or more rheumatologic disorders (RA, SLE, Sjogren’s syndrome, scleroderma, inflammatory myopathies) but does not fit the diagnostic criteria for any specific disorder
MIXED CONNECTIVE TISSUE DISEASE
—a specific overlap syndrome with clinical features of SLE, scleroderma, polymyositis, and antibodies to RNP. Characteristically, Raynaud’s phenomenon, myositis, and synovitis are present
Systemic Lupus Erythematosus
Pathophysiology
POPULATION
—typically affects women aged 15–45
AUTOIMMUNE REACTION
—antibody-immune complex deposition in kidneys (glomerulonephritis), autoantibodies against cell surface antigens on hematopoietic progenitor cells (anemia, neutropenia, thrombocytopenia), antiphospholipid antibodies (thrombosis)
ACR DIAGNOSTIC CRITERIA ★4-RASHES★
4 rashes—malar rash, discoid rash, oral ulcers (usually painless), photosensitivity
Renal—proteinuria >0.5 g/day or ≥3+, or cellular casts
Arthritis ≥2 peripheral joints, non-erosive
Serositis—pleuritis, pericarditis
Hematologic—hemolytic anemia, leukopenia <4.0 × 109/L, lymphopenia <1.5 × 109/L, thrombocytopenia <100 × 109/L
Excitation—seizures, psychosis
Serology—ANA, anti-dsDNA, anti-Smith, antiphospholipid antibodies, false-positive VDRL
Need ≥4 of 11 criteria (each rash counts as one criterion and ANA as a separate criterion) to meet classification criteria. Note that many patients may not ever fulfill four criteria until several years into their disease course
Clinical Features
JOINT SYMPTOMS
—symmetric non-erosive polyarthritis with joint pain, swelling, redness, morning stiffness (>1 h), and dysfunction. Sens 88%
HANDS—Jaccoud’s arthritis (joint deformities are unusual). Fingers and wrists may be involved
LEGS—knees more commonly affected
AVASCULAR NECROSIS—hip, shoulder, and knee may be affected
EXTRA-ARTICULAR MANIFESTATIONS
PULMONARY—pleuritis (sens 50%), pulmonary hypertension, PE, shrinking lung syndrome (dyspnea, pleuritic chest pain, progressive reduction in lung volume, elevated diaphragms)
CARDIAC—pericarditis (sens 30%), myocarditis, Libman–Sacks endocarditis
RENAL—proteinuria or active sediment (sens 50%), glomerulonephritis
WHO CLASSIFICATION OF LUPUS NEPHRITIS
NORMAL / MINIMAL MESANGIAL LUPUS NEPHRITIS (class I)—asymptomaticStay updated, free articles. Join our Telegram channel
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