A. Acute Monoarthritis [2]

1. Differential
   1. Infection: bacterial, mycoplasma, fungal, Lyme Disease, Virus (HIV, HBV)
   2. Crystal Induced: gout, CPPD, calcium oxalate, apatite crystals
   3. Trauma: fracture, internal derangement, hemarthrosis
   4. Osteoarthritis
   5. Ischemic necrosis
   6. Tumor: metastatic disease, osteoid osteoma, pigmented villonodular synovitis, sarcoma
   7. Foreign body
   8. Systemic disease: Rheumatoid arthritis, psoriasis, sarcoidosis, Reiter's, Behcet's
2. Bacterial Infections
   1. Gonococcus: certain strains, now many resistant to PCN
   2. G+ cocci: 80% of non-GC arthritis (S. aureus > ß-hemolytic Strep > pneumococci)
   3. Gram negative bacteria: common in IVDA and immunocompromised hosts
   4. Immunocompromised hosts: gram negative rods (GNR), Mycobacteria, T. pallidum
   5. Less common in immunocompromised: Sporothrix schenckii
3. History
   1. Previous episodes, trauma, rash, diarrhea
   2. Travel, tick bites, fever, intravenous drug abuse, sexual, hepatitis, family history
4. Physical
   1. Must distinguish arthritis (articular space) vs. periarticular area (bursitis, tendinitis)
   2. If full passive flexion of a joint is possible, then it is unlikely to be a true arthritis
   3. Macular Rash: consider psoriasis (elbows, buttocks, ears), lupus
   4. Erythema nodosum: Sarcoidosis, IBD, SLE, Behcet's Syndrome
   5. Skin ulcerations: leukocytoclastic vasculitis
   6. Mouth ulcers: SLE, Behet's disease
   7. Splinter hemorrhages, new murmer: endocarditis, anti-cardiolipin syndrome
5. Radiographic study of Joints
   1. Fractures, tumors, joint space obliteration are often seen on plain films
   2. Chondrocalcinosis of joint suggests pseudogout (CPPD), hemochromatosis, ochranosis
   3. MRI usually superior to CT
6. Other
   1. Bone / Gallium scans - difficult to distinguish infection from other inflammation
   2. Blood cultures and Gram stain of various fluids, lesions etc.
   3. Lyme titers, HIV test, HBV, ESR (<30 or >100 mm/hr may be helpful)
7. Arthrocentesis
   1. Should be performed on nearly all patients with acute arthritis
   2. Computed Tomographic (CT) guidance may be required - hips or sacroiliac joints
   3. 1-2 ml of fluid should be obtained
   4. Evaluation: blood count, differential, Gram stain, crystal analysis, culture
   5. Levels are glucose and lactate dehydrogenase (LDH) are rarely useful
   6. Normal synovial fluid has <180 WBC/µL, >50% monocytes
   7. Fluid is considered "non-inflammatory" if <2000 cells/µL
   8. A fluid count of >100K/µL is nearly pathomnemonic for a septic joint

B. Acute Polyarthritis [3]

1. Bacterial Arthritis
   1. Gonococcal and Meningococcal arthritis - culture of joint and blood often negative
   2. Septic Arthritis - ~15% polyarticular; consider endocarditis if >1 joint
   3. Lyme Disease
   4. IgM Abs appear 4-6 weeks post infection
      1. IgG Abs usually present in joint fluid
   5. Mycobacterial or Fungal Arthritis - usually single joint; fever absent or mild
2. Viral Syndromes (Exanthem)
   1. Hepatitis B Viral Infection - arthritis precedes symptoms, disappears with jaundice
   2. Parvovirus B19 - usually young women, but can occur in older persons and children [4]
   3. Parvovirus arthritis is usually symmetrical, involving large and small joints
   4. Rubella immunization or infection can induce arthritis or arthropathy [5]
   5. Rubella seronegativity and certain vaccine strains
   6. HIV associated arthritis - no fever; consider other causes of fever if present
3. Reactive Arthritis
   1. Enteric infection - especially with Yersinia and Campylobacter ssp.
   2. Urogenital infection - Reiter's Syndrome (especially Chlamydia trachomatis )
   3. Rheumatic Fever - usually migratory
   4. Inflammatory Bowel Disease
4. Crystal Disease
   1. Gout - fever common in polyarticular disease
   2. Pseudogout
   3. Hydroxyapatite Crystal Disease
5. Collagen Vascular Disease
   1. Rheumatoid Arthritis
   2. Lupus (SLE)
   3. Mixed Connective Tissue Disease (MCTD)
   4. Still's Disease - severe arthritis, fevers and rash
   5. Systemic Vasculitis: polyarteritis nodosum, Giant Cell Arteritis, Takayasu Arteritis
   6. Wegener's Granulomatosis - rare presentation with polyarthritis prior to airway disease
6. Miscellaneous
   1. Sarcoidosis - often with low grade fevers
   2. Familial Mediterranean Fever (FMF)
   3. Acute Leukemia - uncommon
   4. Lymphoma - unusual
7. Evaluation of Infectious Symptoms is critical for classification of arthritis [1]
   1. Fever and chills do not help classify specific cause of arthritis
   2. Diarrhea - best differentiator between RA, spondyloarthropathy, and undifferentiated
   3. Genitourinary symptoms
   4. Antibodies to specific bacteria are generally not helpful in classifying early arthritis
8. About 35% of acute arthritis will remain unclassified [1]

References

1. El-Gabalawy HS, Duray P, Goldbach-Mansky R. 2000. JAMA. 284(18):2368
2. Baker DG and Schumacher HR Jr. 1993. NEJM. 329(14):1013
3. Pinals RS. 1994. NEJM. 330(11):769
4. Martin DP, Schlott DW, Flynn JA. 2007. NEJM. 357(18):1856 (Case Discussion)
5. Tingle AJ, Mitchell LA, Grace M, et al. 1997. Lancet. 349:1277