Published December 2025
Authors: Meredith Morcos, MD1, Jennifer Stichman2
Executive editor: Brandon Fainstad, MD3
1Assistant Professor, Division of Rheumatology, University of Colorado
2Associate Professor, Division of Rheumatology, University of Colorado
3Associate Professor, Division of General Internal Medicine, University of Colorado
Objective(s)
- Use acuity (acute vs. chronic) and number of involved joints (mono-, oligo-, polyarticular) to generate a focused differential diagnosis for inflammatory arthritis.
- Determine when synovial fluid analysis, advanced microbiologic testing (e.g., Lyme PCR, GC cultures), or imaging (e.g., chondrocalcinosis, marginal erosions, SI joint changes) is indicated to clarify the etiology of arthritis.
- Select initial management strategies for common arthritides and recognize red-flag presentations requiring urgent antimicrobial therapy, rheumatology involvement, or surgical evaluation.
Teaching Instructions
Preparation
Plan to spend at least 60 minutes preparing for this talk to get familiar with the content and how to function the interactive board. These teaching instructions explain how to navigate through the talk. Every interactive or “clickable” element is denoted with a mouse icon that should serve as a prompt to ask the audience a question before clicking it.
Anticipated time to deliver the talk: 45 minutes.
Arthritis etiologies can be rapidly grouped by time course (acute vs. chronic) and number of joints involved (mono-, oligo-, polyarticular). Acute monoarthritis raises concern for crystal disease or infection, whereas chronic polyarthritis suggests autoimmune, viral, or indolent infectious causes. Synovial fluid WBC count and cell type provide early clues to infectious vs. non-infectious.
Acute
A true emergency. Patients typically present with a hot, swollen, painful joint and limited passive ROM. Synovial fluid is usually >50K WBCs with PMN predominance, though thresholds are lower in prosthetic joints or after partial antibiotic treatment. Gram stain helps guide early therapy: vancomycin for gram-positive cocci, ceftriaxone for gram-negative organisms. Most patients require urgent surgical washout.
Sudden onset of intense pain, classically at the first MTP (90%) or other lower extremity joints. Synovial fluid shows monosodium urate crystals. Risk factors include obesity, hypertension, and chronic kidney disease. Treat with NSAIDs, colchicine, or corticosteroids. Start urate-lowering therapy (ULT, e.g., allopurinol) for those with >2 episodes per year (goal uric acid <6). Consider ULT after one flare if CKD stage >3, serum urate concentration >9, urolithiasis, gouty erosions by x-ray, or tophi. Continue prophylaxis (e.g., colchicine) while escalating urate-lowering therapy.
May mimic gout or RA. Synovial fluid contains CPP crystals. Radiographs may show chondrocalcinosis, particularly in knees and wrists. Risk factors include hemochromatosis and hyperparathyroidism. Treat acute flares similar to acute gout with NSAIDs, colchicine, or corticosteroids.
Acute sarcoid arthritis commonly affects ankles, knees, and wrists. Lofgren’s syndrome includes erythema nodosum, bilateral hilar adenopathy, and acute arthritis. Chronic arthropathy is less common. Management options include NSAIDs and DMARDs such as methotrexate or TNF inhibitors.
Often affects young, sexually active patients. Classic triad: migratory polyarthralgia, tenosynovitis, and pustular dermatitis. Synovial fluid typically 10–50K WBCs, and N. gonorrhoeae may be isolated from joint fluid, blood, or mucosal sites. Treat with ceftriaxone, adding doxycycline or azithromycin for possible Chlamydia co-infection. Prognosis is excellent with timely therapy.
Develops 1–6 weeks after GI or GU infection. Often presents as an asymmetric oligoarthritis of the lower extremities, commonly in HLA-B27–positive patients. Look for uveitis, urethritis, and keratoderma blennorrhagicum. Synovial cultures are negative.
Patterns vary by pathogen. Parvovirus B19 causes an RA-like small-joint polyarthritis with positive IgM. Hepatitis B and C are the next most common. International travel may prompt consideration of Dengue, Chikungunya, or Zika. Many viruses cause transient autoantibody formation, limiting the utility of serologies. Management is generally supportive with NSAIDs, except where specific antiviral or hepatitis‑directed therapy is indicated.
Chronic
Indolent presentations. Often seen in immunosuppressed individuals or with relevant travel exposure. Synovial fluid typically contains 10–20K WBCs and may be culture-negative; biopsy is sometimes required. Surgical evaluation and infectious disease consultation are recommended.
Occurs months after tick exposure. Typically presents as mono- or oligoarthritis of a large joint, especially the knee. Synovial fluid often exceeds 2K WBC. Diagnosis can be supported by Borrelia PCR. Treat with a four-week course of doxycycline; persistent inflammatory arthritis may require DMARDs.
Associated with HLA-B27 and often involves the sacroiliac joints more than other parts of the spine. Peripheral arthritis is asymmetric. Screen for rashes, uveitis, IBD, enthesitis, and dactylitis. Imaging may show marginal erosions, syndesmophytes, or ankylosis. Treat peripheral disease with DMARDs and axial disease with TNF inhibitors.
Other spondyloarthropathies include reactive arthritis (usually acute, see other tab), psoriatic arthritis (see other tab) and IBD-associated arthritis.
Can involve axial and peripheral joints, including the DIPs. Look for nail pitting, onycholysis, dactylitis, and enthesitis. Skin severity does not predict joint severity. Evaluate for inflammatory eye disease and IBD. Imaging of hands/feet and SI joints is useful for classification.
Typically presents with symmetric small-joint polyarthritis. Ask about photosensitive rashes, oral ulcers, alopecia, Raynaud’s, and chest pain or dyspnea. Imaging shows soft tissue swelling more than erosions. NSAIDs or low-dose prednisone treat acute symptoms, and long-term control often includes hydroxychloroquine, methotrexate, or azathioprine.
Characterized by symmetric small-joint involvement of wrists, MCPs, PIPs, ankles, and MTPs, sparing the DIPs and spine. Labs include RF, CCP, ESR, and CRP. Imaging may show periarticular osteopenia and marginal erosions. Methotrexate is first-line DMARD therapy.
Represents chronic urate deposition with tophus formation and recurrent acute episodes. Imaging may reveal punched-out erosions with overhanging edges. Commonly affects cooler joint regions. Long-term management requires urate-lowering therapy with goal uric acid below 6 (may require <5 to resolve tophus).
Handout(s)
Presentation Board
Take Home Points
- Start with time and space – Acuity (acute vs chronic) and joint distribution (mono-, oligo-, polyarticular) are a fast way to narrow the differential for inflammatory arthritis.
- Never miss infection – Acute monoarthritis should be presumed septic until proven otherwise. Synovial fluid analysis (WBC count, crystal analysis, and cultures to distinguish between crystal disease, infection, and inflammatory arthritis) and timely antibiotics and/or surgical consultation are critical.
- Pattern recognition matters – Symmetry, axial involvement, DIP disease, enthesitis, dactylitis, and extra-articular features (skin, eye, GI, GU) help differentiate RA, SLE, psoriatic arthritis, and spondyloarthropathies.
- Match treatment to etiology and trajectory – Acute inflammatory flares require anti-inflammatory therapy, while chronic autoimmune and indolent infectious causes demand early disease-modifying treatment and specialty involvement.
References
- S F Li et al. “Diagnostic utility of laboratory tests in septic arthritis.” Emergency Medicine Journal, 24 (2007): 75 – 77. https://doi.org/10.1136/emj.2006.037929
- Robert B. Lochhead et al. “Lyme arthritis: linking infection, inflammation and autoimmunity.” Nature Reviews Rheumatology, 17 (2021): 449 – 461. https://doi.org/10.1038/s41584-021-00648-5
- M. Miller et al. “Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM)..” Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (2024). https://doi.org/10.1093/cid/ciae104
- Stamp, Lisa K., and Nicola Dalbeth. “Critical appraisal of serum urate targets in the management of gout.” Nature Reviews Rheumatology 18.10 (2022): 603-609.
- FitzGerald, John D., et al. “2020 American College of Rheumatology guideline for the management of gout.” Arthritis & Rheumatology 72.6 (2020): 879-895.