Septic arthritis differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Venkata Sivakrishna Kumar Pulivarthi M.B.B.S [2]

Overview

Septic arthritis should be differentiate from other causes of monoarticular arthritis such as other infectious arthritis, inflammatory arthritis, non inflammatory arthritis, hemorrhagic arthritis and intra articular derangement that causes acute arthritis. Most cases of acute septic arthritis are caused by bacteria such as staphylococcus or streptococcus and it should be differentiated from other causes of arthritis as prompt diagnosis and rapid initiation of treatment is required to limit the complications.

Differential Diagnosis

Differentiating gonococcal arthritis from non-gonococcal arthritis

Characteristic	Gonococcal arthritis	Non gonococcal arthritis
Patient profile	Mostly sexually active young adult Female > male	Patient with history of rheumatoid arthritis or other systemic arthritis Immunocompromised patient Common in extremes of age such as in newborn or elderly
Initial presentation	Migratory polyarthralgia is common Tenosynovitis in majority of patients Dermatitis in majority of patients	Single hot, swollen and painful joint Polyarthralgia is very rare Tenosynovitis and dermatitis are very rare.
Polyarticular involvement	Common (~40–70% of patients) Usually involves 2-3 joints	Rare (~10–20% of patients). Mostly monoarticular involvement (>85%)
Recovery of bacteria	Positive blood culture <10% Positive synovial fluid culture <50%	Positive blood culture 50% Positive synovial fluid culture >90%
Response to antibiotics	Within a few days outcome excellent	Takes weeks Joint drainage must be adequate Outcome often poor

Infectious Differential for Bacterial Arthritis

Microorganism or other infectious disease	Associated risk factors	Key clinical clues
Staphylococcus aureus	Rheumatoid arthritis Diabetes mellitus HIV patients	Healthy adult with skin lesions and previously history of damaged joint (e.g, rheumatoid arthritis) or prosthetic joint
Streptococcus pyogenes Streptococcal pneumonia	Autoimmune diseases Chronic skin infections Trauma	Healthy adults with spleenic dysfunction
Groups B Streptococcal infection	Immunocompromised patients Diabetes mellitus Malignancy Severe genitourinary or gastrointestinal infections	Healthy adults with spleenic dysfunction
Neisseria gonorrhoeae	Complement deficiency Systemic lupus erythematosus Male homosexuality low socioeconomic status	Healthy young and sexually active adult with Tenosynovitis Skin lesions such as vesicular pustules Complement deficiency (C5-9 deficiency) Culture negativity on synovial fluid analysis
Gram-negative bacilli Pseudomonas Escherichia coli	History of intravenous drug abuse Extremes of age Immunocompromised patients	Immunocompromised patients Recent history gastrointestinal infections such as infectious diarrhea caused by Shigella, Salmonella, Campylobacter, or Yersinia
Haemophilus influenzae	Unimmunized children
Anaerobes	Diabetes mellitus Patients with prosthetic joints	Immunocompromised hosts Recent history of gastrointestinal infection
Mycobacterium spp.	Recent history of travel to endemic areas	Immunocompromised patients Recent history of travel to endemic areas (e.g. India, South Africa, Mexico etc.) Incidious onset of monoarthritis
Fungal infection such as Blastomycosis Cryptococcus Coccidioidomycosis Sporotrichosis	Immunocompromised patients	Immunocompromised patients Incidious onset of monoarthritis
Mycoplasma hominis	Recent history of urinary tract procedure	Immunocompromised patients Recent history of urinary tract procedure
Viral arthritis	Immunocompromised patient	Polyarthritis Fever Rash
HIV infection	History of multiple sexual partners History of IVDA	Sterile, acute synovitis or reactive arthritis
Lyme disease	History of recent visit to endemic Lyme area	History of erythema migrans History of recent visit to endemic Lyme area
Reactive arthritis	Recent gastrointestinal/ genitourinary infection	Recent gastrointestinal/ genitourinary infection Enthesopathy Skin lesions Uveitis Conjunctivitis
Endocarditis	History of endocarditis Damaged heart valves Congenital heart diseases	Fever New onset of heart murmur Septic and sterile synovitis Septic joint more common in IVDA

Differentiatial Diagnsosis for Acute Arthritis

Septic arthritis should be differentiated from other causes of acute arthritis:

Type of Arthritis	Color	Transparency	Viscosity	Volume (in ml)	WBC count (per mm3)	PMN cellcount (%)	Gram stain	Gram Culture	polymerase chain reaction (PCR) test	Crystals
Normal	Clear	Transparent	High/thick	< 3.5	< 200	< 25	Negative	Negative	Negative	Negative
Gonococcal arthritis	Yellow	Cloudy-opaque	Low	Often >3.5	34,000 to 68,000	> 75	Variable (< 50 percent)	Positive (25 to 70 percent)	Positive (> 75 percent)	Negative
Non-gonococcal arthritis	Yellowish-green	Opaque	Very low	Often >3.5	> 50,000 (> 100,000 is more specific)	> 75	Positive (60 to 80 percent)	Positive (> 90 percent)	--	Negative
Inflammatory: crystalline arthritis (e.g.Gout, Pseudogout)	Yellow	Cloudy	Low/thin	Often >3.5	2,000 to 100,000	> 50	Negative	Negative	Negative	Positive
Inflammatory: non-crystalline arthritis (e.g. Rheumatoid arthritis, reactive arthritis)	Yellow	Cloudy	Low/thin	Often >3.5	2,000 to 100,000	> 50	Negative	Negative	Negative	Negative
Noninflammatory arthritis (e.g. Osteoarthritis)	Straw	Translucent	High/thick	Often >3.5	200 to 2,000	< 25	Negative	Negative	Negative	Negative
Hemorrhagic	Red	Bloody	Variable	Usually >3.5	Variable	50-75	Negative	Negative	Negative	Negative
Lyme arthritis	Yellow	Cloudy	Low	Often >3.5	3,000 to 100,000 (mean: 25,000)	> 50	Negative	Negative	Positive (85 percent)	Negative

Microorganism Involved Based on The Clinical History and Symptoms

Clinical history	Joints involved	Most likely microorganism
Intravenous drug use	Involvement of axial joints (e.g. sternoclavicular or sacroiliac joint)	Pseudomonas aeruginosa Staphylococcus aureus
Sexual activity	Tenosynovial involvement in hands, wrists, or ankles	Neisseria gonorrhoeae
Terminal complement deficiency	Tenosynovial involvement in hands, wrists, or ankles	Neisseria gonorrhoeae
Dog or cat bite	Small joints involvement	Capnocytophaga species Pasteurella multocida
Ingestion of unpasteurized dairy products	Monoarticular involvement, in specific sacroiliac joint	Brucella sps
Nail through shoe	Foot	Pseudomonas aeruginosa
Soil exposure/gardening	Monoarticular involvement: knee, hand, or wrist	Nocardia sps Sporothrix schenckii
Soil or dust exposure containing decomposed wood (north-central and southern United States)	Monoarticular: knee, ankle, or elbow	Blastomyces dermatitidis
Southwestern United States, Central and South America (primary respiratory illness)	Knee	Coccidioides immitis
Cleaning fish tank	Small joints involvement (e.g. fingers, wrists)	Mycobacterium marinum

Septic arthritis must be differentiated from other causes of rash and arthritis

Disease	Findings
Nongonococcal septic arthritis	Presents with an acute onset of joint swelling and pain (usually monoarticular) Culture of joint fluid reveals organisms
Acute rheumatic fever	Presents with polyarthritis and rash (rare presentation) in young adults. Microbiologic or serologic evidence of a recent streptococcal infection confirm the diagnosis. Poststreptococcal arthritis have a rapid response to salicylates or other antiinflammatory drugs.
Syphilis	Presents with acute secondary syphilis usually presents with generalized, pustular lesions at the palms and soles with generalized lymphadenopathy Rapid plasma reagin (RPR), Venereal Disease Research Laboratory (VDRL) and Fluorescent treponemal antibody absorption (FTA-ABS) tests confirm the presence of the causative agent.
Reactive arthritis (Reiter syndrome)	Musculoskeletal manifestation include arthritis, tenosynovitis, dactylitis, and low back pain. Extraarticular manifestation include conjunctivitis, urethritis, and genital and oral lesions. Reactive arthritis is a clinical diagnosis based upon the pattern of findings and there is no definitive diagnostic test
Hepatitis B virus (HBV) infection	Presents with fever, chills, polyarthritis, tenosynovitis, and urticarial rash Synovial fluid analysis usually shows noninflammatory fluid Elevated serum aminotransaminases and evidence of acute HBV infection on serologic testing confirm the presence of the HBV.
Herpes simplex virus (HSV)	Genital and extragenital lesions can mimic the skin lesions that occur in disseminated gonococcal infection Viral culture, polymerase chain reaction (PCR), and direct fluorescence antibody confirm the presence of the causative agent.
HIV infection	Present with generalized rash with mucus membrane involvement, fever, chills, and arthralgia. Joint effusions are uncommon
Gout and other crystal-induced arthritis	Presents with acute monoarthritis with fever and chills Synovial fluid analysis confirm the diagnosis.
Lyme disease	Present with erythema chronicum migrans rash and monoarthritis as a later presentation. Clinical characteristics of the rash and and serologic testing confirm the diagnosis.