para>Infrequent in pediatric population �
ETIOLOGY AND PATHOPHYSIOLOGY
- Hematogenous invasion is most common.
- Contiguous spread
- Direct penetration via trauma
- Fungal infections may disseminate from primary pulmonary involvement, particularly in immunocompromised hosts.
- Direct contact/consumption of infected animal products
RISK FACTORS
- HIV/AIDS
- Concurrent extra-articular infection
- Chronic inflammatory arthritis (e.g., rheumatoid arthritis [RA])
- Trauma, especially penetrating
- Prosthetic joint(s)
- Prior antibiotic, corticosteroid, or immunosuppressive therapy
- Serious chronic systemic illness (e.g., diabetes mellitus, liver disease, malignancy, primary immunodeficiency)
- Defective phagocytosis (e.g., chronic granulomatous disease)
- Injection drug use
- Exposure to specific infectious agents (e.g., brucellosis, unpasteurized milk, farmers, butchers, veterinarians)
- Travel/habitat history
- Gardening (sporotrichosis)
- Aquatic exposure (e.g., fish hook puncture and Mycobacterium marinum)
COMMONLY ASSOCIATED CONDITIONS
- Systemic infection
- Immunodeficiency/immunosuppression (e.g., from HIV/AIDS, lymphoma, transplantation, medications)
- Poncet disease (reactive arthritis associated with TB)
DIAGNOSIS
HISTORY
- Predominantly monoarticular (90%)
- Fungal arthritis may present as a migratory polyarthritis, particularly with Coccidioides immitisandHistoplasma capsulatum, due to hypersensitivity reaction.
- Oligoarticular reactive arthritis (Poncet disease) associated with systemic TB infection (2)
- Flare of arthritis in a single joint with preexisting joint disease
- Fever in 50% at some time during infection
- Fever of unknown origin (FUO)
- Brucellosis is typically monoarticular (knee) in children; in adults more often involves the sacroiliac joint (3)
- Cutaneous lesions are seen with Blastomyces dermatitidis and Sporothrix schenckii.
- Back pain, especially in TB and brucellosis
- Sternal or rib involvement with TB; Pott disease (vertebral infection with TB)
- Fungal infection of prosthetic joints can occur months to years after initial surgery.
- Prosthetic joint infections can present with subacute onset of pain and swelling.
PHYSICAL EXAM
- Fever
- Joint effusion
- Synovial thickening (doughy consistency); may have minimal joint tenderness
- Limited joint use/motion, especially in children
- Overlying warmth, redness; present in <50%
- Fungal joint infections can form draining sinus tracts.
- Spinal tenderness with TB (Pott disease) and with brucellosis
- Gibbus deformity (kyphosis) with TB
- Tenosynovitis
- Dactylitis ("sausage digit"�-inflammation of entire finger/toe)
- Erythema nodosum (H. capsulatum and TB)
- Nodular skin lesions with Mycobacterium and fungi
- Iritis (with mycobacterial arthritis)
- Brucellosis
- Hepatosplenomegaly
- Lymphadenopathy
DIFFERENTIAL DIAGNOSIS
- Gout
- Pseudogout (calcium pyrophosphate deposition disease)
- Spondyloarthropathy (Reiter syndrome, psoriatic arthritis, ankylosing spondylitis, arthritis of inflammatory bowel disease)
- RA; juvenile RA
- Foreign body synovitis (e.g., plant thorn synovitis)
- Pigmented villonodular synovitis (PVNS)
- Palindromic rheumatism
- Neuropathic arthropathy
- Lyme arthritis
- Sarcoidosis
- Pyogenic arthritis
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- Arthrocentesis if infectious arthritis is considered
- Bacterial: Gram stain, silver, and acid-fast stain and culture, cell count and differential, glucose
- Mycobacterial: Acid-fast smear (positive in 20%), culture (positive in 80%); synovial fluid usually is cloudy with >20,000 WBCs/high-power field (HPF) but may have fewer WBCs present or >100,000/mm3
- Synovial fluid analysis, including wet-mount prep, typically positive in B. dermatitidis
- Polymorphonuclear leukocytes usually predominate in synovial fluid, although granulomatous and viral arthritis may have high mononuclear cell count.
- Rice bodies can be present, similar to RA (3).
- Synovial membrane: biopsy and culture
- Blood, urine, sputum cultures
- Fungal blood cultures or serologies
- Hold cultures for 2 weeks; acid-fast cultures for 6 weeks
- Drug susceptibility testing is recommended.
- Crystals in synovial fluid (e.g., urate or calcium pyrophosphate) do not rule out infectious arthritis
- Interferon-gamma release assays aid diagnosis (4).
- PCR for specific microorganisms such as TB
- Serum testing (i.e., cryptococcal antigen, Brucella antibody >1:160)
- Radiographs:
- X-ray changes are usually a late phenomenon.
- Soft tissue swelling
- Rarefaction of subchondral bone
- Joint space loss
- Joint destruction with ankylosis
- Subchondral erosion with preservation of joint space strongly suggests granulomatous infection.
- CT scan to identify sequestration
- Nuclear imaging with fludeoxyglucose (FDG) (5)
- MRI: T2-weighted signals increase in affected soft tissue and bone.
Diagnostic Procedures/Other
Synovial biopsy or synovectomy �
Test Interpretation
Synovial biopsy may reveal granulomata and possibly the causative organism on microscopy or culture. �
TREATMENT
GENERAL MEASURES
- Fungal: Hospitalize for parenteral therapy.
- Mycobacterial: outpatient
- Brucella: outpatient
- Repeat arthrocentesis if fluid reaccumulates.
- Prosthetic joint infections may be difficult to eradicate without joint replacement.
- For Brucella or fungal infections, continue treatment for 1 to 2 weeks after all signs of inflammation have resolved and for 6 to 8 weeks if joint was previously diseased (e.g., arthritis).
- Antimicrobic therapy requires a long course, particularly in TB, fungal infection, brucellosis.
- Intra-articular antibiotics are not indicated.
- Consider infectious disease and rheumatology consultation.
MEDICATION
First Line
- Tailor therapy based on culture and sensitivity.
- Mycobacterial infection
- Treatment is generally the same as pulmonary TB.
- Initial phase
- Isoniazid (INH) 5 mg/kg (max 300 mg), rifampin (RIF) 10 mg/kg (max 600 mg), pyrazinamide (PZA) 15 to 30 mg/kg, and ethambutol (EMB) 15 to 20 mg/kg daily for 8 weeks
- Continuation phase
- INH/RIF daily for 18 weeks or, if directly observed treatment: INH/RIF 5 days/week for 18 weeks
- Continue therapy for 6 to 9 months if rifampin is included; regimens without rifampin require longer courses (12 to 18 months).
- Brucella: Doxycycline 100 mg PO BID plus streptomycin 1 g IM once daily for the first 14 to 21 days or doxycycline 100 mg PO BID plus rifampin 600 to 900 mg PO once daily; continue therapy for 12 weeks.
- Fungal infection
- Choice of medication depends on organism.
- General length of therapy is several months.
- Amphotericin B 0.5 to 1 mg/kg/day IV for 6 weeks
- Fluconazole 400 mg PO daily for 6 weeks
- Contraindications: Tetracycline is not for use in pregnancy or children <8 years.
- Precautions:
- Observe for allergic reactions/serum sickness.
- Tetracycline may cause photosensitivity; sunscreen is recommended.
- Significant possible interactions
- Tetracycline: Avoid concurrent administration with antacids, dairy products, or iron.
- Azoles: multiple drug interactions
SURGERY/OTHER PROCEDURES
- Arthrotomy if fluid is loculated and/or not amenable to needle drainage
- Prosthetic joints may require replacement.
- Root joints (shoulder and hips) often require surgical intervention.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
- Verify sterilization of joint and normalization of inflammatory markers.
- Treatment of mycobacterial arthritis requires monthly CBC. Assess liver and kidney toxicity, and urinalysis.
- Follow up after stopping antibiotics to detect relapse
PATIENT EDUCATION
Arthritis Foundation, 1314 Spring Street NW, Atlanta, GA 30309; (404) 872-7100 �
PROGNOSIS
- Early initiation of treatment should lead to cure.
- Delayed recognition/treatment is complicated by increased morbidity and mortality.
COMPLICATIONS
- Limited joint range of motion
- Flail or fused joint
- Carpal tunnel syndrome
- Septic necrosis
- Sinus formation
- Ankylosis
- Osteomyelitis
- Shortening of limb (in children)
REFERENCES
11 Magnussen �A, Dinneen �A, Ramesh �P. Osteoarticular tuberculosis: increasing incidence of a difficult clinical diagnosis. Br J Gen Pract. 2013;63(612):385-386.22 Rueda �JC, Crepy �MF, Mantilla �RD. Clinical features of Poncet's disease. From the description of 198 cases found in the literature. Clin Rheumatol. 2013;32(7):929-935.33 Jeong �YM, Cho �HY, Lee �SW, et al. Candida septic arthritis with rice body formation: a case report and review of literature. Korean J Radiol. 2013;14(3):465-469.44 Jia �H, Pan �L, Qin �S, et al. Evaluation of interferon-γ release assay in the diagnosis of osteoarticular tuberculosis. Diagn Microbiol Infect Dis. 2013;76(3):309-313.55 Wang �JH, Chi �CY, Lin �KH, et al. Tuberculous arthritis-unexpected extrapulmonary tuberculosis detected by FDG PET/CT. Clin Nucl Med. 2013;38(2):e93-e94.
ADDITIONAL READING
- Abdulaziz �S, Almoallim �H, Ibrahim �A, et al. Poncet's disease (reactive arthritis associated with tuberculosis): retrospective case series and review of literature. Clin Rheumatol. 2012;31(10):1521-1528.
- Carpenter �CR, Schuur �JD, Everett �WW, et al. Evidence-based diagnostics: adult septic arthritis. Acad Emerg Med. 2011;18(8):781-796.
- Fukushima �M, Kakinuma �K, Hayashi �H, et al. Detection and identification of Mycobacteriumspecies isolates by DNA microarray. J Clin Microbiol. 2003;41(6):2605-2615.
- Golmia �R, Bello �I, Marra �A, et al. Aspergillus fumigatus joint infection: a review. Semin Arthritis Rheum. 2011;40(6):580-584.
CODES
ICD10
- M00.9 Pyogenic arthritis, unspecified
- A18.02 Tuberculous arthritis of other joints
- M00.80 Arthritis due to other bacteria, unspecified joint
- B49 Unspecified mycosis
- M06.9 Rheumatoid arthritis, unspecified
- M01.X0 Direct infection of unspecified joint in infectious and parasitic diseases classified elsewhere
ICD9
- 711.90 Unspecified infective arthritis, site unspecified
- 711.40 Arthropathy associated with other bacterial diseases, site unspecified
- 711.00 Pyogenic arthritis, site unspecified
- 031.8 Other specified mycobacterial diseases
- 714.0 Rheumatoid arthritis
- 711.60 Arthropathy associated with mycoses, site unspecified
SNOMED
- Infective arthritis (disorder)
- tuberculous arthritis (disorder)
- Bacterial arthritis (disorder)
- Arthropathy associated with a mycosis (disorder)
- Rheumatic joint disease (disorder)
- Subacute infective arthritis (disorder)
CLINICAL PEARLS
- Infectious arthritis may present as fever of unknown origin.
- Fungal joint infection may present with synovial thickening and tenderness. Erythema and pain may not be present.
- Spinal TB can result in permanent deformity.
- Synovial biopsy or synovectomy is often needed to diagnose a specific pathogen.