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Arthritis, Infectious, Granulomatous

- 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"пїЅ-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

- 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.

- 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

- 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

para>Infrequent in pediatric population пїЅ

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"пїЅ-inflammation of entire finger/toe)
  • Erythema nodosum (H. capsulatum and TB)
  • Nodular skin lesions with Mycobacterium and fungi
  • Iritis (with mycobacterial arthritis)
  • BrucellosisHepatosplenomegalyLymphadenopathy

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 swellingRarefaction of subchondral boneJoint space lossJoint destruction with ankylosisSubchondral 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 пїЅ

Test Interpretation

Synovial biopsy may reveal granulomata and possibly the causative organism on microscopy or culture. пїЅ

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 infectionTreatment is generally the same as pulmonary TB.Initial phaseIsoniazid (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 weeksContinuation phaseINH/RIF daily for 18 weeks or, if directly observed treatment: INH/RIF 5 days/week for 18 weeksContinue 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 infectionChoice of medication depends on organism.General length of therapy is several months.Amphotericin B 0.5 to 1 mg/kg/day IV for 6 weeksFluconazole 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 interactionsTetracycline: 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 пїЅ

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 пїЅA, Dinneen пїЅA, Ramesh пїЅP. Osteoarticular tuberculosis: increasing incidence of a difficult clinical diagnosis. Br J Gen Pract. 2013;63(612):385-386.22 Rueda пїЅJC, Crepy пїЅMF, Mantilla пїЅRD. 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 пїЅYM, Cho пїЅHY, Lee пїЅSW, 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 пїЅH, Pan пїЅL, Qin пїЅS, et al. Evaluation of interferon-Оі release assay in the diagnosis of osteoarticular tuberculosis. Diagn Microbiol Infect Dis. 2013;76(3):309-313.55 Wang пїЅJH, Chi пїЅCY, Lin пїЅKH, et al. Tuberculous arthritis-unexpected extrapulmonary tuberculosis detected by FDG PET/CT. Clin Nucl Med. 2013;38(2):e93-e94.

ADDITIONAL READING

  • Abdulaziz пїЅS, Almoallim пїЅH, Ibrahim пїЅA, 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 пїЅCR, Schuur пїЅJD, Everett пїЅWW, et al. Evidence-based diagnostics: adult septic arthritis. Acad Emerg Med. 2011;18(8):781-796.
  • Fukushima пїЅM, Kakinuma пїЅK, Hayashi пїЅH, et al. Detection and identification of Mycobacteriumspecies isolates by DNA microarray. J Clin Microbiol. 2003;41(6):2605-2615.
  • Golmia пїЅR, Bello пїЅI, Marra пїЅA, 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.