The patient was referred to rheumatology service for evaluation of crystal-induced arthropathy given chondrocalcinosis. Physical examination revealed right third proximal interphalangeal joint swelling and tenderness with overimposed tophilike nodule. No erythema or palpable effusions were appreciated. Range of motion was preserved. Laboratory workup showed resolved leukocytosis and neutrophilia, and normal sedimentation rate or C-reactive protein levels. Antinuclear antibody panel, rheumatoid factor, and anti–cyclic citrullinated peptide levels were normal. Serum uric acid levels were 5.9 mg/dL. Chlamydia, gonorrhea, and HIV tests were negative. Short course of low-dose oral prednisone starting at 15 mg daily with tapering by 5 mg every 3 days was given for presumptive calcium pyrophosphate deposition vs gout. Nevertheless, right-hand swelling and pain worsened after steroids. Repeat right upper extremity MRI showed persistent soft tissue edema and inflammation along the dorsum of the hand extending to the digits, tenosynovitis, and fluid in the third metacarpophalangeal that could represent a superficial abscess. The patient was hospitalized given concerns of infection.
The relapse of tenosynovitis raised concerns for a persistent infection secondary to a fastidious organism, such as NTM. Thus, inquiries specifically pertaining to any contact with bodies of water were entertained. The patient remembered that he had gone scuba diving in the ocean weeks before symptom onset. This meant scuba diving could then be the inciting event rather than gardening, which placed NTM higher in the differential. ID service did not recommend antibiotics until new cultures were available. Orthopedic service was consulted for surgical debridement. The right dorsal hand, wrist, and distal forearm tendon sheaths were surgically opened to obtain a synovial biopsy.
Synovial fluid was sent for fungal, bacterial, and AFB cultures, and synovial biopsy for AFB stains, PCR amplification/sequencing assay, and cultures. Results showed nonnecrotizing granulomas and all cultures were negative (Figures 3, 4). Rheumatology was again consulted for evaluation for sarcoidosis given negative cultures and noncaseating granulomas. Review of systems was completely negative for sarcoidosis. Computed tomography (CT) of the thorax did not show any pulmonary abnormalities, lymphadenopathy, and hilar adenopathy. Serum calcium and angiotensin-converting enzyme levels were normal. ID service recommended against empiric antibiotics given negative culture. Given persistent pain, and reported cases of isolated sarcoid tenosynovitis, low-dose oral prednisone 20 mg daily was given after clearance by ID service. Nonetheless, the right wrist and hand swelling, erythema, and tenderness relapsed with 1 dose of prednisone, leading to a repeat right upper extremity synovial biopsy due to high suspicion for persistent infection with a fastidious organism. New synovial tissue biopsy revealed fibro-adipose tissue with prominent vessels and fibrosis, nonnecrotizing, sarcoidlike granuloma with giant cell granulomatous reaction. The AFB and Grocott methenamine silver stains were negative. PCR was negative for AFB. No crystals were reported. After 5 weeks, the synovial biopsy culture was positive for M marinum. Patient was started on oral azithromycin 500 mg daily, rifabutin 300 mg daily, and ethambutol 15 mg/kg daily. At the time of this report, the patient was still completing antibiotic therapy with adequate response and undergoing occupational therapy rehabilitation (Figure 5).
Discussion
M marinum is an NTM found in bodies of water and marine settings. Infection arises after direct contact of lacerated skin with contaminated water. In a review article of 5 cases of M marinum tenosynovitis, they found that all individuals had wounds with exposure to fish or shrimp while in the water or while handling seafood.1 The incidence of this infection is infrequent, estimated to be 0.04 cases per 100,000, with only about 25% of these cases presenting as tenosynovitis.2 The incubation period ranges from 2 to 4 weeks.3 Late identification of this organism is common because of its slow development. For example, presentation from first exposure to symptom onset may take as long as 32 days.1 In addition, in the same review, surgical intervention occurred in 63 days.1 It has been reported that AFB stains are positive in just 9% of cases, which confounds diagnosis even more.4 After synovial tissue culture is obtained, it takes approximately 6 weeks for the organism to grow. Moreover, diagnosis may take longer if it is not suspected.5
Four types of M marinum infections have been described.5 The status of the immune system plays a role in how the manifestations present. The first type is limited, which is seen in immunocompetent persons, characterized by skin involvement, such as erythematous nodular lesions, that may improve on their own in months or years.4 Conversely, in immunosuppressed patients, the second type of infection may cause sporotrichoid spreading described as following lymphangitic pattern. The third type presents with musculoskeletal findings, such as arthritis, tenosynovitis, bursitis, or osteomyelitis, as seen in our patient. The fourth type consists of systemic manifestations.5 Medications that lower the immune system, such as corticosteroids, chemotherapy, and biologic disease modifying agents, may increase the risk for developing this entity.4 Specifically, antitumor necrosis factor inhibitors have been historically associated with mycobacterium infections.6
Patients are frequently diagnosed with soft tissue infection, such as abscesses or cellulitis, as in our case. They may at times be found to have other musculoskeletal conditions such as trigger finger.1 Other similar presenting entities are psoriatic arthritis, rheumatoid arthritis, and remitting seronegative arthritis.4 These clinical resemblances complicate the scenario, especially when initial cultures are negative, as the treatment for these rheumatic diseases is immunosuppression, which adversely impact the fastidious infection. In our case, the improved swelling and range of motion after the 3-week course of empiric antibiotics for suppurative tenosynovitis was initially reassuring that the previous infection had been successfully treated. Subsequently, the presence of chondrocalcinosis in the triangular fibrocartilage in the right-hand X-rays, persistent pain, and the tophi-like appearance of the right third proximal interphalangeal nodule raised concerns for crystalline arthropathies, such as calcium pyrophosphate deposition vs gout. Nonetheless, given the lack of response to low-dose steroids, an ongoing infectious process was strongly considered.
Sarcoidosis was a concern after the first synovial biopsy revealed noncaseating granulomas and negative stains and cultures. Sarcoid tenosynovitis is rare with only 22 cases described as per a 2015 report.7 Musculoskeletal involvement in sarcoidosis has been reported in 1 to 13% of sarcoid patients.7 Once again, unresponsiveness to steroids led to another synovial biopsy for culture due to potential infection. Akin to other cases, more than one surgical debridement was required to diagnose our patient.
Conclusions
Our case reinforces the vital role of history gathering in establishing diagnoses. It underscores the value of clinical suspicion especially in patients unresponsive to standard treatment for inflammatory arthritis, namely corticosteroids. Tissue biopsy with culture for AFB is crucial for accurate diagnosis in NTM infection, which may imitate rheumatic inflammatory arthritis. Clinicians should be keenly aware of this fastidious, indolent organism in the setting of persistent localized tenosynovitis.