CTS = carpal tunnel syndrome; AmB = amphotericin B; SS = silver stain; SLE = systemic lupus erythematosus.
Localized tenosynovitis caused by Histoplasma capsulatum: Case report and review of the literature
Version of Record online: 4 FEB 2005
Copyright © 2005 by the American College of Rheumatology
Arthritis Care & Research
Volume 53, Issue 1, pages 129–132, 15 February 2005
How to Cite
Cucurull, E., Sarwar, H., Williams, C. S. and Espinoza, L. R. (2005), Localized tenosynovitis caused by Histoplasma capsulatum: Case report and review of the literature. Arthritis & Rheumatism, 53: 129–132. doi: 10.1002/art.20918
- Issue online: 4 FEB 2005
- Version of Record online: 4 FEB 2005
- Manuscript Accepted: 22 SEP 2004
- Manuscript Received: 9 JUN 2004
Histoplasma capsulatum is endemic in the Ohio and Mississippi river valleys, as well as in certain areas of Central and South America. The soil is the natural habitat and infectious reservoir of the organism. The respiratory tract is the usual portal of entrance. The fungus tends to become disseminated after invading the lungs. However, the vast majority of human infections are asymptomatic and self limited (1). Occasionally, histoplasmosis first presents with isolated extrapulmonary organ involvement. We describe a patient with localized tenosynovitis of the finger caused by H. capsulatum without clinical evidence of disseminated disease or pulmonary involvement.
A 42-year-old white woman, resident of New Orleans, Louisiana, presented on May 2002 with new onset pain and swelling of her left hand in the area between the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of her index finger. Her medical history was significant for systemic lupus erythematosus (SLE) diagnosed in 1975 that presented with fever, arthralgias, pleuritis, pericarditis, and positive antinuclear antibodies (ANA) and anti–double-stranded DNA (anti-dsDNA). In 1988 she developed lupus nephritis and received treatment with corticosteroids, hydroxychloroquine, and azathioprine. The patient went into remission and was able to discontinue corticosteroids and azathioprine by May 2000. Since then, she has been asymptomatic taking only hydroxychloroquine 200 mg twice daily. The patient does not smoke, drink alcohol, or uses other illegal substances. She has been working in an immunology laboratory since 1996. However, she did not report any traumatic inoculation while working at the lab.
Her physical exam was unremarkable except for purple discoloration and swelling on her index finger between her MCP and PIP joints. Her finger exhibited decreased flexion and was tender to touch and movement. Regional lymph nodes were not enlarged. Her laboratory results were also unremarkable, including normal complete blood count, erythrocyte sedimentation rate, and C-reactive protein level. She had a positive ANA with homogeneous pattern, negative anti-dsDNA, and normal complement levels. Her hand radiograph revealed soft-tissue swelling without any bone or joint involvement. Tenosynovitis was diagnosed and she started treatment with oral valdecoxib 20 mg/day and received a local injection of triamcinolone. After a brief improvement, swelling worsened and subsequently involved the PIP and MCP joints (Figure 1A). Three more local injections of triamcinolone were given during the course of 2 months providing only temporary relief but without worsening the symptoms. A magnetic resonance image of the hand revealed mild edematous infiltration between the distal portions of the second and third MCP bones and within the palmar soft tissues between the flexor tendon and proximal phalanges of the index finger (Figure 2A). These findings were consistent with flexor tenosynovitis of the index finger without evidence of osteomyelitis or focal mass lesions. She was then referred to an orthopedic hand surgeon for biopsy. Histologic examination of the synovium revealed fibroadipose tissue with a moderate chronic inflammatory infiltrate and abundant granulomatous inflammation, including the formation of noncaseating granulomas. Special stains (Gram stain, acid-fast bacillus, Gomori's methenamine silver, and Fite stain) were negative for the presence of microorganisms. Polymerase chain reaction results were negative for bacterial and mycobacterial DNA. Four weeks later, the fungal culture of the biopsy specimen grew H. capsulatum. A chest radiograph did not show any pulmonary lesions. She was started on oral itraconazole 200 mg/day and took it for a total of 12 months. Ten months after initiation of therapy, a repeat MRI of the hand showed marked improvement of the edematous signal (Figure 2B). She remains asymptomatic 2 years after the diagnosis was made and 1 year after cessation of therapy (Figure 1B).
The rheumatologic manifestations of primary acute histoplasmosis were described by Rosenthal et al (2) during the Indianapolis epidemic of 1978–79. Twenty four of 381 patients (6.3%) with symptomatic histoplasmosis presented with rapidly additive arthritis or arthralgia involving the knees, ankles, wrists, or small joints of the hand. Ten patients had oligo- or monarticular disease and it was symmetric in 50% of the cases. These manifestations were usually mild and resolved without treatment or with a brief course of nonsteroidal antiinflammatory drugs in the majority of cases. This articular involvement is considered to be part of a systemic inflammatory reaction that often coexists with skin lesions of erythema nodosum and erythema multiforme. Our patient's presentation differs from this clinical picture. She presented with an isolated tenosynovitis of her index finger caused by H. capsulatum. She did not have a previous history of histoplasma infection and no other manifestations, pulmonary or otherwise, were present at the time of diagnosis or have occurred subsequently.
Occasionally, histoplasmosis first presents with isolated extrapulmonary organ involvement. These isolated lesions are usually considered to be manifestations of disseminated disease, despite the lack of pulmonary involvement. In our patient, we considered local inoculation by a cat scratch to explain the mechanism of her infection. She has several cats and often has scratches on her hands and arms. If a cat had been in contact with contaminated soil and immediately scratched our patient, it could have inoculated the fungus in her finger. Cases of primary extrapulmonary infection have been described but they are exceptional and difficult to prove (3, 4). The criteria necessary to establish a diagnosis of primary local infection with a fungus capable of causing pulmonary mycosis were described in the early 1950s (5) and include the following: history of traumatic inoculation, with subsequent development of a chancriform lesion; lymphangitis and regional lymphadenopathy; evidence that the wound was contaminated with the causative fungus; no history or clinical or laboratory evidence of previous pulmonary or systemic mycosis; and confirmation of the skin test result from negative to positive. Primary cutaneous histoplasmosis, which resulted from direct inoculation of the fungus through the skin, has been proven by these criteria in a few cases of accidental inoculation in laboratory workers or other health care–related professions (3, 4). Our patient does not fulfill all of these criteria, therefore whether her localized infection was due to disseminated disease or primary inoculation is difficult to determine.
We reviewed the literature describing cases of histoplasmosis presenting as tenosynovitis using Medline (January 1966 through 2004), and 9 other cases were identified (6–14). Table 1 summarizes the findings in all those cases including our patient. Six cases presented as carpal tunnel syndrome and 4 as tenosynovitis of the hand or fingers. All reported chronic or recurrent symptoms for several months before diagnosis was made. In most of the cases described, an infectious etiology was not suspected until it became apparent incidentally on surgical exploration or carpal tunnel release (11). As in our case, steroid injections (7–9, 12) brought some relief, but the symptoms recurred. Three patients had predisposing conditions (breast cancer, SLE, and chronic oral corticosteroid therapy). Our patient had a history of SLE and had received immunosuppressive therapy in the past. However, we do not believe that she should be considered immunocompromised at the time of the infection because she had been clinically in remission and off immunosuppressive medications for 2 years.
|Case no. (ref.)||Sex/age, years||Clinical manifestation||Symptoms duration, months||Predisposing conditions||Diagnostic tests||Treatment||Recurrence||Outcome|
|1 (6)||M/32||CTS, lytic lesions left triquetrum||12||No||Culture||Surgery, AmB (3.5 gm)||No||Well at 2 years|
|2 (7)||M/24||CTS||7||No||Culture, SS||Surgery||Yes at 1 year||Surgery, AmB, did well at 4 years|
|3 (8)||F/43||CTS||12||No||Culture, SS||Surgery, AmB (1 gm)||No||Well at 4 months|
|4 (9)||F/43||CTS, bone marrow, tongue lesions||11||Breast cancer, recent chemotherapy||SS||Surgery, AmB (1 gm)||No||Well at 4 months|
|5 (10)||F/42||Tenosynovitis 3rd finger, later disseminated histoplasmosis||10||SLE, steroids and azathioprine||Culture, SS||Surgery, AmB (336 mg), miconazole||Died of complications of SLE|
|6 (11)||M/28||CTS||18||No||Culture||Surgery, ketoconazole for 6 months||No||Well at 6 months|
|7 (12)||M/29||CTS||30||No||Culture||Surgery, ketoconazole for 6 months||No||Well at 9 months|
|8 (13)||M/71||Extensor tenosynovitis right hand||16||Low-dose oral corticosteroids for 20 years||Culture||Surgery, itraconazole, fluconazole, AmB (1.14 gm)||No||Well at 2 years|
|9 (14)||M/35||Flexor tenosynovitis, cystic lesion capitate||1||No||Culture, skin testing||Surgery, ketokonazole for 4 months||Yes at 10 years||Surgery, itraconazole for 6 months. Well at 20 months|
|10†||F/42||Flexor tenosynovitis finger||3||No (SLE on remission)||Culture||Itraconazole for 12 months||No||Well at 2 years|
Tenosynovitis was the only site of infection in 8 patients without any evidence of histoplasmosis elsewhere. Whether the mechanism of infection in those cases was the result of direct inoculation of the fungus was not discussed in the case reports. The best response to treatment was achieved with the combination of surgical debridement and antifungal therapy with amphotericin B. Two patients had a recurrence; 1 patient was treated with surgery alone and in the other, tenosynovitis recurred 10 years later. Current antifungal agents are available in oral form, are less toxic, and are highly effective. Our patient responded to prolonged antifungal therapy alone. Recommendations on treatment duration depend on host immune status and the clinical picture. Itraconazole, 200 mg once or twice daily for 6–18 months, is the treatment of choice for immunocompetent hosts with disseminated histoplasmosis with mild or moderately severe symptoms who do not require hospitalization (1).
In summary, Histoplasma capsulatum infection can present as isolated tenosynovitis without evidence of systemic involvement. In an endemic area, histoplasmosis should be included in the differential diagnosis of a chronic monarthritis or persistent tenosynovitis that does not respond to standard treatment.