COPENHAGEN (Reuters Health) Jun 17 - Rheumatoid arthritis patients who develop histoplasmosis are more likely to have had their disease for at least 10 years and to have been treated with two or more immunomodulatory agents at the time of infection than rheumatoid arthritis patients who do not develop histoplasmosis, according to data released at the European League Against Rheumatism (EULAR) 2009.
The findings, reported by a group from the Mayo Clinic in Rochester, Minnesota, are from the largest single series of patients with rheumatoid arthritis and histoplasmosis in the era of anti-tumor necrosis factor alpha (TNF) therapy.
Dr. Timothy Olson and associates examined the frequency of histoplasmosis infection in adult rheumatoid arthritis patients residing in the U.S. Midwest, an endemic area for the fungal infection, and also examined risk factors for infection.
The clinical management of rheumatoid arthritis involves the use of immunomodulatory agents, including anti-TNF agents, which have been linked to an increased risk of serious and opportunistic infections. Dr. Olson pointed out.
Histoplasmosis is the most common endemic mycosis in the U.S, he added. Most infections are asymptomatic or self-limiting, but about one in 2,000 acute infections results in severe and progressive dissemination, usually occurring in immunocompromised hosts.
The FDA recently issued an alert to health care professionals on the risk of invasive fungal infections, specifically histoplasmosis, in patients on anti-TNF therapy and noted that infections were not consistently identified, thereby causing treatment delays.
The present analysis included all rheumatoid arthritis patients who developed new histoplasmosis infection over a recent 10-year period at a tertiary care center in the upper midwest region of the U.S. Histoplasmosis was identified through pathology, serology, microbiological culture, and antigen determinations.
Histoplasmosis was diagnosed in 20 patients whose mean duration of rheumatoid arthritis was 10.5 years. The mean age at the time of infection was 60.5 years, with a mean follow up 2.3 years.
Eighty-nine percent of patients were on two or more immunomodulatory agents at the time of infection. The immunomodulatory agents most frequently used included corticosteroids, methotrexate, and anti-TNF agents.
The site of infection was pulmonary in 17 patients, 8 of which were in combination with other sites. Fever was the most common clinical sign of infection (>38 C), although typical signs and symptoms of infection were often absent. Two patients died of causes not related to histoplasmosis.
Based on these results, Dr. Olson calls for extreme caution "with future anti-TNF agents in these patients given the risk of reactivation of histoplasmosis."