The FDA has ordered stronger warnings for four drugs used to treat rheumatoid arthritis. The FDA warns that patients are at risk of developing potentially fatal fungal infections. According to the agency, there have been "reports of patients developing pulmonary and disseminated histoplasmosis, coccidioidomycosis, blastomycosis and other opportunistic infections while taking TNF blockers. In some patients, the diagnosis of histoplasmosis was initially unrecognized and antifungal treatment was delayed. Some of these patients died from histoplasmosis. There were also deaths in patients with coccidioidomycosis and blastomycosis."

The drugs identified by the FDA are Remicade, Enbrel, Humira and Cimzia are in a class of medications known as TNF inhibitors.

The FDA has cited 240 cases in which it has been reported that users of the drugs had contracted a fungal infection called histoplasmosis. 45 of the reported cases resulted in the death of the consumer.

Histoplasmosis is a fungal infection that exhibits symptoms similar to the flu. It is most prevalent in in states bordering the Ohio River valley and the lower Mississippi River. (Positive histoplasmin skin tests occur in as many as 80% of the people living in areas where H. capsulatum is common, such as the eastern and central United States.) Unless an individual's immune system is suppressed the fungus remains asymptomatic. However, the immune systems of patients taking TNF inhibitors become suppressed as a result of therapy making them more likely to become symptomatic.

In patients who are immune suppressed, most have respiratory complaints like cough or shortness of breath. Others complain of unusual weight loss, fatigue and fevers. Their have also been reports of sores on the skin, bone sores, sores in the mouth or intestines and in some instances neurological complaints.

If untreated, these fungal infections be fatal in 90% of people who are on TNF blockers. Death could occur in as little as three weeks after symptoms were observed.

The FDA has also reported that it is investigating a possible link between these drugs and cancers found in 30 patients. The agency reported that it received 30 reports of cancers found in patients who began taking the drugs before they were 18 years old. It appears that the majority of these patients developed lymphomas. An investigation is underway.