Stronger warnings need to be put on four medications used to treat rheumatoid arthritis, Crohn's disease and other conditions following the deaths of 12 people who contracted fungal infections, the U.S. Food and Drug Administration said Thursday.

The injection drugs — Enbrel, Remicade, Humira and Cimzia – belong to a class of drugs called TNF- alpha blockers, which suppress the immune system.

The drugs are prescribed to relieve swollen and painful joints in people with rheumatoid arthritis, as well to treat Crohn's disease — a disease of the digestive system — juvenile arthritis, certain types of psoriasis and other immune system disorders.

Current warnings "must be upgraded to strongly warn doctors to consider" the possibility of fungal infections in patients who are seriously ill or who are not responding to current antibiotics, said Jeffrey Siegel, a clinical team leader in the FDA's division of anesthesia, analgesia and rheumatology products.

"These infections need to be identified early enough so that treatment is not delayed," he added.

Doctors seemed to be overlooking a fungal infection called histoplasmosis. The FDA received 240 reports of the infection among people taking one of the four drugs. Of these, 45 died, about 20 per cent.

In at least 21 reports, doctors did not initially recognize the infection and treatment with antifungal medication was delayed, the agency said.

Histoplasmosis targets the respiratory system, causing flu-like symptoms, such as a fever and cough. Current treatments for serious cases include drugs that carry highly toxic side-effects, but doctors should consider prescribing them even if an infection is not confirmed by a laboratory test, Siegel said.

People taking the medications should call their doctor if they develop persistent fever, cough, shortness of breath or fatigue, which can be signs of the fungal infection.

Most of the reports of fungal infection involved people in the Ohio River and Mississippi River valleys, where the fungus is commonly found.

Drug makers have 30 days to submit new warnings for approval or give a reason to protest the change, the FDA said.

Some drug labels already contain strong warnings about the serious risk of fungal and other infections but the FDA wants the wording to be consistent, with greater emphasis on histoplasmosis.

Enbrel, Remicade and Humira are approved for sale in Canada but Cimzia is not.