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Airborne Fungal Diseases
Fungal Infection
Immune Compromised Hosts
Cryptococcus
Candida
Skin Infection with Fungi
Fungal Contamination of Buildings
Fungi in Hospitals
Allergy to Fungi
Fungi in Food
Aspergillus

Blastomycosis
Introductory Article
My Blastomycosis Story
Fatal Brain Infection
Dr G's 2 slide culture
Blastomycosis Images
Blastomycosis Medical Literature
Reflections on an Illness

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Stephen Gislason MD

Immune Suppression and Infection

Fungal infections in hospitals are increasing as the number of patients with defective immune defenses increases. Immune deficiency may be inherited, caused by infection, metabolic diseases such as diabetes and may also be caused by immune suppressant medication. The number of immune suppressant  drugs has risen dramatically in the past decade.

Immune Suppressant Drugs

New agents have been introduced to treat immune mediated diseases. The strategy of drug companies has been varied, but the goal with each new agent is to block immune activation at some level or another. While there may be benefits, the research and product hype can be distracting. There is no easy and safe way to block immune activity. The more effective immune blockers are, the more damage they can do. New immunosuppressants come with many possible penalties:

1. The drugs are expensive.

2. The negative effects are often severe.

3.The long term effects both good and bad are not well known

4.The method of administration is often time-consuming,  expensive, and intensifies dependency on medical facilities, laboratories and hospitals.

5. Blocking immune function facilitates infection by a variety of micro-organisms.

6. Blocking immune activity may also increase the rate of cancer emergence.

Tumor Necrosis Factor (TNF) blocking agents

TNF blockers has become popular, despite concerns about serious infection and cancer facilitation. Since the initial approval of the TNF blockers, the prescribing information for these drugs has included information about the risk of serious infections, including tuberculosis and fungal infections.

Knine reported that makers of tumor necrosis factor (TNF)-blocking agents were ordered to strengthen warnings regarding the risk for histoplasmosis and other invasive fungal infections by the US Food and Drug Administration. The FDA is concerned that physician are  not recognizing cases of histoplasmosis and other invasive fungal infections, leading to delays in treatment.

The US FDA has received 240 reports of histoplasmosis in patients receiving infliximab (Remicade); 207 cases, etanercept (Enbrel)  17 cases, adalimumab (Humira) . 1 case occurred during treatment with certolizumab pegol (Cimziac), approved in 2008. Missed diagnoses in 21 patients led to treatment delays and 12 deaths.  Fatal cases of coccidioidomycosis and blastomycosis have also been reported. Healthcare professionals are advised to closely monitor patients for signs and symptoms of  fungal infection during and after treatment with anti-TNF drugs. Patients who develop fever, malaise, weight loss, sweats, cough, dyspnea, pulmonary infiltrates on X-ray, or serious systemic illness should undergo a complete diagnostic workup.

The FDA advised that a high index of suspicion should be maintained for invasive fungal infections in symptomatic patients. If possible, the decision to initiate empiric antifungal therapy should be made in conjunction with an infectious diseases specialist.  An infectious disease consultation is also recommended when determining the duration of antifungal therapy and whether anti-TNF therapy should be resumed on recovery, particularly for patients who reside in regions of endemic mycoses.  TNF blockers are immunosuppressive agents approved to treat  immune system diseases, including juvenile idiopathic arthritis, rheumatoid arthritis, psoriatic arthritis, plaque psoriasis, Crohn's disease, and ankylosing spondylitis.

See Yael Waknine. Patient Deaths Spark Stronger Warnings for TNF Blockers. Medscape Medical News 2008. Accessed online September 4, 2008. In the US, adverse events related to use of anti-TNF agents should be reported to the FDA's MedWatch reporting program by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, MD 20852-9787.

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