INVASIVE LUNG-INFECTIONS WITH ASPERGILLUS SPECIES AS A LIFE-THREATENING COMPLICATION IN PATIENTS SUFFERING FROM CHRONIC GRANULOMATOUS-DISEASE

Chronic granulomatous disease (CGD) is caused by a failure of granuloc ytes and macrophages to kill phagocytized microorganisms by reactive o xygen radicals. Prophylactic and therapeutic administration of cell-pe netrating antibiotics to CGD-patients has clearly improved the unfortu nate prognosis of this disease. To this day infections by Aspergillus species remain the major life-threatening complication of CGD. But the entailing high mortality can be decreased by improving prophylaxis, e arly recognition and early treatment. We evaluated four own and 57 pub lished cases to develop procedural recommendations Results: 1. Boys an d girls are equally at risk. 2. The frequency of Aspergillus-infection s increases with increasing age. 3. Recurrent infections are not rare, 4. In many cases, initial symptoms, laboratorial and Xray findings ar e nonspecific, do not appear to be severe and are easily overlooked. 5 . Preceding or concomitant extrapulmonary symptoms are not rare. 6. Ba cterial superinfections do occur. 7. Even invasive diagnostic procedur es can fail to reveal an invading fungal infection, 8. The risk of a f atal outcome increases if the patient was exposed to a massive polluti on of fungal spores or if the fungal infection was diagnosed belatedly . Conclusions and recommendations: 1. Patients must be advised how to avoid the inhalation of great quantities of fungal spores. 2. All pati ents should be supervised regularly and checked for inflammation, or-A spergillus-titers in the serum, lung function etc. in a specialised me dical center, 3. If a patient presents with any complaints an Aspergil lus infection must always be considered (beside other CGD-specific opp ortunistic pathogens). 4. Even in case of only slight suspicion (semi- )invasive diagnostic procedures are indicated (like: broncho-alveolar- lavage, punctures, biopses etc.). 5. Patients who are doing well, but present any suspicious sign should be treated with itraconazole (for t hree months at least) even if the fungal infection remains doubtful. 6 . Patients suffering from an Aspergillus infection should be treated w ith high doses of Amphotericin B (eventually enclosed into liposomes) for 6 weeks at least, followed by a three months period of itraconazol e administration. Attemps for a continous prophylactic treatment with IFN gamma or itraconazole are promising, but the effectiveness and saf ety are still under discussion.