Teaching Case

Aspergillosis in a patient with chronic granulomatous disease

At age 7, the patient presented with clinical and radiological signs of an apparent "left lower lobe pneumonia" (Fig. 1), with relapsing episodes of mild fever, cough, malaise, and chest pain. Antibiotic therapy achieved only slight clinical improvement with no changes in pulmonary opacity. After four months, broncoscopy and broncography were performed (Fig. 2), mainly to rule out infection superimposed a foreign body or some kind of congenital malformation. No foreign body was found, and bronchography demonstrated only slight distortion of bronchial tree. On that occasion, the X-ray films also showed a slight widening of the paravertebral extremities of the middle ribs; a detail film proved the presence of several fine irregularities of the spongiosa (Fig. 3). The possibility of an abscess or a mass of different origin was considered and the patient was submitted to surgical intervention: a large abscess involving the left lower lobe and adjacent pleura was found. Bacteriological and histological findings indicated that this was due to Aspergillus fumigatus infection. Laboratory investigations were carried out (including immunologic study) and demonstrated that the patient was actually affected by "chronic granulomatous disease" (an immunologic congenital disease characterized by impaired phagocytosis). Between age 9 and 16, the patient showed recurrent bouts of diffuse miliary infiltration of both lungs (with each bout followed by long periods of apparently complete healing of the pulmonary changes) (Fig. 4). An X-ray film at age 19 showed marked lesions of several thoracic vertebral bodies and also several calcifications in the hepatic region (Fig. 5). At age 21, the patient developed neurological signs of spinal compression at the middle thoracic level. MR demonstrated marked compression of the spinal chord due to ossifluent abscess at the level of the most damaged thoracic vertebral bodies (Fig. 6). In the last two years the conditions of the patient have been rapidly deteriorating.

Chronic granulomatous disease is an immunologic congenital deficiency characterized by impaired phagocytosis due to defective oxidative metabolism of both neutrophils and monocytes, resulting in inability to produce H2O2 and loss of microbicidal action, with subsequent predisposition to infections in several organs (especially, by Staphylococcus and Aspergillus). Most often affected are the lungs; chronic granulomatous lesions may also be present in the liver and in the abdominal lymph nodes. Bones can also be affected with foci of low-grade osteomyelitis. Sometimes granulomas may become calcified . Ossifluent abscesses and related neurological signs are quite uncommon. In conclusion, if a radiographic pattern of a chronic nodular pneumonitis is detected in a child, the patient needs appropriate laboratory evaluation to exclude chronic granulomatous disease as an underlying condition. Additionally, since radiological findings for Aspergillus infection may not be specific, confirmation of the etiologic agent through invasive diagnostic procedures is mandatory to undertake appropriate therapeutic measures (amphotericin B, voriconazole, or bone marrow transplantation). Noteworthly, our patient was firstly studied many years ago and, therefore, the diagnostic tests applied were typical for that time; in particular, broncography was utilized to rule out the presence of congenital malformations. At present, this kind of examination would have been replaced by Computed Tomography.