A 3-month-old girl was referred to our hospital with a suspicion of Langerhans cell histiocytosis. She was hospitalized for pneumonia at the fifteenth day of birth followed by recurrent and treatment resistant cervical lymphadenopathies with high CRP levels. She was the first child of a consanguineous family. She had bilateral cervical lymphadenopathies and maculopapular skin eruptions over body and legs on admission. Laboratory investigations revealed anemia, leukocytosis, high CRP level (12 mg/dL), and hypergammaglobulinemia. Histological findings of the skin biopsy and lymph node excision were reported as granulomatous inflammation and necrotizing granulomatous lymphadenitis, respectively. Meanwhile, oxidative burst activity ("Phagoburst" kit, Glycotope, Biotechnology) was insufficient (FMLP 9%, PMA 9%, and opsonized E. Coli 4%; normal values 1-10%, 98-100%, and 97-100%, resp.) leading to a probable diagnosis of CGD later confirmed with mutation analysis disclosing a "homozygous autosomal recessive c.369 + 1G>A mutation" in CYBA gene-  p22phox.
She was admitted again with tachypnea with coarse lung sounds relevant to acute pneumonia at 30 months of age. She had anemia (Hb: 8.9 g/dL), leukocytosis (16800/mm3), and high CRP (3 mg/dL) and ESR (60 mm/hr) levels. CXR showed bilateral extensive infiltrations especially prominent in left upper lobe (Figure 3). Thorax CT revealed pneumonic consolidations with calcifications (Figure 3). These findings were interpreted in favor of tuberculosis (TB) although objective mycobacterial evidence was absent (PPD 9 mm, gastric fluid acid-fast bacilli and PCR negative). Three-drug combination therapy (isoniazid, rifampicin, and pyrazinamide) was initiated. Echocardiography showed pericardial thickening which was also evaluated as TB sequela.
Despite treatment, her clinical condition worsened in a two-month period. Extensive lymph node enlargements in mediastinum and around pericardium reaching to 3 cm in diameter, some showing central necrosis, were recorded in the new thorax CT (Figure 3). During hospitalization, she developed right congestive heart failure signs, fine crackles in lungs, and increased oxygen need. Echocardiography showed findings compatible with pulmonary hypertension, diastolic dysfunction, and constrictive pericarditis (Figure 4). Emergency pericardiectomy was performed. Aspergillus fumigatus was cultured in pericardial fluid and blood Aspergillus antigen was positive for the first time. Parenteral caspofungin and voriconazole infusions were initiated in combination for antifungal therapy. Histological interpretation of the pericardial sample was reported as granulomatous pericarditis.
Fever and respiratory distress continued and thorax CT revealed an abscess of 4.5 x 1.7 cm diameter in left lung inferior lobe, two weeks after the pericardiectomy (Figure 5). The abscess was drained and drainage material culture was positive for Aspergillus fumigatus (Figure 5). Granulocyte transfusions were applied for the subsequent days and fever subsided gradually in a few days. She was discharged with oral voriconazole after her condition stabilized with parenteral antifungal therapy for one month. Blood Aspergillus antigen was still positive in low titers.
Two weeks later, she was brought to emergency department with left hemiparesis, left central facial paralysis, and fever. Glasgow Coma Scale was 12, motor strength was 2/5 in left upper and lower extremities, and left plantar response was abnormal in neurological examination. A hypodense lesion at the level of right basal ganglia was interpreted as acute ischemic infarction in cranial CT (Figure 6). Diffusional restriction consistent with acute ischemia in right basal ganglia and cerebral, cerebellar millimetric enhancing foci consistent with aspergillosis were reported in cranial and diffusion magnetic resonance imaging (MRI) (Figure 6). In MR angiography, right middle cerebral artery was occluded from M2 segment to end which was also associated with Aspergillus infection (Figure 6). Voriconazole, amphotericin B, vancomycin, and meropenem were started. Intravenous immunoglobulin, 1 gr/kg/day, was given for two days. Fever was controlled and her general condition improved. Acetylsalicylic acid treatment was commenced to prevent further infarction.
Neurological findings regressed with decreased facial asymmetry and increased motor strength in the follow-up. Parenteral antifungal treatment was continued for two months and she was discharged with oral voriconazole and negative blood Aspergillus antigen. The ischemic lesion in the right basal ganglia showed chronicity and appeared as cystic encephalomalacia; most of the cerebral/cerebellar foci were smaller than before and some disappeared in the control MRI five months after the initial evaluation (Figure 7). Due to the severe course of her disease, HSCT was planned and due to the lack of full matched relative, an unrelated donor search is initiated.