Chronic granulomatous disease revealed by a pulmonary aspergillosis complication in an adult

Clinical History

42-year-old healthy man presented with cough and flu symptoms for several months. In absence of satisfactory clinical improvement after antibiotic therapy, CT, laboratory investigations and bronchoscopy were performed, suggesting a sarcoïdosis. Despite corticosteroid treatment, symptoms persisted. The patient was hospitalised for further investigation.

Imaging Findings

First ambulatory chest CT examination revealed a bilateral disseminated centrilobular and a septal distribution of micronodular infiltrates, associated with bilaterally enlarged mediastinal lymph nodes, concluding a diagnosis of probable stage II Sarcoidosis (fig. 1-4). Chest CT done at the hospital showed an evolution of the diffuse micronodular distribution associated with area of alveolar condensation predominant in the hilar regions and the upper lobes (fig. 5). The broncho-alveolar lavage and biopsy highlighted histological non-necrotising granulomatous infiltration, with presence of mycelial filaments (Aspergillus fumigatus). In the absence of known immunosuppression, a flow cytometry was performed and revealed strongly reduced activity of NADPH (oxidative activity of neutrophils), compatible with a chronic granulomatous disease (CGD), and confirmed by sequencing the complex NADPH genes.

Discussion

Chronic granulomatous disease (CGD) is a rare type of primary immunodeficiencies, involving dysfunction of the NADPH oxidase system and inability of phagocytes to generate superoxide to fight pathogenic organisms. It is characterised by repeated infections with bacterial and fungal pathogens, as well as the formation of granulomas in tissues [1].
Pulmonary changes are present in as many 60% of patients with primary immunodeficiency [3].
The clinical manifestations of CGD usually occur during childhood as repeated and severe bacterial or fungal necrotising infections. The diagnosis affects approximately 1/250, 000 individuals and it can occur late in adult age, as in our clinical case [1]. Pneumonia is the most common complication (in about 80% of CGD), with descriptions of Aspergillus infection as the major cause of morbidity and mortality [2].
Medical imaging, especially CT, plays an important role in monitoring the response to therapy. Indeed, granulomatosis is an indicator of uncertain prognosis, developing a terminal respiratory failure in 24% of cases [3]. Some authors have described a semiology of sarcoïd or sarcoïdlike pattern to characterise granulomas in patients with primary immunodeficiency (present in as many as 8% of patients with common variable immunodeficiency), which occurs as well-defined nodules with perilymphatic distribution (which can be associated with areas of pulmonary fibrosis in advanced-staged disease), and it can be associated with bilateral mediastinal lymphadenopathies (58% of patient with both primary immunodeficiency and granulomatosis) [3, 4]. Such imagery suggests a differential diagnosis of sarcoidosis, tuberculosis infection, opportunistic infections or lymphoproliferative disease. CGD should also be suggested in the differential diagnosis in a clinical context of immunodeficiency [2].
The final diagnosis of CGD is made by histology, with pattern of non-necrositing granulomatous infiltration, and is confirmed by both flow cytometry and DNA sequencing of the NADPH oxidase system (dysfunctional in CGD) [1].

Differential Diagnosis List

Final Diagnosis

Chronic granulomatous disease, with pulmonary aspergillosis complication.

URL:	https://www.eurorad.org/case/10206
DOI:	10.1594/EURORAD/CASE.10206
ISSN:	1563-4086