Pulmonary granulomatosis of genetic origin

Abstract

Granulomatous inflammation of the lung can be a manifestation of different conditions and can be caused by endogenous inflammation or external triggers. A multitude of different genetic mutations can either predispose patients to infections with granuloma-forming pathogens or cause autoinflammatory disorders, both leading to the phenotype of pulmonary granulomatosis. Based on a detailed patient history, physical examination and a diagnostic approach including laboratory workup, pulmonary function tests (PFTs), computed tomography (CT) scans, bronchoscopy with bronchoalveolar lavage (BAL), lung biopsies and specialised microbiological and immunological diagnostics, a correct diagnosis of an underlying cause of pulmonary granulomatosis of genetic origin can be made and appropriate therapy can be initiated. Depending on the underlying disorder, treatment approaches can include antimicrobial therapy, immunosuppression and even haematopoietic stem cell transplantation (HSCT). Patients with immunodeficiencies and autoinflammatory conditions are at the highest risk of developing pulmonary granulomatosis of genetic origin. Here we provide a review on these disorders and discuss pathogenesis, clinical presentation, diagnostic approach and treatment.

Genetically confirmed chronic granulomatous disease in a Kenyan child: case report

“…These include TB and complications from the BCG vaccine such as scarring or abscess formation at the BCG injection site and disseminated BCG infection since the vaccine is a live attenuated form of Mycobacterium bovis ( 24 ). We suspected BCG disease in this child due to the clinical presentation: axillary lymphadenopathy on the same side as the BCG scar, the strongly positive tuberculin skin test, and multiple large lung nodules that could be pulmonary granulomas ( 25 ). Although the Hain test on lymph node biopsy detected M. tuberculosis , which was sensitive to both isoniazid and rifampicin, this did not rule out M. bovis , which is also part of the M. tuberculosis complex.…”

Noninfectious Granulomatous Lung Disease: Radiological Findings and Differential Diagnosis

“…Sarcoidosis is a cell-mediated immune response to unidentified antigens in genetically susceptible patients [8]. The histological hallmark of sarcoidosis is the presence of wellformed, compact, epithelioid, non-necrotizing granulomas with different degrees of lymphocytic inflammation [2,3,12]. Sarcoid granulomas contain epithelioid cells, macrophages, multinucleated giant cells, and CD4+ T cells in the center, while CD8+ T lymphocytes, B lymphocytes, and fibroblasts are seen at the periphery [13][14][15][16].…”

“…Infectious GLDs generally are caused by mycobacterial (both Mycobacterium tuberculosis and non-tuberculosis mycobacteria) and fungal (e.g., Histoplasma, Cryptococcus, Pneumocystis and Aspergillus) infections. Noninfectious GLDs include a variety of diseases, as inflammatory conditions (sarcoidosis), granuloma formation after environmental exposure (talc 2 of 21 and berylliosis), vasculitis (granulomatosis with polyangiitis (GPA)), autoimmune diseases (rheumatoid nodule and lymphomatoid granulomatosis) and other types as pulmonary Langerhans cell histiocytosis [1][2][3]. A list of the noninfectious GLDs is reported in Table 1.…”

“…Histologically, necrotizing and non-necrotizing granulomas have to be differentiated. Generally, necrotizing granulomas develop in association with an infectious cause [3]. The diagnosis includes clinical evaluation, laboratory testing, and radiological imaging, which especially consists of high-resolution computed tomography (HRCT).…”

“…The diagnosis includes clinical evaluation, laboratory testing, and radiological imaging, which especially consists of high-resolution computed tomography (HRCT). bronchoalveolar lavage (BAL), transbronchial needle aspiration or cryobiopsy, video-assisted thoracoscopic surgical (VATS) biopsy, and positron emission tomography (PET), while genetic evaluation can improve the diagnostic accuracy [3].…”