not-yet-known not-yet-known not-yet-known unknown Discussion A 7-year-old boy with no history of severe infections presented with sudden onset of dyspnea, fever, and acute respiratory insufficiency. Although this clinical condition is usually associated with acute respiratory infection in children, a rare primary immunodeficiency was finally diagnosed to underlie the clinical symptoms. The borderline growth represented the only finding indicative of possible chronicity upon manifestation. Since the respiratory failure did not respond to multifaceted therapeutic approaches, a detailed pulmonary evaluation was performed, starting with a chest CT scan. This investigation revealed acute diffuse lung parenchymal disease. The chest CT pattern can usually narrow the otherwise extensive differential diagnosis in clinical practice (1). In this case, the diffuse nodular involvement, together with skin affection, required the exclusion of sarcoidosis, cutaneous tuberculosis, and vasculitis in the first place. The diffuse nodular pattern with hilar lymphadenopathy also evoked the image of possible lymphoma (2) and substantiated an oncologic screening including whole body PET-CT scan. Finally, a hypersensitivity pneumonitis was highly suspected because of the corresponding CT pattern, history of mold and mulch exposition, and high levels of specific IgG antibodies against molds (3). However, several aspects were elusive. Firstly, the association of hypersensitivity pneumonitis with skin lesions was unclear. Secondly, the unexpected CMV positivity in BAL did not match the short history of symptoms, however in rare cases the CMV infection could be consistent with the diffuse parenchymal CT pattern (4). Therefore, given also the discrepancy between low peripheral blood CMV load and high loads in BAL, the antiviral therapy was substantiated. Thirdly, a fungal lung infection did not seem likely, however, some results commanded an increased level of suspicion. Eventually, an underlying immune pathology was considered and finally confirmed. Primary immunodeficiencies often present with pulmonary symptoms. Beside infections, they can manifest with non-infectious complications of immune dysregulation, including a diffuse lung involvement (5, 6). Perhaps the best-known example is the granulomatous and lymphocytic interstitial lung disease (GLILD) that occurs most typically in inborn errors of antibody immunity, such as common variable immunodeficiency (7). Cutaneous and visceral granulomas are common among patients with chronic granulomatous disease, combined immunodeficiency, and other diseases with immune dysregulation (8) In our patient, no granulomas were found, but it was the opportunistic pathogens and the treatment-refractory condition that prompted the immunologic investigation. The diagnosis of X-linked CGD aligns well with all the patient’s symptoms. In CGD, the immune performance of phagocytes is impaired due to the loss or reduction of function of nicotinamide adenine dinucleotide phosphate complex. This enzyme is essential for the generation of reactive oxygen species (ROS) which play a critical role in killing of internalized pathogens, because ROS are directly highly toxic to microbes, including yeast (particularly Candida spp ., Aspergillus and other opportunistic yeast) and various bacteria. Also, ROS trigger signaling pathways that enhance antiviral immune responses. Typical noninfectious manifestation of CGD include sterile noncaseating granulomatous of the gastrointestinal tract, resembling inflammatory bowel disease, as well as parenchymal and cutaneous granuloma formation(9); however, the picture of diffuse parenchymal lung disease has also been reported in CGD (10, 11).Notably, acute worsening of lung disease mimicking hypersensitivity pneumonia was observed in three children with CGD who developed invasive pulmonary Aspergillus fumigatus infection after administration of systemic glucocorticoid therapy (12). While we did not detect convincing signs of invasive fungal lung infection in our patient, we administered antifungal prophylaxis alongside the steroids because of the abnormal burst test, PCR positivity of Aspergillus in sputum and the presence of mycotic hyphae in the skin. Last but not least, while the very high values of specific antifungal IgG antibodies supported the diagnosis of hypersensitivity pneumonitis (13), the level of galactomannan and beta-D-glucan did not meet the positivity criteria. Interestingly, false negativity of galactomannan was observed in patients with CGD (14) A CMV lung infection is rather rare yet reported complication in CGD patients (15). In our case, we suspect that the immune defect together with the diffuse inflammatory lung damage might have allowed the multiplication of CMV in the lungs. Taken together, we suggest incorporating comprehensive immunologic evaluations, including the oxidative burst test, in the diagnostic workup for children presenting with hypersensitivity pneumonia. This approach not only aids the identification of an underlying immunodeficiency but also enables timely and targeted treatment. We also suggest that clinicians maintain a high index of suspicion of rare immunodeficiencies in cases where standard treatments fail or symptoms are atypical, to ensure all potential underlying causes are thoroughly explored.