Cavitary Lung Lesions in Immunocompromised Patients: Insights From a Case of Non-tuberculous Mycobacterial (NTM) Infection in CD4 Lymphocytopenia

Abstract Idiopathic T CD4 Lymphocytopenia (ICL) is a rare immunological disease characterized by a significant reduction of T CD4 lymphocytes not associated with any primary or secondary immunodeficiencies. ICL diagnosis requires absolute CD4 T cells <300 u/L or less than 20% of total T cells on repeated assessments. This unexplained and severe lymphocytopenia can result in fungal, parasitic, and other opportunistic infections, presenting a diagnostic challenge. We describe a case of persistent Mycobacterium avium complex (MAC) infection leading to the diagnosis of ICL, despite standard medical treatment. 66-year-old male non-smoker with past medical history of benign prostate hyperplasia and hypertension presented for evaluation due to persistent productive cough of white sputum of 3 months of evolution. Patient refers that symptoms are associated with dyspnea on exertion, night sweats and weight loss. Physical examination and laboratories within normal range. Chest computed tomography (CT) showed evidence of a right upper lobe cavitary lesion surrounded by consolidation. Initial pulmonary function test (PFT) demonstrated a mild restrictive ventilatory impairment with normal gas transfer. Bronchoalveolar lavage (BAL) was performed with cytology and cultures. Due to high suspicion of opportunistic infection, further immunologic laboratories were ordered, revealing CD 4 count 169 cells/uL. ICL diagnosis was established following the exclusion of known causes, including HIV, genetic immunodeficiencies, and medication-related conditions, alongside persistent low CD4 T-cell counts observed in the patient. BAL acid fast bacteria culture confirmed MAC infection. Appropriate therapy started with Ethambutol, Azithromycin and Rifampin for 18 months, including Dapsone therapy for prophylaxis, but follow-up bronchoscopy cultures remained positive. Due to ICL and persistent symptomatic MAC pneumonia, patient was transitioned to inhaled amikacin liposomal antibiotic. After two years of therapy, last cultures were negative for acid fast bacteria. ICL is characterized by persistent reduction in CD4 T lymphocytes without an identifiable cause and often present with opportunistic infections. Our patient was healthy, without risk factors, and presented with chest CT findings suggesting opportunistic infection, raising suspicion for ICL. Following the diagnosis, empiric treatment was initiated; however, during follow-up visits, patient's symptoms did not improve as expected despite appropriate medical therapy. An alternative regimen was started, leading to symptom improvement. Prognosis of ICL patients varies and requires vigilant follow up to monitor immune status and manage complications. Further studies are needed to understand the pathophysiology of ICL, biomarkers and protocols. Our case highlights the importance of comprehensive evaluation and tailored management strategies are essential to improve outcomes.