Cystic fibrosis (CF), caused by mutations in the CFTR gene, leads to defective ion transport and multisystem complications. While typically diagnosed in childhood, atypical or late-onset presentations can delay recognition. CF often mimics immunodeficiency with recurrent infections and bronchiectasis, and early diagnosis remains critical for optimizing outcomes.
A 65-year-old female, being seen by multiple subspecialists, ultimately referred for suspected immunodeficiency after decades of multisystem health issues. Her childhood was marked by recurrent sinopulmonary infections, progressing to pneumonia at 13. By her mid-20s, she experienced weight loss and malabsorption, initially diagnosed as celiac disease. Pancreatic insufficiency, identified through low fecal elastase, improved with enzyme replacement.
In her 50s, she was diagnosed with Hansen’s disease and experienced complicated pneumonia with parapneumonic effusions. CT imaging (Figure 1) revealed bronchiectasis and pulmonary nodules. Diagnosed with non-tuberculous mycobacteria (NTM), she initially underwent triple therapy, later switched to inhaled amikacin due to medication intolerance. Despite treatment, sputum cultures persistently grew Mycobacterium abscessus, Mycobacterium avium complex, Pseudomonas, and Aspergillus, the latter treated with voriconazole and steroids for suspected allergic bronchopulmonary aspergillosis.
Red arrows showing bilateral bronchiectatic changes. Green arrow showing pulmonary nodule.
Red arrows showing bilateral bronchiectatic changes. Green arrow showing pulmonary nodule.
An immunodeficiency workup showed mildly low IgG1 subclass and poor pneumococcal vaccine response. However, a detailed history revealed infertility and Ashkenazi Jewish ancestry, raising suspicion for CF. Genetic testing confirmed two pathogenic CFTR variants, including delta F508. Sweat chloride testing revealed intermediate results, and she was started on elexacaftor/tezacaftor/ivacaftor, leading to marked improvement in sputum clearance and overall health.
This case highlights the diagnostic challenge of potential bias in atypical CF in adults, where recurrent infections, bronchiectasis, and pancreatic insufficiency may mimic immunodeficiency. Misattributed symptoms delayed appropriate treatment for decades. CFTR modulators significantly improved outcomes in this patient, emphasizing the need for a high index of suspicion in adults with similar clinical features, particularly those with infertility or high-risk ancestry.
