Cystic Fibrosis in Adults: Why you should keep it on the differential.

Abstract

Background: Cystic Fibrosis (CF) occurs from mutations in the Cystic Fibrosis transmembrane conductance regulator (CFTR) gene. This causes abnormal transport of electrolytes in exocrine tissues, leading to thick secretions that affect multiple organs.1 Newborn screens (NBS) allow for a diagnosis in infancy, but CF can present in adulthood. Adult-onset CF is often due to uncommon mutations that result in atypical presentations.2 Unlike the male predominance seen in children, most adult-onset cases are in females. To diagnose CF, there must be a positive NBS or one symptomatic organ system, with evidence of CFTR dysfunction from a sweat chloride test (ST), nasal potential difference, or gene mutation.1 ST can be inconclusive in adults, requiring multiple STs and genetic testing.3

Case Description: A 47-year-old Spanish-speaking immigrant female was diagnosed with CF at age 40. Prior history includes rheumatoid arthritis, insulin-dependent diabetes, and asthma. Her pancreatic insufficiency, multiple CT findings of chronic bronchiectasis, and hospitalization from Levaquin-resistant pseudomonas pneumonia suggested CF. Subsequent ST results on two occasions confirmed CF. Genetic testing revealed heterogeneity for a single nucleotide variant (SNV) of the CFTR gene, p.Arg352Gln. She has no known family history of CF, but this SNV is reported to have germline origin.4

Clinical Significance: The patient’s delayed diagnosis, immigration status, and lack of insurance served as barriers for proper care. Life expectancy is significantly decreased in uninsured patients with known CF,5 and likely further decreased when a diagnosis is delayed by additional barriers. CF is not screened worldwide, thus should still be evaluated in symptomatic immigrants.6 With most CF diagnosed in children, providers are less likely to consider it in adult patients, leading to several individual diagnoses prior to a CF diagnosis.

Conclusion: Providers must be aware of bias and patient barriers when forming a differential for patients with signs of adult-onset CF.