Resolution of recurrent pancreatitis and nutritional recovery with CFTR modulator therapy in CFTR-related disorder: a...

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have transformed cystic fibrosis care, but their role in CFTR-related disorders is not well defined.

This is a 19 year old man who presented with recurrent acute pancreatitis beginning at 12-14 years of age, with no history of sinusitis, pneumonia, or asthma. He had poor weight gain, indeterminate sweat chloride values (43-49 mmol/L), and carried a single F508del CFTR mutation. He experienced recurrent episodes of parotitis between 8 and 10 years of age. Despite preserved exocrine pancreatic function and the absence of pulmonary symptoms, he experienced persistent nutritional failure despite appetite stimulation (cyproheptadine and mirtazapine). At 18 years of age, elexacaftor/tezacaftor/ivacaftor (ETI) was initiated based on genotype eligibility and the patient's clinical phenotype. Over 19 months, he achieved complete resolution of pancreatitis and substantial weight gain (54.9-69.2 kg; BMI 19.1-23.7 kg/m²). Pulmonary function remained normal and sweat chloride decreased to 42 mmol/L.

This case highlights the potential benefit of CFTR modulators in CFTR-related disorders and supports consideration of therapy in selected non-classic presentations. Although weight gain began after initiation of mirtazapine, it continued following ETI and was accompanied by improvement in gastrointestinal symptoms and resolution of pancreatitis episodes.