PRACTICE RECOMMENDATIONS
• Don’t dismiss a cystic fibrosis diagnosis just because a patient’s sweat chloride levels are <60 mmol/L. A
• Suspect atypical cystic fibrosis in adults with single organ involvement, including mild lung disease, nasal polyposis, recurrent pancreatitis, biliary cirrhosis, portal hypertension, or obstructive azoospermia. A
• Consider respiratory therapies such as tobramycin, hypertonic saline, and recombinant human DNase in cystic fibrosis patients with relatively mild or atypical disease. A
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
CASE 1: Lauren W*
Two years ago, Lauren W, a 57-year-old Caucasian woman, sought care at our medical center after learning that her pregnant daughter tested positive during a prenatal cystic fibrosis mutation genetic screen. Lauren had clinical symptoms of malodorous and greasy bowel movements, dyspepsia, early satiety, and a history of recurrent bronchitis since childhood.
According to her history, she did not suffer from failure to thrive as a child. She’d had 5 episodes of adult-onset acute pancreatitis and had 2 surgeries for sinusitis.
On physical exam, we heard no crackles during lung auscultation. Lauren also had mild digital clubbing.
Testing: We ordered a chest x-ray, which revealed left upper lobe atelectasis, but there was no bronchiectasis.
Pulmonary function tests indicated mild obstructive lung disease with forced vital capacity (FVC) 2.39 L or 84% predicted; forced expiratory volume in 1 second (FEV1) 1.59 L or 68% predicted; and an FEV1/FVC of 0.66.
A sweat chloride test was positive on both arms: 77 and 83 mmol/L. Genetic testing revealed compound heterozygosity for cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations Δ F508 and R117H with a 5T allele. To test for pancreatic insufficiency, we performed a 72-hour fecal fat testing while she was on a low-fat diet; it revealed 5.5 g of fat per 24-hour period, suggesting fat malabsorption. Based on positive quantitative sweat test ≥60 mmol/L and the presence of 2 cystic fibrosis–causing mutations, we made the diagnosis of cystic fibrosis.
Treatment: We put Lauren on albuterol and recombinant human DNase respiratory treatments, pancreatic enzymes, and multivitamins with extra lipid-soluble vitamins and calcium supplements. We also continued her low-fat diet of 1500 to 1800 calories per day due to a diagnosis of coronary artery disease.
*Patients’ names have been changed to protect their privacy.
CASE 2: Zack P*
Zack P, a 6-year-old Caucasian boy, was admitted to the hospital with what we suspected was acute gastroenteritis. Serum testing revealed elevated pancreatic enzymes. He had recently sustained an injury to the mid-abdomen during a soccer game and also had a history of chronic sinusitis. One month after his release from the hospital, his symptoms resolved, but his pancreatic enzymes remained elevated (amylase 130 U/L, lipase 177 U/L).
Testing: He underwent 2 sweat chloride tests, which were borderline elevated at 49 mmol/L on the right arm and 40 mmol/L on the left arm; repeat testing was 49 mmol/L on the left arm, 43 mmol/L on the right arm. Genetic testing revealed heterozygosity for CFTR gene mutation Δ F508 with the presence of 7T and 9T allele variants. Over an 8-month period, Zack remained asymptomatic, but his pancreatic enzymes were persistently elevated.
Zack’s physical exam showed that his weight had dropped from the 75th to the 50th percentile. A magnetic resonance cholangiopancreatography indicated homogeneous parenchyma and normal enhancement throughout his pancreas. Similarly, we could not find evidence of acute pancreatitis or biliary or pancreatic duct dilation, and a 72-hour fecal fat study was normal. Given Zack’s borderline sweat chloride, compound heterozygosity of cystic fibrosis mutations, and his phenotype of recurrent pancreatitis, he was given a diagnosis of atypical cystic fibrosis.
Treatment: Based on our diagnostic workup, pancreatic enzyme therapy was not warranted.
*Patients’ names have been changed to protect their privacy.
These 2 cases illustrate how clinically diverse cystic fibrosis can be. The cystic fibrosis phenotype can range from a patient with 2 disease-causing cystic fibrosis mutations with significant sweat gland dysfunction and childhood onset of mild cystic fibrosis symptomatology with normal growth—Lauren—to a patient who is CFTR heterozygous with pancreatitis and a borderline sweat chloride concentration—Zack. Both cases emphasize the need to think “outside the box” and not expect all patients with cystic fibrosis to come in with typical signs and symptoms.
What does the “nonclassic” cystic fibrosis patient look like?
Patients with cystic fibrosis are usually diagnosed during childhood with pulmonary disease, pancreatic insufficiency, malabsorption, malnutrition, elevated sweat chloride, and male infertility. But more recently, patients have been diagnosed in adulthood because either they lacked significant clinical symptoms in childhood or they came in with atypical signs or symptoms (pancreatic sufficiency and sweat chloride <60 mmol/L).