Elevated sweat chloride test: is it always cystic fibrosis?

Abstract

Background The sweat chloride test (ST) is the gold standard for cystic fibrosis (CF) diagnosis in symptomatic patients, within the newborn screening and in the follow-up of CF patients during molecular therapies. However, false positives have been reported in patients with different diseases. We describe and discuss 4 cases due to different clinical conditions in which we recorded false positive ST, and the test remained altered for a period of varying length. Cases presentation Case 1: Eight months old female child suffering from constipation, recurrent vomiting and failure to thrive, family history of recurrent pancreatitis without mutations in the PRSS1 and SPINK1 genes. Both ST and fecal elastase were altered although no CFTR gene mutations were found. Due to rapid clinical deterioration, celiac disease was suspected and diagnosed by laboratory tests and intestinal biopsy. After 2 weeks of gluten-free diet ST and fecal elastase normalized. Case 2: 14 months old male suffering from bilateral renal dysplasia, episodes of metabolic alkalosis, recurrent respiratory infections and recurrent vomiting. The child had more ST positives, but no CFTR mutations were found. During follow-up, he developed sensorineural hearing loss and an atrial septic defect was found. Finally, a diagnosis of Klinefelter was made, but the ST normalized several years later. Case 3 and 4: Two boys with stubborn constipation and fecal occlusion treated with Poly Ethylene Glycol (PEG) with salts showed pathological ST. The test returned normal a few days after stopping treatment. Conclusions We hypotesized the possible causes of ST alteration in these conditions: in celiac disease it could be due to a transient dysregulation of the aquaporins, rapidly reversed by the diet; in Klinefelter, it may be due to stable pubertal hypoandrogenism; while, the PEG formulation itself contains salts that can temporarily alter ST.

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“…Patients with other underlying disorders, i.e., celiac disease, Klinefelter Syndrome, coprostasis in treatment with polyethylene glycol may show false positive sweat test. Cimbalo et al have tried to explain the reason of this [ 207 ], discriminating false positive and false negative sweat test results into 3 categories, i.e., ‘‘likely’’, ‘‘probable but needs validation,’’ and ‘‘unlikely’’ results based on the number of cases reported and use of genetic testing to exclude CF. They concluded that clinicians must aware the possibility of other conditions, such as adrenal insufficiency, even if two CFTR mutations are identified [ 208 ].…”

Cystic Fibrosis Transmembrane Conductance Regulator Modulator Use Is Associated With Reduced Pancreatitis Hospitalizations in Patients With Cystic Fibrosis

“…Treatment of CF has evolved to personalized CFTR modulator therapy targeting multiple protein activity defects including synthesis, transport, trafficking, and function of CFTR and continues to progress (1,(9)(10)(11)(12). Among patients with PS-CF and recurrent AP, use of CFTR modulators leads to a reduction in the rate of subsequent AP (13)(14)(15). In addition, improved weight and pancreas exocrine function have been described (16)(17)(18).…”