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Sweat Chloride

Cystic fibrosis is the most common lethal genetic disorder of Caucasians in the United States, occurring with a birth rate of 1 in 2000. It is less common in African American and Asians. Cystic fibrosis is inherited as an autosomal recessive trait and has a carrier rate of 1 in 20. The CF gene is located on chromosome 7 and codes for a protein called cystic fibrosis transmembrane conductance regulator (CFTR) that functions as a cAMP dependent chloride channel. Nearly 550 mutations of this gene have been described. Reference laboratories can test for up to 32 of the CFTR mutations, which account for about 90% of cases. Because of the large number of CFTR mutations, confirmation of diagnosis by genetic testing is limited. The sweat test remains the mainstay of diagnosis. The Cystic Fibrosis Foundation consensus statement includes an elevated sweat chloride concentration in its diagnostic criteria.

The sweat test involves iontopheresis of pilocarpine, a cholinergic drug, into the skin to induce sweating in a localized area. Stimulation is preferably done on the volar surface of the forearm. Sweat is collected into a Macroduct coil and the chloride concentration is measured. Results are interpreted as follows:

Chloride

Interpretation

0 - 40 mEq/L

Negative

40 - 60 mEq/L

Borderline

>60 mEq/L

Consistent with CF

Approximately 98% of patients with cystic fibrosis have a sweat chloride concentration greater than 60 mEq/L. The interpretation of the chloride concentration must be made with regard to the patient’s clinical presentation, family history and age. Sweat electrolyte concentration increases with age and healthy adults can have sweat chloride concentrations greater than 60 mEq/L. Elevated levels can also be caused by eczema, skin rash, malnutrition, dehydration and many other diseases listed below.

Metabolic Disorders

  • Fucosidosis
  • G6PD deficiency
  • Glycogen storage disease type 1
  • Mucopolysaccharidosis type 1
  • Malnutrition

Endocrine Disorders

  • Adrenal insufficiency, untreated
  • Hypothyroidism, untreated
  • Hypoparathyroidism
  • Mauriac syndrome
  • Pseudohypaldosteronism
  • Nephrogenic diabetes insipidus

Immunologic Disorders

  • Atopic dermatitis
  • Hypogammaglobulinemia

Genitourinary Tract Disorders

  • Klinefelter syndrome
  • Nephrosis

Neuropsychiatric Disorders

  • Anorexia nervosa
  • Autonomic dysfunction

False negative results can occur if the patient is edematous, is receiving mineralocorticoid therapy or an inadequate volume of sweat is collected

Patients with borderline and positive results should be retested. Duplicate tests should agree within 10 mEq/L for chloride concentrations less than 60 mEq/L and within 15 mEq/L for chloride concentrations greater than 60 mEq/L.

Specimen requirement is 25 uL of sweat.

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