Cystic fibrosis is an inherited disorder that leads to problems throughout the body, especially the lungs. It results in chronic illness and a shortened lifespan. The disease is caused by a mutation in the gene that codes for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This protein is an ion channel--it shuttles salts into and out of cells. When mutated, it causes glands to produce a thick, sticky mucus that obstructs air passages in the lungs and is prone to harbour severe bacterial infections.

Cystic fibrosis is the most common inherited disorder in childhood. The sweat test is the primary test used when cystic fibrosis is suspected. There are various types of screening based on sweat testing, but the gold standard for sweat testing is quantitative pilocarpine iontophoresis. The Cystic Fibrosis Foundation accredits health centers for carrying out sweat testing according to strict guidelines.

Salty Skin

Salty skin is a characteristic sign of cystic fibrosis. Even before the disease was known, salty skin was recognized as a sign that a child would be seriously ill and likely die. The skin becomes salty because people with cystic fibrosis excrete an excessive amount of salt in their sweat. Normally, the skin reabsorbs salt excreted through sweating, but in cystic fibrosis, this mechanism is defective, so high levels of salt remain on the skin. A sweat test can detect elevated levels of chloride in the skin, indicating a diagnosis of cystic fibrosis.

How the Test is Administered

The sweat test begins when an odorless chemical called pilocarpine is applied to a small area of the arm or leg. Mild electrical stimulation is then applied to trigger sweating. There may be a tingling sensation. Sweat is collected for about an hour.

Sweat Test Results

For infants up to six months of age, chloride levels of:

1. 29 mmol/L or less mean that cystic fibrosis is very unlikely
2. 20-59 mmol/L mean that cystic fibrosis is possible
3. 60 mmol/L or more mean that cystic fibrosis is likely

For people over six months, chloride levels of:

1. 39 mmol/L or less mean that cystic fibrosis is very unlikely
2. 40-59 mmol/L mean that cystic fibrosis is possible
3. 60 mmol/L or more mean that cystic fibrosis is likely

Other than the adjustment for infants under six months, sweat test results do not vary with age, activity, or illness.

Accuracy

The pilocarpine iontophoresis sweat test is reliable for about 98 percent of patients with cystic fibrosis. However, in 1-2 percent of cases, patients have clinical signs of cystic fibrosis with normal or borderline sweat test results. Since it is now known that mutations of the CFTR gene cause cystic fibrosis, genetic testing may be used to supplement sweat testing and clinical signs for diagnosis.

For the most reliable results, 50 to 100 mg of sweat must be collected. Infants sometimes do not produce enough sweat.

A sweat test should be performed at least twice in each patient to confirm the diagnosis. Patients with borderline results should be retested.

Indications for sweat testing

Sweat testing should be carried out in infants following a positive newborn screening test. Newborns are screened by checking for levels of immunoreactive trypsinogen (IRT) in the blood.

Any other individual with symptoms suggestive of cystic fibrosis may be given a sweat test.

References

1. Cystic Fibrosis Foundation, Sweat Test, https://www.cff.org/What-is-CF/Testing/Sweat-Test/
2. The Relevance of Sweat Testing for the Diagnosis of Cystic Fibrosis in the Genomic Era, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1320177/
3. Diagnosis of Cystic Fibrosis, https://www.ncbi.nlm.nih.gov/pubmed/18506640
4. Sweat chloride concentrations in infants homozygous or heterozygous for F508 cystic fibrosis, https://www.ncbi.nlm.nih.gov/pubmed/8632940
5. Johns Hopkins, Sweat Test, http://www.hopkinscf.org/what-is-cf/diagnosis/testing/sweat-test/