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Frey Syndrome

NORD is very grateful to Pavel Dulguerov, MD, Chief of Head & Neck Surgery, Department of Oto-Rhino-Laryngology HNS, Geneva University Hospital, for assistance in the preparation of this report.

Synonyms of Frey Syndrome

  • auriculotermporal syndrome
  • gustatory sweating

Disorder Subdivisions

  • No subdivisions found.

General Discussion

Frey syndrome is a rare disorder that most often occurs as a result of surgery in the area near the parotid glands. The parotid glands are the largest salivary glands in the body located just below the ears on either side of the face. The main symptoms of Frey syndrome are undesirable sweating and flushing occurring on the cheek, temple (temporal region), or behind the ears (retroauricular region) after eating certain foods, especially those that produce a strong salivary response. Symptoms are often mild and well-tolerated. In some cases, symptoms may be more severe and therapy may be necessary. The exact underlying mechanisms that cause Frey syndrome are not fully understood. Frey syndrome most often occurs as a complication of surgery to the area of the face near the parotid glands.

Symptoms

The symptoms of Frey syndrome typically develop within the first year after surgery in the area near the parotid glands. In some cases, Frey syndrome may not develop until several years after surgery. The characteristic symptom of Frey syndrome is gustatory sweating, which is excessive sweating on the cheek, forehead, and around the ears shortly after eating certain foods, specifically foods that produce a strong salivary response such as sour, spicy or salty foods.

Additional symptoms that may be associated with Frey syndrome include flushing and warmth in the affected areas. This is rarely an important complaint.

While other symptoms have been associated with the syndrome, they are probably unrelated. Pain is sometimes described, but it is probably more related to the surgery than actually to Frey syndrome. The specific area affected, the size of the area, and the degree of sweating and flushing vary greatly among affected individuals. In some cases, symptoms may be mild and affected individuals may not be bothered by the symptoms. In other cases, such as those that experience profuse sweating, affected individuals may require therapy.

Causes

The exact underlying cause of Frey syndrome is not completely understood. The most widely held theory is that Frey syndrome results from simultaneous damage to sympathetic and parasympathetic nerves in the region of the face or neck near the parotid glands. Parasympathetic nerves are part of the autonomic nervous system, which is the portion of the nerve system that controls or regulates involuntary body functions (i.e., those functions that occur without instruction from the conscious mind). One function of parasympathetic nerves is to regulate the activity of glands including the parotid glands, but not the sweat glands. Sweat glands and blood vessels throughout the body are controlled by sympathetic fibers.

In Frey syndrome, researchers believe that the parasympathetic and sympathetic nerves near the parotid glands are cut, especially tiny branches originating from the auriculotemporal nerve. The auriculotemporal nerve supplies nerves (innervates) to certain structures in the face including the parotid glands.

Normally, damaged nerve fiber(s) eventually heal themselves (regenerate). In Frey syndrome, it is believed that damaged nerve fibers regenerate abnormally by growing along the sympathetic fiber pathways, ultimately connecting to the miniscule sweat glands found along the skin. Therefore, the parasympathetic nerves that normally tell the parotid glands to produce saliva in response to tasting food now respond by instructing the sweat glands to produce sweat and the blood vessels to widen (dilate). The cumulative result is excessive sweating and flushing when eating certain foods.

Damage to the nerves in the parotid gland region of the face may occur for several different reasons including as a complication of surgery or blunt trauma to the side of the face. In older reports, infections of the parotid glands were suspected, but a detailed examination always points to a surgical drainage of a parotid abscess. The most common reported cause of Frey syndrome is a surgical procedure called a parotidectomy (the surgical removal of a parotid gland). Although the exact percentage is not agreed upon in the medical literature, some sources suggest that more than half of all individuals who undergo a parotidectomy eventually develop Frey syndrome.

Another rarely described cause (etiology) of Frey syndrome is damage to the main sympathetic nerve chain in the neck.

In extremely rare cases, Frey syndrome has been described in newborns, possibly following trauma due to delivery with forceps. Actual careful examination reveals that the principal symptom is flushing which might be physiologic at a younger age. The key symptom of facial sweating is not emphasized in newborns rising doubts about the correctness of these observations.

Affected Populations

The exact incidence of Frey syndrome is unknown. The disorder most often occurs as a complication of the surgical removal of a parotid gland (parotidectomy). The percentage of individuals who develop Frey syndrome after a parotidectomy is controversial and reported estimates range from 30-50 percent. In follow-up examinations, approximately 15 percent of affected individuals rated their symptoms as severe. Frey syndrome affects males and females in equal numbers.

The disorder was first reported in the medical literature by Baillarger in 1853. A neurologist from Poland, Dr. Lucja Frey, provided a detailed assessment of the disorder and coined the term "auriculotemporal syndrome" in 1923.

Related Disorders

Symptoms of the following disorders can be similar to those of Frey syndrome. Comparisons may be useful for a differential diagnosis.

General hyperhidrosis refers to any condition that causes excessive sweating (hyperhidrosis) on large areas of the body. A wide variety of conditions can cause profuse sweating as a symptom. These conditions include, but are not limited to, impaired thyroid function, pituitary abnormalities, allergies, metabolic diseases, infectious diseases, diabetes, menopause and a variety of tumors. General hyperhidrosis may occur as a complication of drug use. Generalized hyperhidrosis can affect individuals of any age, race, gender or ethnic background. (For more information on this disorder, choose the specific disorder name as your search term in the Rare Disease Database.)

Standard Therapies

Diagnosis
A diagnosis of Frey syndrome is made based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a specialized test called the Minor Iodine-Starch Test. During this test, an iodine solution is applied to the affected areas of the face. Then, a starch powder such as corn starch is applied over the iodine solution. Individuals are then given an oral stimulus usually a highly acidic food such as a lemon wedge. In affected individuals, discoloration (usually purple) due to excessive sweating occurs on the affected areas.

Treatment
Although Frey syndrome can be mild and well-tolerated, in some cases, it can cause excessive discomfort. Treatment is symptomatic and directed toward relief of symptoms. Until recently, most treatment measures have generally been unsatisfactory. Treatment options include drug therapy or surgery.

Topical application of drugs that block certain activities of the nervous system (anticholinergics) or drugs that hinder sweating (antihidrotics) have been used. Surgical removal (excision) of the affected skin and the insertion (interposition) of new tissue to the affected area (muscle flaps) has been described, but are considered risky because of the presence of facial nerve fibers right below the skin after parotidectomy.

In the last decade botulinum A toxin has become established as a therapy for individuals with bothersome Frey syndrome. The therapy consists of local injections of botulinum A toxin in the affected skin. Initial results have demonstrated that this therapy results in the suppression of sweating and causes no significant side effects. Another advantage of botulinum A toxin is that it is minimally invasive compared to other therapies. As in other indications, the effect of botulinum toxin is not permanent, lasting on average about 9-12 months.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/

Organizations related to Frey Syndrome

References

TEXTBOOKS
Dulguerov P. Frey Syndrome. In: Salivary Gland Disorders, Myers EM, Ferris RL, editors. Springer, New York, NY;2007:111-125.

von Lindern JJ. Frey Syndrome. NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:533.

Gorlin RJ, Cohen MMJr, Hennekam RCM. Eds. Syndromes of the Head and Neck. 4th ed. Oxford University Press, New York, NY; 2001:756.

JOURNAL ARTICLES
de Bree R, Duyndam JE, Kuik DJ, Leemans CR. Repeated botulinum toxin type A injections to treat patients with Frey syndrome. Arch Otolaryngol Head Neck Surg. 2009;135:287-290.

O'Neill JP, Condron C, Curran A, Walsh A. Lucja Frey - historical relevance and syndrome review. Surgeon. 2008;6:178-181.

Rustemeyer J, Eufinger H, Bremerich A. The incidence of Frey's syndrome. J Craniomaxillofac Surg. 2008;36:34-37.

Prattico F, Perfetti P. Images in clinical medicine. Frey's syndrome. N Engl J Med. 2006;355:66.

Marchese-Ragona R, De Filippis C, Marioni G, Staffieri A. Treatment of complications of parotid gland surgery. Acta Otorhinolaryngol Ital. 2005;25:174-178.

von Lindern JJ, Niederhagen B, Berge S, Hagler G, Reich RH. Frey Syndrome. Treatment with Type A Botulinum Toxin. Cancer. 2000. 1659-1663.

Brin MF. Interventional neurology: treatment of neurological conditions with local injection of botulinum toxin. Arch Neurobiol. 1991;54:7-23.

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Report last updated: 2014/01/28 00:00:00 GMT+0

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