Edimer

Written by Alanna Bree, MD - Baylor College of Medicine

Patients with X-linked and autosomal recessive HED manifest obvious classic clinical features, while autosomal dominant and X-linked HED carriers typically have more subtle features.

Affected individuals often present in infancy with unexplained fevers due to their inability to perspire, which can lead to febrile seizures in some patients, and rarely neurologic damage. This is especially true with childhood illnesses. Sweating is reduced or absent in most patients, but reportedly with minimal improvement during adolescence. A clue to the diagnosis in infancy is diffuse, scaly, erythema in a newborn that can be mistaken for a collodian membrane or an ichthyotic disorder. Classic facial features, including frontal bossing, retruded midface, saddle nose, and thick everted lips, can be a subtle clue to diagnosis in infancy; while facial papules resembling sebaceous hyperplasia and periorbital/perioral hyperpigmentation become more obvious in childhood and adolescence. Diagnosis is typically delayed until the eruption of conical or peg-shaped teeth with evidence of hypodontia on radiographs. There is variable hypotrichosis. Hair is typically light, sparse and grows slowly due to easy breakage. Eyebrows and eyelashes are also thin. Secondary sexual hair is usually normal in appearance, but there is early patterned balding. Nails can be mildly abnormal. Skin is dry and fragile-appearing with an increased frequency of atopic dermatitis. The incidence of atopy is higher in these patients, and can manifest as wheezing and asthma, as well as abnormal immunoglobulin production, including elevated IgE levels (Clarke, 1987). Another ongoing questionnaire study with 346 respondents also reveals a higher incidence of asthma, atopic dermatitis, food allergies, and immunodeficiency. Decreased secretions can lead to xerostomia, xerophthalmia, thick nasal concretions, copious cerumen, raspy voice, respiratory infections and dysphagia. Feeding difficulties with weight deficits are noted in young children with HED, but this tends to improve by adolescence (Motil, 2005).

Female carriers of XLHED typically have dental abnormalities, hypotrichosis and hypotrichosis (Freire-Maia, 1982). These affected females may demonstrate subtle skin changes, including dryness, atrophy, and decreased vellus hairs, in the lines of Blaschko due to mosacism and X-inactivation. They have also been shown to have Blaschko-linear hypohidrosis of the back on starch iodine testing (Cambiaghi, 2000).

Diagnosis is usually based on clinical features, but this may be delayed. The demonstration of decreased sweat pores and sweating, sometimes used for diagnostic purposes, has been assessed by a variety of techniques, including direct observation of epidermal ridge sweat pores on the fingertip with use of a stereomicroscope (Frias, 1968), standard fingerprinting to assess for loss of epidermal ridge clarity (Verbov, 1970), sweat pore counts using application of 5% phthalaldehyde to the fingertip (Kleinebrecth, 1981), sweat pore counts on Permlastic impressions from the fingertips (Tso, 1985), scanning electron microscopy (Norval, 1988), identification of sweat pores and skin temperature patterns on whole body thermography (Clark, 1990), and sweat testing with starch iodine (Clarke, 1991). All of these techniques have proven to various degrees that sweating is diminished with decreased sweat pore counts and flattened epidermal ridges on the fingertips of both affected individuals and female carriers.

A more recent study of 13 affected individuals assessed trichograms, palmar impressions on starch iodide paper, and eccrine structure assessment in 4-mm punch biopsies of the scalp and palm (Rouse, 2004). Trichograms revealed an increased incidence of variable shaft thickness, trichorrhexis nodosa and pili torti, but these were not found to be sensitive or highly specific for diagnosis. Absence of eccrine structures was helpful in making the diagnosis with a low sensitivity of 30% but a high specificity and positive predictive value of 100%. Starch iodide testing results varied widely from intense to absent, but it was found that little or no palmar sweating was valuable in identifying a minority of patients. Lack of eccrine structures in a scalp biopsy was found to be the most valuable diagnostic tool with a sensitivity of 67% and a specificity and positive predictive value of 100%.