Information on the following diseases can be found in the Related Disorders section of this report:

• Exfoliative dermatitis
• Netherton syndrome

Peeling skin syndrome is a form of ichthyosis. The ichthyoses comprise a group of dermatological disorders characterized by dry, thickened, scaly skin. Individuals with peeling skin syndrome exhibit lifelong spontaneous peeling of the horny layer (stratum corneum) of the outermost layer of skin (epidermis). In some cases, affected individuals and/or their caregivers can remove sheets of skin manually. In some cases, the condition is limited to the arms and legs (acral extremities). Other findings associated with this disorder may include itching, short stature, and/or newly formed hairs that can be plucked out more easily than normal.

Peeling skin syndrome is inherited as an autosomal recessive trait. Neither the gene, nor its location, has been determined. A gene for the acral form of peeling skin syndrome has been identified.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Recessive genetic disorders occur when an individual inherits two abnormal copies of the disease gene, usually one from each parent. If an individual receives one normal gene copy and one abnormal gene copy for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene copy and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals are thought to carry at least 4-5 abnormal recessive genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Investigators have determined that the acral form of peeling skin syndrome occurs as a result of changes or disruptions (mutations) of the transglutaminase-5 (TGM5) gene located on the long arm (q) of chromosome 15 (15q15.2). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 15q15.2" refers to band 15.2 on the long arm of chromosome 15. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Peeling skin syndrome is an extremely rare inherited disorder that, in theory, affects males and females in equal numbers. About 40 cases have been reported in the medical literature.

Exfoliative dermatitis refers to a scaling skin disorder accompanied by distinct reddening (erythematous dermatitis) involving 90% or more of the skin surface. It is characterized by erythema and scaling involving the skin's surface that often obscures the primary lesions. It is frequently difficult for clinicians to find the cause of exfoliative dermatitis even though the history of illness prior to erythema and scaling is obtained. Often, biopsies and blood studies are required. The term red man syndrome is reserved for idiopathic exfoliative dermatitis in which no primary cause can be found, notwithstanding a variety of examinations and tests. This form of the disorder is characterized by marked hardening of the skin of the palms and soles, swelling (lymphadenopathy), and raised levels of immunoglobulin E.

Netherton syndrome is a rare autosomal recessive skin disorder characterized either by scaly plaques with a peculiar, double-edged border (ichthyosis linearis circumflexa) or by persistent, generalized redness, scaling, or, sometimes, peeling. The hair is often fragile and sparse due to a structural defect of the hair shafts that results in a ball-in-socket or bamboo stick-like appearance (trichorrhexis invaginata, "bamboo hair"). Another characteristic of Netherton syndrome is a predisposition to allergies such as asthma, or food allergies that cause skin eruptions.

Diagnosis
A good history and physical exam are usually sufficient to make the diagnosis. The continual shedding of large sheets of skin distinguishes peeling skin syndrome from Netherton syndrome and from congenital ichthyosiform erythroderma. The skin of so-called "collodion babies" peels off after a few weeks and does not return, in contrast to patients with peeling skin syndrome whose symptoms return time after time.

Treatment
Treating peeling skin syndrome by applying skin softening (emollient) ointments, especially after a bath while the skin is moist, may offer some relief. Plain petroleum jelly or Vaseline are preferred. None of the corticosteroids or systemic retinoids (vitamin A derivatives) are effective, and all may have serious side effects or adverse reactions.

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

TEXTBOOKS
Richard G, Ringpfeil F. Ichthyoses, erythrokeratodermas and related disorders. In: Bolognia J, Jorizzo J, Rapini, et al (eds). Dermatology. Philadelphia, Mosby; 2003.

Champion RH, Burton JL, Ebling FJG, eds. Textbook of Dermatology. 5th ed. Blackwell Scientific Publications. London, UK; 1992.

JOURNAL ARTICLES
Ilknur T, Demirtasoglu M, Akarsu S, et al. Peeling skin syndrome. Eur J Dermatol. 2006;16:287-9.

Cassidy AJ, van Steensel MAM, Steijlen PM, et al. A homozygous missense mutation in TGM5 abolishes epidermal transglutaminase 5 activity and causes acral peeling skin syndrome. Am J Hum Genet. 2005;77:909-17.

Garcia EG, Carreno RG, Martinez Gonzalez MA, Reyes JJ. Acral peeling skin syndrome: report of two cases. Ultrastruct Pathol. 2005;29:65-70.

Geyer AS, Ratajczak P, Pol-Rodriguez M, et al. Netherton syndrome with extensive skin peeling and failure to thrive due to a homozygous frameshift mutation in SPINK. Dermatol. In Press.

Zvulunov A, Cagnano E, Kachko L, et al. A new variant of autosomal recessive exfoliative ichthyosis. Pediatr Dermatol. 2002;19:382-87.

Sardy M, Fay A. Karpati S, et al. Comel-Netherton syndrome and peeling skin syndrome type B: overlapping syndromes or one entity. Int J Dermatol. 2002;41:264-68.

Hashimoto K, Hamzavi I, Tanaka K, et al. Acral peeling skin syndrome. J Am Acad Dermatol. 2000;43:1112-19.

Schneider I, Sebok B, Kosztolanyi G, et al. Comel-Netherton syndrome: evolution of manifestation in a 20-year follow-up and phenotypic overlap with peeling skin syndrome type B. Acta Derma Venereol. 2000;80:209-10.

Tastan HB, Akar A, Gur AR, et al. Peeling skin syndrome. Int J Dermatol. 1999;38:208-10.

Brusasco A, Veraldi S, Tadini G, et al. Localized peeling skin syndrome: case report with ultrastructural study. Br J Dermatol. 1998;139:492-95.

FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Skin Peeling, Familial Continuous. Entry Number; 270300: Last Edit Date; 3/18/2004.

McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Skin Peeling, Familial Continuous. Entry Number; 609796: Last Edit Date; 1/17/2006.

Zambon F. Congenital Ichthyosis. Department of Pediatrics, University of Padua. 2001. 12pp. Available at: http://malattierare.pediatria.unipd.it/pubblicaMR/mr_dx_ing.asp?mr=187