Acral Peeling Skin Syndrome in Two East-African Siblings
Acral Peeling Skin Syndrome in Two East-African Siblings
Patients with continuous peeling of the skin were first reported as Keratolysis Exfoliativa Congenita. This changed when in 1982 Levy and Goldsmith described it as a peeling skin syndrome. Peeling skin syndrome is an extremely rare inherited skin disorder characterized by continual, spontaneous skin peeling (exfoliation). APSS is considered a subtype of peeling skin syndrome in which the peeling of the skin is limited to the dorsa of the hands and the feet. The skin peeling is due to separation of the stratum corneum from the stratum granulosum. Molecular studies among family members with APSS showed homozygous missense mutation in transglutaminase 5 (TGM5). Cassidy et al. conducted a genome-wide linkage analysis and localized the genetic defect on chromosome 15 (at 15q15.2). This region contains nine genes with a small transglutaminase (TGM) gene cluster at its center. However, only TGM5 has a strong expression in the skin. The TGM5 enzyme is responsible for introducing γ-glutamyl- ε-lysine isopeptide bonds into the structural proteins. The weakness of these bonds leads to a split in a region between the granular layer and the stratum corneum, which is similar to a split in APSS.
Laboratory studies in some patients with peeling skin syndrome showed abnormalities in the levels of amino acids, plasma tryptophan, serum copper, ceruplasmin and iron binding capacity. Clinically, APSS is asymptomatic peeling with residual erythema for a few days that later heal spontaneously without scaring. The onset of APSS is variable, but in the majority of the cases reported, the disease developed shortly after birth. One of our patients presented with peeling from birth and the elder sibling at one year. These patients had an earlier age of onset than the Tunisian patients who almost had a similar clinical presentation. APSS has been described to affect predominantly the dorsal aspects of the hands and the feet. However, Hashimoto et al. described a 34 year old patient with peeling of the plantar and the dorsal of the feet. Our patients had involvement of both involvement of the hands and the feet, but it was more severe on the palm and the plantar area than it was on the dorsa. The variability in the phenotypic expression of the two siblings indicates that the heterogeneity of clinical findings is not only between families, but also within family members.
The symptoms of APSS are aggravated by hot temperatures, high humidity and friction .
Hashimoto et al. and Wakade et al. demonstrated that skin hydration by soaking in water for 5-10 minutes induced blistering in their patients The slightly more severe disease in our patients may be due to excessive sweating, the use of occlusive shoes and the hot humid tropical climate. Hyperhidrosis produces a similar effect as soaking the limbs in water.
There is no effective treatment for APSS reported. Management of this condition is largely symptomatic and preventative. Emollients are useful to some patients while the use of keratolytics may enhance the shedding. Topical tretinoin was found to be ineffective in this patient. Similarly, Phototherapy, oral corticosteroids and methotrexate were found to be in effective. Calcipotriol was reported to be effective in one case report.
Discussion
Patients with continuous peeling of the skin were first reported as Keratolysis Exfoliativa Congenita. This changed when in 1982 Levy and Goldsmith described it as a peeling skin syndrome. Peeling skin syndrome is an extremely rare inherited skin disorder characterized by continual, spontaneous skin peeling (exfoliation). APSS is considered a subtype of peeling skin syndrome in which the peeling of the skin is limited to the dorsa of the hands and the feet. The skin peeling is due to separation of the stratum corneum from the stratum granulosum. Molecular studies among family members with APSS showed homozygous missense mutation in transglutaminase 5 (TGM5). Cassidy et al. conducted a genome-wide linkage analysis and localized the genetic defect on chromosome 15 (at 15q15.2). This region contains nine genes with a small transglutaminase (TGM) gene cluster at its center. However, only TGM5 has a strong expression in the skin. The TGM5 enzyme is responsible for introducing γ-glutamyl- ε-lysine isopeptide bonds into the structural proteins. The weakness of these bonds leads to a split in a region between the granular layer and the stratum corneum, which is similar to a split in APSS.
Laboratory studies in some patients with peeling skin syndrome showed abnormalities in the levels of amino acids, plasma tryptophan, serum copper, ceruplasmin and iron binding capacity. Clinically, APSS is asymptomatic peeling with residual erythema for a few days that later heal spontaneously without scaring. The onset of APSS is variable, but in the majority of the cases reported, the disease developed shortly after birth. One of our patients presented with peeling from birth and the elder sibling at one year. These patients had an earlier age of onset than the Tunisian patients who almost had a similar clinical presentation. APSS has been described to affect predominantly the dorsal aspects of the hands and the feet. However, Hashimoto et al. described a 34 year old patient with peeling of the plantar and the dorsal of the feet. Our patients had involvement of both involvement of the hands and the feet, but it was more severe on the palm and the plantar area than it was on the dorsa. The variability in the phenotypic expression of the two siblings indicates that the heterogeneity of clinical findings is not only between families, but also within family members.
The symptoms of APSS are aggravated by hot temperatures, high humidity and friction .
Hashimoto et al. and Wakade et al. demonstrated that skin hydration by soaking in water for 5-10 minutes induced blistering in their patients The slightly more severe disease in our patients may be due to excessive sweating, the use of occlusive shoes and the hot humid tropical climate. Hyperhidrosis produces a similar effect as soaking the limbs in water.
There is no effective treatment for APSS reported. Management of this condition is largely symptomatic and preventative. Emollients are useful to some patients while the use of keratolytics may enhance the shedding. Topical tretinoin was found to be ineffective in this patient. Similarly, Phototherapy, oral corticosteroids and methotrexate were found to be in effective. Calcipotriol was reported to be effective in one case report.