Peeling skin syndrome type B (ORPHA:263553)
A form of generalized peeling skin syndrome (PSS) characterized by superficial patchy peeling of the entire skin with underlying erythroderma, pruritus, and atopy.
Epidemiology
The prevalence is unknown; the disease is rare.
Clinical description
Skin anomalies manifest at birth or shortly thereafter. Patients show painless widespread, superficial asymptomatic and spontaneous peeling. Peeling of the skin consists of exfoliative white flakes of variable shape and size that evolves into mildly erythematous denuded areas with a peeling border. Palms and soles are spared or may show redness and mild skin thickening or hyperlinearity. Underlying erythroderma is present. Seasonal variations are generally observed. Pruritus is frequent and often severe, and is exacerbated with warm temperatures. In most cases, hair can be easily plucked (hair-anchoring deficiency). Mild to moderate nail changes are sometimes reported (koilonychia, onycholysis, thickness, yellowish appearance). Atopic manifestations are frequent (e.g. food allergies, episodes of angioedema, urticaria and asthma) and Staphylococcus aureus skin infections are reported. Patients are usually in good general health but may present with mild failure to thrive.
Etiology
PSS type B is an autosomal recessive monogenic disease caused by mutations in the CDSN gene (6p21.3). CDSN encodes corneodesmosin, an adhesive protein specific to corneodesmosomes, the cell-junction structures responsible for the cohesion of the stratum corneum. Most of these mutations (single nucleotide substitutions or deletions) result in total absence of the mutated protein in the epidermis which leads to impaired cell-cell adhesion, detachment of the epidermal corneal layers and disruption of the epidermal barrier that leads to increased penetration of allergens into the epidermis and an abnormal inflammatory response.
Diagnostic methods
Clinical presentation is highly suggestive of the disease. Total IgE levels can be markedly elevated. Histological examination of skin lesion biopsies reveals acanthosis, hyperkeratosis, parakeratosis and extensive detachment of the stratum corneum from the subjacent stratum granulosum. A moderate mononuclear infiltrate can be seen in the superficial dermis. Immunohistochemistry is a rapid and easy diagnostic test that shows an absence of corneodesmosin. Molecular analysis, confirms the diagnosis and reveals CDSN mutations.
Differential diagnosis
Differential diagnosis includes other forms of PSS (acral peeling skin syndrome, peeling skin syndrome type A), epidermolytic ichthyosis, autosomal recessive congenital ichthyosis, staphylococcal scalded skin syndrome, Netherton syndrome, severe dermatitis-multiple allergies-metabolic wasting (SAM) syndrome, atopic dermatitis and peeling skin induced by retinoid therapy.
Antenatal diagnosis
Genetic prenatal diagnosis is available for inherited ichthyoses and can be proposed for PSS type B because of the potential severity of the disease.
Genetic counseling
Transmission is autosomal recessive. Genetic counseling should be offered to affected families informing them of the risk of 25% for a healthy carrier parent to have an affected child.
Management and treatment
No effective treatment has been reported, especially for pruritus. Emollients are often used to reduce skin peeling. Topical and oral steroids, retinoids, methotrexate, dupilumab and UVB phototherapy have been tested but without any success. Antibiotic therapy is required to treat secondary infection.
Prognosis
The severity of PSS type B is variable. Life expectancy is normal but the disease may severely impair the quality of life because of pruritus, lack of effective treatment and complications due to associated manifestations.

                            Last update: 
                            January 2023


                            - Expert reviewer(s): 
                            Dr Nathalie JONCA  - Pr Juliette MAZEREEUW-HAUTIER | ERN-Skin*


                                * European Reference Network