Peeling skin syndrome

Overview

Peeling skin syndrome (PSS) is a rare group of inherited skin disorders characterized by continuous shedding of the outermost layer of the skin (stratum corneum). This chronic, non-inflammatory condition can be present at birth or appear during early childhood. Depending on the subtype, the skin peeling can occur either spontaneously or be triggered by minor friction or trauma. The syndrome may affect the entire body or be limited to specific areas such as the hands and feet. In some forms, systemic symptoms or other abnormalities may also be present. While PSS is generally non-life-threatening, it can significantly affect quality of life due to discomfort, cosmetic concerns, and skin sensitivity.

Causes

Peeling skin syndrome is caused by mutations in genes responsible for maintaining skin barrier integrity and adhesion between skin layers. The most commonly affected genes include:

• TGM5: Encodes transglutaminase 5, which is crucial for cross-linking proteins in the epidermis

• CDSN: Encodes corneodesmosin, a protein involved in cell adhesion within the stratum corneum

• CHST8: Encodes carbohydrate sulfotransferase 8, associated with glycosaminoglycan metabolism

PSS is typically inherited in an autosomal recessive pattern, meaning a child must inherit two copies of the mutated gene (one from each parent) to manifest the condition. Rarely, it may occur as a de novo mutation with no family history. The condition is genetically heterogeneous, and additional genes and pathways may be involved in its various subtypes.

Symptoms

The hallmark feature of PSS is superficial peeling of the skin, often described as sheets or flakes coming off with little or no inflammation. Symptoms vary depending on the subtype:

Generalized Peeling Skin Syndrome:

• Widespread, continuous skin peeling

• Onset at birth or in early infancy

• Dry, scaly skin (ichthyosis-like appearance)

• Pruritus (itching) in some individuals

• Hyperpigmentation or hypopigmentation at peeling sites

Localized Peeling Skin Syndrome (Acral Type):

• Peeling restricted to hands, feet, and extremities

• Peeling worsens with heat, humidity, or friction

• No systemic involvement

Inflammatory PSS Subtypes:

• Erythema (redness) and irritation associated with peeling

• May present with additional features like hair abnormalities or immune dysfunction

Despite the severity of skin peeling, blisters and deep ulcers are typically absent, distinguishing PSS from other blistering skin disorders.

Diagnosis

Diagnosis of PSS is based on clinical presentation, family history, and specialized tests to confirm the subtype and rule out other conditions. Diagnostic methods include:

• Clinical examination: Assessment of skin appearance, distribution of lesions, and age of onset

• Skin biopsy: Reveals cleavage within the stratum corneum or upper epidermis with minimal inflammation

• Electron microscopy: Can detect ultrastructural abnormalities in skin adhesion components

• Genetic testing: Identifies mutations in genes such as TGM5, CDSN, or CHST8 to confirm the diagnosis and subtype

• Exclusion of other conditions: Such as Netherton syndrome, epidermolysis bullosa, or ichthyosis

Early diagnosis is important for genetic counseling and guiding appropriate skin care and management strategies.

Treatment

There is currently no cure for peeling skin syndrome. Treatment focuses on symptom relief, skin protection, and improving the patient’s quality of life. Management options include:

• Emollients and moisturizers: Frequent application of thick creams and ointments to maintain skin hydration and barrier function

• Keratolytic agents: Mild exfoliants like urea or lactic acid to reduce scaling, used cautiously to avoid irritation

• Topical steroids: May be used in inflammatory subtypes to reduce redness and discomfort, under medical supervision

• Avoidance of triggers: Minimizing heat, friction, and harsh soaps that can exacerbate peeling

• Protective clothing: Soft, breathable fabrics to reduce irritation and trauma

• Infection prevention: Monitoring for signs of secondary bacterial infections and treating promptly with antibiotics if needed

In some experimental cases, treatments like gene therapy or recombinant protein application are being studied, but they are not yet standard practice.

Prognosis

The prognosis of peeling skin syndrome depends on the subtype and severity. The non-inflammatory and acral forms usually have a benign course, with symptoms manageable through skin care routines and lifestyle adjustments. Inflammatory or systemic subtypes may be more challenging, especially if associated with immune deficiencies or other complications. While the condition is lifelong, most individuals can lead a normal life with proper management. Genetic counseling is recommended for affected families to understand inheritance patterns and assess the risk in future pregnancies.