Dermatology Online Journal

Peeling skin syndrome: Current status
Kshitij Garg MBBS MD¹, Devesh Singh MBBS DDVL¹, Devesh Mishra MBBS MD²
Dermatology Online Journal 16 (3): 10

1. Postgraduate Department of Dermatology & STDs, Era's Lucknow Medical College & Hospital, Lucknow, India
2. Professor & Head, Department of Dermatology & STDs, Era’s Lucknow Medical College & Hospital, Sarfarazganj, Hardoi Road, Lucknow, Uttar Pradesh, India-226003. mishradrd@yahoo.co.in

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Abstract

Peeling Skin Syndrome (PSS) is a rare genodermatoses characterized by asymptomatic, localized or generalized, continuous exfoliation of the stratum corneum; it may present at birth or in adulthood. We describe a patient having the type A non-inflammatory variant of PSS showing asymptomatic and continuous skin peeling from the neck, trunk, back, and extremities. Friction appeared to be an aggravating factor, but there was no seasonal variation. Histopathology in this condition reveals hyperkeratosis and splitting of the epidermis between the granular layer and the stratum corneum. No treatment for this disorder has been found to be effective so far.

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Introduction

Peeling Skin Syndrome (PSS) is a rare disorder likely inherited in an autosomal recessive pattern with variable age of onset from birth to adulthood [1, 2]. It is characterized clinically by asymptomatic, localized or generalized, continuous exfoliation of the stratum corneum. Histologically the separation is in the intracorneal or subcorneal layers of the epidermis [3].

Case report

Figure 1
Figure 1. Desquamation from chest and neck with sparing of face

An 8-year-old girl presented with peeling skin that had been present since birth. Sheets of skin were peeling from her neck, trunk, back, and extremities, especially following friction. There was sparing of palms, soles, face, and scalp. (Figure 1) These episodes were continuous, irrespective of any seasonal variation and there was no history of fever or any constitutional symptoms. The disorder showed no improvement through the years. There was no history or presence of any vesiculo-bullous lesions. No systemic manifestation or associated cutaneous involvement was noted. Personal history of atopy manifested by perennial sneezing and nasal discharge was present. The patient had used various topical agents including emollients, calcipotriol, and corticosteroids without benefits. The child was born of a non-consanguineous marriage and of the five siblings, one elder brother and a younger sister showed similar features from infancy.

Figure 2	Figure 3
Figure 2. Peeling of the skin from chest Figure 3. Back showing peeling of skin

Skin examination revealed generalized involvement with areas of peeling skin over the trunk, back, and extremities. (Figures 2 and 3) On gentle rubbing of normal-looking areas, peeling of thin, superficial layers of skin was observed. Sheets of superficial epidermis could be easily peeled off without bruising or pain; the underlying skin was not inflamed. The teeth, hair, nails, and mucosa were normal.

A complete blood count including hemoglobin, total and differential leukocyte count, erythrocyte sedimentation rate, urinalysis, and routine blood chemistry were within normal limits except for the presence of hypoproteinemia (total proteins – 5.2 gm/dl) and raised serum immunoglobulin E levels (355 IU/ml). A skin biopsy specimen revealed slight hyperkeratosis and thinning of the granular cell layer. The stratum corneum was separated from the underlying stratum granulosum. Mild atrophy with loss of rete ridges and irregular dermal papillae was seen. Increased collagen in the dermis was also visible.

The parents were counseled about the benign nature of the condition. Emollients and protein supplementation was advised. The patient was kept under treatment and observation for 10 months, but the condition remained unchanged.

Discussion

The first case of Peeling Skin Syndrome was reported by Fox in 1921 and termed “keratolysis exfoliativa congenita” [4]. Since then, this rare disorder has been designated peeling skin syndrome [5], deciduous skin [1], or familial continual skin peeling syndrome [3]. The true prevalence of the disease has not been worked out.

Figure 4
Figure 4. Histopathology showing intraepidermal split with slight hyperkeratosis

Two main subtypes of PSS based on the presence or absence of inflammatory changes have been suggested: Type A is a non-inflammatory variant characterized by asymptomatic, generalized, continuous skin peeling with intact general health, whereas Type B patients exhibit ichthyotic erythroderma that evolves into pruritic, scaly, and erythematous patches with rare vesiculations, easily removable hair, and summer flaring [3, 6]. In some patients sparing of the face, palms, and soles has been reported [7] as is present in this patient. The condition is life-long and is usually generalized. However, a few localized forms such as acral and facial types have also been described [8, 9]. (Figure 4) Histopathology of PSS usually reveals hyperkeratosis and splitting of the epidermis between the granular layer and the stratum corneum or sometimes shows an intracorneal split. Intracellular, cytoplasmic splitting may also be found in the lower stratum corneum [6]. Electron microscopy demonstrates abnormal and cribriform keratohyalin granules indicating a severe disturbance of keratinization. In a few patients, reduced desmosomal plates or intercellular electrondense globular deposits in the stratum corneum were also found [3, 6, 8].

Other associated features that have been reported include anosmia, distal onycholysis, keratoderma, koilonychia, primary amenorrhea, sexual dysfunction, and short stature. Abnormalities in tryptophan levels, aminoaciduria, elevated serum copper, IgE, ceruloplasmin, iron-binding capacity, and abnormal epidermal retinoid metabolism have also been reported in some cases [5, 10].

Our patient had hypoproteinemia possibly as a result of excessive skin peeling coupled with a low protein diet. Raised IgE levels and history of atopy manifested by perennial allergic rhinitis is perhaps a coexisting and unrelated feature.

The differential diagnosis includes various types of subcorneal dermatosis. Pemphigus foliaceous is excluded by the absence of acantholysis and the presence of disease since birth. Subcorneal pustular dermatosis is excluded by the absence of pustules. Bullous impetigo with subcorneal clefting is an acute disease with honey colored crusting and evidence of infection, whereas the case at hand is a chronic disorder without any infection. At a glance, presentation in a child may be confused with staphylococcal scalded skin syndrome but the absence of fever and cutaneous tenderness combined with the long history of disease favors the diagnosis of PSS.

So far, fourteen cases have been reported from India (Table 1); most of them appear to belong to the type A non-inflammatory variant of PSS, which is otherwise asymptomatic with occasional pruritus. Four of the reported cases belonged to inflammatory subtype showing varied presentations including the presence of vesicles or pustules, a prodrome of fever and sore throat, and involvement of mucous membrane and nails. Hair and teeth were normal in all cases. Two of the reported cases showed only acral involvement. However, no case limited to the face has been reported from India. PSS in India presents a spectrum of clinical features and only a few cases match the classical presentation described by Fox.

The exact etiology and pathogenesis of PSS has not been elucidated. The hypothesis of PSS as being a hyperproliferative disorder with abnormal keratinization was proposed by Azar and Kurban [2]. Silverman et al. [3] believed abnormal lipid deposition within the cells produced decreased cohesiveness of the stratum corneum, which was the pathogenic event. More recently, Hashimoto et al. are of the view that mutations of profilaggrin / filaggrin genes could be responsible for abnormal filaggrin that fails to keep keratin filaments aggregated. This would explain the disruption of horny cells and worsening of the symptoms after soaking and perspiration in the summer [8]. However, substantiation with evidence is still lacking.

In the acral form of peeling skin syndrome, a homozygous missense mutation G113C, which encodes for transglutaminase 5 (TGM5), was identified [11]. Transglutaminase 5 is strongly expressed in the epidermal granular cells where it cross-links a variety of structural proteins in the terminal differentiation of the epidermis to form the cornified cell envelope. Occurrence of G113C, a missense mutation, completely abolishes transglutaminase 5 activity. However, Cassidy et al. were unable to find any evidence of TGM5 mutations in a large, consanguineous kindred of Middle Eastern origin with widespread peeling of the skin or in 3 small, families with the same generalized phenotype [11].

Management of this condition is difficult because no effective treatment has been reported. Topical emollients may help some patients, whereas keratolytic agents might speed up shedding and improve appearance. Other treatment modalities such as methotrexate, UVB phototherapy, isotretinoin, and oral corticosteroid therapy were found to be ineffective [5]. Calcipotriol as reported to be effective in one study, was found to be ineffective in our patient [12].

Conclusion

Peeling skin syndrome is largely a cosmetic disability causing substantial emotional stress to the patient whose diagnosis relies upon the presence of peeling skin without any underlying pathology and characteristic histology showing a split between the stratum corneum and the stratum granulosum. Understanding of the pathogenic events leading to the development of PSS will go a long way in formulating treatment for this presently untreatable lifelong disease. Homozygous missense mutation G113C, in TGM5, which encodes for Transglutaminase 5 in the acral form of PSS but not in generalized types of PSS, requires further investigation and may hold the key to unraveling the pathogenic event in other acantholytic disorders and formulating new treatments for such conditions.

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