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Generalized peeling skin syndrome: Case report and review of the literature

  • Author(s): Kharfi, Monia
  • Khaled, Aida
  • Ammar, Donia
  • Ezzine, Nadia
  • Fekih, Nadia El
  • Fazaa, Becima
  • Jaafoura, Habib
  • Kamoun, Mohamed Ridha
  • et al.
Main Content

Generalized peeling skin syndrome: Case report and review of the literature
Monia Kharfi MD1, Aida Khaled MD1, Donia Ammar1, Nadia Ezzine1, Nadia El Fekih1, Becima Fazaa1, Habib Jaafoura2, Mohamed Ridha Kamoun1
Dermatology Online Journal 16 (3): 1

1. Department of Dermatology, Charles Nicolle Hospital, Tunis, Tunisia. aida.khaled@rns.tn
2. Laboratory of Electronic Microscopy, Medicine University, Tunis, Tunisia


Abstract

Peeling skin syndrome (PSS) is a rare form of ichthyosis with a probable autosomal recessive inheritance that exhibits superficial, painless, continual, or seasonal cutaneous exfoliation. The syndrome generally appears at birth or in infancy. We report a case of generalized PSS and provide a literature review. A 34-year-old woman reported a lifelong history of generalized and painless peeling of the skin that worsened in summer. Her parents were third degree cousins. Her twin sister and her two cousins presented with the same condition. Physical examination showed widespread superficial sheets of variable size that could be easily removed without bleeding or pain. No underlying erythema was noted. Otherwise, the patient was in good health. Histological findings showed an epidermal cleavage within the stratum corneum. The generalized form of PSS is classified into 3 types, A, B, and C, according to the classification system of Traupe and Mevorah. We have tried to classify the cases of generalized PSS already reported in the literature into one of these three types. Thirteen reported cases probably presented PSS-type A. Sixteen patients are best described as PSS-type B. Two patients exhibit PSS-type C. Fifteen reported patients had an acral form of peeling skin syndrome. The classification of the eleven remaining patients was difficult to determine. Our patient presented clinical and histological features of generalized PSS-type A.



Case report


Figure 1Figure 2
Figures 1 and 2. Widespread superficial sheets easily removed without bleeding or underlying erythema

A 34-year-old woman reported a history of generalized and painless peeling of the skin since her early childhood. A worsening of the exfoliation was noted in summer and with exposure to humidity. Her parents were third degree cousins. Her twin sister and her two cousins exhibited the same condition. Physical examination showed widespread superficial sheets of variable size that could be easily removed without bleeding or pain (Figures 1 and 2). No underlying erythema was noted. The patient was, otherwise, in good health. Histological examination of a cutaneous biopsy showed epidermal separation within the stratum corneum. The basal, spinous, and granular layers were normal (Figure 3).


Figure 3
Figure 3. Epidermal cleavage within the stratum corneum. The basal, spinous, and granular layers were normal

The complete blood cell count showed a macrocytic anemia. Liver and renal functions were within normal limits. Total cholesterol and triglycerides were elevated. Total serum Ig E was normal. Serum vitamin A level was slightly but not significantly elevated. The serum vitamin E, zinc and copper levels were normal. Familial history, clinical cutaneous lesions, and histological picture supported the diagnosis of peeling skin syndrome.


Discussion

In 1921, Fox reported the first case of generalized, non-inflammatory and asymptomatic skin shedding called “keratolysis exfoliativa congenita” [1]. In 1938, Behçet described a similar case but he preferred the term “decidious skin” to designate this condition [2]. In 1969, Kurban and Azar described the first report of familial PSS in 4 brothers called “familial continual skin shedding” [3]. The term “skin peeling syndrome” was introduced by Levy and Goldsmith in 1982 [4]. Sixteen years later, an acral form of PSS was described and only recently a familial form (6 cases) of acral PSS was reported in two families [5, 6, 7, 8]. Late onset [9, 10] and drug-induced [11] PSS were also reported. Superficial shedding of the skin represents the main symptom of this cutaneous disorder. As in our patient, peeling is always painless, spontaneous, and superficial. An underlying erythema is noted in almost 50 percent of the reported cases and was absent in our patient. As in our case, worsening of peeling in summer by elevated ambient temperature and humidity is usually noted. Histological examination may be helpful for the diagnosis by showing a superficial cleavage in the epidermis. It is usually localized in the interface of stratum corneum - stratum granulosum [4-7, 10, 12-19] and more rarely in the stratum lucidum [20]. In our patient and in other reported cases, the epidermal separation is intracorneal [9, 11, 21]. Different ultrastructural abnormalities were reported, but their significance remains unclear. An intercellular granular material was described and was considered likely to have a lipidic structure [6, 9, 15]. The presence of abnormal keratohyalin granules containing small ovoid electron-lucent areas was reported in a case of acral PSS [6]. Ultrastructural studies showed a cleavage in the intercellular spaces in 4 cases [15, 16, 20, 21]. This splitting occured especially within the portion of the desmosomal plaque in contact with the corneocyte membrane, leaving the electron-dense part of the desmosomal plaque attached to the membrane of the underlying granular cell [16]. The splitting is reported to be intracellular in 5 cases [5, 10, 22].

The literature, distinguishes two main clinical presentations of PSS: the generalized and the localized forms.

Generalized PSS is usually divided in three types: type A and type B were identified by Traupe [23] and type C by Mevorah et al. [16].

The PSS-type A includes non-inflammatory and asymptomatic peeling. Histological examination shows an orthokeratotic epidermis with a separation that occurs either within the lower part of the stratum corneum or just above the granular layer. Ultrastructural study reveals an intracellular cleavage of the corneocytes and the presence of an electron dense material within corneocytes that may correspond to abnormal lipids.

The PSS-type B is clinically characterized by a congenital ichthyosiform erythroderma, erythematous migratory patches with a peeling border, pruritus, and atopy. Histology can show an absence of the stratum corneum or a few layers of parakeratosis, which tend to be separated from the stratum granulosum. Psoriasisform acanthosis and perivascular infiltration with mononuclear leukocytes can also be seen. Electron microscopy shows an intercellular separation of corneocytes just above the granular layer and a deposit of electron dense ovoid granules. Komatsu et al. suggest that PSS- type B corresponds to a disease of excessive desquamation owing to an over-expression of human tissue kallikreins (hks) and an elevation of stratum corneum protease activities. The excessive desquamation of corneocytes may explain the clinical similarities between PSS-type B and Netherton syndrome [24].

Peeling skin syndrome-type C, usually begins in infancy with erythematous patches surrounded by a superficially peeling collarette. Marked blepharitis, conjunctivitis and cheilitis with fissured perlèche were observed. Atopy and pruritus were also noted. Histological patterns were similar to those of PSS-type B. The typical histological appearance includes orthokeratotic hyperkeratosis with acanthosis; the splitting occurs in the stratum corneum just above the granular layer. Ultrastructural study reveals a separation at the corneocyte-granular cell desmosomal connections.

Generalized PSS (GPSS) is usually described as sparing the palms and soles. Yet, Ilknur et al., described a generalized PSS type-B involving palms and soles [25].

Referring to this classification system, we have tried to classify the reported cases of PSS, so that our case is one of the main types of this disorder. Thirteen reported cases presented clinical, histological, and/or electron microscopic findings compatible with the GPSS-type A [1-3, 10, 17, 25-28]. Sixteen patients probably represented GPSS-type B [4, 12-15, 17-19, 25, 29, 30]. This type is similar clinically to Netherton syndrome. A genetic study of these cases searching for the serine protease inhibitor Kazal-type 5 (SPINK5) gene, characteristic for Netherton syndrome, is necessary to confirm the diagnosis. Two patients probably represented GPSS type C [16, 21]. Clinically, this condition could also mimic a vitamin deficiency.

Fifteen reported patients had an acral form of PSS [5-8, 31-34]. A genetic study of five of these cases from the same family revealed a homozygous missense mutation in transglutaminase 5 (TGM5) that abolishes epidermal TGM5 activity [8]. This mutation was also recently found in two Tunisian brothers with acral PSS [33].

The classification of the eleven remaining patients was difficult to determine. Our patient presented clinical and histological features of PSS-type A.

Peeling skin syndrome includes different clinical presentations. The pathogenesis of PSS-type A is still unknown. Abnormalities of lipid or vitamin A metabolism have been suggested [16]. Because consanguinity has been found in many reported patients, an underlying genetic disorder, with a probable autosomal recessive inheritance, is postulated. A homozygous missense mutation in TGM5, which encodes TGM5 was recently identified in some patients with acral involvement. Transglutaminase 5 is strongly expressed in the epidermal granular layer, where it cross-links a variety of structural proteins in the terminal differentiation of the epidermis to form the cornified cell envelope. Transglutaminase 5 is then vital for maintaining cell-cell adhesion between the outermost layers of the epidermis. The homozygous missense mutation abolishes the epidermal TGM5 activity and is implicated in the occurence of acral PSS [8, 33]. No genetic studies have illuminated a cause for GPSS.

Treatment of PSS remains symptomatic and basically preventive to avoid skin peeling and trauma in involved regions. The efficacy of calcipotriol was recently noted [35].

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