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Peeling skin syndromes

Peeling skin syndromes
Literature review current through: Jan 2024.
This topic last updated: Oct 18, 2022.

INTRODUCTION — Peeling skin syndromes (PSSs) are a heterogeneous group of rare, autosomal recessive disorders characterized by superficial, painless peeling and blistering of the skin without mucosal fragility [1-3]. The two major forms are acral peeling skin syndrome (APSS; also called localized PSS) and generalized PSS [4-7]. The latter is subclassified into noninflammatory (type A) and inflammatory (type B) PSS [8,9].

Although PSS was previously considered a subtype of epidermolysis bullosa simplex, it is now classified as a separate entity in the group of "other disorders with skin fragility."

This topic will review the pathogenesis, clinical features, and management of PSS. Congenital blistering diseases and keratinization disorders are discussed separately.

(See "Epidermolysis bullosa: Epidemiology, pathogenesis, classification, and clinical features".)

(See "Diagnosis of epidermolysis bullosa".)

(See "Overview of the management of epidermolysis bullosa".)

(See "Overview and classification of the inherited ichthyoses".)

ACRAL PEELING SKIN SYNDROME — The localized form of peeling skin syndrome (PSS), called acral peeling skin syndrome (APSS) or PSS type 2 (MIM #609796), is a rare, autosomal recessive disorder caused by mutations in two genes: TGM5, encoding transglutaminase 5 (TGM5), implicated in the large majority of cases [4,10], and CSTA (PSS type 4, MIM #607936), encoding cystatin A, a cysteine protease inhibitor [11,12]. APSS manifests at birth or in early infancy and is characterized by skin exfoliation limited to the hands and feet.

Epidemiology — The precise incidence and prevalence of APSS are unknown due to being underreported, relatively mild, and easily misdiagnosed as other skin fragility disorders (eg, localized forms of epidermolysis bullosa simplex). The vast majority of reported patients are from European countries, suggesting a founder effect. Sporadic cases from Africa have been reported [5,13,14]. However, very few cases have been reported from outside Europe, perhaps reflecting geographical restriction of a common founder mutation. In European populations, the estimated carrier frequency of the most common TGM5 mutation, p.Gly113Cys, is approximately 3 percent, predicting a disease prevalence of up to 1 in 4500 [4,15]. More than 160 patients with APSS have been reported, with TGM5 mutations found in over 90 percent of cases [6,10,16].

Pathogenesis — APSS is caused by biallelic (homozygous or compound heterozygous) mutations in the TGM5 gene, encoding TGM5 [4,10]. Crucial for normal epidermal differentiation, transglutaminases are a family of enzymes involved in the cross-linking of cornified cell envelope proteins through the formation of gamma-glutamyl-lysine isodipeptide bonds between adjacent polypeptides [15,17-19]. Therefore, mutations in TGM5 completely abolish cross-linking activity, leading to the detachment of the stratum corneum from the underlying stratum granulosum at the site of activity and expression of TGM5 (figure 1) [20].

TGM5 is located on 15q15.2, spans 33.7 kb of genomic deoxyribonucleic acid (DNA), and contains 13 exons. The TGM5 protein has three domains (beta-sandwich, beta-barrel 1, and beta-barrel 2) and an additional highly conserved, functionally important domain called the central catalytic core [6,21]. Most mutations affect amino acids located in the catalytic core and the beta-sandwich domains [6]. The most commonly reported mutation, p.Gly113Cys, is located within the beta-sandwich domain and has been found to abolish TGM5 activity [4].

There is no obvious phenotype-genotype correlation or variation in severity between homozygous and compound heterozygous patients. The phenotype can vary in severity both within and among families [6]. It has been shown that homozygous ALOXE3 mutations resulting in a phenotype of autosomal recessive congenital ichthyosis rescue cell-cell adhesion defects due to homozygous TGM5 mutations through corneodesmosin upregulation [22].

Homozygous mutations in the CSTA gene, encoding cystatin A, a member of a superfamily of protease inhibitors expressed in the cornified cell envelope, were reported in families with APSS without evidence of TGM5 mutations [11,12,23]. Other mutations in the same gene have been implicated in the pathogenesis of autosomal recessive exfoliative ichthyosis (AREI; MIM #607936), a rare type of congenital ichthyosis characterized by palmoplantar hyperkeratosis with extension to the dorsal aspects of hands and feet and acral skin peeling [11,24-26]. (See 'Autosomal recessive exfoliative ichthyosis' below.)

Of note, acral peeling of the skin has been reported as a minor feature of cutaneous serpinopathies due to loss-of-function defects in serpins, another class of protease inhibitors [27,28]. (See "Palmoplantar keratoderma", section on 'Palmoplantar keratoderma with SERPINA12 mutations'.)

Pathology — Histologically, APSS is characterized by compact orthokeratosis and detachment of the stratum corneum from the underlying stratum granulosum (picture 1) [20]. Electron microscopy, although not required for analysis, may reveal more subtle morphologic changes, including cleavage between cornified cells and disrupted tonofilament bundles.

Clinical manifestations — Patients with APSS present with superficial peeling or blistering of the dorsal surfaces of hands and feet, palms, and soles, often associated with erythema (picture 2A-B) [29,30]. When present, blisters are superficial and flaccid, have a clear content, and rupture easily, resulting in exfoliation. Lesions occasionally involve the limbs and may be associated with mild pruritus [11,24,31].

Onset of symptoms is shortly after birth or in early childhood. Healing usually occurs spontaneously, sometimes with residual erythema, burning sensation, or pruritus, but without scarring or atrophy. Some patients present with only mild disease characterized by superficial peeling of dorsal and plantar areas of the hands and feet; however, episodes of aggravation may follow exposure to heat, mechanical trauma (friction), humidity, and exposure to water [29].

In most cases, skin peeling persists over time, whereas blistering tends to cease with age [31]. There are no known systemic manifestations nor abnormal laboratory findings.

Diagnosis — The diagnosis of APSS is suspected in children or adults presenting with acral skin blistering and peeling in the absence of mucosal involvement and systemic manifestations. The definitive diagnosis is based upon (algorithm 1):

Histopathologic analysis of a skin biopsy obtained from an area of skin peeling revealing separation between the stratum corneum and stratum granulosum. Electron microscopy analysis, although not required for diagnosis, may reveal more subtle morphologic changes, including cleavage between cornified cells with disrupted tonofilament bundles. (See 'Pathology' below.)

Identification of causative variants in TGM5 (or CSTA) by mutation analysis on DNA isolated from peripheral blood or other appropriate tissue.

Differential diagnosis — The differential diagnosis of APSS includes several inherited and acquired conditions (algorithm 2). Among these, APSS is most frequently confused with localized epidermolysis bullosa simplex.

Epidermolysis bullosa simplex — Localized epidermolysis bullosa simplex is an autosomal dominant disorder most often caused by mutations in the genes KRT5 or KRT14, although numerous additional genes have been implicated [32]. Epidermolysis bullosa simplex is characterized by blisters and erosions on the palms and soles following mechanical trauma (picture 3A-B).

Ultrastructurally, epidermolysis bullosa simplex blisters are located in the basal layer of the epidermis and not in the upper epidermis, as in APSS [33,34]. Histopathologic and ultrastructural analysis of a skin biopsy and mutation analysis can clarify the diagnosis [29,32]. (See "Epidermolysis bullosa: Epidemiology, pathogenesis, classification, and clinical features", section on 'Epidermolysis bullosa simplex'.)

Erythrokeratolysis hiemalis (keratolytic winter erythema) — Erythrokeratolysis hiemalis is an autosomal dominant disorder characterized by recurrent episodes of palmoplantar erythema and epidermal peeling that exacerbate during the winter. A less common finding is a slowly migratory, annular erythema involving the extremities. Itching, hyperkeratosis, and hyperhidrosis are associated features. In contrast to APSS, keratolytic winter erythema features a more pronounced erythema and hyperkeratosis with normal-appearing skin between flares. The disease is caused by genomic changes affecting a regulatory region modulating the expression of the CTSB gene on chromosome 8p22-p23, encoding cathepsin B, a cysteine protease involved in keratinocyte differentiation and desquamation [35-37].

Keratolysis exfoliativa — Keratolysis exfoliativa (also known as "dyshidrosis lamellosa sicca") is a palmoplantar dermatosis characterized by annular erythema over the volar aspects of the hands and feet with air-filled blisters heralding lamellar peeling (picture 4A-B). In contrast to APSS, it is characterized mainly by small, annular collarettes of white scale involving only the palms (and, less commonly, the soles) with no involvement of the dorsal aspects of hands and feet. In addition, no fluid-filled blisters are seen in this condition. Keratolysis exfoliativa worsens under warm weather and may be associated with hyperhidrosis. Friction and water contact may aggravate findings. This may be explained by damage to the stratum corneum in volar skin by mechanical forces or soaking. Histopathologic findings include cleavage within the stratum corneum, without an inflammatory infiltrate [38].

Management of acral peeling skin syndrome — There is no specific therapy for APSS. Patients should be educated about avoidance of exacerbating factors, such as heat, friction, humidity, mechanical trauma, and excessive perspiration. Daily topical application of emollients to affected areas may be beneficial.

Genetic counseling — All patients and their family members should be referred for genetic counseling. In patients of European ancestry suspected to have epidermolysis bullosa simplex but lacking mutations in the keratin genes, screening for the recurrent TGM5 mutation p.Gly113Cys is indicated. If not found, direct sequencing of all coding regions of the TGM5 gene is indicated.

GENERALIZED NONINFLAMMATORY (TYPE A) PEELING SKIN SYNDROME — Generalized noninflammatory peeling skin syndrome (PSS), also called type A PSS (MIM #270300), is a rare, autosomal recessive disorder characterized by generalized, painless peeling of the skin that starts at birth or in early infancy. This type of PSS encompasses three major groups: PSS type 3 (MIM #616265), characterized by asymptomatic, superficial, generalized peeling [8,39]; PSS type 5 (MIM #617115), manifesting with skin peeling over the hands, feet, and knees associated with palmoplantar keratoderma [40]; and PSS type 6 (MIM #618084), characterized by generalized, dry skin and peeling lesions on the trunk and limbs at sites of minor trauma [41-43].

Pathogenesis

Peeling skin syndrome type 3 — In a large consanguineous Pakistani family, type A PSS (generalized noninflammatory PSS) was associated with a homozygous CHST8 mutation, c.229C>T, within exon 4, using a combination of autozygosity mapping and whole exome sequencing [8]. CHST8 encodes a carbohydrate sulfotransferase, N-acetylgalactosamine-4-O-sulfotransferase 1 (GalNAc4-ST1), which is a type II transmembrane protein that functions almost exclusively in the Golgi apparatus and transfers sulfate groups to the C4 hydroxyl group of terminal beta-1,4-linked N-acetylgalactosamine [44]. GalNAc4-ST1 is highly expressed in the pituitary gland, cerebellum, and brain, where it is required for the biosynthesis of the glycoprotein hormones LH and thyrotropin [44].

However, the association of type A PSS with CHST8 has been questioned. A subsequent study indicated that CHST8 is weakly expressed in keratinocytes and that the mutant protein found in association with PSS type 3 in one family resulted in a normal activity [39]. Moreover, the PSS type 3-associated CHST8 variant is frequently found in the general population, which does not fit the rarity of the PSS phenotype, suggesting that it represents a neutral nonpathogenic polymorphism [39].

Peeling skin syndrome type 5 — Homozygous loss-of-function mutations in the gene SERPINB8, encoding serpin peptidase inhibitor, clade B, member 8, result in noninflammatory peeling of the skin, also referred to as "exfoliative ichthyosis." SERPINB8 protein absence in patients' skin results in impaired cell-cell adhesion, especially following exposure to mechanical stress [40]. Of note, homozygous mutation in another member of the same family of peptidase inhibitors, SERPINB7, has been shown to result in the acral peeling phenotype in patients with palmoplantar keratosis Nagashima type through reduced desmoglein 1 and desmocollin 1 expression, which results in desquamation and impaired keratinocyte adhesion [27].

Peeling skin syndrome type 6 — Biallelic loss-of-function mutations in FLG2, encoding filaggrin 2, have been reported in three consanguineous families of Saudi, Moroccan, and Israeli origins with generalized noninflammatory PSS [41-43]. Reduced filaggrin expression at the RNA and protein level in patients' epidermis resulted in impaired cell-cell adhesion through reduction in corneodesmosin expression, which is a crucial component of corneodesmosomes, intercellular junctions located in the uppermost layers of the epidermis. This effect is enhanced by temperature elevation, consistent with the observed clinical exacerbation of PSS type 6 by warm weather [43].

Pathology — Type A PSS is characterized by slight hyperkeratosis, thinning of the granular layer, and separation of the stratum corneum from the underlying stratum granulosum or intracorneal split [8,41-43,45]. Electron microscopy shows intracellular cytoplasmic splitting in the lower stratum corneum and abnormal cribriform or reduced keratohyalin granules, which are indicative of disturbed keratinization [41-43]. In some patients, reduced desmosomal plaques or intracellular electron-dense globular deposits within the stratum corneum have also been observed [46-48].

PSS type 5 is characterized by cell-cell disadhesion within the Malpighian layer of the epidermis [40].

Clinical manifestations — Type A PSS presents at birth or in early childhood with generalized, white to skin-colored scaling, most prominent over the upper and lower extremities, including areas of large joints [40], with painless and easy removal of the stratum corneum of the skin (picture 5) [49,50]. Exacerbations may occur following contact with water, dust, and sand. In addition, sliding friction forces may induce peeling [49]. Thickened skin with diffuse, yellowish, hyperkeratotic plaques over the palms and soles may be seen in PSS type 5 [40,41]. Hyperkeratosis over the knees and elbows is also typical of PSS type 5 [42]. PSS type 6 is characterized by superficial peeling of the skin over the trunk and extremities at sites exposed to trauma, with residual hyperpigmentation following healing.

Erythema; pruritus; atopic manifestations; hair, nail, and mucous abnormalities; and systemic involvement are usually absent [8]. Routine laboratory tests, including immunoglobulin E (IgE) serum levels, are normal. There is a case report of type A PSS associated with aminoaciduria, with increased urine excretion of cystine and histidine [51].

Diagnosis — The diagnosis of type A PSS is often delayed due to late presentation in less severe and asymptomatic cases. Similar to acral peeling skin syndrome, the diagnosis of type A PSS is suspected in a patient presenting with painless skin peeling since birth or early childhood. A skin biopsy from involved areas of skin peeling is necessary for the diagnosis (see 'Pathology' above). Ultrastructural analysis using electron microscopy, if available, may provide additional information, although this is not necessary for the diagnosis.

Molecular analysis for mutations in SERPINB8 or FLG2 is indicated in patients and family members for definitive diagnosis (algorithm 1).

Differential diagnosis — The differential diagnosis of generalized noninflammatory PSS includes a number of genodermatoses characterized by scaly skin in the absence of erythema (algorithm 2).

Superficial epidermolytic ichthyosis — Superficial epidermolytic ichthyosis (formerly called "ichthyosis bullosa of Siemens"; MIM #146800) is a rare, autosomal dominant genodermatosis caused by heterozygous mutations in the gene KRT2, encoding keratin 2. The disease is characterized by mild blistering in early infancy that usually subsides by early childhood when hyperkeratosis develops. An additional characteristic feature is superficial peeling described as "Mauserung (moulting) phenomenon," secondary to superficial blistering and shedding of the stratum corneum [52]. No systemic manifestations or abnormal laboratory findings are evident. Histopathologic findings are characteristic epidermolytic changes. (See "Keratinopathic ichthyoses", section on 'Superficial epidermolytic ichthyosis'.)

PLACK syndrome — Peeling skin, leukonychia, acral punctate keratoses, cheilitis, and knuckle pads (PLACK; MIM #616295) syndrome is a form of peeling skin caused by loss-of-function variants in the CAST gene, encoding calpastatin, which is an inhibitor of the calcium-dependent cysteine protease calpain [53-58]. These variants result in reduced calpastatin expression and activity, resulting in defective adhesion and increased epidermal desquamation. PLACK syndrome has been shown to be associated with low levels of vitamin A and essential fatty acids. In a single case report, treatment with intravenous infusions of lipid emulsions containing fat-soluble vitamins resulted in remarkable improvement in pruritus and skin lesions [59].

Autosomal recessive exfoliative ichthyosis — Autosomal recessive exfoliative ichthyosis (AREI; PSS type 4; MIM #607936) is an autosomal recessive disease caused by loss-of-function mutations in CSTA, encoding cystatin A (see 'Acral peeling skin syndrome' above). AREI is characterized by circumscribed, nonerythematous peeling of the skin on the hands, feet, and neck and by generalized, white scaling. Histopathology shows abnormal cell-cell adhesion in the lower epidermal layers [25,26]. Ultrastructurally, AREI is characterized by impaired desmosome morphology in the lower epidermal layers, reduced thickness of the cornified envelope, disturbed lamellar lipid bilayer, premature lamellar body secretion, and delayed processing of secreted lamellar body contents [25,26]. In contrast to PSS, the level of detachment by electron microscopy is in the basal and lower suprabasal layers of the epidermis [25].

Management of generalized noninflammatory peeling skin syndrome — There is no specific therapy for type A PSS. Patients should be educated about avoiding exacerbating factors, such as heat, friction, humidity, mechanical trauma, and excessive perspiration. Daily topical application of emollients to affected areas may be beneficial.

Systemic retinoids, methotrexate, topical and systemic corticosteroids, tar, and ultraviolet B (UVB) phototherapy have been used without success in a few patients [1,47,49,60-62]. Some improvement with topical calcipotriol has been documented in a single patient [63].

GENERALIZED INFLAMMATORY (TYPE B) PEELING SKIN SYNDROME — Generalized inflammatory peeling skin syndrome (PSS), also called type B PSS (PSS type 1; MIM #270300), is a rare, autosomal recessive genodermatosis that results from loss-of-function mutations in the CDSN gene, encoding corneodesmosin [9]. Type B PSS presents at birth or in early childhood with widespread peeling of the skin associated with erythroderma, severe pruritus, and atopic manifestations.

Pathogenesis — Type B PSS (generalized inflammatory PSS) is caused by loss-of-function mutations in CDSN, encoding corneodesmosin, with complete loss of protein expression in the epidermis [9,64-67]. Genomic deletion at the PSORS1 locus removing the entire CDSN gene and a large, homozygous deletion of six genes, including CDSN, have also been reported as the cause of type B PSS [68,69]. This genomic deletion resulting from a founder mutation has been identified in several Japanese patients with PSS [70].

Corneodesmosin is an extracellular 52 to 56 kDa glycoprotein that contributes to the formation of corneodesmosomes, critical intercellular junctions in the upper epidermal layers. This protein plays a role in reinforcing cell-cell adhesion in the upper epidermis, and its degradation by epidermal proteases is essential for normal desquamation [71,72]. The absence of corneodesmosin in patients with type B PSS results in impaired cell-cell coherence in the upper epidermis [73]. The defective skin barrier function leads to increased permeability to allergens and microbes, predisposing to atopic manifestations and skin infections [73].

Pathology — On histology, type B PSS shows subcorneal separation with mild, inflammatory infiltrate in the upper dermis. Electron microscopy shows evidence of split formation between the keratinocytes of the stratum granulosum and corneocytes of the stratum corneum and loss of corneodesmosomes [9]. Total absence of corneodesmosin expression in the epidermis, demonstrated by immunohistochemistry, can confirm the diagnosis.

Clinical manifestations — Type B PSS presents at birth or during early infancy with spontaneous and widespread peeling of the skin associated with erythroderma that persists into adulthood (picture 6). Additional major features are severe pruritus, food allergies, asthma, repeated episodes of angioedema, and urticaria. Patients may exhibit failure to thrive and recurrent skin infections, especially with Staphylococcus aureus [9,64,66]. The condition is usually not associated with any hair abnormalities. However, a single case associated with trichorrhexis invaginata has been reported [74].

Characteristic laboratory findings are elevated IgE levels and eosinophilia.

Diagnosis — The diagnosis of type B PSS is based upon the combination of clinical and laboratory findings (algorithm 1):

Widespread skin peeling associated with erythroderma, severe pruritus, and atopic manifestations, including food allergies and asthma

Elevated levels of serum IgE and eosinophilia

Histopathologic findings of subcorneal separation with mild, inflammatory infiltrate in the upper dermis and absent corneodesmosin stain on immunohistochemistry

Evidence of loss of corneodesmosomes on electron microscopy

Differential diagnosis — The differential diagnosis of type B PSS includes several acquired and inherited disorders. Due to considerable phenotypic overlap, the differentiation of type B PSS from Netherton syndrome and severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome requires mutational analysis (algorithm 2) [46,73].

Netherton syndrome — Netherton syndrome (MIM #256500) is an autosomal recessive genodermatosis caused by loss-of-function mutations in the serine protease inhibitor of Kazal type 5 (SPINK5) gene, encoding the serine protease inhibitor lympho-epithelial Kazal type related inhibitor type 5 (LEKTI) [75-77]. Netherton syndrome is characterized by congenital erythroderma, occasionally complicated with hypernatremic dehydration and sepsis, which usually evolves into a widespread eruption consisting of serpiginous plaques with typical double-edged scales (known as "ichthyosis linearis circumflexa" (picture 7)) [78-85]. Eosinophilia and elevated IgE levels are common laboratory findings [86]. Additional clinical findings include eczematous, atopic dermatitis-like lesions; characteristic hair abnormalities (trichorrhexis invaginata (picture 8)); failure to thrive; atopic manifestations (eg, asthma, allergic rhinitis, food allergies); urticaria; angioedema; and often severe reactions [87-92]. (See "Overview and classification of the inherited ichthyoses", section on 'Netherton syndrome'.)

SAM syndrome — Severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome (MIM #615508) is a genodermatosis first described in 2013 caused by homozygous mutations in DSG1, encoding desmoglein 1, a cadherin-like transmembrane glycoprotein that is an essential component of the desmosomes in the upper epidermal layers [93-98]. Isolated cases of SAM syndrome caused by a point mutation in the DSP gene, encoding desmoplakin, have been described [99-101]. Desmoplakin is an obligate component of functional desmosomes that anchors intermediate filaments to desmosomal plaques.

SAM syndrome is characterized by congenital erythroderma, striate palmoplantar keratoderma (yellowish papules and plaques at the periphery of the palms, along the fingers, and over weight-bearing areas of the feet), skin erosions, scaling, and hypotrichosis. Additional features are severe food allergies, recurrent skin and respiratory infections, eosinophilic esophagitis, esophageal reflux, minor cardiac defects, failure to thrive, and growth retardation. Elevated IgE level is a common laboratory finding [73,93-98,102-104]. Cases resulting from DSP mutations are also associated with pustular lesions [99-101].

Management of generalized inflammatory peeling skin syndrome — There is no specific therapy for type B PSS. Patients should be educated about avoidance of exacerbating factors, such as heat, friction, humidity, mechanical trauma, and excessive perspiration. Daily topical application of emollients to affected areas may be beneficial.

In a single case report, treatment with dupilumab reduced IgE levels but did not improve the skin manifestations or quality of life [105]. A role for antihistamines and kallikrein inhibitors in the treatment of type B PSS has been hypothesized based upon the observation in vitro that histamine attenuates the expression of desmosomal proteins, including CDSN, in human keratinocytes, and kallikreins are upregulated in type B PSS [106-112]. However, due to the rarity of type B PSS, clinical experience with these agents is lacking.

A preclinical study with liposomal encapsulated recombinant human CDSN demonstrated promising results in primary keratinocytes and human epidermal equivalents [113].

SUMMARY AND RECOMMENDATIONS

Definition and classification – Peeling skin syndromes (PSSs) are a heterogeneous group of rare, autosomal recessive disorders characterized by superficial, painless peeling and blistering of the skin without mucosal fragility. The two major forms of PSS are localized/acral peeling skin syndrome (APSS) and generalized PSS. The latter is subclassified into noninflammatory (type A) and inflammatory (type B) PSS. (See 'Introduction' above.)

Acral peeling skin syndrome – APSS is in most cases caused by mutations in the TGM5 gene, encoding transglutaminase 5, involved in the cross-linking of cornified cell envelope proteins. APSS manifests at birth or in early infancy and is characterized by skin exfoliation limited to the hands and feet. Rare cases may result from mutations in CSTA, encoding cystatin A, a cysteine protease inhibitor. (See 'Acral peeling skin syndrome' above.)

Generalized noninflammatory peeling skin syndrome – Generalized noninflammatory PSS, or type A PSS, may result from homozygous mutations in the genes SERPINB8 or FLG2, encoding serpin peptidase inhibitor, clade B, member 8, and filaggrin 2, respectively. Type A PSS presents at birth or early childhood in most cases with generalized, white to skin-colored scaling that is most prominent over the upper and lower extremities, with painless and easy removal of the skin. (See 'Generalized noninflammatory (type A) peeling skin syndrome' above.)

Generalized inflammatory peeling skin syndrome – Generalized inflammatory PSS, or type B PSS, is caused by loss-of-function mutations in the CDSN gene, encoding corneodesmosin. Type B PSS presents at birth or in early childhood with widespread peeling of the skin associated with erythroderma, severe pruritus, and atopic manifestations. (See 'Generalized inflammatory (type B) peeling skin syndrome' above.)

Diagnosis – The diagnosis and differential diagnosis of PSS are based on the combination of clinical features, routine laboratory tests, histopathologic and ultrastructural analysis of a skin biopsy, and mutation analysis (algorithm 1 and algorithm 2).

Management – There are no specific therapies for PSS. Improvement of scaling and blistering may be observed with avoidance of exacerbating factors, such as heat, friction, humidity, mechanical trauma (eg, using padding or appropriate footwear), and excessive perspiration, as well as daily topical application of emollients to affected areas. (See 'Management of acral peeling skin syndrome' above and 'Management of generalized noninflammatory peeling skin syndrome' above and 'Management of generalized inflammatory peeling skin syndrome' above.)

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Topic 15512 Version 11.0

References

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