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Peeling skin syndrome

Eli Sprecher, MD, PhD
Liat Samuelov, MD
Section Editor
Jennifer L Hand, MD
Deputy Editor
Rosamaria Corona, MD, DSc


Peeling skin syndrome (PSS) is a heterogeneous group of rare autosomal recessive disorders characterized by superficial painless peeling and blistering of the skin without mucosal fragility [1,2]. The two major forms of PSS are acral PSS (APSS) and generalized PSS [3-6]. The latter is subclassified into noninflammatory or type A PSS and inflammatory or type B PSS [7,8].

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

(See "Epidemiology, pathogenesis, classification, and clinical features of epidermolysis bullosa".)

(See "Diagnosis of epidermolysis bullosa".)

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

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Literature review current through: Nov 2017. | This topic last updated: Apr 04, 2017.
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  1. Levy SB, Goldsmith LA. The peeling skin syndrome. J Am Acad Dermatol 1982; 7:606.
  2. Hacham-Zadeh S, Holubar K. Skin peeling syndrome in a Kurdish family. Arch Dermatol 1985; 121:545.
  3. Cassidy AJ, van Steensel MA, Steijlen PM, et al. A homozygous missense mutation in TGM5 abolishes epidermal transglutaminase 5 activity and causes acral peeling skin syndrome. Am J Hum Genet 2005; 77:909.
  4. Kharfi M, El Fekih N, Ammar D, et al. A missense mutation in TGM5 causes acral peeling skin syndrome in a Tunisian family. J Invest Dermatol 2009; 129:2512.
  5. Szczecinska W, Nesteruk D, Wertheim-Tysarowska K, et al. Under-recognition of acral peeling skin syndrome: 59 new cases with 15 novel mutations. Br J Dermatol 2014; 171:1206.
  6. Shwayder T, Conn S, Lowe L. Acral peeling skin syndrome. Arch Dermatol 1997; 133:535.
  7. Cabral RM, Kurban M, Wajid M, et al. Whole-exome sequencing in a single proband reveals a mutation in the CHST8 gene in autosomal recessive peeling skin syndrome. Genomics 2012; 99:202.
  8. Oji V, Eckl KM, Aufenvenne K, et al. Loss of corneodesmosin leads to severe skin barrier defect, pruritus, and atopy: unraveling the peeling skin disease. Am J Hum Genet 2010; 87:274.
  9. van der Velden JJ, van Geel M, Nellen RG, et al. Novel TGM5 mutations in acral peeling skin syndrome. Exp Dermatol 2015; 24:285.
  10. Pigors M, Kiritsi D, Cobzaru C, et al. TGM5 mutations impact epidermal differentiation in acral peeling skin syndrome. J Invest Dermatol 2012; 132:2422.
  11. Cañueto J, Bueno E, Rodríguez-Diaz E, et al. Acral peeling skin syndrome resulting from mutations in TGM5. J Eur Acad Dermatol Venereol 2016; 30:477.
  12. Kalinin AE, Kajava AV, Steinert PM. Epithelial barrier function: assembly and structural features of the cornified cell envelope. Bioessays 2002; 24:789.
  13. Candi E, Schmidt R, Melino G. The cornified envelope: a model of cell death in the skin. Nat Rev Mol Cell Biol 2005; 6:328.
  14. García EG, Carreño RG, Martínez González MA, Reyes JJ. Acral peeling skin syndrome: report of two cases. Ultrastruct Pathol 2005; 29:65.
  15. Grenard P, Bates MK, Aeschlimann D. Evolution of transglutaminase genes: identification of a transglutaminase gene cluster on human chromosome 15q15. Structure of the gene encoding transglutaminase X and a novel gene family member, transglutaminase Z. J Biol Chem 2001; 276:33066.
  16. Krunic AL, Stone KL, Simpson MA, McGrath JA. Acral peeling skin syndrome resulting from a homozygous nonsense mutation in the CSTA gene encoding cystatin A. Pediatr Dermatol 2013; 30:e87.
  17. Muttardi K, Nitoiu D, Kelsell DP, et al. Acral peeling skin syndrome associated with a novel CSTA gene mutation. Clin Exp Dermatol 2016; 41:394.
  18. Pavlovic S, Krunic AL, Bulj TK, et al. Acral peeling skin syndrome: a clinically and genetically heterogeneous disorder. Pediatr Dermatol 2012; 29:258.
  19. Blaydon DC, Nitoiu D, Eckl KM, et al. Mutations in CSTA, encoding Cystatin A, underlie exfoliative ichthyosis and reveal a role for this protease inhibitor in cell-cell adhesion. Am J Hum Genet 2011; 89:564.
  20. Moosbrugger-Martinz V, Jalili A, Schossig AS, et al. Epidermal barrier abnormalities in exfoliative ichthyosis with a novel homozygous loss-of-function mutation in CSTA. Br J Dermatol 2015; 172:1628.
  21. Kavaklieva S, Yordanova I, Bruckner-Tuderman L, Has C. Acral peeling skin syndrome resembling epidermolysis bullosa simplex in a 10-month-old boy. Case Rep Dermatol 2013; 5:210.
  22. Hashimoto K, Hamzavi I, Tanaka K, Shwayder T. Acral peeling skin syndrome. J Am Acad Dermatol 2000; 43:1112.
  23. Kiritsi D, Cosgarea I, Franzke CW, et al. Acral peeling skin syndrome with TGM5 gene mutations may resemble epidermolysis bullosa simplex in young individuals. J Invest Dermatol 2010; 130:1741.
  24. Has C, Bruckner-Tuderman L. The genetics of skin fragility. Annu Rev Genomics Hum Genet 2014; 15:245.
  25. Lane EB, McLean WH. Keratins and skin disorders. J Pathol 2004; 204:355.
  26. Starfield M, Hennies HC, Jung M, et al. Localization of the gene causing keratolytic winter erythema to chromosome 8p22-p23, and evidence for a founder effect in South African Afrikaans-speakers. Am J Hum Genet 1997; 61:370.
  27. Chang YY, van der Velden J, van der Wier G, et al. Keratolysis exfoliativa (dyshidrosis lamellosa sicca): a distinct peeling entity. Br J Dermatol 2012; 167:1076.
  28. Veien NK. Acute and recurrent vesicular hand dermatitis. Dermatol Clin 2009; 27:337.
  29. Al Hasan M, Fitzgerald SM, Saoudian M, Krishnaswamy G. Dermatology for the practicing allergist: Tinea pedis and its complications. Clin Mol Allergy 2004; 2:5.
  30. Liu ZH, Shen H, Xu AE. Severe kerion with dermatophytid reaction presenting with diffuse erythema and pustules. Mycoses 2011; 54:e650.
  31. Romano C, Rubegni P, Ghilardi A, Fimiani M. A case of bullous tinea pedis with dermatophytid reaction caused by Trichophyton violaceum. Mycoses 2006; 49:249.
  32. Boonstra MB, Christoffers WA, Coenraads PJ, Schuttelaar ML. Patch test results of hand eczema patients: relation to clinical types. J Eur Acad Dermatol Venereol 2015; 29:940.
  33. Isaksson M, Olhardt S, Rådehed J, Svensson Å. Children with Atopic Dermatitis Should Always be Patch-tested if They Have Hand or Foot Dermatitis. Acta Derm Venereol 2015; 95:583.
  34. Lachapelle JM. Allergic contact dermatitis: clinical aspects. Rev Environ Health 2014; 29:185.
  35. Barth JH, Fairris GM, Wojnarowska F, White JE. Haemorrhagic pompholyx is a sign of bullous pemphigoid and an indication for low-dose prednisolone therapy. Clin Exp Dermatol 1986; 11:409.
  36. Barth JH, Venning VA, Wojnarowska F. Palmo-plantar involvement in auto-immune blistering disorders--pemphigoid, linear IgA disease and herpes gestationis. Clin Exp Dermatol 1988; 13:85.
  37. Duhra P, Charles-Holmes R. Linear IgA disease with haemorrhagic pompholyx and dapsone-induced neutropenia. Br J Dermatol 1991; 125:172.
  38. Sugimura C, Katsuura J, Moriue T, et al. Dyshidrosiform pemphigoid: report of a case. J Dermatol 2003; 30:525.
  39. Baenziger JU. Glycoprotein hormone GalNAc-4-sulphotransferase. Biochem Soc Trans 2003; 31:326.
  40. Garg K, Singh D, Mishra D. Peeling skin syndrome: Current status. Dermatol Online J 2010; 16:10.
  41. Ishida-Yamamoto A, Igawa S, Kishibe M. Order and disorder in corneocyte adhesion. J Dermatol 2011; 38:645.
  42. Mevorah B, Frenk E, Saurat JH, Siegenthaler G. Peeling skin syndrome: a clinical, ultrastructural and biochemical study. Br J Dermatol 1987; 116:117.
  43. Silverman AK, Ellis CN, Beals TF, Woo TY. Continual skin peeling syndrome. An electron microscopic study. Arch Dermatol 1986; 122:71.
  44. Sarma N, Boler AK, Bhanja DC. Peeling skin syndrome in eight cases of four different families from India and Bangladesh. Indian J Dermatol Venereol Leprol 2012; 78:625.
  45. Aras N, Sutman K, Tastan HB, et al. Peeling skin syndrome. J Am Acad Dermatol 1994; 30:135.
  46. Inamadar AC, Palit A. Peeling skin syndrome with aminoaciduria. Pediatr Dermatol 2005; 22:314.
  47. Handler MZ, Schwartz RA. Staphylococcal scalded skin syndrome: diagnosis and management in children and adults. J Eur Acad Dermatol Venereol 2014; 28:1418.
  48. Cervantes T, Pham C, Browning JC. Superficial epidermolytic ichthyosis: a report of two families. Pediatr Dermatol 2013; 30:469.
  49. Tolat SN, Gharpuray MB. Skin peeling syndrome. Cutis 1994; 53:255.
  50. Köse O, Safali M, Koç E, et al. Peeling skin diseases: 21 cases from Turkey and a review of the literature. J Eur Acad Dermatol Venereol 2012; 26:844.
  51. Kharfi M, Khaled A, Ammar D, et al. Generalized peeling skin syndrome: Case report and review of the literature. Dermatol Online J 2010; 16:1.
  52. Mizuno Y, Suga Y, Hasegawa T, et al. A case of peeling skin syndrome successfully treated with topical calcipotriol. J Dermatol 2006; 33:430.
  53. Israeli S, Zamir H, Sarig O, et al. Inflammatory peeling skin syndrome caused by a mutation in CDSN encoding corneodesmosin. J Invest Dermatol 2011; 131:779.
  54. Mallet A, Kypriotou M, George K, et al. Identification of the first nonsense CDSN mutation with expression of a truncated protein causing peeling skin syndrome type B. Br J Dermatol 2013; 169:1322.
  55. Telem DF, Israeli S, Sarig O, Sprecher E. Inflammatory peeling skin syndrome caused a novel mutation in CDSN. Arch Dermatol Res 2012; 304:251.
  56. Ishida-Yamamoto A, Furio L, Igawa S, et al. Inflammatory peeling skin syndrome caused by homozygous genomic deletion in the PSORS1 region encompassing the CDSN gene. Exp Dermatol 2014; 23:60.
  57. Teye K, Hamada T, Krol RP, et al. Homozygous deletion of six genes including corneodesmosin on chromosome 6p21.3 is associated with generalized peeling skin disease. J Dermatol Sci 2014; 75:36.
  58. Teye K, Suga Y, Numata S, et al. A founder deletion of corneodesmosin gene is prevalent in Japanese patients with peeling skin disease: Identification of 2 new cases. J Dermatol Sci 2016; 82:134.
  59. Caubet C, Jonca N, Lopez F, et al. Homo-oligomerization of human corneodesmosin is mediated by its N-terminal glycine loop domain. J Invest Dermatol 2004; 122:747.
  60. Simon M, Jonca N, Guerrin M, et al. Refined characterization of corneodesmosin proteolysis during terminal differentiation of human epidermis and its relationship to desquamation. J Biol Chem 2001; 276:20292.
  61. Samuelov L, Sprecher E. Peeling off the genetics of atopic dermatitis-like congenital disorders. J Allergy Clin Immunol 2014; 134:808.
  62. Dicken CH. Peeling skin syndrome. J Am Acad Dermatol 1985; 13:158.
  63. Srinivasaraghavan R, Krishnamurthy S, Chandar R, et al. Immunoglobulin A nephropathy in association with generalized inflammatory peeling skin syndrome. Pediatr Dermatol 2015; 32:244.
  64. Lyons JJ, Milner JD, Stone KD. Atopic dermatitis in children: clinical features, pathophysiology, and treatment. Immunol Allergy Clin North Am 2015; 35:161.
  65. Igawa S, Kishibe M, Honma M, et al. Aberrant distribution patterns of corneodesmosomal components of tape-stripped corneocytes in atopic dermatitis and related skin conditions (ichthyosis vulgaris, Netherton syndrome and peeling skin syndrome type B). J Dermatol Sci 2013; 72:54.
  66. Samuelov L, Sprecher E. Inherited desmosomal disorders. Cell Tissue Res 2015; 360:457.
  67. Bitoun E, Micheloni A, Lamant L, et al. LEKTI proteolytic processing in human primary keratinocytes, tissue distribution and defective expression in Netherton syndrome. Hum Mol Genet 2003; 12:2417.
  68. Chavanas S, Bodemer C, Rochat A, et al. Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome. Nat Genet 2000; 25:141.
  69. Mägert HJ, Ständker L, Kreutzmann P, et al. LEKTI, a novel 15-domain type of human serine proteinase inhibitor. J Biol Chem 1999; 274:21499.
  70. Mizuno Y, Suga Y, Muramatsu S, et al. A Japanese infant with localized ichthyosis linearis circumflexa on the palms and soles harbouring a compound heterozygous mutation in the SPINK5 gene. Br J Dermatol 2005; 153:661.
  71. Hausser I, Anton-Lamprecht I. Severe congenital generalized exfoliative erythroderma in newborns and infants: a possible sign of Netherton syndrome. Pediatr Dermatol 1996; 13:183.
  72. Hovnanian A. Netherton syndrome: skin inflammation and allergy by loss of protease inhibition. Cell Tissue Res 2013; 351:289.
  73. Mizuno Y, Suga Y, Haruna K, et al. A case of a Japanese neonate with congenital ichthyosiform erythroderma diagnosed as Netherton syndrome. Clin Exp Dermatol 2006; 31:677.
  74. El Shabrawi-Caelen L, Smolle J, Metze D, et al. Generalized exfoliative erythroderma since birth. Netherton syndrome. Arch Dermatol 2004; 140:1275.
  75. Sun JD, Linden KG. Netherton syndrome: a case report and review of the literature. Int J Dermatol 2006; 45:693.
  76. Haliasos EC, Kerner M, Jaimes-Lopez N, et al. Dermoscopy for the pediatric dermatologist part I: dermoscopy of pediatric infectious and inflammatory skin lesions and hair disorders. Pediatr Dermatol 2013; 30:163.
  77. Burk C, Hu S, Lee C, Connelly EA. Netherton syndrome and trichorrhexis invaginata--a novel diagnostic approach. Pediatr Dermatol 2008; 25:287.
  78. Rakowska A, Kowalska-Oledzka E, Slowinska M, et al. Hair shaft videodermoscopy in netherton syndrome. Pediatr Dermatol 2009; 26:320.
  79. Macknet CA, Morkos A, Job L, et al. An infant with Netherton syndrome and persistent pulmonary hypertension requiring extracorporeal membrane oxygenation. Pediatr Dermatol 2008; 25:368.
  80. Pohl M, Zimmerhackl LB, Hausser I, et al. Acute bilateral renal vein thrombosis complicating Netherton syndrome. Eur J Pediatr 1998; 157:157.
  81. Samuelov L, Sarig O, Harmon RM, et al. Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting. Nat Genet 2013; 45:1244.
  82. Schlipf NA, Vahlquist A, Teigen N, et al. Whole-exome sequencing identifies novel autosomal recessive DSG1 mutations associated with mild SAM syndrome. Br J Dermatol 2016; 174:444.
  83. Cheng R, Yan M, Ni C, et al. Report of Chinese family with severe dermatitis, multiple allergies and metabolic wasting syndrome caused by novel homozygous desmoglein-1 gene mutation. J Dermatol 2016; 43:1201.
  84. Dănescu S, Leppert J, Cosgarea R, et al. Compound heterozygosity for dominant and recessive DSG1 mutations in a patient with atypical SAM syndrome (severe dermatitis, multiple allergies, metabolic wasting). J Eur Acad Dermatol Venereol 2017; 31:e144.
  85. McAleer MA, Pohler E, Smith FJ, et al. Severe dermatitis, multiple allergies, and metabolic wasting syndrome caused by a novel mutation in the N-terminal plakin domain of desmoplakin. J Allergy Clin Immunol 2015; 136:1268.
  86. Has C, Jakob T, He Y, et al. Loss of desmoglein 1 associated with palmoplantar keratoderma, dermatitis and multiple allergies. Br J Dermatol 2015; 172:257.
  87. Ishida-Yamamoto A, Igawa S. Genetic skin diseases related to desmosomes and corneodesmosomes. J Dermatol Sci 2014; 74:99.
  88. Mogensen TH. STAT3 and the Hyper-IgE syndrome: Clinical presentation, genetic origin, pathogenesis, novel findings and remaining uncertainties. JAKSTAT 2013; 2:e23435.
  89. Gschwandtner M, Mildner M, Mlitz V, et al. Histamine suppresses epidermal keratinocyte differentiation and impairs skin barrier function in a human skin model. Allergy 2013; 68:37.
  90. Komatsu N, Suga Y, Saijoh K, et al. Elevated human tissue kallikrein levels in the stratum corneum and serum of peeling skin syndrome-type B patients suggests an over-desquamation of corneocytes. J Invest Dermatol 2006; 126:2338.
  91. Tan X, Bertonati C, Qin L, et al. Identification by in silico and in vitro screenings of small organic molecules acting as reversible inhibitors of kallikreins. Eur J Med Chem 2013; 70:661.
  92. Tan X, Furio L, Reboud-Ravaux M, et al. 1,2,4-Triazole derivatives as transient inactivators of kallikreins involved in skin diseases. Bioorg Med Chem Lett 2013; 23:4547.
  93. Fischer J, Wu Z, Kantyka T, et al. Characterization of Spink6 in mouse skin: the conserved inhibitor of kallikrein-related peptidases is reduced by barrier injury. J Invest Dermatol 2014; 134:1305.
  94. Teixeira TS, Freitas RF, Abrahão O Jr, et al. Biological evaluation and docking studies of natural isocoumarins as inhibitors for human kallikrein 5 and 7. Bioorg Med Chem Lett 2011; 21:6112.
  95. Vasileiou Z, Barlos KK, Gatos D, et al. Synthesis of the proteinase inhibitor LEKTI domain 6 by the fragment condensation method and regioselective disulfide bond formation. Biopolymers 2010; 94:339.