Bullous Diseases in Dark Skin

  • Anes YangEmail author
  • Emily K. Kozera
  • Dédée F. Murrell


Blisters are commonly caused by injuries, in particular by burns or specific skin irritation, and heal relatively rapidly without leaving scars. However, a series of autoimmune disorders affecting the skin and the mucous membranes initiate the formation of antibodies against adhesion proteins in skin and mucosal membranes causing chronic and consistent blistering, occasionally leading to scars. The presence of autoantibodies in tissue is visible by direct immunofluorescence (DIF), and circulating autoantibodies may also occur and be detected. Several clinical entities characterized by bulla formation may then arise and also overlap (Table 28.1). The management of these bullous disorders is difficult, and, if left untreated, life-threatening conditions may result.


  1. 1.
    Venugopal SS, Murrell DF. Diagnosis and clinical features of pemphigus vulgaris. Dermatol Clin. 2011;29:373–80.CrossRefPubMedGoogle Scholar
  2. 2.
    Alpsoy E, Akman-Karakas A, Uzun S. Geographic variations in epidemiology of two autoimmune bullous diseases: pemphigus and bullous pemphigoid. Arch Dermatol Res. 2015;307:291–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Saleh MA. Pemphigus in the Arab world. J Dermatol. 2015;42:27–30.CrossRefPubMedGoogle Scholar
  4. 4.
    Adam BA. Bullous diseases in Malaysia: epidemiology and natural history. Int J Dermatol. 1992;31:42–5.CrossRefPubMedGoogle Scholar
  5. 5.
    Kanwar AJ, De D. Pemphigus in India. Indian J Dermatol Venereol Leprol. 2011;77:439–95.CrossRefPubMedGoogle Scholar
  6. 6.
    Singh R, Pandhi R. A clinicopathological study of pemphigus. Indian J Dermatol Venereol Leprol. 1973;39:126.Google Scholar
  7. 7.
    Patel F, Wilken R, Patel FB, et al. Pathophysiology of autoimmune bullous diseases: nature versus nurture. Indian J Dermatol. 2017;62:262–7.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Capon F, Bharkhada J, Cochrane N, et al. Evidence of an association between desmoglein 3 haplotypes and pemphigus vulgaris. Br J Dermatol. 2006;154:67–71.CrossRefPubMedGoogle Scholar
  9. 9.
    Murrell DF. Blistering diseases: clinical features, pathogenesis, treatment. Berlin: Springer; 2015.CrossRefGoogle Scholar
  10. 10.
    Kanwar AJ, Tsuruta D, Vinay K, et al. Efficacy and safety of rituximab treatment in Indian pemphigus patients. J Eur Acad Dermatol Venereol. 2013;27:e17–23.CrossRefPubMedGoogle Scholar
  11. 11.
    Anandan V, Jameela WA, Sowmiya R, et al. Rituximab: a magic bullet for pemphigus. J Clin Diagn Res. 2017;11:WC01–6.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Shaik F, Botha J, Aboobaker J, et al. Corticosteroid/cyclophosphamide pulse treatment in South African patients with pemphigus. Clin Exp Dermatol. 2010;35:245–50.CrossRefPubMedGoogle Scholar
  13. 13.
    Zhao C, Murrell DF. Pemphigus vulgaris: an evidence-based treatment update. Drugs. 2015;75:271–84.CrossRefPubMedGoogle Scholar
  14. 14.
    Aoki V, Rivitti EA, Diaz LA. Cooperative Group on Fogo Selvagem Research: update on fogo selvagem, an endemic form of pemphigus foliaceus. J Dermatol. 2015;42:18–26.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Morini JP, Jomaa B, Gorgi Y, Saguem MH, Nouira R, Roujeau J-C, Revuz J. Pemphigus foliaceus in young women: an endemic focus in the Sousse area of Tunisia. Arch Dermatol. 1993;129:69–73.CrossRefPubMedGoogle Scholar
  16. 16.
    Mahé A, Flageul B, Cissé I, et al. Pemphigus in Mali: a study of 30 cases. Br J Dermatol. 1996;134:114–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Aboobaker J, Morar N, Ramdial PK, Hammond MG. Pemphigus in South Africa. Int J Dermatol. 2001;40:115–9.CrossRefPubMedGoogle Scholar
  18. 18.
    Orne CM, Hale CS, Meehan SA, Leger M. Pemphigus foliaceus. Dermatol Online J. 2014;20(12). pii: 13030/qt9bf1p1pc.Google Scholar
  19. 19.
    Kridin K, Zelber-Sagi S, Bergman R. Pemphigus vulgaris and pemphigus foliaceus: differences in epidemiology and mortality. Acta Derm Venereol. 2017;97:1095-9.Google Scholar
  20. 20.
    Green MG, Bystryn J-C. Effect of intravenous immunoglobulin therapy on serum levels of IgG1 and IgG4 antidesmoglein 1 and antidesmoglein 3 antibodies in pemphigus vulgaris. Arch Dermatol. 2008;144:1621–4.CrossRefPubMedGoogle Scholar
  21. 21.
    Loh TY, Paravar T. Rituximab in the management of juvenile pemphigus foliaceus. Dermatol Online J. 2017;23(6). pii: 13030/qt0415n1r5.Google Scholar
  22. 22.
    Lo Schiavo A, Ruocco E, Brancaccio G, et al. Bullous pemphigoid: etiology, pathogenesis, and inducing factors: facts and controversies. Clin Dermatol. 2013;31:391–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Ren Z, Hsu DY, Silverberg NB, et al. The inpatient burden of autoimmune blistering disease in US children: analysis of nationwide inpatient sample data. Am J Clin Dermatol. 2017;18:287–97.CrossRefPubMedGoogle Scholar
  24. 24.
    Schmidt E, della Torre R, Borradori L. Clinical features and practical diagnosis of bullous pemphigoid. Dermatol Clin. 2011;29:427–38.CrossRefPubMedGoogle Scholar
  25. 25.
    Stavropoulos PG, Soura E, Antoniou C. Drug-induced pemphigoid: a review of the literature. J Eur Acad Dermatol Venereol. 2014;28:1133–40.CrossRefPubMedGoogle Scholar
  26. 26.
    Joly P, Tanasescu S, Wolkenstein P, et al. Lichenoid erythrodermic bullous pemphigoid of the African patient. J Am Acad Dermatol. 1998;39:691–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Bernard P, Charneux J. Bullous pemphigoid: a review. Ann Dermatol Venereol. 2011;138:173–81.CrossRefPubMedGoogle Scholar
  28. 28.
    Spivey J, Nye AM. Bullous pemphigoid: corticosteroid treatment and adverse effects in long-term care patients. Consult Pharm. 2013;28:455–62.CrossRefPubMedGoogle Scholar
  29. 29.
    Kirtschig G, Middleton P, Bennett C, et al. Interventions for bullous pemphigoid. Cochrane Database Syst Rev. 2010;(10):CD002292.Google Scholar
  30. 30.
    Collin P, Salmi TT, Hervonen K, et al. Dermatitis herpetiformis: a cutaneous manifestation of coeliac disease. Ann Med. 2017;49:23–31.CrossRefPubMedGoogle Scholar
  31. 31.
    Salmi TT, Hervonen K, Kautiainen H, et al. Prevalence and incidence of dermatitis herpetiformis: a 40-year prospective study from Finland. Br J Dermatol. 2011;165:354–9.CrossRefPubMedGoogle Scholar
  32. 32.
    Bolotin D, Petronic-Rosic V. Dermatitis herpetiformis. Part I. Epidemiology, pathogenesis, and clinical presentation. J Am Acad Dermatol. 2011;64:1017–24.CrossRefPubMedGoogle Scholar
  33. 33.
    Tu H, Parmentier L, Stieger M, et al. Acral purpura as leading clinical manifestation of dermatitis herpetiformis: report of two adult cases with a review of the literature. Dermatology. 2013;227:1–4.CrossRefPubMedGoogle Scholar
  34. 34.
    Zone JJ, Meyer LJ. Dermatitis herpetiformis. Immunol Ser. 1989;46:565–82.PubMedGoogle Scholar
  35. 35.
    Benmously-Mlika R, Bchetnia M, Deghais S, et al. Hailey-Hailey disease in Tunisia. Int J Dermatol. 2010;49:396–401.CrossRefPubMedGoogle Scholar
  36. 36.
    Meng L, Gu Y, Du XF, et al. Two novel ATP2C1 mutations in patients with Hailey-Hailey disease and a literature review of sequence variants reported in the Chinese population. Genet Mol Res. 2015;14:19349–59.CrossRefPubMedGoogle Scholar
  37. 37.
    Thompson LD. Hailey-Hailey disease. Ear Nose Throat J. 2016;95:370.PubMedGoogle Scholar
  38. 38.
    Burge SM. Hailey–Hailey disease: the clinical features, response to treatment and prognosis. Br J Dermatol. 1992;126:275–82.CrossRefPubMedGoogle Scholar
  39. 39.
    D’Errico A, Bonciani D, Bonciolini V, et al. Hailey-Hailey disease treated with methotrexate. J Dermatol Case Rep. 2012;6:49–51.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Nanda KB, Saldanha CS, Jacintha M, et al. Hailey-Hailey disease responding to thalidomide. Indian J Dermatol. 2014;59:190–2.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Bertram F, Brocker EB, Zillikens D, et al. Prospective analysis of the incidence of autoimmune bullous disorders in Lower Franconia, Germany. J Dtsch Dermatol Ges. 2009;7:434–40.PubMedGoogle Scholar
  42. 42.
    Chan LS, Ahmed AR, Anhalt GJ, et al. The first international consensus on mucous membrane pemphigoid: definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators. Arch Dermatol. 2002;138:370–9.PubMedGoogle Scholar
  43. 43.
    Fleming TE, Korman NJ. Cicatricial pemphigoid. J Am Acad Dermatol. 2000;43:571–91.CrossRefPubMedGoogle Scholar
  44. 44.
    Queisi MM, Zein M, Lamba N, et al. Update on ocular cicatricial pemphigoid and emerging treatments. Surv Ophthalmol. 2016;61:314–7.CrossRefPubMedGoogle Scholar
  45. 45.
    Sobolewska B, Deuter C, Zierhut M. Current medical treatment of ocular mucous membrane pemphigoid. Ocul Surf. 2013;11:259–66.CrossRefPubMedGoogle Scholar
  46. 46.
    Wojnarowska F, Marsden R, Bhogal B, et al. Chronic bullous disease of childhood, childhood cicatricial pemphigoid, and linear IgA disease of adults: a comparative study demonstrating clinical and immunopathologic overlap. J Am Acad Dermatol. 1988;19:792–805.CrossRefPubMedGoogle Scholar
  47. 47.
    Fortuna G, Marinkovich MP. Linear immunoglobulin A bullous dermatosis. Clin Dermatol. 2012;30:38–50.CrossRefPubMedGoogle Scholar
  48. 48.
    Mahé A, Flageul B, Bobin P. Bullous IgA linear dermatosis of children in Mali. Ann Dermatol Venereol. 1996;123:544–8.PubMedGoogle Scholar
  49. 49.
    Kharfi M, Khaled A, Karaa A, et al. Linear IgA bullous dermatosis: the more frequent bullous dermatosis of children. Dermatol Online J. 2010;16(1):2.PubMedGoogle Scholar
  50. 50.
    Boccaletti V, Di Nuzzo S. Linear IgA bullous disease. N Engl J Med. 2014;370:2228.CrossRefPubMedGoogle Scholar
  51. 51.
    Guide SV, Marinkovich MP. Linear IgA bullous dermatosis. Clin Dermatol. 2001;19:719–27.CrossRefPubMedGoogle Scholar
  52. 52.
    Waldman MA, Black DR, Callen JP. Vancomycin-induced linear IgA bullous disease presenting as toxic epidermal necrolysis. Clin Exp Dermatol. 2004;29:633–6.CrossRefPubMedGoogle Scholar
  53. 53.
    Chen S, Mattei P, Fischer M, et al. Linear IgA bullous dermatosis. Eplasty. 2013;13:ic49.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Billet SE, Kortuem KR, Gibson LE, et al. A morbilliform variant of vancomycin-induced linear IgA bullous dermatosis. Arch Dermatol. 2008;144:774–8.CrossRefPubMedGoogle Scholar
  55. 55.
    Kenani N, Mebazaa A, Denguezli M, et al. Childhood linear IgA bullous dermatosis in Tunisia. Pediatr Dermatol. 2009;26:28–33.CrossRefPubMedGoogle Scholar
  56. 56.
    Passos L, Rabelo RF, Matsuo C, et al. Linear IgA/IgG bullous dermatosis: successful treatment with dapsone and mycophenolate mofetil. An Bras Dermatol. 2011;86:747–50.CrossRefPubMedGoogle Scholar
  57. 57.
    Cobo MF, Santi CG, Maruta CW, et al. Pemphigoid gestationis: clinical and laboratory evaluation. Dermatol Clin. 2009;64:1043–7.Google Scholar
  58. 58.
    Shornick JK, Bangert JL, Freeman RG, Gilliam JN. Herpes gestationis: clinical and histologic features of twenty-eight cases. J Am Acad Dermatol. 1983;8:214–24.CrossRefPubMedGoogle Scholar
  59. 59.
    Boudaya S, Turki H, Meziou TJ, et al. Pemphigoid gestationis: a study of 15 cases. J Gynecol Obstet Biol Reprod (Paris). 2003;32:30–4.Google Scholar
  60. 60.
    Al-Saif F, Elisa A, Al-Homidy A, et al. Retrospective analysis of pemphigoid gestationis in 32 Saudi patients—clinicopathological features and a literature review. J Reprod Immunol. 2016;116:42–5.CrossRefPubMedGoogle Scholar
  61. 61.
    Soutou B, Aractingi S. Skin disease in pregnancy. Best Pract Res Clin Obstet Gynaecol. 2015;29:732–40.CrossRefPubMedGoogle Scholar
  62. 62.
    Hallel-Halevy D, Nadelman C, Chen M, Woodley DT. Epidermolysis bullosa acquisita: update and review. Clin Dermatol. 2001;19:712–8.CrossRefPubMedGoogle Scholar
  63. 63.
    Gupta R, Woodley DT, Chen M. Epidermolysis bullosa acquisita. Clin Dermatol. 2012;30:60–9.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Zumelzu C, Le Roux-Villet C, Loiseau P, et al. Black patients of African descent and HLA-DRB1* 15:03 frequency overrepresented in epidermolysis bullosa acquisita. J Invest Dermatol. 2011;131:2386–93.CrossRefPubMedGoogle Scholar
  65. 65.
    Howard T, Brunner WC. Epidermolysis bullosa acquisita in an 18-year-old African-American male: a case report. S D Med. 2009;62:50–1.PubMedGoogle Scholar
  66. 66.
    Ishii N, Hamada T, Dainichi T, et al. Epidermolysis bullosa acquisita: what’s new? J Dermatol. 2010;37:220–30.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Anes Yang
    • 1
    Email author
  • Emily K. Kozera
    • 1
  • Dédée F. Murrell
    • 1
  1. 1.Department of DermatologySt. George Hospital, University of South WalesSydneyAustralia

Personalised recommendations