Russian Journal of Skin and Venereal DiseasesRussian Journal of Skin and Venereal Diseases1560-95882412-9097Eco-Vector3674810.17816/dv36748Research ArticleHEREDITARY BULLOUS EPIDERMOLYSIS. MODERN CONCEPTS OF ETIOLOGY AND PATHOGENESISAlbanovaV. Ialbanova@rambler.ruGolchenkoV. Aconfiance@bk.ruI.M.Sechenov First Moscow State Medical UniversityA.I. Evdokimov Moscow State Medical Stomatological University1504201316221072020Copyright © 2013, Eco-Vector2013This review of literature describes the modern concepts of the etiology and pathogenesis of hereditary bullous epidermolysis and its modern classification, discusses the molecular genetic, biochemical, and pathomorphological features of the disease, and presents the potentialities of diagnostic approaches. A total of 49 Russian and foreign publications are reviewed.hereditary bullous epidermolysisKindler’s syndromekeratin 5keratin 14laminin 332collagen-7plectinintegrin α6β4kindlinнаследственный буллезный эпидермолизсиндром Киндлеркератин 5кератин 14ламинин 332коллаген 7-го типаплектининтегрин α6β4киндлин 1[Fine J.-D., Hintner H. Life with Epidermolysis Bullosa (EB): etiology, diagnosis, multidisciplinary care and therapy. Wein: Springer-Verlag; 2009: 210—26.][Valle K.J., Bauer E.A. Enhanced biosynthesis of human skin collagenase in fibroblast cultures from recessive dystrophic epidermolysis bullosa. J. Clin. Invest. 1980; 66(2): 176—87.][Bauer E.A. Recessive dystrophic epidermolysis bullosa: evidence for an altered collagenase in fibroblast cultures. Proc. Natl. Acad. Sci. U. S. A. 1977; 74(10): 4646—50.][Stricklin G.P., Welgus H.G., Bauer E.A. Human skin collagenase in recessive dystrophic epidermolysis bullosa. J. Clin. Invest. 1982; 69(6): 1373—83.][Scheinfeld N. Phenytoin in cutaneous medicine: its uses, mechanisms and side effects. Dermatol. Online J. 2003; 9(3): 6.][Talas G., Adams T.S., Eastwood M., Rubio G., Brown R.A. Phenytoin reduces the contraction of recessive dystrophic epidermolysis bullosa fibroblast populated collagen gels. Int. J. Biochem. Cell Biol. 1997; 29(1): 261—70.][Fine J.D., Johnson L. Efficacy of systemic phenytoin in the treatment of junctional epidermolysis bullosa. Arch. Dermatol. 1988; 124(9): 1402—6.][Cooper T. W., Bauer E.A. Therapeutic efficacy of phenytoin in recessive dystrophic epidermolysis. A comparison of short- and long-term treatment. Arch. Dermatol. 1984; 120(4): 490—5.][Caldwell-Brown D., Stern R.S., Lin A.N., Carter D.M. Lack of efficacy of phenytoin in recessive dystrophic epidermolysis bullosa. Epidermolysis Bullosa Study Group. N. Engl. J. Med. 1992; 327(3): 163—7.][Weiner M., Stein A., Cash S., de Leoz J., Fine J.D. Tetracycline and epidermolysis bullosa simplex: a double-blind, placebo-controlled, crossover randomized clinical trial. Br. J. Dermatol. 2004; 150(3): 613—4.][Lara-Corrales I., Parkin P.C., Stephens D., Hamilton J., Koren G., Weinstein M., et al. The efficacy of trimethoprim in wound healing of patients with epidermolysis bullosa: a feasibility trial. J. Am. Acad. Dermatol. 2012; 66(2): 264—70.][Malkinson F.D., Retief C.R., Pearson R.W. Two familial cases of epidermolysis bullosa simplex successfully treated with tetracycline. Arch. Dermatol. 1999; 135(8): 997—8.][Veien N.K., Buus S.K. Treatment of epidermolysis bullosa simplex (EBS) with tetracycline. Arch. Dermatol. 2000; 136(3): 424—5.][Fine J.D., Eady R.A. Tetracycline and epidermolysis bullosa simplex: a new indication for one of the oldest and most widely used drugs in dermatology? Arch. Dermatol. 1999; 135(8): 981—2.][Pehr K., Forsey R.R. Why don’t we use vitamin E in dermatology? Canad. Med. Assoc. J. 1993; 149(9): 1247—53.][Shirakata Y., Shiraishi S., Sayama K., Shinmori H., Miki Y. High-dose tocopherol acetate therapy in epidermolysis bullosa siblings of the Cockayne-Touraine type. J. Dermatol. 1993; 20(11): 723—5.][Hintner H., Schuler G., Fritsch P. Epidermolysis bullosa acquisita: diagnosis by optic immunofluorescent demonstration ofjunctional antigens and vitamin E treatment. Hautarzt. 1982; 33(6): 310—4.][Альбанова В.И. Буллезный эпидермолиз: диагностика и лечение: Автореф. дис.. д-ра мед. наук. М.; 1993.][Kuvat S.V., Bozkurt M. Conservative treatment of a patient with epidermolysis bullosa presenting as bart syndrome: a case report. Case Report Med. 2010; 20(7): 302—5. doi: 10.1155/2010/302345.][Blanchet-Bardon C., Bohbot S. Using Urgotul dressing for the management of epidermolysis bullosa skin lesions. J. Wound Care. 2005; 14(10): 490—1, 494—6.][Rottman S.J., Glat P.M. The use of a biologic tissue matrix (IntegraTM bilayer matrix wound dressing) in the treatment of recessive dystrophic epidermolysis bullosa pseudosyndactyly deformity. Wounds. 2006; 18(11): 315—22.][Zaulyanov L., Kirsner R.S. A review of a bi-layered living cell treatment (Apligraf®) in the treatment of venous leg ulcers and diabetic foot ulcers. Clin Interv Aging. 2007; 2(1): 93—8.][Falabella A.F., Valencia I.C., Eaglstein W.H., Schachner L.A. Tissue-engineered skin (Apligraf) in the healing of patients with epidermolysis bullosa wounds. Arch. Dermatol. 2000; 136(10): 1225—30.][Falabella A.F., Schachner L.A., Valencia I.C., Eaglstein W.H. The use of tissue-engineered skin (Apligraf) to treat a newborn with epidermolysis bullosa. Arch. Dermatol. 1999; 135(10): 1219—22.][Fivenson D.P., Scherschun L., Choucair M., Kukuruga D., Young J., Shwayder T. Graftskin therapy in epidermolysis bullosa. J. Am. Acad. Dermatol. 2003; 48(6): 886—92.][Рахматуллин Р.Р., Бурлуцкая О.И., Адельшина Л.Р., Бурцева Т.И. Эффективность нового метода восстановления дефекта кожи у больного с врожденным буллезным эпидермолизом: клиническое наблюдение. Вопросы современной педиатрии. 2011; 2: 190—2.][Shin K.C., Park B.Y., Kim H.K., Kim W.S., Bae T.H. The use of cultured allogenic keratinocyte grafting in a patient with epidermolysis bullosa simplex. Ann. Dermatol. 2011; 23(3): 393—7.][Igoucheva O., Kelly A., Uitto J., Alexeev V. Protein therapeutics for Junctional Epidermolysis bullosa: incorporation of recombinant β3 chain into laminin 332 in β3 -/- keratinocytes in vitro. J. Invest. Dermatol. 2008; 128(6): 1476—86.][Remington J., Wang X., Hou Y., Lhou H., Burnett J., Muirhead T., et al. Injection of recombinant human type VII collagen corrects the disease phenotype in a murine model of dystrophic epidermolysis bullosa. Mol. Ther. 2009; 17(1): 26—33.][Kern J.S., Loeckermann S., Fritsch A., Hausser I., Roth W., Magin T.M., et al. Mechanisms of Fibroblast Cell Therapy for Dystrophic Epidermolysis Bullosa: High Stability of Collagen VII Favors Long-term Skin Integrity. Mol. Ther. 2009; 17(9): 1605—15.][Chen M., Kim G.H., Prakash L., Woodley T.D. Epidermolysis bullosa acquisita: autoimmunity to anchoring fibril collagen. Autoimmunity. 2012; 45(1): 91—101.][Ito K., Sawamura D., Goto M., Nakamura H., Nishie W., Sakai K., et al. Keratinocyte-/fibroblast-targeted rescue of Col7a1-disrupt-ed mice and generation of an exact dystrophic epidermolysis bullosa model using a human COL7A1 mutation. Am. J. Pathol. 2009; 175(6): 2508—17. doi: 10.2353/ajpath.2009.090347.][Cao T., Longley M.A., Wang X.J., Roop D.R. An Inducible Mouse Model for Epidermolysis Bullosa Simplex. J. Cell Biol. 2001; 152(3): 651—6.][Wally V., Brunner M., Lettner T., Wagner M., Koller U., Trost A., et al. K14 mRNA reprogramming for dominant epidermolysis bullosa simplex. Hum. Mol. Genet. 2010; 19(23): 4715—25.][Petek L.M., Fleckman P., Miller D.G. Efficient KRT 14 Targeting and Functional Characterization of Transplanted Human Keratinocytes for the Treatment of Epidermolysis Bullosa Simplex. Mol. Ther. 2010; 18(9): 1624—32.][Natsuga K., Sawamura D., Goto M., Homma E., Goto-Ohquchi Y., Aoyaqi S., et al. Response of intractable skin ulcers in recessive dystrophic epidermolysis bullosa patients to an allogeneic cultured dermal substitute. Acta Derm. Venereol. 2010; 90(2): 165—9.][Gache Y., Pin D., Gagnoux-Palacios L., Carozzo C., Menequzzi G. Correction of dog dystrophic epidermolysis bullosa by transplantation of genetically modified epidermal autografts. J. Invest. Dermatol. 2011; 131(10): 2069—78.][Titeux M., Pendaries V., Zanta-Boussif M.A., Decha A., Pironon N., Tonasso L., et al. SIN retroviral vectors expressing COL7A1 under human promoters for ex vivo gene therapy of recessive dystrophic epidermolysis bullosa. Mol. Ther. 2010; 18(8): 1509—18. doi: 10.1038/mt.2010.91.][Baldeschi C., Gache Y., Rattenholl A., Bouille P., Danos O., Ortonne J.P., et al. Genetic correction of canine dystrophic epi dermolysis bullosa mediated by retroviral vectors. Hum. Mol. Genet. 2003; 12(15): 1897—905.][Robbins P.B., Lin Q., Goodnough J.B., Hongsheng T., Xinjian C., Khavari P.A. In vivo restoration of laminin 5 β3 expression and function in junctional epidermolysis bullosa. Proc. Natl. Acad. Sci. USA. 2001; 98(9): 5193—8.][Gache Y., Baldeschi C., Del Rio M., Gaqnoux-Palacios L., Larcher F., Lacour J.P., et al. Construction of skin equivalents for gene therapy of recessive dystrophic epidermolysis bullosa. Hum. Gene Ther. 2004; 15(10): 921—33.][Ortiz-Urda S., Lin Q., Green C.L., Keene D.R., Marinkovich M.P., Khavari P.A. Injection of genetically engineered fibroblasts corrects regenerated human epidermolysis bullosa skin tissue. J. Clin. Invest. 2003; 111(2): 251—5.][Wong T., Gammon L., Liu L., Mellerio J.E., Dipping-Hepenstal P.J., Pacy J., et al. Potential of fibroblast cell therapy for recessive dystrophic epidermolysis bullosa. J. Invest. Dermatol. 2008; 128(9): 2179—89.][Tolar J., Ishida-Yamamoto A., Riddle M., McElmurry R.T., Osborn M., Xia L., et al. Amelioration of epidermolysis bullosa by transfer of wild-type bone marrow cells. Blood. 2009; 113(5): 1167—74.][Fujita Y., Abe R., Inokuma D., Hoshina D., Natsuqa K., Nishie W., et al. Bone marrow transplantation restores epidermal basement membrane protein expression and rescues epidermolysis bullosa model mice. Proc. Natl. Acad. Sci. USA. 2010; 107(32): 14345—50.][Wagner J.E., Ishida-Yamamoto A., McGrath J.A., Hordinsky M., Keene D.R., Woodley D.T., et al. Bone marrow transplantation for recessive dystrophic epidermolysis bullosa. N. Engl. J. Med. 2010; 363(7): 629—39.][Tamai K. Stem cell therapy for intractable skin diseases. Nihon. Rinsho. 2011; 69(12): 2167—71.][Itoh M., Kiuru M., Cairo M.S., Christiano A.M. Generation of keratinocytes from normal and recessive dystrophic epidermolysis bullosa-induced pluripotent stem cells. Proc. Natl. Acad. Sci. U. S. A. 2011; 108(21): 8797—802.][Tolar J., Xia L., Riddle M.J., Lees C.J., Eide C.R., McEmurry R.T., et al. Induced pluripotent stem cells from individuals with recessive dystrophic epidermolysis bullosa. J. Invest. Dermatol. 2011; 131(4): 848—56.]