Abstract
Elderly patients are more susceptible to the development of autoimmune blistering disorders such as bullous pemphigoid, mucous membrane pemphigoid, epidermolysis bullosa acquisita, and paraneoplastic pemphigus. This article focuses on the clinical aspects of the aforementioned autoimmune blistering diseases and highlights the important factors involved in treating elderly patients. It is essential for clinicians to offer individualized treatment plans for these patients to optimize outcomes, as elderly patients often have multiple co-morbidities, polypharmacy, and suboptimal socioeconomic status that can adversely influence adequate compliance.
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Farage MA, Miller KW, Berardesca E, Maibach HI. Clinical implications of aging skin: cutaneous disorders in the elderly. Am J Clin Dermatol. 2009;10(2):73–86.
Loo WJ, Burrows NP. Management of autoimmune skin disorders in the elderly. Drugs Aging. 2004;21(12):767–77.
Vodegel RM, Jonkman MF, Pas HH, de Jong MC. U-serrated immunodeposition pattern differentiates type VII collagen targeting bullous diseases from other subepidermal bullous autoimmune diseases. Br J Dermatol. 2004;151(1):112–8.
Gammon WR, Kowalewski C, Chorzelski TP, Kumar V, et al. Direct immunofluorescence studies of sodium chloride-separated skin in the differential diagnosis of bullous pemphigoid and epidermolysis bullosa acquisita. J Am Acad Dermatol. 1990;22(4):664–70.
Poot AM, Diercks GF, Kramer D, et al. Laboratory diagnosis of paraneoplastic pemphigus. Br J Dermatol. 2013;169(5):1016–24.
Borradori L, Murrell DF, Hall RP 3rd. Bullous pemphigoid (cutaneous pemphigoid): the spectrum of clinical presentations. In: Murrell DF, editor. Blistering diseases. Sydney: Springer, Inc.; 2015. p. 335–42.
Marazza G, Pham HC, Scharer L, et al. Incidence of bullous pemphigoid and pemphigus in Switzerland: a 2-year prospective study. Br J Dermatol. 2009;161(4):861–8.
Bertram F, Brocker EB, Zillikens D, Schmidt E. Prospective analysis of the incidence of autoimmune bullous disorders in Lower Franconia, Germany. J Dtsch Dermatol Ges. 2009;7(5):434–40.
Langan SM, Smeeth L, Hubbard R, et al. Bullous pemphigoid and pemphigus vulgaris-incidence and mortality in the UK: population based cohort study. BMJ. 2008;337:a180.
Jung M, Kippes W, Messer G, et al. Increased risk of bullous pemphigoid in male and very old patients: a population-based study on incidence. J Am Acad Dermatol. 1999;41(2 Pt 1):266–8.
Baican A, Baican C, Chiriac G, et al. Pemphigus vulgaris is the most common autoimmune bullous disease in northwestern Romania. Int J Dermatol. 2010;49(7):768–74.
Bernard P, Vaillant L, Labeille B, et al. Incidence and distribution of subepidermal autoimmune bullous skin diseases in three French regions: Bullous Diseases French Study Group. Arch Dermatol. 1995;131(1):48–52.
Joly P, Baricault S, Sparsa A, et al. Incidence and mortality of bullous pemphigoid in France. J Invest Dermatol. 2012;132:1998–2004.
Zillikens D, Wever S, Roth A, et al. Incidence of autoimmune subepidermal blistering dermatoses in a region of central Germany. Arch Dermatol. 1995;131(8):957–8.
Schmidt E, Borradori L, Joly P. Epidemiology of autoimmune bullous diseases. In: Murrell DF, editor. Blistering diseases. Sydney: Springer, Inc.; 2015. p. 687–94.
Gudi VS, White MI, Cruickshank N, et al. Annual incidence and mortality of bullous pemphigoid in the Grampian region of the north-east Scotland. Br J Dermatol. 2005;153(2):424–7.
Cortes B, Marazza G, Naldi L, et al. Mortality of bullous pemphigoid in Switzerland: a prospective study. Br J Dermatol. 2011;165(2):368–74.
Lever WF. Pemphigus. Medicine. 1953;32:1–123.
Rzany B, Partscht K, Jung M, et al. Risk factors for lethal outcome in patients with bullous pemphigoid: low serum albumin level, high dosage of glucocorticosteroids, and old age. Arch Dermatol. 2002;138(7):903–8.
Lamb PM, Abell E, Tharp M, et al. Prodromal bullous pemphigoid. Int J Dermatol. 2006;45:209–14.
Della Tore R, Combescure C, Cortes B, et al. Clinical presentations and diagnostic delay in bullous pemphigoid: a prospective nationwide cohort. Br J Dermatol. 2012;167:1111–7.
Borradori L, Joly P. Toward a practical renaming of bullous pemphigoid and all its variants: cutaneous pemphigoid. JAMA Dermatol. 2014;150(4):459.
Di Zenzo G, Thoma-Uszynski S, Fontao L, et al. Multicenter prospective study of the humoral autoimmune response in bullous pemphigoid. Clin Immunol. 2008;128:415–26.
Cordel N, Chosidow O, Hellot MF, et al. Risk factors for lethal outcome in patients with bullous pemphigoid. Dermatology. 2007;215(3):187–91.
Ogawa H, Sakuma M, Morioka S, et al. The incidence of internal malignancies in pemphigus and bullous pemphigoid in Japan. J Dermatol Sci. 1995;9(2):136–41.
Chen YJ, Wu CY, Lin MW, et al. Comorbidity profiles among patients with bullous pemphigoid: a nation-wide population-based study. Br J Dermatol. 2011;165(3):593–9.
Skandalis K, Spirova M, Gaitanis G, et al. Drug-induced bullous pemphigoid in diabetes mellitus patients receiving dipeptidyl peptidase-IV inhibitors plus metformin. J Eur Acad Dermatol Venereol. 2012;26(2):249–53.
Pasmatzi E, Monastirli A, Habeos J, et al. Dipeptidyl peptidase-4 inhibitors cause bullous pemphigoid in diabetic patients: report of two cases. Diabetes Care. 2011;34(8):e133.
Aouidad I, Fite C, Marinho E, et al. A case report of bullous pemphigoid induced by dipeptidyl peptidase-4 inhibitors. JAMA Dermatol. 2013;149(2):243–5.
Attaway A, Mersfelder TL, Vaishnav S, Baker JK. Bullous pemphigoid associated with dipeptidyl peptidase IV inhibitors: a case report and review of literature. J Dermatol Case Rep. 2014;8(1):24–8.
Ramirez-Quizon MN, Borradori L, Hall RP 3rd, Murrell DF. Management of bullous pemphigoid. In: Murrell DF, editor. Blistering diseases. Sydney: Springer, Inc.; 2015. p. 543–63.
Joly P, Roujeau JC, Benichou J, et al. A comparison of oral and topical corticosteroids in patients with bullous pemphigoid. N Engl J Med. 2002;346(5):321–7.
Joly P, Roujeau JC, Benichou J, et al. A comparison of two regimens of topical corticosteroids in the treatment of patients with bullous pemphigoid: a multicentre randomized study. J Invest Dermatol. 2009;129(7):1681–7.
Frew JW, Murrell DF. Corticosteroid use in autoimmune blistering diseases. Immunol Allergy Clin N Am. 2012;32(2):283–94.
Kirtschig G, Middleton P, Bennett C, et al. Interventions for bullous pemphigoid. Cochrane Database Syst Rev. 2010;10:CD002292.
Morel P, Guillaume JC. Treatment of bullous pemphigoid with prednisolone only: 0.75 mg/kg/day versus 1.25 mg/kg/day. A multicentre randomized study. Ann Dermatol Venereol. 1984;111(10):925–8.
Liu D, Ahmet A, Ward L, et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol. 2013;9(1):30.
Fivenson DP, Breneman DL, Rosen GB, et al. Nicotinamide and tetracycline therapy of bullous pemphigoid. Arch Dermatol. 1994;130(6):753–8.
Chalmers JR, Wojnarowska F, Kirtschig G, BLISTER study group, et al. A randomized controlled trial to compare the safety and effectiveness of doxycycline (200 mg daily) with oral prednisolone (0.5 mg kg(−1) daily) for initial treatment of bullous pemphigoid: a protocol for the Bullous Pemphigoid Steroids and Tetracyclines (BLISTER) Trial. Br J Dermatol. 2015;173(1):227–34.
Czernik A, Toosi S, Bystryn JC, Grando SA. Intravenous immunoglobulin in the treatment of autoimmune bullous dermatoses: an update. Autoimmunity. 2012;45(1):111–8.
Ammann EM, Haskins CB, Fillman KM, et al. Intravenous immune globulin and thromboembolic adverse events: a systematic review and meta-analysis of RCTs. Am J Hematol. 2016;91(6):594–605.
Lourari S, Herve C, Doffoel-Hantz V, et al. Bullous and mucous membrane pemphigoid show a mixed response to rituximab: experience in seven patients. J Am Acad Dermatol. 2011;64(4):773–8.
Kasperkiewicz M, Shimanovich I, Ludwig RJ, et al. Rituximab for treatment-refractory pemphigus and pemphigoid: a case series of 17 patients. J Am Acad Dermatol. 2011;65(3):552–8.
London VA, Kim GH, Fairley JA, Woodley DT. Successful treatment of bullous pemphigoid with omalizumab. Arch Dermatol. 2012;148(11):1241–3.
Yu KK, Crew AB, Messingham KA, et al. Omalizumab therapy for bullous pemphigoid. J Am Acad Dermatol. 2014;71(3):468–74.
Rashid KA, Gürcan HM, Ahmed AR. Antigen specificity in subsets of mucous membrane pemphigoid. J Invest Dermatol. 2006;126(12):2631–6.
Xu HH, Werth VP, Parisi E, Sollecito TP. Mucous membrane pemphigoid. Dent Clin N Am. 2013;57:611–30.
Scully C, Carrozzo M, Gandolfo S, et al. Update on mucous membrane pemphigoid: a heterogenous immune-mediated subepithelial blistering entity. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999;88:56–68.
Egan CA, Lazarova Z, Darling TN, et al. Anti-epiligrin cicatricial pemphigoid: clinical findings, immunopathogenesis, and significant associations. Medicine. 2003;82(3):177–86.
Egan CA, Lazarova Z, Darling TN, et al. Anti-epiligrin cicatricial pemphigoid and relative risk for cancer. Lancet. 2001;357(9271):1850–1.
Matsushima S, Horiguchi Y, Honda T, et al. A case of anti-epiligrin cicatricial pemphigoid associated with lung carcinoma and severe laryngeal stenosis: review of Japanese cases and evaluation of risk for internal malignancy. J Dermatol. 2004;31(1):10–5.
Bernard P, Antonicelli F, Bedane C, et al. Prevalence and clinical significance of anti-laminin 332 autoantibodies detected by a novel enzyme-linked immunosorbent assay in mucous membrane pemphigoid. JAMA Dermatol. 2013;149(5):533–40.
Bruch-Gerharz D, Hertl M, Ruzicka T. Mucous membrane pemphigoid: clinical aspects, immunopathological features and therapy. Eur J Dermatol. 2007;17(3):191–200.
Caux F, Prost-Squarcioni C. Mucous membrane pemphigoid. In: Murrell DF, editor. Blistering diseases. Sydney: Springer, Inc.; 2015. p. 363–73.
Kirzhner M, Jakobiec FA. Ocular cicatricial pemphigoid: a review of clinical features, immunopathology, differential diagnosis, and current management. Semin Ophthalmol. 2011;26(4–5):270–7.
Alexandre M, Brette MD, Pascal F, et al. A prospective study of upper aerodigestive tract manifestations of mucous membrane pemphigoid. Medicine. 2006;85(4):239–52.
Fueston JC, Adams BB, Mutasim DF. Cicatricial pemphigoid-induced phimosis. J Am Acad Dermatol. 2001;46(5 Suppl):S128–9.
Kurzhals G, Stolz W, Meurer M, et al. Acquired epidermolysis bullosa with the clinical feature of Brunsting-Perry cicatricial bullous pemphigoid. Arch Dermatol. 1991;127:391–5.
Yancey KB. Cicatricial pemphigoid. In: Fitzpatrick TB, Eisen AZ, Wolff K, et al., editors. Dermatology in general medicine. New York: McGraw-Hill; 1998. p. 674–9.
Gupta R, Woodley DT, Chen M. Epidermolysis bullosa acquisita. Clin Dermatol. 2012;30(1):60–9.
Caux F, Prost-Squarcioni C. Mucous membrane pemphigoid. In: Murrell DF, editor. Blistering diseases. Sydney: Springer, Inc.; 2015. p. 565–71.
Lee HY, Blazek C, Beltraminelli H, Borradori L. Oral mucous membrane pemphigoid: complete response to topical tacrolimus. Acta Derm Venereol. 2011;91(5):604–5.
Foster CS. Cicatricial pemphigoid. Trans Am Ophthalmol Soc. 1986;84:527–663.
Carrozzo M, Arduino P, Bertolusso G, et al. Systemic minocycline as a therapeutic option in predominantly oral mucous membrane pemphigoid: a cautionary report. Int J Oral Maxillofac Surg. 2009;38(10):1071–6.
Musette P, Pascal F, Hoang-Xuan TM, et al. Treatment of cicatricial pemphigoid with pulse intravenous cyclophosphamide. Arch Dermatol. 2001;137(1):101–2.
Munyangango EM, Le Roux-Villet C, Doan S, et al. Oral cyclophosphamide without corticosteroids to treat mucous membrane pemphigoid. Br J Dermatol. 2013;168(2):381–90.
Sacher C, Rubbert A, Konig C, et al. Treatment of recalcitrant pemphigoid with the tumor necrosis factor alpha antagonist etanercept. J Am Acad Dermatol. 2002;46(1):113–5.
Canizares MJ, Smith DI, Conners MS, et al. Successful treatment of mucous membrane pemphigoid with etanercept in 3 patients. Arch Dermatol. 2006;142(11):1457–61.
Kennedy JS, Devillez RL, Henning JS. Recalcitrant cicatricial pemphigoid treated with the anti-TFF-alpha agent etanercept. J Drugs Dermatol. 2010;9(1):68–70.
John H, Wahllet A, Quinlan M. Successful biologic treatment of ocular mucous membrane pemphigoid with anti-TNF-alpha. Eye (Lond). 2007;21(11):1434–5.
Prey S, Robert PY, Quinlan M. Treatment of ocular cicatricial pemphigoid with the tumour necrosis factor alpha antagonist etanercept. Acta Derm Venereol. 2007;87(1):74–5.
Le Roux-Villet C, Prost-Squarcioni C, Alexandre M, et al. Rituximab for patients with refractory mucous membrane pemphigoid. Arch Dermatol. 2011;147(7):843–9.
Shetty S, Ahmed AR. Critical analysis of the use of rituximab in mucous membrane pemphigoid: a review of the literature. J Am Acad Dermatol. 2013;68:499–506.
Daniel E, Thorne JE, Newcomb CW, et al. Mycophenolate mofetil for ocular inflammation. Am J Ophthalmol. 2010;149(3):423–32.
Letko E, Miserocchi E, Daoud YJ, et al. A nonrandomized comparison of the clinical outcome of ocular involvement in patients with mucous membrane (cicatricial) pemphigoid between conventional immunosuppressive and intravenous immunoglobulin therapies. Clin Immunol. 2004;111(3):303–10.
Kim JH, Kim YH, Kim SC. Epidermolysis bullosa acquisita: a retrospective clinical analysis of 30 cases. Acta Derm Venereol. 2011;91(3):307–12.
Prost-Squarcioni C, Caux F. Epidermolysis bullosa acquisita. In: Murrell DF, editor. Blistering diseases. Sydney: Springer, Inc.; 2015. p. 405–12.
Roenigk HH, Ryan JG, Bergfeld WF. Epidermolysis bullosa acquisita: report of three cases and review of all published cases. Arch Dermatol. 1971;103:1–10.
Jappe U, Zillikens D, Bonnekoh B, Gollnick H. Epidermolysis bullosa acquisita with ultraviolet radiation sensitivity. Br J Dermatol. 2000;142:517–20.
Kubo A, Hashimoto K, Inoue C, et al. Epidermolysis bullosa acquisita exacerbated by systemic estrogen and progesterone treatment and pregnancy. J Am Acad Dermatol. 1997;36:792–4.
Aprey CJ, Elewski BE, Moritz DK, Gammon WR. Childhood epidermolysis bullosa acquisita. J Am Acad Dermatol. 1991;24:706–14.
Callot-Mellot C, Bodemer C, Caux F, et al. Epidermolysis bullosa acquisita in childhood. Arch Dermatol. 1997;133:1122–6.
Berbis P, Privat Y. Value of colchicine in treating acquired epidermolysis bullosa. Ann Dermatol Venereol. 1989;116:301–7.
Cunningham BB, Kirchmann TT, Woodley D. Colchicine for epidermolysis bullosa acquisita. J Am Acad Dermatol. 1996;34:781–4.
Burger J, Gmur J, Bruckner-Tuderman L. Epidermolysis bullosa acquisita, a rare late complication of allogenic bone marrow transplantation? Bone Marrow Transplant. 1992;9:139–41.
Connolly SM, Sander HM. Treatment of epidermolysis bullosa acquisita with cyclosporine. J Am Acad Dermatol. 1987;16:890.
Maize JC Jr, Cohen JB. Cyclosporine controls epidermolysis bullosa acquisita co-occurring with acquired factor VIII deficiency. Int J Dermatol. 2005;44:692–4.
Prost-Squarcioni C, Caux F. Epidermolysis bullosa acquisita. In: Murrell DF, editor. Blistering diseases. Sydney: Springer, Inc.; 2015. p. 579–87.
Le Roux-Villet C, Prost-Squarcioni C. Epidermolysis bullosa acquisita: literature review. Ann Dermatol Venereol. 2011;138:228–46.
Ahmed AR, Gurcan HM. Treatment of epidermolysis bullosa acquisita with intravenous immunoglobulin in patients non-responsive to conventional therapy: clinical outcome and post-treatment long-term follow up. J Eur Acad Dermatol Venereol. 2012;26:1074–83.
Kofler H, Wambacher-Gasser B, Topar G, et al. Intravenous immunoglobulin treatment in therapy-resistant epidermolysis bullosa acquisita. J Am Acad Dermatol. 1997;36:331–5.
Nguyen VT, Ndoye A, Bassler KD, et al. Classification, clinical manifestations, and immunopathological mechanisms of the epithelial variant of paraneoplastic autoimmune multiorgan syndrome: a reappraisal of paraneoplastic pemphigus. Arch Dermatol. 2001;137(2):193–206.
Zimmermann J, Bahmer F, Rose C, et al. Clinical and immunopathological spectrum of paraneoplastic pemphigus. J Dtsch Dermatol Ges. 2010;8(8):598–605.
Leger S, Picard D, Ingen-Housz-Oro S, et al. Prognostic factors of paraneoplastic pemphigus. Arch Dermatol. 2012;148(10):1165–72.
Joly P, Richard C, Gilbert D, et al. Sensitivity and specificity of clinical, histologic, and immunologic features in the diagnosis of paraneoplastic pemphigus. J Am Acad Dermatol. 2000;43(4):619–26.
Anhalt GJ. Paraneoplastic pemphigus. Adv Dermatol. 1997;12:77–96 (discussion 7).
Ohyama M, Amagai M, Hashimoto T, et al. Clinical phenotype and anti-desmoglein autoantibody profile in paraneoplastic pemphigus. J Am Acad Dermatol. 2001;44(4):593–8.
Yong AA, Tey HL. Paraneoplastic pemphigus. Australas J Dermatol. 2013;54(4):241–50.
Nguyen VT, Ndoye A, Bassler KD, et al. Classification, clinical manifestations, and immunopathological mechanisms of the epithelial variant of paraneoplastic autoimmune multiorgan syndrome: a reappraisal of paraneoplastic pemphigus. Arch Dermatol. 2001;137:193–206.
Maldonado F, Pittelkow MR, Ryu JH. Constructive bronchiolitis associated with paraneoplastic autoimmune multi-organ syndrome. Respirology. 2009;14:129–33.
Nikolskaia OV, Nousari CH, Anhalt GJ. Paraneoplastic pemphigus in association with Castleman’s disease. Br J Dermatol. 2003;149:1143–51.
Zhang J, Qiao QL, Chen XX, et al. Improved outcomes after complete resection of underlying tumors for patients with paraneoplastic pemphigus: a single-center experience of 22 cases. J Cancer Res Clin Oncol. 2011;137:229–34.
Nousari HC, Deterding R, Wojtczack H, et al. The mechanism of respiratory failure in panaeoplastic pemphigus. N Engl J Med. 1999;340(18):1406–10.
Cervini AB, Tosi V, Kim SH, et al. Paraneoplastic pemphjigus or paraneoplastic autoimmune multiorgan syndrome: report of 2 cases in children and review of the literature. Actas Dermosifiliogr. 2010;101:879–86.
Borradori L, Lombardi T, Samson J, et al. Anti-CD20 monoclonal antibody (rituximab) for refractory erosive stomatitis secondary to CD20 (+) follicular lymphoma-associated paraneoplastic pemphigus. Arch Dermatol. 2001;157:269–72.
Hertl M, Zillikens D, Borradori L, et al. Recommendations for the use of rituximab (anti-CD20 antibody) in the treatment of autoimmune bullous skin disease. J Dtsch Dermatol Ges. 2008;6:366–73.
Hohwy T, Bang K, Steiniche T, et al. Alemtuzumab-induced remission of both severe paraneoplastic pemphigus and leukaemic bone marrow infiltration in a case of treatment resistant B-cell chronic lymphocytic leukaemia. Eur J Haematol. 2004;75:206–9.
Borradori L, Bernard P. Pemphigoid group. In: Bolognia JL, Jorizzo JL, Schaffer JV, editors. Dermatology. 3rd ed. New York: Elsevier; 2012. p. 431–45.
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Minhee Kim, Luca Borradori, and Dédée F. Murrell have no conflicts of interest.
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Kim, M., Borradori, L. & Murrell, D.F. Autoimmune Blistering Diseases in the Elderly: Clinical Presentations and Management. Drugs Aging 33, 711–723 (2016). https://doi.org/10.1007/s40266-016-0402-1
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DOI: https://doi.org/10.1007/s40266-016-0402-1