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Inpatient Management of Autoimmune Blistering Diseases: an Update, Review, and Practical Guide

  • Anne L. MaranoEmail author
  • Adela R. Cardones
  • Russell P. HallIII
Hospital- based Dermatology (L Guggina and A Zhou, Section Editors)
  • 14 Downloads
Part of the following topical collections:
  1. Topical Collection on Hospital-based Dermatology

Abstract

Purpose of Review

Review the evaluation, management, and treatment of hospitalized autoimmune blistering diseases (AIBD) patients based on the current literature and expert opinion.

Recent Findings

The cost and prevalence of hospitalization for AIBD patients are increasing in the USA. Many factors associated with hospitalization of AIBD patients are related to patient access to dermatology care. Infections are a major cause for hospital admission among AIBD patients. The use of rituximab, especially early in the disease course, has transformed the outcomes among patients with pemphigus.

Summary

After reading this review, dermatologists should be more familiar with the inpatient AIBD clinical evaluation, including the medical history, physical examination, and laboratory work-up; the management of complications of AIBD and therapy; and the treatment ladder for selecting a steroid-sparing therapy for AIBD patients.

Keywords

Autoimmune blistering disease Pemphigus Pemphigoid Inpatient dermatology 

Notes

Compliance with Ethical Standards

Conflict of Interest

Dr. Russell Hall III was on the Data Safety Monitoring Board for Roche-Genentech. He also received grants and was a consultant for the following entities: Principia, Syntimmune, Cabelletta Inc., and the National Institutes of Health.

Anne Marano performed an industry sponsored clinical trial at Viela Bio for cutaneous lupus.

Adela Cardones declares no conflicts of interest.

Human and Animal Rights

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and compiled with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Carson PJ, Hameed A, Ahmed AR. Influence of treatment on the clinical course of pemphigus vulgaris. J Am Acad Dermatol. 1996;34(4):645–52.CrossRefGoogle Scholar
  2. 2.
    Risser J, Lewis K, Weinstock MA. Mortality of bullous skin disorders from 1979 through 2002 in the United States. Arch Dermatol. 2009;145(9):1005–8.  https://doi.org/10.1001/archdermatol.2009.205.CrossRefGoogle Scholar
  3. 3.
    • Ren Z, Hsu DY, Brieva J, Silverberg NB, Langan SM, Silverberg JI. Hospitalization, inpatient burden and comorbidities associated with bullous pemphigoid in the U.S.A. Br J Dermatol. 2017;176(1):87–99.  https://doi.org/10.1111/bjd.14821 Demonstrates that the incidence of pemphigoid hospitalization in the United States is increasing.CrossRefGoogle Scholar
  4. 4.
    • Hsu D, Brieva J, Silverberg JI. Costs of care for hospitalization for pemphigus in the United States. JAMA Dermatology. 2016;152(6):645–54.  https://doi.org/10.1001/jamadermatol.2015.5240 Demonstrates that the cost of care and incidence of pemphigus hospitalization in the United States are increasing.CrossRefGoogle Scholar
  5. 5.
    Langan SM, Smeeth L, Hubbard R, Fleming KM, Smith CJ, West J. Bullous pemphigoid and pemphigus vulgaris--incidence and mortality in the UK: population based cohort study. BMJ (Clinical research ed). 2008;(337):a180.  https://doi.org/10.1136/bmj.a180.
  6. 6.
    Brick KE, Weaver CH, Lohse CM, Pittelkow MR, Lehman JS, Camilleri MJ, et al. Incidence of bullous pemphigoid and mortality of patients with bullous pemphigoid in Olmsted County, Minnesota, 1960 through 2009. J Am Acad Dermatol. 2014;71(1):92–9.  https://doi.org/10.1016/j.jaad.2014.02.030.CrossRefGoogle Scholar
  7. 7.
    • Hsu DY, Brieva J, Sinha AA, Langan SM, Silverberg JI. Comorbidities and inpatient mortality for pemphigus in the U.S.A. Br J Dermatol. 2016;174(6):1290–8.  https://doi.org/10.1111/bjd.14463 Many complications resulting in hospitalization for AIBD patients are infection-related or related to therapy and other medical co-morbidities. The diagnosis of pemphigus increases hospital mortality compared to the general population.CrossRefGoogle Scholar
  8. 8.
    Cardones AR, Hall RP 3rd. Cost of inpatient care of patients with pemphigus in the United States: translating dollars and cents into improved patient care. JAMA dermatology. 2016;152(6):629–30.  https://doi.org/10.1001/jamadermatol.2015.5241.CrossRefGoogle Scholar
  9. 9.
    Harman KE, Brown D, Exton LS, Groves RW, Hampton PJ, Mohd Mustapa MF, et al. British Association of Dermatologists’ guidelines for the management of pemphigus vulgaris 2017. Br J Dermatol. 2017;177(5):1170–201.  https://doi.org/10.1111/bjd.15930.CrossRefGoogle Scholar
  10. 10.
    Chan LS, Ahmed AR, Anhalt GJ, Bernauer W, Cooper KD, Elder MJ, et al. The first international consensus on mucous membrane pemphigoid: definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators. Arch Dermatol. 2002;138(3):370–9.Google Scholar
  11. 11.
    Wojnarowska F, Kirtschig G, Highet AS, Venning VA, Khumalo NP. Guidelines for the management of bullous pemphigoid. Br J Dermatol. 2002;147(2):214–21.CrossRefGoogle Scholar
  12. 12.
    Gogia PP. Physical therapy modalities for wound management. Ostomy Wound Manage. 1996;42(1):46 -8, 50-2, 4.Google Scholar
  13. 13.
    Tao H, Butler JP, Luttrell T. The role of whirlpool in wound care. J AM COLL CLIN WOUND SPEC. 2012;4(1):7–12.  https://doi.org/10.1016/j.jccw.2013.01.002.CrossRefGoogle Scholar
  14. 14.
    • Ren Z, Narla S, Hsu DY, Silverberg JI. Association of serious infections with pemphigus and pemphigoid: analysis of the nationwide inpatient sample. J Eur Acad Dermatol Venereol. 2018;32(10):1768–76.  https://doi.org/10.1111/jdv.14961 Many complications resulting in hospitalization for AIBD patients are infection-related.CrossRefGoogle Scholar
  15. 15.
    Kwa MC, Silverberg JI. Association between inflammatory skin disease and cardiovascular and cerebrovascular co-morbidities in US adults: analysis of nationwide inpatient sample data. Am J Clin Dermatol. 2017;18(6):813–23.  https://doi.org/10.1007/s40257-017-0293-x.CrossRefGoogle Scholar
  16. 16.
    Tran KD, Wolverton JE, Soter NA. Methotrexate in the treatment of pemphigus vulgaris: experience in 23 patients. Br J Dermatol. 2013;169(4):916–21.  https://doi.org/10.1111/bjd.12474.CrossRefGoogle Scholar
  17. 17.
    Smith TJ, Bystryn JC. Methotrexate as an adjuvant treatment for pemphigus vulgaris. Arch Dermatol. 1999;135(10):1275–6.CrossRefGoogle Scholar
  18. 18.
    Du-Thanh A, Merlet S, Maillard H, Bernard P, Joly P, Esteve E, et al. Combined treatment with low-dose methotrexate and initial short-term superpotent topical steroids in bullous pemphigoid: an open, multicentre, retrospective study. Br J Dermatol. 2011;165(6):1337–43.  https://doi.org/10.1111/j.1365-2133.2011.10531.x.CrossRefGoogle Scholar
  19. 19.
    Dereure O, Bessis D, Guillot B, Guilhou JJ. Treatment of bullous pemphigoid by low-dose methotrexate associated with short-term potent topical steroids: an open prospective study of 18 cases. Arch Dermatol. 2002;138(9):1255–6.CrossRefGoogle Scholar
  20. 20.
    Bara C, Maillard H, Briand N, Celerier P. Methotrexate for bullous pemphigoid: preliminary study. Arch Dermatol. 2003;139(11):1506–7.  https://doi.org/10.1001/archderm.139.11.1506-b.CrossRefGoogle Scholar
  21. 21.
    Olszewska M, Kolacinska-Strasz Z, Sulej J, Labecka H, Cwikla J, Natorska U, et al. Efficacy and safety of cyclophosphamide, azathioprine, and cyclosporine (ciclosporin) as adjuvant drugs in pemphigus vulgaris. Am J Clin Dermatol. 2007;8(2):85–92.  https://doi.org/10.2165/00128071-200708020-00004.CrossRefGoogle Scholar
  22. 22.
    Huilaja L, Makikallio K, Hannula-Jouppi K, Vakeva L, Hook-Nikanne J, Tasanen K. Cyclosporine treatment in severe gestational pemphigoid. Acta Derm Venereol. 2015;95(5):593–5.  https://doi.org/10.2340/00015555-2032.CrossRefGoogle Scholar
  23. 23.
    Williams HC, Wojnarowska F, Kirtschig G, Mason J, Godec TR, Schmidt E, et al. Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomised controlled trial. Lancet (London, England). 2017;389(10079):1630–8.  https://doi.org/10.1016/s0140-6736(17)30560-3.CrossRefGoogle Scholar
  24. 24.
    Hornschuh B, Hamm H, Wever S, Hashimoto T, Schroder U, Brocker EB, et al. Treatment of 16 patients with bullous pemphigoid with oral tetracycline and niacinamide and topical clobetasol. J Am Acad Dermatol. 1997;36(1):101–3.CrossRefGoogle Scholar
  25. 25.
    Werth VP, Fivenson D, Pandya AG, Chen D, Rico MJ, Albrecht J, et al. Multicenter randomized, double-blind, placebo-controlled, clinical trial of dapsone as a glucocorticoid-sparing agent in maintenance-phase pemphigus vulgaris. Arch Dermatol. 2008;144(1):25–32.  https://doi.org/10.1001/archderm.144.1.25.CrossRefGoogle Scholar
  26. 26.
    Cunningham BB, Kirchmann TT, Woodley D. Colchicine for epidermolysis bullosa acquisita. J Am Acad Dermatol. 1996;34(5 Pt 1):781–4.CrossRefGoogle Scholar
  27. 27.
    Joly P, Roujeau JC, Benichou J, Picard C, Dreno B, Delaporte E, et al. A comparison of oral and topical corticosteroids in patients with bullous pemphigoid. N Engl J Med. 2002;346(5):321–7.  https://doi.org/10.1056/NEJMoa011592.CrossRefGoogle Scholar
  28. 28.
    Hooten J, Hall R 3rd, Cardones A. Updates on the management of autoimmune blistering diseases. Skin Therapy Lett. 2014;19(5):1–6.Google Scholar
  29. 29.
    Morel P, Guillaume JC. Treatment of bullous pemphigoid with prednisolone only: 0.75 mg/kg/day versus 1.25 mg/kg/day. A multicenter randomized study. Ann Dermatol Venereol. 1984;111(10):925–8.Google Scholar
  30. 30.
    Kirtschig G, Middleton P, Bennett C, Murrell DF, Wojnarowska F, Khumalo NP. Interventions for bullous pemphigoid. Cochrane Database Syst Rev. 2010;(10):Cd002292.  https://doi.org/10.1002/14651858.CD002292.pub3.
  31. 31.
    Chryssomallis F, Dimitriades A, Chaidemenos GC, Panagiotides D, Karakatsanis G. Steroid-pulse therapy in pemphigus vulgaris long term follow-up. Int J Dermatol. 1995;34(6):438–42.CrossRefGoogle Scholar
  32. 32.
    Werth VP. Treatment of pemphigus vulgaris with brief, high-dose intravenous glucocorticoids. Arch Dermatol. 1996;132(12):1435–9.CrossRefGoogle Scholar
  33. 33.
    Siegel J, Eaglstein WH. High-dose methylprednisolone in the treatment of bullous pemphigoid. Arch Dermatol. 1984;120(9):1157–65.CrossRefGoogle Scholar
  34. 34.
    Wolverton S, editor. Comprehensive dermatologic drug therapy. 3rd ed. Edinburgh: Saunders/Elsevier; 2013.Google Scholar
  35. 35.
    Amber KT, Lamberts A, Solimani F, Agnoletti AF, Didona D, Euverman I, et al. Determining the incidence of pneumocystis pneumonia in patients with autoimmune blistering diseases not receiving routine prophylaxis. JAMA dermatology. 2017;153(11):1137–41.  https://doi.org/10.1001/jamadermatol.2017.2808.CrossRefGoogle Scholar
  36. 36.
    Notaro E, Fett N, Shinohara MM. Assessment of risk and use of prophylaxis for glucocorticoidinduced-osteoporosis among dermatologists in the Pacific Northwest: a survey study. Dermatology online journal. 2017;23(9).Google Scholar
  37. 37.
    Buckley L, Guyatt G, Fink HA, Cannon M, Grossman J, Hansen KE, et al. 2017 American College of Rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res (Hoboken). 2017;69(8):1095–110.  https://doi.org/10.1002/acr.23279.CrossRefGoogle Scholar
  38. 38.
    • Murrell DF, Pena S, Joly P, Marinovic B, Hashimoto T, Diaz LA, et al. Diagnosis and management of pemphigus: recommendations by an international panel of experts. J Am Acad Dermatol. 2018.  https://doi.org/10.1016/j.jaad.2018.02.021 Provides an expert consensus on treatment recommendations for pemphigus, including that rituximab should be considered first-line therapy in moderate to severe pemphgius.
  39. 39.
    • Joly P, Maho-Vaillant M, Prost-Squarcioni C, Hebert V, Houivet E, Calbo S, et al. First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial. Lancet (London, England). 2017;389(10083):2031–40.  https://doi.org/10.1016/s0140-6736(17)30070-3 The use of rituximab, particularly early in the disease course of pemphigus, has revolutionized the management of pemphigus in recent years and is more effective than use of prednisone alone.CrossRefGoogle Scholar
  40. 40.
    • Agarwal A, Hall RP 3rd, Banez LL, Cardones AR. Comparison of rituximab and conventional adjuvant therapy for pemphigus vulgaris: a retrospective analysis. PloS one. 2018;13(9):e0198074.  https://doi.org/10.1371/journal.pone.0198074 The use of rituximab, particularly early in the disease course of pemphigus, has revolutionized the management of pemphigus in recent years and results in decreased prednisone dosing.CrossRefGoogle Scholar
  41. 41.
    Palazzo E, Yahia SA. Progressive multifocal leukoencephalopathy in autoimmune diseases. Joint Bone Spine. 2012;79(4):351–5.  https://doi.org/10.1016/j.jbspin.2011.11.002.CrossRefGoogle Scholar
  42. 42.
    Esmaili N, Chams-Davatchi C, Valikhani M, Farshidfar F, Parvaneh N, Tamizifar B. Treatment of pemphigus vulgaris with mycophenolate mofetil as a steroid-sparing agent. Eur J Dermatol. 2008;18(2):159–64.  https://doi.org/10.1684/ejd.2008.0354.Google Scholar
  43. 43.
    Eskin-Schwartz M, David M, Mimouni D. Mycophenolate mofetil for the management of autoimmune bullous diseases. Dermatol Clin. 2011;29(4):555–9.  https://doi.org/10.1016/j.det.2011.06.012.CrossRefGoogle Scholar
  44. 44.
    Beissert S, Mimouni D, Kanwar AJ, Solomons N, Kalia V, Anhalt GJ. Treating pemphigus vulgaris with prednisone and mycophenolate mofetil: a multicenter, randomized, placebo-controlled trial. J Investig Dermatol. 2010;130(8):2041–8.  https://doi.org/10.1038/jid.2010.91.CrossRefGoogle Scholar
  45. 45.
    Beissert S, Werfel T, Frieling U, Bohm M, Sticherling M, Stadler R, et al. A comparison of oral methylprednisolone plus azathioprine or mycophenolate mofetil for the treatment of bullous pemphigoid. Arch Dermatol. 2007;143(12):1536–42.  https://doi.org/10.1001/archderm.143.12.1536.CrossRefGoogle Scholar
  46. 46.
    Orvis AK, Wesson SK, Breza TS Jr, Church AA, Mitchell CL, Watkins SW. Mycophenolate mofetil in dermatology. J Am Acad Dermatol. 2009;60(2):183–99; quiz 200-2.  https://doi.org/10.1016/j.jaad.2008.08.049.CrossRefGoogle Scholar
  47. 47.
    Chams-Davatchi C, Esmaili N, Daneshpazhooh M, Valikhani M, Balighi K, Hallaji Z, et al. Randomized controlled open-label trial of four treatment regimens for pemphigus vulgaris. J Am Acad Dermatol. 2007;57(4):622–8.  https://doi.org/10.1016/j.jaad.2007.05.024.CrossRefGoogle Scholar
  48. 48.
    Meggitt SJ, Anstey AV, Mohd Mustapa MF, Reynolds NJ, Wakelin S. British Association of Dermatologists’ guidelines for the safe and effective prescribing of azathioprine 2011. Br J Dermatol. 2011;165(4):711–34.  https://doi.org/10.1111/j.1365-2133.2011.10575.x.CrossRefGoogle Scholar
  49. 49.
    • Amagai M, Ikeda S, Shimizu H, Iizuka H, Hanada K, Aiba S, et al. A randomized double-blind trial of intravenous immunoglobulin for pemphigus. J Am Acad Dermatol. 2009;60(4):595–603.  https://doi.org/10.1016/j.jaad.2008.09.052 Demonstrates the effectiveness of IVIg as an alternative to corticosteroids early on in the course of pemphigus.CrossRefGoogle Scholar
  50. 50.
    • Amagai M, Ikeda S, Hashimoto T, Mizuashi M, Fujisawa A, Ihn H, et al. A randomized double-blind trial of intravenous immunoglobulin for bullous pemphigoid. J Dermatol Sci. 2017;85(2):77–84.  https://doi.org/10.1016/j.jdermsci.2016.11.003 Demonstrates the effectiveness of IVIg as an alternative to corticosteroids early on in the course of pemphigoid.CrossRefGoogle Scholar
  51. 51.
    Ahmed AR. Intravenous immunoglobulin therapy in the treatment of patients with pemphigus vulgaris unresponsive to conventional immunosuppressive treatment. J Am Acad Dermatol. 2001;45(5):679–90.  https://doi.org/10.1067/mjd.2001.116339.CrossRefGoogle Scholar
  52. 52.
    Sami N, Qureshi A, Ruocco E, Ahmed AR. Corticosteroid-sparing effect of intravenous immunoglobulin therapy in patients with pemphigus vulgaris. Arch Dermatol. 2002;138(9):1158–62.CrossRefGoogle Scholar
  53. 53.
    Elder MJ, Lightman S, Dart JK. Role of cyclophosphamide and high dose steroid in ocular cicatricial pemphigoid. Br J Ophthalmol. 1995;79(3):264–6.CrossRefGoogle Scholar
  54. 54.
    Friedman J, Marcovich AL, Kleinmann G, Schattner A. Low-dose pulsed intravenous cyclophosphamide for severe ocular cicatricial pemphigoid in elderly patients. Cornea. 2014;33(10):1066–70.  https://doi.org/10.1097/ico.0000000000000168.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Anne L. Marano
    • 1
    Email author
  • Adela R. Cardones
    • 2
    • 3
  • Russell P. HallIII
    • 2
  1. 1.Department of DermatologyDuke University Medical CenterDurhamUSA
  2. 2.Department of DermatologyDuke University Medical CenterDurhamUSA
  3. 3.Durham VA Medical Center, Department of Medicine, Section of DermatologyDurhamUSA

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