Pemfigus vulgaris tedavisinde yenilikler

Yıl 2013, Cilt: 30 Sayı: 1s, 1 - 8, 28.11.2013

Müge Güler Özden , Ahmet Turanlı

Öz

Pemfigus vulgaris mortalitesi, tedavi edilmediğinde % 90’a kadar ulaşabilmektedir. Bu yüksek mortalite oranı sistemik kortikosteroidlerin kullanılmaya başlanmasıyla belirgin olarak düşmekle birlikte, şiddetli yan etkiler ve dirençli olguların varlığı nedeniyle adjuvan tedavi kullanımı hemen her zaman gerekmektedir. Son yıllarda pemfigus tedavisinde yeni bir yön vermeyi amaçlayan çok fazla çalışma yayınlanmaktadır. Amaçlanan, ölümcül sonuçları olmayan yan etkilere sahip, düşük dozda kullanılabilen ve uzun süre remisyon sağlayan tedavi seçenekleri bulmaktır. Sistemik steroidler hızlı remisyon sağlamaları nedeniyle halen ilk tedavi seçeneğidir. Ancak bu tedavinin yan etkileri oldukça fazladır ve dozu azaltabilmek amacıyla bir çok toksik yan etkilere sahip adjuvan tedavi eklenmesine gerek duyulmaktadır. Son yıllarda pemfigus tedavisine yeni bir yön veren yeni tedaviler; intravenöz immünglobulin (IVIg), plazmaferez, immünoadsorbsiyon (İA), ekstrakorporeal fotokemoterapi (EKP), rituksimab, tümör nekrozis faktör alfa (TNF-α) inhibitörleri (infliksimab ve etanercept), kolinerjik agonistler, dezmoglein 3 peptitleri ve KC706 gibi deneysel ajanlardır.

Improvements in the treatment of Pemhigus vulgarism

The mortality of Pemphigus vulgaris can reach up to 90% when it is not treated. Although this ratio has declined together with the use of systemic corticosteroids, there is almost always a need to administer adjuvant treatment because of severe adverse effects and resistant cases. There are many publishings aiming to find a new way for pemphigus treatment, recently. No side effects that lead to fatal results and low-dose treatment with long-term remission have become the issue to find. Systemic steroids due to provide fast remission is still the first treatment option. However, depending on the dose and time, side effects are too much. Therefore, almost always an adjuvan treatment is needed to reduce the dose which have many toxic side effects. Pemphigus treatments giving a new direction in recent years are, intravenous immunoglobulin, plasmapheresis, immunoadsorbtion, ekstracorporeal photochemoterapy, rituximab, tumor necrosis factor alpha inhibitors (infliximab and etanercept), cholinergic agonists and experimental agents such as desmoglein 3 peptides and KC706.

Anahtar Kelimeler

Büllöz hastalıklar; pemfigus; pemfigus vulgaris; tedavi (Bullous diseases; pemphigus; pemphigus vulgaris; treatment)

Kaynakça

• Ahmed, A.R., Spigelman, Z., Cavacini, L.A., Posner, M.R., 2006. Treatment of 39 Pemphigus vulgaris with rituximab and intravenous immune globulin. New. Engl. J. Med. 355, 1772-1779.
• Amagai, M., Ikeda, S., Shimizu, H., Iizuka, H., Hanada, K., Aiba, S., Kaneko, F., Izaki, S., Tamaki, K., Ikezawa, Z., Takigawa, M., Seishima, M., Tanaka, T., Miyachi, Y., Katayama, I., Horiguchi, Y., Miyagawa, S., Furukawa, F., Iwatsuki, K., Hide, M., Tokura, Y., Furue, M., Hashimoto, T., Ihn, H., Fujiwara, S., Nishikawa, T., Ogawa, H., Kitajima, Y., Hashimoto, K., Pemphigus Study Group., 2009. A randomized double-blind trial of intravenous immunoglobulin for pemphigus. J. Am. Acad. Dermatol. 60, 595-603.
• Anhalt, G., Werth, V., Strober, B., 2005. An open-label phase I clinical study to assess the safety of PI-0824 in patients with Pemphigus vulgaris. J. Invest. Dermatol. 125, 1088-1092.
• Berkowitz, P., Hu, P., Warren, S., Liu, Z., Diaz, L.A., Rubenstein, D.S., 2006. p38MAPK inhibition prevents disease in Pemphigus vulgaris mice P. Natl. Acad. Sci. USA. 103, 12855-12860.
• Berookhim, B., Fischer, H.D., Weinberg, J.M., 2004. Treatment of recalcitrant 44. Pemphigus vulgaris with tumor necrosis factor alpha antagonist etanercept. Cutis. 74, 245-247.
• Bhol, K., Natarajan, K., Nagarwalla, N., Mohimen, A., Aoki, V., Ahmed, A.R., 1995. Correlation of peptide specificity and IgG subclass with pathogenic and nonpathogenic autoantibodies in Pemphigus vulgaris: A model for autoimmunity. Proc. Natl. Acad. Sci. USA. 92, 5239-5243.
• Bolognia, J.L., Jorizzo, J.L., Rapini, R.P., 2008. Dermatology. Lee T Nesbitt Jr. Glucocorticosteroids. Mosby Elsevier, New York, USA. 1925.
• Bystryn, J.C., Rudolph, J.L., 2005a. Pemphigus. Lancet. 366, 61-73.
• Bystryn, J.C., Rudolph, J.L., 2005b. IVI g treatment of pemphigus: How it works and how to use it. J. Invest. Dermatol. 125, 1093-1098.
• Chams-Davatchi, C., Esmaili, N., Daneshpazhooh, M., Valikhani, M., Balighi, K., Hallaji, Z., Barzegari, M., Akhyani, M., Ghodsi, S.Z., Seirafi, H., Nazemi, M.J., Mortazavi, H., Mirshams-Shahshahani, M. 2007. Randomized controlled open-label trial of four treatment regimens for Pemphigus vulgaris. J. Am. Acad. Dermatol. 57, 622-628.
• Daulat, S., Detweiler, J.G., Pandya, A.G., 2009. Development of Pemphigus vulgaris in a patient with psoriasis treated with etanercept. J. Eur. Acad. Dermatol. 23, 483-484.
• Demirçay, Z., 2005. Developments in the treatment of Pemphigus vulgaris. Turkiye Klinikleri J. Inter. Med. Sci. 1, 23-24.
• Edelson, R.L., 1999. Sézary syndrome, cutaneous T-cell lymphoma, and extracorporeal photopheresis. Arch. Dermatol. 135, 600-601.
• El Tal, A.K., Posner, M.R., Spigelman, Z., Ahmed, A.R., 2006. Rituximab: A monoclonal antibody to CD20 used in the treatment of Pemphigus vulgaris. J. Am. Acad. Dermatol. 55, 449-459.
• Eming, R., Hertl, M., 2006. Immunoadsorption in pemphigus. Autoimmunity. 39, 609-616.
• Femiano, F., Gombos, F., Scully, C. 2002. Pemphigus vulgaris with oral involvement: evaluation of two different systemic corticosteroid therapeutic protocols. J. Eur. Acad. Dermatol. 16, 353-356.
• Frusic-Zlotkin, M., Pergamentz, R., Michel, B., David, M., Mimouni, D., Brégégère, F., Milner, Y., 2005. The interaction of pemphigus autoimmunoglobulins with epidermal cells: Activation of the fas apoptotic pathway and the use of caspase activity for pathogenicity tests of pemphigus patients. Ann. NY. Acad. Sci. 1050, 371-379.
• Grando, S.A., 2004. New approaches to the treatment of pemphigus. J. Invest. Derm. Symp. P. 9, 84-91.
• Green, M.G., Bystryn, J.C., 2008. Effect of intravenous immunoglobulin therapy on serum levels of IgG1 and IgG4 antidesmoglein 1 and antidesmoglein 3 antibodies in Pemphigus vulgaris. Arch Dermatol. 144, 1621-1624.
• Harman, K.E., Albert, S., Black, M.M., 2003. Guidelines for the management of Pemphigus vulgaris. Brit. J. Dermatol. 149, 926-937.
• Herbst, A., Bystryn, J.C., 2000. Patterns of remission in Pemphigus vulgaris. J. Am. Acad Dermatol. 42, 422-427.
• Hertl, M., Zillikens, D., Borradori, L., Bruckner-Tuderman, L., Burckhard, H., Eming, R., Engert, A., Goebeler, M., Hofmann, S., Hunzelmann,
• N., Karlhofer, F., Kautz, O., Lippert, U., Niedermeier, A., Nitschke, M., Pfütze, M., Reiser, M., Rose, C., Schmidt, E., Shimanovich, I., Sticherling, M., Wolff-Franke, S., 2008. Recommendations for the use of rituximab (anti-CD20 antibody) in the treatment of autoimmune bullous skin diseases. J. Dtsch. Dermatol. Ges. 6, 366-373.
• Ikeda, S., Imamura, S., Hashimoto, I., Morioka, S., Sakuma, M., Ogawa, H., 2003. History of the establishment and revision of diagnostic criteria, severity index and therapeutic guidelines for pemphigus in Japan. Arch. Dermatol. Res. 295, 12-16.
• Iraji, F., Yoosefi, A., 2006. Healing effect of pilocarpine gel 4% on skin lesions of Pemphigus vulgaris. Int. J. Dermatol. 45, 743-746.
• Jablonska, S., Chorzelski, T., Blaszczyk, M., 1970. Immunosuppressants in the treatment of pemphigus. Brit. J. Dermatol. 83, 315-323.
• Jacobi, A., Shuler, G., Hertl, M., 2005. Rapid control of therapy-refractory Pemphigus vulgaris by treatment with the tumour necrosis factoralpha inhibitor infliximab. Brit. J. Dermatol. 153, 448-449.
• Jessop, S., Khumalo, N.P., 2008. Pemphigus: A treatment update. Am. J. Clin. Dermatol. 9, 147-154.
• Jolles, S., Sewell, W.A., Misbah, S.A., 2005. Clinical uses of intravenous immunoglobulin. Clin. Exp. Immunol. 142, 1-11.
• Joly, P., Mouquet, H., Roujeau, J.C., D’Incan, M., Gilbert, D., Jacquot, S., Gougeon, M.L., Bedane, C., Muller, R., Dreno, B., Doutre, M.S., Delaporte, E., Pauwels, C., Franck, N., Caux, F., Picard, C., Tancrede-Bohin, E., Bernard, P., Tron, F., Hertl, M., Musette, P. 2007. A single cycle of rituximab for the treatment of severe pemphigus. New. Eng. J. Med. 357, 545-552.
• Küçükoğlu, R., Babuna, G., 2008. Pemphigus-Etiology, Pemphigus Vulgaris, Pemphigus Vegetans, Paraneoplastic Pemphigus: Clinic and Treatment. J. Dermatol-Special. Topics. 1, 16-24.
• Liang, G., Nahass, G., Kerdel, F.A., 1992. Pemphigus vulgaris treated with photopheresis. J. Am. Acad. Dermatol. 26, 779-780.
• Lin, M.H., Hsu, C.K., Lee, J.Y. 2005. Successful treatment of the recalcitrant Pemphigus vulgaris and Pemphigus vegetans with etanercept and carbon dioxide laser. Arch. Dermatol. 141, 680-682.
• Marakli, S.S., Uzun, S., Ozbek, S., Tuncer, I., 2008. Dermatitis herpetiformis in a patient receiving infliximab for ankylosing spondylitis. Eur. J. Dermatol. 18, 88-89.
• McKenna, K.E., Whittaker, S., Rhodes, L.E., Taylor, P., Lloyd, J., Ibbotson, S., Russell-Jones, R., British Photodermatology Group, UK SkinLymphoma Group., 2006. Evidence-based practice of photopheresis 1987-2001: A report of a workshop of the British Photodermatology Group and the U.K. Skin Lymphoma Group. Brit. J. Dermatol. 154, 7-20.
• Mentink, L.F., Mackenzie, M.W., Tóth, G.G., Laseur, M., Lambert, F.P., Veeger, N.J., Cianchini, G., Pavlovic, M.D., Jonkman, M.F., 2006. Randomized controlled trial of adjuvant oral dexamethasone pulse therapy in Pemphigus vulgaris: PEMPULS trial. Arch. Dermatol. 142, 570-576.
• Murrell, D.F., Dick, S., Ahmed, A.R., Amagai, M., Barnadas, M.A., Borradori, L., Bystryn, J.C., Cianchini, G., Diaz, L., Fivenson, D., Hall, R., Harman, K.E., Hashimoto, T., Hertl, M., Hunzelmann, N., Iranzo, P., Joly, P., Jonkman, M.F., Kitajima, Y., Korman, N.J., Martin, L.K., Mimouni, D., Pandya, A.G., Payne, A.S., Rubenstein, D., Shimizu, H., Sinha, A.A., Sirois, D., Zillikens, D., Werth, V.P., 2008. Consensus statement on definitions of disease, end points, and therapeutic response for pemphigus. J. Am. Acad. Dermatol. 58, 1043-1046.
• Mydlarski, P.R., Ho, V., Shear, N.H., 2006. Canadian consensus statement on the use of intravenous immunoglobulin therapy in dermatology. J. Cutan. Med. Surg. 10, 205-221.
• Nagasaka, T., Fujii, Y., Ishida, A., Handa, M., Tanikawa, A., Amagai, M., Nishikawa, T., 2008. Evaluating efficacy of plasmapheresis for patients with pemphigus using desmoglein enzyme-linked immunosorbent assay. Brit. J. Dermatol. 158, 685-690.
• Nguyen, V.T., Arredondo, J., Chernyavsky, A.I., Pittelkow, M.R., Kitajima, Y., Grando, S.A., 2004. Pemphigus vulgaris acantholysis ameliorated by cholinergic agonists. Arch. Dermatol. 140, 327-334.
• Nguyen, V.T., Lee, T.X., Ndoye, A., Shultz, L.D., Pittelkow, M.R., Dahl, M.V., Lynch, P.J., Grando, S.A., 1998. The pathophysiological significance of nondesmoglein targets of pemphigus autoimmunity. Development of antibodies against keratinocyte cholinergic receptors in patients with Pemphigus vulgaris and pemphigus foliaceus. Arch. Dermatol. 134, 971-980.
• Pardo, J., Mercader, P., Mahiques, L., Sanchez-Carazo, J.L., Oliver, V., Fortea, J.M., 2005. Infliximab in the management of severe Pemphigus vulgaris. Brit. J. Dermatol. 153, 222-223.
• Prajapati, V., Mydlarski, P.R., 2008. Advances in pemphigus therapy. Skin. Therapy. Lett. 13, 4-7.
• Ratnam, K.V., Phay, K.L., Tan, C.K., 1990. Pemphigus therapy with oral prednisolone regimens. A 5-year study. Int. J. Dermatol. 29, 363-367.
• Risser, J., Lewis, K., Weinstock, M.A. 2009. Mortality of bullous skin disorders from 1979 through 2002 in the United States. Arch. Dermatol. 145, 1005-1008.
• Rook, A.H., Jegasothy, B.V., Heald, P., Nahass, G.T., Ditre, C., Witmer, W.K., Lazarus, G.S., Edelson, R.L., 1990. Extracorporeal photochemotherapy for drug-resistant Pemphigus vulgaris. Ann. Intern. Med. 112, 303-305.
• Roujeau, J.C., Andre, C., Joneau, Fabre, M., Lauret, P., Flechet, M.L., Kalis, B., Revuz, J., Touraine, R., 1993. Plasma exchange in pemphigus. Uncontrolled study of ten patients. Arch. Dermatol. 119, 215-221.
• Russo, C.G., Mullen, C., 2001. Cutaneous and noncutaneous disorders treated with extracorporeal photopheresis. Int. J. Dermatol. 40, 89-100.
• Schmidt, E., Hunzelmann, N., Zillikens, D., Bröcker, E.B., Goebeler, M., 2006. Rituximab in refractory autoimmune bullous diseases. Clin. Exp. Dermatol. 31, 503-508.
• Shimanovich, I., Herzog, S., Schmidt, E., Opitz, A., Klinker, E., Bröcker, E.B., Goebeler, M., Zillikens, D. 2006. Improved protocol for treatment of Pemphigus vulgaris with protein A immunoadsorption. Clin. Exp. Dermatol. 31, 68-74.
• Shimanovich, I., Nitschke, M., Rose, C., Grabbe, J., Zillikens, D., 2008. Treatment of severe pemphigus with protein A immunoadsorption, rituximab and intravenous immunoglobulins. Brit. J. Dermatol. 158, 382-388.
• Tabrizi, M.N., Chams-Davatchi, C., Esmaeeli, N., Noormohammadpoor, P., Safar, F., Etemadzadeh, H., Ettehadi, H.A., Gorouhi, F., 2007. Accelerating effects of epidermal growth factor on skin lesions of Pemphigus vulgaris: A double-blind, randomized, controlled trial. J. Eur. Acad. Dermatol. 21, 79-84.
• Tan-Lim, R., Bystryn, J.C., 1990. Effect of plasmapheresis therapy on circulating levels of pemphigus antibodies. J. Am. Acad. Dermatol. 22, 35-40.
• Turner, M.S., Sutton, D., Sauder, D.N. 2000. The use of plasmapheresis and immunosuppression in the treatment of Pemphigus vulgaris. J. Am. Acad. Dermatol. 43, 1058-1064.
• Werth, V.P., Fivenson, D., Pandya, A.G., Chen, D., Rico, M.J., Albrecht, J., Jacobus, D. 2008. Multicenter randomized, double-blind, placebocontrolled, clinical trial of dapsone as a glucocorticoid-sparing agent in maintenance-phase Pemphigus vulgaris. Arch. Dermatol. 144, 25-32.
• Wu, C.S., Hsu, H.Y., Hu, S.C., Chiu, H.H., Chen, G.S., 2009. Silver-containing hydrofiber dressing is an effective adjunct in the treatment of Pemphigus vulgaris. Kaohsiung. J. Med. Sci. 25, 622-627.
• van Iperen, H.P., Beijersbergen, van Henegouwen, G.M., 1997. Clinical and mechanistic aspects of photopheresis. J. Photoch. Photobiol. 39, 99-109.
• van Schaik, I.N., Vermeulen, M., Brand, A.J., 1994. In vitro effects of polyvalent immunoglobulin for intravenous use. J. Neurol. Neurosurg. Psychiatry. 57, 15-17.
• Virgolini, L., Marzocchi, V., 2004. Rituximab in autoimmune diseases. Biomed Pharmacother. 58, 299-309.
• Zhu, Y.I., Stiller, M.J., 2001. Dapsone and sulfones in dermatology: Overview and update. J. Am. Acad. Dermatol. 45, 420-434.