CURRENT AND EMERGING TRENDS IN THE MANAGEMENT OF PYODERMA GANGRENOSUM: A LITERATURE REVIEW

Authors

  • Sobia Wali Muhammad Liaquat University of Medical and Health Sciences, Jamshoro-Pakistan
  • Nadia Hassan Dow University of Health Sciences, Karachi-Pakistan
  • Samra Khan International Center for Chemical and Biological Sciences, University of Karachi-Pakistan
  • Atia Gohar Dow Institute of Biology and Advance Research, Karachi-Pakistan

DOI:

https://doi.org/10.55519/JAMC-S4-12085

Keywords:

Pyoderma gangrenosum; Systemic management; Refractory; Immunosuppressive

Abstract

The first description of Pyoderma gangrenosum (PG) was made about a century ago. It is difficult to understand the aetiology, pathophysiology, and therapy of PG. This disease is believed to be caused by a systemic inflammatory response to neutrophil chemotaxis and faulty innate immune system control. Nearly fifty percent of the cases have underlying systemic symptoms. Significant improvements in PG management have been made over the years. The main goals of treatment are to reduce inflammation and speed up the healing of the PG wound. Even though the most recent medicines show promise, they are found on isolated case reports. The majority of patients are typically managed with topical treatment and local wound care, while resistant cases necessitate immunosuppressive medications. More progress can be made with improvements in technology in deciphering this complex disease and getting a greater understanding of the condition. The present standard therapies for refractory PG are not well supported by studies. In refractory PG, corticosteroids and cyclosporine have historically been administered. Tumour necrosis factor inhibitors are becoming a viable option; nonetheless, this requires careful research and upkeep. This review intended to describe the current trends in managing the PG. Several next-generation treatment options including the conventional therapies introduced to treat PG. We encompass the advantages and disadvantages of new treatments for PG.

Author Biographies

Sobia Wali Muhammad, Liaquat University of Medical and Health Sciences, Jamshoro-Pakistan

 

Nadia Hassan, Dow University of Health Sciences, Karachi-Pakistan

 

Samra Khan, International Center for Chemical and Biological Sciences, University of Karachi-Pakistan

 

Atia Gohar, Dow Institute of Biology and Advance Research, Karachi-Pakistan

 

References

George C, Deroide F, Rustin M. Pyoderma gangrenosum - a guide to diagnosis and management. Clin Med (Lond) 2019;19(3):224–8.

Wollina U. Pyoderma gangrenosum--a review. Orphanet J Rare Dis 2007;2:19.

Butcher M. Pyoderma gangrenosum: a diagnosis not to be missed. WOUNDS UK 2005;1(3):84.

Fulbright RK, Wolf JE, Tschen JA. Residents' corner: pyoderma gangrenosum at surgery sites. J Dermatol Surg Oncol 1985;11(9):883–6.

Adachi Y, Kindzelskii AL, Cookingham G, Shaya S, Moore EC, Todd RF 3rd, et al. Aberrant neutrophil trafficking and metabolic oscillations in severe pyoderma gangrenosum. J Invest Dermatol 1998;111(2):259–68.

van de Vijver E, van den Berg TK, Kuijpers TW. Leukocyte adhesion deficiencies. Hematol Oncol Clin North Am 2013;27(1):101–16.

Su WP, Davis MD, Weenig RH, Powell FC, Perry HO. Pyoderma gangrenosum: clinicopathologic correlation and proposed diagnostic criteria. Int J Dermatol 2004;43(11):790–800.

Menter A, Gottlieb A, Feldman SR, Van Voorhees AS, Leonardi CL, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol 2008;58(5):826–50.

Sandborn WJ, Targan SR. Biologic therapy of inflammatory bowel disease. Gastroenterology 2002;122(6):1592–1608.

Chow RK, Ho VC. Treatment of pyoderma gangrenosum. J Am Acad Dermatol 1996;34(6):1047–60.

Wang AS, Armstrong EJ, Armstrong AW. Corticosteroids and wound healing: clinical considerations in the perioperative period. Am J Surg 2013;206(3):410–7.

Hughes AP, Jackson JM, Callen JP. Clinical features and treatment of peristomal pyoderma gangrenosum. JAMA 2000;284(12):1546–8.

Goldstein F, Krain R, Thornton JJ. Intralesional steroid therapy of pyoderma gangrenosum. J Clin Gastroenterol 1985;7(6):499–501.

Jennings J. Pyoderma gangrenosum: successful treatment with intralesional steroids. J Am Acad Dermatol 1983;9(4):575–80.

Homey B, Assmann T, Vohr HW, Ulrich P, Lauerma AI, Ruzicka T, et al. Topical FK506 suppresses cytokine and costimulatory molecule expression in epidermal and local draining lymph node cells during primary skin immune responses. J Immunol 1998;160(11):5331–40.

Schuppe HC, Homey B, Assmann T, Martens R, Ruzicka T. Topical tacrolimus for pyoderma gangrenosum. Lancet 1998;351(9105):832.

Reich K, Vente C, Neumann C. Topical tacrolimus for pyoderma gangrenosum. Br J Dermatol 1998;139(4):755–7.

Sehgal VN, Srivastava G, Dogra S. Tacrolimus in dermatology—pharmacokinetics, mechanism of action, drug interactions, dosages, and side effects: part I. Skinmed 2008;7(1):27–30.

Tamir A, Landau M, Brenner S. Topical treatment with 1% sodium cromoglycate in pyoderma gangrenosum. Dermatology 1996;192(3):252–4.

Saffouri B, Hom BM, Mertesdorf JM, Gardiner JF. Treatment of pyoderma gangrenosum with disodium cromoglycate. Dig Dis Sci 1984;29:183–5.

De Cock K, Thorne M. The treatment of pyoderma gangrenosum with sodium cromoglycate. Br J Dermatol 1980;102(2):231–3.

Sanders C, Hulsmans R. Successful treatment of pyoderma gangrenosum with topical 5-aminosalicylic acid. Cutis 1993;51(4):262–4.

Ahronowitz I, Harp J, Shinkai K. Etiology and management of pyoderma gangrenosum: a comprehensive review. Am J Clin Dermatol 2012;13:191–211.

Tsele E, Yu R, Chu A. Pyoderma gangrenosum—response to topical nitrogen mustard. Clin Exp Dermatol 1992;17(6):437–40.

Nguyen L, Weiner J. Treatment of pyoderma gangrenosum with benzoyl peroxide. Cutis 1977;19(6):842–4.

Vereecken P, Wautrecht JC, De Dobbeleer G, Heenen M. A case of pyoderma gangrenosum stabilized with lymecycline, topical benzoyl peroxide and treated by autograft. Dermatology 1997;195(1):50–1.

Misery L. Nicotine effects on skin: are they positive or negative? Exp Dermatol 2004;13(11):665–70.

Wolf R, Ruocco V. Nicotine for pyoderma gangrenosum. Arch Dermatol 1998;134(9):1071–2.

Heldin CH, Westermark B. Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev 1999;79(4):1283–316.

Braun-Falco M, Kovnerystyy O, Lohse P, Ruzicka T. Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH)–a new autoinflammatory syndrome distinct from PAPA syndrome. J Am Acad Dermatol 2012;66(3):409–15.

Morrissey PJ, Grabstein KH, Reed SG, Conlon PJ. Granulocyte/macrophage colony stimulating factor. A potent activation signal for mature macrophages and monocytes. Int Arch Allergy Immunol 1989;88(1-2):40–5.

White LE, Villa MT, Petronic-Rosic V, Jiang J, Medenica MM. Pyoderma gangrenosum related to a new granulocyte colony-stimulating factor. Skinmed 2006;5(2):96–8.

Callen JP. Pyoderma gangrenosum. Lancet 1998;351(9102):581–5.

Lebbe C, Moulonguet-Michau I, Perrin P, Blanc F, Frja J, Civatte J. Steroid-responsive pyoderma gangrenosum with vulvar and pulmonary involvement. J Am Acad Dermatol 1992;27(4):623–5.

Gupta AK, Brown MD, Ellis CN, Rocher LL, Fisher GJ, Baadsgaard O, et al. Cyclosporine in dermatology. J Am Acad Dermatol 1989;21(6):1245–56.

Matis WL, Ellis CN, Griffiths CE, Lazarus GS. Treatment of pyoderma gangrenosum with cyclosporine. Arch Dermatol 1992;128(8):1060–4.

Gasior-Chrzan B, Stenvold S, Falk E. Treatment of pyoderma gangrenosum with cyclosporine. J Eur Acad Dermatol Venereol 1995;5:S162.

Ahmed AR, Hombal SM. Cyclophosphamide (Cytoxan): a review on relevant pharmacology and clinical uses. J Am Acad Dermatol 1984;11(6):1115–26.

Newell LM, Malkinson FD. Pyoderma gangrenosum: response to cyclophosphamide therapy. Arch Dermatol 1983;119(6):495–7.

Crawford SE, Sherman R, Favara B. Pyoderma gangrenosum with response to cyclophosphamide therapy. J Pediatr 1967;71(2):255–8.

Cronstein BN. Molecular therapeutics. Methotrexate and its mechanism of action. Arthritis Rheum 1996;39(12):1951–60.

Teitel A. Treatment of pyoderma gangrenosum with methotrexate. Cutis 1996;57(5):326–8.

Brown R, Lay L, Graham D. Bilateral pyoderma gangrenosum of the hand: treatment with dapsone. J Hand Surg 1993;18(1):119–21.

Perri III AJ, Hsu S. A review of thalidomide's history and current dermatological applications. Dermatol Online J 2003;9(3):5.

Federman GL, Federman DG. Recalcitrant pyoderma gangrenosum treated with thalidomide. Mayo Clin Proc 2000;75(8):842–4.

Thomsen K, Rothenborg HW. Clofazimine in the treatment of pyoderma gangrenosum. Arch Dermatol 1979;115(7):851–2.

Michaëlsson G, Molin L, Ohmann S, Gip L, Lindström B, Skogh M, et al. Clofazimine: a new agent for the treatment of pyoderma gangrenosum. Arch Dermatol 1976;112(3):344–9.

Abu-Elmagd K, Van Thiel DH, Jegasothy BV, Jacobs JC, Carroll P, Rodriquez-Rilo H, et al. Resolution of severe pyoderma gangrenosum in a patient with streaking leukocyte factor disease after treatment with tacrolimus (FK 506). Ann Intern Med 1993;119(7_Part_1):595–8.

Weichert G, Sauder DN. Efficacy of tacrolimus (FK 506) in idiopathic treatment-resistant pyoderma gangrenosum. J Am Acad Dermatol 1998;39(4):648–50.

Bhat RM. Management of pyoderma gangrenosum–An update. Indian J Dermatol Venereol Leprol 2004;70(6):329–35.

Breathnach S, Wells G, Valdimarsson H. Idiopathic pyoderma gangrenosum and impaired lymphocyte function: failure of azathioprine and corticosteroid therapy. Br J Dermatol 1981;104(5):567.

Davies M, Piper S. Pyoderma gangrenosum: successful treatment with minocycline. Clin Exp Dermatol 1981;6(2):219–23.

Burruss JB, Farmer ER, Callen JP. Chlorambucil is an effective corticosteroid-sparing agent for recalcitrant pyoderma gangrenosum. J Am Acad Dermatol 1996;35(5):720–4.

Gelernt I, Kreel I. Pyoderma gangrenosum in ulcerative colitis: prevention of the gangrenous component. Mt Sinai J Med 1976;43(4):467–70.

Cliff S, Holden CA, Thomas PR, Marsden RA, Harland CC. Split skin grafts in the treatment of pyoderma gangrenosum: a report of four cases. Dermatol Surg 1999;25(4):299–302.

Fonder MA, Lazarus GS, Cowan DA, Aronson-Cook B, Kohli AR, Mamelak AJ. Treating the chronic wound: A practical approach to the care of nonhealing wounds and wound care dressings. J Am Acad Dermatol 2008;58(2):185–206.

Gottrup F, Karlsmark T. Leg ulcers: uncommon presentations. Clin Dermatol 2005;23(6):601–11.

Le Cleach L, Moguelet P, Perrin P, Chosidow O. Is topical monotherapy effective for localized pyoderma gangrenosum? Arch Dermatol 2011;147(1):101–3.

Fonseka HF, Ekanayake SM, Dissanayake M. Two percent topical phenytoin sodium solution in treating pyoderma gangrenosum: a cohort study. Int Wound J 2010;7(6):519–23.

Bellini V, Simonetti S, Lisi P. Successful treatment of severe pyoderma gangrenosum with pimecrolimus cream 1%. J Eur Acad Dermatol Venereol 2008;22(1):113–5.

Piccirillo A, Ricciuti F. Topical tacrolimus for pyoderma gangrenosum: another report. J Dermatol 2006;33(3):232.

Chiba T, Kiehl P, Breuer C, Kapp A, Werfel T. Topical tacrolimus therapy for pyoderma gangrenosum. J Dermatol 2005;32(3):199–203.

Fraccalvieri M, Fierro MT, Salomone M, Fava P, Zingarelli EM, Cavaliere G, et al. Gauze‐based negative pressure wound therapy: a valid method to manage pyoderma gangrenosum. Int Wound J 2014;11(2):164–8.

Chriba M, Skellett A, Levell N. Beclometasone inhaler used to treat pyoderma gangrenosum. Clin Exp Dermatol 2010;35(3):337–8.

Kluger N. Can snus (Swedish moist snuff) be used as a treatment of Pyoderma gangrenosum? Med Hypotheses 2012;78(5):619–20.

Rutgeerts P, Vermeire S, Van Assche G. Biological therapies for inflammatory bowel diseases. Gastroenterology 2009;136(4):1182–97.

Reguiai Z, Grange F. The role of anti-tumor necrosis factor-α therapy in pyoderma gangrenosum associated with inflammatory bowel disease. Am J Clin Dermatol 2007;8:67–77.

Gisondi P, Girolomoni G. Biologic therapies in psoriasis: a new therapeutic approach. Autoimmun Rev 2007;6(8):515–9.

Brooklyn TN, Dunnill MG, Shetty A, Bowden JJ, Williams JD, Griffiths CE, et al. Infliximab for the treatment of pyoderma gangrenosum: a randomised, double blind, placebo controlled trial. Gut 2006;55(4):505–9.

Regueiro M, Valentine J, Plevy S, Fleisher MR, Lichtenstein GR. Infliximab for treatment of pyoderma gangrenosum associated with inflammatory bowel disease. Am J Gastroenterol 2003;98(8):1821–6.

Traczewski P, Rudnicka L. Adalimumab in dermatology. Br J Clin Pharmacol 2008;66(5):618–25.

Fonder MA, Cummins DL, Ehst BD, Anhalt GJ, Meyerle JH. Adalimumab therapy for recalcitrant pyoderma gangrenosum. J Burns Wounds 2006;5:e8.

Heffernan MP, Anadkat MJ, Smith DI. Adalimumab treatment for pyoderma gangrenosum. Arch Dermatol 2007;143(3):306–8.

Goffe B, Cather JC. Etanercept: an overview. J Am Acad Dermatol 2003;49(2):105–11.

Gardam MA, Keystone EC, Menzies R, Manners S, Skamene E, Long R, et al. Anti-tumour necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management. Lancet Infect Dis 2003;3(3):148–55.

Pastor N, Betlloch I, Pascual JC, Blanes M, Bañuls J, Silvestre JF. Pyoderma gangrenosum treated with anti‐TNF alpha therapy (etanercept). Clin Exp Dermatol 2006;31(1):152–3.

Goldenberg G, Jorizzo JL. Use of etanercept in treatment of pyoderma gangrenosum in a patient with autoimmune hepatitis. J Dermatol Treat 2005;16(5-6):347–9.

Charles CA, Leon A, Banta MR, Kirsner RS. Etanercept for the treatment of refractory pyoderma gangrenosum: a brief series. Int J Dermatol 2007;46(10):1095–9.

Ruocco E, Sangiuliano S, Gravina AG, Miranda A, Nicoletti G. Pyoderma gangrenosum: an updated review. J Eur Acad Dermatol Venereol 2009;23(9):1008–17.

Graves JE, Nunley K, Heffernan MP. Off-label uses of biologics in dermatology: rituximab, omalizumab, infliximab, etanercept, adalimumab, efalizumab, and alefacept (part 2 of 2). J Am Acad Dermatol 2007;56(1):e55–79.

Foss CE, Clark AR, Inabinet R, Camacho F, Jorizzo JL. An open‐label pilot study of alefacept for the treatment of pyoderma gangrenosum. J Eur Acad Dermatol Venereol 2008;22(8):943–9.

Miller J, Yentzer BA, Clark A, Jorizzo JL, Feldman SR. Pyoderma gangrenosum: a review and update on new therapies. J Am Acad Dermatol 2010;62(4):646–54.

Wollina U, Haroske G. Pyoderma gangraenosum. Curr Opin Rheumatol 2011;23(1):50–6.

Lorincz M, Kleszky M, Szalóki T Jr, Szalóki T. Pyoderma gangrenosum treated successfully with visilizumab in patients with ulcerative colitis. Orv Hetil 2010;151(4):144–7.

Guenova E, Teske A, Fehrenbacher B, Hoerber S, Adamczyk A, Schaller M, et al. Interleukin 23 expression in pyoderma gangrenosum and targeted therapy with ustekinumab. Arch Dermatol 2011;147(10):1203–5.

Allison AC, Eugui EM. Mycophenolate mofetil and its mechanisms of action. Immunopharmacology 2000;47(2-3):85–118.

Eaton PA, Callen JP. Mycophenolate mofetil as therapy for pyoderma gangrenosum. Arch Dermatol 2009;145(7):781–5.

Cummins DL, Anhalt GJ, Monahan T, Meyerle JH. Treatment of pyoderma gangrenosum with intravenous immunoglobulin. Br J Dermatol 2007;157(6):1235–9.

Qiu L, Zheng S, Wu J, Xiao T, Chen HD. Refractory disseminated pyoderma gangrenosum, with dependence on corticosteroids, responding to potassium iodide. Eur J Dermatol 2012;22(3):426–7.

Saniabadi AR, Hanai H, Takeuchi K, Umemura K, Nakashima M, Adachi T, et al. Adacolumn, an Adsorptive Carrier Based Granulocyte and Monocyte Apheresis Device for the Treatment of Inflammatory and RefractoryDiseases Associated with Leukocytes. Ther Apher Dial 2003;7(1):48–59.

Okuma K, Mitsuishi K, Hasegawa T, Tsuchihashi H, Ogawa H, Ikeda S. A case report of steroid and immunosuppressant‐resistant pyoderma gangrenosum successfully treated by granulocytapheresis. Ther Apher Dial 2007;11(5):387–90.

de Imus G, Golomb C, Wilkel C, Tsoukas M, Nowak M, Falanga V. Accelerated healing of pyoderma gangrenosum treated with bioengineered skin and concomitant immunosuppression. J Am Acad Dermatol 2001;44(1):61–6.

Duchini G, Itin P, Arnold A. A case of refractory pyoderma gangrenosum treated with a combination of Apligraf and systemic immunosuppressive agents. Adv Skin Wound Care 2011;24(5):217–20.

Altunay I, Kucukunal A, Sarikaya S, Tukenmez Demirci G. A favourable response to surgical intervention and hyperbaric oxygen therapy in pyoderma gangrenosum. Int Wound J 2014;11(4):350–3.

Li LF. Treatment of pyoderma gangrenosum with oral Tripterygium wilfordii multiglycoside. J Dermatol 2000;27(7):478–81.

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Published

2024-01-16