Il decorso del PG può essere rapidamente o gradualmente progressivo. A causa della ridotta casistica e del numero esiguo dei trials, le opzioni relative al trattamento del PG vengono decise sulla base dei casi clinici e di piccoli studi.
I trattamenti locali sono indicati negli stadi precoci. Il trattamento di prima linea è rappresentato essenzialmente dai GCS ma nei casi refrattari si possono utilizzare altri farmaci immunosoppressori o farmaci biologici.
In base alla nostra lunga esperienza nel trattamento di ferite difficili, noi proponiamo un possibile algoritmo per il trattamento del PG.
Il nostro algoritmo è basato su un concetto innovativo: l'applicazione del Wound bed preparation e del TIME (Tessuto, Infiammazione/Infezione, Macerazione, Epitelizzazione) nel PG.
Infatti per quanto riguarda il trattamento locale della lesione noi suggeriamo un differente algoritmo terapeutico nella fase infiammatoria e nella fase non infiammatoria al fine di controllare l'infiammazione, ridurre il tempo di guarigione e migliorare la qualità di vita del paziente.
Per quanto riguarda la terapia sistemica concomitante invece seguiamo le raccomandazioni presenti in letteratura.25
L’associazione tra trattamenti locali, sistemici e una corretta gestione dell’ulcera porta a risultati clinici migliori anche nei casi di PG refrattario
.
La qualità di vita del paziente, fortemente ridotta dal dolore, dall'essudazione e dalle infezioni, migliora notevolmente e la guarigione diviene più rapida rispetto a quanto descritto in letteratura.Si ritiene perciò necessaria la validazione di questo algoritmo all’interno di uno studio prospettico che coinvolga un adeguato numero di pazienti ed un gruppo di pazienti di controllo in cui si effettua invece la gestione standard.
Ulcerative
Form PG
PG TIME (Fase Non
inflammatoria)
TISSUE DEVITALIZED
DEBRIDEMENT: debridement meccanico,
autolitico (hydrogel) o enzimatico (collagenasi)
INFECTION: utilizzare medicazioni
antisettiche (ioni di Ag, PHMB, ioni metallici di iodio, miele) e medicazioni captanti batteri
MOISTURE BALANCE: medicazioni
assorbenti (schiume, alginato, hydrofibra), bendaggi compressivi e NPWT
EPITHELIAL EDGES ADVANCEMENT:
medicazioni bioattive, allografts, epidermal grafts, sostituti cutanei (membrana amniotica)
PG TIME (Fase infiammatoria)
TISSUE DEVITALIZED
DEBRIDEMENT: evitare il debridement
meccanico e chirurgico, usare quello autolitico (hydrogel) ed enzimatico (collagenasi)
INFECTION: utilizzare medicazioni
antisettiche (ioni di Ag, PHMB, ioni metallici di iodio, miele) e medicazioni captanti batteri
INFLAMMATION: steroidi topici,
tacrolimus, bendaggi compressivi
MOISTURE BALANCE: medicazioni
assorbenti (schiume, alginato, hydrofibra, bendaggi compressivi)
EPITHELIAL EDGES ADVANCEMENT:
non applicabile
Wound Bed
Terapia locale del Pioderma gangrenoso e PG TIME
Non inflammatory
Inflammatory
Tacrolimus Pimecrolimus Medium high grade Local steroidWound Bed
Perilesional
Skin
Topical Topical1 LINEA
2 LINEA
Terapia sistemica del Pioderma gangrenoso
- GCS
- Se controindicati (obesità, DM, osteoporosi, ulcera peptica, ecc) / GCS resistenti Ciclosporina A
Infliximab
GCS + uno o più tra: - azatioprina - micofenolato mofetile - dapsone - talidomide - tacrolimus - metotrexato - ciclofosfamide - IgEV
Se refrattari alle suddette terapie / con sottostanti malattie infiammatorie
sistemiche (IBD, AR, ecc) Farmaci biologici:
- infliximab - adalimumab - etanercept - ustekinumab - rituximab - alefacept - tocilizumab
Bibliografia
1. Schmieder SJ, Krishnamurthy K. Pyoderma Gangrenosum. StatPearls. Treasure Island (FL): StatPearls PublishingLLC.; 2018.
2. Alavi A, French LE, Davis MD, Brassard A, Kirsner RS. Pyoderma Gangrenosum: An Update on Pathophysiology, Diagnosis and Treatment. American journal of clinical
dermatology 2017; 18(3): 355-72.
3. Saavedra AP, Kovacs SC, Moschella SL. Neutrophilic dermatoses. Clinics in dermatology 2006; 24(6): 470-81.
4. Cugno M, Borghi A, Marzano AV. PAPA, PASH and PAPASH Syndromes: Pathophysiology, Presentation and Treatment. American journal of clinical dermatology 2017;
18(4): 555-62.
5. Hafner J, Nobbe S, Partsch H, et al. Martorell hypertensive ischemic leg ulcer: a model of ischemic subcutaneous arteriolosclerosis. Archives of dermatology 2010; 146(9): 961-8. 6. Langan SM, Groves RW, Card TR, Gulliford MC. Incidence, mortality, and disease associations of pyoderma gangrenosum in the United Kingdom: a retrospective cohort study.
The Journal of investigative dermatology 2012; 132(9): 2166-70.
7. Marzano AV, Borghi A, Wallach D, Cugno M. A comprehensive review of neutrophilic diseases [published online ahead of print July 7, 2017]. Clin Rev Allergy Immunol 0000. 8. Schoch JJ, Tolkachjov SN, Cappel JA, Gibson LE, Davis DM. Pediatric Pyoderma Gangrenosum: A Retrospective Review of Clinical Features, Etiologic Associations, and Treatment. Pediatric dermatology 2017; 34(1): 39-45.
9. Dick DC, Mackie RM, Patrick WJ, Goel KM. Pyoderma gangrenosum in infancy. Acta
dermato-venereologica 1982; 62(4): 348-50.
10. Gameiro A, Pereira N, Cardoso JC, Goncalo M. Pyoderma gangrenosum: challenges and solutions. Clinical, cosmetic and investigational dermatology 2015; 8: 285-93.
11. Fulbright RK, Wolf JE, Tschen JA. Pyoderma gangrenosum at surgery sites. The Journal
of dermatologic surgery and oncology 1985; 11(9): 883-6.
12. Braswell SF, Kostopoulos TC, Ortega-Loayza AG. Pathophysiology of pyoderma gangrenosum (PG): an updated review. Journal of the American Academy of Dermatology 2015; 73(4): 691-8.
13. Crowson AN, Nuovo GJ, Mihm MC, Jr., Magro C. Cutaneous manifestations of Crohn's disease, its spectrum, and its pathogenesis: intracellular consensus bacterial 16S rRNA is associated with the gastrointestinal but not the cutaneous manifestations of Crohn's disease.
Human pathology 2003; 34(11): 1185-92.
14. Cozzani E, Gasparini G, Parodi A. Pyoderma gangrenosum: a systematic review.
Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia 2014; 149(5): 587-600.
15. Thakur N, Sodani R, Chandra J, Singh V. Leukocyte adhesion defect type 1 presenting with recurrent pyoderma gangrenosum. Indian journal of dermatology 2013; 58(2): 158. 16. Bedlow AJ, Davies EG, Moss AL, Rebuck N, Finn A, Marsden RA. Pyoderma gangrenosum in a child with congenital partial deficiency of leucocyte adherence glycoproteins. The British journal of dermatology 1998; 139(6): 1064-7.
17. Marzano AV, Cugno M, Trevisan V, et al. Inflammatory cells, cytokines and matrix metalloproteinases in amicrobial pustulosis of the folds and other neutrophilic dermatoses.
International journal of immunopathology and pharmacology 2011; 24(2): 451-60.
18. Ahn C, Negus D, Huang W. Pyoderma gangrenosum: a review of pathogenesis and treatment. Expert review of clinical immunology 2018; 14(3): 225-33.
19. Sagami S, Ueno Y, Tanaka S, Nagai K, Hayashi R, Chayama K. Successful Use of Adalimumab for Treating Pyoderma Gangrenosum with Ulcerative Colitis under Corticosteroid- tapering Conditions. Internal medicine (Tokyo, Japan) 2015; 54(17): 2167-72.
20. Brooklyn TN, Williams AM, Dunnill MG, Probert CS. T-cell receptor repertoire in pyoderma gangrenosum: evidence for clonal expansions and trafficking. The British journal of
dermatology 2007; 157(5): 960-6.
21. Caproni M, Antiga E, Volpi W, et al. The Treg/Th17 cell ratio is reduced in the skin lesions of patients with pyoderma gangrenosum. The British journal of dermatology 2015;
173(1): 275-8.
22. Marzano AV, Fanoni D, Antiga E, et al. Expression of cytokines, chemokines and other effector molecules in two prototypic autoinflammatory skin diseases, pyoderma gangrenosum and Sweet's syndrome. Clinical and experimental immunology 2014; 178(1): 48-56.
23. Marzano AV, Damiani G, Ceccherini I, Berti E, Gattorno M, Cugno M. Autoinflammation in pyoderma gangrenosum and its syndromic form (pyoderma gangrenosum, acne and suppurative hidradenitis). British Journal of Dermatology 2017; 176(6): 1588-98.
24. Marzano AV, Borghi A, Meroni PL, Cugno M. Pyoderma gangrenosum and its syndromic forms: evidence for a link with autoinflammation. British Journal of Dermatology 2016; 175(5): 882-91.
25. Garcovich S, De Simone C, Berti E, Marzano AV. Drug management of neutrophilic dermatoses. Expert review of clinical pharmacology 2017; 10(10): 1119-28.
26. Oka M, Berking C, Nesbit M, et al. Interleukin-8 overexpression is present in pyoderma gangrenosum ulcers and leads to ulcer formation in human skin xenografts. Laboratory
investigation; a journal of technical methods and pathology 2000; 80(4): 595-604.
27. Ortega-Loayza AG, Nugent WH, Lucero OM, Washington SL, Nunley JR, Walsh SW. Dysregulation of inflammatory gene expression in lesional and nonlesional skin of patients with pyoderma gangrenosum. The British journal of dermatology 2018; 178(1): e35-e6. 28. Tan MH, Gordon M, Lebwohl O, George J, Lebwohl MG. Improvement of Pyoderma gangrenosum and psoriasis associated with Crohn disease with anti-tumor necrosis factor alpha monoclonal antibody. Archives of dermatology 2001; 137(7): 930-3.
29. Wu BC, Patel ED, Ortega-Loayza AG. Drug-induced pyoderma gangrenosum: a model to understand the pathogenesis of pyoderma gangrenosum. The British journal of dermatology 2017; 177(1): 72-83.
30. Gangaram HB, Tan LP, Gan AT, Suraiya HH, Ganesapillai T. Pyoderma gangrenosum following treatment with isotretinoin. The British journal of dermatology 1997; 136(4): 636-7. 31. Srebrnik A, Shachar E, Brenner S. Suspected induction of a pyoderma gangrenosum- like eruption due to sulpiride treatment. Cutis 2001; 67(3): 253-6.
32. Ross HJ, Moy LA, Kaplan R, Figlin RA. Bullous pyoderma gangrenosum after granulocyte colony-stimulating factor treatment. Cancer 1991; 68(2): 441-3.
33. Patel F, Fitzmaurice S, Duong C, et al. Effective strategies for the management of pyoderma gangrenosum: a comprehensive review. Acta dermato-venereologica 2015; 95(5): 525-31.
34. Powell FC, Su WP, Perry HO. Pyoderma gangrenosum: classification and management.
Journal of the American Academy of Dermatology 1996; 34(3): 395-409; quiz 10-2.
35. Brooklyn T, Dunnill G, Probert C. Diagnosis and treatment of pyoderma gangrenosum.
BMJ (Clinical research ed) 2006; 333(7560): 181-4.
36. Vallini V, Andreini R, Bonadio A. Pyoderma Gangrenosum: A Current Problem as Much as an Unknown One. The international journal of lower extremity wounds 2017; 16(3): 191- 201.
37. Crowson AN, Mihm MC, Jr., Magro C. Pyoderma gangrenosum: a review. Journal of
cutaneous pathology 2003; 30(2): 97-107.
38. Beiteke U, Bigge S, Reichenberger C, Gralow I. Pain and pain management in dermatology. Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German
Society of Dermatology : JDDG 2015; 13(10): 967-87.
39. Langeland T, Rokkones E. Pyoderma gangrenosum as a cause of spontaneous vulvovaginal ulceration. Acta obstetricia et gynecologica Scandinavica 2004; 83(12): 1220-1.
40. Gungor E, Karakayali G, Alli N, Artuz F, Lenk N. Penile pyoderma gangrenosum. Journal
of the European Academy of Dermatology and Venereology : JEADV 1999; 12(1): 59-62.
41. Wollina U. Pyoderma gangrenosum--a review. Orphanet journal of rare diseases 2007;
2: 19.
42. Horner B, El-Muttardi N, Mercer D. Pyoderma gangrenosum complicating bilateral breast reduction. British journal of plastic surgery 2004; 57(7): 679-81.
43. Kruger S, Piroth W, Amo Takyi B, Breuer C, Schwarz ER. Multiple aseptic pulmonary nodules with central necrosis in association with pyoderma gangrenosum. Chest 2001; 119(3): 977-8.
44. Miserocchi E, Modorati G, Foster CS, Brancato R. Ocular and extracutaneous involvement in pyoderma gangrenosum. Ophthalmology 2002; 109(10): 1941-3.
45. Mijuskovic ZP, Zecevic RD, Pavlovic MD. Pyoderma gangrenosum with spleen involvement and monoclonal IgA gammopathy. Journal of the European Academy of
Dermatology and Venereology : JEADV 2004; 18(6): 697-9.
46. Marie I, Levesque H, Joly P, et al. Neutrophilic myositis as an extracutaneous manifestation of neutrophilic dermatosis. Journal of the American Academy of Dermatology 2001; 44(1): 137-9.
47. Sedda S, Caruso R, Marafini I, et al. Pyoderma gangrenosum in refractory celiac disease: a case report. BMC gastroenterology 2013; 13: 162.
48. Sandhu K, Handa S, Kanwar AJ. Idiopathic pyoderma gangrenosum in a child. Pediatric
dermatology 2004; 21(3): 276-7.
49. Steele RB, Nugent WH, Braswell SF, Frisch S, Ferrell J, Ortega-Loayza AG. Pyoderma gangrenosum and pregnancy: an example of abnormal inflammation and challenging treatment. The British journal of dermatology 2016; 174(1): 77-87.
50. Pinato DJ, Sharma R. Imatinib induced pyoderma gangrenosum. Journal of
postgraduate medicine 2013; 59(3): 244-5.
51. McElnea E, Stephenson K, Fulcher T. Pyoderma gangrenosum affecting the eye, orbit, and adnexa. A review. Orbit (Amsterdam, Netherlands) 2018; 37(1): 26-31.
52. Kennedy KS, Prendergast ML, Sooy CD. Pyoderma gangrenosum of the oral cavity, nose, and larynx. Otolaryngology--head and neck surgery : official journal of American
Academy of Otolaryngology-Head and Neck Surgery 1987; 97(5): 487-90.
53. Bhat RM. Pyoderma gangrenosum: An update. Indian dermatology online journal 2012;
3(1): 7-13.
54. Ratnagobal S, Sinha S. Pyoderma gangrenosum: guideline for wound practitioners.
Journal of wound care 2013; 22(2): 68-73.
55. Lear JT, Atherton MT, Byrne JP. Neutrophilic dermatoses: pyoderma gangrenosum and Sweet's syndrome. Postgraduate medical journal 1997; 73(856): 65-8.
56. Puechguiral-Renaud I, Carpentier O, Piette F, Delaporte E. Subcorneal pustulosis and Pyoderma gangrenosum associated with a biclonal gammopathy. European journal of
dermatology : EJD 2006; 16(6): 687-90.
57. Delaney TA, Clay CD, Randell PL. The bowel-associated dermatosis--arthritis syndrome.
The Australasian journal of dermatology 1989; 30(1): 23-7.
58. Ahronowitz I, Harp J, Shinkai K. Etiology and management of pyoderma gangrenosum: a comprehensive review. American journal of clinical dermatology 2012; 13(3): 191-211. 59. Chan HL, Lee YS, Kuo TT. Sweet's syndrome: clinicopathologic study of eleven cases.
International journal of dermatology 1994; 33(6): 425-32.
60. Lachapelle JM, Marot L, Jablonska S. Superficial granulomatous pyoderma gangrenosum of the face, successfully treated by ciclosporine: a long-term follow-up.
Dermatology (Basel, Switzerland) 2001; 202(2): 155-7.
61. Mesina C, Vasile I, Mogoanta SS, et al. Pyoderma vegetans of the posterior area of the neck: case presentation. Romanian journal of morphology and embryology = Revue roumaine
62. Azar MM, Relich RF, Schmitt BH, Spech RW, Hage CA. Cutaneous blastomycosis masquerading as pyoderma gangrenosum. Journal of clinical microbiology 2014; 52(4): 1298- 300.
63. Su WPD, Duncan SC, Perry HO. Blastomycosis-like Pyoderma. Archives of dermatology 1979; 115(2): 170-3.
64. Kim RH, Lewin J, Hale CS, Meehan SA, Stein J, Ramachandran S. Vegetative pyoderma gangrenosum. Dermatology online journal 2014; 20(12).
65. Uchino M, Ikeuchi H, Matsuoka H, et al. Clinical features and management of parastomal pyoderma gangrenosum in inflammatory bowel disease. Digestion 2012; 85(4): 295-301.
66. Sheldon DG, Sawchuk LL, Kozarek RA, Thirlby RC. Twenty cases of peristomal pyoderma gangrenosum: diagnostic implications and management. Archives of surgery
(Chicago, Ill : 1960) 2000; 135(5): 564-8; discussion 8-9.
67. Watts JM, de Dombal FT, Goligher JC. Long-term complications and prognosis following major surgery for ulcerative colitis. The British journal of surgery 1966; 53(12): 1014-23. 68. Palumbo PJ, Ward LE, Sauer WG, Scudamore HH. Musculoskeletal manifestations of inflammatory bowel disease. Ulcerative and granulomatous colitis and ulcerative proctitis.
Mayo Clinic proceedings 1973; 48(6): 411-6.
69. Charles CA, Bialy TL, Falabella AF, Eaglstein WH, Kerdel FA, Kirsner RS. Poor prognosis of arthritis-associated pyoderma gangrenosum. Archives of dermatology 2004; 140(7): 861-4. 70. DeFilippis EM, Feldman SR, Huang WW. The genetics of pyoderma gangrenosum and implications for treatment: a systematic review. The British journal of dermatology 2015;
172(6): 1487-97.
71. Lazarus GS, Goldsmith LA, Rocklin RE, Pinals RS, de Buisseret JP, David JR. Pyoderma gangrenosum, altered delayed hypersensitivity and polyarthritis. Archives of dermatology 1972; 105(1): 46-51.
72. Duguid CM, Powell FC. Pyoderma gangrenosum. Clinics in dermatology 1993; 11(1): 129-33.
73. Ishikawa K, Minamimoto T, Mizuki T, Furukawa H. Surgical management of extensive peristomal pyoderma gangrenosum associated with colon cancer. Journal of wound, ostomy,
and continence nursing : official publication of The Wound, Ostomy and Continence Nurses Society 2015; 42(1): 102-5.
74. Ashchyan HJ, Butler DC, Nelson CA, et al. The Association of Age With Clinical Presentation and Comorbidities of Pyoderma Gangrenosum. JAMA Dermatol 2018; 154(4): 409-13.
75. Vacas AS, Bollea-Garlatti ML, Torre AC, Galimberti RL. Bullous pyoderma gangrenosum as a predictor of hematological malignancies. Anais brasileiros de dermatologia 2018; 93(1): 133-4.
76. Maverakis E, Ma C, Shinkai K, et al. Diagnostic Criteria of Ulcerative Pyoderma Gangrenosum: A Delphi Consensus of International Experts. JAMA Dermatol 2018; 154(4): 461- 6.
77. Kratzsch D, Ziemer M, Milkova L, Wagner JA, Simon JC, Kendler M. Facial pyoderma gangrenosum in senescence. Case reports in dermatology 2013; 5(3): 295-300.
78. Su WP, Davis MD, Weenig RH, Powell FC, Perry HO. Pyoderma gangrenosum: clinicopathologic correlation and proposed diagnostic criteria. International journal of
dermatology 2004; 43(11): 790-800.
79. Al Ghazal P, Klode J, Dissemond J. Diagnostic criteria for pyoderma gangrenosum: results of a survey among dermatologic wound experts in Germany. Journal der Deutschen
Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG 2014.
80. Spiers EM, Hendrick SJ, Jorizzo JL, Solomon AR. Sporotrichosis masquerading as pyoderma gangrenosum. Archives of dermatology 1986; 122(6): 691-4.
81. Lissner D, Sonnenberg E, Siegmund B. [Inflammatory bowel disease: cardinal signs and their diagnostics]. Deutsche medizinische Wochenschrift (1946) 2018; 113(13): 937-44. 82. Manz B, Rytter M, Mittag M, Seidel W, Nenoff P. [ANCA-positive vasculitis of the skin and kidneys associated with acne conglobata]. Der Hautarzt; Zeitschrift fur Dermatologie,
Venerologie, und verwandte Gebiete 2002; 53(11): 730-4.
83. Savoia F, Gaddoni G, Patrizi A, et al. Calciphylaxis in dialysis patients, a severe disease poorly responding to therapies: report of 4 cases. Giornale italiano di dermatologia e
venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia 2013; 148(5):
531-6.
84. Jasch KC, Hermes B, Scheller U, Harth W. Pyoderma gangrenosum-like primary cutaneous cryptococcosis. Acta dermato-venereologica 2008; 88(1): 76-7.
85. Yang CC, Hsieh FS, Lee JY. Pyoderma gangrenosum complicated by ecthyma gangrenosum. The British journal of dermatology 2004; 150(5): 1025-6.
86. Ehling A, Karrer S, Klebl F, Schaffler A, Muller-Ladner U. Therapeutic management of pyoderma gangrenosum. Arthritis and rheumatism 2004; 50(10): 3076-84.
87. Walling HW, Snipes CJ, Gerami P, Piette WW. The relationship between neutrophilic dermatosis of the dorsal hands and sweet syndrome: report of 9 cases and comparison to atypical pyoderma gangrenosum. Archives of dermatology 2006; 142(1): 57-63.
88. Smith GL, Bunker CB, Dinneen MD. Fournier's gangrene. British journal of urology 1998; 81(3): 347-55.
89. Baskin LS, Dixon C, Stoller ML, Carroll PR. Pyoderma gangrenosum presenting as Fournier's gangrene. The Journal of urology 1990; 144(4): 984-6.
90. Feldman SR, Lacy FA, Huang WW. The safety of treatments used in pyoderma gangrenosum. Expert opinion on drug safety 2018; 17(1): 55-61.
91. Nieto D, Sendagorta E, Rueda JM, Herranz P. Successful treatment with ustekinumab and vacuum-assisted closure therapy in recalcitrant myelodysplastic syndrome-associated pyoderma gangrenosum: case report and literature review. Clinical and experimental
dermatology 2018.
92. Mosti G. Wound care in venous ulcers. Phlebology 2013; 28 Suppl 1: 79-85.
93. Varol A, Seifert O, Anderson CD. The skin pathergy test: innately useful? Archives of
dermatological research 2010; 302(3): 155-68.
94. Pichler M, Thuile T, Gatscher B, et al. Systematic review of surgical treatment of pyoderma gangrenosum with negative pressure wound therapy or skin grafting. Journal of the
European Academy of Dermatology and Venereology : JEADV 2017; 31(2): e61-e7.
95. Chiba T, Isomura I, Suzuki A, Morita A. Topical tacrolimus therapy for pyoderma gangrenosum. The Journal of dermatology 2005; 32(3): 199-203.
96. Bellini V, Simonetti S, Lisi P. Successful treatment of severe pyoderma gangrenosum with pimecrolimus cream 1%. Journal of the European Academy of Dermatology and
Venereology : JEADV 2008; 22(1): 113-5.
97. Patel GK, Rhodes JR, Evans B, Holt PJ. Successful treatment of pyoderma gangrenosum with topical 0.5% nicotine cream. The Journal of dermatological treatment 2004; 15(2): 122-5. 98. Langenbach N, Goetz A, Hohenleutner U, Landthaler M. Effectiveness of 4% disodium cromoglycate in the treatment of disseminated pyoderma gangrenosum. Acta dermato-
venereologica 1996; 76(6): 501-2.
99. Soto Vilches F, Vera-Kellet C. Pyoderma gangrenosum: Classic and emerging therapies.
Medicina clinica 2017; 149(6): 256-60.
100. Lyon CC, Smith AJ, Beck MH, Wong GA, Griffiths CE. Parastomal pyoderma gangrenosum: clinical features and management. Journal of the American Academy of
Dermatology 2000; 42(6): 992-1002.
101. Fletcher J. Wound bed preparation and the TIME principles. Nursing standard (Royal
102. Halim AS, Khoo TL, Saad AZ. Wound bed preparation from a clinical perspective. Indian
journal of plastic surgery : official publication of the Association of Plastic Surgeons of India
2012; 45(2): 193-202.
103. Stojadinovic A, Carlson JW, Schultz GS, Davis TA, Elster EA. Topical advances in wound care. Gynecologic oncology 2008; 111(2 Suppl): S70-80.
104. Carville K. Which dressing should I use? It all depends on the 'TIMEING'. Australian
family physician 2006; 35(7): 486-9.
105. Falabella AF. Debridement and wound bed preparation. Dermatologic therapy 2006;
19(6): 317-25.
106. Douglass J. Wound bed preparation: a systematic approach to chronic wounds. British
journal of community nursing 2003; 8(6 Suppl): S26-34.
107. Dowsett C, Ayello E. TIME principles of chronic wound bed preparation and treatment.
British journal of nursing (Mark Allen Publishing) 2004; 13(15): S16-23.
108. Liaqat M, Elsensohn AN, Hansen CD, Maughan JA, Petersen MJ. Acute postoperative pyoderma gangrenosum case and review of literature identifying chest wall predominance and no recurrence following skin grafts. Journal of the American Academy of Dermatology 2014;
71(4): e145-6.
109. Jones JE, Nelson EA, Al-Hity A. Skin grafting for venous leg ulcers. The Cochrane
database of systematic reviews 2013; (1): Cd001737.
110. Stephenson AJ, Griffiths RW, La Hausse-Brown TP. Patterns of contraction in human full thickness skin grafts. British journal of plastic surgery 2000; 53(5): 397-402.
111. Webster J, Scuffham P, Sherriff KL, Stankiewicz M, Chaboyer WP. Negative pressure wound therapy for skin grafts and surgical wounds healing by primary intention. The Cochrane
database of systematic reviews 2012; (4): Cd009261.
112. Ali Z, Anjum A, Khurshid L, Ahad H, Maajid S, Dhar SA. Evaluation of low-cost custom made VAC therapy compared with conventional wound dressings in the treatment of non- healing lower limb ulcers in lower socio-economic group patients of Kashmir valley. Journal of
orthopaedic surgery and research 2015; 10: 183.
113. Ormerod AD, Thomas KS, Craig FE, et al. Comparison of the two most commonly used treatments for pyoderma gangrenosum: results of the STOP GAP randomised controlled trial.
BMJ (Clinical research ed) 2015; 350: h2958.
114. Reichrath J, Bens G, Bonowitz A, Tilgen W. Treatment recommendations for pyoderma gangrenosum: an evidence-based review of the literature based on more than 350 patients.
Journal of the American Academy of Dermatology 2005; 53(2): 273-83.
115. Staub J, Pfannschmidt N, Strohal R, et al. Successful treatment of PASH syndrome with infliximab, cyclosporine and dapsone. Journal of the European Academy of Dermatology and
Venereology : JEADV 2015; 29(11): 2243-7.
116. Dini V, Romanelli M, Bertone M, Talarico S, Bombardieri S, Barachini P. Improvement of idiopathic pyoderma gangrenosum during treatment with anti-tumor necrosis factor alfa monoclonal antibody. The international journal of lower extremity wounds 2007; 6(2): 108-13. 117. Tofteland ND, Shaver TS. Clinical efficacy of etanercept for treatment of PAPA syndrome. Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal
diseases 2010; 16(5): 244-5.
118. Ormerod AD, Thomas KS, Craig FE, et al. Comparison of the two most commonly used treatments for pyoderma gangrenosum: Results of the STOP GAP randomised controlled trial.
BMJ (Online) 2015; 350.
119. Craig FF, Thomas KS, Mitchell EJ, et al. UK Dermatology Clinical Trials Network's STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum): protocol for a randomised controlled trial. Trials 2012; 13: 51.
120. Nordstrom D. Intravenous cyclophosphamide pulses in the treatment of pyoderma gangrenosum associated with rheumatoid arthritis. The Journal of rheumatology 1995; 22(5): 1000-1.
121. Reynoso-von Drateln C, Perla-Navarro AV, Gamez-Nava JI, Gonzalez-Lopez L, Galvan- Villegas F, Ramos-Remus C. Intravenous cyclophosphamide pulses in pyoderma gangrenosum: an open trial. The Journal of rheumatology 1997; 24(4): 689-93.
122. Li J, Dai G, Zhang Z. General adverse response to cyclophosphamide in Chinese patients with systemic autoimmune diseases in recent decade-a single-center retrospective study.
Clinical rheumatology 2015; 34(2): 273-8.
123. Li J, Kelly R. Treatment of pyoderma gangrenosum with mycophenolate mofetil as a steroid-sparing agent. Journal of the American Academy of Dermatology 2013; 69(4): 565-9. 124. Androutsakos T, Stamopoulos P, Aroni K, Hatzis G. A case report of successful treatment of pyoderma gangrenosum in a patient with autoimmune hepatitis, and review of the literature. BMC gastroenterology 2015; 15: 149.
125. Hagman JH, Carrozzo AM, Campione E, Romanelli P, Chimenti S. The use of high-dose immunoglobulin in the treatment of pyoderma gangrenosum. The Journal of dermatological
treatment 2001; 12(1): 19-22.
126. de Zwaan SE, Iland HJ, Damian DL. Treatment of refractory pyoderma gangrenosum with intravenous immunoglobulin. The Australasian journal of dermatology 2009; 50(1): 56-9. 127. Ferkolj I, Hocevar A, Golouh R, Dolenc Voljc M. Infliximab for treatment of resistant pyoderma gangrenosum associated with Crohn's disease. Acta dermatovenerologica Alpina,