Abstract
Pyoderma gangrenosum (PG) and Sweet’s syndrome (SS) are skin diseases usually presenting with recurrent ulcers and erythematous plaques, respectively. The accumulation of neutrophils in the skin, characteristic of these conditions, led to coin the term of neutrophilic dermatoses to define them. Recently, neutrophilic dermatoses have been included in the group of autoinflammatory diseases, which classically comprises genetically determined forms due to mutations of genes regulating the innate immune response. Both PG and SS are frequently associated with inflammatory bowel diseases (IBDs); however, IBD patients develop PG in 1–3 % of cases, whereas SS is rarer. Clinically, PG presents with deep erythematous-to-violaceous painful ulcers with well-defined borders; bullous, pustular, and vegetative variants can also occur. SS is characterized by the abrupt onset of fever, peripheral neutrophilia, tender erythematous skin lesions, and a diffuse neutrophilic dermal infiltrate. It is also known as acute febrile neutrophilic dermatosis. Treatment of PG involves a combination of wound care, topical medications, antibiotics for secondary infections, and treatment of the underlying IBD. Topical therapies include corticosteroids and the calcineurin inhibitor tacrolimus. The most frequently used systemic medications are corticosteroids and cyclosporine, in monotherapy or in combination. Dapsone, azathioprine, cyclophosphamide, methotrexate, intravenous immunoglobulins, mycophenolate mofetil, and plasmapheresis are considered second-line agents. Hyperbaric oxygen, as supportive therapy, can be added. Anti-TNF-α agents such as etanercept, infliximab, and adalimumab are used in refractory cases. SS is usually responsive to oral corticosteroids, and the above-mentioned immunosuppressants should be considered in resistant or highly relapsing cases.
Similar content being viewed by others
References
Cohen PR (2009) Neutrophilic dermatoses: a review of current treatment options. Am J Clin Dermatol 10:301–312
Ahronowitz I, Harp J, Shinkai K (2012) Etiology and management of pyoderma gangrenosum: a comprehensive review. Am J Clin Dermatol 13:191–211
Marzano AV, Trevisan V, Lazzari R, Crosti C (2011) Pyoderma gangrenosum: study of 21 patients and proposal of a ‘clinicotherapeutic’ classification. J Dermatol Treat 22:254–260
Nesterovitch AB, Gyorfy Z, Hoffman MD, Moore EC, Elbuluk N, Tryniszewska B, Rauch TA, Simon M, Kang S, Fisher GJ, Mikecz K, Tharp MD, Glant TT (2011) Alteration in the gene encoding protein tyrosine phosphatase nonreceptor type 6 (PTPN6/SHP1) may contribute to neutrophilic dermatoses. Am J Pathol 178:1434–1441
Aksentijevich I, Kastner DL (2011) Genetics of monogenic autoinflammatory diseases: past successes, future challenges. Nat Rev Rheumatol 7:469–78
McDermott MF, Aksentijevich I, Galon J, McDermott EM, Ogunkolade BW, Centola M, Mansfield E, Gadina M, Karenko L, Pettersson T, McCarthy J, Frucht DM, Aringer M, Torosyan Y, Teppo AM, Wilson M, Karaarslan HM, Wan Y, Todd I, Wood G, Schlimgen R, Kumarajeewa TR, Cooper SM, Vella JP, Amos CI, Mulley J, Quane KA, Molloy MG, Ranki A, Powell RJ, Hitman GA, O'Shea JJ, Kastner DL (1999) Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell 97:133–144
Kastner DL, Aksentijevich I, Goldbach-Mansky R (2010) Autoinflammatory disease reloaded: a clinical perspective. Cell 140:784–90
Doria A, Zen M, Bettio S, Gatto M, Bassi N, Nalotto L, Ghirardello A, Iaccarino L, Punzi L (2012) Autoinflammation and autoimmunity: bridging the divide. Autoimmun Rev 12:22–30
Wise CA, Gillum JD, Seidman CE, Lindor NM, Veile R, Bashiardes S, Lovett M (2002) Mutations in CD2BP1 disrupt binding to PTP PEST and are responsible for PAPA syndrome, an autoinflammatory disorder. Hum Mol Genet 11:961–9
Dinarello CA (2011) A clinical perspective of IL-1β as the gatekeeper of inflammation. Eur J Immunol 41:1203–1217
Abraham C, Cho JH (2009) Inflammatory bowel disease. N Engl J Med 361:2066–2078
Rothfuss KS, Stange EF, Herrlinger KR (2006) Extraintestinal manifestations and complications in inflammatory bowel diseases. World J Gastroenterol 12:4819–4831
Larsen S, Bendtzen K, Nielsen OH (2010) Extraintestinal manifestations of inflammatory bowel disease: epidemiology, diagnosis, and management. Ann Med 42:97–114
Wollina U (2002) Clinical management of pyoderma gangrenosum. Am J Clin Dermatol 3:149–158
Powell FC, Su WP, Perry HO (1996) Pyoderma gangrenosum: classification and management. J Am Acad Dermatol 34:395–409, quiz 410–392
Callen JP (1996) Pyoderma gangrenosum. Lancet 351:581–585
Marzano AV, Ishak RS, Lazzari R, Polloni I, Vettoretti S, Crosti C (2012) Vulvar pyoderma gangrenosum with renal involvement. Eur J Dermatol 22:537–539
Ruocco E, Sangiuliano S, Gravina AG, Miranda A, Nicoletti G (2009) Pyoderma gangrenosum: an updated review. J Eur Acad Dermatol Venereol 23:1008–1017
Marzano AV, Cugno M, Trevisan V, Fanoni D, Venegoni L, Berti E, Crosti C (2010) Role of inflammatory cells, cytokines and matrix metalloproteinases in neutrophil-mediated skin diseases. Clin Exp Immunol 162:100–107
O'Loughlin S, Perry HO (1978) A diffuse pustular eruption associated with ulcerative colitis. Arch Dermatol 114:1061–1064
Su WP, Davis MD, Weenig RH, Powell FC, Perry HO (2004) Pyoderma gangrenosum: clinicopathologic correlation and proposed diagnostic criteria. Int J Dermatol 43:790–800
Conrad C, Trueb RM (2005) Pyoderma gangrenosum. J Dtsch Dermatol Ges 3:334–342
Perry HO, Winkelmann RK (1972) Bullous pyoderma gangrenosum and leukemia. Arch Dermatol 106:901–905
Marzano AV, Trevisan V, Galloni C, Alessi E (2008) Fatal bullous pyoderma gangrenosum in a patient with Klinefelter’s syndrome. Acta Derm Venereol 88:158–159
Wilson-Jones E, Winkelmann RK (1988) Superficial granulomatous pyoderma: a localized vegetative form of pyoderma gangrenosum. J Am Acad Dermatol 18:511–521
Marzano AV, Tourlaki A, Alessi E, Caputo R (2008) Widespread idiopathic pyoderma gangrenosum evolved from ulcerative to vegetative type: a 10-year history with a recent response to infliximab. Clin Exp Dermatol 33:156–159
Lyon CC, Smith AJ, Beck MH, Wong GA, Griffiths CE (2000) Parastomal pyoderma gangrenosum: clinical features and management. J Am Acad Dermatol 42:992–1002
Tjandra JJ, Hughes LE (1994) Parastomal pyoderma gangrenosum in inflammatory bowel disease. Dis Colon Rectum 37:938–942
Cohen PR, Kurzrock R (2003) Sweet’s syndrome revisited: a review of disease concepts. Int J Dermatol 42:761–778
Cohen PR, Almeida L, Kurzrock R (1989) Acute febrile neutrophilic dermatosis. Am Fam Physician 39:199–204
Carpentier O, Piette F, Delaporte E (2002) Sweet’s syndrome after BCG vaccination. Acta Derm Venereol 82:221
Arbetter KR, Hubbard KW, Markovic SN, Gibson LE, Phyliky RL (1999) Case of granulocyte colony-stimulating factor-induced Sweet’s syndrome. Am J Hematol 61:126–129
Kawakami T, Ohashi S, Kawa Y, Takahama H, Ito M, Soma Y, Mizoguchi M (2004) Elevated serum granulocyte colony-stimulating factor levels in patients with active phase of sweet syndrome and patients with active Behcet disease: implication in neutrophil apoptosis dysfunction. Arch Dermatol 140:570–574
Kumar G, Bernstein JM, Waibel JS, Baumann MA (2004) Sweet’s syndrome associated with sargramostim (granulocyte-macrophage colony stimulating factor) treatment. Am J Hematol 76:283–285
Dereure O, Hillaire-Buys D, Guilhou JJ (2004) Neutrophil-dependent cutaneous side-effects of leucocyte colony-stimulating factors: manifestations of a neutrophil recovery syndrome? Br J Dermatol 150:1228–1230
Cohen PR (2007) Sweet’s syndrome: a comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis 2:34
Cohen PR, Kurzrock R (2000) Sweet’s syndrome: a neutrophilic dermatosis classically associated with acute onset and fever. Clin Dermatol 18:265–282
Neoh CY, Tan AW, Ng SK (2007) Sweet’s syndrome: a spectrum of unusual clinical presentations and associations. Br J Dermatol 156:480–485
Bielsa S, Baradad M, Marti RM, Casanova JM (2005) Sweet’s syndrome with bullous lesions. Actas Dermosifiliogr 96:315–316
Voelter-Mahlknecht S, Bauer J, Metzler G, Fierlbeck G, Rassner G (2005) Bullous variant of Sweet’s syndrome. Int J Dermatol 44:946–947
Sommer S, Wilkinson SM, Merchant WJ, Goulden V (2000) Sweet’s syndrome presenting as palmoplantar pustulosis. J Am Acad Dermatol 42:332–334
Cohen PR (2005) Subcutaneous Sweet’s syndrome: a variant of acute febrile neutrophilic dermatosis that is included in the histopathologic differential diagnosis of neutrophilic panniculitis. J Am Acad Dermatol 52:927–928
Sweet RD (1964) An acute febrile neutrophilic dermatosis. Br J Dermatol 76:349–356
Cooper PH, Frierson HF, Greer KE (1983) Subcutaneous neutrophilic infiltrates in acute febrile neutrophilic dermatosis. Arch Dermatol 119:610–611
Cullity J, Maguire B, Gebauer K (1991) Sweet’s panniculitis. Australas J Dermatol 32:61–64
Suzuki Y, Kuroda K, Kojima T, Fujita M, Iseki T, Shinkai H (1995) Unusual cutaneous manifestations of myelodysplastic syndrome. Br J Dermatol 133:483–486
Cohen PR, Kurzrock R (1993) Sweet’s syndrome and cancer. Clin Dermatol 11:149–157
Cohen PR, Kurzrock R (1987) Sweet’s syndrome and malignancy. Am J Med 82:1220–1226
Vind I, Riis L, Jess T, Knudsen E, Pedersen N, Elkjaer M, Bak Andersen I, Wewer V, Nørregaard P, Moesgaard F, Bendtsen F, Munkholm P, DCCD study group (2006) Increasing incidences of inflammatory bowel disease and decreasing surgery rates in Copenhagen City and County, 2003–2005: a population-based study from the Danish Crohn colitis database. Am J Gastroenterol 101:1274–1282
Vavricka SR, Brun L, Ballabeni P, Pittet V, Prinz Vavricka BM, Zeitz J, Rogler G, Schoepfer AM (2011) Frequency and risk factors for extraintestinal manifestations in the Swiss inflammatory bowel disease cohort. Am J Gastroenterol 106:110–119
Williams H, Walker D, Orchard TR (2008) Extraintestinal manifestations of inflammatory bowel disease. Curr Gastroenterol Rep 10:597–605
Requena L, Yus ES (2008) Erythema nodosum. Dermatol Clin 26:425–438
Danese S, Semeraro S, Papa A, Roberto I, Scaldaferri F, Fedeli G, Gasbarrini G, Gasbarrini A (2005) Extraintestinal manifestations in inflammatory bowel disease. World J Gastroenterol 11:7227–7236
Bernstein CN, Blanchard JF, Rawsthorne P, Yu N (2001) The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study. Am J Gastroenterol 96:1116–1122
Trost LB, McDonnell JK (2005) Important cutaneous manifestations of inflammatory bowel disease. Postgrad Med J 81:580–585
Thornton JR, Teague RH, Low-Beer TS, Read AE (1980) Pyoderma gangrenosum and ulcerative colitis. Gut 21:247–248
Levitt MD, Ritchie JK, Lennard-Jones JE, Phillips RK (1991) Pyoderma gangrenosum in inflammatory bowel disease. Br J Surg 78:676–678
Menachem Y, Gotsman I (2004) Clinical manifestations of pyoderma gangrenosum associated with inflammatory bowel disease. Isr Med Assoc J 6:88–90
Goudet P, Dozois RR, Kelly KA, Ilstrup DM, Phillips SF (2001) Characteristics and evolution of extraintestinal manifestations associated with ulcerative colitis after proctocolectomy. Dig Surg 18:51–55
Mir-Madjlessi SH, Taylor JS, Farmer RG (1985) Clinical course and evolution of erythema nodosum and pyoderma gangrenosum in chronic ulcerative colitis: a study of 42 patients. Am J Gastroenterol 80:615–620
Marzano AV, Trevisan V, Lazzari R, Crosti C (2010) Topical tacrolimus for the treatment of localized, idiopathic, newly diagnosed pyoderma gangrenosum. J Dermatol Treat 21:140–143
Timani S, Mutasim DF (2008) Skin manifestations of inflammatory bowel disease. Clin Dermatol 26:265–273
Huang BL, Chandra S, Shih DQ (2012) Skin manifestations of inflammatory bowel disease. Front Physiol 3:13
Wasserteil V, Bruce S, Sessoms SL, Guntupalli KK (1992) Pyoderma gangrenosum treated with hyperbaric oxygen therapy. Int J Dermatol 31:594–596
Brooklyn TN, Dunnill MG, Shetty A, Bowden JJ, Williams JD, Griffiths CE, Forbes A, Greenwood R, Probert CS (2006) Infliximab for the treatment of pyoderma gangrenosum: a randomised, double blind, placebo controlled trial. Gut 55:505–509
Alkhouri N, Hupertz V, Mahajan L (2009) Adalimumab treatment for peristomal pyoderma gangrenosum associated with Crohn’s disease. Inflamm Bowel Dis 15:803–806
Guenova E, Teske A, Fehrenbacher B, Hoerber S, Adamczyk A, Schaller M, Hoetzenecker W, Biedermann T (2011) Interleukin 23 expression in pyoderma gangrenosum and targeted therapy with ustekinumab. Arch Dermatol 147:1203–1205
Vij A, Modi GM, Suwattee P, Cockerell CJ, Hsu S (2010) Chronic, recurrent neutrophilic dermatosis: a case report. Dermatol Online J 16:1
Kemmett D, Hunter JA (1990) Sweet’s syndrome: a clinicopathologic review of twenty-nine cases. J Am Acad Dermatol 23:503–507
Souissi A, Benmously R, Fenniche S, Zarrouk M, Marrek H, Debbiche A, Ayed MB, Mokhtar I (2007) Sweet’s syndrome: a propos of 8 cases. Tunis Med 85:49–53
Kemmett D, Gawkrodger DJ, Wilson G, Hunter JA (1988) Sweet’s syndrome in Crohn’s disease. BMJ 297:1513–1514
Paoluzi OA, Crispino P, Amantea A, Pica R, Iacopini F, Consolazio A, Di Palma V, Rivera M, Paoluzi P (2004) Diffuse febrile dermatosis in a patient with active ulcerative colitis under treatment with steroids and azathioprine: a case of Sweet’s syndrome. Case report and review of literature. Dig Liver Dis 36:361–366
Burrows NP (1995) Sweet’s syndrome in association with Crohn’s disease. Clin Exp Dermatol 20:279–280
Ytting H, Vind I, Bang D, Munkholm P (2005) Sweet’s syndrome—an extraintestinal manifestation in inflammatory bowel disease. Digestion 72:195–200
Ardizzone S, Puttini PS, Cassinotti A, Porro GB (2008) Extraintestinal manifestations of inflammatory bowel disease. Dig Liver Dis 40(Suppl 2):S253–259
Darvay A (1996) Sweet’s syndrome preceding inflammatory bowel disease. Clin Exp Dermatol 21:175
Travis S, Innes N, Davies MG, Daneshmend T, Hughes S (1997) Sweet’s syndrome: an unusual cutaneous feature of Crohn’s disease or ulcerative colitis. The South West Gastroenterology Group. Eur J Gastroenterol Hepatol 9:715–720
Greenstein AJ, Janowitz HD, Sachar DB (1976) The extra-intestinal complications of Crohn's disease and ulcerative colitis: a study of 700 patients. Medicine (Baltimore) 55:401–412
Cohen PR, Talpaz M, Kurzrock R (1988) Malignancy-associated Sweet’s syndrome: review of the world literature. J Clin Oncol 6:1887–1897
Ali M, Duerksen DR (2008) Ulcerative colitis and Sweet's syndrome: a case report and review of the literature. Can J Gastroenterol 22:296–298
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Marzano, A.V., Ishak, R.S., Saibeni, S. et al. Autoinflammatory Skin Disorders in Inflammatory Bowel Diseases, Pyoderma Gangrenosum and Sweet’s Syndrome: a Comprehensive Review and Disease Classification Criteria. Clinic Rev Allerg Immunol 45, 202–210 (2013). https://doi.org/10.1007/s12016-012-8351-x
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12016-012-8351-x