Abstract
Neutrophilic dermatoses are a group of conditions characterized by the accumulation of neutrophils in the skin and clinically presenting with polymorphic cutaneous lesions, including pustules, bullae, abscesses, papules, nodules, plaques and ulcers. In these disorders, the possible involvement of almost any organ system has lead to coin the term ‘neutrophilic diseases’. Neutrophilic diseases have close clinicopathological similarities with the autoinflammatory diseases, which present with recurrent episodes of inflammation in the affected organs in the absence of infection, allergy and frank autoimmunity. Neutrophilic diseases may be subdivided into three main groups: (1) deep or hypodermal forms whose paradigm is pyoderma gangrenosum, (2) plaque-type or dermal forms whose prototype is Sweet’s syndrome and (3) superficial or epidermal forms among which amicrobial pustulosis of the folds may be considered the model. A forth subset of epidermal/dermal/hypodermal forms has been recently added to the classification of neutrophilic diseases due to the emerging role of the syndromic pyoderma gangrenosum variants, whose pathogenesis has shown a relevant autoinflammatory component. An increasing body of evidence supports the role of pro-inflammatory cytokines like interleukin (IL)-1-beta, IL-17 and tumour necrosis factor (TNF)-alpha in the pathophysiology of neutrophilic diseases similarly to classic monogenic autoinflammatory diseases, suggesting common physiopathological mechanisms. Moreover, mutations of several genes involved in autoinflammatory diseases are likely to play a role in the pathogenesis of neutrophilic diseases, giving rise to regarding them as a spectrum of polygenic autoinflammatory conditions. In this review, we focus on clinical aspects, histopathological features and pathophysiological mechanisms of the paradigmatic forms of neutrophilic diseases, including pyoderma gangrenosum, Sweet’s syndrome, amicrobial pustulosis of the folds and the main syndromic presentations of pyoderma gangrenosum. A simple approach for diagnosis and management of these disorders has also been provided.
Similar content being viewed by others
References
Ahronowitz I, Harp J, Shinkai K (2012) Etiology and management of pyoderma gangrenosum: a comprehensive review. Am J Clin Dermatol 13:191–211. doi:10.2165/11595240-000000000-00000
Wallach D, Vignon-Pennamen MD (2006) From acute febrile neutrophilic dermatosis to neutrophilic disease: forty years of clinical research. J Am Acad Dermatol 55:1066–1071. doi:10.1016/j.jaad.2006.07.016
Kastner DL, Aksentijevich I, Goldbach-Mansky R (2010) Autoinflammatory disease reloaded: a clinical perspective. Cell 140:784–790. doi:10.1016/j.cell.2010.03.002
Alavi A, French LE, Davis MD, Brassard A, Kirsner RS (2017) Pyoderma gangrenosum: an update on pathophysiology, diagnosis and treatment. Am J Clin Dermatol (in press). doi:10.1007/s40257-017-0251-7
Wallach D, Vignon-Pennamen MD (2015) Pyoderma gangrenosum and Sweet syndrome: the prototypic neutrophilic dermatoses. Br J Dermatol. doi:10.1111/bjd.13955
Prat L, Bouaziz JD, Wallach D, Vignon-Pennamen MD, Bagot M (2014) Neutrophilic dermatoses as systemic diseases. Clin Dermatol 32:376–388. doi:10.1016/j.clindermatol.2013.11.004
Marzano AV, Borghi A, Stadnicki A, Crosti C, Cugno M (2014) Cutaneous manifestations in patients with inflammatory bowel diseases: pathophysiology, clinical features, and therapy. Inflamm Bowel Dis 20:213–227. doi:10.1097/01.MIB.0000436959.62286.f9
Callen JP (1998) Pyoderma gangrenosum. Lancet 351:581–585. doi:10.1016/S0140-6736(97)10187-8
Jaimes-Lopez N, Molina V, Arroyave JE, Vasquez LA, Ruiz AC, Castano R, Ruiz MH (2009) Development of pyoderma gangrenosum during therapy with infliximab. J Dermatol Case Rep 3:20–23. doi:10.3315/jdcr.2009.1027
White LE, Villa MT, Petronic-Rosic V, Jiang J, Medenica MM (2006) Pyoderma gangrenosum related to a new granulocyte colony-stimulating factor. Skinmed 5:96–98
Sagara R, Kitami A, Nakada T, Iijima M (2006) Adverse reactions to gefitinib (Iressa): revealing sycosis- and pyoderma gangrenosum-like lesions. Int J Dermatol 45:1002–1003. doi:10.1111/j.1365-4632.2006.02749.x
Marzano AV, Borghi A, Meroni PL, Cugno M (2016) Pyoderma gangrenosum and its syndromic forms: evidence for a link with autoinflammation. Br J Dermatol 175:882–891. doi:10.1111/bjd.14691
Cugno M, Borghi A, Marzano AV (2017) PAPA, PASH and PAPASH syndromes: pathophysiology, Presentation and Treatment. Am J Clin Dermatol. doi:10.1007/s40257-017-0265-1
Langan SM, Groves RW, Card TR, Gulliford MC (2012) Incidence, mortality, and disease associations of pyoderma gangrenosum in the United Kingdom: a retrospective cohort study. J Invest Dermatol 132:2166–2170. doi:10.1038/jid.2012.130
Von den Driesch P (1997) Pyoderma gangrenosum: a report of 44 cases with follow-up. Br J Dermatol 137:1000–1005
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. doi:10.3109/09546631003686069
Varol A, Seifert O, Anderson CD (2010) The skin pathergy test: innately useful? Arch Dermatol Res 302:155–168. doi:10.1007/s00403-009-1008-9
Tolkachjov SN, Fahy AS, Wetter DA, Brough KR, Bridges AG, Davis MD, El-Azhary RA, McEvoy MT, Camilleri MJ (2015) Postoperative pyoderma gangrenosum (PG): the Mayo Clinic experience of 20 years from 1994 through 2014. J Am Acad Dermatol 73:615–622. doi:10.1016/j.jaad.2015.06.054
Tuffaha SH, Sarhane KA, Mundinger GS, Broyles JM, Reddy SK, Azoury SC, Seal S, Cooney DS, Bonawitz SC (2016) Pyoderma gangrenosum after breast surgery: diagnostic pearls and treatment recommendations based on a systematic literature review. Ann Plast Surg 77:e39–e44. doi:10.1097/SAP.0000000000000248
Barbosa NS, Tolkachjov SN, El-Azhary RA, Davis MD, Camilleri MJ, McEvoy MT, Bridges AG, Wetter DA (2016) Clinical features, causes, treatments, and outcomes of peristomal pyoderma gangrenosum (PPG) in 44 patients: the Mayo Clinic experience, 1996 through 2013. J Am Acad Dermatol 75:931–939. doi:10.1016/j.jaad.2016.05.044
Marzano AV, Ishak RS, Saibeni S, Crosti C, Meroni PL, Cugno M (2013) Autoinflammatory skin disorders in inflammatory bowel diseases, pyoderma gangrenosum and Sweet’s syndrome: a comprehensive review and disease classification criteria. Clin Rev Allergy Immunol 45:202–210. doi:10.1007/s12016-012-8351-x
Perry HO, Winkelmann RK (1972) Bullous pyoderma gangrenosum and leukemia. Arch Dermatol 106:901–905
Ho KK, Otridge BW, Vandenberg E, Powell FC (1992) Pyoderma gangrenosum, polycythemia rubra vera, and the development of leukemia. J Am Acad Dermatol 27:804–808
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. doi:10.1111/j.1365-2230.2007.02607.x
Bennett ML, Jackson JM, Jorizzo JL, Fleischer AB Jr, White WL, Callen JP (2000) Pyoderma gangrenosum. A comparison of typical and atypical forms with an emphasis on time to remission. Case review of 86 patients from 2 institutions. Medicine (Baltimore) 79:37–46
Hughes AP, Jackson JM, Callen JP (2000) Clinical features and treatment of peristomal pyoderma gangrenosum. JAMA 284:1546–1548
Brunsting LA, Goeckerman WH, O’Leary PA (1930) Pyoderma (ecthyma) gangrenosum. Arch Dermatol Syphilol 22:655–680
Powell FC, Su WP, Perry HO (1996) Pyoderma gangrenosum: classification and management. J Am Acad Dermatol 34:395–409
Ruocco E, Sangiuliano S, Gravina AG, Miranda A, Nicoletti G (2009) Pyoderma gangrenosum: an updated review. J Eur Acad Dermatol Venereol 23:1008–1017. doi:10.1111/j.1468-3083.2009.03199.x
Langan SM, Powell FC (2005) Vegetative pyoderma gangrenosum: a report of two new cases and a review of the literature. Int J Dermatol 44:623–629. doi:10.1111/j.1365-4632.2005.02591.x
Kitagawa KH, Grassi M (2008) Primary pyoderma gangrenosum of the lungs. J Am Acad Dermatol 59(5 Suppl):S114–S116. doi:10.1016/j.jaad.2008.06.017
Vignon-Pennamen MD, Wallach D (1995) The neutrophilic disease: a review of extracutaneous neutrophilic manifestations. Eur J Dermatol 5:449–455
Marzano AV, Ishak RS, Lazzari R, Polloni I, Vettoretti S, Crosti C (2012) Vulvar pyoderma gangrenosum with renal involvement. Eur J Dermatol 22(4):537–539. doi:10.1684/ejd.2012.1776
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. doi:10.1111/j.1365-4632.2004.02128.x
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. doi:10.2340/00015555-0346
Binus AM, Qureshi AA, Li VW, Winterfield LS (2011) Pyoderma gangrenosum: a retrospective review of patient characteristics, comorbidities and therapy in 103 patients. Br J Dermatol 165:1244–1250. doi:10.1111/j.1365-2133.2011.10565.x
Koester G, Tarnower A, Levisohn D, Burgdorf W (1993) Bullous pyoderma gangrenosum. J Am Acad Dermatol 29:875–878
Sweet RD (1964) An acute febrile neutrophilic dermatosis. Br J Dermatol 76:349–356
Rochet NM, Chavan RN, Cappel MA, Wada DA, Gibson LE (2013) Sweet syndrome: clinical presentation, associations, and response to treatment in 77 patients. J Am Acad Dermatol 69:557
Cohen PR (2007) Sweet’s syndrome—a comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis 2:34. doi:10.1186/1750-1172-2-34
von den Driesch P, Gomez RS, Kiesewetter F, Hornstein OP (1989) Sweet’s syndrome: clinical spectrum and associated conditions. Cutis 44:193–200
Cohen PR, Kurzrock R (1989) Diagnosing the Sweet syndrome. Ann Intern Med 110:573–574
Boatman BW, Taylor RC, Klein LE (1994) Sweet’s syndrome in children. South Med J 87:193–196
Sommer S, Wilkinson SM, Merchant WJ, Goulden V (2000) Sweet’s syndrome presenting as palmoplantar pustulosis. J Am Acad Dermatol 42:332–334
Sutra-Loubet C, Carlotti A, Guillemette J, Wallach D (2004) Neutrophilic lobular panniculitis. J Am Acad Dermatol 50:280–285. doi:10.1016/j.jaad.2003.10.006
Chan MP, Duncan LM, Nazarian RM (2013) Subcutaneous Sweet syndrome in the setting of myeloid disorders: a case series and review of the literature. J Am Acad Dermatol 68:1006–1015. doi:10.1016/j.jaad.2012.12.954
Drago F, Ciccarese G, Agnoletti AF, Sarocchi F, Parodi A (2017) Neuro sweet syndrome: a systematic review. A rare complication of Sweet syndrome. Acta Neurol Belg 117:33–42
von den Driesch P (1994) Sweet’s syndrome (acute febrile neutrophilic dermatosis). J Am Acad Dermatol 31:535–556
Kemmett D, Hunter JAA (1990) Sweet’s syndrome: a clinicopathologic review of twenty-nine cases. J Am Acad Dermatol 23:503–507
Sitjas D, Cuatrecasas M, De Moragas JM (1993) Acute febrile neutrophilic dermatosis (Sweet’s syndrome). Int J Dermatol 32:261–268
Muster AJ, Bharati S, Herman JJ, Esterly NB, Gonzales-Crussi F, Holbrook KA (1983) Fatal cardiovascular disease and cutis laxa following acute febrile neutrophilic dermatosis. J Pediatr 102:243–248
Attias D, Laor R, Zuckermann E, Naschitz JE, Luria M, Misselevitch I, Boss JH (1995) Acute neutrophilic myositis in Sweet’s syndrome: late phase transformation into fibrosing myositis and panniculitis. Hum Pathol 26:687–690
Walker DC, Cohen PR (1996) Trimethoprim-sulfamethoxazole-associated acute febrile neutrophilic dermatosis: case report and review of drug induced Sweet’s syndrome. J Am Acad Dermatol 34:918–923
Mensing H, Kowalzick L (1991) Acute febrile neutrophilic dermatosis (Sweet’s syndrome) caused by minocycline. Dermatologica 182:43–46
Thompson DF, Montarella KE (2007) Drug-induced Sweet’s syndrome. Ann Pharmacother 41:802–811. doi:10.1345/aph.1H563
Marzano AV, Capsoni F, Berti E, Gasparini G, Bottelli S, Caputo R (1996) Amicrobial pustular dermatosis of cutaneous folds associated with autoimmune disorders: a new entity? Dermatology 193:88–93
Lagrange S, Chosidow O, Flette JC, Wechsler B, Godeau P, Frances C (1997) A peculiar form of amicrobial pustulosis of the folds associated with systemic lupus erythematosus and other autoimmune diseases. Lupus 6:514–520
Stefanidou MP, Kanavaros PE, Stefanaki KS, Tosca AD (1998) Amicrobial pustulosis of the folds: a cutaneous manifestation associated with connective tissue disease. Dermatology 197:394–396
Kuyama M, Fujimoto W, Kambara H, Egusa M, Saitoh M, Yamasaki O, Maehara K, Ohara A, Arata J, Iwatsuki K (2002) Amicrobial pustular dermatosis in two patients with immunological abnormalities. Clin Exp Dermatol 27:286–289
Kerl K, Masouyé I, Lesavre P, Saurat JH, Borradori L (2005) A case of amicrobial pustulosis of the folds associated with neutrophilic gastrointestinal involvement in systemic lupus erythematosus. Dermatology 211:356–359. doi:10.1159/000088508
Marzano AV, Ramoni S, Caputo R (2008) Amicrobial pustulosis of the folds. Report of 6 cases and a literature review. Dermatology 216:305–311. doi:10.1159/000113942
Méndez-Flores S, Charli-Joseph Y, Saeb-Lima M, Orozco-Topete R, Fernández Sánchez M (2013) Amicrobial pustulosis of the folds associated with autoimmune disorders: systemic lupus erythematosus case series and first report on the association with autoimmune hepatitis. Dermatology 226:1–4. doi:10.1159/000343595
Crickx B, Diego ML, Guillevin L, Picard C, Grossins M, Belaïch S (1991) Pustulose amicrobienne et lupus érythémateux systémique. Communication n° 11 (letter). Journées Dermatologiques de Paris París, March 1991
Oberlin P, Bagot M, Perrussel M, Leteinturier F, Wechsler J, Revuz J (1991) Pustulose amicrobienne et lupus érythémateux systémique. Ann Dermatol Vénéréol 118:824–825
Saiag PH, Blanc F, Marinho E, De La Blanchardière A, Leconte I, Cocheton JJ, Tulliez M (1993) Pustulose amicrobienne et lupus érythémateux systémique: un cas. Ann Dermatol Vénéréol 120:779–781
Bénéton N, Wolkenstein P, Bagot M, Cosnes A, Wechsler J, Roujeau JC, Revuz J (2000) Amicrobial pustulosis associated with autoimmune diseases: healing with zinc supplementation. Br J Dermatol 143:1306–1310
Claeys A, Bessis D, Cheikhrouhou H, Pouaha J, Cuny JF, Truchetet F (2011) Amicrobial pustulosis of the folds revealing asymptomatic autoimmune thyroiditis. Eur J Dermatol 21:641–642. doi:10.1684/ejd.2011.1406
Lim YL, Ng SK, Lian TY (2012) Amicrobial pustulosis associated with autoimmune disease in a patient with Sjögren syndrome and IgA nephropathy. Clin Exp Dermatol 37:374–378. doi:10.1111/j.1365-2230.2011.04262.x
Marzano AV, Tavecchio S, Berti E, Gelmetti C, Cugno M (2015) Cytokine and chemokine profile in amicrobial pustulosis of the folds: evidence for autoinflammation. Medicine (Baltimore) 94:e2301. doi:10.1097/MD.0000000000002301
Marzano AV, Tavecchio S, Berti E, Gelmetti C, Cugno M (2015) Paradoxical autoinflammatory skin reaction to tumor necrosis factor alpha blockers manifesting as amicrobial pustulosis of the folds in patients with inflammatory bowel diseases. Medicine (Baltimore) 94:e1818. doi:10.1097/MD.0000000000001818
Vignon-Pennamen MD, Wallach D (1991) Cutaneous manifestations of neutrophilic disease. Dermatologica 183:255–264
Natsuga K, Sawamura D, Homma E, Nomura T, Abe M, Muramatsu R, Mochizuki T, Koike T, Shimizu H (2007) Amicrobial pustulosis associated with IgA nephropathy and Sjögren’s syndrome. J Am Acad Dermatol 57:523–526. doi:10.1016/j.jaad.2007.05.023
Hoch O, Herbst RA, Gutzmer R, Kiehl P, Kapp A, Weiss J (1998) Amicrobial intertriginous pustulosis in autoimmune disease: a new entity? Hautarzt 49:634–640
López-Navarro N, Alcaide A, Gallego E, Herrera-Acosta E, Gallardo M, Bosch RJ, Herrera E (2009) Amicrobial pustulosis of the folds associated with Hashimoto’s thyroiditis. Clin Exp Dermatol 34:e561–e563. doi:10.1111/j.1365-2230.2009.03370.x
Lee HY, Pelivani N, Beltraminelli H, Hegyi I, Yawalkar N, Borradori L (2011) Amicrobial pustulosis-like rash in a patient with Crohn’s disease under anti-TNF-alpha blocker. Dermatology 222:304–310. doi:10.1159/000329428
Boms S, Gambichler T (2006) Review of literature on amicrobial pustulosis of the folds associated with autoimmune disorders. Am J Clin Dermatol 7:369–374
Naik HB, Cowen EW (2013) Autoinflammatory pustular neutrophilic diseases. Dermatol Clin 31:405–425. doi:10.1016/j.det.2013.04.001
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 11:961–969
Smith EJ, Allantaz F, Bennett L, Zhang D, Gao X, Wood G, Kastner DL, Punaro M, Aksentijevich I, Pascual V, Wise CA (2010) Clinical, molecular, and genetic characteristics of PAPA syndrome: a review. Curr Genomics 11:519–527. doi:10.2174/138920210793175921
Kistowska M, Gehrke S, Jankovic D, Kerl K, Fettelschoss A, Feldmeyer L, Fenini G, Kolios A, Navarini A, Ganceviciene R, Schauber J, Contassot E, French LE (2014) IL-1β drives inflammatory responses to Propionibacterium acnes in vitro and in vivo. J Invest Dermatol 134:677–685. doi:10.1038/jid.2013.438
Qin M, Pirouz A, Kim MH, Krutzik SR, Garbán HJ, Kim J (2014) Propionibacterium acnes induces IL-1β secretion via the NLRP3 inflammasome in human monocytes. J Invest Dermatol 134:381–388. doi:10.1038/jid.2013.309
Li ZJ, Choi DK, Sohn KC, Seo MS, Lee HE, Lee Y, Seo YJ, Lee YH, Shi G, Zouboulis CC, Kim CD, Lee JH, Im M (2014) Propionibacterium acnes activates the NLRP3 inflammasome in human sebocytes. J Invest Dermatol 134:2747–2756. doi:10.1038/jid.2014.221
Braun-Falco M, Kovnerystyy O, Lohse P, Ruzicka T (2012) Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH)—a new autoinflammatory syndrome distinct from PAPA syndrome. J Am Acad Dermatol 66:409–415. doi:10.1016/j.jaad.2010.12.025
Marzano AV, Ceccherini I, Gattorno M, Fanoni D, Caroli F, Rusmini M, Grossi A, De Simone C, Borghi OM, Meroni PL, Crosti C, Cugno M (2014) Association of pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) shares genetic and cytokine profiles with other autoinflammatory diseases. Medicine (Baltimore) 93:e187. doi:10.1097/MD.0000000000000187
van der Zee HH, Horvath B, Jemec GB, Prens EP (2016) The association between hidradenitis suppurativa and Crohn’s disease: in search of the missing pathogenic link. J Invest Dermatol 136:1747–1748. doi:10.1016/j.jid.2016.05.102
Damiani G, Della Valle V, Iannone M, Dini V, Marzano AV (2016) Autoinflammatory Disease Damage Index (ADDI): a possible newborn also in hidradenitis suppurativa daily practice. Ann Rheum Dis (in press). doi:10.1136/annrheumdis-2016-210901
Marzano AV (2016) Hidradenitis suppurativa, neutrophilic dermatoses and autoinflammation: what’s the link? Br J Dermatol 174:482–483. doi:10.1111/bjd.14364
Jemec GB (2012) Clinical practice. Hidradenitis suppurativa. N Engl J Med 366:158–164. doi:10.1056/NEJMcp1014163
Dessinioti C, Katsambas A, Antoniou C (2014) Hidradenitis suppurativa (acne inversa) as a systemic disease. Clin Dermatol 32:397–408. doi:10.1016/j.clindermatol.2013.11.006
Zouboulis CC, Desai N, Emtestam L, Hunger RE, Ioannides D, Juhász I, Lapins J, Matusiak L, Prens EP, Revuz J, Schneider-Burrus S, Szepietowski JC, van der Zee HH, Jemec GB (2015) European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa. J Eur Acad Dermatol Venereol 29:619–644. doi:10.1111/jdv.12966
Duchatelet S, Miskinyte S, Join-Lambert O, Ungeheuer MN, Francès C, Nassif A, Hovnanian A (2015) First nicastrin mutation in PASH (pyoderma gangrenosum, acne and suppurative hidradenitis) syndrome. Br J Dermatol 173:610–612. doi:10.1111/bjd.13668
Calderón-Castrat X, Bancalari-Diaz D, Román-Curto C, Romo-Melgar A, Amorós-Cerdán D, Alcaraz-Mas LA, Fernández-López E, Cañueto J (2016) PSTPIP1 gene mutation in a pyoderma gangrenosum, acne and suppurative hidradenitis (PASH) syndrome. Br J Dermatol 175:194–198. doi:10.1111/bjd.14383
Bruzzese V (2012) Pyoderma gangrenosum, acne conglobata, suppurative hidradenitis, and axial spondyloarthritis: efficacy of anti-tumor necrosis factor α therapy. J Clin Rheumatol 18:413–415. doi:10.1097/RHU.0b013e318278b84c
Marzano AV, Trevisan V, Gattorno M, Ceccherini I, De Simone C, Crosti C (2013) Pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PAPASH): a new autoinflammatory syndrome associated with a novel mutation of the PSTPIP1 gene. JAMA Dermatol 149:762–764. doi:10.1001/jamadermatol.2013.2907
Garzorz N, Papanagiotou V, Atenhan A, Andres C, Eyerich S, Eyerich K, Ring J, Brockow K (2016) Pyoderma gangrenosum, acne, psoriasis, arthritis and suppurative hidradenitis (PAPASH)-syndrome: a new entity within the spectrum of autoinflammatory syndromes? J Eur Acad Dermatol Venereol 30:141–143. doi:10.1111/jdv.12631
Saraceno R, Babino G, Chiricozzi A, Zangrilli A, Chimenti S (2015) PsAPASH: a new syndrome associated with hidradenitis suppurativa with response to tumor necrosis factor inhibition. J Am Acad Dermatol 72:e42–e44. doi:10.1016/j.jaad.2014.10.002
Navarini AA, Satoh TK, French LE (2016) Neutrophilic dermatoses and autoinflammatory diseases with skin involvement–innate immune disorders. Semin Immunopathol 38:45–56. doi:10.1007/s00281-015-0549-6
Satoh TK, Mellett M, Contassot E, French LE (2016) Are neutrophilic dermatoses autoinflammatory disorders? Br J Dermatol (in press). doi:10.1111/bjd.15105
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
Dinarello CA (2011) Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 117:3720–3732. doi:10.1182/blood-2010-07-273417
Broderick L, De Nardo D, Franklin BS, Hoffman HM, Latz E (2015) The inflammasomes and autoinflammatory syndromes. Annu Rev Pathol 10:395–424. doi:10.1146/annurev-pathol-012414-040431
Hoffman HM, Mueller JL, Broide DH, Wanderer AA, Kolodner RD (2001) Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nat Genet 29:301–305
Martinon F, Burns K, Tschopp J (2002) The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell 10:417–426
Saïd-Sadier N, Ojcius DM (2012) Alarmins, inflammasomes and immunity. Biom J 35:437–449. doi:10.4103/2319-4170.104408
Marzano AV, Damiani G, Ceccherini I, Berti E, Gattorno M, Cugno M (2016) Autoinflammation in pyoderma gangrenosum and its syndromic form PASH. Br J Dermatol. doi:10.1111/bjd.15226
Tallon B, Corkill M (2006) Peculiarities of PAPA syndrome. Rheumatology 45:1140–1143. doi:10.1093/rheumatology/kei178
Yeon HB, Lindor NM, Seidman JG, Seidman CE (2000) Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome maps to chromosome 15q. Am J Hum Genet 66:1443–1448
Heymann MC, Rosen-Wolff A (2013) Contribution of the inflammasomes to autoinflammatory diseases and recent mouse models as research tools. Clin Immunol 147:175–184. doi:10.1016/j.clim.2013.01.006
Wollina U, Tchernev G (2014) Pyoderma gangrenosum: pathogenetic oriented treatment approaches. Wien Med Wochenschr 164:263–273. doi:10.1007/s10354-014-0285-x
Wollina U, Haroske G (2011) Pyoderma gangraenosum. Curr Opin Rheumatol 23:50–56. doi:10.1097/BOR.0b013e328341152f
Palanivel JA, Macbeth AE, Levell NJ (2013) Pyoderma gangrenosum in association with Janus kinase 2 (JAK2V617F) mutation. Clin Exp Dermatol 38:44–46. doi:10.1111/j.1365-2230.2012.04375.x
DeFilippis EM, Feldman SR, Huang WW (2015) The genetics of pyoderma gangrenosum and implications for treatment: a systematic review. Br J Dermatol 172:1487–1497. doi:10.1111/bjd.13493
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. doi:10.1111/j.1365-2249.2010.04201.x
Marzano AV, Fanoni D, Antiga E, Quaglino P, Caproni M, Crosti C, Meroni PL, Cugno M (2014) Expression of cytokines, chemokines and other effector molecules in two prototypic autoinflammatory skin diseases, pyoderma gangrenosum and Sweet’s syndrome. Clin Exp Immunol 178:48–56. doi:10.1111/cei.12394
Lima AL, Karl I, Giner T, Poppe H, Schmidt M, Presser D, Goebeler M, Bauer B (2016) Keratinocytes and neutrophils are important sources of proinflammatory molecules in hidradenitis suppurativa. Br J Dermatol 174:514–521. doi:10.1111/bjd.14214
Shoham NG, Centola M, Mansfield E, Hull KM, Wood G, Wise CA, Kastner DL (2003) Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever andPAPA syndrome as disorders in the same pathway. Proc Natl Acad Sci U S A 100:13501–13506. doi:10.1073/pnas.2135380100
Braswell SF, Kostopoulos TC, Ortega-Loayza AG (2015) Pathophysiology of pyoderma gangrenosum (PG): an updated review. J Am Acad Dermatol 73:691–698. doi:10.1016/j.jaad.2015.06.021
Caproni M, Antiga E, Volpi W, Verdelli A, Venegoni L, Quaglino P, Fabbri P, Marzano AV (2015) The Treg/Th17 cell ratio is reduced in the skin lesions of patients with pyoderma gangrenosum. Br J Dermatol 173:275–278. doi:10.1111/bjd.13670
Amazan E, Ezzedine K, Mossalayi MD, Taieb A, Boniface K, Seneschal J (2014) Expression of interleukin-1 alpha in amicrobial pustulosis of the skin folds with complete response to anakinra. J Am Acad Dermatol 71:e53–e56. doi:10.1016/j.jaad.2013.12.041
Marzano AV, Cugno M, Trevisan V, Lazzari R, Fanoni D, Berti E, Crosti C (2011) Inflammatory cells, cytokines and matrix metalloproteinases in amicrobialpustulosis of the folds and other neutrophilic dermatoses. Int J Immunopathol Pharmacol 24:451–460. doi:10.1177/039463201102400218
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. doi:10.1136/gut.2005.074815
Ormerod AD, Thomas KS, Craig FE, Mitchell E, Greenlaw N, Norrie J, Mason JM, Walton S, Johnston GA, Williams HC, UK Dermatology Clinical Trials Network’s STOP GAP Team (2015) Comparison of the two most commonly used treatments for pyoderma gangrenosum: results of the STOP GAP randomised controlled trial. BMJ 350:h2958. doi:10.1136/bmj.h2958
Reichrath J, Bens G, Bonowitz A, Tilgen W (2005) Treatment recommendations for pyoderma gangrenosum: an evidence-based review of the literature based on more than 350 patients. J Am Acad Dermatol 53:273–283. doi:10.1016/j.jaad.2004.10.006
Miller J, Yentzer BA, Clark A, Jorizzo JL, Feldman SR (2010) Pyoderma gangrenosum: a review and update on new therapies. J Am Acad Dermatol 62:646–654. doi:10.1016/j.jaad.2009.05.030
Maalouf D, Battistella M, Bouaziz JD (2015) Neutrophilic dermatosis: disease mechanism and treatment. Curr Opin Hematol 22:23–29. doi:10.1097/MOH.0000000000000100
Thomas KS, Ormerod AD, Craig FE, Greenlaw N, Norrie J, Mitchell E, Mason JM, Johnston GA, Wahie S, Williams HC, UK Dermatology Clinical Trials Network’s STOP GAP Team (2016) Clinical outcomes and response of patients applying topical therapy for pyoderma gangrenosum: a prospective cohort study. J Am Acad Dermatol 75:940–949. doi:10.1016/j.jaad.2016.06.016
Bhat YJ, Hassan I, Sajad P, Akhtar S, Sheikh S (2015) Sweet’s syndrome: an evidence-based report. J Coll Physicians Surg Pak 25:525–527
Chokoeva AA, Cardoso JC, Wollina U, Tchernev G (2017) Pyoderma gangrenosum—a novel approach? Wien Med Wochenschr 167(3–4):58–65. doi:10.1007/s10354-016-0472-z
Pazyar N, Feily A, Yaghoobi R (2012) An overview of interleukin-1 receptor antagonist, anakinra, in the treatment of cutaneous diseases. Curr Clin Pharmacol 7:271–275
Lukens JR, Kanneganti TD (2014) SHP-1 and IL-1α conspire to provoke neutrophilic dermatoses. Rare Dis 2:e27742. doi:10.4161/rdis.27742
Brenner M, Ruzicka T, Plewig G, Thomas P, Herzer P (2009) Targeted treatment of pyoderma gangrenosum in PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) syndrome with the recombinant human interleukin-1 receptor antagonist anakinra. Br J Dermatol 161:1199–1201. doi:10.1111/j.1365-2133.2009.09404.x
Dierselhuis MP, Frenkel J, Wulffraat NM, Boelens JJ (2005) Anakinra for flares of pyogenic arthritis in PAPA syndrome. Rheumatology (Oxford) 44:406–408. doi:10.1093/rheumatology/keh479
Dinarello CA, van der Meer JW (2013) Treating inflammation by blocking interleukin-1 in humans. Semin Immunol 25:469–484. doi:10.1016/j.smim.2013.10.008
Jaeger T, Andres C, Grosber M, Zirbs M, Hein R, Ring J, Traidl-Hoffmann C (2013) Pyoderma gangrenosum and concomitant hidradenitis suppurativa—rapid response to canakinumab (anti-IL-1β). Eur J Dermatol 23:408–410. doi:10.1684/ejd.2013.2018
Geusau A, Mothes-Luksch N, Nahavandi H, Pickl WF, Wise CA, Pourpak Z, Ponweiser E, Eckhart L, Sunder-Plassmann R (2013) Identification of a homozygous PSTPIP1 mutation in a patient with a PAPA-like syndrome responding to canakinumab treatment. JAMA Dermatol 149:209–215. doi:10.1001/2013.jamadermatol.717
Kolios AG, Maul JT, Meier B, Kerl K, Traidl-Hoffmann C, Hertl M, Zillikens D, Röcken M, Ring J, Facchiano A, Mondino C, Yawalkar N, Contassot E, Navarini AA, French LE (2015) Canakinumab in adults with steroid-refractory pyoderma gangrenosum. Br J Dermatol 173:1216–1223. doi:10.1111/bjd.14037
Krause K, Tsianakas A, Wagner N, Fischer J, Weller K, Metz M, Church MK, Maurer M (2017) Efficacy and safety of canakinumab in Schnitzler syndrome: a multicenter randomized placebo-controlled study. J Allergy Clin Immunol 139:1311–1320. doi:10.1016/j.jaci.2016.07.041
Stichweh DS, Punaro M, Pascual V (2005) Dramatic improvement of pyoderma gangrenosum with infliximab in a patient with PAPA syndrome. Pediatr Dermatol 22:262–265. doi:10.1111/j.1525-1470.2005.22320.x
Tofteland ND, Shaver TS (2010) Clinical efficacy of etanercept for treatment of PAPA syndrome. J Clin Rheumatol 16:244–245. doi:10.1097/RHU.0b013e3181e969b9
Lee H, Park SH, Kim SK, Choe JY, Park JS (2012) Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome (PAPA syndrome) with E250K mutation in CD2BP1 gene treated with the tumor necrosis factor inhibitor adalimumab. Clin Exp Rheumatol 30:452
Langley RG, Elewski BE, Lebwohl M, Reich K, Griffiths CE, Papp K, et al (2014) ERASURE Study Group.; FIXTURE Study Group. Secukinumab in plaque psoriasis-results of two phase 3 trials. N Engl J Med 371:326–338. doi: 10.1056/NEJMoa1314258
Burkett PR, Kuchroo VK (2016) IL-17 blockade in psoriasis. Cell 167:1669. doi:10.1016/j.cell.2016.11.044
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
The authors declare that they have no conflict of interest.
Funding
None.
Ethical Approval and Informed Consent
Not necessary.
Rights and permissions
About this article
Cite this article
Marzano, A.V., Borghi, A., Wallach, D. et al. A Comprehensive Review of Neutrophilic Diseases. Clinic Rev Allerg Immunol 54, 114–130 (2018). https://doi.org/10.1007/s12016-017-8621-8
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12016-017-8621-8