Amicrobial pustulosis of the folds (APF) is a recently described entity characterized by relapsing pustular lesions predominantly involving the cutaneous flexures and scalp. This disease typically occurs in association with systemic lupus erythematosus and a variety of other autoimmune diseases. We here describe an APF-like pustular eruption predominantly affecting the scalp, face and trunk, occurring during long-term infliximab treatment for Crohn’s disease. Immunohistochemical staining of skin biopsy specimens for myxovirus resistance protein A, a marker for type 1 interferon-inducible proteins, showed increased staining in the epidermis and dermal mononuclear inflammatory infiltrate. Our observation further extends the spectrum of cutaneous adverse reactions potentially related to anti-tumor necrosis factor-α, the clinical context in which APF can occur as well as its clinical presentations.

1.
Crickx B: Pustulose amicrobienne et lupus érythémateux systémique. Journées Dermatologiques de Paris, Paris 1991, C11.
2.
Kerl K, Masouyé I, Lesavre P, Saurat JH, Borradori L: A case of amicrobial pustulosis of the folds associated with neutrophilic gastrointestinal involvement with systemic lupus erythematosus. Dermatology 2005;211:356–359.
3.
Antille C, Frei M, Sorg O, Tran C, Kaya G, Masouyé I, Fontao L, Prins C, Saurat JH: Amicrobial pustulosis of the folds associated with auto-immune disorders: a case report with an analysis of cytokine expression profile in skin lesions of cutaneous neutrophilic lupus. Dermatology 2008;216:324–329.
4.
Lagrange S, Chowsidow O, Piette JC, Wechsler B, Godeau P, Frances C: A peculiar form of amicrobial pustulosis of the folds associated with systemic lupus erythematosus and other auto-immune diseases. Lupus 1997;6:514–520.
5.
Marzano AV, Capsoni F, Berti E, Gasparini G, Bottelli S, Caputo R: Amicrobial pustular dermatosis of cutaneous folds associated with autoimmune disorders: a new entity? Dermatology 1996;193:88–93.
6.
Marzano AV, Ramoni S, Caputo R: Amicrobial pustulosis of the folds. Dermatology 2008;216:305–311.
7.
Saiag P, Blanc F, Marinho E, De la Blanchardière A, Leconte I, Cocheton JJ, Tulliez M: Amicrobial pustulosis and systemic lupus erythematosus: a case. Ann Dermatol Venereol 1993;120:779–781.
8.
Stefanidou MP, Kanavaros PE, Stefanaki KS, Tosca AD: Amicrobial pustulosis of the folds: a cutaneous manifestation associated with connective tissue disease. Dermatology 1998;197:394–396.
9.
Kuyama M, Fujimoto W, Kambara H, Egusa M, Saitoh M, Yamasaki O, Maehara K, Ohara A, Arata J, Iwatsuki K: Amicrobial pustular dermatosis in two patients with immunological abnormalities. Clin Exp Dermatol 2002;27:286–289.
10.
Lopez-Navarro, Alcaide A, Gallego E, Herrera-Acosta E, Gallardo M, Bosch RJ, Herrera E: Amicrobial pustulosis of the folds associated with Hashimoto’s thyroiditis. Clin Exp Dermatol 2009;34:e561–e563.
11.
Lipsker D, Saurat JH: Neutrophilic cutaneous lupus erythematosus: at the edge between innate and acquired immunity? Dermatology 2008;216:283–286.
12.
De Gannes G, Ghoreishi M, Pope J, Russell A, Bell D, Adams S, Shojania K, Martinka M, Dutz JP: Psoriasis and pustular dermatitis triggered by TNF-alpha inhibitors in patients with rheumatologic conditions. Arch Dermatol 2007;143:223–231.
13.
Laga AC, Vleugels RA, Qureshi AA, Velazquez EF: Histopathologic spectrum of psoriasiform skin reactions associated with tumour necrosis factor-alpha inhibitor therapy: a study of 16 biopsies. Am J Dermatol 2010;32:568–573.
14.
Seneschal J, Milpied B, Vergier B, Lepreux S, Schaverbeke T, Taieb A: Cytokine imbalance with increased production of interferon- alpha in psoriasiform eruptions associated with anti-tumour necrosis factor-alpha treatments. Br J Dermatol 2009;161:1081–1088.
15.
Harrison MJ, Dixon WG, Watson KD, King Y, Groves R, Hyrich KL, Symmons DPM: Rates of new-onset psoriasis in patients with rheumatoid arthritis receiving anti-tumour necrosis factor alpha therapy: results from the British Society for Rheumatology biologics register. Ann Rheum Dis 2009;68:209–215.
16.
Moustou AE, Matekovits A, Dessinioti C, Antoniou C, Sfikakis PP, Stratigos AJ: Cutaneous side effects of anti-tumor necrosis factor biologic therapy: a clinical review. J Am Acad Dermatol 2009;61:486–504.
17.
Vazquez J, Almagro M, del Pozo J, Fonseca E: Neutrophilic pustulosis and ulcerative colitis. J Eur Acad Dermatol Venereol 2003;17:77–79.
18.
Callen JP: Pustular eruptions in systemic diseases. Clin Dermatol 2000;18:349–353.
19.
Sarkany R, Burrows NP, Grant JW, Pye RJ, Norris PG: The pustular eruption of ulcerative colitis. Br J Dermatol 1998;138:365–366.
20.
Wenzel J, Tuting T: An IFN-associated cytotoxic cellular immune response against viral, self- or tumor antigens is a common pathogenic feature in ‘interface dermatitis’. J Invest Dermatol 2008;128:2392–2402.
21.
Kelly-Scumpia KM, Scumpia PO, Delano MJ, Weinstein JS, Cuenca AG, Wynn JL, Moldawer LL: Type 1 interferon signaling in hematopoietic cells is required for survival in mouse polymicrobial sepsis by regulating CXCL 10. J Exp Med 2010;207:319–326.
22.
Kerbleski JF, Gottlieb AB: Dermatological complications and safety of anti-TNF treatments. Gut 2009;58:1033–1039.
23.
Flendrie M, Vissers WHPM, Creemer MCW, de Jong Elke MGJ, van de Kerkhof PC, van Riel PLCM: Dermatological conditions during TNF-alpha blocking therapy in patients with rheumatoid arthritis: a prospective study. Arthritis Res Ther 2005;7:R666–R676.
24.
Lee HH, Song IH, Friedrich M, Gauliard A, Detert J, Rowert H, Audring H, Kary S, Burmester GR, Sterry W, Worm M: Cutaneous side-effects in patients with rheumatic diseases during application of tumour necrosis factor-alpha antagonists. Br J Dermatol 2007;156:486–491.
25.
Asarch A, Gottlieb AB, Lee J, Masterpol KS, Scheinman PL, Stadecker M, Massaroti EM, Bush ML: Lichen planus-like eruptions: an emerging side effect of tumor necrosis factor-alpha antagonists. J Am Acad 2009;61:104–111.
26.
Fernandez-Torres R, Paradela S, Valbuena L, Fonseca E: Infliximab induced lichen planopilaris. Ann Pharmacother 2010;44:1501–1503.
27.
Deng A, Harvey V, Sina B, Strobel D, Badros A, Jukins-Hopkins J, Samuels A, Oghilikhan M, Gaspari A: Interstitial granulomatous dermatitis associated with the use of tumour necrosis factor alpha inhibitors. Arch Dermatol 2006;142:198–202.
28.
Voulgari PV, Markatseli TE, Exarchou SA, Zioga A, Drosos AA: Granuloma annulare induced by anti-tumour necrosis factor therapy. Ann Rheum Dis 2008;67:567–570.
29.
Dhaille F, Viseux V, Caudron A, Dadban A, Tribout C, Bournier P, Clabaut A, Lok C: Cutaneous sarcoidosis occurring during anti-TNF-alpha treatment: report of two cases. Dermatology 2010;220:234–237.
30.
Vandevyvere K, Luyten FP, Verschueren P, Lories R, Segaert S, Westhovens R: Pyoderma gangrenosum developing during therapy with TNF-alpha antagonists in a patient with rheumatoid arthritis. Clin Rheumatol 2007;26:2205–2206.
31.
Williams EL, Gadola S, Edwards CJ: Anti-TNF-induced lupus. Rheumatology 2009;48:716–720.
32.
Ramos-Casals M, Brito-Zeron P, Munoz S, Soria N, Galiana D, Bertolaccini L, Cuadradro MJ, Khamashta MA: Autoimmune diseases induced by TNF-targeted therapies: analysis of 233 cases. Medicine 2007;86:242–251.
33.
Ramos-Casals M, Roberto-Perez-Alvarez, Diaz-Lagares C, Cuadrado MJ, Khamashta MA, BIOGEAS Study Group: Autoimmune diseases induced by biological agents: a double-edged sword. Autoimmun Rev 2010;9:188–193.
34.
Klein R, Rosenbach M, Kim EJ, Kim B, Werth VP, Dunham J: Tumor necrosis factor inhibitor-associated dermatomyositis. Arch Dermatol 2010;146:780–784.
35.
Boussemart L, Jacobelli S, Batteux F, Goulvestre C, Grange P, Carlotti A, Morini JP, Gorin I, Ziza JM, Avril MF, Dupin N: Autoimmune bullous skin diseases occurring under anti-tumor necrosis factor therapy: two case reports. Dermatology 2010;221:201–205.
36.
Daulat S, Detweiler JG, Pandya AG: Development of pemphigus vulgaris in a patient with psoriasis treated with etanercept. J Eur Acad Dermatol Venereol 2009;23:483–484.
37.
Leombruno JP, Einarso TR, Keystone EC: The safety of anti-tumour necrosis factor treatments in rheumatoid arthritis: meta and exposure-adjusted pooled analyses of serious adverse events. Ann Rheum Dis 2009;68:1136–1145.
38.
Askling J, Fahrbach K, Nordstrom B, Ross S, Schmid CH, Symmons D: Cancer risk with tumor necrosis factor alpha inhibitors: meta-analysis of randomized controlled trials of adalimumab, etanercept and infliximab using patient level data. Pharmacoepidemiol Drug Saf 2011;20:119–130.
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