Subcorneal pustular dermatosis treated successfully with adalimumab

ARTICLE

Auteur(s) : Filipa de Encarnação Roque Diamantino, Joana Miguel Ramos Dias Coelho, Ana Maria Macedo Ferreira, Ana Isabel Pina Clemente Fidalgo

Department of Dermatology, Hospital dos Capuchos, Centro Hospitalar de Lisboa Central, Alameda Santo António dos Capuchos, 1169-050 Lisboa, Portugal

A 43-year-old, overweight, but otherwise healthy woman presented with a 3-year history of a relapsing eruption of numerous, grouped, itchy pustules affecting her trunk and intertriginous areas, which had been diagnosed as subcorneal pustular dermatosis (SCPD). Over those 3 years, she had been treated with topical corticosteroids, dapsone and sulfapyridine, all without sustained effect. Dermatological examination revealed an eruption of multiple, superficial, flaccid pustules, with mild background erythema. The lesions formed circinate and serpiginous patterns and were symmetrically distributed on her neck, axillae, groin and trunk (figures 1A and B). She denied systemic symptoms and had no fever. A biopsy of lesional skin showed a sterile, subcorneal pustule filled with neutrophils, an unspecific inflammatory infiltrate in the papillary dermis (figure 1C) and negative direct immunofluorescence. These clinicopathological findings led to the diagnosis of SCPD. The peripheral blood cell counts, erythrocyte sedimentation rate and serum immuno-electrophoresis were normal.

After admission for flaring SCPD we started a therapeutic trial with acitretin (25 mg twice daily) and deflazacort (0.6 mg/kg/day). Despite this therapy, the patient experienced progressive pustular eruptions. Recent published reports [1-3] indicate the effectiveness of anti-tumour necrosis factor (TNF)-α therapies in treating SCPD. Adalimumab 40 mg bi-weekly was started and the lesions significantly improved after the third dose and healed with desquamation and mild erythema within 4 weeks (figures 1D and E). At this point, deflazacort was progressively reduced from 45 mg to 7.5 mg daily and the acitretin dose reduced to 25 mg every other day. Both drugs were stopped after 6 weeks. For the past 12 months, the patient has remained in complete remission on monotherapy with adalimumab.

Subcorneal pustular dermatosis, first described by Sneddon and Wilkinson in 1956, is a rare, benign, chronic, relapsing, sterile, pustular eruption, typically involving the intertriginous areas, trunk and proximal limbs, which most commonly affects middle-aged women. Dapsone, often considered to be the first-line treatment, provided no therapeutic value in our patient. Other treatments have been found to be irregularly efficient for SCPD: corticosteroids, acitretin, phototreatment, cyclosporin and, recently, anti-TNF-α agents [1-5].

The exact aetiology and pathophysiology of SCPD remains unclear. The main pathogenic event in SCPD is the migration of neutrophils towards the epidermis to form sterile pustules, which suggests the presence of chemotactic factors in the uppermost epidermis [2]. TNF-α, which is known to activate neutrophils, may be a potential pathogenic factor, as evidenced by increased blister fluid and serum TNF-α levels of patients with SCPD [5]. This hypothesis is also supported by recent published reports that indicate the effectiveness of anti-TNF-α therapy [1-4]. Other pro-inflammatory cytokines such as interleukin (IL)-1β, -6, -8 and -10 and interferon (INF)-γ have also been found to be eventually involved in the pathogenesis of SCPD [3]. The stimulus behind the production of these chemoattractants is still unknown.

Adalimumab is a fully human, anti-TNF monoclonal antibody, that through inhibition of TNF-α is able to decrease neutrophil infiltration in the epidermis. This is the probable mechanism for its effect in the treatment of SCPD. Although, in most cases, anti-TNF-α therapy provides beneficial effects on pustular eruptions, it can also induce them. The development of a paradoxical pustular eruption following the use of anti-TNF-alpha agents is being increasingly described [6]. The interpretation of this side effect remains controversial.

Over the years, the clinical course of the disease in our patient had been controlled only partially and temporarily by various therapies. In contrast, administration of adalimumab led to a rapid improvement and control of the condition for more than 12 months, on monotherapy. To our knowledge, this is the first case in the literature of SCPD being successfully treated by adalimumab.

Acknowledgements

References

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3 Bonifati C, Trento E, Cordiali Fei P, et al. Early but not lasting improvement of recalcitrant subcorneal pustular dermatosis (Sneddon-Wilkinson disease) after infliximab therapy: relationships with variations in cytokine levels in suction blister fluids. Clin Exp Dermatol 2005; 30: 662-5.

4 Cheng S, Edmonds E, Ben-Gashir M, Yu RC. Subcorneal pustular dermatosis: 50 years on. Clin Exp Dermatol 2008; 33: 229-33.

5 Grob JJ, Mege JL, Capo C, et al. Role of tumor necrosis factor-alpha in Sneddon-Wilkinson subcorneal pustular dermatosis. A model of neutrophil priming in vivo. J Am Acad Dermatol 1991; 25: 944-7.

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