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Advances in dermatology and venereology Acta Dermato-Venereologica
Ustekinumab as Effective Treatment for Refractory Amicrobial Pustulosis of the Folds Associated with Crohn’ s Disease
Reem AL-RADDADI 1, Camille FRANCES 1, 2, Philippe MOGUELET 3, Claude BACHMEYER 4 and Sarah GUÉGAN 1, 2 *
1
Service de dermatologie-allergologie, 3 Service d’ anatomie pathologique and 4 Service de médecine interne, Hôpital Tenon, AP-HP, 4, rue de la Chine, FR-75020 Paris, and 2 Université Paris VI, Paris, France. * E-mail: sarah. guegan. bart @ gmail. com Accepted Oct 6, 2016; Epub ahead of print Oct 10, 2016
Amicrobial pustulosis of the folds( APF) is characterized by relapsing pustular lesions associated with erosive macerated areas and crusts, affecting the cutaneous folds, face and scalp( 1). It is usually reported in females in the third decade, mainly in association with systemic and cutaneous lupus erythematosus and, rarely, with connective tissue disease, scleroderma, myasthenia gravis, Hashimoto’ s thyroiditis, idiopathic thrombocythemia and coeliac disease( 1 – 4).
APF belongs to the spectrum of neutrophilic dermatoses, diseases all characterized by similar pathological features, namely an intense inflammatory infiltrate composed primarily of neutrophils, in the absence of patent infection. In APF, intraepidermal subcorneal spongiform abscesses are associated with a neutrophilic dermal infiltrate. Diagnostic criteria were established by Marzano et al. in 2008( Table SI 1)( 2).
We report here a case of refractory APF, which preceded by 11 years the onset of lupus erythematosus tumidus( LET), and by 15 years the onset of Crohn’ s disease( CD). Both APF and CD were controlled by ustekinumab, a monoclonal antibody directed against the p40 subunit common to interleukin( IL) 12 / IL23.
CASE REPORT
A 26-year-old woman was referred for evaluation of recurrent episodes of pustular skin lesions affecting predominantly her major body folds over the last 10 years. Upon examination, the patient was healthy, afebrile. Axillary, submammary and inguinal folds were involved with multiple symmetrically distributed erythematous pustules. The gluteal folds, perianal area and buttocks were mostly affected( Fig. 1a). Isolated pustules were observed on the arms, back, abdomen and thighs. Nikolsky’ s sign was negative. In the course of evolution, similar lesions involved the face and scalp, together with erosive and crusted lesions( Fig. 1b). Pustular lesions affecting the scalp eventually coalesced into larges plaques with hair loss, quickly followed by regrowth. All of these lesions regressed following topical corticosteroid therapy, and relapsed after withdrawal of treatment. Histology of skin biopsy specimens revealed intraepidermal subcorneal spongiform abscesses as well as a dermal inflammatory infiltrate with predominant neutrophils( Fig. 1c). Direct immunofluorescence of lesional skin showed non-specific IgM deposits at the dermoepidermal junction. Micro biological cultures
from recent closed pustules were sterile. A diagnosis of APF was thus established.
Of note, 11 years after the onset of APF, the patient presented smooth erythematous infiltrated plaques affecting the face. Histology confirmed LET. Antinuclear antibodies( ANA) were positive, with a titre of 1:320 and a nuclear speckled pattern; search for other autoimmune antibodies( anti-dsDNA, anti-SS-A, anti-SS-B, anti- Sm, anti-RNP, ANCA) was negative. Hydroxychloroquine( 200 mg twice daily) combined with a short course of topical corticosteroids was quickly effective in treating LET with no further relapse.
Initially, various courses of treatment failed to control APF: topical and systemic corticosteroids( up to 1.5 mg / kg / day), colchicine( 2 mg / day), isotretinoin( 40 mg / day), hydroxychloroquine, dapsone( 100 mg / day), and zinc( 30 mg / day). When necessary, bacterial superinfections were treated with empirical antibiotic therapy. The patient responded partially to a 4-year course of cyclosporine( 5 mg / kg / day) with gradual tapering. After 4 years of this treatment, as no complete remission was seen, anakinra( 100 mg daily subcutaneously) was introduced and continued for 2 years; a significant decrease in the episodes of flare-ups was noted.
Fifteen years after the onset of APF, the patient experienced persistent weight loss and abdominal pains. Upper and lower gastrointestinal endoscopy and biopsies revealed erosive pancolitis with epithelioid cell granuloma, a diagnostic characteristic of CD. In the months following CD diagnosis, several flares of APF occurred. Anakinra was stopped; ustekinumab was introduced at a dose of 90 mg subcutaneously every 8 weeks and has been on-going for
1 https:// www. medicaljournals. se / acta / content / abstract / 10.2340 / 00015555-2544
Fig. 1. A case of refractory amicrobial pustulosis of the folds.( a – c) Crusted erythematous pustular lesions of the scalp, ear and buttocks, respectively.( d) Haematoxylin-eosin staining showing spongiform subcorneal epidermal and follicular pustule with a mixed neutrophil and mononuclear infiltrate in the upper and middle dermis( original magnification × 200).
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2017 Acta Dermato-Venereologica. doi: 10.2340 / 00015555-2544 Acta Derm Venereol 2017; 97: 389 – 390