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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