Emmanuel Laffitte

Tuberculosis screening in patients with psoriasis before antitumour necrosis factor therapy: comparison of an interferon‐γ release assay vs. tuberculin skin test

Background  Antitumour necrosis factor (anti‐TNF) treatments may reactivate latent tuberculosis infection (LTBI). For detecting LTBI, the tuberculin skin test (TST) has low sensitivity and specificity. Interferon‐γ release assays (IGRA) have been shown to be more sensitive and specific than TST.

Bullous pemphigoid antigen 1 isoforms: potential new target autoantigens in multiple sclerosis?

Background  The simultaneous occurrence of bullous pemphigoid (BP) and multiple sclerosis (MS), two autoimmune diseases involving the skin and the central nervous system (CNS), respectively, has been described.

Autoantibodies to the extracellular and intracellular domain of bullous pemphigoid 180, the putative key autoantigen in bullous pemphigoid, belong predominantly to the IgG1 and IgG4 subclasses

Background Autoantibodies to the extracellular domain (ECD) of bullous pemphigoid (BP) antigen 180 (BP180) are thought to play a crucial part in the pathophysiology of BP.

Plectin, an unusual target antigen in bullous pemphigoid

Background  Bullous pemphigoid (BP) is a blistering disease associated with autoantibodies directed against two components of hemidesmosomes, BP180 and BP230.

Intralesional Infliximab in Noninfectious Cutaneous Granulomas: Three Cases of Necrobiosis Lipoidica

Background: Necrobiosis lipoidica is a rare granulomatous noninfectious skin disease. Treatment of this chronic debilitating disease is of importance because ulceration of the plaques may induce important psychological and physical morbidity. Objective: Infliximab, an anti-TNF-α chimeric monoclonal antibody used intravenously and intralesionally for other extradermatological granulomatous diseases including Crohn’s disease and sarcoidosis, was administered by intradermal injection in necrobiosis lipoidica. The aim of this study was to evaluate the efficacy and safety profile of a locally delivered drug compared to its systemic use. Patients and Methods: Weekly injections of intralesional infliximab for 3 weeks were followed by a 1-week treatment interruption. This treatment schedule was repeated thrice. Results: Two patients who benefitted from complete treatment experienced almost complete remission for up to 18 months. The third patient, who had treatment interruptions, showed partial improvement. No serious side effects were noticed, although the injections caused pain. Conclusions: This is the first report about the efficacy and safety of a therapy consisting of intralesional injections of infliximab for a granulomatous skin disease. Although this approach was clearly effective for necrobiosis lipoidica, the disease recurred several months after treatment interruption, raising the question of the need for maintenance therapy. Further controlled long-term trials are thus necessary.

Sirolimus-induced acneiform eruption.

Sirolimus is a new immunosuppressive agent used to prevent rejection in renal allograft recipients in order to reduce the need of potentially nephrotoxic calcineurin inhibitors (cyclosporine, tacrolimus). The cutaneous side effects of sirolimus are not well known and they may have been underestimated. We report 2 cases of follicular acneiform eruptions induced by sirolimus in renal allograft recipients. This dermatologic complication was severe and difficult to treat, and resolved only after discontinuation of sirolimus.

Refractory Chronic Cutaneous Sarcoidosis Responsive to Dose Escalation of TNF-Alpha Antagonists

Cutaneous sarcoidosis may be a chronic disease with important morbidity requiring aggressive therapy. The efficacy of different anti-tumor necrosis factor α(anti-TNF-α) treatments in refractory cutaneous and systemic sarcoidosis has been reported previously. We report the first patient with chronic cutaneous sarcoidosis who responded to dose escalation of anti-TNF-α agents that have been ineffective at the standard dosage, illustrating that the optimal dosing regimen has still to be defined for this indication before considering difficult-to-treat patients as nonresponders. Our case report also illustrates that the fusion protein etanercept, even used at a high dosage, may be less effective for the treatment of cutaneous sarcoidosis than the monoclonal antibodies infliximab and adalimumab.

First Case of Bacteremia and Multifocal Cellulitis Due to Helicobacter canis in an Immunocompetent Patient

ABSTRACT Bacteremia due to Helicobacter canis has been reported in a patient with X-linked hypogammaglobulinemia. Here we report on the first human case of H. canis bacteremia in an immunocompetent host. Identification of the organism was made by genetic and phylogenetic analyses of the complete 16S rRNA sequence.

Eczematous drug eruption after infliximab

SIR, Infliximab (Remicade , Schering-Plough), a humanized antitumour necrosis factor (TNF)-a monoclonal antibody, has been associated with several cutaneous side-effects. We report a patient with an eczematous eruption that appeared after the administration of infliximab. A 36-year-old man presented with a diffuse pruritic rash of 1 week’s duration. He had been receiving treatment for 3 months with oral leflunomide 20 mg daily and intravenous infliximab 3 mg kg at weeks 0, 2 and 6 for a palmoplantar pustular psoriasis with severe arthritis. Four days after the third infusion of infliximab he developed a pruriginous maculopapulovesicular erythematosquamous eruption of the limbs and trunk (Fig. 1a). There was no history of allergy or eczema. Abnormal laboratory results included elevated erythrocyte sedimentation rate at 35 mm in the first hour (normal <10), white blood cell count of 15Æ1 · 10 L with 71% neutrophils and 1% eosinophils, and C-reactive protein at 49 mg L (normal <10). Human immunodeficiency virus, syphilis and Chlamydia serology were negative and there was no evidence for any viral disease. Skin biopsy showed spongiform dermatitis with oedema in the epidermis between keratinocytes and the upper dermis, associated with keratinocyte necrosis, and a lymphocytic infiltrate in the upper dermis (Fig. 1b). The skin condition improved within 2 weeks after stopping the two drugs and the use of topical steroids. One month later, patch tests to leflunomide and infliximab were negative. As infliximab had been proving beneficial for the arthritic condition in this patient, rechallenge with a perfusion of 50 mg of infliximab was attempted. Two days later, the eczematous rash reappeared with an identical histological pattern. Thereafter, infliximab was switched to subcutaneous etanercept (Enbrel , Wyeth), another TNF-a inhibitor, without recurrence of the rash. TNF-a inhibitors are highly effective in the treatment of early and chronic rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, Crohn’s disease and psoriatic skin lesions. In clinical studies with infliximab, a humanized mouse monoclonal antibody against human TNF-a, adverse drug reactions were most frequently reported in the respiratory system (upper and lower respiratory tract infections), and in the skin and appendages. The most frequently described skin side-effects are mainly delayed hypersensitivity reactions: erythema multiforme, leucocytoclastic vasculitis, annular lichenoid eruption, lupus-like syndrome, bullous skin lesions and eczematide-like purpura. Several eczematous skin eruptions following infliximab have been reported previously. Skin reactions typically arise after one or several repeated treatments, and at 1–14 days after the injection. In arthritic conditions, infliximab is classically given with methotrexate to reduce the incidence of human antichimeric Figure 1. (a) First eczematous rash 4 days after the third infusion of infliximab in combination with leflunomide. (b) Histopathology confirmed a spongiform dermatitis associated with keratinocyte necrosis and a lymphocytic infiltrate in the upper dermis (haematoxylin and eosin; original magnification ·100). British Journal of Dermatology 2004; 151: 1272–1288.

High IL-17E and low IL-17C dermal expression identifies a fibrosis-specific motif common to morphea and systemic sclerosis

Background High interleukin (IL)-17A levels are characteristically found in the skin of systemic sclerosis (SSc) individuals. Our aim was to investigate whether the dermal expression of IL-17A and related IL-17 family members (i.e. IL-17C, IL-17E and IL-17F) could distinguish fibrotic from healthy skin and could show similarities in SSc and morphea, two disorders with presumed distinct pathogenesis, but characterized by skin fibrosis. Methods Biopsies were obtained from the involved skin of 14 SSc, 5 morphea and 8 healthy donors (HD) undergoing plastic surgery. Immunohistochemistry/immunofluorescence techniques were coupled to a semi-automated imaging quantification approach to determine the presence of the IL-17 family members in the skin. The in vitro effects induced by the IL-17 family members on fibroblasts from normal and SSc individuals were assessed by ELISA and RIA. Results Positive cells for each of the IL-17 isoforms investigated were present in the dermis of all the individuals tested, though with variable frequencies. SSc individuals had increased frequency of IL-17A+ (p = 0.0237) and decreased frequency of IL-17F+ (p = 0.0127) and IL-17C+ cells (p = 0.0008) when compared to HD. Similarly, morphea individuals had less frequent IL-17C+ cells (p = 0.0186) in their skin but showed similar number of IL-17A+ and IL-17F+ cells when compared to HD. Finally, IL-17E+ cells were more numerous in morphea (p = 0.0109) and tended to be more frequent in SSc than in HD. Fibroblast production of IL-6, MMP-1 and MCP-1 was enhanced in a dose-dependent manner in the presence of IL-17E and IL-17F, but not in the presence of IL-17C. None of the cytokine tested had significant effect on type I collagen production. Of interest, in SSc the frequency of both IL-17A and IL-17F positive cells increased with disease duration. Conclusions The frequency of IL-17A and IL-17F distinguish SSc to morphea individuals while dermal expression of IL-17C (low) and IL-17E (high) identifies a fibrosis-specific motif. The specific IL-17C/IL-17E cytokine combination may thus play a role in the development of fibrosis.