[Misdiagnosis of hidradenitis suppurativa continues to be a major issue. The R-ENS Verneuil study]. / Errance médicale des patients atteints d'hidradénite suppurée : un problème majeur et persistant. Étude « R-ENS Verneuil ¼.

OBJECTIVE: To provide physicians with an understanding of the factors behind significant delays in the diagnosis of hidradenitis suppurativa (HS) in France. PATIENTS AND METHODS: This prospective multicentre national study conducted from October 2015 to March 2016 included all patients consulting for HS. Patient data were collected by means of a standardized questionnaire. Univariate and multivariate analyses were conducted to collect factors associated with a significant time to diagnosis of at least 5.5years, defined as the period between the onset of initial clinical signs and the time of formal diagnosis. RESULTS: The 16 participating centres enrolled 312 patients (62% women), of average age 35years. The average age at onset of HS was 22years. Before formal diagnosis by a dermatologist (64% of cases), 170 (54%), 114 (37%) and 45 (15%) patients had previously consulted at least 3, 5 and 10 general physicians, respectively. The average time between the initial clinical signs of HS, the first dermatology visit and the definitive diagnosis was 6.2 and 8.4 years, respectively. Active smoking (OR adjusted 1.85; P=0.027) and disease onset at a younger age (adjusted OR 0.92; P<0.001) were both associated with significant delays in diagnosis. CONCLUSION: These results emphasized misdiagnosis among HS patients but did not evidence any association between either sociodemographic or economic characteristics and the existence of significant times to diagnosis.

Protease-modulating polyacrylate-based hydrogel stimulates wound bed preparation in venous leg ulcers--a randomized controlled trial.

BACKGROUND: Stringent control of proteolytic activity represents a major therapeutic approach for wound-bed preparation. OBJECTIVES: We tested whether a protease-modulating polyacrylate- (PA-) containing hydrogel resulted in a more efficient wound-bed preparation of venous leg ulcers when compared to an amorphous hydrogel without known protease-modulating properties. METHODS: Patients were randomized to the polyacrylate-based hydrogel (n = 34) or to an amorphous hydrogel (n = 41). Wound beds were evaluated by three blinded experts using photographs taken on days 0, 7 and 14. RESULTS: After 14 days of treatment there was an absolute decrease in fibrin and necrotic tissue of 37.6 ± 29.9 percentage points in the PA-based hydrogel group and by 16.8 ± 23.0 percentage points in the amorphous hydrogel group. The absolute increase in the proportion of ulcer area covered by granulation tissue was 36.0 ± 27.4 percentage points in the PA-based hydrogel group and 14.5 ± 22.0 percentage points in the control group. The differences between the groups were significant (decrease in fibrin and necrotic tissue P = 0.004 and increase in granulation tissue P = 0.0005, respectively). CONCLUSION: In particular, long-standing wounds profited from the treatment with the PA-based hydrogel. These data suggest that PA-based hydrogel dressings can stimulate normalization of the wound environment, particularly in hard-to-heal ulcers.

Erythrodermic cutaneous T-cell lymphoma with disseminated pustulosis. Production of high levels of interleukin-8 by tumour cells.

Interleukin (IL) -8 is a neutrophil chemoattractant cytokine with proinflammatory and growth-promoting activities, which is involved in the pathogenesis of several inflammatory diseases. It is found in high amounts in lesional biopsies of pustular diseases such as psoriasis and palmoplantar pustulosis. We report a 50-year-old woman with a 10-year history of erythroderma with disseminated pustulosis. Skin biopsies showed an epidermotropic infiltrate composed of atypical CD4+ CD8+ lymphocytes with numerous admixed neutrophils. Peripheral blood flow cytometric analysis revealed a major clonal subset of CD3+ CD4+ CD8+ T-cell receptor Vbeta22+ atypical lymphocytes. Bone marrow biopsy, lymph node biopsy and computed thoracoabdominal tomography were normal. Serologies for human T-cell lymphotropic virus type I and human immunodeficiency virus were negative. Our patient's status deteriorated despite topical (nitrogen mustard, psoralen plus ultraviolet A) and systemic (interferon, methotrexate, multiagent chemotherapy) treatments, and she finally died. We showed that our patient's peripheral blood lymphocytes (PBL) spontaneously produced high amounts of IL-8. In contrast, PBL of patients with classical Sézary syndrome produced lower amounts of IL-8. The production of IL-8 by tumour T cells could explain this unusual clinical and histopathological presentation of cutaneous T-cell lymphoma as disseminated pustulosis.

["Idiopathic" white atrophy]. / Atrophie blanche "idiopathique".

INTRODUCTION: Livedoid vasculitis is a clinico-pathological entity which may be idiopathic or secondary to various disorders. The aim of this study was to search for a thrombogenic biological abnormality in patients with apparently idiopathic livedoid vasculitis. PATIENTS AND METHODS: All the patients with histologically confirmed and apparently idiopathic livedoid vasculitis were evaluated. Blood study included search for anticardiolipin, anti-anionic phospholipids and anti-beta 2 glycoprotein 1 antibodies, platelet aggregation and fibrinolytic system tests, cryofibrinogen and homocysteine serum level and factor V Q506 mutation and prothrombin 20210 G/A variant investigation. Clinical data and effects of treatments were reviewed retrospectively. RESULTS: Eleven of the 21 patients with livedoid vasculitis had an apparently idiopathic form. Seven of them (64 p. 100) had a thrombophilic state: antiphospholipid antibodies (n = 3), increased platelet aggregation (n = 1), cryofibrinogen (n = 1), decreased antithrombin III activity (n = 1) and factor V mutation (n = 1). The necrotic lesions were always localized on the lower limbs with a sensitive neuropathy in 2 cases. Complete remission was sometimes obtained with antiaggregant or anticoagulant therapy, but was unrelated to the thrombophilic abnormalities. CONCLUSION: Various thrombophilic abnormalities are frequently observed in livedoid vasculitis which seems to be the clinical expression of a thrombotic process of the microcirculation of the skin and sometimes of the peripheral nerves. The idiopathic feature of numerous cases gives evidence for the lack of our knowledge on thrombosis of the microcirculation.

[Resistant acquired bullous epidermolysis with severe ocular involvement: the success of extracorporeal photochemotherapy]. / Epidermolyse bulleuse acquise résistante avec atteinte oculaire sévère: succès de la photochimiothérapie extracorporelle.

BACKGROUND: Epidermolysis bullosa aquisista can leave several functional sequelae. The lesions sometimes resist treatment. CASE REPORT: We report a case of a 25-year-old young man presenting with a severe epidermolysis bullosa acquisita confirmed by the electronic immunomicroscopy. He had a major ocular involvement with symblepharon and cicatricial synechial lesions. He was almost blind because of corneal scars. All immunosuppressive treatments had failed: systemic corticoids, cyclosporin, azathioprine. The introduction of extracorporeal photochemotherapy resulted in the healing of the lesions, after a total of 32 procedures. All treatment are now stopped, and the lesions are purely cicatricial, without any relapse of the disease since 9 months. Corneal grafts are now under process, to try to recover a part of the lost visual acuity. DISCUSSION: This case demonstrates the efficacy of extracorporeal chemotherapy to be tried in case other treatments failed.

Critical role of nitric oxide during the apoptosis of peripheral blood leukocytes from patients with AIDS.

BACKGROUND: Highly active antiretroviral therapies (HAART) increase the CD4(+) cell count, but complete normalization of this parameter has not been obtained in some patients. As oxidative stress plays an important role during human immunodeficiency virus type 1 (HIV-1)-associated dementia and lymphocyte apoptosis, we asked whether the nitric oxide (NO) pathway plays a role in the in vitro survival of peripheral blood mononuclear cells (PBMC) from HIV-1(+) patients and how it correlates with peripheral CD4(+) cell levels. MATERIALS AND METHODS: PBMC were isolated from patients with AIDS and assayed for apoptosis and proliferation in the presence of various chemicals, including agonists or antagonists of the NO pathway. Data were then compared with several in vivo parameters from the same patients. RESULTS: Apoptosis of PBMC in the presence of exogenous NO is significantly higher in patients with low peripheral CD4(+) cell levels than in patients with high CD4(+) cell numbers or seronegative individuals. In addition, endogenous NO inhibition rescues cells from apoptosis in AIDS patients with low circulating CD4(+) cell numbers and helps recovery of the T cell proliferative response. NO-mediated apoptosis does not require cGMP but involves peroxynitrite generation, PARP activation, and NAD(+) depletion. CONCLUSIONS: Taken together, the data suggest the involvement of NO during the apoptosis and functional impairment of lymphocytes in patients with AIDS.

Tripe palms associated with systemic mastocytosis: the role of transforming growth factor-alpha and efficacy of interferon-alfa.

Tripe palms are thickened, moss-like or velvety textured exaggerations of the normal dermatoglyphics. The disease belongs to the spectrum of papulosquamous paraneoplastic syndromes. Although suspected, the role of transforming growth factor-alpha (TGF-alpha) has not been clearly established. A 54-year-old man with systemic mastocytosis presented with thickening and darkening of the palms and soles. We performed skin biopsies for light microscopy (including toluidine blue), in situ hybridization and double labelling, and determination of serum tryptase, histamine and TGF-alpha levels. Toluidine blue stained the mast cells that had massively infiltrated the dermis. Tripe palm samples showed extensive hyperkeratosis. The TGF-alpha probe reacted strongly with the mast cells that also reacted with the antitryptase monoclonal antibody. Elevated tryptase, histamine and TGF-alpha levels prior to interferon-alfa administration decreased under treatment. The demonstration of TGF-alpha in infiltrating mast cells, the clinical regression of tripe palms and the lowering of the serum level and the mast cell molecular signal of the cytokine when systemic mastocytosis was controlled by interferon-alfa, suggest a key role for TGF-alpha in this cutaneous paraneoplastic syndrome.

Inducible nitric oxide synthase and proinflammatory cytokine expression by human keratinocytes during acute urticaria.

BACKGROUND: IgE/allergen-dependent activation of skin mast cells is involved in acute urticaria and leads to their IL-4 release. Previously we have demonstrated in vitro the induction of the low-affinity receptor for IgE (CD23/Fc epsilon RII) in human keratinocytes (HK) upon stimulation with IL-4. In addition, we have observed that ligation of CD23 on keratinocytes induced type II nitric oxide synthase (iNOS), leading to the release of nitric oxide (NO) and proinflammatory cytokines (TNF-alpha, IL-6). According to these in vitro data, we explored whether keratinocytes could also express iNOS, TNF-alpha, IL-6, and CD23 in acute urticaria, an in vivo model in which activation of mast cells by IgE/allergen immune complexes is involved. MATERIALS AND METHODS: INOS, TNF-alpha, IL-6, and CD23 expression by keratinocytes was studied in acute urticaria (n = 11) in biopsies from lesional and autologous normal skin by immunohistochemistry, in situ hybridization, or RT-PCR. Nitrites and TNF-alpha synthesis were assayed in supernatants of cultured lesional keratinocytes. RESULTS: INOS mRNA expression was demonstrated with RT-PCR in 10 biopsies out of 11 sections of acute urticaria lesional skin. Immunohistochemistry showed that this iNOS positivity originated from keratinocytes located close to the dermoepidermal junction; TNF-alpha and IL-6 mRNA transcription was observed in all but one iNOS+ biopsy. Immunostaining and in situ hybridization with CD23-specific probes were strong in all but one iNOS+ skin biopsy. Noninflamed autologous skin was negative for iNOS (except for a weak positivity in one case), cytokines, and CD23. CONCLUSION: The colocalization of iNOS, proinflammatory cytokines, and CD23 within keratinocytes in acute urticaria demonstrates that these cells play an important role in the initiation and maintenance of the inflammatory reaction during this disease in humans through activation of the iNOS pathway by CD23 ligation with IgE/allergen immune complexes.

Interleukin-10 and interleukin-4 inhibit intracellular killing of Leishmania infantum and Leishmania major by human macrophages by decreasing nitric oxide generation.

The host response to Leishmania infection is regulated by a specific pattern of local cytokine production. We investigated the effect of interleukin (IL)-10 and IL-4 on the leishmanicidal activity of human macrophages (M phi). As with L. major, intracellular killing of L. infantum by human M phi was obtained following ligation of surface CD23 or cell treatment with interferon-gamma (IFN-gamma). This leishmanicidal activity required nitric oxide (NO) generation by activated M phi, and it was partially mimicked by cell treatment with chemical NO donors. Addition of recombinant human IL-10 or IL-4 to CD23 mAb or IFN-gamma decreased L. infantum and L. major killing by infected M phi. IL-10 was more potent than IL-4 in inhibiting the leishmanicidal activity of human M phi. Inhibition of Leishmania killing by IL-4 and IL-10 correlated with decreased NO generation from M phi, and was reversed when exogenous NO was added to cell cultures. Therefore, IL-10 and IL-4 down-regulate leishmanicidal activity of human M phi, in part by inhibiting NO generation by these cells.