Philippe Berbis

Pepper mild mottle virus, a plant virus associated with specific immune responses, Fever, abdominal pains, and pruritus in humans.

Background Recently, metagenomic studies have identified viable Pepper mild mottle virus (PMMoV), a plant virus, in the stool of healthy subjects. However, its source and role as pathogen have not been determined. Methods and Findings 21 commercialized food products containing peppers, 357 stool samples from 304 adults and 208 stool samples from 137 children were tested for PMMoV using real-time PCR, sequencing, and electron microscopy. Anti-PMMoV IgM antibody testing was concurrently performed. A case-control study tested the association of biological and clinical symptoms with the presence of PMMoV in the stool. Twelve (57%) food products were positive for PMMoV RNA sequencing. Stool samples from twenty-two (7.2%) adults and one child (0.7%) were positive for PMMoV by real-time PCR. Positive cases were significantly more likely to have been sampled in Dermatology Units (p<10−6), to be seropositive for anti-PMMoV IgM antibodies (p = 0.026) and to be patients who exhibited fever, abdominal pains, and pruritus (p = 0.045, 0.038 and 0.046, respectively). Conclusions Our study identified a local source of PMMoV and linked the presence of PMMoV RNA in stool with a specific immune response and clinical symptoms. Although clinical symptoms may be imputable to another cofactor, including spicy food, our data suggest the possibility of a direct or indirect pathogenic role of plant viruses in humans.

Dipeptidyl peptidase IV inhibitors, a risk factor for bullous pemphigoid: Retrospective multicenter case-control study from France and Switzerland

Background: Case reports have suggested an association between dipeptidyl peptidase‐4 inhibitors (DPP4is) and development of bullous pemphigoid (BP). Objective: To evaluate the association between DPP4i treatment and development of BP. Methods: We conducted a retrospective 1:2 case‐control study, comparing case patients with diabetes and BP with age‐ and sex‐matched control patients with diabetes issued from Swiss (Bern) and French (Marseille) dermatologic departments from January 1, 2014, to July 31, 2016. Results: We collected 61 case patients with diabetes and BP and 122 controls. DPP4is were associated with an increased risk for development of BP (adjusted odds ratio, 2.64; 95% confidence interval, 1.19–5.85; P = .02), with vildagliptin showing the highest adjusted odds ratio (3.57 [95% confidence interval, 1.07–11.84; P = .04]). Stratified analysis showed a stronger association in males and patients age 80 years or older. DPP4i withdrawal and the initiation of first‐line treatments led to clinical remission in 95% of cases. Limitations: This was a retrospective study in tertiary referral hospitals. We focused the analysis on DPP4i intake, without analyzing the potential isolated effect of metformin. Conclusions: DPP4is, especially vildagliptin, are associated with an increased risk for development of BP. Their use needs to be carefully evaluated, particularly in high‐risk patients, such as males and those age 80 years or older.

Cutaneous and pulmonary dirofilariasis due to Dirofilaria repens

Dirofilariasis is a worldwide zoonotic infection that accidentally affects humans. It is caused by filarial nematodes of the genus Dirofilaria, which are transmitted by mosquitoes. Cutaneous dirofilariasis appears as inflammatory lesions that could be consistent with Wells’ cellulitis. We present a remarkable case of human infection with Dirofilaria repens, causing both subcutaneous and pulmonary nodules.

Sensitivity and specificity of BP180 NC16A enzyme-linked immunosorbent assay for the diagnosis of pemphigoid gestationis

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Pyoderma gangrenosum arising during treatment of psoriasis with adalimumab: Effectiveness of ustekinumab

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Increased serum levels of fractalkine and mobilisation of CD34+CD45− endothelial progenitor cells in systemic sclerosis

BackgroundThe disruption of endothelial homeostasis is a major determinant in the pathogenesis of systemic sclerosis (SSc) and is reflected by soluble and cellular markers of activation, injury and repair. We aimed to provide a combined assessment of endothelial markers to delineate specific profiles associated with SSc disease and its severity.MethodsWe conducted an observational, single-centre study comprising 45 patients with SSc and 41 healthy control subjects. Flow cytometry was used to quantify circulating endothelial microparticles (EMPs) and CD34+ progenitor cell subsets. Colony-forming unit-endothelial cells (CFU-ECs) were counted by culture assay. Circulating endothelial cells were enumerated using anti-CD146-based immunomagnetic separation. Blood levels of endothelin-1, vascular endothelial growth factor (VEGF) and soluble fractalkine (s-Fractalkine) were evaluated by enzyme-linked immunosorbent assay. Disease-associated markers were identified using univariate, correlation and multivariate analyses.ResultsEnhanced numbers of EMPs, CFU-ECs and non-haematopoietic CD34+CD45− endothelial progenitor cells (EPCs) were observed in patients with SSc. Patients with SSc also displayed higher serum levels of VEGF, endothelin-1 and s-Fractalkine. s-Fractalkine levels positively correlated with CD34+CD45− EPC numbers. EMPs, s-Fractalkine and endothelin-1 were independent factors associated with SSc. Patients with high CD34+CD45− EPC numbers had lower forced vital capacity values. Elevated s-Fractalkine levels were associated with disease severity, a higher frequency of pulmonary fibrosis and altered carbon monoxide diffusion.ConclusionsThis study identifies the mobilisation of CD34+CD45− EPCs and high levels of s-Fractalkine as specific features of SSc-associated vascular activation and disease severity. This signature may provide novel insights linking endothelial inflammation and defective repair processes in the pathogenesis of SSc.

Febrile ulceronecrotic Mucha-Habermann disease after levamisole-adulterated cocaine use: an unusual case

A 47-year-old man presented with a febrile ulceronecrotic dermatosis. He reported intense use of levamisole-contaminated cocaine during the previous weeks. Physical examination revealed a high fever (40°C) combined with diffuse necrotic papulopustules involving 90% of the body surface (Fig. 1a,b). The patient’s condition rapidly worsened with severe respiratory distress. Biological investigation revealed elevated C-reactive protein (60 mg/L, normal range 0–5 mg/ L) normocytic anaemia (haemoglobin 9.5 g/dL; normal range 13.0–18.0 g/dL) and hepatic cytolysis (transaminases and alkaline phosphatase three times the normal value, and gamma-glutamyltransferase 2fold above the normal value). Tests for infectious disease (blood tests for varicella zoster virus, herpes simplex virus, human immunodeficiency virus, hepatitis B and C viruses, human herpes virus(HHV)-6 and HHV-8, syphilis, Epstein–Barr virus, cytomegalovirus, Pneumococcus, Mycoplasma pneumoniae, bacterial and mycological cutaneous samples and blood cultures) were negative, as were screening tests for autoimmunity. Thoracic computed tomography scan showed ground-glass opacities in the upper lobes combined with perihilar cylindrical bronchodilation. Histopathology of a skin biopsy revealed a diffuse dermoepidermal lymphocyte and neutrophil infiltrate. Leucocytoclastic vasculitis was associated with necrosis of the blood vessel walls and extravasation of erythrocytes (Fig. 2). Based on the clinicopathological findings, febrile ulceronecrotic Mucha–Habermann disease (FUMHD) was suggested. Systemic steroids 1 mg/kg/day were promptly administered, but the patient’s condition deteriorated with severe dyspnoea and extension of the cutaneous lesions. Chest radiography confirmed a worsened interstitial pneumonia, leading to an emergency orotracheal intubation. Intravenous immunoglobulin (IVIG) 2 g/kg (IVIG) resulted in a favourable respiratory and cutaneous response in a few days. IVIG was continued twice a month for a year, producing improvement in skin lesions (Fig. 1c) and liver function tests. After 22 months of follow-up, only hyperpigmented scars (Fig. 1d) were noted. Since then, the patient has completely stopped his cocaine use. FUMHD is considered as a rare and severe variant of pytiriasis lichenoid and varioliformis acuta (PLEVA), with a potentially life-threatening prognosis due to severe systemic visceral involvement. The pathogenesis of FUMHD is unclear. A complex immune vasculitis related to a hypersensitivity reaction towards an infectious antigen has been suspected. The infiltration of CD8 lymphocytes around the epidermis and dermis, suggesting a cytotoxic attack of lymphocytes to altered epidermal antigens, could be an argument in favour of an immunological process. Levamisole is an imidazothiazole drug often used as an adulterant in drugs to produce a better stimulant effect and to increase the drug weight. It has immunostimulant properties, which may result in a leucocytoclastic vasculitis. Levamisole has been reported to cause severe cutaneous vasculopathy syndrome, manifesting as extensive purpura, which can be necrotic with severe skin involvement. Correspondence: Dr Jessica Fongue, Dermatology Service, Hôpital Nord, Assistance Publique Hôpitaux de Marseille, Aix Marseille Universit e, Chemin des Bourelly, 13915 Marseille, France E-mail: jessica.fongue@ap-hm.fr

A pseudotumoral facial mass revealing tertiary syphilis

A 69-year-old man presented with a 10-year history of an asymptomatic erythematous nodular lesion on his left malar area (Fig. 1a). His medical history included placement of coronary stents following an atherosclerosis-related myocardial infarction. Physical examination revealed a painless and nonpruritic pseudotumoral nodule on the patient’s left cheek, which had been enlarging slowly over a number of years, despite repeated use of topical corticosteroids and antibiotics. There were no lesions on the mucosal surfaces, palms or soles, and there was no lymphadenopathy. The results of the examination were unremarkable. All laboratory tests, including blood count, liver enzymes and creatinine, were within normal limits. Serological assays for human immunodeficiency virus (HIV) and hepatitis B and C viruses were negative, as were tests for anti-soluble nuclear antigens, antinuclear antibodies, anti-double-stranded DNA antibodies, and anti-neutrophil cytoplasmic antibodies. Histological examination of a skin biopsy revealed a perivascular and perifollicular inflammatory infiltrate with numerous plasma cells and lymphocytes (Fig. 2). The marked presence of plasma cells in the skin biopsy prompted us to order serological testing for syphilis. Serum venereal disease research laboratory (VDRL) test was negative, but Treponema pallidum test using ELISA method was positive, with a ratio of 10.3. A diagnosis of pseudotumoral tertiary syphilis was suggested. The patient was heterosexual, unmarried and did not recall any risky sexual exposure. Cerebrospinal fluid (CSF) analysis with CSF-VDRL test was negative. Full-body computed tomography scan did not show any systemic involvement. The patient was treated with three intramuscular injections of benzathine benzylpenicillin 2.4 MU at weekly intervals, which led to complete healing of the nodular lesion (Fig. 1b), without any Jarisch– Herxheimer reaction, and definitely confirmed the suspected diagnosis. There was no clinical recurrence during a follow-up of 3 years. Cutaneous lesions revealing tertiary syphilis are very rare. A prospective study following 1978 patients with primary or secondary syphilis from 1891 to 1951 showed that 28% of patients with untreated syphilis developed late signs such as late cutaneous syphilis (16% of tertiary syphilis), cardiovascular syphilis or neurosyphilis. Most cases of late cutaneous syphilis appear in the superficial, noduloulcerative type or the deeper, more destructive, gummatous type. Histologically, granulomas are confined to the dermis within a lymphocytic and plasma cell infiltrate. Marked presence of plasma cells is characteristic and should bring to mind the diagnosis of syphilis. Ours was a rare case of a pseudotumoral facial mass revealing tertiary cutaneous syphilis. The differential diagnoses include lupus tumidus, cutaneous lymphoma, sarcoidosis, rhinoscleroma, leprosy and sporotrichosis. In a review of the literature, we found only three cases of nodular cutaneous tertiary syphilis. These cases did not share the clinical features of our case, making ours even more unusual and interesting. The first case was a 52-year-old black man with a 10-month history of well-circumscribed pruritic violaceous papules and nodules on his left suprascapular area. The second was a 57-year-old black woman who presented with a 30-year history of enlarging plaques on her face, previously diagnosed as discoid lupus erythematosus but unresponsive to Correspondence: Dr Michael Benzaquen, Service de Dermatologie, Hôpital Nord, Chemin des Bourrely, Assistance Publique – Hôpitaux de Marseille, Aix-Marseille Universit e, Marseille 13015, France E-mail: michael.benzaquen@ap-hm.fr

Scabietic vasculitis: Report of 2 cases

BACKGROUND The infectious causes of cutaneous vasculitis are well known and include streptococcal infections among others. Cases resulting from parasitic infection are less frequent. Scabies, which is currently on the increase, has only been reported in a few isolated cases. Herein, we report two noteworthy cases of profuse scabies complicated by cutaneous vasculitis. PATIENTS AND METHODS Case 1: a 90-year-old woman, residing in a nursing home, was admitted to our dermatology department complaining of pruritus, present for one month, predominantly on the inside of the thighs and on the buttocks, associated with purpuric lesions on the lower limbs. A skin biopsy revealed leukocytoclastic vasculitis. A diagnosis of scabies was based on severe pruritus and hypereosinophilia and was confirmed by microscopic examination of the parasitology sample and the skin biopsy sample. Despite thorough investigation, no other cause of vasculitis could be found. Complete regression of the skin lesions was achieved with scabies treatment only, without any specific treatment for the vasculitis. Case 2: a 74-year-old man, living in a nursing home, was hospitalized for purpuric papules on the lower limbs, present for one month. Physical examination revealed linear patterns in the interdigital spaces associated with scabies evident on dermoscopic examination. The skin biopsy revealed signs of vasculitis. As in our first case, no aetiology of vasculitis was found and a favorable outcome was achieved by means of scabies treatment alone with no specific treatment for vasculitis. DISCUSSION Both of our patients presented scabies and vasculitis. In view of the absence of other causes of vasculitis and of the complete regression of lesions due to vasculitis without recurrence achieved with the scabies treatment alone, a diagnosis was made of scabietic vasculitis, probably as a result of cutaneous hypersensitivity reaction to humeral mediators.

AB0826 Does Etanercept Influence Tweak Modulation of Inflammation During Psoriatic Arthritis

Background TWEAK (TNF weakly inducer of apoptosis) is a type II-transmembrane protein, member of the TNF ligand superfamily that can be cleaved to function as a soluble cytokine. Depending on target cell type and micro-environmental conditions, TWEAK triggers multiple cellular responses ranging from modulation of inflammation to cell death. Various data support that TWEAK produced by synovial macrophages may contribute to synovitis in human chronic inflammatory arthritis especially in psoriatic arthritis (PsoA). In PsoA, anti-TNF therapy has been successful in agreement with the key role of TNF in the pathogenesis of this disease and the generation by psoriatic patients of neutralizing anti-TNF autoantibodies referred as “beneficial autoimmunity to pro-inflammatory mediators”. However, the role of TNF-alpha in the regulation of TWEAK modulation of inflammation during PsoA remains unknown. Objectives To assess if anti-TNF therapy affects TWEAK modulation of inflammation during PsoA by evaluating if i) levels of serum soluble TWEAK and ii) levels of anti-TWEAK auto-antibodies generated by PsoA patients are influenced by etanercept therapy. Methods Serum samples from 13 patients with PsoA were collected before and at two time points during etanercept therapy (weeks 12 and 24). Serum samples of 53 healthy blood donors (HBD) were also collected and analyzed. Serum TWEAK concentrations were evaluated with a commercially available ELISA kit and circulating anti-TWEAK auto-antibodies were detected by a homemade-western blot. Disease activity was assessed according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Results Patients with PsoA had significantly higher serum levels of TWEAK compared with controls (respective Means (±SEM) were 645 pg/ml (64) and 467 pg/ml (23); (p=0.006)) but serum soluble TWEAK levels were not correlated with BASDAI (Spearmans coefficients <0.003, p>0.05). Our study showed that soluble TWEAK levels were not modulated by etanercept therapy (respective Means (±SEM) were 645 pg/ml (64)(week 0), 605 (94) (week 12) and 744 (97) (week 24) pg/ml; (p>0.23)). Anti-TWEAK autoantibodies were detected in 9/13 (69.2%) PsoA patients at inclusion and only in 3/53 (5.7%) HBD (p<0.0001). These circulating antibodies were persistent in PsoA patients and detected at similar levels during etanercept therapy. Conclusions We showed here for the first time that during PsoA a significant elevation of TWEAK serum levels and a production of circulating anti-TWEAK autoantibodies occurred. Our data indicated that these two parameters were not significantly modified by anti-TNF therapy. Acknowledgements This work was supported by a grant by Pfizer (Pfizer WS 1797055). We thank Françoise Couranjou for her helpful contribution to this work. Disclosure of Interest None declared