Michael Benzaquen

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.

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

1. Lowitt M, Dover J. Necrobiosis lipoidica. J. Am. Acad. Dermatol. 1991; 25: 735–48. 2. Reid S, Ladizinski B, Lee K et al. Update on necrobiosis lipoidica: a review of etiology, diagnosis, and treatment options. J. Am. Acad. Dermatol. 2013; 69: 783–91. 3. Sibbald C, Reid S, Alavi A. Necrobiosis lipoidica. Dermatol. Clin. 2015; 33: 343–60. 4. Gebauer K, Armstrong M. Kobner phenomenon with necrobiosis lipoidica diabeticorum. Int. J. Dermatol. 1993; 32: 895–6. 5. Khunger N, Molpariya A, Khunger A. Complications of tattoos and tattoo removal: stop and think before you ink. J. Cutan. Aesthet. Surg. 2015; 8: 30–6. 6. Wood A, Hamilton S, Wallace W et al. Necrobiotic granulomatous tattoo reaction. Am. J. Dermatopathol. 2014; 36: e152–5. 7. Babin-muise D, Miller R, Murray S et al. Necrobiosis lipoidica diabeticorum in a tattoo site. J. Cutan. Med. Surg. 2012; 16: 286–7.

Does mandibular third molar have an impact on dental mandibular anterior crowding? A literature review

Mandibular dental anterior crowding is a common multi-factorial phenomenon. The involvement of the lower third molar remains unclear. These pending questions led us to conduct a literature review to evaluate the impact of the lower third molar on mandibular dental anterior crowding. Twelve articles were selected, published from 1974 to 2014. Four studies were prospective. Sample size ranged from 30 to 9044. The average age was 20.56 years old. Seven studies considered patient with orthodontic treatment. The studies compared two to four groups. Studying tools were radiographs, casts and clinical examinations. Littles irregularity index, TSALD and Ganss ratio were used. In total, 83% of articles (n=10/12) did not find any significant relationship between lower third molar and mandibular dental anterior crowding. However, methods and designs of these studies being questionable, a definite conclusion on the impact of mandibular third molar on mandibular dental anterior crowding cannot be set.

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

Pulmonary embolism induced by methotrexate in a dermatomyositis patient

Joint Bone Spine - In Press.Proof corrected by the author Available online since mardi 20 septembre 2016

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

Primary cutaneous nocardiosis caused by Nocardia takedensis with pulmonary dissemination in an immunosuppressed patient.

We present a remarkable case of primary cutaneous nocardiosis with pulmonary dissemination due to Nocardia takedensis in a 76‐year‐old man suffering from marginal zone lymphoma and hypogammaglobulinaemia. We also discuss an alternative treatment to trimethoprim‐sulfamethoxazole, which could be contraindicated due to haematological and cutaneous toxicities. This case report is of interest due to the emergence of cutaneous nocardiosis in dermatology.

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.