Bullous haemorrhagic dermatitis induced by heparins and other anticoagulants: 94 cases from French pharmacovigilance centres and a literature review.

BACKGROUND: Bullous haemorrhagic dermatitis (BHD) is an uncommon and highly particular side effect of various forms of heparins. METHODS: To better characterise the disease, we collected all cases from French Pharmacovigilance centres recorded over a 20-year period (37 cases) and performed a Medline literature search up to June 2020 (57 cases). RESULTS: In all, 94 patients were identified (male/female ratio: 2.2) of mean age 73.5±12.1 years (31-94). Patients were treated with enoxaparin (n=66), unfractionated heparin (n=11), fondaparinux (n=10), tinzaparin (n=4), bemiparin (n=1), reviparin (n=1), dalteparin (n=1), and 4 with other anticoagulants: warfarin (n=3) and rivaroxaban (n=1). All cases presented with 1 to more than 100 haemorrhagic vesicles and bullae, distant from the injection sites, located mainly on the lower (75%) or upper limbs (69%). The lesions were asymptomatic, except in 5 patients who had pruritic or painful lesions. The interval between treatment initiation and BHD ranged from 6 hours to 30 days (mean: 8.4±7 days). Biopsy (n=53) showed intraepidermal or subcorneal cavity with red cells (n=39) or junctional blisters (n=10), with eosinophilic infiltrate only rarely. Direct immuno-fluorescence was negative in 19/20 cases and indirect immunofluorescence was negative in 8/8. The outcome was favourable in all cases, including in 12 patients for whom heparin was maintained. A 93-year-old patient died of compressive haematomas unrelated to BHD. We found 5 cases similar to BHD due to other anticoagulants. DISCUSSION: This is the largest comprehensive series of this adverse effect due to heparins or, more rarely, to other anticoagulants. Dermatologists must be aware of BHD, since this benign side effect does not necessarily require interruption of treatment. It is rare, considering the large-scale prescription of heparins, and occurs mainly in male patients aged over 70. Although the presentation is highly typical, the physiopathology is difficult to understand, as coagulation parameters are usually normal. Aging, skin fragility or mechanical factors might play a role.

Clinical, Radiological and Therapeutic Characteristics of Patients with COVID-19 in Saudi Arabia

BACKGROUNDCoronavirus disease 2019 (COVID-19) is a rapidly spreading global pandemic. The clinical characteristics of COVID-19 has been reported; however, there are limited researches that investigated the clinical characteristics of COVID-19 in the Middle East. The aim of this study is to investigate the clinical, radiological and therapeutic characteristics of patients diagnosed with COVID19 in Saudi Arabia. METHODSThis study is a retrospective single-centre case series study. We extracted data for patients who were admitted to the Al-Noor Specialist hospital with a PCR confirmed SARS-COV-2 between 12th and 31st of March 2020. Descriptive statistics were used to describe patients characteristics. Continuous data were reported as mean {+/-} SD. Chi-squared test/Fisher test were used as appropriate to compare proportions for categorical variables. RESULTSA total of 150 patients were hospitalised for COVID-19 during the study period. The mean age was 46.1 years (SD: 15.3 years). Around 61.0% (n= 90) were males and six patients (3.9%) reported working in the healthcare sector. The most common comorbidities were hypertension (28.8%, n= 42) and diabetes mellitus (26.0%, n= 38). The majority of the patients, 64.4% (n = 96) had a recent contact history with a COVID patient. Regarding the severity of the hospitalised patients, 105 patients (70.0%) were mild, 29 (19.3%) were moderate, and 16 patients (10.7%) were severe or required ICU care. From the 105 mild patients, around 31.3% (n= 47) were asymptomatic. CONCLUSIONThis case series provides clinical, radiological and therapeutic characteristics of hospitalised patients with confirmed COVID-19 in Saudi Arabia.

[Multiple erythema annulare centrifugum associated with knee monoarthritis revealing Capnocytophagacanimorsus infection]. / Erythème annulaire centrifuge multiple et monoarthrite révélateurs d'une infection à Capnocytophaga canimorsus.

INTRODUCTION: Capnocytophagacanimorsus (C. canimorsus), a commensal Gram-negative bacillus found in the oral cavity of dogs and cats, is pathogenic for humans, with the most common clinical manifestations being septicemia, meningitis and endocarditis. Herein we report a case of CC bacteremia manifesting as multiple plaques of erythema annulare centrifugum associated with monoarthritis of the knee. PATIENTS AND METHODS: A 66-year-old man consulted for a skin rash and monoarthritis of the right knee with fever following an insect bite on his right hallux. Cutaneous examination revealed numerous erythematous annular plaques on the trunk and limbs with centrifugal extension. Analysis of synovial fluid from the right knee showed an inflammatory liquid with a sterile bacteriological culture and PCR was negative for Borrelia. C. canimorsus bacteria were isolated from blood cultures. 16S RNA PCR performed on the synovial fluid was positive for the same organism. The patient's history revealed that his hallux wound had been licked by his dog. DISCUSSION: C. canimorsus most frequently affects immunosuppressed subjects. Cutaneous signs are seen in half of all cases, most frequently presenting as cellulitis, pathological livedo or thrombotic purpura. We report herein a case of CC bacteremia in an immunocompetent patient manifesting as multiple plaques of erythema annulare centrifugum, an unusual sign, and monoarthritis of one knee.

The 2020 International Alliance for the Control of Scabies Consensus Criteria for the Diagnosis of Scabies.

BACKGROUND: Scabies is a common parasitic skin condition that causes considerable morbidity globally. Clinical and epidemiological research for scabies has been limited by a lack of standardization of diagnostic methods. OBJECTIVES: To develop consensus criteria for the diagnosis of common scabies that could be implemented in a variety of settings. METHODS: Consensus diagnostic criteria were developed through a Delphi study with international experts. Detailed recommendations were collected from the expert panel to define the criteria features and guide their implementation. These comments were then combined with a comprehensive review of the available literature and the opinion of an expanded group of international experts to develop detailed, evidence-based definitions and diagnostic methods. RESULTS: The 2020 International Alliance for the Control of Scabies (IACS) Consensus Criteria for the Diagnosis of Scabies include three levels of diagnostic certainty and eight subcategories. Confirmed scabies (level A) requires direct visualization of the mite or its products. Clinical scabies (level B) and suspected scabies (level C) rely on clinical assessment of signs and symptoms. Evidence-based, consensus methods for microscopy, visualization and clinical symptoms and signs were developed, along with a media library. CONCLUSIONS: The 2020 IACS Criteria represent a pragmatic yet robust set of diagnostic features and methods. The criteria may be implemented in a range of research, public health and clinical settings by selecting the appropriate diagnostic levels and subcategories. These criteria may provide greater consistency and standardization for scabies diagnosis. Validation studies, development of training materials and development of survey methods are now required. What is already known about this topic? The diagnosis of scabies is limited by the lack of accurate, objective tests. Microscopy of skin scrapings can confirm the diagnosis, but it is insensitive, invasive and often impractical. Diagnosis usually relies on clinical assessment, although visualization using dermoscopy is becoming increasingly common. These diagnostic methods have not been standardized, hampering the interpretation of findings from clinical research and epidemiological surveys, and the development of scabies control strategies. What does this study add? International consensus diagnostic criteria for common scabies were developed through a Delphi study with global experts. The 2020 International Alliance for the Control of Scabies (IACS) Criteria categorize diagnosis at three levels of diagnostic certainty (confirmed, clinical and suspected scabies) and eight subcategories, and can be adapted to a range of research and public health settings. Detailed definitions and figures are included to aid training and implementation. The 2020 IACS Criteria may facilitate the standardization of scabies diagnosis.

Trace element contamination in fish impacted by bauxite red mud disposal in the Cassidaigne canyon (NW French Mediterranean).

From 1966 to 2015, the Gardanne alumina refinery discharged some 20 million tons of bauxite residue (called red mud) into the Cassidaigne Canyon (northwest French Mediterranean) with impacts on local ecosystem functioning. Although these red muds contained high levels of trace elements (TE), in particular titanium (Ti), vanadium (V), aluminum (Al) and arsenic (As), surprisingly, their impacts on fish contamination levels and the risk related to fish consumption have been little studied until now. Here, 11 trace elements (Al, As, Cd, Cr, Co, Cr, Mn, Ni, Pb, Ti and V) were analyzed in muscle and, when possible, liver, from 1308 fish of 26 species from an impacted zone in the vicinity of the Cassidaigne Canyon and a reference zone, unaffected by red mud disposals. Moreover, 66 arsenic speciation analyses were performed. Although the impact of human activities on the levels of fish contamination by trace elements is generally not easy to assess in situ because it is blurred by interaction with biological effects, we highlighted significant contamination of the fish species collected from the Cassidaigne Canyon, especially by the main trace elements attributable to the discharges of the Gardanne alumina refinery, namely Al, V and Ti. Moreover, inorganic toxic As concentrations were higher in the impacted zone. The results of this baseline research also confirmed the concern previously raised regarding Hg in Mediterranean organisms and that trace element contamination levels in fish are generally negatively related to fish length for all TE except Hg.

[Intravascular lymphoma simulating relapse of breast cancer: An original clinical case]. / Lymphome intravasculaire simulant une récidive de cancer du sein : une présentation clinique originale.

BACKGROUND: Intravascular lymphoma is a rare form of non-Hodgkin's lymphoma with varied but highly evocative clinical presentations, particularly in terms of dermatology. Histological examination of the skin may be sufficient to allow diagnosis. PATIENTS AND METHODS: Herein, we report the case of a 75-year-old woman with a history of infiltrative ductal carcinoma of the left breast who was hospitalised for neurological evaluation following repeated falls. During the course of her hospital stay, the patient's neurological state deteriorated rapidly, and onset of marked laboratory-documented inflammatory syndrome was observed, together with disseminated intravascular coagulation (DIC). At the same time, she developed orange-peel type skin lesions on her left breast followed by a rapidly-spreading livedoid infiltrated plaque on her side. The skin biopsy enabled a diagnosis to be made of intravascular lymphoma based on immunohistochemical demonstration of intravascular tumoral proliferation of lymphoid cells expressing CD45 marker and B-cell marker CD20, as well as Bcl2, MUM 1 and CD5. DISCUSSION: Intravascular B-cell lymphoma is a rare subtype of diffuse large B-cell lymphoma. It carries a poor prognosis and the clinical appearance varies extremely widely. The signs are primarily neurological and dermatological. Because of the varied nature of presentations as well as the rarity of the disease, diagnosis may be delayed, with worsening of the prognosis of the disease, which nevertheless requires rapid and aggressive management. However, the appearance of infiltrated and livedoid lesions on the trunk or limbs is evocative and skin biopsy constitutes a readily accessible diagnostic tool that offers rapid confirmation.

[Histopathological study of basaloid follicular hamartoma]. / Hamartome folliculaire basaloïde : étude anatomoclinique.

INTRODUCTION: Basaloid follicular hamartoma (BFH) is a rare tumor first described in 1985. It bears clinical and histologic similarities with basal cell carcinoma (BCC), in particular the so-called infundibulocystic form. We performed a single-center clinicopathological study of a series of typical cases of this entity that is occasionally difficult to diagnose. MATERIALS AND METHODS: All cases of BFH seen at the Dermatopathology Laboratory of Strasbourg University Hospital were included and analyzed by means of HE staining and Ber-EP4 and PHLDA1 immunolabelling. Diagnosis was made in the event of basaloid proliferation with anastomosing cords developed from a hair follicle. Clinical data were collected from clinical files. RESULTS: We identified 15 cases in 13 patients of mean age 44.8 years (range: 4 to 90) and the sex-ratio was 5/8. Lesions consisted of flesh-colored papules measuring 0.3 to 1.2cm in diameter, without any preferential site. Three patients had multiple lesions consisting of several coalescent papules on a breast for one, sparse papules on the back for another, and hundreds of linear unilateral BFHs, associated with osseous abnormalities, characteristic of Happle-Tinschert syndrome, for the third. All tumors were limited to the superficial and mid dermis, with a vertical orientation and connection to the epidermis in 14 of the 15 patients. In some cases, the outermost cells were basophilic while the central cells were eosinophilic. Peripheral palisading and clefting were frequently observed. Keratin cysts or sebaceous ducts were consistently present, indicating follicular differentiation. Ber-EP4+ cells were restricted to the periphery of the cords and PHLDA1 was weakly expressed. DISCUSSION: BFH is a rare entity that must be differentiated from BCC. It presents as solitary or multiple lesions, either grouped in plaques or with a generalized or linear unilateral distribution. Generalized BFH may be associated with autoimmune diseases and linear unilateral BFH with osseous, dental and cerebral abnormalities in Happle-Tinschert syndrome. It is important to distinguish BFH from BCC to avoid inappropriate aggressive treatment.

[What's new in clinical dermatology?] / Quoi de neuf en dermatologie clinique?

In this article, we performed a review of all new data of clinical relevance for the dermatologists that were published in the medical literature between September, 2017 and September, 2018. Besides advances that will be useful in day-to-day dermatological practice, we intended to give a more general perspective to this review by taking into account certain international health issues that might in final concern each of us in a globalized world. Focus were more particularly done on the following topics: infectious diseases (including sexually transmitted infections), neglected tropical diseases, adverse effects of drugs, bullous diseases, allergology, wound healing, dermatology on black skin, and public health dermatology.

[A new case of Rowell's syndrome]. / Un nouveau cas de syndrome de Rowell.

INTRODUCTION: This article introduces a new case of Rowell's syndrome, a controversial entity defined by the association of lupus erythematosus and erythema multiforme. OBSERVATION: A 43-year-old woman was diagnosed with lupus erythematosus induced by esomeprazole. Because her eruption did not improve after withdrawal of the drug, hydroxychloroquine was administered. Two weeks later, the patient described new annular lesions on her chest and arms, both erosive and crusted, and some had a target-like appearance. The oral mucosa was also affected. Histology revealed sub-epidermal blistering with keratinocytic necrosis, strongly suggesting erythema multiforme. Screening for other causes of erythema multiforme proved negative. A positive outcome was achieved with corticosteroids and hydroxychloroquine. One year later, the patient was in complete remission for both lupus erythematosus and erythema multiforme. DISCUSSION: The association of lupus erythematosus and erythema multiforme first described in 1963 is known as Rowell's syndrome. While diagnostic criteria have been established in the literature, the reality of this entity is still contested. The annular lesions of subacute lupus erythematosus may be confused with the lesions of erythema multiforme. As suggested in the above section, other authors consider Rowell's syndrome to be a singular entity. Indeed, our patient developed lesions distinct from those initially suggesting subacute lupus erythematosus, in particular: the target-like aspect of the elementary lesions, mucosal involvement, a distinct histological aspect, and dissociated outcomes. Ultimately, the definition of Rowell's syndrome remains highly debated.

[Ganulomatosis with polyangiitis revealed by a cutaneous ulceration mimicking a pyoderma gangrenosum: Two patients]. / Granulomatose avec polyangéite révélée par une ulcération cutanée mimant un pyoderma gangrenosum : à propos de 2 cas.

INTRODUCTION: Granulomatosis with polyangiitis is a systemic and necrotizing vasculitis, and cutaneous involvement is uncommon. We report two cases of skin ulceration mimicking a pyoderma gangrenosum, and revealing granulomatosis with polyangiitis. CASE REPORTS: We report two patients who presented with atypical cutaneous ulcerations, with a chronic course. These wounds were large ulcerations with abrupt edges, with purulent and hemorrhagic exudates. The first hypothesis was a pyoderma gangrenosum, but the biopsies were not specific. New biopsies performed distant from the edges showed a necrotizing vasculitis associated with giant cells granuloma, typical from granulomatosis with polyangiitis. CONCLUSION: Cutaneous manifestations are uncommon in granulomatosis with polyangiitis, and can be misleading as they may precede the systemic symptoms. We report two cases of granulomatosis with polyangiitis revealed by cutaneous symptoms mimicking a pyoderma gangrenosum. Repetition of the skin biopsies were necessary to obtain the diagnosis.

[A second case of white lentiginosis]. / Un second cas de lentiginose blanche.

INTRODUCTION: White lentiginosis is characterized by white guttate macules with a typical histological structure: lentiginosis hyperplasia with hypopigmentation. OBSERVATION: A 23-year-old woman, from Algeria, presented with white macules from 5 years ago. Few women in her family had the same trouble. Cutaneous examination revealed diffused white little macules. Histological examination showed a lentiginous hyperplasia of the epidermis, with elongated club-shaped rete ridges and an unusual loss of pigmentation. DISCUSSION: Different diagnosis should be discussed with disseminated leucoderma macules. Nevertheless, the only one which corresponds with our case is the white lentiginosis. To our knowledge, it is the first case described since Grosshans et al. in 1994. Our patient is a descendant of the original case's family. This new case appears to confirm the genetic origin of the disorder and suggests autosomal dominant or X-linked inheritance.