It is not always chlorhexidine: Identification of benzoxonium chloride and lauramine oxide as culprit allergens in a popular antiseptic in Switzerland.

BACKGROUND: A popular antiseptic spray in Switzerland (Merfen spray), containing chlorhexidine digluconate, benzoxonium chloride and lauramine oxide, is frequently used to treat skin wounds. However, it is also increasingly reported as a major cause of adverse skin reactions, including allergic contact dermatitis (ACD). OBJECTIVES: To investigate the contact allergens responsible for ACD from this antiseptic. PATIENTS/METHODS: Patch tests were performed on seven patients with a clinical history compatible with contact dermatitis from this antiseptic mixture. RESULTS: All patients presented with acute eczematous reactions following contact with either Merfen spray alone, or with multiple products including this spray. Patients showed positive reactions to this product in both patch tests and repeated open application tests (ROATs). Four patients showed dose-dependent reactions to both benzoxonium chloride and lauramine oxide. One patient showed a dose-dependent reaction to the former and a non-dose-dependent reaction to the latter. Finally, two subjects showed responses only to lauramine oxide. One patient reacted to chlorhexidine digluconate 0.5% aq. in addition to both other allergens. CONCLUSIONS: Two commercially unavailable allergens, that is, benzoxonium chloride and/or lauramine oxide were identified as major causes of ACD from Merfen antiseptic spray, whereas chlorhexidine digluconate was a contributing culprit in only one patient.

Management of dupilumab-associated ocular surface diseases in atopic dermatitis patients.

Atopic dermatitis is a chronic inflammatory skin disease characterised by eczematous skin lesions and intense pruritus. It is often associated with other atopic diseases such as allergic rhinitis and conjunctivitis, bronchial asthma and eosinophilic oesophagitis. Dupilumab is the first biologic approved for the treatment of moderate-to-severe atopic dermatitis in Switzerland. Dupilumab targets the interleukin (IL)-4/IL-13 receptor and thus inhibits the signalling of IL-4 and IL-13, two key mediators of type 2 inflammation, resulting in an improvement of clinical signs and symptoms of atopic dermatitis. Patients with atopic dermatitis present more often with ocular surface diseases (OSDs), such as allergic conjunctivitis, blepharitis and keratitis as well as infectious conjunctivitis and keratoconus compared with the general population. Upon dupilumab therapy, increased rates of ocular surface diseases have been reported in clinical trials. Interestingly, dupilumab-associated (da) OSD is restricted to atopic dermatitis patients and has not been observed in asthma and chronic rhinosinusitis trials. Fortunately, most cases of dupilumab-associated OSD are mild-to-moderate and transient. Thus, ocular surface disease presents a particular adverse event of treatment with dupilumab in dermatology. This article aims at providing a practical guide for physicians, with a special focus on dermatologists, allergists and ophthalmologists in Switzerland, to the diagnosis and management of dupilumab-associated OSD in atopic dermatitis patients.For this purpose, an expert group of dermatologists and ophthalmologists from university and cantonal hospitals in Switzerland reviewed data on ocular surface diseases published in clinical trial and real-life reports of dupilumab therapy, published case reports and case series on the management of dupilumab-associated OSD, as well as recent recommendations provided by experts of national and international boards. Based on the observations of dupilumab-associated OSD and practical experiences in identifying and treating OSD, an algorithm has been developed that is specific to the needs in Switzerland. Considering concomitant ocular diseases and differential diagnoses, the clinical presentation of dupilumab-associated OSD and its response to therapeutic measures, a stepwise approach is recommended. Mild dupilumab-associated OSD can be managed by dermatologists and allergists, whereas patients with moderate-to-severe OSD requiring corticosteroid or calcineurin inhibitor therapy should necessarily be referred to an ophthalmologist. The effects of preventive measures, such as artificial tears, are uncertain. The recommendations provided here should guarantee a prompt and effective treatment of OSD for patients under dupilumab therapy in order to prevent that an otherwise potent therapy has to be ceased because of ocular adverse events.

[Cutaneous manifestations of nutritional deficiencies]. / Manifestations cutanées de carences nutritionnelles, ou quand l'examen de la peau alimente le diagnostic.

In elderly or chronically ill patients, nutritional deficiencies are common and the presence of related skin lesions is not unusual. Recognition of such cutaneous involvement is important regarding the diagnosis essentially based on clinical elements. By using some clinical case reports, we will describe several pathologies related to nutritional deficiencies like scurvy, pellagra and acquired acrodermatitis enteropathica.

Dans nos populations de patients vieillissants ou atteints de maladies chroniques, les carences nutritionnelles sont fréquentes et la présence de manifestations dermatologiques associées n'est pas rare. La reconnaissance de telles atteintes cutanées est importante pour le diagnostic qui est essentiellement clinique. A l'aide de vignettes cliniques, nous allons discuter ici de pathologies carentielles comme le scorbut, la pellagre ainsi que l'acrodermatite entéropathique acquise.

Effectiveness of lenalidomide in relapsed primary cutaneous diffuse large B-cell lymphoma, leg type.

The primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) has a poor prognosis. R-CHOP with or without radiotherapy is the available recommendations for first-line treatment. Relapses/refractory cases are frequent with no standardized therapeutic guidelines. Lenalidomide seems to be an excellent therapeutic option as a second-line treatment of relapsed PCDLBCL-LT.

[From isolated cutaneous vasculitis to systemic disease†: a diagnostic approach to purpura in the adult patient]. / De la vasculite cutanée isolée aux atteintes systémiques†: l'approche diagnostique d'un purpura chez l'adulte.

Purpura can be a clinical manifestation of various diseases. The causes of purpura are divided into two main categories: thrombocytopenia and vasculopathies. Cutaneous vasculitis belongs to the latter group. Cutaneous vasculitis should be considered a symptom rather than a medical entity. Some forms of cutaneous vasculitis are limited to the skin and are known as isolated cutaneous vasculitis, while other forms may be part of a systemic disease with a more serious prognosis. It is essential to clarify the type and severity of the disease for optimal patient care. A delay in the identification and start of treatment can be the cause of serious and potentially irreversible complications. Through this article, we will propose a step-by-step approach from diagnosis to patient care.

Le purpura peut être la manifestation d'un large spectre de pathologies. Les causes sont généralement séparées en deux groupes principaux : les thrombopénies et les vasculopathies, dont fait partie la vasculite cutanée. Elle doit être considérée comme un symptôme plutôt que comme une entité en soi. Certaines formes peuvent être limitées à la peau alors que d'autres s'inscrivent dans un tableau systémique, potentiellement de mauvais pronostic. Savoir clarifier le type et la sévérité des atteintes est important pour la prise en charge optimale du patient. Un diagnostic précis et précoce est essentiel afin d'éviter des complications sévères et potentiellement irréversibles. A travers cet article, nous proposons un algorithme de raisonnement pour porter le diagnostic étiologique d'un purpura et proposer une prise en charge adaptée.

Netting Neutrophils Activate Autoreactive B Cells in Lupus.

Lupus erythematosus (LE) patients develop autoantibodies that form circulating immune complexes (ICs) with extracellular self-nucleic acids. These ICs are deposited into peripheral tissues, where they trigger detrimental organ inflammation. Recent evidence suggests that ICs contain LL37-DNA complexes derived from neutrophil extracellular traps (NETs) and that LE patients develop pathogenic autoantibodies against these structures, including Abs to LL37. However, the mechanism that leads to the generation of these Abs is unknown. In this study, we show that NETs directly trigger Ab production by human memory B cells. This occurs via LL37-DNA complexes present in NETs, which have the unique ability to gain access to endosomal compartments of B cells and to trigger TLR9 activation. In LE patients, NET-derived LL37-DNA complexes trigger polyclonal B cell activation via TLR9, but also specifically expand self-reactive memory B cells producing anti-LL37 Abs in an Ag-dependent manner. These findings suggest a unique link between neutrophils and B cells in which NETs trigger a concerted activation of TLR9 and BCR leading to anti-NET autoantibody production in lupus.

[If you go looking for trouble you'll find it. Urticarial reactions to insects of our local areas]. / "Qui s'y frotte s'y pique": réactions urticariennes aux insectes de nos regions.

Itchy skin rashes are a frequent reason to seek medical advice. The symptoms may be caused by hypersensitivity reactions to arthropod bites, waterborne parasites or setae from moth caterpillars and are sometimes mistaken for spontaneous urticaria or eczema. Some of these pests are resurging in Switzerland and elsewhere and increasingly responsible for emergency consultation. In this article we review itchy skin rashes caused by bed bugs, scabies, lice, cercariae, Pyemotes spp, caterpillars and harvest mites, which may be confounded with urticaria and allergic contact dermatitis. We detail here clinical manifestations, topographical distribution of skin lesions, epidemiology, treatment and preventive measures.

PASS Syndrome: An IL-1-Driven Autoinflammatory Disease.

PASS syndrome is a rare inflammatory disease characterized by a chronic-relapsing course of pyoderma gangrenosum, acne vulgaris, hidradenitis suppurativa and ankylosing spondylitis. Here, we describe a case of a patient with spontaneously recurrent purulent skin lesions along with seronegative spondylarthritis consistent with the PASS syndrome. During his disease exacerbation, the patient displayed episodes of fever along with elevated serum levels of interleukin (IL)-1ß. Skin lesions were characterized by sterile neutrophilic infiltrates and showed a rapid response to the IL-1 receptor antagonist anakinra (Kineret®) consistent with the autoinflammatory nature of this disease. However, unlike other autoinflammatory diseases such as PAPA and PAPASH, we did not find mutations in the gene PSTPIP1, raising the possibility that other specific mutations in the IL-1 pathway may be involved.

Clinical activity of lenalidomide in visceral human immunodeficiency virus-related Kaposi sarcoma.

IMPORTANCE: Curative treatment of aggressive Kaposi sarcoma (KS) with conventional chemotherapy in human immunodeficiency virus (HIV)-infected patients remains difficult. The administration of thalidomide, an immunomodulatory drug with antiangiogenic effects, is limited by its toxicity. This engenders interest in evaluating thalidomide analogues such as lenalidomide with better toxicity profiles. To our knowledge, we describe for the first time a patient with visceral KS successfully treated with lenalidomide. OBSERVATIONS: A man with advanced visceral HIV-related KS progressing after 11 months of highly active antiretroviral therapy (HAART) and 2 lines of conventional chemotherapy (pegylated liposomal doxorubicin and docetaxel) was treated with lenalidomide on a compassionate use basis. He showed a rapid partial response without any substantial adverse effect but experienced relapse after 5 months of treatment, in a context of virologic failure. CONCLUSIONS AND RELEVANCE: Similar to our observation, good partial response without toxic effects has been reported in 3 patients with only skin involvement. Because immune reconstitution syndrome may occur in HIV-infected patients with KS undergoing HAART, KS improvement may be partly explained by immune recovery. An ongoing US phase 1/2 trial will better evaluate the efficacy and tolerance of lenalidomide in patients with HIV-related KS with and without visceral involvement.

Variants of the xeroderma pigmentosum variant gene (POLH) are associated with melanoma risk.

PURPOSE: Xeroderma pigmentosum variant (XPV) is a rare recessive autosomal genodermatosis predisposing to multiple early onset skin cancers, including melanoma. XPV results from mutations of the POLH gene that encodes a DNA translesion polymerase. In this work, we tested the hypothesis that POLH variants could be associated with melanoma risk. EXPERIMENTAL DESIGN: A common non-synonymous POLH variant, c.1783A>G p.M595V, was genotyped in 1075 melanoma patients and in 1091 ethnic-matched controls from France. In addition, we searched for rare POLH variants by sequencing the entire coding sequence in 201 patients having a familial history of melanoma (n=123), sporadic multiple melanomas (n=65) and a melanoma associated with a skin carcinoma (n=13). RESULTS: Overall, the c.1783G, p.595V allele was statistically associated with melanoma (respective allelic frequencies, 0.040 versus 0.022, P-value=1.17 x 10(-3), odds ratio (OR)=1.86 [1.27-2.71]), which was further confirmed by a meta-analysis including 274 patients and 174 matched controls from Italy (P-value=7.7 x 10(-4), OR=1.84 [1.29-2.63]). Interestingly, three non-synonymous POLH variants were identified in three patients (c.295G>A p.V99M, c.815T>C p.I272T and c.1745C>T p.S582L) which were absent in 352 chromosome controls from healthy subjects. CONCLUSIONS: Besides severe deficiencies in translesion synthesis which are major risks factors for skin carcinomas and melanomas, less deleterious POLH variants could act as low penetrance melanoma predisposing alleles. The ongoing identification of genetic markers implied in skin cancer predisposition could help to identify high-risk subjects as targets for clinical follow-up. Replication studies in other populations are awaited to assess these data.