Treatment of congenital Langerhans cell histiocytosis with cobimetinib.

We report a case of congenital multisystem Langerhans cell histiocytosis with cutaneous and hematopoietic involvement. After the failure of first-line (vinblastine and prednisolone) and second-line (vincristine and cytarabine) therapies, treatment with cobimetinib, a mitogen-activated protein kinase (MEK) inhibitor, led to the remission of disease and a sustained response after 11 months of ongoing treatment. Protein kinase inhibitors targeting BRAF or MEK could represent a promising future therapeutic option, also in children with LCH.

Sofa dermatitis: Value of patch test with 2-(thiocyanomethylthio)benzothiazole.

BACKGROUND: In 2008, numerous cases of allergic contact dermatitis caused by leather chairs (sofa dermatitis) were reported, with dimethylfumarate being the culprit allergen. However, octylisothiazolinone, methylisothiazolinone and cobalt have also been associated with cases of sofa dermatitis. An antifungal agent, 2-(thiocyanomethylthio)benzothiazole (TCMTB), has also previously been described as a contact allergen in leather. MATERIALS AND METHODS: Seven patients were referred to the Department of Dermatology of the Cliniques universitaires Saint-Luc, Brussels, Belgium with suspicion of allergic contact dermatitis caused by leather sofas. They were patch tested with the European Baseline Series, additional series (according to the patients' history and clinical aspect of the eruption), dimethylfumarate (4/7 patients) and with TCMTB. RESULTS: All seven patients presented a positive reaction to TCMTB and only one presented a concomitant positive reaction to dimethylfumarate. All patients showed clinical improvement after avoiding contact with their leather sofa. CONCLUSION: 2-(Thiocyanomethylthio)benzothiazole (TCMTB) is probably an underestimated allergen present in leather chairs (responsible for the so-called 'sofa dermatitis'), and more generally in leather objects. It is, therefore, important to test with TCMTB 0.1% petrolatum in case of contact dermatitis related with leather products.

Pandemic chilblains: Are they SARS-CoV-2-related or not?

The exact etiopathology of chilblains observed during the Coronavirus Disease 2019 (COVID-19) pandemic is still unclear. Initially, SARS-CoV-2 appeared as the obvious causing agent, but two years of various investigations have failed to convincingly support its direct implication. Most affected individuals have no detectable virus, no anti-SARS-CoV-2 antibodies and no symptoms of COVID-19. Analyses of skin biopsies similarly failed to unambiguously demonstrate presence of the virus or its genome. In a recent hypothesis, SARS-CoV-2 would cause the lesions before being promptly eliminated by unusually strong type I interferon responses. With others, we feel that environmental factors have not been sufficiently considered, in particular cold exposure related to unprecedented containment measures. The cause of pandemic chilblains remains a stimulating puzzle which warrants further investigation.

Short- and Long-Term Evaluation of General Practitioners' Competences After a Training in Melanoma Diagnosis: Refresher Training Sessions May Be Needed.

General practitioners (GPs) are first-line clinicians in melanoma diagnosis. It is, therefore, important to ensure that they maintain their melanoma diagnostic accuracy over time. The objective of this study was to assess the short- and long-term competences of GPs after a training session in naked-eye melanoma diagnosis. An interventional prospective study was conducted whereby, over a 6-month period, GPs attended a 1-h melanoma diagnostic training session. To assess their acquired competences, GPs were asked to fill in a questionnaire on basic melanoma knowledge and to evaluate 10 clinical images of pigmented skin lesions prior to training, immediately after and 1 year later. In total, 89 GPs completed the questionnaire prior and immediately after training. As expected, the number of GPs who appropriately managed [Formula: see text] 50% of the melanoma cases increased after training (P < 0.001). One year after training, only 27 (30%) of the 89 GPs completed the questionnaire. This number of participants was too low to obtain significant figures but the GPs' mean overall score of appropriately managed clinical cases was much lower than in the immediate post-test. In conclusion, although this short training improved the GPs' diagnostic accuracy and management of melanoma in the short-term, participating GPs do not seem to have maintained these competences in the long-term. Further studies are needed to assess whether refresher training sessions are able to sustain acquired diagnostic and management skills.

Unique molecular signatures typify skin inflammation induced by chemical allergens and irritants.

BACKGROUND: Skin exposure to chemicals may induce an inflammatory disease known as contact dermatitis (CD). Distinguishing the allergic and irritant forms of CD often proves challenging in the clinic. METHODS: To characterize the molecular signatures of chemical-induced skin inflammation, we conducted a comprehensive transcriptomic analysis on the skin lesions of 47 patients with positive patch tests to reference contact allergens and nonallergenic irritants. RESULTS: A clear segregation was observed between allergen- and irritant-induced gene profiles. Distinct modules pertaining to the epidermal compartment, metabolism, and proliferation were induced by both contact allergens and irritants; whereas only contact allergens prompted strong activation of adaptive immunity, notably of cytotoxic T-cell responses. Our results also confirmed that: (a) unique pathways characterize allergen- and irritant-induced dermatitis; (b) the intensity of the clinical reaction correlates with the magnitude of immune activation. Finally, using a machine-learning approach, we identified and validated several minimal combinations of biomarkers to distinguish contact allergy from irritation. CONCLUSION: These results highlight the value of molecular profiling of chemical-induced skin inflammation for improving the diagnosis of allergic versus irritant contact dermatitis.

A case report of cutaneous leishmaniasis: a misleading clinical presentation.

BACKGROUND: The diagnosis of cutaneous leishmaniasis (CL) is often difficult because of the diversity of clinical presentations, its often-misleading appearance and the very long incubation period (time between the endemic stay and the onset of skin lesions). CASE: We report the case of an otherwise healthy 67-year-old man who presented with inflammatory skin lesions on the scalp and face for the past 7 years. The lesions were first mistaken as cutaneous sarcoidosis, mycobacterial infection, and cutaneous lymphoma. Finally, the diagnosis was made by RT-PCR analysis on a punch-biopsy specimen, which was positive for Leishmania infantum. DISCUSSION AND CONCLUSION: To date, the choice of treatment for complex cutaneous leishmaniases is based on the Leishmania species. Our patient successfully responded to liposomal amphotericin B.

Evolution of methylisothiazolinone sensitization: A Belgian multicentric study from 2014 to 2019.

BACKGROUND: In the 2010s an epidemic of allergic contact dermatitis to methylisothiazolinone (MI) occurred in Europe. European authorities banned the use of methylisothiazolinone in leave-on cosmetics in 2017 and limited its use in rinse-off products in 2018. OBJECTIVES: To investigate the sensitization rate to MI in Belgium between January 2014 and December 2019, and to assess cosensitizations to octylisothiazolinone (OIT) and benzisothiazolinone (BIT) in MI-sensitized patients. METHODS: A retrospective study of patch test results with MI, OIT, and BIT observed in patients attending five Belgian hospitals. RESULTS: Overall, 560 of 10 029 patients (5.58%) had a positive patch test reaction to MI, and its sensitization rate decreased from 7.9% in 2014 to 3.1% in 2019. Rinse-off cosmetics, paints, and detergents were the most prevalent sensitization sources in recent years. Simultaneous reactions readily occurred to OIT, and, surprisingly, and increasingly, also to BIT. CONCLUSIONS: Contact allergy to MI in Belgium has reached a pre-epidemic level, reflecting the impact of recent regulatory measures. Leave-on cosmetics, in contrast to rinse-off products, have almost disappeared as sensitization sources in Europe. Paints and detergents also remain problematic. The remarkably high number of patients (co)sensitized to BIT should be a focus of future research.

Linear IgA dermatosis in association with angioimmunoblastic T-cell lymphoma infiltrating the skin: A case report with literature review.

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive form of peripheral T-cell lymphoma, characterized by systemic symptoms, diffuse lymphadenopathy, hepatosplenomegaly and immunodysregulation. Half of AITL is associated with cutaneous symptoms, but only few cases with bullous eruption have been described. Association with a linear IgA dermatosis is extremely rare. Linear IgA dermatosis can be idiopathic, or linked with drug intake or neoplastic disorders. Some cases of linear IgA dermatosis presenting as toxic epidermal necrolysis (TEN) have been described, most of them being drug induced. We here present the case of a 72-year-old man recently diagnosed with AITL who developed a bullous eruption, presenting as TEN. Histopathology showed deep cutaneous involvement of the lymphoma with a sub-epidermal blistering and direct immunofluorescence revealed a heavy IgA linear deposit on the dermal-epidermal junction. A diagnosis of linear IgA dermatosis associated with cutaneous involvement of an angioimmunoblastic T-cell lymphoma was made. Chemotherapy and corticosteroids allowed cutaneous improvement but the patient died of his lymphoma shortly after.

Adverse cutaneous reaction to diabetic glucose sensors and insulin pumps: Irritant contact dermatitis or allergic contact dermatitis?

BACKGROUND: Adverse cutaneous reactions to diabetes medical devices (glucose sensors and insulin pumps) are described, notably allergic contact dermatitis (ACD) with isobornyl acrylate (IBOA) and N,N dimethylacrylamide (DMAA) as the main allergen. OBJECTIVES: To determine if all cases of adverse cutaneous reactions observed with diabetes medical devices (ie FreeStyle Libre, Enlite sensors or insulin pumps), referred to our department with suspected allergies are confirmed as ACD. PATIENTS AND METHODS: Fifty-two patients who presented skin reactions to diabetes medical devices were patch tested with the European baseline series, a plastic and glues series, a (meth) acrylates series, a piece of the adhesive part of the device, as well as IBOA 0.1% and DMAA 0.1% pet. RESULTS: Seventeen patients had no positive reaction to IBOA nor to the adhesive part of the device; 11 of these also tested with DMAA with negative result. No other relevant allergen was identified. CONCLUSION: Some cutaneous reactions, otherwise very similar to those of patients sensitized to IBOA, can be explained either by the presence of an untested allergen not yet discovered, or by irritant contact dermatitis. Therefore, European legislation on the full labelling of ingredients by manufacturers, in order to facilitate the identification of allergens and irritants, is imperative.

Contact dermatitis caused by glucose sensors in diabetic children.

BACKGROUND: Allergic contact dermatitis caused by glucose sensors has been recently described in diabetics, mostly in adult patients. Isobornyl acrylate and N-N dimethylacrylamide are the potent causative agents. OBJECTIVES: To describe a child population with contact dermatitis caused by glucose sensors, determine the causative allergen, and assess the prevalence of isobornyl acrylate (IBOA) sensitization. PATIENTS AND METHODS: Overall, 12 children with a reaction to medical devices, either glucose sensors or insulin sets, were patch tested with the European baseline series, glues and rubber, (meth) acrylates series, and with piece of the adhesive part of the glucose sensor FreeStyle Libre. Isobornyl acrylate 0.1% pet. was patch tested in 11 patients, and N-N dimethylacrylamide in two. Some patients were tested with adhesive parts of the infusion set. RESULTS: Overall, 10 children reacted to the adhesive part of the sensor FreeStyle Libre, and 10 children were sensitized to IBOA. One patient turned out to be negative in all patch tests. CONCLUSION: Allergic contact dermatitis caused by glucose sensors is common in the pediatric diabetic patient population. Like in the adult patient population, IBOA was the culprit allergen, with 83.3% sensitization prevalence in children exhibiting adverse cutaneous reactions caused by FreeStyle Libre.

Allergic contact dermatitis caused by synthetic rubber gloves in healthcare workers: Sensitization to 1,3-diphenylguanidine is common.

BACKGROUND: The frequency of allergic contact dermatitis has significantly increased in healthcare workers since the transition from latex to synthetic rubber gloves, with 1,3-diphenylguanidine being identified as the most frequently implicated allergen. OBJECTIVES: To highlight the role of 1,3-diphenylguanidine as the culprit allergen in contact allergies to synthetic rubber gloves, to propose recommendations for patch testing, and to discuss alternatives for sensitized subjects. MATERIALS AND METHODS: Patch test data from healthcare workers who developed hand dermatitis after wearing rubber gloves and who reacted positively to glove samples and rubber additives were collected from September 2010 to December 2017 in a Belgian hospital. RESULTS: A total of 44 caregivers were included in this study. Patch tests showed that: (a) 84% of the study population reacted positively to carba mix; (b) 86% reacted positively to 1,3-diphenylguanidine; and (c) 13 (30%) reacted positively to thiuram mix. Half of the subjects reacted positively to gloves containing 1,3-diphenylguanidine, whereas none reacted to accelerator-free gloves. CONCLUSION: The most commonly identified allergen was 1,3-diphenylguanidine, far ahead of thiurams, which were previously described as the most sensitizing accelerators. The use of 1,3-diphenylguanidine-free gloves is recommended. No subject reacted to gloves without accelerators, thus confirming their efficiency among accelerator-sensitized patients. We recommend that 1,3-diphenylguanidine be added to the European baseline series.

Allergic contact dermatitis caused by isobornyl acrylate in the Enlite glucose sensor and the Paradigm MiniMed Quick-set insulin infusion set.

BACKGROUND: The FreeStyle Libre glucose sensor has caused many cases of allergic contact dermatitis, and isobornyl acrylate (IBOA) in this sensor has been identified as one of the culprit allergens. OBJECTIVES: To report on the presence of IBOA in devices produced by Medtronic, namely, the Enlite sensor and the insulin infusion set Paradigm MiniMed Quick-set. PATIENTS AND METHODS: Five patients reacting to the glucose sensor Enlite and/or the insulin infusion set Paradigm MiniMed Quick-set observed in three clinics (two Belgian and one Swedish) were patch tested with the baseline and other series, as well as with IBOA; four of them also with pieces of adhesive patches from the devices, and two with a thin layer chromatogram of Enlite glucose sensor extracts. Gas chromatography-mass spectrometry (GC-MS) analyses were performed. RESULTS: Four patients reacted to IBOA and one to colophonium, a known allergen in Enlite, and three to the adhesive part of the sensor or the insulin infusion set. IBOA was identified in the sensor by GC-MS, and its presence was indicated in the infusion set. CONCLUSIONS: IBOA is a contact allergen in Enlite glucose sensor, and likely also in the infusion set. Therefore, these devices are not suitable alternatives for patients sensitized to the FreeStyle Libre sensor.

The preservative 2-(thiocyanomethylthio)benzothiazole: A potential allergen in leather products.

BACKGROUND: Allergic contact dermatitis caused by leather is common, and several responsible allergens, such as tanning agents, glues, mercaptobenzothiazole derivatives, and dyes, but also antimicrobials and antifungals, are involved. MATERIAL AND METHODS: Three female patients were referred to the Departments of Dermatology in a Belgian university hospital following skin reactions caused by leather products (shoes, belt, and car seats). They were patch tested with the European baseline series and samples of suspected leather products, and additionally with 2-(thiocyanomethylthio)benzothiazole (TCMTB), an antifungal agent previously reported to be a contact allergen in footwear. Chromatographic analyses of samples of all the leather materials tested were performed at the Department of Occupational and Environmental Dermatology in Malmö, Sweden. RESULTS: The patients reacting to the leather samples were shown to be sensitized to TCMTB, the presence of which could be confirmed by chemical analyses of samples obtained from the patients. CONCLUSION: Patch tests with TCMTB should be considered in patients with contact dermatitis caused by leather items.

N,N-dimethylacrylamide-A new sensitizer in the FreeStyle Libre glucose sensor.

BACKGROUND: Isobornyl acrylate (IBOA) has recently been identified as one sensitizer in the FreeStyle Libre glucose sensor. Analyses with gas chromatography-mass spectrometry (GC-MS) have indicated the presence of N,N-dimethylacrylamide (DMAA) in the sensor. MATERIAL AND METHODS: Seven patients were referred for patch testing after developing skin reactions when using FreeStyle Libre. All patients were patch tested with IBOA and DMAA. Two patients were tested with adhesive patches that had been removed from the sensors "as is," and two patients were tested with acetone extracts of materials from the sensor. The extracts were analysed with GC-MS. RESULTS: Six patients reacted to both IBOA and DMAA, and one patient reacted only to DMAA. Positive reactions were also observed in both patients tested with the adhesive patch "as is". One patient reacted to both an extract of the adhesive patch and an extract of the sensor itself. When analysed with GC-MS, IBOA was found in both extracts and DMAA was found in the extract of the sensor. CONCLUSION: Both IBOA and DMAA may be present in adhesives used in medical devices such as glucose sensors or insulin pumps, and should be patch tested when suspected contact allergic reactions to these products are investigated.

Unexpected positive patch test reactions to sesquiterpene lactones in patients sensitized to the glucose sensor FreeStyle Libre.

BACKGROUND: Most diabetic patients sensitized to FreeStyle Libre react to isobornyl acrylate (IBOA), with a considerable number of them also showing unexpected positive patch test reactions to sesquiterpene lactone (SL) mix (SLM) tested in the baseline series. OBJECTIVES: To compile patch test results of subjects affected, and provide potential explanations for this association. PATIENTS AND METHODS: Fifty-three Freestyle Libre-allergic patients were patch tested with IBOA and/or SLM, and several were also patch tested with the components of SLM. Chromatographic analyses were performed on the glucose sensor, IBOA, and the components of SLM. RESULTS: Thirty-three patients reacted positively to the components of SLM, and 11 of 27 patients reacted positively to alantolactone, in particular. Gas chromatography-mass spectrometry (GC-MS) analyses did not detect these chemicals in the different parts of the glucose sensor, or in IBOA. CONCLUSION: Significant co-sensitizations between SLs on the one hand and the glucose sensor FreeStyle Libre and/or isobornyl acrylate on the other hand exist, without evidence of the presence of SLs via GC-MS analysis. Cross-reactions between them seem improbable. As a possible hypothesis, a common precursor for both, such as camphene, may exist.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome caused by first-line antituberculosis drugs: Two case reports and a review of the literature.

BACKGROUND: Patients suffering from drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome caused by first-line antituberculosis drugs often need to be retreated rapidly. Patch tests prior to the reintroduction of antituberculosis drugs are rarely performed. OBJECTIVES: To highlight those drugs most often involved in DRESS caused by antituberculosis drugs, illustrate the potential value of patch tests to identify these culprit(s), and provide insights into how to rapidly retreat these patients. METHODS: A detailed description of the work-up of two illustrative patients, together with a literature review of similar cases, is provided. RESULTS: All first-line antituberculosis drugs may cause DRESS syndrome, but rifampicin and isoniazid are most frequently involved. Patch tests can be performed sooner than usually advised in the context of DRESS syndrome, and potentially with lower test concentrations, but false-negative results are possible. Sequential reintroduction of patch test-negative drugs is feasible, although the dose and order of drugs to be readministered, as well as the use of concomitant systemic corticosteroids, remain a matter of debate. CONCLUSION: Patch tests in the context of DRESS syndrome caused by antituberculosis drugs, despite their shortcomings, may potentially guide rapid retreatment of these patients.

Treatment of chronic spontaneous urticaria: Immunomodulatory approaches.

This paper summarizes and reviews the mechanisms of action and data concerning efficacy of recommended treatments as well as other treatments that have been tested, independently of the outcomes, in the management of chronic spontaneous urticaria. Due to the central role of mast cells, basophils and histamine in the pathophysiology of this disease, H1-antihistamines remain the first-line treatment. However, current knowledge about this complex disease, also recognizes an important role for T lymphocytes, B lymphocytes, and autoantibodies. Implications of these others mediators thus provide further targets for treatment. Indeed, agents previously used to treat other autoimmune and inflammatory diseases, have demonstrated efficacy in chronic spontaneous urticaria and are therefore potential therapeutic alternatives for antihistamine unresponsive patients.