Bier anemic spots, cyanosis, and urticaria-like eruption (BASCULE) syndrome: Report of two new cases and literature review.

We herein report two new adolescent cases of Bier anemic spots, cyanosis, and urticaria-like eruption (BASCULE) syndrome. This rare, recently described condition may be associated with postural orthostatic tachycardia syndrome (POTS) and other forms of orthostatic intolerance. This report provides details on two cases and a literature review.

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.

Allergic contact dermatitis caused by isobornyl acrylate in Freestyle® Libre, a newly introduced glucose sensor.

BACKGROUND: Glucose sensors, such as FreeStyle® Libre, are innovative medical devices developed for diabetes patients as a replacement for classic glucose meters, ensuring continuous glucose monitoring without the disadvantage of regular skin finger pricks. OBJECTIVES: To report several cases of allergic contact dermatitis caused by FreeStyle® Libre, and to report on isobornyl acrylate as a culprit allergen. PATIENTS AND METHODS: Fifteen patients presented with allergic contact dermatitis caused by FreeStyle® Libre. All but 1 were patch tested with a baseline series, and with pieces and/or ultrasonic bath extracts of (the adhesive part of) the glucose sensor. Isobornyl acrylate was patch tested, in various concentrations and vehicles, in 13 patients. Gas chromatography-mass spectrometry (GC-MS) of the sensors was performed. RESULTS: All patients reacted to the adhesive part of the sensor, and 12 patients were shown to be sensitized to isobornyl acrylate. Simultaneous reactions to other allergens were rarely observed. GC-MS showed the presence of isobornyl acrylate in the sensors. CONCLUSIONS: Cases of allergic contact dermatitis caused by FreeStyle® Libre are increasingly being observed, and isobornyl acrylate is a relevant culprit allergen. Cross-reactivity to other acrylates was infrequently observed, but other, hitherto unidentified, contact allergens may still be present in the device.

Eight Novel Mutations Confirm the Role of AAGAB in Punctate Palmoplantar Keratoderma Type 1 (Buschke-Fischer-Brauer) and Show Broad Phenotypic Variability.

Punctate palmoplantar keratoderma (PPKP1; Buschke-Fischer-Brauer) is a rare autosomal dominant inherited skin disease characterized by multiple hyperkeratotic papules involving the palms and soles. Mutations have been found at 2 loci, on chromosomes 15q22-15q24 and 8q24.13-8q24.21. We recently identified mutations in 3 families, in the AAGAB gene on 15q, which encodes the alpha- and gamma-adaptin-binding protein p34. The current study examined 14 additional families, comprising a total of 26 affected individuals and identified 8 novel mutations in 9 families. In one family a mutation that was present only in the affected individuals was found, and in 4 other families, previously reported mutations were found (1, 2). These results confirm the role of AAGAB in PPKP1. Our findings suggest that there is no correlation with age, but with mechanical factors. No additional obvious genotype-phenotype correlation was observed, even when comparing different types of mutations. Rather, identical genotypes presented a very broad interfamilial and intrafamilial variability of phenotypes.

Characterization of the T cell response in allergic contact dermatitis caused by corticosteroids.

BACKGROUND: Delayed allergic hypersensitivity reactions have classically been described as type IV reactions, which are caused by T cells; however, the respective roles of CD4(+) and CD8(+) cells are yet to be defined. A central role for CD8(+) cytotoxic T cells as effector cells has been suggested. OBJECTIVES: To determine the type of T cell involved in corticosteroid allergy. METHODS: We analysed the kinetics of T cell recruitment and the cytokine production profile in positive patch tests of 27 corticosteroid-sensitized patients, as compared with control sites and control subjects. Skin biopsies, collected at 8, 24 and 48 hr following drug application, were embedded in paraffin for histological and immunohistological staining, and, in some cases, also deep-frozen for gene expression analyses. RESULTS: CD3(+) T cells were rapidly recruited in concert with the positivity of the patch test sites. High levels of interleukin (IL)-4, IL-5 and, to a lesser extent, interferon-γ suggested that both Th2 and Th1 cytokines were implicated. IL-4 was also produced by γδ T cell receptor (TCR) lymphocytes. CONCLUSIONS: This study showed that, in allergic contact dermatitis caused by corticosteroids, the inflammatory infiltrate is composed of CD3(+) T cells with a predominant Th2 cytokine profile, among which IL-4 is also produced by γδ TCR lymphocytes.

Quality of life of parents living with a child suffering from atopic dermatitis before and after a 3-month treatment with an emollient.

Atopic dermatitis (AD) can be extremely disabling and may cause psychological problems for affected children and their families. Moisturizers and emollients are important in the baseline daily skin care of patients with AD. To assess the effect of a 3-month, twice-daily treatment with an emollient on the quality of life (QoL) of parents with a child with mild to moderate AD (SCORing Atopic Dermatitis [SCORAD] ≤ 30, a multicenter open trial was performed by eight dermatologists on 191 volunteers. Evaluation by the dermatologist of the child's clinical condition (SCORAD) and of the efficacy and overall safety of the treatment was associated with a QoL questionnaire completed by one parent of the atopic child. A self-assessment of the global QoL and of the efficacy and overall safety was also performed. During the study, mean SCORAD dropped from 28 to 12 (p < 0.001), with good improvement in skin dryness and pruritus criteria. At the same time, the self-assessment of the global parent QoL scores dropped from 4.4 to 2.1 (p < 0.001) with 60%, 48% and 79% favorable parent opinions regarding wellbeing or improvement of the health condition, quality of sleep, and efficacy of the emollient, respectively. This trial revealed the efficacy of the product in improving parent QoL (85% of parents noted improvement in QoL), and its global safety was considered to be very good or good, with 80% favorable opinions in parents' declarative judgements and dermatologists' assessments. The emollient evaluated improves the course of AD and can improve the QoL of patients and their families.

Cannabis and skin diseases.

From time out of mind, man has grown hemp for both "industrial" and "recreational" use (it is then referred to as cannabis). Of course, cannabis has strong psychoactive properties and is one of the most commonly used "soft drugs" in the world. Clinicians should know the adverse effects on mucous membranes and on skin, which may sometimes entail an absolutely necessary stopping of consumption. Raynaud's phenomenon, as well as arteritis due to cannabis consumption may be extremely severe and result in worrying situations for both clinicians and patients.

Patch, prick or intradermal tests to detect delayed hypersensitivity to corticosteroids?

BACKGROUND: Contact allergy to topical corticosteroids is usually detected by patch testing. OBJECTIVES: This study compares the test results obtained with patch, prick and intradermal testing, to assess the most sensitive method for diagnosing corticosteroid hypersensitivity. PATIENTS/METHODS: Nineteen corticosteroid-allergic subjects and three control subjects were included. Patch, prick and intradermal tests were performed with five commercial corticosteroid preparations, as well as with the respective active principles diluted in ethanol. The test readings were performed at different time points, i.e. at 8, 24, 48 and 96 hr, and at 7 days. RESULTS: Patch tests with ethanolic preparations produced more positive reactions than the commercial ones. The intradermal tests became positive earlier than the patch tests, a concordance between patch and intradermal tests being found in 11/15 (two positive intradermal test results with negative patch test results and vice versa). However, several subjects developed skin atrophy (14/22) at intradermal injection sites. CONCLUSION: Patch testing with the active principles diluted in ethanol remains the diagnostic method of choice for the detection of delayed hypersensitivity to corticosteroids. Intradermal tests with late readings, despite detecting additional contact allergy cases, should not be routinely performed, because of an important risk of atrophy, particularly with corticosteroid suspensions.

Fragrance allergy: assessing the safety of washed fabrics.

BACKGROUND: Previously, a quantitative risk assessment suggested there was no risk of induction of fragrance allergy from minor residues of fragrance chemicals on washed fabrics. OBJECTIVE: To investigate whether there was any risk of the elicitation of contact allergy from fragrance chemical residues on fabric in individuals who were already sensitized. METHODS: Thirty-six subjects with a positive patch test to isoeugenol (n = 19) or hydroxyisohexyl 3-cyclohexene carboxaldehyde (n = 17) were recruited. Dose-response and fabric patch tests were performed, respectively, with filter paper and a cotton sample loaded with fragrance in ethanol-diethylphthalate (DEP) and applied in a Finn Chamber or a Hill Top Chamber. RESULTS: Only two subjects reacted to an isoeugenol patch test concentration of 0.01% (>20x the estimated likely skin exposure level), none reacted to lower concentrations. Of 36 subjects, 18 reacted to the fabric patch treated with ethanol-DEP vehicle alone and 20 to the fragrance-chemical-treated fabric patch. These were only minor non-specific skin reactions. They were also quite evenly distributed between the two fragrance chemical allergic groups. CONCLUSIONS: On the basis of the examples studied, fragrance chemical residues present on fabric do not appear to present a risk of the elicitation of immediate or delayed allergic skin reactions on individuals already sensitized.

Evaluation of Chilblains as a Manifestation of the COVID-19 Pandemic.

Importance: During the coronavirus disease 2019 (COVID-19) pandemic, several cases of chilblains have been reported. Objective: To determine if chilblains are associated with COVID-19. Design, Setting, and Participants: This monocentric case series was conducted at the Department of Dermatology at Cliniques universitaires Saint-Luc, a tertiary care hospital in Brussels, Belgium, between April 10 and April 17, 2020. We evaluated a total of 31 referred patients who had recently developed chilblains. Main Outcomes and Measures: Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA on nasopharyngeal swabs for all patients and in skin biopsy specimens for 22 patients. Blood samples from all patients were tested for specific anti-SARS-CoV-2 immunoglobulin (Ig) M and IgG antibodies. All patients had extended blood analyses. Histologic (22 patients) and immunofluorescence examinations (15 patients) were performed on the skin biopsy specimens. Results: The 31 patients were generally in good health; most were teenagers or young adults, and 19 were women. Histopathologic analysis of skin biopsy specimens (22 patients) confirmed the diagnosis of chilblains and showed occasional lymphocytic or microthrombotic phenomena. Immunofluorescence analyses showed vasculitis of small-diameter vessels in 7 patients. In all patients, SARS-CoV-2 RNA remained undetected by RT-PCR on nasopharyngeal swabs and in biopsy samples of the skin lesions. The IgM and IgG antibody titers were negative for SARS-CoV-2 in all patients (<1.0 arbitrary unit/mL). No significant abnormalities in blood test results were suggestive of systemic disease. Antinuclear antibody titers were low in 7 patients and higher in 1 patient. Conclusions and Relevance: Chilblains appeared not to be directly associated with COVID-19 in this case series. Lifestyle changes associated with community containment and lockdown measures are a possible explanation for these lesions.

Real-time PCR and DNA sequencing for detection and identification of Trichophyton rubrum as a cause of culture negative chronic granulomatous dermatophytosis.

A 31-year-old patient presented with a diagnosis of granulomatous dermatophytosis based on the clinical aspect of the lesions and the rare presence of hyphae on direct microscopic examination of clinical material. A chronic evolution and progression of the disease, its resistance to a wide range of antifungal agents, the occasional presence of hyphae on direct examination but consistently negative cultures over a 5-year period prompted the use of amplification-based DNA analyses of several successive swab samples or skin biopsies. DNA was extracted using a combination of two semi-automated DNA isolation methods (FastPrep preparation and NucliSENS lysis magnetic extraction method). Identification relied both on sequence analysis of amplicons after SYBR Green real-time PCR of the panfungal internal transcribed spacer 1 (ITS1) genetic target, as well as the unique amplicon melting curve profile of positive samples. Accordingly, Trichophyton rubrum was unambiguously identified in several clinical samples collected over a 7-month period. This case illustrates the contribution of DNA-based assays applied directly to sample biopsies for identifying causative agents in cases in which fungal pathogens are highly suspected but culture are repeatedly negative. It also pinpoints the benefit of combining semi-automated DNA preparation methods, analysis of ITS1 amplicon melting curve profiles and sequence analysis on repeated skin biopsy samples for unambiguous identification of the causative fungal species.

Allergic contact dermatitis from transdermal buprenorphine.

BACKGROUND: Buprenorphine is a low-molecular-weight, lipophilic, opioid analgesic. The transdermal delivery system (TDS) containing it has skin irritation potential, but at least two cases of contact allergy to the active principal have been described previously. OBJECTIVE: To confirm allergic contact dermatitis from transdermal buprenorphine (TDB) in five older patients suffering from chronic pain and who developed persistent, pruritic erythematous plaques at the contact sites, with two of them also presenting with a generalized skin eruption. METHODS: Besides the baseline patch test series, all five patients were tested with the TDB, four of whom were also tested with the placebo transdermal delivery system as provided by the manufacturer; one patient was also tested with other preparations containing buprenorphine. RESULTS: All reacted to the TDB containing the active principal, the placebo being negative in the four patients tested. The patient tested with the other buprenorphine preparations did react positively to them as well. Tests with TDB in 28 healthy controls were negative. CONCLUSION: We report five cases of delayed hypersensitivity reactions to a TDS containing buprenorphine. Such adverse reactions might be under-reported. A fentanyl-containing TDS is a good alternative in these cases.