Formaldehyde 2% is not a useful means of detecting allergy to formaldehyde releasers- results of the ESSCA network, 2015-2018.

BACKGROUND: Studies suggest that patch testing with formaldehyde releasers (FRs) gives significant additional information to formaldehyde 1% aq. and should be considered for addition to the European baseline series (EBS). It is not known if this is also true for formaldehyde 2% aq. OBJECTIVES: To determine the frequency of sensitization to formaldehyde 2% aq. and co-reactivity with FRs. To establish whether there is justification for including FRs in the EBS. MATERIALS AND METHODS: A 4-year, multi-center retrospective analysis of patients with positive patch test reactions to formaldehyde 2% aq. and five FRs. RESULTS: A maximum of 15 067 patients were tested to formaldehyde 2% aq. and at least one FR. The percentage of isolated reactions to FR, without co-reactivity to, formaldehyde 2% aq. for each FR were: 46.8% for quarternium-15 1% pet.; 67.4% imidazolidinyl urea 2% pet.; 64% diazolidinyl urea 2% pet.; 83.3% 1,3-dimethylol-5, 5-dimethyl hydantoin (DMDM) hydantoin 2% pet. and 96.3% 2-bromo-2-nitropropane-1,3-diol 0.5% pet. This demonstrates that co-reactivity varies between FRs and formaldehyde, from being virtually non-existent in 2-bromo-2-nitropropane-1,3-diol 0.5% pet. (Cohen's kappa: 0, 95% confidence interval [CI] -0.02 to 0.02)], to only weak concordance for quaternium-15 [Cohen's kappa: 0.22, 95%CI 0.16 to 0.28)], where Cohen's kappa value of 1 would indicate full concordance. CONCLUSIONS: Formaldehyde 2% aq. is an inadequate screen for contact allergy to the formaldehyde releasers, which should be considered for inclusion in any series dependant on the frequency of reactions to and relevance of each individual allergen.

Targeted Therapy for Chronic Spontaneous Urticaria: Rationale and Recent Progress.

Chronic spontaneous urticaria (CSU) is characterized by the presence of wheals, angioedema, or both for at least 6 weeks. It may persist for a long time-up to 50% of the patients have been reported to be symptomatic 5 years after the onset. Some patients can suffer more than one episode of CSU during their lifetime. Considering the recurrences, disabling symptoms, and significant impact on quality of life, proper and effective treatment of CSU is critical. The use of antihistamines (AHs) is still the mainstay of treatment. However, given the low rates of response to AHs (38.6% and 63.2% to standard doses and higher doses, respectively), the complete control of symptoms seems difficult to attain. The use of omalizumab for CSU has been a major breakthrough in the care of patients with CSU. However, the partial response and lack of response to omalizumab in a subgroup of patients, as high as 70% in some studies, make the development of alternative treatments desirable. Ever-increasing knowledge on the pathogenesis is making new target molecules available and enabling drug development for CSU. In addition to drug repurposing as in anti-IL-4/13, IL-5, and IL-17 antibodies, novel targeted therapy options such as ligelizumab and Bruton's tyrosine kinase inhibitors are currently undergoing clinical trials and will be available in the near future. This article reviews the current challenges in the treatment of CSU, the pathogenesis and potential target molecules, and the rationale for novel treatments and their rapidly developing status.

Circulating CLA+ T lymphocytes as peripheral cell biomarkers in T-cell-mediated skin diseases.

T lymphocytes expressing the CLA antigen constitute a subset of effector memory lymphocytes that are functionally involved in T-cell-mediated cutaneous diseases. Skin-seeking lymphocytes recirculate between inflamed skin and blood during cutaneous inflammation. Many studies in different T-cell-mediated inflammatory cutaneous diseases have clearly related their pathologic mechanisms to CLA+ T cells. Based on common features of these cells in different cutaneous disorders mediated by T cells, we propose that circulating CLA+T cells could constitute very useful peripheral cellular biomarkers for T-cell-mediated skin diseases.

Patch testing with 2.0% (0.60 mg/cm 2) formaldehyde instead of 1.0% (0.30 mg/cm 2) detects significantly more contact allergy.

BACKGROUND: The currently used patch test concentration for formaldehyde is 1.0% (wt/vol) in water. However, clinical experience and previous studies suggest that 1.0% might be insufficient for detecting an optimized number of clinically relevant cases of contact allergy to formaldehyde. OBJECTIVES: To validate earlier patch test results for comparison of 1% (wt/vol) and 2% (wt/vol) formaldehyde in water, and to investigate co-reactivity with quaternium-15. MATERIALS AND METHODS: In 12 dermatology clinics, 3591 patients were routinely patch tested simultaneously with 2.0% (wt/vol) (0.60 mg/cm(2)) and 1.0% (wt/vol) (0.30 mg/cm(2)) formaldehyde. Micropipettes were used for delivering the exact dosage of the allergen. RESULTS: Significantly more patients reacted to 2.0% formaldehyde than to 1.0% (3.4% versus 1.8%, p < 0.001). Overall, there were no sex differences between those reacting positively to 2.0% and 1.0%. Of 25 quaternium-15-positive patients, 4 (0.1%) reacted positively without reacting to formaldehyde. CONCLUSION: On the basis of the results of this multicentre study, as well as of previous studies, it can be suggested that 2.0% (wt/vol) in water formaldehyde should be used in routine patch testing in the baseline series.

Self-testing for contact sensitization to hair dyes--scientific considerations and clinical concerns of an industry-led screening programme.

The cosmetic industry producing hair dyes has, for many years, recommended that their consumers perform 'a hair dye allergy self-test' or similar prior to hair dyeing, to identify individuals who are likely to react upon subsequent hair dyeing. This review offers important information on the requirements for correct validation of screening tests, and concludes that, in its present form, the hair dye self-test has severe limitations: (i) it is not a screening test but a diagnostic test; (ii) it has not been validated according to basic criteria defined by scientists; (iii) it has been evaluated in the wrong population group; (iv) skin reactions have been read by dermatologists and not by the targeted group (consumers and hairdressers); (v) hair dyes contain strong and extreme sensitizers that are left on the skin in high concentrations, potentially resulting in active sensitization; and (vi) recommendations and instructions on how to perform the hair dye self-test vary greatly even among products from the same company, again suggesting that the basis for safe use of the test has not been determined. If the use of a hair dye self-test to predict contact sensitization becomes widespread, there is severe risk that a tool has been marketed that may cause morbidity in European consumers.

Principles and methodology for translation and cross-cultural adaptation of the Nordic Occupational Skin Questionnaire (NOSQ-2002) to Spanish and Catalan.

BACKGROUND: Occupational skin diseases are among the most frequent work-related diseases in industrialized countries. The Nordic Occupational Skin Questionnaire (NOSQ-2002), developed in English, is a useful tool for screening of occupational skin diseases. OBJECTIVES: To culturally adapt the NOSQ-2002 to Spanish and Catalan and to assess the clarity, comprehension, cultural relevance and appropriateness of the translated versions. METHODS: The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) principles of good practice for the translation and cultural adaptation of patient-reported outcomes were followed. RESULTS: After translation into the target language, a first consensus version of the questionnaire was evaluated in multiple cognitive debriefing interviews. The expert panel introduced some modifications in 39 (68%) and 27 (47%) items in the Spanish and Catalan version, respectively (e.g. addition of examples and definitions, reformulation of instructions and use of direct question format). This version was back translated and submitted to the original authors, who suggested a further seven and two modifications in the Spanish and Catalan versions, respectively. A second set of cognitive interviews were performed. A consensus version of both questionnaires was obtained after final modifications based on comments by the patients. CONCLUSIONS: The final versions of the Spanish and Catalan NOSQ-2002 questionnaires are now available at www.NRCWE.dk/NOSQ.

Cutaneous venous malformations in familial cerebral cavernomatosis caused by KRIT1 gene mutations.

BACKGROUND: Cerebral cavernous malformations (CCMs) are vascular lesions characterized by abnormally enlarged capillary cavities without intervening brain parenchyma. Although often asymptomatic, seizures, cerebral haemorrhages and focal neurological deficits are well-documented complications. Mutations in the CCM1 (7q21-22), CCM2 (7p13-15) and CCM3 (3q25.2-27) genes have been identified in familial CCM. In rare instances, the association of congenital hyperkeratotic cutaneous capillary-venous malformations (HCCVMs) with CCM1 has been reported. OBSERVATIONS: We studied 6 members of a family with CCMs. Four members of the family developed late-onset multiple, tiny, bluish, soft, cutaneous papules, mainly located on the face, arm and abdominal area, corresponding histologically to venous malformations. A splice donor site mutation in intron 4 (c. 1146 + 1 G-->A) in the CCM1 gene was identified. CONCLUSIONS: Our findings suggest that mutations in the KRIT1 gene may cause phenotypically heterogeneous cutaneous vascular lesions other than those previously described as HCCVMs.

Circulating CLA+ T cell subsets inversely correlate with disease severity and extension in acute psoriasis but not in chronic plaque psoriasis.

Circulating CLA+ T cells represent a subset of lymphocytes functionally associated to several cutaneous diseases. This population of peripheral lymphocytes is poorly characterized in acute stage psoriasis. We studied, by flow cytometry, the relationship between disease severity and extension and different subsets of circulating T cells in 31 psoriatic patients (7 guttate, 8 acute and 16 chronic psoriasis). An inverse correlation between circulating CLA+ CD3+/CD4+ subsets and disease severity and extension was found in the acute form of psoriasis. Interestingly, we also observed that circulating CLA+CD4+CD25+ cells inversely correlated with PASI and BSA in guttate patients, which had not been shown previously. These results may contribute to clarify the role of circulating T cells in psoriasis, especially in early stages of psoriasis.