Occupational hand dermatitis secondary to methacrylates-The 'manual tray' sign.

A case report of a dentist presenting with allergic contact dermatitis to methacrylates present in dental bonding agent applied on the dorsum of a gloved hand. The patient presented with a localized dermatitis to the dorsum of the non-dominant hand which can be described as a 'manual tray sign'.

Tricyclic antidepressant-induced photosensitivity; A case report and systematic review.

BACKGROUND/PURPOSE: Tricyclic antidepressants (TCAs) are still widely used and are available to purchase without prescription in some countries. Awareness of adverse cutaneous drug reactions is essential. METHOD: We reported a case of photo-distributed hyperpigmentation due to imipramine and carried out a systematic search of the related articles using the search terms "tricyclic antidepressants" or "tricyclic antidepressive agents", and "hyperpigmentation" or "photosensitivity disorder". Fifty non-duplicate citations were identified of which 28 articles which were independently assessed in full. The review was registered in PROSPERO, CRD42018107338. RESULTS: The remaining 25 articles met our inclusion criteria. Photo-distributed hyperpigmentation tricyclic antidepressant-induced photosensitivity reactions (TIPs) was the most common presentation. In 21 cases, this presented as an asymptomatic discolouration of exposed sites. Imipramine (81%), amitriptyline (9.5%), desipramine hydrochloride (4.8%) and mirtazapine (4.8%) were reported to be the culprit drugs. Nineteen were female with a mean age at presentation of 55 years. Mean duration from commencing the culprit drug until the development of discolouration was 10.4 years. Mean daily dose was 222.7 mg for imipramine. Histology was characteristic with golden-brown or brownish granules deposited in dermis. Staining for Masson-Fontana and MEL-5 was positive in all cases. Phototesting had not been done in cases prior to ours (negative 3 months after discontinuation of imipramine). Three further reports of suspected TIP presented with non-specific and eczematous eruption. The two presentations were reported along with systemic problems (thrombocytopenia and hepatic injury). CONCLUSIONS: This systematic review highlights the characteristic features of exposed site hyperpigmentation of TCA-induced photosensitivity occurring after prolonged drug exposure in many cases.

Gradient boosting approaches can outperform logistic regression for risk prediction in cutaneous allergy.

BACKGROUND: Contact allergy is a major clinical and public health challenge. It is important to identify individuals who are at risk and perform patch testing to identify relevant allergens. Predicting clinical risk on the basis of input parameters is common in clinical medicine and traditionally has been achieved with linear models. OBJECTIVES: We hypothesized that the risk of a clinically relevant positive patch test could be predicted according to clinical and demographic parameters. METHODS: We compared the predictive accuracy of logistic regression with more sophisticated machine learning approaches such as gradient boosting, in the prediction of patch testing results. RESULTS: We found that both logistic regression and more sophisticated machine learning approaches were able to predict the risk of positive patch tests. For certain predictions, including the overall risk of a clinically relevant positive patch test, gradient boosting approaches can outperform logistic regression. CONCLUSIONS: These findings suggest that complex nonlinear interactions between input variables are relevant in risk prediction. While a risk prediction model cannot replace the judgment of an experienced clinician, quantifying the risk of a clinically relevant positive patch test result has the potential to assist in decision making and to inform discussions with patients.

Optimization of quantitative susceptibility mapping for regional estimation of oxygen extraction fraction in the brain.

PURPOSE: We sought to determine the degree to which oxygen extraction fraction (OEF) estimated using quantitative susceptibility mapping (QSM) depends on two critical acquisition parameters that have a significant impact on acquisition time: voxel size and final echo time. METHODS: Four healthy volunteers were imaged using a range of isotropic voxel sizes and final echo times. The 0.7 mm data were downsampled at different stages of QSM processing by a factor of 2 (to 1.4 mm), 3 (2.1 mm), or 4 (2.8 mm) to determine the impact of voxel size on each analysis step. OEF was estimated from 11 veins of varying diameter. Inter- and intra-session repeatability were estimated for the optimal protocol by repeat scanning in 10 participants. RESULTS: Final echo time was found to have no significant effect on OEF. The effect of voxel size was significant, with larger voxel sizes underestimating OEF, depending on the proximity of the vein to the superficial surface of the brain and on vein diameter. The last analysis step of estimating vein OEF values from susceptibility images had the largest dependency on voxel size. Inter-session coefficients of variation on OEF estimates of between 5.2% and 8.7% are reported, depending on the vein. CONCLUSION: QSM acquisition times can be minimized by reducing the final echo time but an isotropic voxel size no larger than 1 mm is needed to accurately estimate OEF in most medium/large veins in the brain. Such acquisitions can be achieved in under 4 min.

Perforin, COVID-19 and a possible pathogenic auto-inflammatory feedback loop.

During COVID-19 infection, reduced function of natural killer (NK) cells can lead to both compromised viral clearance and dysregulation of the immune response. Such dysregulation leads to overproduction of cytokines, a raised neutrophil/lymphocyte ratio and monocytosis. This in turn increases IL-6 expression, which promotes scar and thrombus formation. Excess IL-6 also leads to a further reduction in NK function through downregulation of perforin expression, therefore forming a pathogenic auto-inflammatory feedback loop. The perforin/granzyme system of cytotoxicity is the main mechanism through which NK cells and cytotoxic T lymphocytes eliminate virally infected host cells, as well as being central to their role in regulating immune responses to microbial infection. Here, we present epidemiological evidence suggesting an association between perforin expression and resistance to COVID-19. In addition, we outline the manner in which a pathogenic auto-inflammatory feedback loop could operate and the relationship of this loop to genes associated with severe COVID-19. Such an auto-inflammatory loop may be amenable to synergistic multimodal therapy.

Harnessing co-operative immune augmentation by contact allergens to enhance the efficacy of viral vaccines.

Although the development of successful vaccines against coronaviruses may be achieved, for some individuals the immune response that they stimulate may prove to be insufficient for effective host defence. The principle that a relatively strong contact allergen will have an enhancing effect on sensitization compared with a less potent contact allergen if they are co-administered, may not, at first, appear relevant to this issue. However, this augmentation effect is thought to be due to the sharing of common or complementary pathways. Here, we briefly consider aspects of the shared and complementary pathways between skin sensitization induced by exposure to a contact allergen and the immune response to viruses, with particular reference to COVID-19. The relationship leads us to explore whether this principle, which we name here as "co-operative immune augmentation" may be extended to include viral vaccination. We consider evidence that even relatively weak contact allergens, used in vaccines for other purposes, can show enhanced sensitization, which is in keeping with a co-operative augmentation principle. Finally, we consider how the potent contact allergen diphenylcyclopropenone could be employed safely as an enhancer of vaccine responses.

Addressing the conundrums of p-phenylenediamine hair dye allergy by applying Friedmann's principles of contact sensitization.

In the first conundrum, permanent hair dyeing involves the use of aromatic amines such as p-phenylenediamine (PPD), whose oxidation is pivotal to the dyeing process, but also generates potent allergens. Despite prolonged efforts by industry to search for safer alternatives, hair dyeing is still reliant on this type of aromatic amine. In the second conundrum, patch testing with 1% PPD remains the most useful screen for hair dye contact allergy. However, there is a very small but real risk of actively sensitizing the patient. Lowering the PPD concentration below 1% significantly reduces test sensitivity and diagnostic utility. Here, we argue that by applying Friedmann's principles of contact sensitization each conundrum can be addressed from a new perspective. These principles indicate that, when the exposed area of skin is small (<1 cm2 ), induction of contact allergy is sharply reduced, whereas elicitation of allergy is unaffected. Careful reflection on this principle suggests that we can predict where hair dye sensitization is most likely to occur, indicates a strategy to reduce the chance of contact sensitization occurring in consumers as a result of hair dyeing, and how we might mitigate the risk of active sensitization resulting from diagnostic patch testing.

Allergic contact dermatitis in atopic individuals: Results of a 30-year retrospective study.

BACKGROUND: The association between atopic dermatitis (AD) and contact allergy, remains unclear, with studies to date showing conflicting results. OBJECTIVES: To investigate the prevalence of contact allergy in AD individuals compared to those without AD. METHODS: Results of 46 250 patients patch tested in a single centre over a span of 30 years were reviewed, comparing those with AD with those without AD. Collected data were analysed with corrections for multiple confounding variables, including date of patch testing to account for changes in allergens tested over the period. RESULTS: Nine allergens showed a statistically significant difference between the two groups. Contact allergy to nickel, cobalt and primin was less likely to arise in those with AD, whilst substances found in topical dermatological products were more likely to be associated with AD. CONCLUSIONS: This is the largest single centre study of contact sensitization in atopy reported to date. The previously reported association between contact allergy to sesquiterpene lactone and AD is reinforced. The decreased incidence of metal allergy suggests distinct immunological effector mechanisms in sensitization to these allergens. In keeping with previous publications, exposure to topical treatments for AD can result in sensitisation and contact allergy and clinicians should consider patch testing in AD individuals who report worsening of their skin despite continued treatment with topical medicaments.

The epidemic of methylisothiazolinone: a European prospective study.

BACKGROUND: The use of methylisothiazolinone (MI) in cosmetic products has caused an unprecedented epidemic of MI contact allergy. Current data concerning exposures at a European level are required. OBJECTIVES: To describe demographics and MI exposures for European patients with MI contact allergy. METHODS: Eleven European dermatology departments from eight European countries prospectively collected data between 1 May and 31 October 2015 among consecutive patients who had positive patch test reactions to MI (2000 ppm aq.). RESULTS: A total of 6.0% (205/3434; range 2.6-13.0%) of patients had positive patch test reactions to MI. Dermatitis most frequently affected the hands (43.4%), face (32.7%), arms (14.6%), and eyelids (11.7%); 12.7% had widespread dermatitis. For 72.7% (149/205), MI contact allergy was currently relevant mainly because of exposure to cosmetic products (83.2%; 124/149). Of these 124 patients, 19.5% were exposed to leave-on and rinse-off cosmetic products, 24.8% only to leave-on cosmetic products and 38.9% only to rinse-off cosmetic products containing MI or methylchloroisothiazolinone/MI. The majority of these (79%) noted onset of their dermatitis between 2013 and 2015. Fifteen patients (7.3%) had previously experienced allergic reactions when they were in newly painted rooms. CONCLUSION: Clinically relevant MI contact allergy remains prevalent across European countries, mainly because of exposure to rinse-off and leave-on cosmetic products.

Influence of vitamin C on the elicitation of allergic contact dermatitis to p-phenylenediamine.

BACKGROUND: Hair dyes represent one of the most important causes of allergic contact dermatitis resulting from the use of cosmetic products. The principal causative chemistry is associated with oxidation products of p-phenylenediamine (PPD) and closely related substances. OBJECTIVES: To examine whether prior application of the antioxidant vitamin C to the skin was able to reduce the cutaneous allergic response to PPD. METHODS: Twenty eight volunteers with a proven history of contact allergy to PPD were recruited. Each was tested with a range of PPD doses and PPD-containing hair dye on untreated skin and skin pretreated for 10 min with a vitamin C formulation. RESULTS: Pretreatment of skin sites with vitamin C led to a reduction in the intensity, or even ablation, of the cutaneous allergic reaction to PPD in ∼75% of cases as compared with untreated skin. CONCLUSIONS: The results suggest that treatment of the skin adjacent to the hair-bearing area with antioxidant could form part of a strategy to reduce the burden of cosmetic allergic contact dermatitis caused by hair dyeing.