American Contact Dermatitis Society Core Allergen Series: 2020 Update.

The American Contact Dermatitis Society Core Allergen series was introduced in 2013 and updated in 2017. Changes in our recommended allergens are again necessary, taking into account data from the American Contact Dermatitis Society's Contact Allergen Management Program top 100 allergens from 2018. For the updated series, we removed methyldibromoglutaronitrile and added new haptens: Lyral, Limonene, Linalool, carmine, benzyl salicylate, disperse yellow 3, jasmine, peppermint, pramoxine, shellac, and lauryl polyglucose (glucosides). These additional allergens should increase the yield of relevant positive reactions for our patients.

Application of the dermal sensitization threshold concept to chemicals classified as high potency category for skin sensitization assessment of ingredients for consumer products.

Skin sensitization evaluation is a key part of the safety assessment of ingredients in consumer products, which may have skin sensitizing potential. The dermal sensitization threshold (DST) concept, which is based on the concept of the thresholds of toxicological concern, has been proposed for the risk assessment of chemicals to which skin exposure is very low level. There is negligible risk of skin sensitization if a skin exposure level for the substance of interest was below the reactive DST which would protect against 95% of protein-reactive chemicals. For the remaining 5%, the substance with the defined knowledge of chemical structure (i.e., High Potency Category (HPC) rules) needs to be excluded from the application. However, the DST value for HPC chemicals has not yet been proposed. In this study, we calculated the 95th percentile probabilities estimate from distributions of skin sensitization potency data and derived a novel DST for HPC chemicals (HPC DST) of 1.5 µg/cm2. This value presents a useful default approach for unidentified substances in ingredients considering, as a worst-case scenario, that the unidentified compound may be a potent skin sensitizer. Finally, we developed a novel risk assessment workflow incorporating the HPC DST along with the previously published DSTs.

Proposed ICDRG Classification of the Clinical Presentation of Contact Allergy.

The International Contact Dermatitis Research Group proposes a classification for the clinical presentation of contact allergy. The classification is based primarily on the mode of clinical presentation. The categories are direct exposure/contact dermatitis, mimicking or exacerbation of preexisting eczema, multifactorial dermatitis including allergic contact dermatitis, by proxy, mimicking angioedema, airborne contact dermatitis, photo-induced contact dermatitis, systemic contact dermatitis, noneczematous contact dermatitis, contact urticaria, protein contact dermatitis, respiratory/mucosal symptoms, oral contact dermatitis, erythroderma/exfoliative dermatitis, minor forms of presentation, and extracutaneous manifestations.

Eccema de labios. Experiencia en la Unidad de Eccema de Contacto de un centro terciario español / Lip eczema. Experience in the Contact Dermatitis Unit of a Spanish tertiary hospital

Fundamento: El eccema labial es un problema poco frecuente en las Unidades de Eccema de Contacto (UEC). Hasta el momento han sido publicadas escasas series que muestren el perfil de estos pacientes y las causas de su eccema, ninguna de ellas española. El objetivo de este estudio fue el de analizar el perfil epidemiológico de los pacientes que acuden a la UEC en nuestro entorno, los diagnósticos principales y los alérgenos relevantes. Material y métodos: Se realizó una revisión retrospectiva de los pacientes remitidos a la UEC en el periodo 2005-2014. Se realizaron pruebas epicutáneas con la serie estándar ampliada del Grupo Español de Investigación en Dermatitis Alérgica de contacto (GEIDAC), productos propios y otras baterías complementarias. Resultados: En los 78 pacientes estudiados, los diagnósticos más frecuentes fueron la dermatitis de contacto alérgica y la dermatitis atópica. Los alérgenos relevantes más frecuentes fueron los cosméticos y los fármacos tópicos. Conclusiones: Es fundamental estudiar a los pacientes con eccema labial con pruebas epicutáneas para poder filiar correctamente su etiología y según esto, realizar un tratamiento más adecuado (AU)

Background: Lip eczema is an infrequent problem in Contact Dermatitis Units (CDU). Very few series have been published to date that show the profiles of such patients and the causes of their eczemas, and none are Spanish. The goal of this study was to analyze the epidemiological profile of the patients who attend a CDU in our setting, the main diagnoses and the relevant allergens. Methods: A retrospective review was made of the patients referred to the CDU in the 2005-2014 period. Patch tests were carried out with the extended standard series of the Spanish Research Group on Allergic Contact Dermatitis (Grupo Español de Investigación en Dermatitis Alérgica de contacto - GEIDAC), our own products and other complementary sets. Results: The most frequent diagnoses in the 78 patients studied were allergic contact dermatitis and atopic dermatitis. The most frequent relevant allergens were cosmetics and topical medications. Conclusions: It is essential to study the patients with lip eczema with patch tests to be able to correctly determine their etiology and accordingly to carry out the most suitable treatment (AU)

[Reactivity and evolution of 4022 patch tests in Chilean patients with contact dermatitis]. / Reactividad y evolución de 4.022 tests de parche en dermatitis de contacto realizadas entre 1995 y 2011 en Santiago de Chile.

BACKGROUND: Allergic Contact Dermatitis is a classic delayed hypersensitivity reaction. AIM: To study the reactivity and evolution in Chilean patients by gender, using the standard European patch test. MATERIALS AND METHODS: The results of the European standard patch test applied to 4,022 patients aged 1 to 93 years (64% female) with Allergic Contact Dermatitis, diagnosed between January 1995 and August 2011, were retrospectively analyzed. RESULTS: From a total of 4,022 patients, 2,439 (60.6%) had a positive reaction. Among reactive patients, 1,854 (76.04%) were female and 584 (23.96%) male. The most common positive allergens were nickel (35.3%), cobalt (15.1%), fragrance mix (14%), chromium (8.7%) and balsam of Peru (8.5%). In females, nickel was the most common reactive antigen (34.28%), and in males, fragrance mix (15.7%). During the period 2003-2011, an increased reactivity to nickel (26.6%) and a decreased reactivity to p-phenylenediamine (29.6%) and fragrance (42.8%), was observed. CONCLUSIONS: Fragrance mix is the most common reactive allergen in males and the third for females. Nickel is the leading allergen in the female group and the second of importance for males, making it the most significant allergen for the Chilean population. We also observed that the reactivity of some allergens evolves and varies over time.

Reactividad y evolución de 4.022 tests de parche en dermatitis de contacto realizadas entre 1995 y 2011 en Santiago de Chile / Reactivity and evolution of 4022 patch tests in Chilean patients with contact dermatitis

Background: Allergic Contact Dermatitis is a classic delayed hypersensitivity reaction. Aim: To study the reactivity and evolution in Chilean patients by gender, using the standard European patch test. Materials and Methods: The results of the European standard patch test applied to 4,022 patients aged 1 to 93 years (64% female) with Allergic Contact Dermatitis, diagnosed between January 1995 and August 2011, were retrospectively analyzed. Results: From a total of 4,022 patients, 2,439 (60.6%) had a positive reaction. Among reactive patients, 1,854 (76.04%) were female and 584 (23.96%) male. The most common positive allergens were nickel (35.3%), cobalt (15.1%), fragrance mix (14%), chromium (8.7%) and balsam of Peru (8.5%). In females, nickel was the most common reactive antigen (34.28%), and in males, fragrance mix (15.7%). During the period 2003-2011, an increased reactivity to nickel (26.6%) and a decreased reactivity to p-phenylenediamine (29.6%) and fragrance (42.8%), was observed. Conclusions: Fragrance mix is the most common reactive allergen in males and the third for females. Nickel is the leading allergen in the female group and the second of importance for males, making it the most significant allergen for the Chilean population. We also observed that the reactivity of some allergens evolves and varies over time.

Patch test results of hand eczema patients: relation to clinical types.

BACKGROUND: Allergic contact dermatitis is a well-known cause of hand eczema, although the influence of contact allergens on different clinical types of hand eczema remains still unclear. OBJECTIVE: To identify most common positive tested allergens among hand eczema patients and to define the relation between specific contact allergies and clinical types of hand eczema according to the guidelines of the Danish Contact Dermatitis Group (DCDG). METHODS: We included 1571 hand eczema subjects who were patch tested from 1 January 2002 to 31 December 2013. They were retrospectively classified according to the guidelines of the DCDG into six clinical types: recurrent vesicular hand eczema, chronic fissured hand eczema, hyperkeratotic palmar eczema, pulpitis, interdigital eczema and nummular hand eczema according to a newly developed flow chart. The prevalence of sensitizations and association with clinical type, atopic dermatitis, age and gender were studied. RESULTS: A total of 1395 subjects were classified into one of the six clinical types. The most frequently found clinical types were recurrent vesicular hand eczema (39.7%) and chronic fissured hand eczema (35.5%). Subjects with recurrent vesicular hand eczema were significantly more likely to have a contact allergy (OR 1.55), whereas subjects with hyperkeratotic palmar eczema and pulpitis were less likely to be sensitized (OR 0.51; OR 0.44). Overall, metals (nickel sulphate, cobalt chloride), fragrances and preservatives (methylchloroisothiazoline/methylisothiazoline, methyldibromoglutaronitrile) were the most frequent sensitizers in patients with hand eczema. This did not deviate in the different clinical types, although subjects with recurrent vesicular hand eczema were significantly more frequently sensitized to nickel sulphate and other allergens compared to other clinical types of hand eczema. CONCLUSION: In the diagnostic work up of hand eczema subjects with recurrent vesicular hand eczema should be patch tested, especially women of older age, although the need for patch testing in males with hyperkeratotic palmar eczema might be less imperative.

[Delayed-type cutaneous drug reactions. Pathogenesis, clinical features and histology]. / Kutane Arzneimittelreaktionen vom Spättyp. Pathogenese, Klinik und Histologie.

BACKGROUND: Cutaneous reactions to drugs can be subdivided in different ways. In addition to the standard classification according to the etiopathogenesis there are also classifications based predominantly on morphological criteria. The majority of drug-related cutaneous adverse reactions are immunological reactions which are collectively classified under the term hypersensitivity. These reactions are based on drug-specific immunoglobulin E (IgE) or cell-mediated mechanisms, not on the mechanism of action of the drug and are unpredictable. Delayed type reactions to drugs are forms of type IV T-cell mediated hypersensitivity. A prerequisite is a stable association of a pharmaceutical substance with a protein so that hapten-protein conjugates can be produced. The most common clinical symptom is maculopapular (morbilliform) drug-related exanthema. This article also examines lichen planus like drug reaction and drug-induced (hematogenic) allergic contact dermatitis in more detail. DIAGNOSTICS: The diagnostics are never trivial but also include the differentiation from viral exanthema and initial phases of severe cutaneous adverse reactions, such as toxic epidermal necrolysis. In addition to the morphological classification, the final diagnosis encompasses the interpretation of histopathological alterations in the skin biopsy, analysis of patient medication history, laboratory results and inclusion of data from the literature. Patch tests can also have additional diagnostic benefits. In vitro tests which involve the cellular incubation of the drug responsible should be reserved for specialized laboratories. A prerequisite for successful treatment is immediate termination of the drug responsible. THERAPY AND PROGNOSIS: Therapy is symptomatic with topical and also short-term systemic steroids and antihistamines. The prognosis is very good.

Allergy to cosmetics: a literature review.

The term cosmetic has a broad definition and includes personal care products, hair care products, nail care products, and sunscreens. Modern cosmetics are safe for most users, and adverse reactions are very rare because the manufacturers invest heavily in safety, quality control, and product testing before releasing the product to the market. Despite these efforts, adverse reactions occur. Skin care products are major contributors to cosmetic allergic contact dermatitis (ACD), followed by hair care and nail care products. The most common allergens are fragrances and preservatives. The diagnosis of cosmetic allergy is established by reviewing the patient's clinical history and physical examination findings and confirmed with skin patch testing. Patch testing is the standard method for detecting allergens responsible for eliciting ACD. The purpose of this article was to review the prevalence, legislative laws, and role of patch testing in ACD.

Is dermatitis palmaris sicca an irritant contact dermatitis?

BACKGROUND: Dermatitis palmaris sicca (DPS) is a common dry-fissured palmar dermatitis in Asian women. It may be an irritant contact dermatitis, but the immunophenotype of the cells in its infiltrate is unknown. OBJECTIVE: The aim of this study was to evaluate the role of inflammatory cells in the pathogenesis of DPS. METHODS: Patch testing was done in 68 patients with DPS, 87 subjects with hand eczema, and 31 healthy subjects. Immunophenotyping of cutaneous inflammatory cells was performed in 8 patients with DPS, 10 subjects with hand eczema, and 8 healthy individuals. RESULTS: Positive patch rates were higher in patients with DPS and those with hand eczema compared with healthy controls, but strong positive (++ or +++) reactions in DPS were fewer compared with hand eczema. Density of CD3, CD4, CD8, and CD68 cells in skin lesions of DPS and hand eczema was significantly higher than that in normal skin. Sparse CD20 cells were present only in hand eczema. Compared with hand eczema, the number of CD3, CD8, CD68, and dermal CD1a cells decreased, but epidermal CD1a cells and CD4/CD8 ratio increased in DPS. CONCLUSIONS: The absolute lack of CD20 cells and relative scarcity of dermal CD8 and CD1a cells in skin lesions might be insufficient to induce contact hypersensitivity, so DPS may be an irritant but not allergic contact dermatitis.

Detection and visualization of intracutaneous allergic type-specific elements using long-wavelength near-infrared hyperspectral imaging.

BACKGROUND/PURPOSE: This study aimed to develop a method for the assessment of allergic dermatitis by using the long-wavelength near-infrared spectrum (more than 1000 nm) to detect intracutaneous allergic type-specific elements. Such a method was realized by establishing a spectral classifier for the spectra of type I and type IV allergic dermatitis reactions. METHODS: Near-infrared spectral images of histamine-induced cutaneous reaction (type I) and contact hypersensitivity erythema elicited by squaric acid dibutylester (SADBE; type IV) were obtained, and the absorption spectra of normal and inflamed skin were extracted from these spectral images. A spectral classifier was established from these training datasets, and it was then applied to two test cases, red flare by methyl nicotinate (normal) and metal allergy (type IV). RESULTS: The spectral classifier established by canonical discriminant analysis (CDA) achieved very accurate detection (normal: 87.67%, type I: 87.00%, type IV: 98.5%). Furthermore, the test cases were also correctly classified: the red flare induced by methyl nicotinate was categorized as normal skin and the metal allergy was categorized as a type IV allergic reaction. CONCLUSIONS: These results suggest a possible application of near-infrared spectral imaging to the assessment of allergic dermatitis.

Shape and configuration of skin lesions: targetoid lesions.

What is probably the first description of targetoid or iris lesions, as they appear in erythema multiforme (EM), can be found in Thomas Bateman's 1836 textbook "Practical Synopsis of Cutaneous Diseases According to the Arrangement of Dr. Willan." EM was initially described by Bateman and later by von Hebra as an acute self-limiting skin disease, symmetrically distributed on the extremities with typical concentric "targetoid" or "iris" lesions, and often recurrent. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) were added to this syndrome later. A newer classification has created two disease spectra: EM consisting of EM minor and EM major (or bullous EM), and SJS and TEN. EM minor and EM major are often recurrent, postinfectious (especially after herpes and mycoplasma) disorders with low morbidity and almost no mortality. SJS and TEN are usually severe drug-induced reactions with high morbidity and poor prognosis. The target lesions found in each form of the disease are described and defined. Although the term "target lesion" originated from the description of EM and despite its being the dominant lesion in this disease, it is not pathognomonic for EM, and these lesions can sometimes appear in other diseases. Short descriptions of these other diseases are presented.

Symmetrical drug-related intertriginous and flexural exanthema.

PURPOSE OF REVIEW: Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), previously termed drug-related baboon syndrome, is a benign and self-limiting type IV hypersensitivity reaction characterized by symmetrical erythema involving the gluteal and intertriginous areas in the absence of systemic involvement. It may also occur in the absence of previous drug exposure. RECENT FINDINGS: Antibiotics, in particular beta-lactams, comprise the majority of causes of SDRIFE. Other drugs which have been implicated include antihypertensives, radiocontrast media, chemotherapeutic agents, and biologics. Histology of lesional skin is variable with predominance of superficial perivascular inflammatory cell infiltrates. Outcomes of allergy tests are variable with positive delayed intradermal tests reported for penicillin V, allopurinol; positive patch tests for erythromycin, mitomycin, nystatin, pseudoephdrine; positive lymphocyte transformation tests for erythromycin; and positive drug provocation tests for clindamycin, cimetidine, corticosteroids, terbinafine, and valacyclovir. SUMMARY: Diagnosis of SDRIFE is dependent upon recognition of the clinical morphology and distribution of the rash, and its temporal relationship to the use of the suspected drug. Outcomes of in-vivo and in-vitro tests have been inconsistent, and thus may not be useful in the identification of the putative drug.

Hand dermatitis/eczema: current management strategy.

Ever since its inception a couple of centuries ago, hand dermatitis/eczema has been in the reckoning. Idiosyncrasies continued to loom large thereafter, till it acquired its appropriate position. Dermatitis/eczema are synonymous, often used to indicate a polymorphic pattern of the inflammation of the skin, characterized by pruritus, erythema and vesiculation. A spectrum delineated into acute sub-acute and chronic dermatitis of the hands. Pompholyx, recurrent focal palmer peeling, ring, wear and tear and fingertip eczema, apron, discoid eczema, chronic acral dermatitis, gut and patchy papulosquamous eczema are its clinical variants. Occupational dermatitis/eczema may be contributory. Etiological definitions are clinched by detailed history of exogenous and endogenous factors. However, scientific confirmation of the entity is through patch testing by using available antigens.

[Skin sensitizers in cosmetics and skin care products].

Cosmetics are defined as "articles with mild action on the human body, which are intended to be applied to the human body through rubbing, sprinkling or other methods, aiming to clean, beautify and increase the attractiveness, alter the appearance or to keep the skin or hair in good condition (The Pharmaceutical Affairs Law: Article 2)." Consequently, they include personal hygiene products such as shampoos, soaps and toothpaste. In Europe, 1% of the population is estimated to be allergic to fragrances and 2-3% to ingredients of cosmetics; 10% of outpatients patch-tested for cosmetics allergy were found to be positive. Allergenic ingredients of cosmetics can be fragrances, hair dye, preservatives, antioxidants, emollients, surfactants, UV absorbers, pigments or resins used in nail cosmetics. Among standard allergen series, eight substances are related to cosmetics; in Japan in 2003, p-phenylenediamine (hair dyes) induced allergic reactions with the highest rate of 7.9% in outpatients patch-tested (n=805), followed by fragrance mix No. 1 (4.0%, mixture of eight fragrances frequently used), colophony (3.2%, main contents of pine resin), lanolin alcohol (2.7%,emollients), and formaldehyde, parabens, Kathon CG (2.7% ,1.9% and 1.0%, respectively; preservatives). Cosmetic allergy symptoms tend to be mild except those caused by hair dye. However, the population exposed to cosmetics is huge and the number of ingredients used in cosmetics increased up to more than 6000. Here, major cosmetic ingredient allergens, mainly reported in Japan, are reviewed and discussed.

Potency values from the local lymph node assay: application to classification, labelling and risk assessment.

Hundreds of chemicals are contact allergens but there remains a need to identify and characterise accurately skin sensitising hazards. The purpose of this review was fourfold. First, when using the local lymph node assay (LLNA), consider whether an exposure concentration (EC3 value) lower than 100% can be defined and used as a threshold criterion for classification and labelling. Second, is there any reason to revise the recommendation of a previous ECETOC Task Force regarding specific EC3 values used for sub-categorisation of substances based upon potency? Third, what recommendations can be made regarding classification and labelling of preparations under GHS? Finally, consider how to integrate LLNA data into risk assessment and provide a rationale for using concentration responses and corresponding no-effect concentrations. Although skin sensitising chemicals having high EC3 values may represent only relatively low risks to humans, it is not possible currently to define an EC3 value below 100% that would serve as an appropriate threshold for classification and labelling. The conclusion drawn from reviewing the use of distinct categories for characterising contact allergens was that the most appropriate, science-based classification of contact allergens according to potency is one in which four sub-categories are identified: 'extreme', 'strong', 'moderate' and 'weak'. Since draining lymph node cell proliferation is related causally and quantitatively to potency, LLNA EC3 values are recommended for determination of a no expected sensitisation induction level that represents the first step in quantitative risk assessment.

[Patch tests: indications or when testing should be performed]. / Tests épicutanés : indications ou quand les réaliser ?

Patch testing may be desirable or even essential for cases of suspected allergic contact dermatitis. Such testing allows identification with absolute certainty of the causative agent in "supposed" allergic contact dermatitis.

Nothing is perfect, not even the local lymph node assay: a commentary and the implications for REACH.

For many regulatory authorities, the local lymph node assay (LLNA) is the preferred assay for the predictive identification of skin-sensitizing chemicals. It is the initial requirement for sensitization testing within the new REACH (Registration, Evaluation, Authorization and Restriction of Chemical substances) regulations in the European Union. The primary reasons for the preferment of the LLNA are the animal welfare benefits it provides compared with traditional guinea-pig methods (refinement and reduction of animal usage) and the general performance characteristics of the assay with regard to overall reliability, accuracy, and interpretation. Moreover, a substantial published literature on the LLNA is available making it appropriate for use as a benchmark against which new approaches, including in vitro alternatives, can be evaluated and validated. There is, therefore, a view that the LLNA represents the 'gold standard' for skin sensitization testing. However, although this is probably correct, it is important to recognize and acknowledge that in common with all other predictive tests (whether they be validated or not), the LLNA has limitations, in addition to strengths, some of which were mentioned above. Arguably, it is the limitations (e.g., the occurrence of false positive and false negative results) of test methods that are most important to understand. With respect to the LLNA, these limitations are similar to those associated with guinea-pig skin sensitization methods. Among these are the occurrence of false positive and false negative results, susceptibility of results to changes in vehicle, and the possibility that interspecies differences may confound interpretation. In this commentary, these issues are reviewed and their impact on the utility of the LLNA for identification, classification, and potency assessment of skin sensitizers are considered. In addition, their relevance for the future development and validation of novel in vitro and in silico alternatives is explored.