Differential diagnosis of contact dermatitis: A practical-approach review by the EADV Task Force on contact dermatitis.

The diagnosis of eczema ('dermatitis') is mostly clinical and depends on the clinical history and exploratory objective findings (primary lesions, patterns). Contact dermatitis remains as an important condition in the group of eczematous disorders, with important socioeconomic and occupational relevance. Although irritant and allergic contact dermatitis have a different pathogenesis, both are characterized by a rather typical morphology, are triggered by external factors and tend to occur primarily in the area of contact with the exogenous agent. In addition, allergic and irritant dermatitis may also co-exist. The importance of diagnosing contact dermatitis, especially when allergic in nature, is both due to the possibility of avoiding the trigger, and due to its role in aggravating other skin conditions. Nevertheless, the heterogeneity of clinical presentations in daily practice may pose an important challenge for the suspicion and correct diagnosis of contact dermatitis. Furthermore, other conditions, with different pathogenesis and treatment, may clinically simulate contact dermatitis. The Task Force aims to conduct a review of the unifying clinical features of contact dermatitis and characterize its main clinical phenotypes, and its simulators, in order to contribute to an early suspicion or recognition of contact dermatitis and enable a correct differential diagnosis.

Exclusion of Disperse Orange 3 is possible from the textile dye mix present in the Swedish baseline patch test series. A study by the Swedish Contact Dermatitis Research Group.

BACKGROUND: The textile dye mix (TDM) 6.6% in petrolatum contains Disperse Blue (DB) 35, Disperse Yellow 3, Disperse Orange (DO) 1 and 3, Disperse Red 1 and 17, and DB 106 and 124. The most frequent allergen in TDM-positive patients is DO 3. Around 85% of para-phenylenediamine (PPD)-allergic dermatitis patients have been positive to DO 3. There has been a discussion to exclude DO 3 from TDM 6.6% because of strong simultaneous reactions to TDM and PPD. OBJECTIVES: To study if DO 3 can be excluded from TDM 6.6%. METHODS: Patch tests were performed on 1481 dermatitis patients with TDM 6.6%, TDM 7.0% (without DO 3 but the other disperse dyes at 1.0% each), DO 3 1.0%, and PPD 1.0% pet. RESULTS: Contact allergy to TDM 6.6% was 3.6% and to TDM 7.0% was 3.0%. All 26 DO 3-positive patients were positive to PPD. The 44 patients positive to TDM 7.0% plus the 13 positive to PPD and TDM 6.6% but negative to TDM 7.0% were 57, outnumbering the 53 positive to TDM 6.6%. CONCLUSION: TDM 7.0% can replace TDM 6.6% in the Swedish baseline series, since TDM 7.0% together with PPD 1.0% will detect patients with textile dye allergy.

Patch test results to extracts of synthetic garments in textile dye positive patients.

BACKGROUND: Disperse dyes (DDs) are the most prevalent causes of textile-related allergic contact dermatitis and are used for colouring synthetic textile materials based on fibres such as polyester, acrylic, acetate and polyamide. Eight DDs are included in a textile dye mix (TDM) 6.6% petrolatum (pet.) in the European baseline patch test series. OBJECTIVES: The aim of this study was to patch test TDM 6.6% pet. positive individuals with the extracts of synthetic fibre clothes that do not contain any of the pure DDs present in the TDM 6.6% to study the reactivity pattern. METHODS: Seventy-three TDM-positive former patients tested between 2012 and 2017 at the Department of Occupational and Environmental Dermatology in Malmö, Sweden were invited to join the study, 10 participated. Twenty-four textile items (collected in nine countries in Europe, Asia and North America in 2012) were extracted in dichloromethane. The TDM 6.6% was patch tested simultaneously with the 24 textile item preparations in petrolatum made from the extracts. Prior to patch testing the participants filled the 7-question questionnaire regarding possible symptoms from textile exposure. RESULTS: Ten individuals, agreed to join the study. Eight of them reacted to TDM 6.6%. Nine participants reacted to 20 of 24 extracts. One reacted to 19 extracts, another to 14, 3 to 5 extracts, 1 to 4, 1 to 3 extracts and 2 to 2 extracts. One was negative to all tested preparations including TDM 6.6%. The participants mainly reacted to six textile extracts. All controls tested negatively to tested extracts. Four individuals of the 10 TDM-allergic individuals previously had had problems after wearing clothes. Four out of the 10 participants had had atopic eczema in childhood. All women had dyed their hair with permanent hair dyes but none of the males. CONCLUSION: TDM-positive patients react to textile extracts made from synthetic garments, even if they do not contain any of the pure DDs present in TDM 6.6%. More studies are needed to pin-point the culprit haptens in these extracts.

Patch Testing with Propolis of Different Geographical Origins in a Baseline Series.

The chemical composition of propolis varies with geographical origin; however, it is not known whether this affects the frequency of contact allergy to propolis. In order to study the frequency of contact allergy to propolis of different geographical origins and concomitant reactions, 1,470 consecutive patients with dermatitis from Denmark, Lithuania and Spain were patch tested with propolis from China, Lithuania, North America and Sweden, and with a baseline series. Patch test reactions to any type of propolis ranged from 1.3% to 5.8%. There were no statistically significant differences in the frequency of positive reactions between the 4 types of propolis in the respective countries. Testing with a single commercially available type of propolis detects only approximately half of propolis-allergic patients. In patients allergic to propolis, concomitant reactions to Myroxylon pereirae resin, colophonium and Fragrance mix I were common, ranging from 12.5% to 50.0%.

Occupational exposure to nickel, cobalt, and chromium in the Lithuanian hard metal industry.

BACKGROUND: Metalworkers are said to have heavy exposure to metals, but the amount of released metal ions from alloys and deposition on the hands is unknown. OBJECTIVE: To analyze nickel, cobalt, and chromium in vitro release to the artificial sweat from nails and wire made of different alloys, and to test metal deposition on the fingers of metalworkers. MATERIAL AND METHODS: Six different samples of nails and wire were kept in artificial sweat for 24 hours and one week, respectively. The metal release was determined by atomic absorption spectrometry (AAS). Eighty-eight consecutive metal plant workers immersed their index fingers and thumbs in separate laboratory tubes filled with deionized water for 2 minutes. The sample analysis for metals was carried out with an inductively coupled plasma mass spectrometer (ICP-MS). RESULTS: The average released concentration of Ni was 0.0012 µg/cm2 , for Co it was 0.0007 µg/cm2 , and for Cr 0.0037 µg/cm2 after 24 hours and 0.0135, 0.0029, and 0.0042 µg/cm2 , respectively, after 1 week. There was a statistically significant increase in released concentration of Ni during one week: 0.0012 µg/cm2 vs 0.0135 µg/cm2 (P = .04). Medians of the detected Co amount on fingers reflected a statistically significant difference between workplaces: 0.004 µg/cm2 for metalworkers vs 0.001 µg/cm2 for office staff (P = .04). CONCLUSION: Nickel (Ni), cobalt (Co), and chromium (Cr) can be released in different concentrations from nails and wire. Detected Ni and Cr levels can elicit dermatitis in already sensitized patients. Co can be extracted from alloys even if not mentioned on material safety data sheets. The finger immersion technique was used for cobalt and chromium detection on fingers for the first time.

Follow-Up Analysis of Pulmonary Function, Exercise Capacity, Radiological Changes, and Quality of Life Two Months after Recovery from SARS-CoV-2 Pneumonia.

Background and objective: According to the World Health Organization (WHO), more than 100 million people have already recovered from SARS-CoV-2 infection. Therefore, it is imperative to understand the possible outcomes of COVID-19. The aim of our study was to evaluate pulmonary function, exercise capacity, residual radiological changes, and health-related quality of life (HRQoL) at follow-up in a cohort of SARS-CoV-2 pneumonia survivors. Materials and Methods: Patients with SARS-CoV-2 infection and radiologically confirmed lung injury, with no chronic lung disease prior to this infection, were included in the study. Patients' evaluation 2 months after their discharge from hospital included spirometry (FVC, FEV1, FEV1/FVC), determination of lung volume (TLC, VC, RV) and diffusing capacity of lung for carbon monoxide (DLCO, adjusted for hemoglobin), 6-Minute Walk Test (6MWT), chest CT scan, and 36-Item Short Form General Health Survey (SF-36). Results: Fifty-one patients (25 men, 26 women) were included. The mean age was 56 years (SD-11,72). Eighteen patients (35.3%) had experienced moderate COVID-19, 21 (41.2%) severe COVID-19, and 12 (23.5%) were critically ill. The mean follow-up visit time after the discharge from hospital was 60 days (SD-17). Pulmonary function at follow-up was impaired in 24 (47.2%) patients. Reduced lung volume was observed in 15 (29.4%) patients, DLCO reduction in 15 (29.4%) patients, and only one patient displayed obstruction. Twelve patients out of 51 (12/51, 27.3%) showed reduced physical capacity in the 6 MWT, and 3/51 (9.1%) showed desaturation, with SO2 < 90%. Different levels of abnormality were found in 49/51 (96,1%) patients on follow-up chest CT; the median radiological score was 10.9 (SD ± 8.87, possible maximal score, 25). Ground-glass opacity was the most common radiological feature, found in 45 (88.2%) patients. The SF-36 scores demonstrated a reduction in health status across all domains, with the lowest scores for limitations in social activities because of physical problems, vitality, and general health. Conclusion: In the group of COVID-19 pneumonia survivors 2 months after hospital discharge, residual changes in the lungs on chest CT and in lung function and reduced physical and HRQoL status were found in a significant number of patients. To evaluate COVID-19 long-term consequences, a longer follow-up period is needed.

Heavy metals and the skin: Sensitization patterns in Lithuanian metalworkers.

BACKGROUND: Metalworkers are exposed to many sensitizing and irritant substances. There are no published data on contact allergy in this population in the Baltic countries. OBJECTIVES: To detect skin symptoms related to occupational exposure and to describe the reactivity pattern to the European baseline series in workers from two metal plants in Lithuania. METHODS: In this cross-sectional study 185 metalworkers (154 production workers and 31 office staff) filled an interviewer-administered questionnaire. Patch testing was performed in 135 metalworkers and office staff, as a control group. RESULTS: Metalworkers younger than 40 years complained statistically significantly more often of skin symptoms, especially on the hands and face, than older workers. Physician-diagnosed skin diseases were reported in 1.7% of cases. Metalworkers, working <20 years in the factory, more often had skin symptoms. Contact with chemicals at the workplace was suspected as the main factor provoking skin symptoms. Metalworkers were sensitized mainly to cobalt, and nickel was the most prevalent allergen among office staff. CONCLUSION: Younger metalworkers more often had skin symptoms suspected of being work-related compared to older ones. Sensitization to cobalt was more prevalent in the metalworkers than in the control group.

Time trends of contact allergy to the European baseline series in Lithuania.

BACKGROUND: Monitoring trends of positive patch test reactions is useful for epidemiological surveillance and contact allergy prevention, and has not previously been reported in Lithuania. OBJECTIVES: To examine and compare changes in the prevalence of contact allergy to European baseline series allergens in adults with suspected contact dermatitis during a 9-year period. METHODS: In this retrospective study, patch test results of 297 consecutive patients, tested with the European baseline series in 2014-2015, were analysed and compared with the data published earlier in Lithuania. RESULTS: The most common allergens were nickel sulfate (30.6%), methylisothiazolinone (MI) (13.5%), methylchloroisothiazolinone (MCI)/MI (7.4%), potassium dichromate (6.1%), cobalt chloride (6.1%), Myroxylon pereirae resin (5.4%), p-phenylenediamine (5.4%), fragrance mix I (4.7%), formaldehyde (4.4%), and methyldibromo glutaronitrile (3.7%). Increases in the prevalence of sensitization to MCI/MI (2.3% in 2006-2008 and 7.4% in 2014-2015; p < 0.0001) and nickel sulfate (16.4% in 2006-2008 and 30.6% in 2014-2015; p < 0.0001) and decreases in the prevalence of sensitization to paraben mix (3.2% in 2006-2008 and 0.3% in 2014-2015; p = 0.006) were observed. Prevalences for the other allergens remained stable or showed a decreasing trend (Myroxylon pereirae resin; p = 0.06). CONCLUSION: This study provides current information on the prevalence of contact allergy in Lithuania. Changing trends in sensitivity to some allergens probably reflect changes in exposure.

Prevention of Flares in Children with Atopic Dermatitis with Regular Use of an Emollient Containing Glycerol and Paraffin: A Randomized Controlled Study.

BACKGROUND/OBJECTIVES: Emollients are part of the standard treatment for atopic dermatitis (AD), although there is limited evidence that regular use of emollients as management therapy reduces the frequency of flares and corticosteroid consumption. The objective of this study was to evaluate the benefit of emollient use in the management of mild to moderate AD in children by assessing the ability of two different emollients (particularly V0034CR) to prevent flares and to reduce the use of corticosteroids. METHODS: In this randomized, open-label study, patients with a current flare were treated with a potent topical corticosteroid. After flare resolution, patients were centrally randomized to V0034CR emollient, reference emollient, or no emollient (1:1:1 ratio) for 12 weeks. New flares were medically assessed before being treated with a moderately potent corticosteroid. RESULTS: A total of 335 children 2 to 6 years of age were randomized. At 12 weeks, the percentage of patients with one or more flares was statistically significantly lower with V0034CR (35.1%) than without emollient (67.6%; p < 0.001). Fewer patients treated with V0034CR required any corticosteroids or immunosuppressants (23.6%) than patients with no emollient (43.3%) at 12 weeks. The difference was significant at all time points (p = 0.002). Patients treated with emollients had a longer time to first flare, fewer flares, higher complete remission rates, less corticosteroid consumption, lower Investigator Global Assessment scores, and lower Scoring Atopic Dermatitis scores than those who were not. V0034CR was well tolerated, with no specific safety concerns. CONCLUSION: Regular emollient use in children with mild to moderate AD reduces flares and corticosteroid consumption.

Diagnosis and treatment of Hymenoptera venom allergy in adults: A single-center experience in Lithuania.

Background: Venom-specific immunotherapy (VIT) is a major treatment for patients allergic to Hymenoptera venom. Thus, correct diagnosis of sensitization, identification of the risk factors, and choice of venom for the treatment are the key issues. Objective: We aimed to describe diagnostic and treatment experience data of VIT performed in a single center in Lithuania. Methods: In this retrospective study, we analyzed 9 years of clinical data (severity of the allergic reaction, recognition of the culprit insects, diagnostics, VIT protocol safety and efficacy, sting challenge outcomes) of patients treated with cluster VIT. Sting challenge helped to reveal the influence of venom preparation quality and to adjust the dosage of venom. Results: Data from 83 patients were analyzed. Double sensitization confirmed by component diagnosis was found in 39.4% (13/33), and double immunotherapy was initiated in 9.1% (n = 3/33). The cluster immunotherapy protocol was used in 81 patients. Systemic reactions occurred in 7.4% (n = 6/81) patients during the build-up phase. VIT failure was related to bee venom immunotherapy and systemic reactions during a build-up phase. The efficacy in the short term of our approach to cluster VIT was confirmed by the sting challenge in 97% (42/43). Nine patients (10.8%, n = 9/83) voluntarily stopped the treatment due to a lack of motivation. Conclusion: Our protocol regarding the investigation and treatment of patients allergic to Hymenoptera venom has been safe and effective. Patient's motivation to continue VIT is one of the concerns, but the biggest challenge is the patients with bee venom allergy and repeated systemic reactions during VIT.

A Core Outcome Set for Efficacy of Acute Treatment of Hereditary Angioedema.

BACKGROUND: Clinical trials investigating drugs for the acute treatment of hereditary angioedema attacks have assessed many different outcomes. This heterogeneity limits the comparability of trial results and may lead to selective outcome reporting bias and a high burden on trial participants. OBJECTIVE: To achieve consensus on a core outcome set composed of key outcomes that ideally should be used in all clinical efficacy trials involving the acute treatment of hereditary angioedema attacks. METHODS: We conducted a Delphi consensus study involving all relevant parties: patients with hereditary angioedema, hereditary angioedema expert clinicians and clinical researchers, pharmaceutical companies, and regulatory bodies. Two Internet-based survey rounds were conducted. In round 1, panelists indicated the importance of individual outcomes used in clinical trials on a 9-point Likert scale. Based on these results, a core outcome set was developed and voted on by panelists in round 2. RESULTS: A total of 58 worldwide panelists completed both rounds. The first round demonstrated high importance scores and substantial agreement among the panelists. In the second round, a consensus of 90% or greater was achieved on a core outcome set consisting of five key outcomes: change in overall symptom severity at one predetermined time point between 15 minutes and 4 hours after treatment, time to end of progression of all symptoms, the need for rescue medication during the entire attack, impairment of daily activities, and treatment satisfaction. CONCLUSIONS: This international study obtained a high level of consensus on a core outcome set for the acute treatment of hereditary angioedema attacks, consisting of five key outcomes.

Contact allergy from disperse dyes in textiles: a review.

Several disperse dyes (DDs) are still considered to be the most important allergens in textile dermatitis, but there are sparse data about their current use in textiles. The aim of this review was to evaluate published studies and reports on contact allergy to DDs published in PubMed during the last 22 years (1990-2012). Prevalence data are provided by study and by dye, as well as by the described clinical peculiarities of DD dermatitis. We reviewed 54 studies. In total, 26 DDs were tested. The average prevalence in screening studies was >1% for Disperse Blue 106, Disperse Blue 124, and Disperse Orange 3. There is a lack of data on patch testing with Disperse Blue 26, Disperse Blue 102, Disperse Orange 37, Disperse Orange 149, Disperse Yellow 23 and Disperse Yellow 49, which are listed as allergens by the EU Commission. It is necessary to check the purity and identity of dyes used for patch testing, confirm the clinical relevance of positive reactions by patch testing with suspected textiles, and, if the results are positive, determine the culprit dye.

Sensitizing capacity of Disperse Orange 1 and its potential metabolites from azo reduction and their cross-reactivity pattern.

BACKGROUND: Simultaneous contact allergies to Disperse Orange 1, 4-nitroaniline and p-aminodiphenylamine (PADPA), as well as to other disperse azo dyes and to p-phenylenediamine (PPD), have been reported. Cross-reactivity is one of the possible explanations for simultaneous reactions between PPD and disperse azo dyes. Some metabolites from the azo reduction of these disperse azo dyes could be sensitizers, as human skin bacteria produce azo reductases. OBJECTIVES: To investigate the sensitizing capacity of Disperse Orange 1, PADPA and 4-nitroaniline, and the cross-reactivity between these substances and Disperse Yellow 3, its potential metabolites from azo reduction (4-aminoacetanilide and 2-amino-p-cresol), and PPD. METHOD: The guinea-pig maximization test was used. RESULTS: It was found that both Disperse Orange 1 and PADPA are strong sensitizers and cross-react with each other. We were unable to sensitize guinea-pigs with 4-nitroaniline tested in equimolar concentrations to Disperse Orange 1. CONCLUSIONS: The results indicate that patients sensitized primarily to Disperse Orange 1 will also react to PADPA, which can be found mainly in hair dyes. PPD, 4-nitroaniline, 4-aminoacetanilide, 2-amino-p-cresol and Disperse Yellow 3 did not show any cross-reactivity with Disperse Orange 1 or PADPA.