Real-world clinical, psychosocial and economic burden of atopic dermatitis: Results from a multicountry study.

BACKGROUND: Atopic dermatitis (AD), a relapsing, inflammatory skin disease, is associated with pruritus that can negatively affect patients' quality of life. Understanding the burden of AD is critical for informing and tailoring treatment and disease management to improve patient outcomes. This study characterized global treatment patterns and the clinical, psychosocial and economic burden of moderate-to-severe AD. METHODS: MEASURE-AD was a cross-sectional 28-country study in patients with physician-confirmed moderate-to-severe AD who were either receiving or eligible for systemic therapy for AD. Patients ≥12 years were enrolled between December 2019 and December 2020 while attending routine office or clinic visit. Primary outcomes included Worst Pruritus Numeric Rating Scale (WP-NRS; range: 0-10) and Dermatology Life Quality Index (DLQI; range: 0-30) and Children's DLQI (CDLQI; range: 0-30). Secondary outcomes included physician- and patient-reported clinical, psychosocial and economic burden. RESULTS: Of the 1591 patients enrolled, 1558 (1434 adults and 124 adolescents) fulfilled all patient selection criteria and were included in this analysis. Almost all patients (98.4%) in the total population were using AD medications and more than half (56%) were receiving systemic medication (15% systemic monotherapy). The most used systemic therapies were dupilumab (56.3%), systemic glucocorticoids (18.1%) and methotrexate (16.2%). Mean WP-NRS was 5.3 in the total population, and most patients (≥55%) reported moderate-to-severe pruritus (WP-NRS ≥4). Mean DLQI was 10.8 and mean CDLQI was 9.6. Secondary endpoints demonstrated substantial clinical, psychosocial, and economic burden of disease. Subgroup analysis demonstrated that patients receiving systemic therapy had lower disease burden than those not taking systemic medications. CONCLUSIONS: While systemic therapy lowers overall disease burden, patients with moderate-to-severe AD continue to have substantial multidimensional disease burden and uncontrolled disease. Overall, there is a need for effective disease management, including effective treatments that improve patients' psychosocial outcomes and reduce the economic burden of AD.

Polysensitization in the Spanish Contact Dermatitis Registry (REIDAC): A 2019-2022 prospective study with cluster and network analysis.

BACKGROUND: There is still limited clinical-practice data on specific clinical and patch test features, as well as on allergen clusters in polysensitization (PS). OBJECTIVES: To determine the frequency, relevance, symptoms duration and risk factors in polysensitized patients and to assess possible allergen aggregation. METHODS: Prospective multicentric study (January 2019-December 2022) conducted in setting of the Spanish Contact Dermatitis Register (REIDAC). Clinical and patch test data of polysensitized and oligosensitized patients were compared, and risk factors of PS were investigated with logistic multivariate regression. Unsupervised hierarchical clustering and network analysis were used to study allergen aggregation in PS. RESULTS: A total of 10,176 patients were analysed. PS was found in 844 (8.3%). Current relevance was significantly higher in polysensitized patients (p < 0.01). Risk factors for PS were atopic dermatitis (OR: 1.58, 95% CI: 1.24-2.02), age (≥60 years vs. ≤24 years, OR: 1.75, 95% CI: 1.25-2.44) and some special locations (legs vs. face OR: 1.54, 95% CI: 1.05-2.25, hands vs. face OR: 1.46, 95% CI:1.15-1.85, arms vs. face OR: 1.49, 95% CI:1.01-2.20, trunk vs. face OR: 1.40, 95% CI:1.06-1.85). Cluster and network analyses revealed specific-allergen clusters and significant associations, including allergens belonging to metals group, fragrances and botanicals group, topical drugs group, rubber allergens and biocides. CONCLUSIONS: This study confirms that PS is structured by discernible patterns of specific-allergen clusters and reinforces significant allergen associations in PS. Cross-reactivity and/or concomitant sensitization could explain the formation of allergen clusters in PS.

A re-assessment of the value of markers of corticosteroid contact allergy in the Spanish baseline series: Clobetasol propionate in the spotlight.

BACKGROUND: Budesonide and tixocortol pivalate as markers of contact allergy to corticosteroids have been questioned, as they are not able to detect a significant percentage of allergic patients. OBJECTIVES: To investigate the potential role of clobetasol propionate in enhancing corticosteroid sensitisation detection. METHODS: Between January 2022 and December 2023, patients who attended centres involved in the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy were tested with an extended baseline series that included budesonide, tixocortol pivalate, clobetasol propionate 0.1% in ethanol and 1% in petrolatum. RESULTS: A total of 4338 patients were tested. Twenty-four patients were allergic to budesonide (0.55%, 95% CI: 0.37-0.82); nine patients were allergic to tixocortol pivalate (0.21%, 95% CI: 0.11-0.39); and 23 patients were allergic to clobetasol (0.53%, 95% CI: 0.35-0.79). Only four of those patients allergic to clobetasol were detected by budesonide and one by tixocortol pivalate. No significant differences in the number of positive tests were found between clobetasol in petrolatum or ethanol. CONCLUSIONS: In Spain budesonide remains the main corticosteroid allergy marker whereas the role of tixocortol pivalate is questionable. The addition of clobetasol propionate to the Spanish baseline series would improve the ability to detect patients allergic to corticosteroids.

2-Hydroxyethyl methacrylate (2-HEMA) sensitization, a global epidemic at its peak in Spain?

BACKGROUND: A global epidemic of allergic contact dermatitis to (meth)acrylates has been described in relation to the widespread use of manicure products. OBJECTIVES: To evaluate the frequency of sensitization to 2-hydroxyethyl methacrylate (2-HEMA) among consecutively patch tested patients with eczema in Spain; the percentage of current relevance; the MOAHLFA index; and, the potential sources of exposure to (meth)acrylates. METHODS: From January 2019 to December 2022, 2-HEMA 2% pet. was prospectively patch tested in 24 REIDAC (Spanish Allergic Contact Dermatitis Registry) centres. RESULTS: Six thousand one hundred thirty-four patients were consecutively patch tested with 2-HEMA 2% pet. 265/6134 (4.3%) were positive. Positive reactions of current relevance were identified to involve 184/265 (69%). The efficiency (number of patch tests needed to detect relevant positive patch test reactions) was 34 (6134/184). The variable 'occupational' was found to be significantly associated with a higher risk for relevant positive reactions to 2-HEMA (OR: 10.9; 95% CI: 8.1-14.9). CONCLUSION: (Meth)acrylate sensitization is a prevalent health issue in Spain. 2-HEMA 2% pet. has been identified to be a highly effective (meth)acrylate allergy marker in the GEIDAC baseline series. The responsible authorities should implement policies guaranteeing accurate labelling of industrial, medical, and consumer materials while ensuring the enforcement of said labelling through appropriate legal means.

The Treat-to-Target Project in Atopic Dermatitis: One Year On.

Atopic dermatitis is a chronic skin condition for which a range of systemic treatments have recently been approved. A treat-to-target strategy has been developed previously alongside an algorithm to guide the management of patients with atopic dermatitis. Here, we review the strategy and algorithm in the context of the evolving therapeutic landscape, and identify areas for further refinement and development.

Drug reexposure in children with severe mucocutaneous reactions.

In pediatric patients, severe cutaneous adverse reactions (SCARs) frequently occur in the course of acute illnesses, mostly infections, which are usually treated with antibiotics or analgesics. The drug provocation test (DPT) is contraindicated in such situations, due to the risk of triggering a new severe reaction. As a consequence, lifelong avoidance is recommended. However, causation is uncertain in most cases. The dilemma arises when avoiding the drug is not harmless for the patient. We have attended three patients who were referred to our pediatric allergy unit with a history of SCAR related in time to simultaneous use of paracetamol and ibuprofen. Medical records and images of the patients were reviewed with the assistance of a dermatologist, and alternative diagnoses were considered in both cases. The ALDEN score for implicated drugs was calculated. After considering a high probability of ibuprofen tolerance and obtaining informed consent from the patients, we performed a sequential allergy workup including in vitro tests, skin tests, and finally DPT in two of the patients, confirming ibuprofen tolerance. In conclusion, although generally contraindicated, DPT may be considered for some useful drugs after careful evaluation of the risk-benefit balance, preceded by a sequential study including in vitro and skin tests.

Psychometric properties of the Spanish version of the once-daily Urticaria Activity Score (UAS) in patients with chronic spontaneous urticaria managed in clinical practice (the EVALUAS study).

BACKGROUND: The daily diary Urticaria Activity Score (UAS) and its weekly score (UAS7) are widely used to assess signs and symptoms in patients with chronic spontaneous urticaria (CSU). The objective of this study was to assess the psychometric properties of a Spanish version of the once-daily UAS. METHODS: Observational study in patients ≥18 years old receiving usual care for CSU (daily or almost daily occurrence of generalized hives or angioedema for ≥6 weeks). Patients were included consecutively and completed the UAS, EQ-5D, and the Chronic Urticaria Quality of Life scale (CU-Q2oL) at two study visits 6 weeks apart. On each occasion, the UAS was completed once-daily for 7 consecutive days to be able to calculate the UAS7 score. Psychometric properties of reliability, construct validity, and responsiveness were assessed. The Minimal Important Difference (MID) was estimated for the UAS7 using anchor- and distribution-based approaches. RESULTS: Data from 166 patients was available for analysis (mean age 49 years, 65.7% female). Floor (5.4% of patients with the lowest possible score) and ceiling (1.2%) effects were low; 15% of patients had missing values. Internal consistency and test-retest reliability were good (Cronbach's alpha of 0.83 and an ICC of 0.84, respectively). Convergent validity was demonstrated through the pattern of correlations with the EQ-5D and CU-Q2oL and known groups' validity was demonstrated by the instrument's ability to discriminate between patients with different overall levels of urticaria severity, with between-group effect-sizes (ES) ranging from 0.36 to 1.19. The UAS7 proved responsive to change with effect sizes ranging from 0.3 to 1.52 in patients reporting improvement or deterioration in overall urticaria status. The MID for the UAS7 score was estimated at 7-8 points, on a scale of 0-42. CONCLUSIONS: The Spanish version of the UAS score has demonstrated a robust psychometric performance in patients with CSU managed in conditions of usual care. It can therefore be considered a suitable instrument to assess disease activity in clinical practice in Spanish-speaking patients. The Spanish version's reliability and validity are similar to those reported for other language versions of the once- and twice-daily variants of the UAS.

Irritant contact dermatitis due to ammonium bifluoride in two infant twins.

Ammonium bifluoride is one of the most corrosive acids that may produce severe chemical burns when in contact with skin. This hazardous chemical is widely used in household products. We report two pediatric cases of irritant contact dermatitis after exposure to a rust remover, which contained ammonium bifluoride.

Pruritus and Pain Constitute the Main Negative Impact of Atopic Dermatitis From the Patient's Perspective: A Systematic Review.

Atopic dermatitis (AD) is an inflammatory skin disease characterized by intense itching and highly visible signs, representing a great burden to the patient. Despite its straightforward diagnosis, AD severity and burden can be underestimated in routine clinical practice. This review aims to determine the impact of AD on patients' lives, establish which domains of life are most affected, and identify symptom drivers of AD burden. A systematic literature review was conducted in Pubmed/Medline, Web of Science, and Scopus following Cochrane and PRISMA recommendations. Observational studies published in English or Spanish between January 1, 2018, and August 31, 2022, evaluating the impact of AD and its symptoms from the patient's perspective, were included. Reviewed studies were assessed for quality following the STrengthening the Reporting of OBservational studies in Epidemiology Checklist. A total of 28 observational studies evaluating the impact of AD and its symptoms from the patient's perspective were included in the review. All domains of the AD patient's life were found to be greatly affected, including health-related quality of life (HRQoL), emotional health, sleep disorders, work impairment, health care resource utilization, cognitive function, and development of comorbidities. The more severe the disease, the greater the impact, worsening in patients with moderate and severe AD. Pruritus and pain are reported to be the disease symptoms with the greatest impact. In conclusion, AD impacts several domains of patients' lives, especially HRQoL and mental health. Pruritus and pain are identified as the main drivers of AD impact, suggesting that optimal symptom control may reduce the burden and improve disease management.

Contact allergy to beryllium chloride: report of 12 cases.

BACKGROUND: Isolated cases of allergic contact dermatitis, gingivitis and stomatitis caused by beryllium have been previously reported. We have been able to study a series of 12 patients with patch test reactions to beryllium chloride. OBJECTIVES: The study was aimed at defining the clinical and patch testing characteristics in this group of patients, and determining whether some were delayed elicitation reactions or late reactions of active sensitizations by patch testing. MATERIAL AND METHODS: We performed a 5-year retrospective study of patients tested with a metal series, and studied a subgroup who showed reactions to beryllium chloride. RESULTS: A total of 1799 patients were patch tested, 62 of whom were also tested with a specific metal series; 12 of them reacted to beryllium chloride. Eight of the 12 patients showed reactions to other metals. Based on the time of positive reaction to beryllium chloride, three patterns emerged: (i) 3 patients showed positive reactions on D2-D4; (ii) 6 patients showed positive reactions between D7 and D10; and (iii) 3 patients showed positive reactions later than D10. CONCLUSIONS: Contact allergy to beryllium chloride may not be as unusual as the literature suggests. In order to avoid undetected contact allergies, we recommend performing later readings, between D7 and D10, whenever patch testing is performed with beryllium chloride. Active sensitization may occur.

Correlation between lesion site and concentration of dimethyl fumarate in different parts of shoes in patients with contact dermatitis caused by dimethyl fumarate in footwear.

BACKGROUND: Dimethyl fumarate (DMF) has been identified as being responsible for an outbreak of shoe contact dermatitis in Europe. All reported cases to date have involved the dorsa of the toes and the dorsa of the feet, sometimes in association with other areas. OBJECTIVES: To establish a correlation between the site of the lesions and the concentration of DMF in different parts of the footwear from patients suffering from shoe contact dermatitis. METHODS: We performed a retrospective study of 8 patients with shoe contact dermatitis caused by DMF. Clinical data and patch test results obtained with DMF were recorded. The contents of DMF in different parts of eight samples of shoes involved were analysed with gas chromatography-mass spectrometry. RESULTS: The chemical analysis of all samples studied showed the presence of DMF, both in the uppers and the soles of the shoes. A clinical-analytical correlation was found in all cases. The presence of DMF in a child's boot was detected 1 year after withdrawal of the sachet with DMF from the shoe box. CONCLUSIONS: A correlation exists between the concentrations of DMF in the different parts of the shoe and the localization of the lesions. Although DMF is a volatile substance, it can remain impregnated in shoes for a long period of time.

Patch testing with formaldehyde and formaldehyde-releasers: multicentre study in Spain (2005-2009).

BACKGROUND: Formaldehyde and formaldehyde-releasers are common causes of allergic contact dermatitis. OBJECTIVES: To determine the frequency of sensitization to formaldehyde and seven formaldehyde-releasers. To establish and characterize groups of patients according to the results of patch testing. MATERIALS AND METHODS: We performed a 5-year retrospective study, in six Spanish hospitals, of patients with positive patch test reactions to formaldehyde or any of seven formaldehyde-releasers. RESULTS: The most frequent allergens were formaldehyde (1.72%), imidazolidinyl urea (1.05%), quaternium-15 (0.88%), and diazolidinyl urea (0.79%). Patients with sensitization to only formaldehyde had a higher frequency of occupational dermatitis (25%) than patients with sensitization to only formaldehyde-releasers (9.5%). The most common sites of dermatitis were the hands (31.7%) in patients with sensitization to only formaldehyde and the face and legs (31.3% and 24.6%) in patients with sensitization to only formaldehyde-releasers. We found a subgroup of 25 patients who were sensitized to both imidazolidinyl urea and diazolidinyl urea, and only 6 of these (24%) were also sensitized to formaldehyde. CONCLUSIONS: The inclusion of imidazolidinyl urea and diazolidinyl urea in the baseline series of the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC) should enable better classification of patients allergic to formaldehyde, and could aid in their management.

Patch testing in children with hand eczema. A 5-year multicentre study in Spain.

BACKGROUND: Hand eczema is common in children, but affected children are seldom patch tested. Relatively few studies have assessed patch testing in the paediatric population, and none has specifically evaluated its use in hand eczema in children. OBJECTIVES: The aim of this study was to determine the prevalence of contact allergy in children with hand eczema, and to identify the most frequent allergens and their relevance. MATERIAL AND METHODS: We performed a 5-year retrospective study of children (aged 0-15 years) with hand eczema tested with the Spanish baseline series at the Dermatology Departments of 11 Spanish hospitals. RESULTS: During the study period, 11 729 patients were patch tested, of whom 480 were children. Hand eczema was present in 111 (23.1%) of the children and in 3437 (30.5%) of the adults. Of the children with hand eczema, 46.8% had at least one positive reaction in the patch tests. Current relevance was found for 78% of the allergens detected. The most common allergens were nickel sulfate, methylchloroisothiazolinone/methylisothiazolinone, and fragrance mix I. Allergic contact dermatitis was the most frequent diagnosis (36%), followed by atopic dermatitis. CONCLUSIONS: Allergic contact dermatitis was the most usual diagnosis in our series of children with hand eczema. We recommend patch testing of all children with chronic hand eczema, as is already performed in adults.

Fragrance contact allergy: a 4-year retrospective study.

BACKGROUND: Fragrance chemicals are the second most frequent cause of contact allergy. The mandatory labelling of 26 fragrance chemicals when present in cosmetics has facilitated management of patients allergic to fragrances. OBJECTIVES: The study was aimed to define the characteristics of the population allergic to perfumes detected in our hospital district, to determine the usefulness of markers of fragrance allergy in the baseline GEIDAC series, and to describe the contribution made by the fragrance series to the data obtained with the baseline series. MATERIAL AND METHODS: We performed a 4-year retrospective study of patients tested with the Spanish baseline series and/or fragrance series. There are four fragrance markers in the baseline series: fragrance mix I (FM I), Myroxylon pereirae, fragrance mix II (FM II), and hydroxyisohexyl 3-cyclohexene carboxaldehyde. RESULTS: A total of 1253 patients were patch tested, 117 (9.3%) of whom were positive to a fragrance marker. FM I and M. pereirae detected 92.5% of the cases of fragrance contact allergy. FM II and hydroxyisohexyl 3-cyclohexene carboxaldehyde detected 6 additional cases and provided further information in 8, enabling improved management. A fragrance series was tested in a selected group of 86 patients and positive results were obtained in 45.3%. Geraniol was the allergen most frequently found in the group of patients tested with the fragrance series. CONCLUSIONS: Classic markers detect the majority of cases of fragrance contact allergy. We recommend incorporating FM II in the Spanish baseline series, as in the European baseline series, and using a specific fragrance series to study patients allergic to a fragrance marker.

Consensus on the Clinical Approach to Moderate-to-Severe Atopic Dermatitis in Spain: A Delphi Survey.

BACKGROUND: The purpose of this study was to gather information on the current assessment and management of patients with moderate-to-severe AD in routine daily practice. METHODS: A cross-sectional two-round Delphi survey with the participation of dermatologists and allergologists throughout Spain was conducted. They completed a 46-item questionnaire, and consensus was defined when responses of ≥80% of participants coincided in the categories of a 5-point Likert scale for that item. RESULTS: A total of 105 specialists (aged 40-59 years) completed the two rounds. Participants agreed regarding the consideration of AD as a multifaceted disease and the differences in clinical presentation of AD according to the patient's age. It is recommendable to perform a skin biopsy to exclude early stage T-cell cutaneous lymphoma, psoriasis, or dermatitis herpetiformis, among others (99.1%). Also, consensus was reached regarding the use of the SCORAD index to quantify the severity of the disease (86.7%), the use of wet wraps to increase the effect of topical corticosteroids (90.4%), the usefulness of proactive treatment during follow-up (85.6%) and tacrolimus ointment (91.2%) to reduce new flares, and the fact that crisaborole is not the treatment of choice for severe AD (92.4%). AD was not considered a contraindication for immunotherapy in patients with allergic respiratory diseases (92.4%). In patients with severe AD, the use of immune response modifier drugs (97.6%) or phototherapy (92.8%) does not sufficiently cover their treatment needs. Consensus was also obtained regarding the role of the new biologic drugs (93.6%) targeting cytokines involved in the Th2 inflammatory pathway (92.0%) and the potential role of dupilumab as first-line treatment (90.4%) in moderate-to-severe AD patients. CONCLUSION: This study contributes a reference framework to the care of AD patients. There is no diagnostic test or biomarkers to direct treatment or to assess the severity of the disease, and many therapeutic challenges remain.

Shoe contact dermatitis from dimethyl fumarate: clinical manifestations, patch test results, chemical analysis, and source of exposure.

BACKGROUND: The methyl ester form of fumaric acid named dimethyl fumarate (DMF) is an effective mould-growth inhibitor. Its irritating and sensitizing properties were demonstrated in animal models. Recently, DMF has been identified as responsible for furniture contact dermatitis in Europe. OBJECTIVE: To describe the clinical manifestations, patch test results, shoe chemical analysis, and source of exposure to DMF-induced shoe contact dermatitis. PATIENTS, MATERIALS, AND METHODS: Patients with suspected shoe contact dermatitis were studied in compliance with the Declaration of Helsinki. Patch test results obtained with their own shoe and the European baseline series, acrylates and fumaric acid esters (FAE), were recorded according to international guidelines. The content of DMF in shoes was analysed with gas chromatography and mass spectrometry. RESULTS: Acute, immediate irritant contact dermatitis and non-immunological contact urticaria were observed in eight adults and two children, respectively. All the adult patients studied developed a delayed sensitization demonstrated by a positive patch testing to DMF < or = 0.1% in pet. Cross-reactivity with other FAEs and acrylates was observed. At least 12 different shoe brands were investigated. The chemical analysis from the available shoes showed the presence of DMF. CONCLUSION: DMF in shoes was responsible for severe contact dermatitis. Global preventive measures for avoiding contact with DMF are necessary.