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.

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.

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.

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.

Clinical Approach to Patients with Moderate-to-Severe Atopic Dermatitis: A Spanish Delphi Consensus.

Despite emerging evidence and advances in the management of atopic dermatitis there a lack of consensus regarding the diagnostic criteria, therapeutic approach, method to assess severity, and patient follow-up for this condition. An expert consensus study was conducted to provide recommendations on the management of patients with moderate-to-severe atopic dermatitis. The study used Delphi-like methodology based on a literature review, a summary of the scientific evidence, and a 2-round survey. The agreement of 60 panellists on 21 statements was evaluated. Consensus was pre-defined as ≥ 80% agreement of all respondents. In the first round 6 statements reached consensus. Unanimous consensus was achieved regarding therapeutic goals and patient satisfaction (maintained in the long term and periodic goals reassessment recommended every 3-6 months). In the second round, half of the statements reached consensus, all related to patient follow-up, treatment goals, and atopic comorbidities. The statements that did not reach consensus were related to diagnosis (biomarkers, allergy, and food testing) and starting patients on conventional systemic treatment rather than advanced treatment. The study assessed expert opinion regarding a variety of topics related to the clinical approach to patients with moderate-to-severe atopic dermatitis, in order to provide guidance on the diagnosis and management of patients with atopic dermatitis.

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.

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.

Patch Testing in Patients With Severe Atopic Dermatitis Treated With Dupilumab: A Multicentric Approach in Spain.

Background: Persistent localized dermatitis (PLD) or eczema flare-ups (EF) may occur in atopic dermatitis (AD) patients treated with dupilumab. They may reflect concomitant allergic contact dermatitis (ACD) exposed by the inhibition of the Th2 pathway by dupilumab in some cases. Objective: To evaluate the prevalence and etiology of these events and the impact of dupilumab on patch test outcome. Methods: We performed patch tests on 54 AD patients treated with dupilumab and evaluated the prevalence and final diagnosis of EF and PLD as well as the patch test results. Results: The patch test results were positive in 20/54 (37.0%). 21/54 patients (38.9%) had PLD and 12/54 (22.2%) had EF. Ten of 54 (18.5%) had both conditions and 11/54 (20.4%) had neither PLD nor EF. 64.5% of PLD involved the face. 83.9% patients with PLD and 90.9% patients with EF were diagnosed with inadequately controlled AD. 9.7% patients with PLD and 4.5% patients with EF were finally diagnosed with ACD. Nine of 21 (42.9%) patients patch tested twice were positive either before and/or during dupilumab. Patch tests results changed over time in all of them. Conclusions: Patch testing assisted us to exclude ACD as the cause of PLD/EF in AD patients treated with dupilumab. Most PLD and EF were, however, diagnosed as poorly controlled AD. Dupilumab appeared to impact the patch test outcomes.

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 (AU)

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.

Frequency of sensitization to the individual fragrances of fragrance mix I and II according to the factors included in the MOAHLFA index.

BACKGROUND: Fragrances constitute the second most frequent cause of allergic contact dermatitis in Spain. OBJECTIVES: To determine the rate of sensitization to the individual fragrances of fragrance mix (FM) I and FM II for each of the demographic and clinical factors included in the MOAHLFA (male, occupational dermatitis, atopic dermatitis, hand dermatitis, leg dermatitis, facial dermatitis, age) index. METHODS: We conducted a 5-year retrospective study in 23 Spanish centres. We identified the patients who had undergone patch testing with a specific fragrance series after reacting positively to fragrance markers in a baseline series. We obtained the MOAHLFA index items in this population, then calculated for each demographic and clinical factor the frequencies of sensitization to the individual fragrances of FM I and FM II. RESULTS: A specific fragrance series was patch tested in 1013 patients. The most frequent allergens in men, women, children, and retired people were Evernia prunastri (16%), geraniol (16.6%), isoeugenol (17.9%), and geraniol (22.4%), respectively. Citral (20.5%) and hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) (14.5%) were the most common allergens in occupational eczemas and were also associated with a large proportion of hand and facial dermatitis. CONCLUSIONS: Frequency of sensitization to the individual fragrances of FM I and FM II varies with age, sex, affected body region, and history of occupational or atopic dermatitis.

Treat-to-Target in Atopic Dermatitis: An International Consensus on a Set of Core Decision Points for Systemic Therapies.

Currently no treat-to-target framework to guide systemic treatment in adults with moderate-to-severe atopic dermatitis exists. We sought to reach international consensus through an eDelphi process on a core set of recommendations for such an approach. Recommendations were developed by an international Steering Committee, spanning 3 areas (Guiding Principles, Decision Making, and Outcome Thresholds) and 2 specific time-points; an initial acceptable target at 3 months and an optimal target at 6 months, each based on improvements in patient global assessment plus at least one specific outcome domain. These treat-to-target- orientated recommendations were evaluated by an extended international panel of physicians, nurses and patients. Proposed recommendations were rated using a 9-point Likert scale; for each recommendation, consensus agreement was reached if ≥ 75% of all respondents rated agreement as ≥ 7. Consensus on 16 core recommendations was reached over 2 eDelphi rounds. These provide a framework for shared decision-making on systemic treatment continuation, modification, or discontinuation.

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.

Trend of relevant contact allergens of the feet in Spain over a period of 10 years.

INTRODUCTION: Allergic contact dermatitis (ACD) of the feet accounts for approximately 10% of all patch tested patients. OBJECTIVE: To study the clinical profile of patients with feet dermatitis and relevant contact allergens in Spain over a 10-year period. METHODS: Retrospective observational study of patients with suspected ACD from the GEIDAC (Spanish Research Group on Contact Dermatitis and Cutaneous Allergy) baseline series from eight hospitals in Spain between 2004 and 2014. The clinical data collected from each patient were age, sex, occupation, history of atopic dermatitis, and eczema location. RESULTS: A total of 450 cases clinically presented dermatitis affecting the feet; of these, 41% of were males and 5.6% were suspected to be of occupational origin. As much as 47% were diagnosed with ACD, 20% with atopic dermatitis/dyshidrotic eczema, and 5% with psoriasis. The "feet group" included statistically significantly more females in the age range of 21 to 60 years. The most frequent relevant contact allergens were potassium dichromate, cobalt(II) chloride, p-tert-butylphenol formaldehyde resin, mercapto mix, and mercaptobenzothiazole. CONCLUSIONS: ACD is the most frequent clinical diagnosis of feet dermatitis in our series. The most frequent allergens are similar to those published in other series of foot ACD in Europe and the trend has not changed in the studied decade.