Solar Urticaria: An Ambispective Study in a Long-term Follow-up Cohort with Emphasis on Therapeutic Predictors and Outcomes.

Solar urticaria is a rare photodermatosis with several unknown pathogenic, clinical and therapeutic aspects. This study analysed the clinical and therapeutic features of a long-term follow-up solar urticaria cohort, with a focus on omalizumab management and outcomes, and characterized omalizumab response with the use of the high-affinity immunoglobulin E (IgE) receptor (FcεRI) and the Urticaria Control Test. An observational, unicentric, ambispective study was conducted from 2007 to 2023. Solar urticaria was diagnosed in 41 patients with a median follow-up of 60 months. Thirteen patients were prescribed omalizumab, with a median treatment time of 48 months. A significant decrease in FcεRI baseline levels and subsequent median increase in Urticaria Control Test was evidenced after omalizumab prescription in all patients. Drug survival at 48 months was at 88.9%. Omalizumab stepping-down protocol led to sustained omalizumab discontinuation in only 1 patient. Median basal Urticaria Control Test was lower (p < 0.01) in patients who were prescribed omalizumab and in patients without remission. This study contributes to our knowledge of omalizumab outcomes in real-life clinical practice and highlights the pathogenic importance of IgE-mediated pathways in solar urticaria, where FcεRI emerges as a possible biomarker of omalizumab response.

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.

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.

Which outcomes should be measured in hand eczema trials? Results from patient interviews and an expert survey.

BACKGROUND: Hand eczema (HE) is a common skin disease characterized by itch, pain and visible skin changes such as fissures, erythema and vesicles. It is not yet clear which outcome domains are most important for patients. The Hand Eczema Core Outcome Set (HECOS) initiative is developing a consented set of core domains and suitable measurement instruments for the future application in all HE trials. This includes an online Delphi survey about core domains, which requires a 'Long List' of all domains that might be important to measure. OBJECTIVES: To compile a 'Long List' of candidate outcome domains for therapeutic HE trials with suggestions from patients and experts. METHODS: First, 60 patients with chronic HE were interviewed at seven study sites in Croatia, Denmark, Germany, the Netherlands and Spain. Patients were asked about domains that were important from their perspectives. Second, 185 HE experts were invited by email to complete an online survey. With an open question, they were asked to suggest up to six domains. RESULTS: Suggestions were provided by 58 patients and 82 experts. Most patients and experts suggested to measure the domains 'signs', 'symptoms' and 'HE-related quality of life'. Specifically, >25% of patients said that less itch, pain or fissures indicated a successful treatment. Among experts, >25% suggested 'itch' and 'ability to work' as core sub-domains. Further outcomes from the domains 'HE control over time', 'patient-reported treatment experience' and 'skin barrier function' were mentioned. CONCLUSION: 'Itch' was rated high among patients with HE and professional HE experts. While patients emphasized fissures as important, experts underlined the ability to work. This investigation allowed us to define a 'Long List' of 7 candidate outcome domains with 58 sub-domains. From this list, a panel of stakeholders will select core domains during an online Delphi survey.

Risk factors for systemic reactions in typical cold urticaria: Results from the COLD-CE study.

BACKGROUND: Cold urticaria (ColdU), that is, the occurrence of wheals or angioedema in response to cold exposure, is classified into typical and atypical forms. The diagnosis of typical ColdU relies on whealing in response to local cold stimulation testing (CST). It can also manifest with cold-induced anaphylaxis (ColdA). We aimed to determine risk factors for ColdA in typical ColdU. METHODS: An international, cross-sectional study COLD-CE was carried out at 32 urticaria centers of reference and excellence (UCAREs). Detailed history was taken and CST with an ice cube and/or TempTest® performed. ColdA was defined as an acute cold-induced involvement of the skin and/or visible mucosal tissue and at least one of: cardiovascular manifestations, difficulty breathing, or gastrointestinal symptoms. RESULTS: Of 551 ColdU patients, 75% (n = 412) had a positive CST and ColdA occurred in 37% (n = 151) of the latter. Cold-induced generalized wheals, angioedema, acral swelling, oropharyngeal/laryngeal symptoms, and itch of earlobes were identified as signs/symptoms of severe disease. ColdA was most commonly provoked by complete cold water immersion and ColdA caused by cold air was more common in countries with a warmer climate. Ten percent (n = 40) of typical ColdU patients had a concomitant chronic spontaneous urticaria (CSU). They had a lower frequency of ColdA than those without CSU (4% vs. 39%, p = .003). We identified the following risk factors for cardiovascular manifestations: previous systemic reaction to a Hymenoptera sting, angioedema, oropharyngeal/laryngeal symptoms, and itchy earlobes. CONCLUSION: ColdA is common in typical ColdU. High-risk patients require education about their condition and how to use an adrenaline autoinjector.

Unilateral ulcerations on the forehead and scalp.

We describe a patient with unilateral ulcerations on the forehead and scalp, occurring 3 months after herpes zoster infection. Further investigations were unremarkable. Histology showed epidermal and upper dermal ulceration associated with a mild nonspecific dermal inflammatory infiltrate composed of lymphoid cells and histiocytes.

Cutaneous Involvement of Angioimmunoblastic T-Cell Lymphoma Masquerading as B-Cell Reactive Lymphoid Hyperplasia.

ABSTRACT: A 59-year-old woman presented with a persistent eruption manifested as multiple agminated miliary facial papules. Histopathological examination showed prominent nodular dermal lymphoid infiltrates with hyperplastic follicles that were initially interpreted as B-cell reactive lymphoid hyperplasia. Several years later, an additional biopsy showed a dense perifollicular infiltrate with reactive primary and secondary follicles. Accompanying T cells corresponded to CD3/CD4/PD1/CXCL13-positive cells and scattered Epstein-Barr virus-positive B cells were identified by in situ hybridization. A monoclonal T-cell population was demonstrated by TCRγ and TCRß Polymerase Chain Reaction amplification, as well as a minor abnormal circulating T-cell population by flow cytometry (0.62% of the white blood cells, CD4+CD3s-CD7-). A biopsy specimen from an enlarged right supraclavicular lymph node disclosed nodal involvement by angioimmunoblastic T-cell lymphoma. The observation of B-cell dermal nodular infiltrates with well-demarcated lymphoid aggregates forming primary lymphoid follicles may lead to overlook the T-cell component in some cases of angioimmunoblastic T-cell lymphoma. In such cases, a careful assessment of the apparently minor T-cell component is important to establish a correct diagnosis.

Adrenaline autoinjector is under-prescribed in typical cold urticaria patients living in tropical climate countries.

Background: The diagnosis of typical cold urticaria (ColdU) relies on whealing in response to local cold stimulation testing (CST). It can also manifest with cold-induced anaphylaxis (ColdA). Till date, it is largely unclear how often patients with ColdU receive adrenaline treatment and are provided with an adrenaline autoinjector (AAI). Methods: An international, cross-sectional study, COLD-CE (i.e., comprehensive evaluation of ColdU and other cold-induced reactions), was carried out at 32 UCAREs. Detailed histories were taken and CST with an ice cube and/or TempTest® performed. ColdA was defined as an acute cold-induced (i.e., by cold water, air, or surfaces) involvement of the skin and/or visible mucosal tissue and at least one of the symptoms (cardiovascular manifestations, difficulty breathing, or gastrointestinal symptoms). Results: Of the 551 ColdU patients, 75% (n = 412) had a positive CST. Of them, concomitant chronic spontaneous urticaria was diagnosed in 10%. Of 372 patients with stand-alone ColdU, 69% were women and 91% adults. Their median age was 36 (IQR 26 - 48) years. Patients were also categorized into residents of countries with a tropical (n = 33), temperate (n = 264), or cold (n = 75) climate (Table 1: R13C1, R17C1, R21C1). AAI was more often prescribed to residents of temperate than tropical countries (30% vs. 12%, p = .038; Table 1: R31C1), although the frequency of ColdA did not significantly differ between these countries (44% vs. 42%, p = 1.000; R29C2). Residents of tropical countries had a higher frequency of ColdA induced by cold air than residents of temperate (36% vs. 12%, p = .001; R29C4) or cold (36% vs. 12%, p = .007; R25C4) countries. Cardiovascular manifestations induced by cold air were diagnosed in 33% (n = 11) of residents of tropical countries, but only 18% (n = 2) and 36% (n = 4) of them had received adrenaline and AAI, respectively (R13 - 15C7). Furthermore, hypotension and/or loss of consciousness induced by cold air occurred in 18% (n = 6) of patients, but only 17% (n = 1) received adrenaline (R13 - 14C10). ColdA was induced by complete cold water immersion in 9% (n = 3) of patients, and none of them received adrenaline treatment nor AAI (R13 - 15C3). Conclusion: Our findings suggest that ColdA is undertreated and call for changes in ColdU management.

Bikini textile contact dermatitis: A Sherlockian approach revealing 2,4-dichlorophenol as a potential textile contact allergen.

BACKGROUND: Different textile constituents may act as allergens and/or irritants and provoke textile contact dermatitis (TCD). OBJECTIVES: To report a case of TCD caused by ethylene glycol monododecyl ether and 2,4-dichlorophenol, present in a bikini. METHODS: A woman presented with an eczematous, pruritic rash in the area of the bikini straps and back. Patch testing was performed with the European baseline, textile, sunscreen, and photo-patch series, the bikini "as is", and ethanol and acetone extracts of the bikini. Thin-layer chromatography (TLC) of the extracts and gas chromatography-mass spectrometry (GC-MS) analysis were used to elucidate the culprit agents. RESULTS: Positive reactions were found to the bikini "as is" and to the ethanol and acetone extracts. Patch testing with TLC strips showed a strong reaction to spots-fractions 3 and 4. GC-MS was performed to identify substances in each fraction and those suspected to be skin sensitisers were patch tested. On day (D) 4 positive reactions to ethylene glycol monododecyl ether (irritant reaction) and 2,4-dichlorophenol (++) were observed. CONCLUSION: A myriad of chemical compounds can be found in clothing. Ethylene glycol monododecyl ether and 2,4-dichlorophenol were identified as the potential culprits of this bikini TCD.

Non-Skin Related Symptoms Are Common in Chronic Spontaneous Urticaria and Linked to Active and Uncontrolled Disease: Results From the Chronic Urticaria Registry.

BACKGROUND: Chronic spontaneous urticaria (CSU) can present with non-skin related symptoms (NSRS), including recurrent unexplained fever, joint, bone, or muscle pain (JBMP), and malaise, which also occur in other conditions that manifest with wheals (eg, urticarial vasculitis or autoinflammatory disorders) or without wheals (eg, infection). OBJECTIVE: We sought to determine the rate of patients with CSU affected by fever, JBMP, and malaise, their trigger factors, links with clinical and laboratory characteristics, and their impact on everyday life and treatment responses. METHODS: We analyzed baseline data from the Chronic Urticaria Registry of 2,521 patients with CSU who were aged 16 years or older. RESULTS: One third of CSU patients (31.2%; 786 of 2,521) had one or more NSRS, including recurrent fever (5.3%), JBMP (19.1%), and/or malaise (18.6%). In a multivariable analysis, having one or more of these NSRS correlated with food and infection as trigger factors of urticaria (adjusted odds ratio [aOR] = 1.7 and 1.5), wheals of 24 hours or greater duration (aOR = 2.5), sleep disturbance (aOR = 2.4), anxiety (aOR = 2.8), comorbid atopic dermatitis (aOR = 2.1), gastrointestinal disease (aOR = 1.8), elevated leukocytes (aOR = 1.7) and erythrocyte sedimentation rate (aOR = 1.5). In a bivariate analysis, these NSRS were additionally associated with higher disease activity (weekly Urticaria Activity Score, median: 21 vs 14; P = .009), longer disease duration (years, median: 2 vs 1; P = .001), the presence of angioedema (74.6% vs 58.7%; P < .001), worse quality of life (Chronic Urticaria Quality of Life Questionnaire, median: 42 vs 29; P < .001) and more frequent poor control of CSU (78% vs 69%; P < .001). CONCLUSIONS: The presence of NSRS in a subpopulation of patients with CSU points to the need for better control of the disease, exclusion of comorbid conditions, and/or exclusion of urticarial vasculitis and urticarial autoinflammatory diseases.

Patient-Reported Outcome Measures in Atopic Dermatitis and Chronic Urticaria Are Underused in Clinical Practice.

BACKGROUND: Patient-reported outcome measures (PROMs) are validated and standardized tools that complement physician evaluations and guide treatment decisions. They are crucial for monitoring atopic dermatitis (AD) and chronic urticaria (CU) in clinical practice, but there are unmet needs and knowledge gaps regarding their use in clinical practice. OBJECCTIVE: We investigated the global real-world use of AD and CU PROMs in allergology and dermatology clinics as well as their associated local and regional networks. METHODS: Across 72 specialized allergy and dermatology centers and their local and regional networks, 2,534 physicians in 73 countries completed a 53-item questionnaire on the use of PROMs for AD and CU. RESULTS: Of 2,534 physicians, 1,308 were aware of PROMs. Of these, 14% and 15% used PROMs for AD and CU, respectively. Half of physicians who use PROMs do so only rarely or sometimes. Use of AD and CU PROM is associated with being female, younger, and a dermatologist. The Patient-Oriented Scoring Atopic Dermatitis Index and Urticaria Activity Score were the most common PROMs for AD and CU, respectively. Monitoring disease control and activity are the main drivers of the use of PROMs. Time constraints were the primary obstacle to using PROMs, followed by the impression that patients dislike PROMs. Users of AD and CU PROM would like training in selecting the proper PROM. CONCLUSIONS: Although PROMs offer several benefits, their use in routine practice is suboptimal, and physicians perceive barriers to their use. It is essential to attain higher levels of PROM implementation in accordance with national and international standards.

Autoimmune Diseases and Low Baseline IgE in Chronic Spontaneous Urticaria: A Clinical and Therapeutic Prospective Analysis in Real-Life Clinical Practice.

BACKGROUND: Autoimmunity contributes to the pathogenesis of chronic spontaneous urticaria (CSU). The subtyping of CSU has revealed an autoimmune form of CSU. Despite autoimmune diseases having been associated with CSU, there are few prospective studies that have evaluated the characteristics and biomarkers of patients with CSU and autoimmune disease in a real-life practice setting. OBJECTIVE: To evaluate the presence of specific biomarkers for the presence of autoimmune disease in CSU and to analyze the clinical and therapeutic features of patients with CSU and autoimmune disease. METHODS: The clinical, laboratory, and therapeutic features of patients with CSU at a tertiary-level center were prospectively collected. Data obtained were compared in function of the presence/absence of autoimmune disease and typified according to IgE levels. RESULTS: Patients with CSU who had associated autoimmune disease corresponded to middle-aged women with a common pattern of blood test findings: both low baseline IgE and high-affinity receptor of IgE expression, basopenia, eosinopenia, higher baseline erythrocyte sedimentation rate and D-dimer, increased presence of antinuclear antibodies, IgG against thyroid peroxidase, and positive autologous serum skin test result. Total baseline IgE less than or equal to 43.8 IU/mL was both the optimal cutoff to predict autoimmune disease in the CSU cohort and a significant risk factor for the presence of autoimmune disease in the regression analysis. CONCLUSIONS: In real-life clinical practice, characteristics of patients with CSU and autoimmune disease share common features with type IIb autoimmune CSU. Total baseline IgE less than or equal to 43.8 IU/mL has been detected as a possible biomarker of autoimmune disease in patients with CSU.

Remibrutinib inhibits hives effector cells stimulated by serum from chronic urticaria patients independently of FcεR1 expression level and omalizumab clinical response.

BACKGROUND: Despite advances in the treatment of chronic urticaria, in a significant percentage of the patients symptoms are not fully controlled with conventional approaches. New strategies under development include blocking intracellular mediators of mast cell and basophil activation. OBJECTIVE: We aim to investigate the effects of the Bruton's tyrosine kinase (BTK) inhibitor remibrutinib on human blood basophils and CD34+ -derived mast cells activation induced by serum obtained from chronic urticaria patients. METHODS: Twenty-two patients with chronic spontaneous urticaria (mean age 52 years, 27% women) and 22 patients with chronic inducible urticaria (46 years, 27% women) were included in the study together with a sex-matched control group. Patients were classified as responders or non-responders to anti-IgE therapy on the basis of their clinical data, FcεR1a expression on blood basophils and total IgE levels. Changes on CD63 expression-as an activation marker-, were used to evaluate in vitro the response of basophils and mast cells to serum exposure and the inhibitory effects of remibrutinib. RESULTS: Remibrutinib inhibits degranulation induced by IgE cross-linking in mast cells and basophils and also the activation triggered by factors present in the sera of spontaneous and inducible chronic urticaria patients. Patient's serum induces a greater degranulation of effector cells than controls. Activation of mast cells and basophils by patient sera and remibrutinib effects were not related to omalizumab responsiveness. CONCLUSION: Remibrutinib inhibits activation of human basophils and mast cells induced in vitro by exposure to the serum of chronic urticaria patients independently of their response to omalizumab.