Non-Skin-Related Symptoms are Common in Chronic Spontaneous Urticaria and Linked to Active and Uncontrolled Disease: Results from CURE.

BACKGROUND: Chronic spontaneous urticaria (CSU) can present with non-skin-related symptoms (NSRS), including recurrent unexplained fever, joint/bone/muscle pain (JBMP), and malaise, which also occur in other conditions that manifest with wheals (e.g., urticarial vasculitis or autoinflammatory disorders) or without wheals (e.g., 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 (CURE) of 2,521 patients with CSU who were ≥16 years old. RESULTS: One-third of CSU patients (31.2%, 786/2,521) had ≥1 NSRS, including recurrent fever (5.3%), JBMP (19.1%), and/or malaise (18.6%). In a multivariable analysis, having ≥1 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 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 (UAS7, median: 21 vs. 14, p=0.009), longer disease duration (years, median: 2 vs. 1, p=0.001), presence of angioedema (74.6% vs. 58.7%, p<0.001), worse quality of life (CU-Q2oL, median: 42 vs. 29, p<0.001) and more frequent poor control of CSU (78% vs. 69%, p<0.001). CONCLUSION: The presence of NSRS in a subpopulation of CSU patients points to a need for better control of the disease, exclusion of comorbid conditions and/or exclusion of urticarial vasculitis and urticarial autoinflammatory diseases.

Development and Validation of a Patient-Reported Outcome Measure to Assess Disease Control in Chronic Prurigo.

Importance: Chronic prurigo (CPG), including prurigo nodularis, is a difficult disease to treat and considerably affects patients' quality of life. Helping patients obtain control of CPG is a major treatment goal. Objective: To develop and validate the Prurigo Control Test (PCT), a tool for assessing disease control in CPG, and to identify a cutoff value for controlled disease to aid treatment decisions. Design, Setting, and Participants: This qualitative study followed the current recommendations for patient-reported outcome measure development in the generation and validation of the PCT. The final PCT was obtained after item generation, followed by reduction and selection, and was then tested for internal consistency and test-retest reliability, convergent validity, known-group validity, screening accuracy, and banding. The item-generation phase resulted in an unselected list of 69 potential PCT items. Impact analysis, interitem correlation, and review for content (face) validity resulted in final set of 5 PCT items. The validation study was performed among patients across 2 expert centers in Germany. Data were analyzed from February 2017 to November 2019. Main Outcomes and Measures: A 5-item PCT with a recall period of 2 weeks was developed. A cutoff value of 10 points or higher was determined as suitable for identifying patients with well-controlled vs poorly controlled CPG. Results: Of the 95 patients included in the validation study, the median (range) age was 63 (19-87) years, 50 patients (53%) were women, and the median (range) disease duration was 72 (9-774) months. The validation study yielded good internal consistency reliability (Cronbach α, 0.86) and a high degree of convergent validity. The PCT demonstrated good known-group validity and could discriminate between patients who differed in prurigo control. Test-retest reliability was high, and the intraclass correlation coefficient was 0.94, indicating excellent reproducibility. Conclusions and Relevance: This qualitative study showed that the PCT is able to assess disease control in patients with CPG. Its retrospective approach, brevity, and simple scoring likely make the PCT suitable for clinical practice and trials.

Patients With Chronic Spontaneous Urticaria Who Have Wheals, Angioedema, or Both, Differ Demographically, Clinically, and in Response to Treatment-Results From CURE.

BACKGROUND: Patients with chronic spontaneous urticaria (CSU) have spontaneous wheals (W), angioedema (AE), or both, for longer than 6 weeks. Clinical differences between patients with standalone W, standalone AE, and W and AE (W+AE) remain incompletely understood. OBJECTIVE: To compare W, AE, and W+AE CSU patients regarding demographics, disease characteristics, comorbidities, disease burden, and treatment response. METHODS: Baseline data from 3,698 CSU patients in the ongoing, prospective, international, multicenter, observational Chronic Urticaria REgistry (CURE) were analyzed (data cut: September 2022). RESULTS: Across all CSU patients, 59%, 36%, and 5% had W+AE, W, and AE, respectively. The W+AE patients, compared with W and AE patients, showed the lowest male-to-female ratio (0.33), higher rates of concomitant psychiatric disease (17% vs 11% vs 6%, respectively), autoimmune disease (13% vs 7% vs 9%, respectively), and nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity (9% vs 5% vs 2%, respectively) and the highest disease impact. The W patients, compared with W+AE and AE patients, showed the lowest rates of concomitant hypertension (15% vs 21% vs 40%, respectively) and obesity (11% vs 16% vs 17%, respectively), the highest rate of concomitant inducible urticaria (24% vs 22% vs 6%, respectively), and shorter W duration. The AE patients, compared with W+AE and W patients, were older at disease onset, showed longer AE duration, and the best response to increased doses of H1-antihistamines (58% vs 24% vs 31%, respectively) and omalizumab (92% vs 67% vs 60%, respectively). CONCLUSIONS: Our findings provide a better understanding of CSU phenotypes and may guide patient care and research efforts that aim to link them to pathogenic drivers.

An update on mechanisms of pruritus and their potential treatment in primary cutaneous T-cell lymphoma.

Primary cutaneous T-cell lymphomas (CTCL), which include mycosis fungoides (MF) and Sézary syndrome (SS), are a group of lymphoproliferative disorders characterized by clonal accumulation of neoplastic T-lymphocytes in the skin. Severe pruritus, one of the most common and distressing symptoms in primary CTCL, can significantly impair emotional well-being, physical functioning, and interpersonal relationships, thus greatly reducing quality of life. Unfortunately, effectively managing pruritus remains challenging in CTCL patients as the underlying mechanisms are, as of yet, not fully understood. Previous studies investigating the mechanisms of itch in CTCL have identified several mediators and their corresponding antagonists used for treatment. However, a comprehensive overview of the mediators and receptors contributing to pruritus in primary CTCL is lacking in the current literature. Here, we summarize and review the mediators and receptors that may contribute to pruritus in primary CTCL to explore the mechanisms of CTCL pruritus and identify effective therapeutic targets using the PubMed and Web of Science databases. Studies were included if they described itch mediators and receptors in MF and SS. Overall, the available data suggest that proteases (mainly tryptase), and neuropeptides (particularly Substance P) may be of greatest interest. At the receptor level, cytokine receptors, MRGPRs, and TRP channels are most likely important. Future drug development efforts should concentrate on targeting these mediators and receptors for the treatment of CTCL pruritus.

Safety and efficacy of lirentelimab in patients with refractory indolent systemic mastocytosis: a first-in-human clinical trial.

BACKGROUND: Indolent systemic mastocytosis (ISM) is characterized by excessive mast cell (MC) accumulation and MC-driven signs and symptoms. Currently used therapies are not approved and have limited efficacy. Lirentelimab (AK002) is a monoclonal antibody against sialic acid-binding immunoglobulin-like lectin (Siglec)-8 that inhibits MC activation. OBJECTIVES: To determine the safety, tolerability and efficacy of lirentelimab in reducing the symptoms of ISM. METHODS: At a specialty centre for mastocytosis in Germany, we conducted a phase I first-in-human single-ascending and multidose clinical trial of lirentelimab in patients with ISM. Eligible adults had World Health Organization-confirmed ISM and an unsatisfactory response to available treatment. In part A, patients received a single dose of lirentelimab 0.0003, 0.001, 0.003, 0.01 or 0.03 mg kg-1; in part B, patients received one lirentelimab dose of 0.3 mg kg-1 or 1.0 mg kg-1; and in part C, patients received either 1.0 mg kg-1 lirentelimab every 4 weeks for 6 months or ascending doses of lirentelimab (one dose of 1 mg kg-1 followed by five doses of 3-10 mg kg-1 every 4 weeks). The primary endpoint was safety/tolerability. Secondary endpoints included changes from baseline in Mastocytosis Symptom Questionnaire (MSQ), Mastocytosis Activity Score (MAS) and Mastocytosis Quality of Life Questionnaire (MC-QoL) scores at 2 weeks after the final dose. RESULTS: In 25 patients with ISM (13 in parts A + B and 12 in part C; median age 51 years, 76% female, median 4.6 years from diagnosis), the most common treatment-related adverse events (AEs) were feeling hot (76%) and experiencing a headache (48%). No serious AEs occurred. Median MSQ and MAS symptom severity scores in part C improved (vs. baseline) across all symptoms [MSQ: skin (38-56%), gastrointestinal (49-60%), neurological (47-59%), musculoskeletal (26-27%); MAS: skin (53-59%), gastrointestinal (72-85%), neurological (20-57%), musculoskeletal (25%)]. Median MC-QoL scores improved across all domains: symptoms (39%), social life/functioning (42%), emotions (57%) and skin (44%). CONCLUSIONS: Lirentelimab was generally well tolerated and improved symptoms and quality of life in patients with ISM. The therapeutic potential of lirentelimab should be considered for ISM.

Urticarial Vasculitis Differs From Chronic Spontaneous Urticaria in Time to Diagnosis, Clinical Presentation, and Need for Anti-Inflammatory Treatment: An International Prospective UCARE Study.

BACKGROUND: Chronic spontaneous urticaria (CSU) and urticarial vasculitis (UV) share several clinical features including the occurrence of wheals. As of yet, the criteria for differentiating the 2 disorders are not clearly defined. OBJECTIVE: Here, we aimed to identify differences, similarities, and the likelihood for specific clinical features in patients with UV versus those with CSU. METHODS: Across 10 Urticaria Centers of Reference and Excellence, 106 patients with skin biopsy-confirmed UV and 126 patients with CSU were prospectively recruited to complete a questionnaire on the clinical features, course, and response to treatment of their disease. RESULTS: As compared with CSU, patients with UV more often experienced postinflammatory skin hyperpigmentation, wheals of ≥24-hour duration, eye inflammation, and fever (6.9, 4.0, 3.6, and 2.4 times, respectively). Clinical features that increased the risk for UV diagnosis when present at the onset of disease included wheals of ≥24-hour duration (7.3-fold), pain of the skin (7.0-fold), postinflammatory hyperpigmentation (4.1-fold), and fatigue (3.1-fold). The diagnostic delay was markedly longer for normocomplementemic UV as compared with hypocomplementemic UV and CSU (21 vs 5 vs 6 months, respectively). Oral corticosteroids and omalizumab were the most effective treatments in patients with UV and CSU, respectively. Patients with UV showed a higher need for immunosuppressive and anti-inflammatory therapies than patients with CSU. CONCLUSIONS: Long wheal duration, skin pain and hyperpigmentation, and systemic symptoms point to UV rather than CSU as the underlying disease and should prompt further diagnostic workup including a skin biopsy.

Anti-KIT antibody, barzolvolimab, reduces skin mast cells and disease activity in chronic inducible urticaria.

BACKGROUND: Chronic inducible urticaria (CIndU) is characterized by mast cell (MC)-mediated wheals in response to triggers: cold in cold urticaria (ColdU) and friction in symptomatic dermographism (SD). KIT receptor activation by stem cell factor (SCF) is essential for MC function. Barzolvolimab (CDX-0159) is a humanized antibody that inhibits KIT activation by SCF and was well tolerated in healthy volunteers with dose-dependent plasma tryptase suppression indicative of systemic mast cell ablation. METHODS: This is an open-label, trial in patients with antihistamine refractory ColdU or SD, receiving one IV dose of barzolvolimab (3 mg/kg), with a 12-week follow-up. Primary endpoint was safety/tolerability; pharmacodynamic (PD)/clinical endpoints included serum tryptase, plasma SCF, skin MC histology, provocation tests, urticaria control test (UCT), and dermatology life quality index (DLQI). RESULTS: Analysis populations were safety (n = 21) and pharmacodynamics/clinical activity (n = 20). Barzolvolimab was well tolerated; most adverse events were mild and resolved. Treatment resulted in significant depletion of skin MCs, decreased tryptase (

The Benefit of Complete Response to Treatment in Patients With Chronic Spontaneous Urticaria-CURE Results.

BACKGROUND AND OBJECTIVE: Chronic spontaneous urticaria (CSU) is a distressing disease. We report real-world data from the global Chronic Urticaria Registry (CURE) about associations between various CSU states and sleep impairment, plus important health-related quality-of-life (HRQoL) outcomes and compared different methods to assess CSU states. METHODS: CURE data were collected at baseline and 6-monthly follow-ups (FU). Assessments included CSU states using the Urticaria Control Test (UCT), weekly Urticaria Activity Score (UAS7), and Physician Global Assessment (PhyGA) of treatment response. Complete response to treatment (CR, UAS7 = 0), complete control of disease (CC, UCT = 16), and PhyGA = CR were assessed, plus the Dermatology Life Quality Index and the Chronic Urticaria Quality-of-Life Questionnaire (CU-Q2oL) sleep domain. RESULTS: Overall, 2078 patients were included. At baseline, 9.8%, 17.9%, and 42.3% of patients had UCT = 16, UAS7 = 0, or PhyGA = CR, respectively, which increased at FU1 and FU2. Patients with higher UCT scores had better sleep and HRQoL. The presence of angioedema without wheals, episodic disease, omalizumab treatment, and male sex were associated with CC (P < .05). Among 469 patients who achieved CC or CR, 16.4% (n = 77) showed CC or CR with all 3 instruments. Agreement between UCT = 16 and UAS7 = 0 measurements was moderate (κ = 0.581), but poor between UCT = 16 and PhyGA = CR (κ = 0.208). CONCLUSIONS: Few patients had CR/CC of their CSU at baseline entry. Disease control strongly related to good sleep and better HRQoL; therefore, it is important to aim for CR in CSU treatment. Patient-reported UCT and UAS7 assessments demonstrated a more accurate measurement of CSU state versus physician assessments.

Evidence for histamine release in chronic inducible urticaria - A systematic review.

Background: Chronic inducible urticaria (CIndU) constitutes a group of nine different CIndUs in which pruritic wheals and/or angioedema occur after exposure to specific and definite triggers. Histamine released from activated and degranulating skin mast cells is held to play a key role in the pathogenesis of CIndU, but evidence to support this has, as of yet, not been reviewed systematically or in detail. We aim to characterize the role and relevance of histamine in CIndU. Methods: We systematically searched 3 electronic databases (PubMed, Scopus, and Embase) for studies that reported increased serum or skin histamine concentration (direct evidence) or in vitro or ex vivo histamine release (indirect evidence) following trigger exposure. Results: An initial total of 3,882 articles was narrowed down to 107 relevant studies of which 52 were in cold urticaria, 19 in cholinergic urticaria, 14 in heat urticaria, 10 in contact urticaria, 7 each in solar urticaria and vibratory angioedema, 4 each in symptomatic dermographism and aquagenic urticaria, and 3 in delayed pressure urticaria. The results of our review support that histamine has a key pathogenic role in the pathogenesis of all CIndUs, but it is not the sole mediator as evidenced by the often poor relationship between the level of histamine and severity of symptoms and the variable clinical efficacy of H1-antihistamines. Conclusions: Histamine released from skin mast cells is a key driver of the development of signs and symptoms and a promising therapeutic target in CIndU.

Chronic spontaneous urticaria activity, impact and control as well as their changes are strongly linked, and these links are not affected by angioedema or comorbid inducible urticaria - Results from the validation of the Polish Urticaria Control Test.

Background: Monitoring the effects of treatment on disease activity, impact, and control in patients with chronic spontaneous urticaria (CSU) is essential. We do not have enough information on how these features of CSU and its response to treatment are linked. Also, there is no information on how recurrent angioedema or coexisting chronic inducible urticaria (CIndU) affect their relation. The aim of this study was to analyse the link between disease activity, impact, and control in CSU patients and possible effects of recurrent angioedema and comorbid CIndU. Methods: To perform these analyses, we validated the Polish version of the Urticaria Control Test (UCT) in 106 chronic urticaria patients. The relationship between CSU activity, impact, and control was assessed in regard to recurrent angioedema and coexisting CIndU. Results: The Polish UCT showed high levels of validity, reliability, and sensitivity to change. Disease activity, impact, and control as well as their changes, assessed by the UAS, the CU-Q2oL, and the UCT, respectively, were strongly correlated. Recurrent angioedema or comorbid CIndU did not significantly affect the link of CSU activity, impact, and control or the relation of their changes. Conclusions: In CSU, there is a strong, albeit not perfect correlation of disease activity, impact, and control, which underlines the need to assess all 3 features of the disease in routine clinical practice. Recurrent angioedema and comorbid CIndU, which are both common and relevant in CSU, do not affect how disease activity, impact and control in patients with CSU are related to each other.

Autoimmune Diseases Are Linked to Type IIb Autoimmune Chronic Spontaneous Urticaria.

PURPOSE: Patients with chronic spontaneous urticaria (CSU) have an increased risk for comorbid autoimmune diseases. In this retrospective multicenter study of CSU patients, we evaluated clinical and laboratory features of CSU associated with a higher risk of comorbid autoimmune diseases. METHODS: We analyzed records of CSU patients (n = 1,199) for a history or presence of autoimmune diseases. Patients were diagnosed with type IIb autoimmune CSU (aiCSU) if all 3 tests were positive: autologous serum skin test (ASST), basophil histamine release assay (BHRA) and/or basophil activation test (BAT), and IgG autoantibodies against FcεRIα/IgE detected by immunoassay. RESULTS: Twenty-eight percent of CSU patients had at least 1 autoimmune disease. The most prevalent autoimmune diseases were Hashimoto's thyroiditis (HT) (≥ 21%) and vitiligo (2%). Two percent of CSU patients had ≥ 2 autoimmune diseases, most frequently HT plus vitiligo. Comorbid autoimmune diseases, in patients with CSU, were associated with female sex, a family history of autoimmune diseases, and higher rates of hypothyroidism and hyperthyroidism (P < 0.001). Presence of autoimmune diseases was linked to aiCSU (P = 0.02). The risks of having autoimmune diseases were 1.7, 2.9 and 3.3 times higher for CSU patients with a positive ASST, BHRA and BAT, respectively. In CSU patients, markers for autoimmune diseases, antinuclear antibodies and/or IgG anti-thyroid antibodies were associated with non-response to omalizumab treatment (P = 0.013). CONCLUSIONS: In CSU, autoimmune diseases are common and linked to type IIb autoimmune CSU. Our results suggest that physicians assess and monitor all adult patients with CSU for signs and symptoms of common autoimmune diseases, especially HT and vitiligo.

A novel histopathological scoring system to distinguish urticarial vasculitis from chronic spontaneous urticaria.

BACKGROUND: Urticarial vasculitis (UV) is defined by long-lasting urticarial lesions combined with the histopathologic findings of leukocytoclastic vasculitis. As one of the major unmet needs in UV, diagnostic criteria are rather vague and not standardized. Moreover, there seems to be considerable overlap with chronic spontaneous urticaria (CSU), particularly for the normocomplementemic variant of UV. Therefore, this study aimed to develop a diagnostic scoring system that improves the histopathologic discrimination between UV and CSU. METHODS: Lesional skin sections of patients with clinical and histopathologic diagnosis of UV (n = 46) and CSU (n = 51) were analyzed (blinded to the diagnosis) for the following pre-defined criteria: presence of leukocytoclasia, erythrocyte extravasation, fibrin deposits, endothelial cell swelling, ectatic vessels, blurred vessel borders, dermal edema, intravascular neutrophil, and eosinophil numbers and numbers of dermal neutrophils, macrophages and mast cells. RESULTS: The greatest differences between UV and CSU samples were observed for leukocytoclasia (present in 76% of UV vs. 3.9% of CSU samples; p < 0.0001), erythrocyte extravasation (present in 41.3% of UV vs. 2.0% of CSU samples; p < 0.0001), and fibrin deposits (present in 27.9% of UV vessels vs. 9.7% of CSU vessels; p < 0.0001). Based on these findings, we developed a diagnostic score, the urticarial vasculitis score (UVS), which correctly assigned 37 of 46 cases of UV and 49 of 51 cases of CSU to the previously established diagnosis. CONCLUSION: Our results suggest that the UVS, a combined quantitative assessment of the three criteria leukocytoclasia, fibrin deposits and extravasated erythrocytes, distinguishes UV from CSU in skin histopathology. The UVS, if validated in larger patient samples, may help to improve the diagnostic approach to UV.

Sleep disturbance in adult dermatologic patients: A cross-sectional study on prevalence, burden, and associated factors.

BACKGROUND: Sleep disturbance remains insufficiently characterized in many dermatoses. OBJECTIVE: To investigate the prevalence, burden, and factors associated with sleep disturbance in dermatologic patients. METHODS: We recruited 800 patients and recorded pruritus characteristics and sociodemographic and clinical parameters. Validated questionnaires were used to assess sleep disturbance, psychological distress, health-related quality of life, and work productivity. RESULTS: Two thirds of patients met criteria of poor sleep, which was associated with psychological distress, diminished health-related quality of life, and lost work productivity. Patients with average and maximum pruritus on the visual analog scale exceeding 5 and 6.5 points, respectively, were at high risk of suffering pruritus-related sleep disturbance. Overall pruritus intensity and its nocturnal exacerbation contributed independently to sleep disturbance. Psychological distress was of even higher impact on sleep than pruritus and almost a third of the relationship between pruritus intensity and sleep was mediated by psychological distress. CONCLUSION: Sleep disturbance is prevalent in dermatologic patients and constitutes a considerable burden. CLINICAL IMPLICATION: Dermatologic patients with intense pruritus and psychological distress should be examined for sleep disorders. Adequate antipruritic therapy and complementary psychotherapy in affected patients may help them regain restorative sleep.

The Diagnostic Workup in Chronic Spontaneous Urticaria-What to Test and Why.

BACKGROUND: In chronic spontaneous urticaria (CSU), the guidelines recommend very limited diagnostic procedures during the routine workup, although additional investigations might be indicated in some patients with CSU. For physicians treating patients with CSU, it is often difficult to decide which diagnostic tests are useful. OBJECTIVE: To provide recommendations on what diagnostic tests should be performed on which patients with CSU. METHODS: We performed an extensive literature search on the respective topics and identified relevant questions that should prompt diagnostic procedures based on the published evidence and expert consensus among all authors. RESULTS: We provide questions, diagnostic testing, where appropriate, and recommendation that should be included when assessing the history of a patient with CSU, to explore and rule out differential diagnoses, to assess patients for underlying causes and modifying conditions, to explore patients for comorbid diseases and consequences of having CSU, and to assess patients for CSU components that can help to predict their disease course and response to treatment. CONCLUSIONS: Here, we provide physicians treating patients with CSU with information about which clues should lead to which tests and why.

A group of cationic amphiphilic drugs activates MRGPRX2 and induces scratching behavior in mice.

BACKGROUND: Mas gene-related G protein-coupled receptors (MRGPRs) are a G protein-coupled receptor family responsive to various exogenous and endogenous agonists, playing a fundamental role in pain and itch sensation. The primate-specific family member MRGPRX2 and its murine orthologue MRGPRB2 are expressed by mast cells mediating IgE-independent signaling and pseudoallergic drug reactions. OBJECTIVES: Our aim was to increase knowledge about the function and regulation of MRGPRX2/MRGPRB2, which is of major importance in prevention of drug hypersensitivity reactions and drug-induced pruritus. METHODS: To identify novel MRGPR (ant)agonists, we screened a library of pharmacologically active compounds by utilizing a high-throughput calcium mobilization assay. The identified hit compounds were analyzed for their pseudoallergic and pruritogenic effects in mice and human. RESULTS: We found a class of commonly used drugs activating MRGPRX2 that, to a large extent, consists of antidepressants, antiallergic drugs, and antipsychotics. Three-dimensional pharmacophore modeling revealed structural similarities of the identified agonists, classifying them as cationic amphiphilic drugs. Mast cell activation was investigated by using the 3 representatively selected antidepressants clomipramine, paroxetine, and desipramine. Indeed, we were able to show a concentration-dependent activation and MRGPRX2-dependent degranulation of the human mast cell line LAD2 (Laboratory of Allergic Diseases-2). Furthermore, clomipramine, paroxetine, and desipramine were able to induce degranulation of human skin and murine peritoneal mast cells. These substances elicited dose-dependent scratching behavior following intradermal injection into C57BL/6 mice but less so in MRGPRB2-mutant mice, as well as wheal-and-flare reactions following intradermal injections in humans. CONCLUSION: Our results contribute to the characterization of structure-activity relationships and functionality of MRGPRX2 ligands and facilitate prediction of adverse reactions such as drug-induced pruritus to prevent severe drug hypersensitivity reactions.

The characteristics and impact of pruritus in adult dermatology patients: A prospective, cross-sectional study.

BACKGROUND: Pruritus often accompanies chronic skin diseases, exerting considerable burden on many areas of patient functioning; this burden and the features of pruritus remain insufficiently characterized. OBJECTIVE: To investigate characteristics, including localization patterns, and burden of pruritus in patients with chronic dermatoses. METHODS: We recruited 800 patients with active chronic skin diseases. We assessed pruritus intensity, localization, and further characteristics. We used validated questionnaires to assess quality of life, work productivity and activity impairment, anxiety, depression, and sleep quality. RESULTS: Nine out of every 10 patients had experienced pruritus throughout their disease and 73% in the last 7 days. Pruritus often affected the entire body and was not restricted to skin lesions. Patients with moderate to severe pruritus reported significantly more impairment to their sleep quality and work productivity, and they were more depressed and anxious than control individuals and patients with mild or no pruritus. Suicidal ideations were highly prevalent in patients with chronic pruritus (18.5%) and atopic dermatitis (11.8%). CONCLUSIONS: Pruritus prevalence and intensity are very high across all dermatoses studied; intensity is linked to impairment in many areas of daily functioning. Effective treatment strategies are urgently required to treat pruritus and the underlying skin disease.

Worsening of chronic spontaneous urticaria after intake of hot pepper.

BACKGROUND: Patients with chronic spontaneous urticaria (CSU) have been reported to experience increased disease activity in response to the oral intake of hot pepper (Capsicum spp.). As of now, it is unclear how common this is. OBJECTIVE: We assessed patients with CSU for the prevalence of disease worsening after the intake of hot pepper and characterized its effects on their urticaria. METHODS: A questionnaire-based survey study in adult patients with CSU and a history of hot pepper consumption was carried out at a reference center for urticaria in Turkey. CSU patients who had co-existing chronic inducible urticaria were excluded from the study. RESULTS: Of the eighty-five patients with CSU included in this study, 46% (39 of 85) reported worsening of their urticaria after consuming hot pepper. Demographic features, duration of CSU and control status of urticaria were not different between patients who experienced worsening of their urticaria after the intake of hot pepper and those who did not. In affected patients, worsening of their symptoms started 1.2 ± 1.2 hours after the intake of hot pepper and lasted for 3.3 ± 6.8 hours. Symptoms disappeared significantly faster in patients who took antihistamines after worsening of their urticaria with hot pepper (0.7 ± 0.6 vs. 5.8 ± 8.8 hours; p = 0.003). CONCLUSIONS: Worsening of urticaria is common and relevant in patients with CSU in Turkey. Further studies are needed to explore if this is also the case in other geographical regions and to identify and characterize the underlying mechanisms.