BACKGROUND: Skin reaction patterns vary across patients with cholinergic urticaria (CholU), but their definition, prevalence, and clinical significance remain ill characterized.
METHODS: Patients with CholU underwent pulse-controlled ergometry provocation testing to analyze skin reaction patterns and their correlation with location, onset, severity, sweating behaviour, clinical features, disease control, and quality of life (QoL) impairment.
RESULTS: Based on the size, color, spacing, and shape of wheals as well as their surrounding skin responses, we identified six distinct types of CholU skin reactions, which differed in prevalence, from 83% (Type I) to 11% (Type VI) of patients affected. Almost all patients (94%) had ≥1 type of skin reaction pattern. Sweating was reduced in the majority of CholU patients and most prominently reduced in patients with Type VI skin signs (very small, round, red, widely spaced wheals with surrounding anemic halo), which emerged exclusively on the extremities. Type V skin signs (large, irregular, anemic, widely spaced wheals with moderate size erythema) were associated with the most severe clinical presentation and poorest QoL.
CONCLUSIONS: Our analysis showed that most patients have more than one type of skin reaction patterns and that different skin signs are linked to distinct features. Future studies should determine any links between treatment response and types of skin signs in CholU.

The skin prick test (SPT) is a key tool for identifying sensitized allergens associated with immunoglobulin E-mediated allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, urticaria, angioedema, and anaphylaxis. However, the SPT is labor-intensive and time-consuming due to the necessity of measuring the sizes of the erythema and wheals induced by allergens on the skin. In this study, we used an image preprocessing method and a deep learning model to segment wheals and erythema in SPT images captured by a smartphone camera. Subsequently, we assessed the deep learning model\'s performance by comparing the results with ground-truth data. Using contrast-limited adaptive histogram equalization (CLAHE), an image preprocessing technique designed to enhance image contrast, we augmented the chromatic contrast in 46 SPT images from 33 participants. We established a deep learning model for wheal and erythema segmentation using 144 and 150 training datasets, respectively. The wheal segmentation model achieved an accuracy of 0.9985, a sensitivity of 0.5621, a specificity of 0.9995, and a Dice similarity coefficient of 0.7079, whereas the erythema segmentation model achieved an accuracy of 0.9660, a sensitivity of 0.5787, a specificity of 0.97977, and a Dice similarity coefficient of 0.6636. The use of image preprocessing and deep learning technology in SPT is expected to have a significant positive impact on medical practice by ensuring the accurate segmentation of wheals and erythema, producing consistent evaluation results, and simplifying diagnostic processes.

UNASSIGNED: The presence of wheals or hives has been viewed as a hallmark symptom of urticaria, a highly debilitating disease. This study explores our experience with omalizumab in patients with apparent mast-cell mediated pruritus in the absence of hives.
UNASSIGNED: This is a retrospective case series examining all patients with mast cell-mediated pruritus in the absence of hives from April 2022 to May 2024 at a tertiary referral clinic at Icahn School of Medicine at Mount Sinai in New York. Peak pruritus-numerical rating scale (PP-NRS) itch score changes over time were recorded and analyzed.
UNASSIGNED: Six patients (67% women; mean [SD] age, 47.67 [13.52] years) were included in the analysis. The median [IQR] pruritus PP-NRS itch score before omalizumab injection was 9 [6 - 10] and the final median [IQR] PP-NRS itch score was 2.5 [0 - 5]. The mean [SD] reduction in the PP-NRS itch score was 6 [3.16].
UNASSIGNED: This study suggests that patients with evidence of mast cell-mediated pruritus can be identified based on clinical features and may benefit from omalizumab therapy.

Urticarial vasculitis is a rare autoimmune disorder characterized by persistent edematous papules and plaques on the skin that last longer than 24 hours, often accompanied by systemic symptoms such as joint pain and fever. Unlike common urticaria, this condition involves inflammation of small blood vessels, leading to more severe and long-lasting skin lesions with a tendency to leave a bruiselike appearance. Diagnosis is challenging and may require a skin biopsy. Associated with underlying autoimmune diseases, treatment involves managing symptoms with medications such as antihistamines and corticosteroids, addressing the immune system\'s dysfunction, and treating any concurrent autoimmune conditions.

UNASSIGNED: The skin prick test (SPT) is the gold standard for identifying allergic sensitization in individuals suspected of having an inhalant allergy. Recently, it was demonstrated that SPT using a novel skin prick automated test (SPAT) device showed increased reproducibility and tolerability compared to the conventional SPT, among other benefits.
UNASSIGNED: This study aimed to evaluate prick location bias using the novel SPAT device.
UNASSIGNED: A total of 118 volunteers were enrolled in this study and underwent SPATs with histamine (nine pricks) and glycerol control (one prick) solutions on the volar side of their forearms. Imaging of the skin reactions was performed using the SPAT device, and the physician determined the longest wheal diameter by visually inspecting the images using a web interface. Prick location bias was assessed along the medial vs. lateral and proximal vs. distal axes of the forearm.
UNASSIGNED: In total, 944 histamine pricks were analyzed. Four medial and four lateral histamine pricks were grouped, and wheal sizes were compared. The longest wheal diameters were not significantly different between the medial and lateral prick locations (p = 0.41). Furthermore, the pricks were grouped by two based on their position on the proximal-distal axis of the forearm. No significant difference was observed among the four groups of analyzed prick locations (p = 0.73).
UNASSIGNED: The prick location on the volar side of the forearm did not influence wheal size in SPAT-pricked individuals.

Die Lebenszeitprävalenz für Urtikaria, die zu den schweren allergischen Erkrankungen zählt, liegt bei nahezu 20%. Sie schränkt nicht nur die Lebensqualität der Betroffenen ein, sondern die generelle Leistungsfähigkeit in Beruf und Alltag. Die vorliegende Publikation ist der erste Abschnitt der Leitlinie Urtikaria. Dieser Teil der Leitlinie umfasst deren Klassifikation und Diagnostik unter Einbeziehung der wesentlichen Fortschritte in der Erforschung ihrer Ursachen, auslösenden Faktoren und Pathomechanismen. Zudem befasst sie sich mit Strategien zur ökonomischen Diagnostik der verschiedenen Unterformen der Urtikaria. Dies ist entscheidend für eine individuelle, patientenorientierte Therapie, die im zweiten Teil behandelt wird. Diese deutschsprachige Leitlinie wurde auf der Basis der internationalen englischsprachigen S3-Leitlinie unter besonderer Berücksichtigung der medizinischen Gegebenheiten im deutschsprachigen Raum entsprechend den Kriterien der AWMF erstellt. Die Leitlinie beschreibt in diesem Abschnitt die Klassifikation der Urtikaria, wobei spontan auftretende Quaddeln und Schwellungen von Urtikariaformen mit induzierbaren Symptomen abgegrenzt werden. Urtikaria wird als plötzlich auftretende Quaddeln, Schwellungen oder beides definiert, ist dabei aber abzugrenzen von Zuständen bei denen Quaddeln als kurzfristiges Symptom auftreten, wie zum Beispiel bei der Anaphylaxie. Die Diagnostik stützt sich auf (eingeschränkte) Laboruntersuchungen, aber insbesondere auch die Anamnese. Darüber hinaus stehen validierte Instrumente zur Verfügung, die den Schweregrad, die Aktivität und den Verlauf erfassen.

The lifetime prevalence of urticaria, a severe allergic disease, is almost 20%. It not only limits the quality of life of those affected, but also their general performance at work and in their daily activities. This publication is the first section of the Urticaria Guideline. It covers the classification and diagnosis of urticaria, taking into account the major advances in research into its causes, triggering factors and pathomechanisms. It also addresses strategies for the efficient diagnosis of the different subtypes of urticaria. This is crucial for individual, patient-oriented treatment, which is covered in the second part of the guideline, published separately. This German-language guideline was developed according to the criteria of the AWMF on the basis of the international English-language S3 guideline with special consideration of health system characteristics in the German-speaking countries. This first part of the guideline describes the classification of urticaria, distinguishing spontaneously occurring wheals (hives) and angioedema from forms of urticaria with inducible symptoms. Urticaria is defined as sudden onset of wheals, angioedema, or both, but is to be distinguished from conditions in which wheals occur as a short-term symptom, such as anaphylaxis. The diagnosis is based on (a limited number of) laboratory tests, but especially on medical history. In addition, validated instruments are available to measure the severity, activity and course of the disease.

Urticaria is a heterogeneous inflammatory disorder that can be acute or chronic and is defined by the appearance of wheals, angioedema, or both. Very recently, the newest update and revision of the international European Academy of Allergy and Clinical Immunology/Global Allergy and Asthma European Network/European Dermatology Forum/Asia Pacific Association of Allergy Asthma Clinical Immunology guideline for the definition, classification, diagnosis, and management of urticaria was published. It aims to help primary care physicians and specialists in the management of their patients with urticaria. The guideline applied the Grading of Recommendations Assessment Development and Evaluations approach to developing consensus recommendations. These recommendations were then discussed in a Delphi conference that included more than 250 specialists in the field, and they are endorsed by more than 50 international societies. Here, we highlight changes from previous versions of the international urticaria guideline and their impact on clinical practice.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: Histamine released from skin mast cells is a key driver of the development of signs and symptoms and a promising therapeutic target in CIndU.

Cholinergic urticaria (CholU), a frequent form of chronic inducible urticaria, is characterized by itchy wheals and angioedema in response to sweating. As of now, the rate and pathophysiological relevance of impaired sweating in patients with CholU are ill-defined.
To assess in CholU patients the rate and extent of impaired sweating and its links to clinical and pathophysiological features of CholU.
We assessed sweating in patients with CholU (n = 13) subjected to pulse-controlled ergometry (PCE) provocation testing. Pre- and post-PCE biopsies of lesional (L) and non-lesional (NL) skin were analyzed for the expression of acetylcholine receptor M3 (CHRM3) and acetylcholine esterase (ACh-E) by quantitative histomorphometry and compared to those of healthy control subjects (HCs). CholU patients were assessed for disease duration and severity as well as other clinical features.
Of the 13 patients with CholU, 10 showed reduced sweating in response to PCE provocation, and 3 had severely reduced sweating. Reduced sweating was linked to long disease duration and high disease severity. CholU patients with impaired sweating responses showed reduced sweat gland epithelial expression of CHRM3 and ACh-E.
Reduced sweating is common in CholU patients, especially in those with long-standing and severe disease, and it can be severe. Reduced expression of CHRM3 and ACh-E may be the cause or consequence of CholU in patients with impaired sweating, and this should be explored by further studies.