Clinical trial NCT06201780: Assessment of Serum Levels of Janus Kinase 1 and 2 in Patients With Cholinergic Urticaria
Official title: Assessment of Serum Levels of Janus Kinase 1 and 2 in Patients With Cholinergic Urticaria
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cholinergic Urticaria
Lead sponsor: Sohag University
Sponsor class: OTHER
First posted: 2024-01-11
Enrollment: 90
Sex: ALL
Minimum age (years): 15
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: Cholinergic Urticaria (CholU) is as a subtype of CIndU caused by an increase in the core body temperature, such as to activate the sweating reflex. It can occur in response to physical exercise, hot bathing and/or emotional stress. Clinically it appears as pinpointing and highly pruritic wheals with surrounding erythema, CholU can be accompanied by severe symptoms such as angioedema, respiratory symptoms or anaphylaxi CholU is frequently associated with atopic dermatitis (AD) The JAK-STAT is a mast cell (MC) signaling pathway activated downstream of IgE and IL-3 with important roles in MC homeostasis via regulation of proliferation, survival, and release of mediators. JAK-STAT activation is associated with polarization toward Th2, B cell isotype switching to IgE production, and IgE-dependent degranulation and cytokine release .

Because both IL-4 and IL-13 use the IL-4Rα as a receptor component, these cytokines activate any common signaling pathways. Both of these cytokines use Janus kinases (JAKs) to initiate signaling and activate signal transducer and activator of transcription-6 (STAT6), which is a transcription factor required for many of their biologic functions.

The non-receptor protein tyrosine kinases JAK1 and JAK3 associate with the IL-4Rα and γC, respectively. The binding of IL-4 to its receptor induces the transphosphorylation of JAK1 and JAK3, an event that activates these kinases and thereby initiates the early events of signal transduction .


Eligibility criteria: Inclusion Criteria:

* The study will include 45 adult patients complaining of CholU as well as 45 healthy controls.

Exclusion Criteria:

* Patients with one or more of the following criteria will be excluded:

  * Pregnancy and lactation.
  * Patients with systemic diseases especially those with autoimmune diseases and infections.
  * Patients with skin diseases.
  * Patients on medications such as: antibiotics, non-steroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, anticonvulsants, penicillin, combined oral contraceptives.
  * Patient refusal

Primary outcomes:
measure: serum levels of janus kinase 1
timeFrame: 1 year
Secondary outcomes:
measure: serum levels of janus kinase 2
timeFrame: 1 year
Other outcomes:
Locations:
city: Sohag
country: Egypt
facility: Sohag university Hospital
Study officials:
References:
citation: Altrichter S, Koch K, Church MK, Maurer M. Atopic predisposition in cholinergic urticaria patients and its implications. J Eur Acad Dermatol Venereol. 2016 Dec;30(12):2060-2065. doi: 10.1111/jdv.13765. Epub 2016 Jun 21.
citation: Altrichter S, Salow J, Ardelean E, Church MK, Werner A, Maurer M. Development of a standardized pulse-controlled ergometry test for diagnosing and investigating cholinergic urticaria. J Dermatol Sci. 2014 Aug;75(2):88-93. doi: 10.1016/j.jdermsci.2014.04.007. Epub 2014 May 1.
citation: Burchett JR, Dailey JM, Kee SA, Pryor DT, Kotha A, Kankaria RA, Straus DB, Ryan JJ. Targeting Mast Cells in Allergic Disease: Current Therapies and Drug Repurposing. Cells. 2022 Sep 27;11(19):3031. doi: 10.3390/cells11193031.
citation: Fricke J, Avila G, Keller T, Weller K, Lau S, Maurer M, Zuberbier T, Keil T. Prevalence of chronic urticaria in children and adults across the globe: Systematic review with meta-analysis. Allergy. 2020 Feb;75(2):423-432. doi: 10.1111/all.14037. Epub 2019 Oct 11.