Cutaneous JAK in Vitiligo and Acne Vulgaris.

Assiut University

Status: Unknown

Conditions: Vitiligo and Acne Vulgaris

Treatments: Diagnostic Test: skin biopsy

Study type: Observational

Funder types: Other

Identifiers

NCT03185312

CJEIVAA

Details and patient eligibility

About

The Janus kinase/signal transducer and activator of transcription (JAK-STAT) cytokine signaling pathway is an emerging area of interest in dermatology, and emerging evidence suggests that this pathway may play a crucial role in pathogenesis of inflammatory skin disorders.

Recent advances on the role of cytokines in the pathophysiology of immune mediated inflammatory diseases lead to the understanding that many pro inflammatory interleukins use JAK/STAT components for signal transduction .

Full description

The JAK/STAT signaling pathway transmits information from extracellular chemical signals to the nucleus resulting in DNA transcription. Binding of ligands, such as interferon and interleukins, to their specific transmembrane receptors activate associated JAKs. Phosphorylation of STAT follows, and the phosphorylated STAT translocates to the cell nucleus and activates transcription or suppression of target genes .

The JAK family of non-receptor intracellular tyrosine kinases is comprised of four members, JAK1, JAK2, JAK3 and tyrosine kinase (TyK)2. The JAKs are selectively activated by different receptors and have, therefore, distinct in vivo roles. JAK1 is mainly activated by type II cytokine receptors. JAK2 is crucial in transducing signals for cytokine receptors involved in hematopoiesis (erythropoietin, thrombopoietin and haematopoietic cell development cytokines). JAK3 is mainly expressed in B and T lymphocytes, and TYK2 associates commonly with other JAKs.

Cutaneous JAK overexpression has already been demonstrated in a number of inflammatory skin diseases (ISDs) including psoriasis, lichen planus (LP), atopic dermatitis (AD), pyoderma gangrenosum (PG) and alopecia areata (AA); indicating its crucial role in inflammatory keratinocytes.

Furthermore, the recent discovery of the JAK/STAT signaling pathway opened a new window of opportunity for the treatment of ISDs and promoted the development of drugs that block JAK activation.

JAK inhibitors in oral and topical formulations have shown beneficial results in psoriasis and alopecia areata. Patients suffering from vitiligo might also benefit from JAK inhibition. Recently, significant repigmentation was reported in a patient with vitiligo after treatment with tofacitinib, an oral JAK 1/3 inhibitor . However, the knowledge of the cutaneous JAK involvement in vitiligo is scarce. Similarly, little is known about cutaneous JAK expression in acne vulgaris.

Considering the previous findings, there is a need for further elucidation of the JAK signaling in other skin diseases as vitiligo and acne vulgaris.

Enrollment: 60 estimated patients

Sex: All

Ages: 12+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• patients with vitiligo and acne vulgaris.

Exclusion criteria

• patients below 12 years of age, or receiving systemic treatments in the last month

Trial design

60 participants in 3 patient groups

patients with acne vulgaris

Description:

Clinical evaluation including full history taking and dermatological examination will be done for all patients. Assessment of disease severity will be performed using Global acne severity grading for acne vulgaris Skin biopsies will be taken from lesional and non-lesional skin .immunohistochemical staining using specific antibodies for detection of expression of JAK1, JAK2 and JAK3.

Treatment:

Diagnostic Test: skin biopsy

patients with vitiligo

Description:

Clinical evaluation including full history taking and dermatological examination will be done . Assessment of disease severity will be performed using VASI score Skin biopsies will be taken from lesional and non-lesional skin .immunohistochemical staining using specific antibodies for detection of expression of JAK1, JAK2 and JAK3..

Treatment:

Diagnostic Test: skin biopsy

control

Description:

Skin biopsies will be taken from skin of controls. . Five micron thick sections will be cut from paraffin blocks for immunohistochemical staining using specific antibodies for detection of expression of JAK1, JAK2 and JAK3.

Treatment:

Diagnostic Test: skin biopsy