Alopecia Areata: additional treatment options

• Alopecia Areata (AA) is an inflammatory cause of non-scarring alopecia which carries a lifetime risk 1.7%

• Treatment options now available include, topical and intralesional steroids, Diphencyprone (DCP), oral steroids (in pulse dose)

• Genetics is poorly understood:
  • innate and adaptive immunity
  • The cause of the infiltrate of T cells at the base of hair follicles is unknown (swarm of bees)
  • The disease appears to be triggered by a collapse of immune privilege (alpha MSH, TGF beta 1, IGF1, NK cell suspension) and the subsequent activation of danger signals

• Genes associated with AA:
  • ULBP3/ ULBP6 (H60 in the mice)= ligands for receptor NKG2D
    • is a ligand on NK cells (and CD8+ T cells) and is required to induce T-cell mediated action in AA when stimulated by antigen presenting cells (APC)
    • Marked ULBP3 overexpression is observed when compared to the hair follicle in controls(also HLA A and HLA DQ beta 2 although less interesting in this study)
    • NKG2D positive cells when injected enable mice to lose their hair
    • (NKG2D negative cells when injected DO NOT induce mice to lose their hair)

• Diseases genomically related to AA:
  • Type 1 diabetes
  • Rheumatoid Arthritis (RA)
  • Celiac disease

• Facts revealed by this study:
  • IFN-gamma is upregulated in Alopecia Areata (AA): Anti-IFN gamma and anti-IL15 blockade enable mice NOT to lose their hair
  • JAK-STAT signalling: Janus kinases (JAK) inhibitors appear to play an important role
    • In mice (C3H/ HeJ ):
      • JAK1 and 2 are inhibited by Ruxolitinib (Jakafi)
      • JAK 3 is inhibited by Tofacitinib (Xelajanz)
      • Indeed, topical application of  tofacitinib and ruxolitinib topicaly hindered hair loss when compared with untreated mice
      • When the disease was already present, systemic administration of these drugs reversed the disease

Human open-label studies with Jakafi are being conducted and the results are not published here.

Contributors

Dr Christophe Hsu – dermatologist. Geneva, Switzerland

Source of information: Christiano A et al. Genetics and Immunology of Alopecia Areata.Tanioku Kihei Memorial lecture. JSID Annual Meeting (Japanese Society of Investigative Dermatology, 日本研究皮膚科学会) 2014 – Osaka, Japan