How skin pH could affect disease activity in Atopic Dermatitis

• Atopic Dermatitis (AD), beyond filaggrin mutations is better understood, but still remains (at the time of publication) full of gaps. pH alterations in AD are a matter of debate, but they do have an effect on its symptoms (itching) and appearance. This study shows molecular as well as physical alterations in AD.

• KLK5 can catalyze (increase and activate): Protease Activated Receptor (PAR2) and induces the production of Thymic Stromal Lymphopoierin (TSLP)

• The pH is reported in several studies to be higher in atopic dermatitis (AD) patients compared with healthy controls (http://www.ncbi.nlm.nih.gov/pubmed/22185924)

• Methods
  • 5 to 12 week old mice: either Specific Pathogen Free (SPF) or Conventional NC/Tnd mice, which is the standard  mice used for the study of atopic dermatitis (AD)
  • Detection of KLK5, PAR2 and TSLP was done by Western Blot or ELISA
  • Acid topical application: 2.5% (pH 2.8) and 5 (pH2.6) of lactobionic acid (LBA) twice a day for 2 weeks. Controls consisted of application of neutralized 5% LBA
  • Alkaline topical application: 0.65% 1,1,3,3 tetramethylguanidine (TMG, pH13) and controls consisting of both neutralized 0.65% TMG (pH7) and vehicle only

• Results
  • Levels of all three proteins (KLK5, PAR2 and TSLP) increased in NC/Tnd mice vs SPF mice
  • Acid topical application (2.5% and  5%) increased trans epidermal water loss (TEWL) tewl and clinical symptoms of dermatitis (hind leg scratch frequency)
    • Decrease of all protein levels (KLK5, PAR2 and TSLP)
    • No clinical improvement when neutralized LBA is applied
  • Alkaline topical application :
    • Increase in all protein levels ( (KLK5, PAR2 and TSLP) when compared with neutralized group and vehicle group
    • Increased TEWL and scratching frequency
    • No clinical improvement when neutralized LBA is applied

Comment: the study does not necessarily reflect the clinical reality as it is done in mice and that the application of acid or alkaline substances does not necessarily affect skin pH in the end, but it does suggest that pH alterations whatever they may be lead to symptoms of AD

Contributors

Dr Christophe Hsu – dermatologist. Geneva, Switzerland

Source of information: p05-11 Jang H et al. Involvement of skin surface pH on development of atopic dermatitis. JSID Annual Meeting (Japanese Society of Investigative Dermatology, 日本研究皮膚科学会) 2014 – Osaka, Japan