What’s new in hair — May 2016 | Dr. Yuval Ramot

Pulse corticosteroid therapy with oral dexamethasone for the treatment of adult alopecia totalis and universalis

J Am Acad Dermatol. 2016 May;74(5):1005-7. doi: 10.1016/j.jaad.2015.12.026

Alopecia totalis (AT) and alopecia universalis (AU) are two subtypes of alopecia areata (AA) which are known to be highly recalcitrant to treatment. The use of pulse corticosteroid therapy for these conditions has been suggested in order to decrease possible side effects from continuous corticosteroid treatment. In this paper, Vañó-Galván et al. describe their results with a new regimen of pulse corticosteroid therapy with oral dexamethasone, administered at a dosage of 0.1/mg/kg/day twice weekly. They achieved therapeutic response in 80.6% of the patients, and complete response in 71% of the patients. All patients with AT had complete response. They conclude that this treatment regimen might be considered as a potential therapeutic option for adults with AT/AU. However, this study lacked a control group, and adverse events were experienced by 10 patients. Additionally, duration of follow-up of patients after cessation of therapy is not reported by the authors. However, they state that persistent response was observed in only 10 patients. Recently, a systematic review on pulse corticosteroid therapy for AA has been published (Shreberk-Hassidim et al., J Am Acad Dermatol, 2016), which summarizes the available literature on this treatment modality, and is recommended for further reading on this issue.


Mitochondrial aerobic respiration is activated during hair follicle stem cell differentiation, and its dysfunction retards hair regeneration

PeerJ. 2016 May 3;4:e1821. doi: 10.7717/peerj.1821. eCollection 2016.

The essential role of the mitochondria in proper hair growth has been ascertained in several studies. In addition, its role in normal function and differentiation of stem cells has also been well-described in the scientific literature. However, changes in mitochondria characteristics and function during hair follicle stem cells (HFSCs) differentiation is not well established. In this study, Tang et al. used the C57BL/6 mouse to explore the changes observed during HFSCs differentiation in mitochondrial morphology and activity and how alterations in mitochondrial function affect hair regeneration. They show that there is increased activity of the mitochondria upon HFSCs differentiation, and this is accompanied by activated aerobic respiration. Furthermore, inhibition of mitochondrial respiration by injecting the respiratory inhibitor, antimycin A, resulted in delay of hair follicle regrowth after hair plucking. This study, therefore, further emphasizes the importance of the hair follicle mitochondria to normal hair growth and function, and points at changes in HFSC function as a possible controlling mechanism.


Cold thermal injury from cold caps used for the prevention of chemotherapy-induced alopecia

Breast Cancer Res Treat. 2016 May 5. [Epub ahead of print]

Since its introduction in the 1970s, the induction of scalp hypothermia has been gaining popularity as a method to prevent chemotherapy-induced alopecia (CIA). However, protocols for proper use of this methodology are not well established. In this paper, Belum et al. describe four patients who developed grade 1/2 cold thermal injuries on the scalp after using cold caps to prevent CIA, resulting in grade 1 persistent alopecia in three patients. This study shows that while most adverse events reported with cold caps use are mild in nature, and include mainly cold sensation, headache, dizziness, pruritus, application-site discomfort, local pain, neck pain, sensation of heaviness, and claustrophobia, they can also include more severe events like cold injury. Therefore, this report highlights the critical need in establishing treatment protocols and proper training programs to prevent such injuries in the future.


Cardiovascular risk in patients with alopecia areata (AA): A propensity-matched retrospective analysis

J Am Acad Dermatol. 2016 May 13. pii: S0190-9622(16)01504-8. doi: 10.1016/j.jaad.2016.02.1234. [Epub ahead of print]

Increased risk for cardiovascular diseases has been well established for a number of inflammatory skin condition, such as psoriasis. One study from Taiwan has also showed an increased risk for stroke in aleopecia areata (AA) patients (Kang et al., Sci Rep, 2015). In this paper, Huang et al. conducted a propensity-matched retrospective analysis to evaluate the risk of AA patients to develop stroke and acute myocardial infarction (AMI). By comparing 1377 AA cases to 4131 controls, they found that AA patients actually had a decreased risk for the development of stroke and a trend towards decreased risk for AMI. This study suggests that AA is protective for development of stroke and can reduce the risk for AMI, although the exact mechanism by which AA leads to this protection are unclear. Additional studies with large cohorts like this one would be necessary to confirm these findings.


Correction of Hair Shaft Defects through Allele-Specific Silencing of Mutant Krt75

J Invest Dermatol. 2016 Jan;136(1):45-51. doi: 10.1038/JID.2015.375.

RNA interference ex vivo has been used as a way to achieve allele specific inhibition in a number of skin disorders resulting from dominant mutations in keratin genes. However, it is unclear whether such approach can also benefit hair-related keratin diseases. In this paper, Liu et al targeted the Krt75 gene, which is known to be expressed in the companion layer and the medulla of hair. Dominant mutations in this gene lead to the appearance of blebs along the hair shaft. After silencing mutant Krt75 in epidermal keratinocyte progenitor cells using a lentiviral vector expressing mutant Krt75-specific short hairpin RNA, they could supress the blebbing phenotype in the hair regenerated from these cells in vivo. This study, therefore, establishes the feasibility of using ex vivo modification of epidermal keratinocyte progenitor cells as a method to correct hair shaft structural disorders.


Activating hair follicle stem cells via R-spondin2 to stimulate hair growth

J Invest Dermatol. 2016 Apr 21. pii: S0022-202X(16)31054-5. doi: 10.1016/j.jid.2016.01.041. [Epub ahead of print]

It has been shown before that Wnt-dependent activation of hair follicle stem cells can lead by itself to stimulation of hair growth. However, constituent activation of this signalling pathway by over-expression or ligand-independent activation of Wnt signalling carries the risk of skin cancer formation. Therefore, in this paper, Smith et al. used a different approach, aiming to amplify endogenous Wnt signalling using R-spondin (Rspo2). They injected this protein into mice intradermally, resulting in enhanced expression of Axin2 and Lgr5. This led to delay in the onset of catagen, and to thicker and longer hair. They conclude by suggesting that Rspo2 might be utilized in the future for promoting hair growth, after overcoming the technical hurdles of administration and protecting from degradation.

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