Matthew J. Harries

Evidence that the bulge region is a site of relative immune privilege in human hair follicles

Background  Recent gene profiling data suggest that, besides the anagen hair bulb, the epithelial stem cell region in the outer root sheath of hair follicles (HFs), termed the bulge, may also represent an area of relative immune privilege (IP).

Management of primary cicatricial alopecias: options for treatment.

Primary cicatricial alopecias (PCAs) are a poorly understood group of disorders that result in permanent hair loss. Clinically, they are characterized not only by permanent loss of hair shafts but also of visible follicular ostia along with other visible changes in skin surface morphology, while their histopathological hallmark usually (although not always) is the replacement of follicular structures with scar‐like fibrous tissue. As hair follicle neogenesis in adult human scalp skin is not yet a readily available treatment option for patients with cicatricial alopecias, the aim of treatment, currently, remains to reduce symptoms and to slow or stop PCA progression, namely the scarring process. Early treatment is the key to minimizing the extent of permanent alopecia. However, inconsistent terminology, poorly defined clinical end‐points and a lack of good quality clinical trials have long made management of these conditions very challenging. As one important step towards improving the management of this under‐investigated and under‐serviced group of dermatoses, the current review presents evidence‐based guidance for treatment, with identification of the strength of evidence, and a brief overview of clinical features of each condition. Wherever only insufficient evidence‐based advice on PCA management can be given at present, this is indicated so as to highlight important gaps in our clinical knowledge that call for concerted efforts to close these in the near future.

Lichen planopilaris is characterized by immune privilege collapse of the hair follicle's epithelial stem cell niche.

Lichen planopilaris (LPP) is a chronic inflammatory disease of unknown pathogenesis that leads to permanent hair loss. Whilst destruction of epithelial hair follicle stem cells (eHFSCs) that reside in an immunologically protected niche of the HF epithelium, the bulge, is a likely key event in LPP pathogenesis, this remains to be demonstrated. We have tested the hypotheses that bulge immune privilege (IP) collapse and inflammation‐induced eHFSC death are key components in the pathogenesis of LPP. Biopsies of lesional and non‐lesional scalp skin from adult LPP patients (n = 42) were analysed by quantitative (immuno)histomorphometry, real‐time quantitative polymerase chain reaction (qRT–PCR), laser capture microdissection and microarray analysis, or skin organ culture. At both the protein and transcriptional level, lesional LPP HFs showed evidence for bulge IP collapse (ie increased expression of MHC class I and II, β2microglobulin; reduced TGFβ2 and CD200 expression). This was accompanied by a Th1‐biased cytotoxic T cell response (ie increased CD8+ GranzymeB+ T cells and CD123+ plasmacytoid dendritic cells, with increased CXCR3 expression) and increased expression of interferon‐inducible chemokines (CXCL9/10/11). Interestingly, lesional LPP eHFSCs showed both increased proliferation and apoptosis in situ. Microarray analysis revealed a loss of eHFSC signatures and increased expression of T cell activation/binding markers in active LPP, while bulge PPARγ transcription was unaltered compared to non‐lesional LPP HFs. In organ culture of non‐lesional LPP skin, interferon‐γ (IFNγ) induced bulge IP collapse. LPP is an excellent model disease for studying and preventing immune destruction of human epithelial stem cells in situ. These novel findings raise the possibility that LPP represents an autoimmune disease in whose pathogenesis IFNγ‐induced bulge IP collapse plays an important role. Therapeutically, bulge IP protection/restoration may help to better manage this highly treatment‐resistant cicatricial alopecia. Copyright

Management of alopecia areata

#### Summary points Alopecia areata is a common condition characterised by sudden onset of patchy hair loss without signs of skin inflammation or scarring. It accounts for about 2% of new referrals for dermatology in the UK and United States and has an estimated lifetime risk of 1.7%.1 Data from the National Health and Nutrition Examination Survey indicated a prevalence of 0.15% in the population of the United States.w1 The extent of hair loss can vary greatly, ranging from a single coin sized patch to very extensive alopecia involving the entire scalp and the rest of the body. The condition is unpredictable; spontaneous regrowth of hair can occur at any time during its course with the possibility of subsequent relapse. Alopecia areata is particularly difficult to manage and most of the available therapeutic options are unsatisfactory. It is a psychologically distressing disease and doctors should provide patients with realistic advice about treatments and their effectiveness. Although several medical treatments have been reported for the condition, the evidence is quite difficult to interpret because of differing study methods, non-homogeneous patient populations, variability in outcome measures, and failure to control for spontaneous regrowth. A recent Cochrane …

How not to get scar(r)ed: Pointers to the correct diagnosis in patients with suspected primary cicatricial alopecia

Primary cicatricial alopecias (PCAs) are a rare, but important, group of disorders that cause irreversible damage to hair follicles resulting in scarring and permanent hair loss. They may also signify an underlying systemic disease. Thus, it is of paramount importance that clinicians who manage patients with hair loss are able to diagnose these disorders accurately. Unfortunately, PCAs are notoriously difficult conditions to diagnose and treat. The aim of this review is to present a rational and pragmatic guide to help clinicians in the professional assessment, investigation and diagnosis of patients with PCA. Illustrating typical clinical and histopathological presentations of key PCA entities we show how dermatoscopy can be profitably used for clinical diagnosis. Further, we advocate the search for loss of follicular ostia as a clinical hallmark of PCA, and suggest pragmatic strategies that allow rapid formulation of a working diagnosis.

Fumaric acid esters for severe psoriasis: a retrospective review of 58 cases.

Background  Fumaric acid esters (FAE) have been used to treat severe psoriasis in northern Europe for over 20 years. A recent systematic review has shown FAE to be an effective systemic treatment for severe psoriasis. However, FAE remain unlicensed in the U.K.

Lichen Planopilaris following Hair Transplantation and Face-lift Surgery.

Cosmetic surgical procedures, including hair transplantation and face‐lift surgery, are becoming increasingly popular. However, there is very little information regarding the associated development of dermatological conditions following these procedures. Lichen planopilaris (LPP) is an uncommon inflammatory hair disorder of unknown aetiology that results in permanent alopecia and replacement of hair follicles with scar‐like fibrous tissue. Frontal fibrosing alopecia (FFA), a variant of LPP, involves the frontal hairline and shares similar histological findings with those of LPP. We report 10 patients who developed LPP/FFA following cosmetic scalp surgery. Seven patients developed LPP following hair transplantation, and three patients developed FFA following face‐lift surgery. In all cases there was no previous history of LPP or FFA. There is currently a lack of evidence to link the procedures of hair transplantation and cosmetic face‐lift surgery to LPP and FFA, respectively. This is the first case series to describe this connection and to postulate the possible pathological processes underlying the clinical observation. Explanations include Koebner phenomenon induced by surgical trauma, an autoimmune process targeting an (as yet, unknown) hair follicle antigen liberated during surgery or perhaps a postsurgery proinflammatory milieu inducing hair follicle immune privilege collapse and follicular damage in susceptible individuals.

Frontal fibrosing alopecia: possible association with leave-on facial skin care products and sunscreens; a questionnaire study†

Since its first description in 1994, frontal fibrosing alopecia (FFA) has become increasingly common, suggesting that environmental factors are involved in the aetiology.

Does collapse of immune privilege in the hair-follicle bulge play a role in the pathogenesis of primary cicatricial alopecia?

Background.  The hair‐follicle bulge has recently been added to a growing list of human tissue compartments that exhibit a complex combination of immunosuppressive mechanisms, termed immune privilege (IP), which seem to restrict immune‐mediated injury in specific locations. As epithelial hair‐follicle stem cells (eHFSC) reside in the hair‐follicle bulge region, it is conceivable that these IP mechanisms protect this vital compartment from immune‐mediated damage, thereby ensuring the ongoing growth and cyclic regeneration of the hair follicle. Primary cicatricial alopecias (PCA) are a group of inflammatory hair disorders that result in hair‐follicle destruction and permanent alopecia. Growing evidence suggests that eHFSC destruction is a key factor in the permanent follicle loss seen in these conditions.

Allergic contact dermatitis to methyl aminolevulinate (Metvix®) cream used in photodynamic therapy

Topical photodynamic therapy (PDT) is increasingly used in the treatment of superficial skin malignancies including actinic keratosis, Bowens disease and superficial basal cell carcinoma. Contact allergy to the prodrug is rarely reported. We report a case of allergic contact dermatitis to methyl aminolevulinate cream used in PDT.