Alopecia areata: a review on diagnosis, immunological etiopathogenesis and treatment options.

Patients suffering from alopecia areata (AA) can lose hair in focal regions, the complete scalp, including eyelashes and eyebrows, or even the entire body. The exact pathology is not yet known, but the most described theory is a collapse of the immune privilege system, which can be found in some specific regions of the body. Different treatment options, local and systemic, are available, but none of them have been proven to be effective in the long term as well for every treatment there should be considered for the possible side effects. In many cases, treated or non-treated, relapse often occurs. The prognosis is uncertain and is negatively influenced by the subtypes alopecia totalis and alopecia universalis and characteristics such as associated nail lesions, hair loss for more than 10 years and a positive familial history. The unpredictable course of the disease also makes it a mental struggle and AA patients are more often associated with depression and anxiety compared to the healthy population. Research into immunology and genetics, more particularly in the field of dendritic cells (DC), is recommended for AA as there is evidence of the possible role of DC in the treatment of other autoimmune diseases such as multiple Sclerosis and cancer. Promising therapies for the future treatment of AA are JAK-STAT inhibitors and PRP.

Evaluation of platelet-rich plasma on hair regrowth and lesional T-cell cytokine expression in alopecia areata: A randomized observer-blinded, placebo-controlled, split-head pilot study.

BACKGROUND: Platelet-rich plasma has shown some promise in the treatment of alopecia areata. OBJECTIVE: To evaluate the effect of platelet-rich plasma on hair regrowth and lesional T-cell cytokine expression in alopecia areata. METHODS: This was a randomized, placebo-controlled, split-head study involving 27 patients with alopecia areata (Severity of Alopecia Tool score ≥25%). Alopecia patches on either side of the scalp were randomized to receive 3 intradermal injections of platelet-rich plasma or normal saline at monthly intervals and evaluated 3 months after the last session. Lesional T-cell cytokine messenger RNA expression was compared pre- and posttreatment in the platelet-rich plasma-treated sites. RESULTS: The mean Severity of Alopecia Tool score did not change significantly compared with baseline with either platelet-rich plasma or placebo injections at any visit; however, the mean percentage reduction in the score in the platelet-rich plasma arm was more than in the placebo arm (9.05% ± 36.48% vs 4.99% ± 33.88%; P = .049) at final assessment. The mean interferon gamma (P = .001) and interleukin 17 cytokine (P = .009) messenger RNA expression decreased, whereas the mean interleukin 10 (P = .049) and FOXP3 (P = .011) messenger RNA expression increased significantly after platelet-rich plasma treatment. LIMITATIONS: Small sample size and a relatively short follow-up. CONCLUSION: Platelet-rich plasma was found to have limited efficacy in alopecia areata. However, it may play a role in restoring immune balance in the alopecic patches.

A clinical and immunological study of phototoxic regimen of ultraviolet A for treatment of alopecia areata: a randomized controlled clinical trial.

Background: Various therapeutic agents have been described for alopecia areata but none is satisfactory. The use of ultraviolet A phototherapy in phototoxic regimens has emerged lately with promising results. Objective: To determine the efficacy and safety of phototoxic regimen of psoralen ultraviolet A (PUVA) in comparison to conventional therapy with intralesional corticosteroids in patients with alopecia areata. Methods: In this randomized controlled clinical trial, 40 patients were randomized to either phototoxic regimen of psoralen ultraviolet A group or potent intralesional corticosteroids group for three months. Study ended at six months. The primary outcome was treatment success: sustained regrowth of hair in ≥80% of the affected areas at six months. Tissue cytokines were assessed at zero and three months. Results: At six months, treatment success was achieved by 45% of patients, similarly in both groups. Tissue cytokine expression correlated well with clinical response. Conclusion: Phototoxic regimen of topical PUVA deserves a place among therapeutic tools used in management of alopecia areata especially in more extensive conditions where intralesional corticosteroids would not be suitable. Trial registration: https://clinicaltrials.gov/ct2/show/record/NCT01559584.

The Role of Micronutrients in Alopecia Areata: A Review.

Alopecia areata (AA) is a common, non-scarring form of hair loss caused by immune-mediated attack of the hair follicle. As with other immune-mediated diseases, a complex interplay between environment and genetics is thought to lead to the development of AA. Deficiency of micronutrients such as vitamins and minerals may represent a modifiable risk factor associated with development of AA. Given the role of these micronutrients in normal hair follicle development and in immune cell function, a growing number of investigations have sought to determine whether serum levels of these nutrients might differ in AA patients, and whether supplementation of these nutrients might represent a therapeutic option for AA. While current treatment often relies on invasive steroid injections or immunomodulating agents with potentially harmful side effects, therapy by micronutrient supplementation, whether as a primary modality or as adjunctive treatment, could offer a promising low-risk alternative. However, our review highlights a need for further research in this area, given that the current body of literature largely consists of small case-control studies and case reports, which preclude any definite conclusions for a role of micronutrients in AA. In this comprehensive review of the current literature, we found that serum vitamin D, zinc, and folate levels tend to be lower in patients with AA as compared to controls. Evidence is conflicting or insufficient to suggest differences in levels of iron, vitamin B12, copper, magnesium, or selenium. A small number of studies suggest that vitamin A levels may modify the disease. Though understanding of the role for micronutrients in AA is growing, definitive clinical recommendations such as routine serum level testing or therapeutic supplementation call for additional studies in larger populations and with a prospective design.

Understanding autoimmunity of vitiligo and alopecia areata.

PURPOSE OF REVIEW: Vitiligo and alopecia areata are common, disfiguring skin diseases. Treatment options are limited and include nontargeted approaches, such as corticosteroids, topical calcineurin inhibitors, narrow band ultraviolet B phototherapy, and other immune-modifying agents. The purpose of this article is to review shared, novel mechanisms between vitiligo and alopecia areata, as well as discuss how they inform the development of future targeted treatments. RECENT FINDINGS: Vitiligo and alopecia areata are both autoimmune diseases, and striking similarities in pathogenesis have been identified at the level of both the innate and adaptive immune system. Increased reactive oxygen species and high cellular stress level have been suggested as the initiating trigger of the innate immune system in both diseases, and genome-wide association studies have implicated risk alleles that influence both innate and adaptive immunity. Most importantly, mechanistic studies in mouse models of vitiligo and alopecia areata have specifically implicated an interferon (IFN)γ-driven immune response, including IFNγ, IFNγ-induced chemokines, and cytotoxic CD8 T cells as the main drivers of disease pathogenesis. These recent discoveries may reveal an effective strategy to develop new treatments, and several proof-of-concept clinical studies support this hypothesis. SUMMARY: The identification of IFNγ-driven immune signaling pathways has enabled discoveries of potential new treatments for vitiligo and alopecia areata, and supports initiation of larger clinical trials.

A randomized controlled trial comparing total glucosides of paeony capsule and compound glycyrrhizin tablet for alopecia areata.

OBJECTIVE: To observe the efficacy and safety of total glucosides of paeony capsule (TGPC) in patients with mild and moderate alopecia areata. METHODS: A total of 86 outpatients were randomly allocated into two groups of TGPC (treatment, 44 cases) and compound glycyrrhizin tablet (control, 42 cases). The treatment group was given oral TGPC, three times daily and 600 mg per time; the control group was given oral compound glycyrrhizin tablets, three times daily and 50 mg per time. In addition, both groups were given 10 mg of vitamin B(2) and tapped the bold patches with massage. The treatment course was three months for both groups. Peripheral blood T-cell subsets (CD3(+)CD4(+), CD3(+)CD8(+), Th, Ts, Th/Ts) of 10 patients randomly selected from each group respectively were tested before and after three months of treatment. The effectiveness and adverse reaction of all cases were observed each month. The safety was evaluated according to the incidence rate of adverse reaction. RESULTS: In the treatment group, the cured and markedly effective rate was 36.36% (16/44), 50.00% (22/44) and 68.18% (30/44) at the end of first, second and third month of treatment, respectively, and the incidence rate of adverse reaction was 13.64% (6/44). In the control group, the cured and markedly effective rate was 38.10% (16/42), 57.14% (24/42) and 71.43% (30/42), respectively, and the incidence rate of adverse reaction was 16.67% (7/42). The cured and markedly effective rate and the incidence rate of adverse reaction were similar in both groups (P>0.05). TGPC and compound glycyrrhizin tablet can inhibit CD3(+)CD4(+) and CD3(+)CD8(+), and decrease the ratio of Th/Ts (P<0.05). CONCLUSION: TGPC is effective and safe in the treatment of alopecia areata.

Epitopes, avidity and IgG subclasses of tyrosine hydroxylase autoantibodies in vitiligo and alopecia areata patients.

BACKGROUND: We previously detected antibodies against tyrosine hydroxylase (TH) in 23% of patients with nonsegmental vitiligo and in 19% of patients with alopecia areata (AA). OBJECTIVES: To identify TH epitopes recognized by TH antibodies in patients with vitiligo and AA. METHODS: Recombinant plasmids containing defined fragments of TH cDNA were constructed. The cloned TH cDNA fragments were subsequently translated in vitro to produce a series of [(35) S]-labelled TH protein fragments which were then used in radioimmunoassays to analyse the immunoreactivity of sera from 18 TH antibody-positive patients with vitiligo and so initially define TH epitope domains. Further localization of TH epitopes was investigated by antibody absorption experiments using synthetic TH peptides and nonradiolabelled, in vitro-expressed TH protein fragments. Antibody binding to identified epitopes was confirmed in TH peptide enzyme-linked immunosorbent assays. RESULTS: Analysis of the results obtained indicated the presence of two major antibody-binding sites on TH between amino acids 1 and 14 (epitope 1-14) and between amino acids 61 and 80 (epitope 61-80). Of 18 patients with vitiligo and six with AA, 17 (94%) and five (83%), respectively, had antibodies against epitope 1-14. In addition, 11/18 (61%) vitiligo and 2/6 (33%) AA patient sera displayed immunoreactivity against epitope 61-80. CONCLUSIONS: Two major binding sites for human TH antibodies are located at the N-terminus of the protein. The humoral immune response to TH in vitiligo and AA is heterogeneous in nature in that patients may have antibodies to more than one TH epitope. TH antibodies from patients with vitiligo or AA can recognize identical epitopes.

An update on alopecia areata.

PURPOSE OF REVIEW: Alopecia areata is one of the most frequent organ-restricted autoimmune diseases, yet its pathogenesis is still unclear. In addition, although alopecia areata often results in significant psychological distress, effective treatment is lacking. RECENT FINDINGS: New potential susceptibility loci have been implicated, but the strongest evidence points to certain class II human leukocyte antigen alleles. There is new evidence for the collapse of hair follicle immune privilege as a key step in the pathogenesis of alopecia areata. There is also new basic science evidence for stress as a contributing factor in the development of alopecia areata. Few treatments for alopecia areata have been well evaluated in randomized trials. SUMMARY: Although multiple potential susceptibility loci have been implicated, the genetics of alopecia areata is still unclear. The role of any potential environmental contributors is also unclear. Quality evidence for efficacy of currently used treatments for alopecia areata is lacking.

Alopecia areata: evidence-based treatments.

Alopecia areata is a common condition causing nonscarring hair loss. It may be patchy, involve the entire scalp (alopecia totalis) or whole body (alopecia universalis). Patients may recover spontaneously but the disorder can follow a course of recurrent relapses or result in persistent hair loss. Alopecia areata can cause great psychological distress, and the most important aspect of management is counseling the patient about the unpredictable nature and course of the condition as well as the available effective treatments, with details of their side effects. Although many treatments have been shown to stimulate hair growth in alopecia areata, there are limited data on their long-term efficacy and impact on quality of life. We review the evidence for the following commonly used treatments: corticosteroids (topical, intralesional, and systemic), topical sensitizers (diphenylcyclopropenone), psoralen and ultraviolet A phototherapy (PUVA), minoxidil and dithranol.

Combination therapy with oral PUVA and corticosteroid for recalcitrant alopecia areata.

Alopecia areata (AA) is regarded as a tissue-specific autoimmune disease for which several therapies have been suggested to modify the immune reaction against HFs, such as contact immunotherapy, psoralen plus ultraviolet A (PUVA), corticosteroids, cyclosporine, minoxidil, and dithranol. However, severe type AA, such as alopecia totalis (AT) and alopecia universalis (AU), often show resistance against these therapies. We applied a combination therapy with oral corticosteroid and oral PUVA for intractable cases of AT and AU. These patients took 20 mg/day corticosteroid and were irradiated with UVA on the whole body 2 h after taking methoxsalen for 1 month. In all patients, the terminal hair on the whole scalp regrew after 2 months. Two patients had a relapse of hair loss 3 months after the termination of the treatment. FACS analysis revealed that the CD4+CD25(high) and CD4+CD25+FOXP3+ Treg population in PBMC was increased after the combination therapy. Furthermore, the number of infiltrating cells decreased and FOXP3+ cells were often found in lesion skin after the combination therapy. Mitogen-induced proliferation tests showed low responses against PHA and Con A after the combination therapy. Taken together, the combination therapy may modify the systemic immune system and increase the number of Treg cells, resulting in improvement of recalcitrant AA.

[Regulatory effect of procyanidins on the expressions of interferon-gamma, interleukin-12 and transcription factor T-bet mRNA in peripheral blood mononuclear cell of patients with alopecia areata].

OBJECTIVE: To investigate the regulatory effect of procyanidins (PC) on the expressions of Th1 type cytokines (IFN-gamma and IL-12) and the transcription factor T-bet mRNA in peripheral blood mononuclear cell (PBMC) in patients with alopecia areata (AA). METHODS: Above-mentioned expressions were detected using RT-PCR technique in 20 AA patients (8 of mild and 12 of severe degree) and 10 healthy subjects after phytoaemagglutinin (PHA) or PHA + PC stimulation. RESULTS: After being stimulated by PHA and PHA + PC, in patients with severe AA, the expression of T-bet mRNA was 0.581 +/- 0.148 and 0.419 +/- 0.113 respectively; that of IFN-gamma mRNA, 0.689 +/- 0.219 and 0.430 +/- 0.162; and that of IL-12 mRNA, 0.198 +/- 0.056 and 0.136 +/- 0.035, respectively. As compared with those before stimulation, the respective difference was statistically significant (P < 0.05). CONCLUSIONS: PC can inhibit the expressions of Th1 type cytokines and transcription factor T-bet in PBMC of severe AA patients, and reverse the Th1 responses. The authors offered that it maybe part of the acting mechanism of pine needle for treatment of AA.

Current and potential agents for the treatment of alopecia areata.

Alopecia areata is considered to be a T-cell mediated autoimmune disease of the hair follicle. Current immunosuppressive approaches and immunomodulatory treatment with contact sensitizers such as diphenylcyclopropenone and squaric acid dibutylester are dealt with in this review article. The efficacy of the various modes of treatment is evaluated by a review of literature and their mode of action is discussed. In accordance with the mechanism of autoimmune pathogenesis of AA, improved future treatments may be immunosuppressive or immunomodulatory, or they should otherwise protect the hair follicle from the injurious effects of the inflammation. Such possible future therapeutic approaches include the use of liposomes as an improved vehicle, application of immunosuppressive cytokines like TGF-beta and IL-10, inhibition of apoptosis mediated by the Fas-FasL system, inhibition of the lymphocyte homing receptor CD44v10, induction of tolerance as well as principles of gene therapy.

Alopecia areata / Alopecia Areata

La alopecia areata es una enfermedad de base autoinmune crónica de etiología incierta. La información recolectada en el presente artículo se presenta de forma clara y concisa, enfatizando los aspectos más relevantes de la etiopatogenia, epidemiología, clasificación, características clínicas, histopatología, diagnóstico diferencial y tratamiento. Además, se incluye un test de autoevaluación como parte de la actividad de aprendizaje de la sección Formación Médica Continuada (AU)

Alopecia areata: pathogenesis and treatment.

Although its etiology remains unknown, evidence has accumulated to support an autoimmune pathogenesis for alopecia areata. Our review summarizes the immunologic data and also examines the role of genetics, atopy, and psychologic stress in this disorder. Until etiology is better understood, treatments for alopecia areata are likely to remain palliative. Nevertheless, newer therapies such as photochemotherapy, topical immunotherapy, and perhaps systemic immunotherapy (e.g., inosiplex) offer new hope for patients with extensive disease.