Possible role of ß-hydroxybutyrate in inducing inflammation in alopecia areata.

Alopecia areata (AA) is an autoimmune inflammatory disease characterized by non-scarring hair loss due to an immune response that targets hair follicles. The current treatment approach for AA involves the use of immunosuppressants and immunomodulators to reduce cytokine levels around affected hair follicles. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as potential anti-inflammatory agents with diverse beneficial effects in various medical conditions. This study investigates the role of beta-hydroxybutyrate (BHB), a ketone body produced during SGLT2 inhibition, in the pathogenesis of AA. Serum BHB levels were found to be significantly elevated in patients with AA compared with healthy controls, with higher levels correlating with severity of hair loss. BHB treatment increased inflammatory cytokine production in outer root sheath (ORS) cells, mimicking the inflammatory conditions seen in AA. The results suggest that elevated BHB levels may exacerbate the inflammatory immune response in AA patients and may be associated with chronic hair loss and resistance to treatment. Serum BHB levels may serve as a potential marker of poor prognosis in patients with severe AA. Further research is needed to elucidate the precise role of BHB in the pathogenesis of AA and its implications for disease management.

Serum lipids may causally affect the occurrence of alopecia areata: A Mendelian randomization study.

PURPOSE: The etiology of alopecia areata (AA) in relation to serum lipids remains unclear, thereby prompting our intention to do Mendelian study on this subject. DESIGN: Two-sample Mendelian randomization (MR) analysis was performed in the study. The inverse variance-weighted method was used as the primary method. METHODS: In our study, we integrated a set of 123 single-nucleotide polymorphisms (SNPs) into our analysis. These SNPs have been extensively studied and are known to exhibit associations with serum lipids. We sourced these SNPs from a variety of relevant studies and consortia that specifically focus on lipid-related research, such as the MRC Integrative Epidemiology Unit. These carefully curated SNPs were then utilized as instrumental variables in our analysis, allowing us to explore and evaluate the causal relationships between these genetic variants and serum lipids. By incorporating this comprehensive set of SNPs, we aimed to enhance the precision and robustness of our findings, shedding light on the intricate interplay between genetics and serum lipids. RESULTS: In the MR analysis, a higher total lipid concentration in large low-density lipoprotein (LDL) particles (odds ratio [OR] = 1.502; 95% confidence interval [CI] = 1.086-1.953; p = 0.006), a greater ratio of cholesteryl esters to total lipids in chylomicrons and extremely large very LDL (VLDL) particles (OR = 2.174; 95% CI = 1.300-2.500; p = 0.010), and a greater ratio of cholesterol to total lipids in chylomicrons and extremely large VLDL particles (OR = 2.363;95% CI = 1.556-4.438; p = 0.004), were genetically predicted to be causally associated with an increased risk of AA, while patients with a higher triglyceride to total lipids ratio in chylomicrons and extremely large VLDL particles had a lower risk of AA (OR = 0.481; 95% CI = 0.191-1.270; p = 0.002). CONCLUSION: This study found that serum lipids may be causally implicated in AA.

Explore the genetic exposure to alopecia areata.

BACKGROUND: Alopecia areata is an autoimmune hair loss disorder with an incompletely understood etiology. Although trace elements, serum metabolites, and inflammatory factors are implicated in the disease, the potential causal relationships between these factors and alopecia areata require further investigation. METHODS: This study employed Mendelian randomization (MR), utilizing data from genome-wide association studies, to explore the causal relationships between 15 trace elements, 1400 serum metabolites, and 91 inflammatory factors and alopecia areata. The analysis was conducted using the inverse variance weighted (IVW) method complemented by various sensitivity analyses, including Cochran's Q test, MR-Egger regression intercept test, MR-PRESSO global test, and leave-one-out analysis, to assess the robustness of the results. RESULTS: MR analysis indicated a negative correlation between copper levels and the risk of developing alopecia areata (odds ratio = 0.86, 95% confidence interval: 0.75-0.99, p = 0.041). Additionally, causal relationships were identified between 15 serum metabolites and 6 inflammatory factors and the risk of alopecia areata (IVW, all p values < 0.05). CONCLUSION: This study provides genetic evidence of the relationships between trace elements, serum metabolites, and alopecia areata, underscoring the potential value of targeted therapeutic strategies and preventive measures. Future research should expand to diverse populations and further explore the specific roles of these biomarkers in the disease mechanism.

To evaluate the role of interleukin-6 in alopecia areata.

Objective: TTo investigate the level of interleukin-6 in alopecia areata patients. METHODS: The exploratory study was conducted from September to December 2021 at the Sindh Institute of Skin Disease, Karachi, and comprised alopecia areata patients regardless of age and gender in group A, while healthy controls matched for age and gender formed group B. Alopecia areata classification and severity were done using the Severity of Alopecia Tool. Serum interleukin-6 was measured using enzyme-linked immune sorbent assay. Data was analysed using R statistical software v4.2.1. RESULTS: Of the 100 subjects, 50(50%) with mean age 15.52±10.14 years were cases in group A; 26(52%) females with mean age 16.78±10.77 years, and 24(48%) males with mean age 16.44±10.3 years. The remaining 50(50%) were controls in group B. Interleukin-6 concentration was significantly higher in group A (p<0.05). The concentration was not significantly different between the genders (p>0.05). The concentration was the highest in patients aged 11-20 years, followed by 21-30 years, 31-40 years and 1-10 years. Conclusion: The concentration of circulatory pro-inflammatory interleukin-6 was significantly higher in alopecia areata patients than in the healthy controls.

Diphenylcyclopropenone plays an effective therapeutic role by up-regulating the TSLP/OX40L/IL-13 pathway in severe alopecia areata.

Topical immunotherapy with diphenylcyclopropenone (DPCP) is considered to be the most effective treatment of severe AA. However, the mechanism is unclear and an early predictor for the efficacy needs to be explored. The TSLP/OX40L/IL-13 pathway is an important pathway to initiate and maintain Th2 immune responses. Our previous work suggests this pathway may play a role in severe AA treated with DPCP. Thus, to further investigate the mechanism of TSLP/OX40L/IL-13 pathway in severe AA treated with DPCP and explore the predictor for the efficacy of DPCP therapy, we conducted a prospective study to compare expression levels of TSLP, OX40L, Th2 cytokines IL-4, IL-5 and IL13, and Th1 cytokine IFN-γ in severe AA patients before and after the treatment. Results showed that 21 AA patients were responsive (responders) to the DPCP therapy and 12 were not responsive (non-responders). Responders had lower levels of TSLP, OX40L and IL-13 than non-responders before the treatment. After the DPCP treatment, TSLP, IL-5 and IL-13 increased and IFN-γ decreased in responders while there were no changes of TSLP, IL-4, IL-13 and IFN-γ in non-responders. Our data suggest that the TSLP/OX40L/IL-13 pathway is down-regulated in some severe AA patients and DPCP might play a therapeutic role by up-regulating the pathway in these severe AA patients. The TSLP/OX40L/IL-13 pathway could be a predictor of response to the DPCP therapy for severe AA patients.

Cross-sectional study of blood biomarkers of patients with moderate to severe alopecia areata reveals systemic immune and cardiovascular biomarker dysregulation.

BACKGROUND: Although there is increased understanding of the alopecia areata (AA) pathogenesis based on studies in scalp tissues, little is known about its systemic profile. OBJECTIVE: To evaluate the blood proteomic signature of AA and determine biomarkers associated with increased disease severity. METHODS: In a cross-sectional study, we assessed 350 inflammatory and cardiovascular proteins using OLINK high-throughput proteomics in patients with moderate to severe AA (n = 35), as compared with healthy individuals (n = 36), patients with moderate to severe psoriasis (n = 19), and those with atopic dermatitis (n = 49). RESULTS: Seventy-four proteins were significantly differentially expressed between AA and control individuals (false discovery rate, <.05) including innate immunity (interleukin [IL] 6/IL-8), T helper (Th) type 1 (interferon [IFN] γ/CXCL9/CXCL10/CXCL11), Th2 (CCL13/CCL17/CCL7), Th17 (CCL20/PI3/S100A12), and cardiovascular-risk proteins (OLR1/OSM/MPO/PRTN3). Eighty-six biomarkers correlated with AA clinical severity (P < .05), including Th1/Th2, and cardiovascular/atherosclerosis-related proteins, including SELP/PGLYRP1/MPO/IL-18/OSM (P < .05). Patients with AA totalis/universalis showed the highest systemic inflammatory tone, including cardiovascular risk biomarkers, compared to control individuals and even to patients with atopic dermatitis and those with psoriasis. The AA profile showed some Th1/Th2 differences in the setting of concomitant atopy. LIMITATIONS: Our analysis was limited to 350 proteins. CONCLUSION: This study defined the abnormalities of moderate to severe AA and associated circulatory biomarkers. It shows that AA has systemic immune, cardiovascular, and atherosclerosis biomarker dysregulation, suggesting the need for systemic treatment approaches.

Evaluation of serum cardiac troponin I and N-terminal pro-B-type natriuretic peptide levels in patients with alopecia areata.

Alopecia areata (AA) is a recurrent, immune-mediated, hair-loss disorder. It is associated with other autoimmune disorders that carry a high risk of cardiovascular disease (CVD). However, there is a lack of reports on the association of cardiovascular comorbidities and AA. Cardiac troponin I is a biomarker of myocardial ischaemia and inflammation, while N-terminal pro-B-type natriuretic peptide is used in the diagnosis of congestive heart failure. This study was conducted to assess the serum level of both markers by ELISA in 44 patients with AA compared with 44 healthy controls (HCs). None of the participants had CVD, CVD risk factors or other diseases associated with elevation of either marker. The study revealed that serum levels of both markers were significantly higher in patients with AA compared with HCs (P < 0.001). The inflammatory milieu encountered in AA may be associated with subtle myocardial inflammation that causes elevation of levels of both of these cardiac markers.

Serum level of IL-4 predicts response to topical immunotherapy with diphenylcyclopropenone in alopecia areata.

BACKGROUND: This study investigated predictors of response to topical diphenylyclopropenone (DPCP) immunotherapy in patients with alopecia areata (AA). OBJECTIVE: To identify predictors of response, or resistance, to treatment for AA through clinical observations and serum tests. METHODS: Eighty four AA patients were treated with DPCP. Serum cytokine levels were measured in 33 AA patients pre- and post-treatment, and in 18 healthy controls, using ELISA assays. RESULTS: Of patients, 56.1% responded to DPCP with satisfactory hair regrowth; the response rate was negatively correlated with hair loss extent. Before DPCP treatment, higher serum IFN-γ and IL-12 cytokine levels were observed in AA patients compared to healthy controls. Non-responders to DPCP had significantly elevated serum IL-4 pre-treatment (3.07 fold higher) and lower IL-12 levels compared with responders. After DPCP treatment, non-responders had persistently high IL-4, increased IL-12, negligible decrease in IFN-γ and decreased IL-10. Post-treatment DPCP responders exhibited significantly decreased IFN-γ and IL-12, and increased IL-4 and IL-10. Development of adverse side-effects was significantly associated with higher pre-treatment serum IgE levels. LIMITATIONS: A small number of subjects were evaluated. CONCLUSIONS: Potentially, elevated pre-treatment serum levels of IL-4 and IL-12 can be used as unfavorable and favorable predictors of DPCP therapeutic effect, respectively. In addition, pre-treatment elevated serum total IgE may predict increased risk for severe adverse side-effects to DPCP application. Whether serum cytokine expression levels can be used as predictors of response to other forms of treatment is unknown, but it may warrant investigation in the development of personalized treatments for AA.

Elevated serum tumour necrosis factor-like weak inducer of apoptosis in alopecia areata: a possible marker of disease severity.

BACKGROUND: Alopecia areata (AA) is, an organ-specific autoimmune disease, characterized by an aberrant expression of cytokines of the T helper 1 type. Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifactorial cytokine that exerts a role in the pathogenesis of inflammatory and autoimmune diseases, especially in cutaneous diseases. AIM: To estimate the serum level of TWEAK in AA and to correlate it with different parameters. METHODS: This case-control study enrolled 40 patients with AA and 50 clinically healthy volunteers matched for age and sex. A blood sample (5 mL) was extracted from each participant for analysis of serum TWEAK levels by ELISA. RESULTS: Levels of TWEAK were significantly higher in patients with AA (mean ± SD 213.7 ± 59.2 pg/mL, range 109.1-341.6 pg/mL) than in controls (95.97 ± 13.28 pg/mL, range 80.1-152.3 pg/mL) (P < 0.001). A significant positive correlation was found between serum TWEAK level and the Severity of Alopecia Tool (SALT) score (r = 0.56, P < 0.001). CONCLUSION: To our knowledge, this study highlights for the first time a possible link between higher serum TWEAK level and AA. Serum TWEAK level appears to reflect AA disease severity.

Ginger (Zingiber officinale (L.) Rosc) improves oxidative stress and trace elements status in patients with alopecia areata.

BACKGROUND: Alopecia areata (AA) involves oxidative reactions in the hair follicle. Its treatment is difficult due to both the unknown etiology and the adverse drug effects. Aims: This study aimed to evaluate the effects of orally administered ginger powder on the oxidative stress markers of the plasma and blood cells in Iraqi patients with AA. SUBJECTS AND METHODS: Twenty patients (9 females and 11 males), with a mean age of 26.0 ± 8.0 years, with different lesions of stable alopecia areata localized on the scalp, were enrolled in this pilot study. Exclusion criteria include the use of any medication that may influence the course of the disease. All patients were treated with 500 mg of ginger powder once daily for 60zz days. Blood samples were obtained at zero time, day-30 and day-60 and utilized for the evaluation of the erythrocytes and lymphocytes contents of reduced glutathione (GSH), malondialdehyde (MDA) and total antioxidant status (TAS), in addition to the assessment of serum zinc (Zn) and copper (Cu) levels. The results are compared with those of 20 healthy subjects served as a control group. RESULTS: Treatment of the AA patients with ginger significantly improves the antioxidant/oxidant balance of the erythrocytes and lymphocytes, which is known to be impaired in the patient group as compared with healthy subjects. The ginger powder also elevates the serum concentration of zinc up to that reported in controls and associated with normalizing serum copper levels at the end of the treatment period. CONCLUSION: Consumption of ginger as a supplement by the patients with AA could improve the oxidant/antioxidant balance of the erythrocytes and lymphocytes and restoring the normal level of serum zinc.

Identification of blood microRNA alterations in patients with severe active alopecia areata.

BACKGROUND: Alopecia areata (AA) is a common inflammatory disease characterized by cellular infiltration of T cells targeting the anagen-stage hair follicle. Lack of efficacious treatment for AA may be due to little knowledge about its exact cellular mechanism. Studies have demonstrated that microRNAs (miRNAs) play an important role in the regulation of inflammatory skin diseases such as atopic dermatitis and psoriasis. However, little is known about the role of miRNAs in AA. OBJECTIVE: The present study aimed to explore the blood miRNAs alterations in patients with severe active AA. METHODS: We constructed a bipartite miRNA-messenger RNA (mRNA) regulatory network by the validated miRNA-mRNA relationships. Subsequently, the miRNA-miRNA synergistic network was formed in consideration of the Gene Ontology function enrichment of coregulated target genes. Lastly, the functional network was identified by the ingenuity pathway analysis. RESULTS: By using an Agilent microarray that covers 2549 human miRNAs, we identified 36 significantly differentially expressed miRNAs in severe active AA patients. miRNA target gene prediction and functional annotation analysis showed significant enrichment in several pathways including the ribosome, cancer, cell cycle, insulin signaling, transforming growth factor-ßsignaling, and p53 signaling pathways. Analysis of the three kinds of network showed that miR-185-5p, miR-125b-5p, and miR-186-5p might play important and synergistic roles in the active phase of AA. According to the receiver operating characteristic curve analysis, several miRNAs were selected for the quantitative real-time polymerase chain reaction validation. Among the miRNAs, miR-210 and miR-1246 had high prediction with high accuracy. CONCLUSION: Blood dysregulated miRNAs are potentially associated with the severe active AA. These miRNAs could function synergistically and might be promising targets for the development of novel treatments for AA in the future.

Differential expression patterns of specific long noncoding RNAs and competing endogenous RNA network in alopecia areata.

BACKGROUND: Long noncoding RNAs (lncRNAs) regulate gene expression by acting with microRNAs (miRNAs) and indirectly interact with messenger RNA (mRNAs). However, the roles of specific lncRNA and its related competing endogenous RNAs (ceRNA) network in alopecia areata (AA) are not fully understood. METHODS: The blood lncRNA profiles were obtained by microarray from 10 samples, including five alopecia areata samples and five normal samples. Based on bioinformatics generated from miRcode, starBase, and miRTarBase, we constructed an lncRNA-miRNA-mRNA network (ceRNA network) in alopecia areata. RESULTS: We found 154 differentially expressed lncRNAs and 46 differentially expressed genes (DEGs). The functional enrichment indicated that the DEGs mainly regulated the pathways of focal adhesion, Mucin type O-glycan biosynthesis, and so on. The differentially expressed lncRNA (DElncRNA) involved in the pathway of thyronamine and iodothyronamine metabolism and so on. Through integrated lncRNA-mRNA and miRNA-mRNA pairs, the ceRNA network was constructed, thereafter, six ceRNA subnetworks were identified and subnetwork 1 were found to be significantly associated with the occurrence of alopecia areata. CONCLUSION: Our results showed blood lncRNA expression patterns and a complex ceRNA network in alopecia areata. However, futher studies on blood and tissue verification of these lncRNAs and relative pathways are needed.

Examination of Fluconazole-Induced Alopecia in an Animal Model and Human Cohort.

Fluconazole-induced alopecia is a significant problem for patients receiving long-term therapy. We evaluated the hair cycle changes of fluconazole in a rat model and investigated potential molecular mechanisms. Plasma and tissue levels of retinoic acid were not found to be causal. Human patients with alopecia attributed to fluconazole also underwent detailed assessment and in both our murine model and human cohort fluconazole induced telogen effluvium. Future work further examining the mechanism of fluconazole-induced alopecia should be undertaken.

Screening of thyroid function and autoantibodies in patients with alopecia areata: A systematic review and meta-analysis.

BACKGROUND: Several studies have reported associations between alopecia areata and diverse thyroid diseases. OBJECTIVE: To investigate the odds ratio and prevalence rate of thyroid dysfunction and autoimmune thyroid diseases in patients with alopecia areata. METHODS: A systematic review of the studies published before March 20, 2018, was performed by using the MEDLINE, Embase, Web of Science, and Cochrane Library databases. The clinical and laboratory findings associated with thyroid dysfunction and autoimmunity were extracted for quantitative analysis. RESULTS: A total of 50 studies were analyzed. Patients with alopecia areata had higher odds of abnormal findings on thyroid function tests, thyroid dysfunction, positive thyroid autoantibodies, and autoimmune thyroid diseases. Moreover, their prevalence rate was much higher than that in the general population. LIMITATIONS: The heterogeneity in baseline characteristics and outcome reporting across the studies. CONCLUSION: Current evidence suggests that thyroid dysfunction and autoimmune thyroid diseases are more prevalent in patients with alopecia areata. Clinicians may be encouraged to screen for the associated signs and symptoms to achieve better outcomes.

Evaluation of Serum Paraoxonase, Arylesterase, Prolidase Activities and Oxidative Stress in Patients with Alopecia Areata.

BACKGROUND: Alopecia areata (AA) is a disease characterized by the hair loss sharply limited in any part of the body, especially on the scalp, in circular or oval areas. The purpose of this study is to search the serum paraoxonase 1 (PON1), arylesterase and oxidative status with serum prolidase activities in people with AA. METHODS: The study included 60 AA and 50 healthy control subjects. In both groups, serum PON1, prolidase, arylesterase activities, total oxidative status (TOS) and total antioxidant capacity (TAS) levels and oxidative stress index (OSI) were calculated. RESULTS: TOS, OSI levels and prolidase activity in patients with AA were found to be significantly higher compared to the control group (p = 0.02, p = 0.004, p < 0.001, respectively), whereas PON1 and arylesterase activities were significantly lower (p < 0.001, p = 0.005, respectively). There was no difference in serum TAS levels between the two groups. CONCLUSION: This comprehensive work shows that the role of oxidative stress is very important in the pathogenesis of AA. In this study, we believe that we clarified the pathogenesis of oxidative stress for AA patients by investigating the TAS, TOS, OSI levels, PON1, arylesterase and prolidase enzyme activity parameters.

Ischemic modified albumin as a new biomarker in predicting oxidative stress in alopecia areata

Background/aim: Results show that oxidative stress is a pathophysiologic factor for alopecia areata (AA); however, the markers used can be confounding. Thus, we aimed to investigate the role of oxidative stress in the pathogenesis of AA through an evaluation of ischemia-modified albumin (IMA); other markers of the oxidant/antioxidant system, such as SOD, CAT, GSH-ST, and MDA; and contributing clinical risk factors. Materials and methods: The usefulness of IMA as a new marker for oxidative stress was compared with that of other markers and evaluated in patients with AA. Results: The mean serum level of IMA was of higher statistical significance in AA patients than in the control group (IMA: 0.57 ± 0.01 vs. 0.52 ± 0.02 ΔABSU, P < 0.0001). IMA (P = 0.03, OR = 25.8, 95% CI = 1.4­482.7) was found to be an independent predictor of oxidative stress in patients with AA. Increased severity of AA was found as an independent risk factor for IMA. Conclusion: Long-lasting disease, male sex, >1 site of involvement of disease, and increased severity of disease were correlated with increased oxidation. Presence of AA, male sex, and severe disease were determined to be independent risk factors for antioxidant and oxidant systems. IMA has great potential as a biomarker of oxidative stress in AA when compared to other studied biomarkers.

Alopecia areata is characterized by expansion of circulating Th2/Tc2/Th22, within the skin-homing and systemic T-cell populations.

BACKGROUND: Characterizing blood profile of alopecia areata (AA) is important not only for treatment advancements, but also for possibly identifying peripheral biomarkers that will eliminate the need for scalp biopsies. We aimed to compare frequencies of skin homing (CLA+ ) vs systemic (CLA- ) "polar" CD4+ and CD8+ and activated T-cell subsets in AA vs atopic dermatitis (AD) and control blood. METHODS: Flow cytometry was used to measure IFN-γ, IL-13, IL-9, IL-17, and IL-22 cytokines in CD4+ and CD8+ T cells. Inducible co-stimulator molecule (ICOS) and HLA-DR were used to define mid- and long-term T-cell activation. We compared peripheral blood from 32 moderate-to-severe AA adults with 43 moderate-to-severe AD patients and 30 age-matched controls. RESULTS: AA patients had increased CLA+ /CLA- Th2 (P < .007), CLA+ Tc2 (P = .04), and CLA+ Th22 (P < .05) frequencies than controls. Except of CLA- Tc1 cells (P = .03), IFN-γ levels were mostly similar between AA, AD, and controls (P > .1). ICOS and HLA-DR activation were significantly higher in AA than controls (P < .05). T regulatory cells were significantly decreased in AA patients than controls (P < .01) and were correlated with activated CD8+ T cells and with multiple cytokine subsets (P < .05). While Th2 and Tc2 clustered with disease severity, IFN-γ producing cells were linked with AA duration. CONCLUSIONS: Alopecia areata is accompanied by Th2/Tc2 activation in skin-homing and systemic subsets, correlating with disease severity, while IFN-γ is linked to disease chronicity. These data hint for a possible role of diverse T-cells subsets in disease pathogenesis and emphasize the systemic nature of AA supporting the need for systemic therapeutic strategies in severe patients.

Alopecia Areata is Associated with Increased Expression of Heart Disease Biomarker Cardiac Troponin I.

The development of androgenetic alopecia is associated with a risk of developing cardiovascular diseases, but the association of alopecia areata with cardiovascular diseases in humans is largely unexplored. We measured the plasma level of two common cardiovascular disease markers, cardiac troponin I and C-reactive protein, in alopecia areata and androgenetic alopecia affected subjects. Also, we investigated the possible presence of pro-apoptotic factors in the plasma of hair loss subjects. The mean plasma cardiac troponin I level was highest in alopecia areata subjects, moderately higher in androgenetic alopecia subjects, and lowest in subjects without hair loss (p <0.05). Alopecia areata subjects not receiving treatments had highest levels of cTnI (p <0.05). Alopecia areata plasma samples with high cardiac troponin I levels also induced significantly higher rates of cardiomyocyte apoptosis in cell culture assays. The results suggest the potential for increased heart remodelling. Close monitoring of cardiovascular health in alopecia areata subjects, as well as subsets of androgenetic alopecia patients, may be appropriate.

Increased prevalence of vitamin D deficiency in patients with alopecia areata: a systematic review and meta-analysis.

BACKGROUND: Alopecia areata (AA) is a hair follicle-specific autoimmune disorder. Vitamin D deficiency has been associated with various autoimmune disorders for its immunomodulatory effects. However, in previous studies, there had been inconsistent association found between AA and vitamin D deficiency. OBJECTIVE: To demonstrate the differences of the mean serum 25-hydroxyvitamin D level and prevalence of vitamin D deficiency between AA patients and non-AA population. METHODS: A systematic review and meta-analysis of observational studies on AA and serum vitamin D levels and/or prevalence of vitamin D deficiency was performed searching MEDLINE, Cochrane, Web of Science and Google Scholar databases. RESULTS: In all, 14 studies including a total of 1255 AA subjects and 784 non-AA control were analysed. The mean serum 25-hydroxyvitamin D level was significantly lower in AA subjects (-8.52 ng/dL; 95% confidential interval; -5.50 to -11.53). The AA subjects had higher odds of vitamin D deficiency (odds ratio of 3.89; 2.02 to 7.49, mean prevalence of 73.8%; 59.1 to 84.6%). However, it was difficult to find clear correlation between serum 25-hydroxyvitamin D level and extent of hair loss in AA subjects. CONCLUSION: The AA subjects had lower serum 25-hydroxyvitamin D level, and vitamin D deficiency was highly prevalent compared to non-AA controls. Hence, vitamin D deficiency should be assessed in AA patients. Furthermore, nutritional supplementation of vitamin D or topical vitamin D analogues can be considered for AA patients with vitamin D deficiency. The limitation of this study is the highly heterogeneity of the included studies.

[ADAPTIVE REGULATORY MECHANISMS OF ALOPECIA AREATA].

Failure of adaptive mechanisms leads to structural and functional damage at all levels and of neuroendocrinal and immune systems, which are pathogenetic basis of development of autoimmune diseases, in particular. The objective of this work was to assess the condition of adaptive hormones, such as cortisol and insulin, coefficient of stress of adaptive potential "K" and also dermatologic life quality index (DLQI) of the diseased with alopecia areata (AA). 48 patients with different forms of AA aged between 18 and 52 were examined. Correlation analysis identified positive correlation between DLQI and early age of patients, severe stage and hair loss for the period of over 12 months (p<0.01). Two types of reactions were identified - increase and decrease of content of cortisol and insulin in blood depending on the activity, severity stage and length of AA. The diseased with signs of progression of the disease, severe stage and duration of up to 3 years AA experienced increase of the coefficient "K" (p<0.05) indicates increase of tension of adaptive potential of the organism. Decrease of the coefficient "K" (p<0.05) during chronisation and duration of the disease of over 3 years indicates depletion of adaptive mechanisms of organism with possible failure of regulatory processes. Identified disorders demonstrate existence of maladaptive processes in the diseased with FF and may be considers as potential therapeutic targets.