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Stem Cell Research & Therapy Jun 2024The aim of this study is to systematically review randomized controlled clinical trials (RCTs) studying various types of regenerative medicine methods (such as...
AIMS AND OBJECTIVES
The aim of this study is to systematically review randomized controlled clinical trials (RCTs) studying various types of regenerative medicine methods (such as platelet-rich plasma, stromal vascular fraction, cell therapy, conditioned media, etc.) in treating specific dermatologic diseases. Rejuvenation, scarring, wound healing, and other secondary conditions of skin damage were not investigated in this study.
METHOD
Major databases, including PubMed, Scopus, and Web of Science, were meticulously searched for RCTs up to January 2024, focusing on regenerative medicine interventions for specific dermatologic disorders (such as androgenetic alopecia, vitiligo, alopecia areata, etc.). Key data extracted encompassed participant characteristics and sample sizes, types of regenerative therapy, treatment efficacy, and adverse events.
RESULTS
In this systematic review, 64 studies involving a total of 2888 patients were examined. Women constituted 44.8% of the study population, while men made up 55.2% of the participants, with an average age of 27.64 years. The most frequently studied skin diseases were androgenetic alopecia (AGA) (45.3%) and vitiligo (31.2%). The most common regenerative methods investigated for these diseases were PRP and the transplantation of autologous epidermal melanocyte/keratinocyte cells, respectively. Studies reported up to 68.4% improvement in AGA and up to 71% improvement in vitiligo. Other diseases included in the review were alopecia areata, melasma, lichen sclerosus et atrophicus (LSA), inflammatory acne vulgaris, chronic telogen effluvium, erosive oral lichen planus, and dystrophic epidermolysis bullosa. Regenerative medicine was found to be an effective treatment option in all of these studies, along with other methods. The regenerative medicine techniques investigated in this study comprised the transplantation of autologous epidermal melanocyte/keratinocyte cells, isolated melanocyte transplantation, cell transplantation from hair follicle origins, melanocyte-keratinocyte suspension in PRP, conditioned media injection, a combination of PRP and basic fibroblast growth factor, intravenous injection of mesenchymal stem cells, concentrated growth factor, stromal vascular fraction (SVF), a combination of PRP and SVF, and preserving hair grafts in PRP.
CONCLUSION
Regenerative medicine holds promise as a treatment for specific dermatologic disorders. To validate our findings, it is recommended to conduct numerous clinical trials focusing on various skin conditions. In our study, we did not explore secondary skin lesions like scars or ulcers. Therefore, assessing the effectiveness of this treatment method for addressing these conditions would necessitate a separate study.
Topics: Adult; Female; Humans; Male; Platelet-Rich Plasma; Randomized Controlled Trials as Topic; Regenerative Medicine; Skin Diseases
PubMed: 38886861
DOI: 10.1186/s13287-024-03800-6 -
Frontiers in Immunology 2024The objective of this study is to evaluate the risk of secondary autoimmune diseases in multiple sclerosis (MS) patients treated with alemtuzumab (ALZ) through a... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
The objective of this study is to evaluate the risk of secondary autoimmune diseases in multiple sclerosis (MS) patients treated with alemtuzumab (ALZ) through a meta-analysis.
METHODS
PubMed, Web of Science, OVID, EMBASE, and Cochrane central register of controlled trials were searched. Information and data were screened and extracted by 2 researchers. The obtained data were analyzed using the R software meta package. Quality assessment was conducted using the Newcastle-Ottawa Scale (NOS). The causes of heterogeneity were analyzed using subgroup analysis and sensitivity analysis. Publication bias was evaluated using funnel plots and Egger's test.
RESULTS
The search retrieved a total of 3530 papers from the databases. After screening, a total of 37 studies were included in the meta-analysis. The analysis results indicate that the pooled incidence rate of overall secondary autoimmune events (SAEs) in the included studies was 0.2824 [0.2348, 0.3300] (I²=94%, p<0.01). The overall incidence of autoimmune thyroid events (ATE) was 0.2257 [0.1810, 0.2703] (I²=94%, p<0.01). Among them, the rate of serious autoimmune thyroid events (SATE) was 0.0541 [0.0396, 0.0687] (I²=0%, p=0.44). The incidence rates of different thyroid events were as follows: Graves' disease (GD), 0.2266 [0.1632, 0.2900] (I²=83%, p<0.01); Hashimoto thyroiditis (HT), 0.0844 [0.0000, 0.2262] (I²=81%, p=0.02); Hashimoto thyroiditis with hypothyroidism (HTwH), 0.0499 [0.0058, 0.0940] (I²=37%, p=0.21); fluctuating thyroid dysfunction (FTD), 0.0219 [0.0015, 0.0424] (I²=0%, p=0.40); transient thyroiditis (TT), 0.0178 [0.0062, 0.0295] (I²=0%, p=0.94). The overall incidence of hematological events was 0.0431 [0.0274, 0.0621] (I²=70%, p<0.01). The incidence rates from high to low were as follows: lymphopenia, 0.0367 [0.0000, 0.0776] (I²=81%, p=0.02); Idiopathic thrombocytopenic purpura (ITP), 0.0258 [0.0199, 0.0323] (I²=25%, p=0.15); Hemolytic anemia (HA), 0.0177 [0.0081, 0.0391] (I²=29%, p=0.23); pancytopenia, 0.0136 [0.0000, 0.0314] (I²=0%, p=0.67); Neutropenia, 0.0081 [0.0000, 0.0183] (I²=0%, p=0.42). After excluding thyroid and hematological diseases, the combined incidence of other related SAEs was 0.0061 [0.0014, 0.0109] (I²=50%, p=0.02). The incidence of each disease ranked from highest to lowest as: skin psoriasis (SP), 0.0430 [0.0000, 0.0929] (I²=0%, p=0.57); alopecia areata (AA), 0.0159 [0.0024, 0.0372] (I²=19%, p=0.29); vitiligo, 0.0134 [0.0044, 0.0223] (I²=0%, p=0.81); inflammatory atrichia (IA), 0.0103 [0.0000, 0.0232] (I²=0%, p=0.43); chronic urticaria (CU), 0.0107 [0.0000, 0.0233] (I²=0%, p=0.60); and nephropathy, 0.0051 [0.0000, 0.0263] (I²=62%, p=0.02).
CONCLUSION
The occurrence of secondary autoimmune diseases in patients with MS treated with ALZ is noteworthy, particularly in the form of thyroid events and hematological events. Clinicians should monitor the overall condition of patients promptly for early management and avoid delayed diagnosis and treatment.
SYSTEMATIC REVIEW REGISTRATION
inplasy.com/inplasy-2024-4-0048/, identifier INPLASY202440048.
Topics: Humans; Alemtuzumab; Multiple Sclerosis; Autoimmune Diseases; Incidence; Hashimoto Disease
PubMed: 38690271
DOI: 10.3389/fimmu.2024.1343971 -
Frontiers in Pharmacology 2024We performed a Bayesian network meta-analysis to indirectly compare the relative efficacy and safety of the latest JAK inhibitors for moderate-to-severe alopecia areata...
We performed a Bayesian network meta-analysis to indirectly compare the relative efficacy and safety of the latest JAK inhibitors for moderate-to-severe alopecia areata (AA). 13 trials totaling 3,613 patients were included. Two low-dose groups of oral formulations (ritlecitinib 10mg and ivarmacitinib 2mg) and two topical formulations (delgocitinib ointment and ruxolitinib cream) appeared to be relatively ineffective against moderate-to-severe AA. Ranking analysis suggested that brepocitinib 30mg has the best relative effect in reducing the SALT score (sucra = 0.9831), and demonstrated comparable efficacy to deuruxolitinib 12mg (sucra = 0.9245), followed by deuruxolitinib 8mg (sucra = 0.7736). Regarding the SALT response, brepocitinib 30mg ranked highest (sucra = 0.9567), followed by ritlecitinib 50mg (sucra = 0.8689) and deuruxolitinib 12mg (sucra = 0.7690). For achieving the SALT response, deuruxolitinib 12mg had the highest probability (sucra = 0.9761), followed by deuruxolitinib 8mg (sucra = 0.8678) and brepocitinib 30mg (sucra = 0.8448). Deuruxolitinib 12mg might be the most effective therapy for patients with severe AA (sucra = 0.9395), followed by ritlecitinib 50mg (sucra = 0.8753) and deuruxolitinib 8mg (sucra = 0.8070). Deuruxolitinib 12mg/8mg demonstrated notable efficacy for moderate-to-severe AA, and is expected to be a new treatment option for AA. It was worth noting that deuruxolitinib exhibit a greater likelihood of causing adverse events in comparison to other JAK inhibitors. Ritlecitinib 50mg seemed to exhibit fewer adverse effects in the high-dose groups of oral JAK inhibitors and might be an optimal choice to balance safety and efficacy. The majority of JAK inhibitors exhibited acceptable short-term safety profiles. To enhance the applicability and accuracy of our research, further head-to-head trials with longer follow-up periods are needed. identifier [CRD42022368012].
PubMed: 38659584
DOI: 10.3389/fphar.2024.1372810 -
Medicine Feb 2024Alopecia areata (AA) is an autoimmune disease which results in non-scarring hair loss on the scalp or any surface with hair. Several genetic polymorphisms of the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alopecia areata (AA) is an autoimmune disease which results in non-scarring hair loss on the scalp or any surface with hair. Several genetic polymorphisms of the interleukin genes have been linked with this disease but the results are inconsistent. This systematic review and meta-analysis were done to find the association between rs3118470, rs2275913, rs3212227, and rs10889677 of the IL2RA, IL17A, IL12B, and IL23R genes, respectively, of the interleukin family with alopecia areata.
METHODS
A comprehensive search for relevant research articles was conducted in Pubmed, Google Scholar, and Embase databases. Our search yielded 8 relevant articles with 1940 cases and 1788 controls. The odds ratio with 95% confidence intervals was calculated using fixed effect and random effect models. Heterogeneity was determined using the Q-test and I2 test. Publication bias was determined and funnel plots were used to adjust the odds ratio.
RESULTS
We found a significant risk effect for rs3118470 of the IL2RA gene with alopecia areata in the dominant model (CC + CT vs TT; OR = 1.54, 95% confidence interval = 1.05-2.26, P < .05, I2 = 69.03%) and homozygous model (CC vs TT; OR = 2.00, 95% confidence interval = 1.07-3.71, P < .05, I2 = 72.84%). For the other single nucleotide polymorphisms, we could not find any statistically significant association with the disease.
CONCLUSION
Our analysis showed that mutation of rs3118470 of IL2RA gene possesses a significant risk effect for alopecia areata. Future studies with larger sample sizes and ethnic backgrounds are warranted to confirm our findings.
Topics: Humans; Alopecia Areata; Genetic Predisposition to Disease; Interleukins; Polymorphism, Single Nucleotide
PubMed: 38394507
DOI: 10.1097/MD.0000000000037300 -
Annals of Dermatology Dec 2023
PubMed: 38086361
DOI: 10.5021/ad.22.095 -
Dermatology and Therapy Dec 2023Treatments for alopecia areata (AA) have traditionally been prescribed off-label, and there has been no universal agreement on how to best manage the condition.... (Review)
Review
Treatments for alopecia areata (AA) have traditionally been prescribed off-label, and there has been no universal agreement on how to best manage the condition. Baricitinib is the first oral selective Janus kinase (JAK) inhibitor approved for the treatment of adults with severe AA. As a better understanding of the evidence supporting the management of AA in clinical practice is needed, we conducted a systematic literature review and subsequent narrative review to describe available evidence pertaining to the efficacy and tolerability of treatments currently recommended for adults with moderate-to-severe forms of AA. From 2557 identified records, a total of 53 records were retained for data extraction: 9 reported data from 7 randomized controlled trials (RCTs) versus placebo, and 44 reported data from unique RCTs with no placebo arm, non-randomized trials, or observational studies. Across drug classes, data were reported heterogeneously, with little consistency of data collection or clinical endpoints used. The most robust evidence was for the JAK inhibitor class, in particular the JAK1/JAK2 inhibitor baricitinib. Five RCTs (three for baricitinib) demonstrated a consistent benefit of JAK inhibitor therapy over placebo across various clinical outcomes in adult patients with at least 50% scalp hair loss. Overall, hair regrowth varied widely for the other drug classes and was generally low for patients with moderate-to-severe AA. Relapses were commonly observed during treatment and upon discontinuation. Adverse effects were generally consistent with the known safety profile of each intervention. The heterogeneity observed prevented the conduct of a network meta-analysis or an indirect comparison of different treatments. We found that the current management of patients with moderate-to-severe AA often relies on the use of treatments that have not been well evaluated in clinical trials. The most robust evidence identified supported the use of baricitinib, and other oral JAK inhibitors, in patients with severe AA.
PubMed: 37833617
DOI: 10.1007/s13555-023-01044-5 -
JAMA Network Open Jun 2023Alopecia areata (AA) is a common chronic tissue-specific autoimmune disease. Several studies have reported outcomes of Janus kinase (JAK) inhibitors for treating AA, but... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Alopecia areata (AA) is a common chronic tissue-specific autoimmune disease. Several studies have reported outcomes of Janus kinase (JAK) inhibitors for treating AA, but limited evidence has emerged.
OBJECTIVE
To evaluate the effectiveness and safety associated with JAK inhibitors for AA.
DATA SOURCES
MEDLINE, Embase, and CENTRAL (Cochrane Central Register of Controlled Trials) were searched from inception until August 2022.
STUDY SELECTION
Only randomized clinical trials (RCTs) were included. Pairs of reviewers independently and in duplicate selected the studies.
DATA EXTRACTION AND SYNTHESIS
Hartung-Knapp-Sidik-Jonkman random-effects models were used for meta-analysis. Certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. This study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.
MAIN OUTCOMES AND MEASURES
The primary outcomes of interest were (1) proportion of patients who achieved 30%, 50%, and 90% improvement in Severity of Alopecia Tool (SALT) score from baseline, (2) change from baseline SALT score, and (3) treatment-related adverse event (AE).
RESULTS
Seven RCTs with 1710 patients (1083 females [63.3%]; mean [SD] age range, 36.3 [10.4] to 69.7 [16.2] years) were eligible and included in the study. JAK inhibitors were associated with more patients achieving 50% improvement (odds ratio [OR], 5.28 [95% CI, 1.69-16.46]; GRADE assessment: low certainty) and 90% improvement (OR, 8.15 [95% CI, 4.42-15.03]; GRADE assessment: low certainty) in SALT score from baseline compared with placebo. JAK inhibitors were associated with more lowered SALT scores from the baseline compared with placebo (mean difference [MD], -34.52 [95% CI, -37.80 to -31.24]; GRADE assessment: moderate certainty), and JAK inhibitors were not associated with more treatment-related AEs (relative risk [RR], 1.25 [95% CI, 1.00-1.57]; GRADE assessment: high certainty) compared with placebo. High certainty of evidence showed that JAK inhibitors may not be associated with more severe AEs compared with placebo (RR, 0.77; 95% CI, 0.41-1.43). The subgroup analysis showed that oral JAK inhibitors were more efficient than placebo (change from baseline SALT scores: MD, -36.80; 95% CI, -39.57 to -34.02), and no difference was found between external JAK inhibitors and placebo (change from baseline SALT scores: MD, -0.40; 95% CI, -11.30 to 10.50).
CONCLUSIONS AND RELEVANCE
Results of this systematic review and meta-analysis suggest that JAK inhibitors, compared with placebo, were associated with hair regrowth and that the outcome of oral JAK inhibitors was better than the external route of administration. Although the safety and tolerability of JAK inhibitors were acceptable, longer RCTs are needed to further assess the effectiveness and safety of these treatments for AA.
Topics: Female; Humans; Adult; Janus Kinase Inhibitors; Alopecia Areata; Chronic Disease; Network Meta-Analysis
PubMed: 37368402
DOI: 10.1001/jamanetworkopen.2023.20351 -
Skin Research and Technology : Official... Jun 2023The incidence of alopecia areata (AA) has increased over the last few decades. Trichoscopy is a noninvasive procedure performed in dermatology clinics and is a helpful... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The incidence of alopecia areata (AA) has increased over the last few decades. Trichoscopy is a noninvasive procedure performed in dermatology clinics and is a helpful tool in determining the correct diagnosis of hair loss presentations.
OBJECTIVE
Through mapping the researches that have been done to represent the spectrum of trichoscopic findings in AA and to identify the most characteristic patterns.
METHODS
Thirty-nine studies were eligible for the quantitative analysis. Meta-analysis and subgroup analysis were performed.
RESULTS
Thirty-nine studies (29 cross-sectional, five retrospective, two descriptive, one case series, one observational, and one cohort) with a total of 3204 patients were included. About 66.7% of the studies were from Asia, 25.6% from Europe, and 7.7% from Africa. The most characteristic trichoscopic findings of AA were as follows; yellow dots, black dots, broken hairs, short vellus hairs, and tapering hairs.
CONCLUSION
There is no single pathognomonic diagnostic trichoscopic finding in AA rather than a constellation of characteristic findings. The five most characteristic trichoscopic findings in AA are: yellow dots, black dots, broken hairs, short vellus hairs, and tapering hairs. Yellow dots and short vellus hairs considered the most sensitive clues for AA, while black dots and tapering hairs are the most specific ones. Furthermore, trichoscopy is a useful tool that allows monitoring of response during the treatment of AA. Treatment responded cases will show an increase in short vellus hairs, but loss of tapering hairs, broken hairs, and black dots, while yellow dots are the least responsive to the treatment.
Topics: Alopecia Areata; Dermoscopy; Vitamin D Deficiency; Humans
PubMed: 37357664
DOI: 10.1111/srt.13378 -
Frontiers in Immunology 2023JAK inhibitors treat various autoimmune diseases, but an updated systematic review in treating alopecia areata is currently lacking. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
JAK inhibitors treat various autoimmune diseases, but an updated systematic review in treating alopecia areata is currently lacking.
OBJECTIVE
Evaluate the specific efficacy and safety of JAK inhibitors in alopecia areata by systematic review and meta-analysis.
METHODS
Eligible studies in PubMed, Embase, Web of Science, and Clinical Trials up to May 30, 2022, were searched. We enrolled in randomized controlled trials and observational studies of applying JAK inhibitors in alopecia areata.
RESULTS
6 randomized controlled trials with 1455 patients exhibited SALT (odd ratio [OR], 5.08; 95% confidence interval [CI], 3.49-7.38), SALT (OR, 7.40; 95% CI, 4.34-12.67) and change in SALT score (weighted mean difference [WSD], 5.55; 95% CI, 2.60-8.50) compared to the placebo. The proportion of 26 observational studies with 563 patients of SALT was 0.71(95% CI, 0.65-0.78), SALT was 0.54(95% CI 0.46-0.63), SALT was 0.33(95% CI, 0.24-0.42), and SALT score (WSD, -2.18; 95% CI, -3.12 to -1.23) compared with baseline. Any adverse effects occurred in 921 of 1508 patients; a total of 30 patients discontinued the trial owing to adverse reactions.
LIMITATIONS
Few randomized controlled trials met the inclusion criteria and insufficiency of eligible data.
CONCLUSION
JAK inhibitors are effective in alopecia areata, although associated with an increased risk.
Topics: Humans; Janus Kinase Inhibitors; Alopecia Areata; Autoimmune Diseases; Odds Ratio
PubMed: 37334349
DOI: 10.3389/fimmu.2023.1195858 -
Skin Health and Disease Jun 2023For many years, clinical observations have suggested that there is an intrinsic connection between psychological state and skin diseases. Stress responses are typically...
For many years, clinical observations have suggested that there is an intrinsic connection between psychological state and skin diseases. Stress responses are typically mediated by several hormones, which are modulated the hypothalamic-pituitary-adrenal axis. This typical stress response is not only one theory for psychiatry disorder pathophysiology, but it also modifies hair growth by altering the skin's inflammatory environment. Given that different forms of hair loss, such as androgenetic alopecia, alopecia areata, or telogen effluvium, and hair follicle cycling can be altered by immune cells within the follicle milieu, we hypothesized that specific forms of hair loss are correlated to psychiatric illnesses. To address this, we conducted a systematic review by searches in April and May 2021 through Ovid MEDLINE and PUBMED (ranging from 1951 to the present day), identifying 179 reports. A further 24 reports were identified through website and citation searches giving a total of 201 reports. After applying exclusion criteria, 21 papers were reviewed, and 17 were included for data analysis. It is undeniable that hair loss greatly affects Health-related Quality of Life (HrQol) and it is heavily associated with major depressive disorder and anxiety. The correlation between hair loss and mental health disorders was significant, however, due to the low number of publications with quantitative data we were not able to identify correlations between each hair loss type with each psychiatric disorder. Further studies to better connect specific hair loss diseases to specific disorders are therefore critical in bettering the way both psychiatric disease, and hair loss, are managed.
PubMed: 37275427
DOI: 10.1002/ski2.194