Journal Summaries provide a quick review of recent journal articles with current or near-term clinical significance. Here, catch up on key research on vitiligo from the past year.
Vitiligo is a pigmentary disorder of the skin that is characterized by defined, depigmented macules and patches; it affects 1%-2% of the population. It is frequently associated with autoimmune disorders, particularly with thyroid abnormalities. Although the diagnosis of vitiligo generally is made on the basis of clinical findings, on rare occasions when the diagnosis is uncertain, biopsy may be needed to differentiate vitiligo from other pigmentation disorders. Treatment consists of both surgical and nonsurgical options. Research into the treatment and pathophysiology of vitiligo is ongoing.
Li M, Xiang L, Li Y. Efficacy and safety of compound glycyrrhizin in the patients with vitiligo: a systematic review and meta-analysis. Expert Rev Clin Pharmacol. 2023;16:601-611. Source
Compound glycyrrhizin (CG) is used widely in China to treat vitiligo. A meta-analysis was conducted to reevaluate the efficacy and safety of CG for its treatment. Eight literature databases were searched from inceptions to a cut-off date of December 31, 2022, to find randomized controlled trials (RCTs) that compared CG plus conventional treatments with conventional treatments alone.
Inclusion criteria were (1) patients diagnosed with vitiligo on the basis of clinical features; (2) types of interventions and comparisons based on study criteria of CG plus conventional therapies vs conventional therapies alone; and (3) types of outcomes — the primary outcome was total efficacy rate, which was ≥ 50% repigmentation rate, and the secondary outcomes were cure rate (proportion of patients achieving 100% repigmentation of the lesion), serum cytokine levels, and blood ratio of CD4+/CD8+ T cells. Exclusion criteria were (1) studies that were not RCTs; (b) studies for which the full text was unavailable, (3) shorter treatment duration of CG of the conventional treatments; and (4) studies published in neither Chinese nor English.
A total of 17 single-center studies conducted in China were included, comprising 1492 patients. Of these, 768 were treated with CG plus conventional therapies and 724 received conventional treatment only. Patients ranged in age from 3 to 68 years.
Results showed that the efficacy of CG as an adjunctive therapy to conventional vitiligo treatment was superior to that of monotherapy with conventional treatments (relative risk [RR], 1.54; 95% CI, 1.40-1.69; P < .00001); cure rate (RR, 1.62; 95% CI, 1.32-1.99; P < .00001); the levels of serum interleukin (IL)-6, tumor necrosis factor alpha, IL-17, and transforming growth factor beta; and the ratio of CD4+/CD8+ T cells in blood.
No serious adverse events occurred in either treatment arm. The most common adverse events were erythema and skin discomfort such as pruritus, burning sensation, and pain, which occurred only in patients who received phototherapy and laser therapy.
Conclusion: When used as an add-on treatment, CG may be an effective therapy for vitiligo, with mild and tolerable side effects. Larger sample studies are needed to provide more detailed data regarding use of CG for treatment of vitiligo.
Hasan MS, Almohsen AM, Nasr MI, Rageh MA. Dermabrasion versus microneedling in transplantation of autologous noncultured melanocyte-keratinocyte cell suspension in patients with vitiligo. Dermatol Surg. 2023;49:494-502. Source
This randomized comparative study aimed to assess the efficacy of transplanting autologous melanocyte–keratinocyte suspension in patients with stable vitiligo and to compare site preparation using dermabrasion vs microneedling. The study was conducted from March 2020 to September 2022 and included 40 patients with 40 stable vitiligo lesions that were managed by suspension transplants of melanocytes.
Patients were excluded if they (1) were younger than 12 years; (2) received treatment within 2 months of the study; (3) had > 30% body surface area involved, mucosal lesions, vitiligo disease activity score > 0, and vitiligo signs of activity score grade 1-3; or (4) had a history of Koebnerization, a history of keloid or hypertrophic scar formation, allergy to anesthesia, bleeding issues, active infection, or skin cancer or were pregnant or lactating.
Patients were divided into group A, in which recipient sites were prepared with dermabrasion, and group B, in which sites were prepared with microneedling. Assessment was performed 3 months posttreatment and was based on the degree of repigmentation.
The mean surface area of the lesions in all patients decreased from 7.07 ± 6.3 cm2 before treatment to 3.6 ± 3.6 cm2 after treatment. This decrease was statistically significant (P = .049) in the dermabrasion group vs the microneedling group. With regard to improvement rates, 32.5% showed poor improvement, 17.5% showed fair improvement, 30% showed good improvement, and 20% showed excellent improvement. A statistically significant difference was found between the studied groups for improvement (P = .028). A satisfactory repigmentation rate was demonstrated in 50% of patients; there was a statistically significant increase in the proportion of satisfactory repigmentation in the dermabrasion group vs the microneedling group (P = .011). With regard to patient satisfaction with treatment results, 32.5% of patients were not satisfied, 15% were slightly satisfied, 15% were satisfied, and 37.5% were very satisfied. There was a significantly higher proportion of pain and discomfort in the dermabrasion group.
Conclusion: Autologous melanocyte transplantation is a safe and effective treatment method for stable vitiligo lesions that have been unresponsive to other treatment modalities. Dermabrasion produced better outcomes for site preparation compared with microneedling.
Speeckaert R, Belpaire A, Speeckaert MM, van Geel N. A meta-analysis of chemokines in vitiligo: recruiting immune cells towards melanocytes. Front Immunol. 2023;14:1112811. Source
Chemokines hold promise as potential biomarkers for patients with vitiligo. In this study, a meta-analysis was performed to compare chemokine expression in blood and skin samples from vitiligo patients vs those in healthy controls. In addition, the relationship between chemokine expression and disease activity was evaluated.
A systematic search was done in PubMed and EMBASE; all articles from inception to October 2022 were eligible. Only human studies investigating chemokine levels in the blood and/or skin of vitiligo patients were included. Abstracts were excluded, as were results comparing chemokine levels before and after treatment. A total of 21 articles were identified.
Results indicated that the most consistently elevated chemokines in the circulation across several studies were CXCL10 (n = 15), followed by CXCL9 (n = 11), CCL5 (n = 5), CXCL12 (n = 4), CXCL8 (n = 3), CXCL11 (n = 4), CCL2 (n = 2), CCL1 (n = 1), CXCL1 (n = 1), CCL3 (n = 1), CCL4 (n = 1), CXCL13 (n = 1), CXCL16 (n = 2), CCL17 (n = 1), CCL20 (n = 2), CCL22 (n = 1), CCL27 (n = 1), and CCL28 (n = 1). In 10 studies, chemokine levels in the skin were measured for CXCL10 (n = 9), CXCL9 (n = 7), CXCL11 (n = 4), CCL5 (n = 2), CCL20 (n = 2), CXCL8 (n = 1), CCL17 (n = 1), and CCL22 (n = 1).
Conclusion: A large number of studies have confirmed a specific chemokine profile associated with vitiligo. Prominent CXCR3 signaling is due to increased expression of CXCL9, CXCL10, CXCL11, and CXCL4. Of these, CXCL10 seems to display the most prominent change in the blood circulation of patients with vitiligo and is elevated in patients with active disease, whereas the levels of CXCL9 and CXCL11 tend to be more variable. Because most studies have focused on a small number of chemokines, future broad chemokine profile studies are suggested; they should be large and determine whether chemokine levels are related to the extent of disease.
Lee JH, Ju HJ, Seo JM, et al. Comorbidities in patients with vitiligo: a systematic review and meta-analysis. J Invest Dermatol. 2023;143:777-789.e6. Source
A comprehensive MEDLINE and EMBASE search was performed to find observational studies that identified previously unreported prevalent diseases in patients with vitiligo and quantify those associations compared with those in healthy controls. A total of 78 studies were eligible for analysis (17 cross-sectional, 49 case-control, and 12 cohort studies); 37 evaluated comorbid diseases in patients with vitiligo, 42 examined the association of vitiligo as a comorbid disease in patients with other diseases, and one used both of these approaches. Studies limited to pediatrics or those that provided only lab results were excluded.
It was found that patients with vitiligo showed higher risks of having comorbid autoimmune and connective tissue diseases, including alopecia areata (odds ratio, 2.63; 95% CI, 2.50-2.78), discoid lupus erythematosus (OR, 2.54; 95% CI, 1.74-3.72), Sjogren syndrome (OR, 2.50; 95% CI, 1.98-3.16), myasthenia gravis (OR, 2.30; 95% CI, 1.74-3.02), systemic lupus erythematosus (OR, 1.96; 95% CI, 1.52-2.52), and rheumatoid arthritis (OR, 1.82; 95% CI, 1.55-2.15). Diabetes, metabolic syndrome, sensorineural hypoacusis, and ophthalmic conditions were more prevalent in this patient cohort; thyroid diseases, in particular, were of note in these patients, especially autoimmune thyroid conditions.
Conclusion: There is an association of various systemic comorbid conditions with vitiligo. Providers treating patients with vitiligo should consider screening for these conditions regularly in patients at high risk for certain comorbidities — especially those related to the thyroid — to provide early intervention and optimal management for their patients. Additional longitudinal observations are warranted to clarify the interaction and causality between vitiligo and other comorbidities.
Ezzedine K, Peeva E, Yamaguchi Y, et al. Efficacy and safety of oral ritlecitinib for the treatment of active nonsegmental vitiligo: a randomized phase 2b clinical trial. J Am Acad Dermatol. 2023;88:395-403. Source
This phase 2b trial (NCT03715829) was conducted to evaluate the efficacy and safety of ritlecitinib, an oral Janus kinase 3 (JAK3) inhibitor, in patients with active nonsegmental vitiligo. Patients were randomized to receive once-daily oral ritlecitinib with or without a 4-week loading dose (200/50 mg, 100/50 mg, 30 mg, or 10 mg) or placebo for the dose-ranging period of 24 weeks. Patients subsequently received ritlecitinib 200/50 mg daily during a 24-week extension period. The primary endpoint for efficacy was the percent change from baseline in the Facial Vitiligo Area Scoring Index (F-VASI) at week 24. The key secondary endpoint was the proportion of patients with ≥ 75% improvement on the centrally read F-VASI (F-VASI75) at week 24; the percent change from baseline in locally read F-VASI and Total Vitiligo Area Scoring Index were secondary endpoints at designated time points during the dose-ranging period and exploratory endpoints during the extension period.
A total of 364 patients were treated during the dose-ranging period, and 187 patients participated in the extension period. Patients with stable vitiligo only (no new lesions or progression of existing lesions in the past 3 months) were excluded from the study. There were substantial differences in percent change from baseline in F-VASI from placebo in the ritlecitinib 50-mg groups with (-21.2 vs 2.1; P < .001) or without (-18.5 vs 2.1; P < .001) a loading dose and ritlecitinib 30-mg group (-14.6 vs 2.1; P = .01). Accelerated improvement was observed after treatment with ritlecitinib 200/50 mg in the extension period.
The proportion of patients who were "very much improved" or "much improved" on the Patient Global Impression of Change-Vitiligo increased from week 24 to week 48 in all treatment sequences, ranging from 2.9% (90% CI, 0.3-11.9) to 19.4% (90% CI, 8.8, 32.7) at week 24 and 10.7% (90% CI, 4.0, 23.8) to 57.9% (90% CI, 38.6, 76.2) at week 48. In addition, as a key secondary endpoint, the proportion of patients who achieved F-VASI75 at week 24 was 12.1% in the ritlecitinib 200/50-mg group, 8.5% in the 100/50-mg group, 7.7% in the 50-mg group, 2.7% in the 30-mg group, and 2.3% in the 10-mg and 0% in the placebo group. The most common adverse events were nasopharyngitis, upper respiratory tract infection, and headache.
Conclusion: Oral ritlecitinib was effective and well tolerated over 48 weeks in patients with active nonsegmental vitiligo. Longer treatment duration may be needed for optimal repigmentation.
Lee YH, Song GG. Association between vitamin D receptor polymorphisms and vitiligo susceptibility: an updated meta-analysis. J Cosmet Dermatol. 2023;22:969-979. Source
A meta-analysis of study participants and Asian, Arab, European, and Latin American groups was conducted to determine whether polymorphisms in the vitamin D receptor (VDR) are associated with susceptibility to vitiligo. VDR polymorphisms (VDR ApaI, TaqI, BsmI, and Fokl) in patients with vitiligo and controls were identified using PubMed/Medline and EMBASE. References in selected papers were reviewed to determine whether there were additional studies that were not otherwise listed. There were no language or country limitations.
Studies were considered if (1) they were case-control studies, (2) they examined VDR polymorphisms in vitiligo and control groups, and (3) they contained adequate data to construct an odds ratio (OR). Exclusion criteria were (1) studies containing overlapping data, (2) studies in which the numbers of null and wild genotypes/alleles could not be ascertained, and (3) studies in which family members had been included. The search was limited to papers published in English. Thirteen papers with 2034 patients and 2771 controls were included. Eleven studies looked at the VDR ApaI polymorphism, 12 looked at the VDR TaqI polymorphism, 7 examined the BsmI polymorphism, and 8 examined the VDR FokI polymorphism.
In all participants, including Asian, European, Arab, and Latin American populations, there was no link between vitiligo and the VDR ApaI A allele (OR, 0.889; 95% CI, 0.713-1.109, P = .298). However, in Asian persons (OR, 0.721; 95% CI, 0.553-0.940, P = .016) but not European, Arab, or Latin American persons, there was a link between the VDR ApaI A allele and vitiligo.
In Asian persons, meta-analysis of the VDR BsmI polymorphism identified a significant association between vitiligo and the B allele (OR, 0.812; 95% CI, 0.686-0.961; P = .015). This association was not seen in European, Arab, and Latin American persons. No connection between vitiligo and VDR TaqI and FokI polymorphisms was seen.
Conclusion: Among Asian persons, the VDR ApaI and BsmI polymorphisms in VDR have been correlated with vitiligo susceptibility. However, the VDR TaqI and FokI polymorphisms are not associated with vitiligo susceptibility in European, Asian, Arab, and Latin American persons. On the basis of these ethnic variations, additional research and large-scale studies on the link between VDR polymorphisms and vitiligo in diverse ethnic groups are warranted.
McCrary MR, Gibbs DC, Alharthi M, Krueger LD. Utilization of our toolkit: a systematic review and meta-analysis of surgical therapies in vitiligo treatment. Dermatol Surg. 2022;48:815-821. Source
A systematic review of surgical treatments for vitiligo was conducted to review the efficacy of nonphototherapy surgical treatments in comparative or placebo-controlled trials. Surgical treatments reviewed included platelet-rich plasma (PRP), microneedling, ablative therapies, and surgical modalities. Primary outcomes were (1) treatment success (equal to > 75% repigmentation) and (2) treatment failure (considered < 25% repigmentation) for which meta-analyses were performed.
A total of 73 studies comprising 2911 patients were included in the meta-analysis. Study eligibility were (1) ≥ 10 patients of any age and type of vitiligo; (2) intervention study with at least 1 surgical therapy, experimental group, and a control group; and (3) quantitative repigmentation outcomes.
For PRP, in one study group, > 75% repigmentation was higher for patients treated with PRP plus excimer laser compared with laser alone; in another study group, > 75% repigmentation was observed in 40% of patients treated with PRP plus CO2 laser, 20% with PRP alone, and 10% with CO2 laser alone. In the microneedling arm, the addition of microneedling lowered the odds of treatment failure and yielded better repigmentation than laser alone.
Multiple studies noted significantly better repigmentation with ablation after 1-6 months of treatment. Overall, nonphototherapy surgical treatments revealed greater repigmentation rates but also higher incidences of adverse events (eg, cobblestoning with punch grafting, hyperpigmentation, or infection with suction blister and cellular grafting).
Conclusion: Meta-analyses suggest that the addition of microneedling or ablative laser therapy to narrow-band ultraviolet B phototherapy may improve repigmentation with minimal adverse effects. Surgical therapies (eg, suction blister or punch grafting) may offer the highest chance of repigmentation but have significant risks for adverse effects, including scarring and hyperpigmentation.
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Cite this: Journal Summary: Vitiligo - Medscape - Sep 06, 2023.
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