100 Most-Cited Articles in Vitiligo: A Bibliometric Analysis

Abstract

Introduction:

Vitiligo is a skin disease affecting melanocytes, characterised by the development of depigmented skin lesions.

Methods:

We used bibliometric analysis (BA) to identify high-quality research articles on vitiligo using criteria such as total citations, annual citations (AC) and journal impact factors. We extracted the 100 most-cited articles on vitiligo using the Web of Science database and analysed the results using Microsoft Excel 2019. Our search was limited to manuscript titles or abstracts containing the keyword ‘vitiligo’. The data extracted information such as title, author, year of publication, journal of publication, total citations and research area. We also calculated the AC rate to account for bias.

Results:

A total of 6,189 studies were retrieved. The 100 most-cited articles were published between 1976 and 2017. Of those, 75 were original articles, with the research foci being mainly pathogenesis (29%) and treatment (26%). The US was the most prolific publisher overall. We separately retrieved the highest cited data from 2018 to 2022 and tabled the top 10. Of those, 50% were original articles.

Discussion:

Our BA shows that developed countries published most of the vitiligo literature. Additionally, recent research has focused on targeted treatment approaches. We also highlight the increasing paediatric vitiligo research, specifically regarding therapies.

Introduction

Vitiligo is a skin disease affecting melanocytes that is characterised by the development of areas of depigmented skin lesions. It typically develops between the ages of 10 and 30 years and affects 0.5% to 1% of the global population.[1] It is more prevalent in relatives of patients with the disease, but no association of ethnicity or sex with prevalence has been reported.

Several theories surround the pathogenesis of vitiligo. One suggests that it is an autoimmune disease in which autoreactive cytotoxic CD8+ T cells attack melanocytes and stimulate the secretion of Interferon gamma (IFNγ) and chemokines from surrounding keratinocytes.[2] A strong stigma surrounds vitiligo, and the navigation of these changes can often cause depression, anxiety or embarrassment.[3] Thus, homogenisation of skin colour can provide psychological benefits.

The latest 2021 guidelines[4] provide an algorithm for vitiligo diagnosis and treatment according to disease severity and onset. Treatments currently focus on blocking IFNγ signalling by using Janus kinase inhibitors. Unfortunately, relapse occurs with treatment discontinuation. To prevent relapse, new treatments, such as ruxolitinib, focus on memory T cells and provide long-lasting therapeutic benefits.[5,6] The use of sunscreen and clothing to protect affected areas is important to prevent severe sunburn.[7]

Bibliometric analysis (BA) comprises a scientific analysis of the existing literature on a chosen topic. It assesses the quality, quantity and major ideas through the most-cited articles. Additionally, it identifies aspects where improvements could benefit the topic.

Several fields in dermatology have been explored by BAs, including atopic dermatitis,[8] psoriasis,[9] nail psoriasis,[10] psoriatic arthritis,[11] melanoma,[12] hidradenitis suppurativa[13] and rosacea.[14] The last BA on vitiligo was published three years ago and included all literature related to vitiligo from 1975 to 2017.[15] However, we chose a different approach, deciding to focus solely on highly cited articles to extract the most significant data possible. Thus, here we have detailed the publications framing vitiligo practice by determining the crucial bibliometric characteristics of the 100 most-cited vitiligo articles since 1972.

Materials and Methods

Search strategy

We extracted the 100 most-cited articles on vitiligo from the Clarivate Web of Science (WoS) database on 18 September 2022. Our search was limited to the keyword ‘vitiligo’ in the title or abstract of the papers. Article type, country of origin, language and research area were not limited in order to include all trends and novelties in the field between 1972 and 2022. Our BA did not require approval from an ethics committee because the researcher did not analyse patient data or interact with patients in any way.

Data extraction and bibliometric parameters

Data on the 100 most-cited articles on vitiligo was downloaded from the WoS and extracted to Microsoft Excel 2019. These data included title, first author, corresponding author, institutional affiliation, year of publication, journal of publication, total citations (TCs) and research area.

We calculated an annual citation (AC) rate (TCs divided by the age of publication) to counter the bias arising from some publications being older than others. We included both TCs and annual rates in our table of the 100 most-cited vitiligo articles.

The manuscript type was recorded as an original article, review, rapid communication or editorial material. The study design and research foci were identified by screening the abstracts, available full texts and keywords of each of the 100 articles. The research area was extracted directly from WoS and examined. Country and institutional affiliation were identified based on the first author’s information for each article. The journal impact factor for 2021 was acquired from the WoS database.

Results

A total of 6,189 studies were retrieved. The 100 most-cited articles are listed in Table 1 and were ranked by AC.

Table 1.

Table of the 100 most.cited articles in vitiligo literature between 1972 and 8 September 2022

Year of publication

The 100 most-cited articles were published between 1976 and 2017. Figure 1 shows the number of articles published in each 10-year interval. The publication rate began to increase after 1992, with the prior two intervals accounting for just 15 articles. The rate peaked between 1993 and 2002 (n = 37), which was followed by 34 articles in the next decade and a significant decrease between 2013 and 2022 (n = 11).

Figure 1.

Publications per decade since 1972

Citations

The TCs of the top 100 articles ranged between 113 and 477 per individual article, for a total of 19,528. The median TC number was 163 (133, 248). The 10 most-cited articles accounted for 19.68% (n = 3,843) of the TCs. Five of the top 10 ranked articles by AC remained in the top 10 when ranked according to TC. The AC ranged from 2.9 to 69.7 and had a median of 8.5 (5.83, 15.14). The average AC increased throughout the decades, but the increase was not steady. Figure 2 shows the citation analysis for the average AC and TC in each 10-year interval from 1972 to 2017. From 1972 to 2017, the average AC increased in parallel with the average TC until 2003. Between 2013 and 2017, the TC sum was 2678 compared with 7217 in the previous 10-year interval.

Figure 2.

Total citations and annual citations

Countries, institutes and corresponding authors

When the articles were sorted by country of origin, the US, the Netherlands and England were the most prolific publishers, with 35, 13 and 12 publications, respectively [Figure 3]. After controlling for population, the Netherlands (n = 7.45 × 10⁰), Belgium (n = 2.59 × 10⁷) and England (n = 2.14 × 10⁷) were the three most prolific countries and the US (n = 1.06 × 10⁷) was in the 8^th position. The most prolific countries for original articles are shown in Figure 3, while the most productive institute, corresponding author and the respective number of published articles are listed in Table 2.

Figure 3.

Country of origin of the 100 most-cited articles

Table 2.

Most published authors with their affiliated institution and countries

Country of origin	No of articles	Most affiliated institution	No of articles2	Most publishing senior author	No of articles
England, UK	12	University of Bradford	6	Schallreuter, KU	11
USA	35	University of Colorado	8	Spritz, RA	7
Italy	8	N/A		Picardo, M	4
Netherlands	13	University of Amsterdam	9	Njoo, MD	4
France	9	CHU Bordeaux	4	Taieb, A	3
Netherlands	13	N/A		Westerhof, W	3

Journal of publication

The 100 articles were published in 28 different journals. The core journals were the Journal of Investigative Dermatology (n = 16), followed by Pigment Cell Research (n = 13), Archives of Dermatology (n = 13) and the Journal of the American Academy of Dermatology (n = 10). The top four journals published 52% of the articles included in the BA [Figure 4]. The median impact factor, which reflects the worldwide exposure of a study [Figure 5], was 9. A total of 46 articles were published in journals with an impact factor of 9 or above.

Figure 4.

Top journals of publication

Figure 5.

Impact factor of journal 2021

Article design, research focus and research area

Of the 100 most-cited articles, 75 were original articles, 21 were reviews, two were rapid communications, one was editorial material and one was a note. The 100 most-cited articles were classified into different research foci: pathogenesis (29%), treatment (26%), epidemiology (16%), immunopathology (10%) and others (19%). In addition, they were divided by research area: dermatology (71%), general and internal medicine (7%), oncology (5%) and others (17%) [Table 3]. The original articles were subdivided by study design per decade: 40% were case-control studies (n = 30), 12% were clinical trials (n = 9) and 12% were cohort studies (n = 9) [Figure 6]. The original articles were then classified into research foci per decade: treatment (28%), pathogenesis (28%), epidemiology (14.7%), immunopathology (10.7%), genetics (5.3%), treatment outcome (4%), basic science (4%), pathophysiology (2.7%), comprehensive review (1.3%) and diagnostics (1.3%) [Figure 7].

Table 3.

Research areas of the 100 most-cited articles

Research area	Number of publications
Dermatology	71
General and Internal Medicine	7
Oncology	5
Science and Technology	3
Genetics and Heredity	3
Biochemistry and Molecular Biology	3
Immunology	3
Research and Experimental Medicine	2
Cell Biology	1
Pathology	1
Psychology	1

Figure 6.

Study design of original articles per decade

Figure 7.

Research focus of original articles per decade

Recent articles

Although the latest of the top 100 articles dates from 2017, we extracted and sub-analysed the top articles since 2018 separately because these data could indicate upcoming trends in vitiligo research. We tabled the 10 most-cited articles since 2018 [Table 4]. TCs ranged between 49 and 108, with a median of 64.5 (55.5, 92.25). The AC was between 16.3 and 46.5, with a median of 24 (18.5, 30.8). The median AC was significantly higher than that of the top 100 articles (24 vs. 8.5). However, the opposite was observed for TCs. The TC number of recent articles was much lower than that of older articles, with a median of 64.5 compared to 163 (a 2.5-fold difference). Of the 10 most-cited articles since 2018, 5 were original articles and 5 were reviews. The countries of origin included the US (n = 5), France (n = 3) and the People’s Republic of China (n = 2). The study designs included 50% reviews (n = 5), 40% basic or applied science (n = 4) and 10% randomised controlled trials (RCTs) (n = 1). The research foci of the 10 articles were immunopathology (n = 4), epidemiology (n = 3), pathogenesis (n = 2) and treatment (n = 1).

Table 4.

Top 10 articles since 2018

Rank	Article title	First author	Journal	Year published	Impact factor	Times cited	Average citation/Year	Corresponding author	Institution affiliation	Country of origin	Manuscript type	Study design	Research focus	Research area
1	Vitiligo: a review	Bergqvist, C	Dermatology	2020	3.69	93	46.5	Ezzedine, K	UPEC	France	Review	Review	Epidemiology	Dermatology
2	Ruxolitinib cream for treatment of vitiligo: a randomised, controlled, phase 2 trial	Rosmarin, D	Lancet	2020	202.7	65	32.5	Rosmarin, D	Tufts Med Ctr	USA	Article	RCT	Treatment	General & Internal Medicine
3	Vitiligo: mechanisms of pathogenesis and treatment	Frisoli, ML	Annual Review of Immunology, Vol 38	2020	28.53	64	32.0	Frisoli, ML	Univ Massachusetts	USA	Review	Review	Epidemiology	Immunology
4	Vitiligo skin is imprinted with resident memory CD8 T Cells expressing CXCR3	Boniface, K	Journal of Investigative Dermatology	2018	8.55	108	27.0	Boniface, K	Univ Bordeaux	France	Article	Basic or Applied Science	Immunopathology	Dermatology
5	Vitiligo: focus on clinical aspects, iImmunopathogenesis, and therapy	Boniface, K	Clinical Reviews In Allergy & Immunology	2018	8.67	102	25.5	Taieb, A	Univ Bordeaux	France	Review	Review	Epidemiology	Immunology
6	Antibody blockade of IL-15 signaling has the potential to durably reverse vitiligo	Richmond, JM	Science Translational Medicine	2018	17.99	90	22.5	Harris, JE	Univ Massachusetts	USA	Article	Basic or Applied Science	Immunopathology	Cell Biology
7	Perspectives of new advances in the pathogenesis of vitiligo: from oxidative stress to autoimmunity	Wang, YH	Medical Science Monitor	2019	1.43	60	20.0	Li, CY	Fourth Mil Med Univ	China, PRC	Review	Review	Pathogenesis	Research & Experimental Medicine
8	SIRT3-dependent mitochondrial dynamics remodeling contributes to oxidative stress-induced melanocyte degeneration in vitiligo	Yi, XL	Theranostics	2019	11.56	54	18.0	Li, CY	Fourth Mil Med Univ	China, PRC	Article	Basic or Applied Science	Pathogenesis	Research & Experimental Medicine
9	The role of memory CD8(+) T Cells in vitiligo	Riding, RL	Journal of Immunology	2019	5.42	50	16.7	Harris, JE	Univ Massachusetts	USA	Review	Review	Immunopathology	Immunology
10	Resident memory and recirculating memory T Cells cooperate to maintain disease in a mouse model of vitiligo	Richmond, JM	Journal of Investigative Dermatology	2019	8.55	49	16.3	Harris, JE	Univ Massachusetts	USA	Article	Basic or Applied Science	Immunopathology	Dermatology

Discussion

In this BA, we identified trends in data related to vitiligo and the areas where research was lacking. The largest number of articles published in a single decade was between 1993 and 2002, with 37 published articles [Figure 1]. This finding could be explained by the fact that three articles in our top 100 list were published in 1993. Specifically, the article ‘Vitiligo: where do we stand’ (Ortonne et al.[16]), which reviewed the advances in vitiligo research, treatment and epidemiology, could have encouraged subsequent publications. Another possible explanation for the popularity of the vitiligo topic at that time is the breadth of scientific advances and techniques that emerged in the 1990s and 2000s. For example, clustered regularly interspaced short palindromic repeats (CRISPR), a gene-editing system, was first characterised in that decade. CRISPR can be used to target dermatologic conditions, which is appealing to researchers.[17]

TCs divided by 10-year intervals mostly increased until 2002, stabilised until 2012 and have declined since. However, ACs divided by a 10-year interval have greatly increased since 1972, with a sharp increase beginning in 2002 [Figure 2]. These combined findings concerning ACs and TCs can be correlated to the number of publications emerging between 1993 and 2002 (37% of total vitiligo publications). It is possible that, due to recent articles being more up-to-date, they will tend to be more highly cited in recent years.[18] Additionally, in 2002, research output emphasised the oxidative stress link to vitiligo and elicited curiosity around the topic. Such research included the correlation of the CAT gene with hydrogen peroxide (H₂O₂) accumulation[19] and the photo-oxidation of proteins producing H₂O₂.[20]

The existing vitiligo BA, published in 2020,[15] focused on the correlation between the gross domestic product (GDP) per capita and publications per country. Their main finding was that developed countries published most of the vitiligo literature. Similarly, our research found that the most prolific countries, after controlling for population, were the Netherlands, Belgium and England. Interestingly, regardless of population, the Netherlands (2^nd) and England (3^rd) are still among the most prolific countries [Figure 3]. This may be because research shows that Europe has a slightly higher vitiligo prevalence than the US (1.6% vs. 1.4%)[21,22] and a much higher prevalence than light-skin Asian countries such as Japan (0.5%).[23]

Over half of the top-cited articles were published in the Journal of Investigative Dermatology, followed by Pigment Cell Research, Archives of Dermatology and the Journal of the American Academy of Dermatology [Figure 4]. This can be attributed to the high standard of these journals.[24]

Additionally, the median Impact factor (IF) was 9, which is high and signifies that researchers are prone to choosing high-IF journals for publication.[25] Journal selection is a complex decision but IF is almost always an important factor.[25]

Our study revealed that the study design by decade remained relatively stable throughout the years, except for case-control studies [Figure 6]. Case-control studies peaked between 1993 and 2002 at 20 articles. A possible reason could be that case-control studies require fewer resources than controlled trials (CTs) or RCTs. Additionally, during that same decade, treatment and pathogenesis research culminated. Case-control studies lend themselves well to more general investigations of the treatment or pathogenesis of vitiligo.[26]

It is widely believed that case-control studies are less valuable than CTs/RCTs. They provide odds ratios, while RCTs yield relative risk (a superior measure of association). The hierarchy of these two research designs is challenged because carefully constructed observational studies such as case-control studies yield similar results to RCTs. However, because bias is still more prevalent in observational studies, it would be beneficial to produce more RCTs on vitiligo in the future.[25]

Out of the top cited original articles, the main research foci were treatment (28%) and pathogenesis (28%) [Figure 7]. Of the treatment-related articles, 26.9% discuss treatment using Ultraviolet B (UVB) therapy.[6] This historical treatment has the most data supporting it compared to other treatment options, making it a trending research topic.[6] While older vitiligo treatments target non-specific autoimmune suppression,[27,28] newer therapies focus on targeted approaches and aim to provide greater efficacy and safety, such as Janus kinase inhibitors.[29] Indeed, the US Food and Drug Administration recently approved one such inhibitor, Opzelura (ruxolitinib), as a revolutionary treatment for vitiligo.[30] Nonetheless, the pathogenesis/immunopathology of the disease must be understood to develop better treatments.[31] This explains why research into vitiligo pathogenesis, immunopathology and epidemiology has increased drastically since 1993. Interestingly, in the top 10 recent articles (2018–2020), this trend was also observed, with immunopathology at 40% and epidemiology at 30% [Table 4].

Vitiligo was found to be more progressive and extensive if it began in childhood.[32] Out of the top 100 cited articles, seven articles address the paediatric population. While vitiligo can have different implications in adult versus paediatric populations, the comparison of vitiligo prevalence in adults and children is a delicate affair because many criteria are at play. Repigmentation following treatment is largely more significant in children.[33] Ultimately, studies suggest that vitiligo is more common in adults, with fewer lesions than in children but with poorer repigmentation. This could explain why a larger proportion of research is conducted on adults, to determine a more efficient treatment for that population. Further research on the impact of childhood vitiligo, early detection and treatment outcomes on the patient’s state in adulthood would yield a better understanding of the disease progression.

This BA has some limitations. Firstly, older articles are more likely to be cited, which causes a bias. We aimed to tackle that bias by analysing ACs as well. Additionally, highly cited authors tend to cite their previous work on the topic, thereby increasing their TCs. This did not reflect article quality and significance but caused a bias in the TCs. This study also contains limited information regarding the psychological impact of vitiligo on individuals of colour. While it is briefly mentioned, extensive research should be conducted in this field due to the strong mental distress vitiligo can cause. In skin of colour, vitiligo increases the risk of depression and anxiety, which in turn can potentially promote flares. As the research in this area is limited and articles on the topic do not appear extensively in the 100 most-cited articles on vitiligo, our BA’s information on it is restricted. However, it is essential to conduct further research in this field, as it could impact treatment options for the population in question.

To conclude, this BA highlights ramifications such as the focus of recent research on targeted treatment approaches such as Opzelura (ruxolitinib) and the need for additional RCTs in vitiligo research. Further investigation into the pathogenesis of vitiligo, and the impact of early detection of vitiligo in childhood is warranted.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.