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Bibliometric analysis of literature on toxic epidermal necrolysis and Stevens-Johnson syndrome: 1940 – 2015 | Orphanet Journal of Rare Diseases | Full Text

 Source: https://ojrd.biomedcentral.com/articles/10.1186/s13023-017-0566-8



Open Access

Bibliometric analysis of literature on toxic epidermal necrolysis and Stevens-Johnson syndrome: 1940 – 2015

Orphanet Journal of Rare Diseases201712:14
DOI: 10.1186/s13023-017-0566-8
Received: 19 October 2016
Accepted: 6 January 2017
Published: 18 January 2017

Abstract

Background

Stevens Johnson Syndrome (SJS)
and toxic epidermal necrolysis (TEN) are rare but fatal adverse skin
reactions that affect all age groups. In order to better understand
literature on this topic, we conducted a bibliometric study using Scopus
database to shed light on number and growth of publications, most
active countries, institutions, journals and authors involved in
publishing articles in this field, citation analysis, top cited
articles, international collaboration, role of medications and genetic
association. Bibliometric analysis will enrich the literature on these
rare conditions and will provide baseline data for future comparison.

Results

Three thousand eight hundred fifty-six journal articles were retrieved. The h-index
of retrieved documents was 95. Growth rates of publications were
highest from 1966 to 1975 and from 2006 to 2015. The United States of
America (n = 640; 16.57%)
was the leading country in number of publications. However, French and
Japanese researchers and institutions were most active in publishing
articles on SJS and TEN. International collaboration among active
countries was relatively low and ranges from 32.5% for Swiss researchers
and 1.47% for Spanish researchers. The most frequently mentioned
medication in retrieved articles was carbamazepine (n = 146) followed by phenytoin (n = 114) and allopurinol (n = 112).
Mycoplasma infection was mentioned in 111 articles. Most documents on
SJS and TEN were published in dermatology journals, specifically Archives of Dermatology.
However, in the last decade, top cited articles appeared in dermatology
and pharmacogenetic journals. Carbamazepine was frequently encountered
with Han Chinese and HLA-B 1502 terms while allopurinol was frequently
encountered with HLA-B 5801 and Japanese terms.

Conclusion

Bibliometric analysis reveals
that research publications on SJS and TEN have been increasing since the
l940s, with relatively low international collaboration. Documents are
being published, not only in dermatology journals, but also in genetic,
public health and general medicine journals. Research on SJS and TEN can
be helpful to clinicians and researchers not only to document
complications and fatal outcomes, but also to identify potential
causative agents and potential ethnic variations to note gaps in
research.

Keywords

Stevens-Johnsons Syndrome
Toxic epidermal necrolysis
Bibliometric analysis

Background

Stevens-Johnson
syndrome (SJS) and toxic epidermal necrolysis (TEN) are uncommon, but
serious and sometimes fatal adverse skin and mucous reactions [1]. Stevens and Johnson were the first to describe SJS in 1922 while Lyell was the first to describe TEN in 1956 [2, 3].
Up until early 1990s, erythema multiforme major (EMM) and SJS were
considered similar clinical conditions. However, in 1993 EMM and SJS
were identified as two distinct disorders [4].
TEN and SJS are now considered part of a continuum with SJS
representing the less severe form of the reaction, and TEN representing
the more severe end. The TEN involves larger total body surface area
than SJS. The “SJS/TEN” is considered an intermediate form [5, 6, 7]. Incidence rates of TEN and SJS varies across the studies but it is generally less than two cases per million each year [7].
The reported mortality in patients with SJS varies from 3 to 10% while
those with TEN have higher mortality rate and ranges from 20 to 40% [8].
The medical outcome of SJS and TEN varies depending on the medical
condition of the patient when initiating therapy of the condition [9].
Both
SJS and TEN are most often triggered by certain medications, most
commonly anticonvulsants, non-steroidal anti-inflammatory drugs, and
antibiotics [10, 11]. Unfortunately, a recent study showed that there is an under reporting of drug – induced SJS and TEN [12]. Common over-the-counter drugs such as paracetamol and ibuprofen have been reported in some cases of SJS and TEN [13].
According to Stevens Johnson Syndrome foundation (SJSF), any
medication, including cocaine and Ginseng containing herbal products,
can cause SJS and TEN [14]. Other causes of SJS and TEN include certain infections [15].
For unclear reasons, it was found that patients with human immune
deficiency virus (HIV) have higher risk of developing SJS and TEN
compared to un-infected people [7, 16, 17, 18, 19, 20, 21]. Other infections such as Mycoplasma pneumoniae infections and herpes simplex viral infections were linked to SJS and TEN even without previous exposure to medications [22, 23, 24, 25, 26, 27]. SJS and TEN are associated with certain HLA types [28, 29, 30, 31, 32].
The genetic basis of SJS and TEN might be responsible for variations in
reporting of drug-induced SJS and TEN in different parts of the world [33]. Better understanding of these variation can help in developing preventive and therapeutic policies for SJS and TEN [34].
Being
considered rare conditions, studies on SJS and TEN are required. Such
studies are beneficial for pharmacologists, clinical toxicologists, and
clinicians in various medical specialties such as dermatologists,
pediatricians, and critical care specialists. One method to enrich
literature about a certain topic is to provide detailed analysis of
published literature on that particular topic. Such analysis of
literature is called bibliometric analysis. Therefore, this study was
carried out to give a bibliometric overview of literature on TEN and
SJS. Bibliometric analysis is not intended to be a review article of
scientific information on TEN and SJS, rather an analysis of published
literature in terms of annual growth, productivity of various countries,
institutions and authors, international collaboration, highly cited
articles, and to lesser extent discussion of the content of highly cited
articles. Bibliometric analysis on various medical subjects, including
new subjects such as telemedicine have been carried out and published [35, 36, 37, 38, 39, 40, 41, 42, 43, 44].
Such studies added new information to the scientific literature of
these conditions and added momentum to research aspects of these
conditions. Rare diseases and conditions should be given priority in
bibliometric studies to establish baseline data for future comparison.
Therefore, we believe that such a study will be a positive addition to
the field of rare diseases in general and to SJS and TEN in particular.

Methods

In
bibliometric studies, literature on a certain topic need to be
retrieved and analyzed as an initial step. To accomplish this, the
largest database need to be used. Unfortunately, no single database is
perfect. However, Scopus database is believed to be the largest and most
accurate when compared with other databases [45, 46]. Therefore, for this study, Scopus was used and accessed through Hinari website.
The
keywords entered in Scopus search engine were straight forward and
consisted of “Toxic epidermal necrosis”, “Stevens-Johnson syndrome”, and
“Lyell”s syndrome”. These keywords were used in title search separated
by “OR” function. The time span of the study was determined from 1940 to
2015. The search query was limited to published journal articles with
errata (corrections) documents being excluded. The search query looked
like this in Scopus: (TITLE(“Toxic epidermal necrolysis”) OR
TITLE(“Lyell”s syndrome”) OR TITLE(“Stevens-Johnson syndrome”) AND
(EXCLUDE(PUBYEAR,2016)) AND (LIMIT-TO(SRCTYPE,“j”)) AND
(EXCLUDE(DOCTYPE,“er”)).
One
might question the validity of using title search instead of
title-abstract-keyword approach. The use of title-abstract-keyword
research will retrieve so many false positive results that will
compromise the validity of retrieved data. However, the use of title
search will minimize both false positive and false negative results. The
validity of retrieved articles was based on manual check of the content
of 10% of retrieved documents across all years and found to be free of
false positive articles.
Retrieved
articles can be analyzed from different aspects. Growth of publications
was presented in decade interval. Growth rate was determine by
calculating the difference in number of publications between two
consecutive decades and dividing by the number of publications in the
earlier decade. Scopus has the ability to rank countries, institutions
and authors based on the number of articles they participated in.
Articles with authors having different country affiliation are called
multiple country publication (MCP) and considered to represent
international collaboration of that country. On the other hand, articles
in which all authors have the same country affiliation are called
single country publication (SCP) and are considered to represent
intra-country (within) collaboration.
Scopus
provides researchers with the opportunity to do citation analysis.
Retrieved documents can be sorted based on number of citations they
received. Top cited articles are those that received the highest number
of citations while articles with a minimum number of 100 citations are
considered to be highly cited articles. Scopus provides total citations
for retrieved articles and Hirsch index (h-index).
Visualization
and mapping of specific results could be achieved through using a
mapping program such as VOSviewer. In this study, data for countries,
institutions, authors, and journals were presented in tables on the
basis of a minimum contribution of 20 articles.
This
study did not require approval of ethic committee and therefore,
approval of study by medical ethics committee was not sought. Data
presentation did not involve statistical analysis and Microsoft Excel
program was used to accomplish most of the data presented in this study.

Results


General information

Three
thousand eight hundred fifty-six journal articles were retrieved. The
majority of retrieved articles were research articles (n = 2948; 76.45%) followed by letters (n = 529; 13.72%) and reviews (n = 211; 5.47%) (Table 1). The majority of retrieved articled were written in English (n = 2,575; 66.78%). Other encountered languages are shown in Table 2. An article published in 1946 was the oldest record of SJS and TEN in Scopus database [47]. The growth of publications on SJS and TEN is presented in decade intervals in Fig. 1.
The highest growth rates were seen during the periods from 1956 to 1965
and from 2006 to 2015. The annual growth of publication of various
types of journal articles is shown in Fig. 2.
Table 1
Types of retrieved documents
Type of document
Frequency
N = 3856
Percent
Article
2948
76.45
Letter
529
13.72
Review
211
5.47
Note
70
1.82
Conference Paper
51
1.32
Short Survey
25
0.65
Editorial
15
0.39
Article in Press
7
0.18

Table 2
Types of languages encountered in retrieved documents
Language
Frequency
N = 3856
Percent
English
2575
66.78
French
231
5.99
Spanish
191
4.95
Russian
189
4.90
German
165
4.28
Italian
107
2.77
Japanese
91
2.36
Polish
79
2.05
Dutch
29
0.75
Korean
26
0.67
Portuguese
25
0.65
Chinese
19
0.49
Czech
19
0.49
Turkish
18
0.47
Hungarian
15
0.39
Norwegian
14
0.36
Romanian
14
0.36
Danish
13
0.34
Serbian
9
0.23
Swedish
7
0.18
Ukrainian
7
0.18
Hebrew
6
0.16
Slovak
5
0.13
Bulgarian
3
0.08
Croatian
3
0.08
Finnish
1
0.03
Greek
1
0.03
Undefined
24
0.62
SJS Stevens – Johnson Syndrome
TEN Toxic Epidermal Necrolysis

https://static-content.springer.com/image/art%3A10.1186%2Fs13023-017-0566-8/MediaObjects/13023_2017_566_Fig1_HTML.gif
Fig. 1
Growth of publications on SJS and TEN presented in decade intervals

https://static-content.springer.com/image/art%3A10.1186%2Fs13023-017-0566-8/MediaObjects/13023_2017_566_Fig2_HTML.gif
Fig. 2
Annual growth of publications of various types of retrieved journal articles


Frequently encountered terms

Network visualization of most frequently encountered terms is shown in Fig. 3.
The map included four clusters: the first cluster (red) included terms
that describes the SJS and TEN skin eruption and associated factors; the
second cluster (green) included terms pertaining to treatment and
potential outcome; the third cluster (blue) included terms pertaining to
medications and genetic association with HLA types; and the fourth
cluster (yellowish green) included terms pertaining to ophthalmic
complications of SJS and TEN.
https://static-content.springer.com/image/art%3A10.1186%2Fs13023-017-0566-8/MediaObjects/13023_2017_566_Fig3_HTML.gif
Fig. 3
Network visualization of most frequently encountered terms


Citation analysis

Retrieved
documents received a total of 4908 citations. The mean ± standard
deviation of number of citations per article was 12.73 ± 41.57 while the
median (Q1 – Q3) was 2 (0 – 10). The h-index
of retrieved documents was 95. The cumulative number of citations
showed a linear increase with time indicative of continuous interest,
readability, and citations of SJS and TEN publications (Fig. 4). The review article entitled “Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis” [48] published in New England Journal of Medicine (NEJM) in 1995 received the highest number of citations (938). A total of 87 articles (2.25%) were highly cited.
https://static-content.springer.com/image/art%3A10.1186%2Fs13023-017-0566-8/MediaObjects/13023_2017_566_Fig4_HTML.gif
Fig. 4
Growth of publications versus number of cumulative citations


Top cited articles

Table 3
represents top cited articles across different time periods. Top cited
articles during the period from 1946 to 1985 were mainly published in
dermatology journals and the main theme of the top cited articles was
description of SJS and TEN cases with emphasis on medication – induced
skin reactions. During the period from 1986 to 2005, the top cited
articles were published in dermatology journals and prestigious general
science journals such as Nature and Science.
The main theme of top cited articles during that period was
classification of the condition, illness severity score, and molecular
pathogenesis of the SJS and TEN skin reaction. During the time period
from 2006 to 2015, top cited articles were published in pharmacogenetic
journals as well as dermatology journals. The emphasis of top cited
articles during that period was on the association between SJS. TEN,
medications, and HLA typing.
Table 3
Top 10 cited articles on SJS and TEN in three different time periods
Rank
Top 10 cited articles for the time period
1946 – 1985
N = 1246
Top 10 cited articles for the time period
1986 - 2005
N = 1288
Top 10 cited articles for the time period
2006 – 2015
N = 1322
Reference
Number of citation
Reference
Number of citation
Reference
Number of citation
1
392
[72]
938
[73]
404
2
[74]
159
[75]
829
[76]
321
3
[77]
153
[78]
825
[79]
299
4
[80]
101
[81]
771
[82]
278
5
[83]
94
[84]
438
[49]
244
6
[85]
89
[86]
393
[87]
230
7
[88]
86
[89]
325
[90]
206
8
[91]
75
[92]
322
[93]
205
9
[94]
72
[95]
316
[96]
178
10
[97]
66
[98]
288
[99]
173
Main journals
7 Dermatology
6 Dermatology
4 Dermatology and 4 Genetic
Main focus
Descriptive studies, ocular consequences, drug etiology
Illness severity Score,
classification of TEN, and molecular aspects of therapy
Ethnic variations, role of genetics, and anti-epileptics induced TEN
SJS Stevens – Johnson Syndrome
TEN Toxic Epidermal Necrolysis


Active countries

Researchers from 96 different countries contributed to the advancement of knowledge on SJS and TEN. Table 4
shows a list of active countries which had published a minimum of 20
publications on SJS and TEN. The total number of publications produced
by these active countries was 2640 (68.46%). The United States of
America (USA) (n = 640; 16.57%) ranked first in number of publications followed by Japan (n = 237; 6.14%), France (n = 234, 6.06%) and the United Kingdom (UK) (n = 199;
5.15%). When research productivity was stratified by world region, the
European union had the greatest share followed by north America and Asia
(Fig. 5a). Geographic distribution of research productivity is presented in Fig. 5b.
Table 4
List of active countries/territoris in publishing on SJS and TEN
Country/Territory
Frequency
% N = 3856
Number of collaborating countries
SCP
Percent
MCP
Percent
United States
640
16.60
36
572
89.38
68
10.63
Japan
237
6.15
7
225
94.94
12
5.06
France
234
6.07
19
193
82.48
41
17.52
United Kingdom
199
5.16
16
178
89.45
21
10.55
Germany
163
4.23
19
121
74.23
42
25.77
India
159
4.12
6
153
96.23
6
3.77
Italy
152
3.94
14
133
87.50
19
12.50
Spain
136
3.53
1
134
98.53
2
1.47
Turkey
71
1.84
3
68
95.77
3
4.23
South Korea
70
1.82
4
66
94.29
4
5.71
Taiwan
68
1.76
8
59
86.76
9
13.24
Canada
58
1.50
10
43
74.14
15
25.86
Belgium
54
1.40
4
49
90.74
5
9.26
Poland
50
1.30
4
49
98.00
1
2.00
Australia
46
1.19
4
43
93.48
3
6.52
China
45
1.17
4
37
82.22
8
17.78
Netherlands
44
1.14
8
33
75.00
11
25.00
Switzerland
40
1.04
9
27
67.50
13
32.50
Singapore
37
0.96
9
30
81.08
7
18.92
Israel
36
0.93
9
25
69.44
11
30.56
Brazil
28
0.73
7
22
78.57
6
21.43
Portugal
26
0.67
5
22
84.62
4
15.38
Austria
25
0.65
8
17
68.00
8
32.00
Mexico
22
0.57
4
18
81.82
4
18.18
SJS Stevens – Johnson Syndrome
TEN Toxic Epidermal Necrolysis
SCP Single Country Publication (intra-country publication)
MCP Multiple Country Publication (inter-country publication = International collaboration)

https://static-content.springer.com/image/art%3A10.1186%2Fs13023-017-0566-8/MediaObjects/13023_2017_566_Fig5_HTML.gif
Fig. 5
a Productivity of various world regions. b Geographic distribution of SJS and TEN publications using ArcMap 10.1 software

Network visualization of citations received by articles produced by active countries is shown in Fig. 6.
Publications form the USA received the highest number of citation
followed by those from France, Germany, Italy and the UK. The volume of
citations is correlated with size of the circle representing each
country in network visualization map.
https://static-content.springer.com/image/art%3A10.1186%2Fs13023-017-0566-8/MediaObjects/13023_2017_566_Fig6_HTML.gif
Fig. 6
Network visualization map of citations for articles produced by active countries

International
collaboration (MCP) was also assessed for the active countries.
Approximately one third of articles (32.5%) produced by Switzerland had
international authors. In contrast, only 1.47% of articles produced by
Spain had lowest international authors. International collaboration
among active countries is presented by network visualization map (Fig. 7).
The thickness of the link between any two countries represents the
strength of collaboration while the size of the circle assigned for that
country represents the extent of international collaboration. The
network visualization map showed that the strongest collaboration was
between Germany and France. The USA had the largest circle size
indicative of the highest extent of international collaboration. The
percentage of MCP for the USA was not the highest. However, because of
the very large number of published articles by the USA, the extent of
international collaboration by the USA was the highest. When network
visualization map was presented as a density visualization map,
countries such as Germany, France, UK, Netherlands, Belgium, Israel, and
Italy were found in a close cluster while the USA, China, Taiwan,
Singapore, Thailand, and Australia were found in a second close cluster
suggestive of close collaboration.
https://static-content.springer.com/image/art%3A10.1186%2Fs13023-017-0566-8/MediaObjects/13023_2017_566_Fig7_HTML.gif
Fig. 7
Network visualization map of country co-authorship (international collaboration)


Active institutions

Active institutions in publishing articles on SJS and TEN were presented in Fig. 8. The most active institution was Universite Paris 12 Val de Marne in France (n = 66; 1.71%) followed by Hospital Henri Mondor in France (n = 58; 1.5%) and Kyoto Prefectural University of Medicine in Japan (n = 40;
1.03%). The first two active institutions were in France. When
institutions with a minimum productivity of ten articles were analyzed
for country/territory affiliation, the USA ranked first with eight
institutions followed by Italy with six institutions, France with five
institutions, Japan with five institutions, and Taiwan with four
institutions.
https://static-content.springer.com/image/art%3A10.1186%2Fs13023-017-0566-8/MediaObjects/13023_2017_566_Fig8_HTML.gif
Fig. 8
Active institutions in publishing about SJS and TEN


Active authors

Active authors in publishing about SJS and TEN are shown in Table 5.
Professor Roujeau, J.-C. from France had the highest contribution with
113 articles. Furthermore, Professor Roujeau, J.-C. had the highest h-index.
Five active authors were French and three were Japanese. The other
active authors were from Germany and Belgium. Co-citation analysis of
active authors shows that Roujeau, J.-C was the most commonly co-cited
author followed by Revuz, J. and Mockenhaupt, M (Fig. 9). Active authors were mainly from France, japan, and Belgium
Table 5
Active authors in publishing articles on SJS and TEN
Author
Frequency
% N = 3856
h-index
Country Affiliation
Roujeau, J.C.
113
2.93
48
France
Revuz, J.
57
1.48
28
France
Mockenhaupt, M.
51
1.32
23
Germany
Sotozono, C.
39
1.01
18
Japan
Paquet, P.
36
0.93
17
Belgium
Ueta, M.
30
0.78
13
Japan
Wolkenstein, P.
29
0.75
17
France
Aihara, M.
25
0.65
10
Japan
Touraine, R.
22
0.57
10
France
Piérard, G.E.
26
0.67
16
Belgium
Valeyrie-Allanore, L.
20
0.52
9
France
h-index Hirsch index
SJS Stevens – Johnson Syndrome
TEN Toxic Epidermal Necrolysis

https://static-content.springer.com/image/art%3A10.1186%2Fs13023-017-0566-8/MediaObjects/13023_2017_566_Fig9_HTML.gif
Fig. 9
Co-citation analysis of active authors publishing articles on SJS and TEN


Active journals

Table 6
shows a list of 24 active journals involved in publishing articles on
SJS and TEN. Each journal had published at least 20 articles on SJS and
TEN. As expected, the majority of these journals were in the field of
dermatology. Three journals were in the field of burns, two were in the
field of ophthalmology and two were in the field of general medicine.
Journal of Archives of Dermatology ranked first in number of publications followed by British Journal of Dermatology and Lancet. Citation analysis showed that articles on SJS and TEN published in Archives of Dermatology received the highest number of citations while those published in Journal of The American Academy of Dermatology and British Journal of Dermatology ranked second and third respectively (Fig. 10).
Table 6
Active journals in publishing articles on SJS and TEN
Journal
Frequency
% N = 3856
IF
Archives of Dermatology
123
3.19
0.14
British Journal of Dermatology
88
2.28
4.275
Lancet
83
2.15
45.217
Journal of The American Academy of Dermatology
80
2.07
4.449
International Journal of Dermatology
63
1.63
1.312
Clinical and Experimental Dermatology
46
1.19
1.315
Acta Dermato Venereologica
39
1.01
0.54
Journal of Dermatology
39
1.01
1.577
Annales De Dermatologie Et De Venereologie
36
0.93
0.07
Klinicheskaya Meditsina
33
0.86
0.08
Dermatology
32
0.83
1.569
Journal of Burn Care and Research
32
0.83
1.37
American Journal of Ophthalmology
30
0.78
3.831
British Medical Journal
28
0.73
19.967
Burns
28
0.73
0.89
Journal of The European Academy of Dermatology and Venereology
28
0.73
2.826
Korean Journal of Dermatology
27
0.70
0.04
Pediatric Dermatology
27
0.70
1.163
Actas Dermo Sifiliograficas
26
0.67
0.61
Annals of Pharmacotherapy
26
0.67
2.35
Journal of Burn Care and Rehabilitation
26
0.67
N/A
Indian Journal of Dermatology Venereology and Leprology
25
0.65
1.488
Cornea
21
0.54
1.18
Bulletin De La Societe Francaise De Dermatologie Et De Syphiligraphie
20
0.52
N/A
IF impact factor
N/A not applicable
SJS Stevens – Johnson Syndrome
TEN Toxic Epidermal Necrolysis

https://static-content.springer.com/image/art%3A10.1186%2Fs13023-017-0566-8/MediaObjects/13023_2017_566_Fig10_HTML.gif
Fig. 10
Citation analysis of active journals in publishing articles on SJS and TEN


Drug induced SJS and TEN, co-morbid conditions, and complications

The
most commonly encountered medication in retrieved documents was
carbamazepine which was mentioned in 146 documents followed by phenytoin
which was mentioned in 114 and allopurinol which was mentioned in 112.
Lamotrigene was mentioned in 93 documents while the antiviral nevirapine
was mentioned in 53. Other mentioned medications include: valproic acid
(n = 50), phenobarbital (n = 45), and sulfamethoxazole (n = 44).
The over-the counter analgesic, paracetamol/acetaminophen was mentioned
in 37 documents. Other causative agents include infections which
include mycoplasma that had been mentioned in 111 documents. Other
infectious agents include cytomegalovirus which was mentioned in seven
documents. Vaccinations as a causative agent had been mentioned in 26
documents.
Human
immune deficiency virus was co-mentioned in a total of 116 documents on
SJS and TEN while cancer was co-mentioned in 91, tuberculosis in 29,
hypertension in 19, and diabetes mellitus in 16 documents.
A
total of 375 documents listed ocular/ophthalmic problems as
complications of SJS/TEN, 26 mentioned urinary tract infections, and 95
mentioned sepsis/septicemia.

Genetic predisposition

A
total of 65 documents discussed the genetic risk factors for developing
SJS and TEN. Visualization map for terms present in title/abstract of
these documents is shown in Fig. 11.
The map consisted of three cluster (red, green and blue). Each cluster
represents terms that were commonly mentioned together. Cluster number
one included the following items: (carbamazepine/CBZ, genetic marker,
Han Chinese/Han Chinese population, HLA b allele, HLA b 1502/HLA b 1502
allele, phenytoin, and Taiwan. The second cluster included the following
items: (gene, genetic predisposition, HLA-A, HLA-A0206, HLA class,
Human Leukocyte Antigen, Japanese patients, and Ocular complications.
The third cluster included the following terms: (Allopurinol, HLA
allele, HLA-B 5801, and Japanese).
https://static-content.springer.com/image/art%3A10.1186%2Fs13023-017-0566-8/MediaObjects/13023_2017_566_Fig11_HTML.gif
Fig. 11
Network visualization map of predisposing genetic factors to SJS and TEN


Discussion

In
this study, we presented a bibliometric overview of literature on SJS
and TEN published in the past seven decades. SJS and TEN are associated
with high mortality rate and medications play a role as causative agents
of SJS and TEN. Therefore, SJS and TEN are conditions with
multidisciplinary aspects from a research and clinical management points
of view [49, 50].
Our results showed that international collaboration in research
pertaining to SJS and TEN is relatively low when compared with other
fields. This might be due to the clinical nature and time course of the
conditions. SJS and TEN are not chronic condition and except for the
genetic component of these conditions, little can be done for
international collaboration in research on SJS and TEN.
Our
study showed that number of publications on SJS and TEN increased
slowly and gradually over the past half century. This increase might be
due to natural growth of medical publications in the past half century
or due to increased reported cases of drug-induced SJS and TEN in the
past half century. No doubt that the increasing number of newly approved
drugs could be associated with new cases of SJS and TEN. Another
potential explanation for the increased number of publications on SJS
and TEN is the potential association of some infectious diseases such as
Mycoplasma pneumonia, HIV, hepatitis, Cytomegalovirus, and others with SJS and TEN.
Our
study showed that only two thirds of retrieved articles were in
English. This suggests that cases of SJS and TEN are found and reported
by non-English language from all over the world. Results of our study
indicated that countries in northern America, Latin America, Europe,
Middle East, and Southeast Asia were among active countries in
publishing on SJS and TEN. Together with the high value of h-index
of retrieved documents, it can be deduced that SJS and TEN are
considered a serious and important research topic with high number of
readers. Furthermore, the fact that some journals in the active list
have high IF is suggestive of the clinical importance of SJS and TEN as a
research and medical topic.
Our
finding that the USA had the largest share of publications was not
surprising given the huge budget allocated for research and the vast
number of research centers in the USA. Several bibliometric studies on
various medical topics concluded that the USA ranked first in research
productivity [39, 40, 51, 52, 53].
However, it was surprising that most active authors were either French
or Japanese and none were Americans. This could be attributed to
regional differences in commonly prescribed drugs or due to differences
in genetic predisposition [54, 55].
The analysis of Japanese Adverse Drug Event Report (JADER) database and
analysis of the time-to-onset profile of SJS and TEN yielded data that
are different from the Europeans [54].
A similar study was the EuroSCAR-study which is a multicenter European
study carried out to evaluate medication induced severe cutaneous
adverse reactions (SCAR) [55].
The EuroSCAR registry classified drugs that induce SJS/TEN into high,
moderate, and low risk drugs with allopurinol and carbamazepine being in
the high-risk category [56].
Our
study showed that anti-epileptic drugs, particularly carbamazepine,
phenytoin, lamotrigene and others were most commonly encountered in SJS
and TEN literature. Different studies reported different main causative
drugs of SJS and TEN possibly due to ethnic and genetic variations or
due to different types of prescribing pattern. An Indian multicentric
retrospective study of drug – induced SJS and TEN found that
antimicrobials, nonsteroidal anti-inflammatory drugs, and antiseizure
drugs were the most commonly associated groups with SJS and TEN and that
antiseizure drugs were more often associated with TEN than other drugs [57].
A 20-year study in children in tertiary care hospital in Thailand found
that antiepileptic drug group was the most common causative drug,
followed by antibiotic drug group, and others which included
nonsteroidal antiinflammtory drugs (NSAIDs) and chemotherapy drugs [10].
A study in Indonesia found that most common causative drugs were
paracetamol, carbamazepine, amoxicillin, ibuprofen, rifampicin, and
trihexyphenidyl [58].
Our
study showed and emphasized previous findings of associations between
certain genes and drug – induced SJS/TEN. For example, SJS/TEN induced
by anti-epileptics such as carbamazepine and phenytoin is associated
with HLA-B*15:02 in Han Chinese people [59]. Association of HLA-A 31:01 with carbamazepine – induced SJS have been reported in children [60].
A study in Thailand concluded that there is an association between HLAB
(*) 58:01 and allopurinol-induced SJS-TEN in a Thai population [61]. Similar findings were obtained in Korean cases [62]. Presence of sever ocular complications in SJS/TEN have been linked to certain HLA types such as HLA-A*02:06 [63].
The
top cited articles on SJS and TEN discussed several important issues in
the field including ones on medication – induced SJS and TEN, genetic
and ethnic role, illness severity scoring, treatment potential and
others. The role of immunoglobulin in treatment of SJS/TEN is one of the
top cited issues on SJS and TEN. Intravenous immunoglobulin as a
therapeutic option has shown efficacy in reducing length of skin
reactions and reducing severity of symptoms [64, 65, 66].
Recent published guidelines for the management of SJS and TEN included
the removal of offending cause plus the initiation of high dose
parenteral corticosteroids [67]. Use of plasmapheresis as an adjuvant therapy in SJS and TEN have shown beneficial effects [68, 69, 70, 71].
Bibliometric
studies are not without limitations. Despite that Scopus is the largest
database available, articles published in non-indexed journals were not
included in this study. Furthermore, the interchangeable use of SJS and
EMM in the 1980s made the accuracy of results obtained during that
period less than ideal. The keywords were used in title search which
might have caused some data loss. However, title search is important to
maintain high level accuracy and minimize false positive results. Scopus
database retrieved not only countries but also distinct territories and
that is why China and Taiwan appeared as separate countries/territories
in genetic map despite that both are of similar ethnic group because
Scopus database has China and Taiwan as separate entities/territories.
Finally, the use of Web of Science (WoS) is believed to give data
published in journals with impact factor as reported by Journal Citation
Report. Therefore, WoS is believed to retrieve data in influential
journals. In this manuscript we sought to cover the largest number of
publications and therefore we did not utilize WoS.

Conclusion

Our
study showed that there was a gradual growth of publications on SJS and
TEN in the past six decades. Bibliometric analysis of literature on SJS
and The USA is important for clinicians and research to pinpoint gaps
and understand worldwide aspect of these conditions regarding
differential epidemiology and ethnic variations. Young researchers will
learn from such bibliometric analysis studies about top cited articles
on the conditions and names of institutions and authors who are leaders
in the subject. Mapping genetic background and ethnicities is also of
benefit for understanding medication – induced SJS and TEN among various
ethnic groups. Despite the importance of the topic, the extent of
international collaboration on the topic was relatively low, something
which needs to addressed and encouraged.

Abbreviations

SJS: 
Stevens – Johnson Syndrome
TEN: 
Toxic epidermal necrolysis

Declarations

Acknowledgement

The author would like to acknowledge professors Saed Zyoud and Adham Abu-Taha for their technical and professional editing.

Funding

None.

Availability of data and materials

All data present in this article can be retrieved from Scopus using keywords listed in the methodology.

Authors’ contributions

This is a single author publication. The author was in charge of data collection, writing, analysis, submission and revision.

Competing interests

The author declares that he has no competing interests.

Consent for publication

Not applicable.

Ethics approval and consent to participate

Not applicable.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/),
which permits unrestricted use, distribution, and reproduction in any
medium, provided you give appropriate credit to the original author(s)
and the source, provide a link to the Creative Commons license, and
indicate if changes were made. The Creative Commons Public Domain
Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Bibliometric analysis of literature on toxic epidermal necrolysis and Stevens-Johnson syndrome: 1940 – 2015 | Orphanet Journal of Rare Diseases | Full Text

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