Volume 2025, Issue 1 6527730

Review Article

Open Access

Allopurinol-Induced Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis: A Systematic Review of Case Reports and Case Series

Shirin Borjikhani,

Shirin Borjikhani

orcid.org/0009-0001-2929-0924

Student Research Committee , Alborz University of Medical Sciences , Karaj , Iran , abzums.ac.ir

Search for more papers by this author

Sholeh Ebrahimpour,

Sholeh Ebrahimpour

orcid.org/0000-0002-6278-2509

Department of Clinical Pharmacy , School of Pharmacy , Alborz University of Medical Sciences , Karaj , Iran , abzums.ac.ir

Pharmaceutical Care Department , Shahid Madani Hospital , Alborz University of Medical Sciences , Karaj , Iran , abzums.ac.ir

Search for more papers by this author

Mehdi Mohammadi,

Corresponding Author

Mehdi Mohammadi

[email protected]

orcid.org/0000-0001-8970-479X

Department of Clinical Pharmacy , School of Pharmacy , Alborz University of Medical Sciences , Karaj , Iran , abzums.ac.ir

Search for more papers by this author

Shirin Borjikhani,

Shirin Borjikhani

orcid.org/0009-0001-2929-0924

Student Research Committee , Alborz University of Medical Sciences , Karaj , Iran , abzums.ac.ir

Search for more papers by this author

Sholeh Ebrahimpour,

Sholeh Ebrahimpour

orcid.org/0000-0002-6278-2509

Department of Clinical Pharmacy , School of Pharmacy , Alborz University of Medical Sciences , Karaj , Iran , abzums.ac.ir

Pharmaceutical Care Department , Shahid Madani Hospital , Alborz University of Medical Sciences , Karaj , Iran , abzums.ac.ir

Search for more papers by this author

Mehdi Mohammadi,

Corresponding Author

Mehdi Mohammadi

[email protected]

orcid.org/0000-0001-8970-479X

Department of Clinical Pharmacy , School of Pharmacy , Alborz University of Medical Sciences , Karaj , Iran , abzums.ac.ir

Search for more papers by this author

First published: 15 April 2025

https://doi.org/10.1155/dth/6527730

Academic Editor: Snejina G. Vassileva

Share a link

Email
Wechat
Bluesky

Abstract

Background: Allopurinol is a known cause of mucocutaneous adverse drug reactions, including Stevens–Johnson syndrome and toxic epidermal necrolysis. The aim of this systematic review was to characterize the clinical presentation, identify risk factors, and evaluate the best treatment strategies for allopurinol-induced severe skin reactions.

Methods: The PubMed, Embase, and Scopus databases were systematically searched to identify English case reports and case series of allopurinol-induced Stevens–Johnson syndrome and toxic epidermal necrolysis. Animal studies, reviews, book chapters, randomized and nonrandomized human studies, observational studies, and conference abstracts were excluded. The Joanna Briggs Institute (JBI) critical appraisal checklists were used to assess the quality of the included studies.

Results: Forty-seven case reports and 21 case series were included in the analysis, which reported 91 individual patient datasets. The reaction occurred after a median of 16 days (8.5 days in those with prior reactions to allopurinol). Rapid dose escalation was observed in half of the patients (21 of 43) for whom dose-increment schedules were reported. Mucosal involvement was observed in 72 (90.0%) patients. Corticosteroids, IVIG, cyclosporine, and plasma exchange were the most common treatment modalities. Twenty-one patients (23.6%) died, and 68 (76.4%) were discharged.

Conclusion: Although gout is 2–3 times more common in men, the numbers of cases were similar in both sexes, likely due to higher reporting rates in women. Rapid dose escalation is a risk factor for the occurrence of severe skin reactions. Corticosteroids, IVIG, and plasma exchange appear to be reasonable treatment options.

1. Introduction

Allopurinol, a xanthine oxidase inhibitor, is commonly used for the treatment of gout, cancer therapy-induced hyperuricemia, and recurrent calcium oxalate calculi [1]. Moreover, it is increasingly being used in patients with asymptomatic hyperuricemia [2].

Although allopurinol is generally well tolerated, it has been associated with severe hypersensitivity reactions, including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) [2]. These reactions occur in approximately 1 in 1000 patients receiving allopurinol and are associated with a mortality rate of 20%–25% [3]. Many patients indicated for allopurinol therapy have other underlying medical conditions, such as chronic kidney disease and cardiovascular disorders, which are considered independent risk factors for hypersensitivity reactions to allopurinol [3].

SJS and TEN are considered the same reaction, and the difference lies in the extent of skin involvement. In SJS, SJS/TEN overlap, and TEN, skin detachment occurs in less than 10%, 10%–30%, and greater than 30% of the body surface area (BSA), respectively. These reactions begin with general malaise, fever, and flu-like symptoms, followed by the appearance of pruritic macules and painful blisters. The mucosal surfaces of the eyes, oral cavity, and genitalia are frequently affected. In addition, other organs, such as the cardiovascular, pulmonary, and gastrointestinal systems, are involved [4].

Although case reports of severe allopurinol-induced skin reactions have been published, they have not been comprehensively reviewed. We conducted a systematic review of biomedical databases to identify case reports and case series of allopurinol-induced SJS/TEN. The aims of this systematic review were to characterize the clinical presentation, identify contributing factors, and evaluate the efficacy of various treatment modalities used in the management of these reactions.

2. Methods

This systematic review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist [5]. After the study protocol was reviewed, the research council and the research ethics committee of the Alborz University of Medical Sciences approved the study (IR.ABZUMS.REC.1401.155).

2.1. Literature Search

A systematic literature search was conducted via a predefined search strategy in the PubMed, Embase, and Scopus databases. Both free text and Medical Subject Heading (MeSH) terms were used to perform the literature search. The search strategy is presented in the Supporting Table 1. All English case reports or case series studies that reported at least one case of SJS, TEN, or SJS/TEN overlap associated with allopurinol use were included. Animal studies, reviews, book chapters, randomized and nonrandomized human studies, observational studies, and conference abstracts were excluded. No age or time limits were applied. The last date of the search in the PubMed database was March 31, 2023; that in Scopus was April 2, 2023; and that in Embase was May 6, 2023.

2.2. Study Selection

Two independent researchers (SB and MM) explored the titles and abstracts of the records. Relevant studies were exported to EndNote (Version 21.1 for Windows; Thomson Reuters, Philadelphia, PA, USA). References of narrative reviews, systematic reviews, case reports, and case series were also searched to find additional studies.

The duplicates were then removed, and the two investigators evaluated each record according to the inclusion criteria of the study. In cases of disagreement, a third investigator (SE) was consulted, and the decision to include the study was made on the basis of consensus. Figure 1 shows the PRISMA flowchart of the study.

Details are in the caption following the image — **Figure 1**
Open in figure viewer PowerPoint

The PRISMA flow diagram of the study.

2.3. Data Extraction

Two authors performed the data extraction (SB and MM). A comprehensive set of data, including the first author’s name, year of publication, age, sex, race, and country of the patient, indication of allopurinol, dosage administered, duration of drug use before the onset of rash, HLA-B^∗5801 status, history of drug allergy, signs and symptoms of the reaction, concomitant medications, laboratory data, paraclinical findings, SCORTEN score [6], management strategies, and patient outcome, was extracted from each study.

In addition, the Naranjo adverse drug reaction probability scale was recorded for each patient [7]. If the author(s) of the case report did not mention the Naranjo score, we calculated it on the basis of the data of the report.

2.4. Quality Assessment

Two investigators (SB and MM) evaluated the quality of the studies via the Joanna Briggs Institute (JBI) critical appraisal checklists for case reports [8] and case series [9]. A third investigator (SE) was consulted in case of disagreement.

2.5. Statistical Analysis

Data analysis was conducted via IBM SPSS Statistics Software (Version 26.0. IBM Corp., Armonk, NY, USA). Frequencies and percentages were used to describe qualitative variables.

3. Results

3.1. Characteristics of the Studies

As presented in Figure 1, 928 articles were identified through the database search. After the removal of duplicates, full-text searches, and eligibility assessments, 66 articles were included in the review. Two additional records were also retrieved via Google Scholar and reference searching. Finally, 68 articles, including 47 case reports and 21 case series, were included in the study, which reported 91 individual patient datasets.

The quality assessment of the studies is presented in Supporting Table 2 (case reports) and Supporting Table 3 (case series) of the Supporting file. The overall quality of case reports was good, but most studies did not report or were unclear about treatment-related adverse effects. Except for two questions, the case series studies were of good quality. First, 12 of the 21 studies did not include consecutive patients. Second, 14 of the 21 studies were unclear regarding complete patient inclusion.

3.2. Patient Characteristics

The detailed characteristics of the included patients are presented in Table 1. Forty-eight (52.7%) patients were male, and 43 (47.3%) were female. The patients’ ages ranged from 8 to 96 years, with a median of 62.

Table 1. Detailed characteristics of the included patients.

Case no.	Author/year	Age/sex	Dose (mg)/duration (days)	Presentation	Naranjo score	SCORTEN score	Mucosal involvement/BSA%	Management	Outcome
1	Kantor, 1970 [10]	72/M	100 BD/7	TEN	Probable	NR	+/NR	Supportive, corticosteroid	Death

2	Stratigos et al., 1972 [11]	58/F	600 QD/2	TEN	Probable	NR	−/NR	Supportive, corticosteroid	Death

3	Ellman et al., 1975 [12]	76/F	100 QID/24	TEN	Probable	NR	+/NR	Supportive, corticosteroid	Death
4		60/F	100 TID/30	TEN	Probable	NR	+/NR	Corticosteroid	Discharge
5		45/M	100 QID/27	TEN	Probable	NR	+/NR	Supportive, corticosteroid	Discharge

6	Chan et al., 1977 [13]	58/F	100 TID/21	SJS	Probable	NR	+/NR	Supportive, corticosteroid	Discharge
7		35/M	100 TID/28	SJS	Probable	NR	+/NR	Supportive, corticosteroid	Discharge
8		62/M	100 TID/21	TEN	Possible	NR	+/NR	Supportive, corticosteroid	Discharge

9	Bennett et al., 1977 [14]	54/M	100 TID/21	TEN	Probable	NR	+/NR	Supportive, corticosteroid	Discharge

10	Assaad et al., 1978 [15]	38/M	200 TID/37	SJS	Probable	NR	+/NR	Supportive, corticosteroid	Discharge

11	Lang, 1979 [16]	45/M	NR/30	TEN	Probable	NR	+/NR	Supportive, corticosteroid	Discharge
12		61/M	NR/14	TEN	Probable	NR	+/NR	Supportive, corticosteroid	Discharge
13		76/F	NR/42	TEN	Probable	NR	+/NR	Supportive, corticosteroid	Death
14		62/F	NR/14	TEN	Probable	NR	+/NR	Supportive, corticosteroid	Discharge
15		47/F	NR/21	TEN	Probable	NR	+/NR	Supportive, corticosteroid	Discharge

16	Marra et al., 1982 [17]	47/F	NR	TEN	Probable	NR	+/NR	Supportive, corticosteroid	Discharge

17	Davies et al., 1983 [18]	53/M	NR/60	SJS	Probable	NR	+/NR	Supportive, corticosteroid	Discharge

18	Vinciullo, 1984 [19]	24/M	NR/29	TEN	Probable	NR	−/NR	Supportive, corticosteroid	Discharge

19	Pennell et al., 1984 [20]	71/M	100 BD/38	SJS	Possible	NR	+/NR	Corticosteroid	Death

20	Dan et al., 1984 [21]	84/M	NR/5	TEN	Probable	NR	+/NR	Supportive, corticosteroid	Discharge

21	Edwards and Ridder et al., 1985 [22]	46/M	100 TID/28	SJS	Probable	NR	+/NR	Supportive, corticosteroid	Discharge

22	Renwick, 1985 [23]	78/M	300 QD/7	SJS	Probable	NR	+/NR	Supportive	Death

23	Auböck et al., 1985 [24]	52/F	300 QD/14	TEN	Probable	NR	NR	Supportive, corticosteroid	Discharge
24		72/F	300 QD/35	TEN	Possible	NR	NR	Supportive, corticosteroid	Discharge
25		73/M	300 QD/7	TEN	Probable	NR	NR	Supportive, corticosteroid	Discharge
26		77/F	300 QD/28	TEN	Probable	NR	NR	Supportive, corticosteroid	Discharge
27		62/F	300 QD/21	TEN	Probable	NR	NR	Supportive, corticosteroid	Death
28		32/M	300 QD/14	TEN	Probable	NR	NR	Supportive, corticosteroid	Discharge

29	Sakellariou et al., 1991 [25]	65/M	NR/10	TEN	Probable	NR	+/50	Supportive, plasma exchange, corticosteroid, IVIG	Discharge

30	Heng et al., 1991 [26]	47/M	NR/2	TEN	Probable	NR	+/NR	Corticosteroid, cyclophosphamide	Discharge

31	Ashworth, 1992 [27]	70/F	300 QD/25	SJS	Possible	NR	+/NR	Supportive	Discharge

32	Alfandari et al., 1994 [28]	32/M	NR	TEN	Possible	NR	+/30	NR	Discharge

33	Halevy et al., 1999 [29]	58/M	300 QD/13	SJS	Possible	NR	+/10	Supportive	Discharge

34	Bashir et al., 2000 [30]	65/F	300 BID/14	SJS	Probable	NR	+/36	Supportive, corticosteroid	Discharge

35	Zakrzewski et al., 2002 [31]	35/F	300 QD/4	TEN	Possible	NR	−/50	Supportive	Death

36	Yeung et al., 2005 [32]	76/F	NR	TEN	Probable	3	NR/70	Supportive, IVIG	Discharge
37		29/M	NR	TEN	Probable	1	NR/50	Supportive, corticosteroid, IVIG	Discharge
38		82/M	NR	TEN	Probable	3	NR/40	Supportive, IVIG	Discharge
39		51/F	NR	SJS	Probable	4	NR/10	Supportive, IVIG	Discharge
40		77/F	NR	SJS/TEN	Probable	NR	NR/20	Supportive, corticosteroid, IVIG	Discharge

41	Kakeda et al., 2005 [33]	68/M	NR/23	TEN	Probable	NR	+/NR	Supportive, corticosteroid	Death

42	Saxena et al., 2005 [34]	72/M	NR/21	TEN	Probable	NR	+/80	Supportive, corticosteroid	Death

43	Stenton et al., 2005 [35]	81/M	300 QD/1	TEN	Probable	NR	+/NR	Supportive, corticosteroid, IVIG	Discharge

44	Paquet et al., 2007 [36]	51/F	200 QD/14	TEN	Probable	NR	+/80	Supportive, IVIG	Discharge

45	Dainichi et al., 2007 [37]	57/M	NR/8	SJS	Probable	NR	+/NR	NR	NR
46	Dainichi et al., 2007 [37]	93/M	NR/14	TEN	Probable	NR	+/NR	NR	NR

47	Kemen et al., 2009 [38]	8/F	NR/14	TEN	Probable	NR	−/95	Supportive, IVIG	Discharge

48	Hsieh et al., 2009 [39]	82/F	100 QD/56	SJS	Possible	NR	+/20	Supportive, corticosteroid	Discharge

49	Ventura et al., 2010 [40]	76/F	150 QD/9	TEN	Probable	NR	+/70	Corticosteroid	Death
50	Ventura et al., 2010 [40]	77/F	300 QD/NR	TEN	Probable	NR	+/30	Supportive, corticosteroid	Death

51	Hanken et al., 2010 [41]	80/F	NR/14	TEN	Probable	NR	−/45	Supportive, corticosteroid	Discharge

52	Fernando et al., 2010 [42]	35/M	NR/14	SJS/TEN	Probable	NR	+/NR	Supportive, IVIG, cyclosporine	Discharge

53	Lee et al., 2010 [43]	63/F	200 QD/7	SJS/TEN	Probable	NR	+/20	Supportive, corticosteroid, IVIG	Discharge

54	Ranu et el., 2011 [44]	81/F	NR/10	TEN	Probable	NR	+/60	Supportive, IVIG	Death
55		67/M	NR/14	TEN	Probable	NR	+/80	Supportive, corticosteroid, IVIG	Death
56		56/F	NR/30	TEN	Probable	NR	−/70	Supportive, IVIG	Discharge
57		78/F	NR/21	TEN	Probable	NR	+/90	Supportive, IVIG	Death

58	Comparin et al., 2012 [45]	55/F	NR/15	TEN	Probable	4	+/80	Corticosteroid	Discharge

59	Lee et al., 2012 [46]	68/F	NR/14	SJS	Definite	NR	+/NR	Supportive	Discharge

60	Kamal et al., 2012 [47]	62/M	NR/0.5	TEN	Probable	5	+/90	Supportive, IVIG	Discharge

61	Sawicki et al., 2013 [48]	64/M	NR/2920	SJS	Probable	NR	+/NR	IVIG	Discharge

62	Lee et el., 2013 [49]	72/M	300 QD/7	SJS	Probable	NR	−/NR	Supportive, corticosteroid, cyclosporine	Discharge

63	Watanabe et al., 2013 [50]	73/F	300 QD/12	TEN	Probable	NR	+/80	Supportive, plasma exchange, corticosteroid, IVIG	Death

64	Caldarola et al., 2015 [51]	82/M	300 QD/10	SJS	Probable	NR	+/70	Corticosteroid	Death

65	Villano et al, 2015 [52]	60/F	NR/1	TEN	Probable	3	+/NR	Supportive	Discharge

66	Paik et al., 2015 [53]	43/F	100 TID/10	SJS	Probable	NR	+/9	Supportive, corticosteroid	Discharge

67	Rodgers et al., 2016 [54]	60/F	NR/21	TEN	Probable	4	+/80	Supportive, IVIG	Discharge

68	Casagranda et al., 2017 [55]	86/F	NR/30	DRESS/SJS	Probable	NR	+/NR	Supportive, corticosteroid	Discharge

69	Banerjee et al., 2017 [56]	62/M	300 QD/2	TEN	Probable	NR	+/50	Supportive, corticosteroid	Death

70	Brown et al., 2017 [57]	71/F	NR/7	TEN	Probable	5	+/30	Supportive, plasma exchange, corticosteroid, IVIG	Discharge

71	Wallenborn et al., 2017 [58]	44/M	NR/21	TEN	Probable	2	+/80	Supportive, corticosteroid, infliximab	Discharge

72	Irfan et al, 2017 [59]	45/M	NR/3	TEN	Probable	3	+/50	Supportive, plasma exchange	Discharge

73	Wang F et al., 2019 [60]	33/M	250 QD/9	TEN	Probable	NR	+/60	Supportive, corticosteroid, IVIG	Discharge

74	Buenrostro-Rubio et al., 2019 [61]	35/M	100 QD/21	TEN	Probable	3	+/95	Supportive, corticosteroid	Discharge

75	Claytor et al., 2019 [62]	71/F	NR/7	SJS/TEN	Probable	4	+/25	Supportive, corticosteroid, IVIG	Death

76	Chhabra M et al., 2019 [63]	50/F	NR/2	SJS	Probable	NR	+/25	Supportive, corticosteroid, cyclosporine	Discharge

77	Ponzo et al., 2019 [64]	81/F	NR/32	TEN	Probable	4	+/50	Supportive, cyclosporine	Discharge

78	Gupta et al., 2019 [65]	85/F	300 QD/6	SJS	Probable	NR	+/NR	Supportive	Discharge

79	Bozca et al., 2020 [66]	81/F	NR/17	TEN	Probable	2	+/30	Cyclosporine	Discharge

80	Xiong et al., 2020 [67]	47/M	NR/10	SJS	Probable	NR	+/NR	Supportive, corticosteroid, IVIG	Discharge

81	Gopan et al., 2021 [68]	25/M	NR/26	SJS	Probable	NR	+/NR	Supportive, corticosteroid	Discharge

82	Lavu A et al, 2021 [69]	28/M	300 QD/20	SJS/TEN	Probable	NR	+/13.5	Supportive	Discharge

83	Srivastava et al., 2021 [70]	22/M	100 BD/3	SJS	Probable	NR	−/NR	Supportive, corticosteroid	Discharge

84	Hoyer et al., 2021 [71]	75/F	NR/19	TEN	Probable	5	+/85	Supportive, corticosteroid, cyclosporine	Discharge

85	Ikediobi et al., 2021 [72]	42/M	300 QD/53	SJS/TEN	Probable	NR	+/80	Supportive, corticosteroid, IVIG	Death

86	Ferdiana et al., 2022 [73]	63/M	200 QD/60	SJS	Probable	NR	+/30	Supportive, corticosteroid	Discharge
87	Ferdiana et al., 2022 [73]	43/M	NR/28	SJS	Probable	NR	+/30	Supportive, corticosteroid	Discharge

88	Manciuc et al., 2022 [74]	77/M	100 BD/14	SJS	Probable	3	+/10	Supportive, corticosteroid	Death

89	Zeller et al., 2022 [75]	74/M	300 QD/34	TEN/DRESS	Probable	4	+/50	Supportive, corticosteroid, IVIG, benralizumab	Discharge

90	Reyes-Ramos et al., 2023 [76]	58/M	NR	SJS	Probable	NR	+/NR	Supportive, corticosteroid	Discharge

91	Anis et al., 2023 [77]	96/F	100 QD/10	SJS	Probable	3	+/10	Supportive, corticosteroid	Discharge

Note: M, male; F, female; BD, twice daily; TID, three times per day; QID, four times per day: QD, once daily.
Abbreviations: DRESS, drug reaction with eosinophilia and systemic symptoms; IVIG, intravenous immune globulins; NR, not reported; SJS, Stevens–Johnson syndrome; TEN, toxic epidermal necrolysis.

The daily allopurinol dose at the time of reaction ranged from 100 to 600 mg, with a median of 300 mg. The time from the initiation of allopurinol to the onset of the reaction was reported for 82 patients in our study, the median of which was 14 days (min = 0.5 days, max = 2920 days). Six patients had a history of prior skin reactions to allopurinol (patient numbers 20, 43, 46, 62, 63, and 91 in Table 1), and the median time to onset was 8.5 days (min = 1, max = 14). Among the 76 patients who experienced skin reactions for the first time, the median duration was 16 days (min = 0.5 days, max = 2920 days). The time distribution of SJS/TEN based on the number of days after the initiation of allopurinol therapy is shown in Supporting Figure 1. As shown, the reaction occurred in 51 (67.1%) patients within the first 3 weeks and 65 (85.5%) patients within 1 month after the initiation of allopurinol.

The HLA-B^∗5801 genotyping results were reported for 13 patients who were positive for this variant (patient numbers 45–47, 52, 62–64, 73, 77, 82, and 85–87 in Table 1), and the status of other patients was unknown in this regard. The ethnicities of eight of these patients were reported, six of whom were South Asian or Southeast Asian.

The distribution of clinical presentations was as follows: TEN in 55 (60.4%), SJS in 28 (30.8%), SJS/TEN in 6 (6.6%), and overlap with DRESS in 2 (2.2%) patients. The percentage of body surface involved during the reaction ranged from 5% to 95% (median of 50%). Mucosal involvement was present in 72 (90.0%) patients and absent in 8 (10.0%) patients (not reported for 11 patients).

According to the Naranjo probability scale, only one reaction (1.1%) could be definitely attributed to allopurinol. The reaction was “probable” in 82 (90.1%) cases and “possible” in 8 (8.8%) cases.

In addition to supportive care, other therapeutic interventions were used to manage the reaction. These included corticosteroids (65 patients), IVIG (25 patients), cyclosporine (6 patients), plasma exchange (4 patients), infliximab, benralizumab, and cyclophosphamide (each in one patient). Among the 89 patients for whom the outcome was reported, 21 (23.6%) died and 68 (76.4%) were discharged.

4. Discussion

In this systematic review, the number of reported cases of allopurinol-induced SJS/TEN was almost equal in males and females. Notably, the prevalence of gout in men is 2–3 times greater than that in women [78]; therefore, more men are treated with allopurinol. Whether this finding indicates a greater prevalence of allopurinol-induced cutaneous reactions in women should be interpreted with caution because there are at least two points that make establishing such a relationship difficult. First, our study only retrieved SJS/TEN data and not all skin reactions caused by allopurinol. Second, women are more likely to report adverse drug reactions than men are, and there appears to be a bias in the reporting of adverse drug reactions in favor of a greater probability of reporting in women [79]. In general, on the basis of the findings of this review, establishing a relationship between sex and the occurrence of allopurinol-induced SJS/TEN is not possible.

The relationship between the starting or maintenance doses of allopurinol and the risk of SJS/TEN is controversial. Higher starting doses of allopurinol are associated with an increased risk of SJS/TEN [80]. Although it has not been confirmed by clinical trials, starting allopurinol at lower doses with gradual dose escalations has been suggested as an effective strategy to prevent SJS/TEN [81]. In patients with normal renal function, the American College of Rheumatology 2020 gout guidelines recommend starting doses of ≤ 100 mg daily [82], and the prescribing information of allopurinol suggests increasing the dose by 100 mg/day every week to prevent the risk of SJS/TEN [1]. In patients with compromised renal function, a more conservative dose escalation should be considered. Among the 91 patients in this review, the drug dose and onset time of SJS/TEN were reported for 43 patients. In 21 patients (48.9%), the dose increase rates were higher than the recommended values, confirming the correlation between rapid dose escalation and SJS/TEN occurrence.

Most cases of drug-induced SJS/TEN occur in the first 4 weeks after the initiation of the culprit drug [83]. The time between drug initiation and the occurrence of SJS/TEN differs for various pharmacologic classes. For example, the median durations reported for macrolide antibiotics [84], acetaminophen [85], and anticonvulsants [86] were 3, 4, and 15–24 days, respectively. The median time to the onset of the reaction was 14 days in our review, which was somewhat shorter than the latency times reported in previous studies [86, 87]. This difference can be attributed to the fact that our data were derived from the studies included in our review and may not fully correspond to clinical practice because many cases have not been reported.

The time to SJS/TEN occurrence was considerably shorter in the six patients with prior reactions to allopurinol. This was an expected finding, and a more rapid occurrence of hypersensitivity reactions after re-exposure to an offending drug has been reported previously [88].

Another important finding was that six of the eight patients with known ethnicities who tested positive for HLA-B^∗5801 were from South or Southeast Asia. As recommended by the American College of Rheumatology 2020 gout guidelines [82], this finding also provides a rationale for HLA-B^∗5801 genotyping before the initiation of allopurinol in patients of these ethnicities.

The distribution of reaction subtypes is not consistent in published studies on drug-induced severe cutaneous adverse reactions. The reported proportions differ according to the pharmacologic categories and studied populations. For example, a systematic review of SJS and TEN cases revealed that, compared with SJS, a greater percentage of TEN cases were associated with antibiotic use and anticonvulsants [89]. In the present study, 55 (60.4%) patients presented with TEN, 28 (30.8%) with SJS, and 6 (6.6%) with SJS/TEN overlap. This finding may be inconsistent with the epidemiological findings, which showed that the prevalence of SJS is 3–4 times higher than that of TEN [89]. Our findings probably do not correspond to actual clinical data and may simply reflect publication bias because more clinically severe cases are more likely to be reported.

In this review, mucosal lesions were present in 90.0% of the patients for whom they were reported. This finding is consistent with other SJS/TEN studies in which mucosal lesions were present in approximately 90% of patients.

SCORTEN is a prognostic scoring system that incorporates seven clinical and laboratory variables, including age, malignancy, heart rate, extent of epidermal detachment, and serum urea, glucose, and bicarbonate levels. All these parameters are equally weighted and transformed into dichotomous variables. Higher SCORTEN scores denote higher mortality risk; for example, a score of 0–1 predicts a 3.2% mortality rate, and a score of ≥ 5 predicts a 90% mortality rate [6]. There have been criticisms regarding the accuracy of SCORTEN in estimating the mortality rate of patients with SJS/TEN. The risk of death may be underestimated for scores < 3 and overestimated for scores > 3 [90]. Efforts have been made to optimize the SCORTEN score; however, these scores are not readily available for clinical use because SJS/TEN is a rare condition, and prospective studies with adequate sample sizes are difficult to conduct. SCORTEN scores were reported for only 19 patients in our study. Therefore, this systematic review did not have sufficient power to evaluate the predictive accuracy of SCORTEN. Interestingly, the patients with the highest scores in our study were three patients with scores of 5, and all three patients were eventually discharged. This finding is consistent with the overestimation of mortality risk in patients with SCORTEN scores > 3.

The identification and discontinuation of the culprit drug are the most important therapeutic interventions for the management of SJS/TEN. Causality assessment tools, such as Naranjo and ALDEN [91], have been developed to help identify the culprit drug. In our study, only one reaction could be definitely attributed to allopurinol on the basis of the Naranjo score; 82 reactions were probable, and 8 reactions were possible. The answers to some questions in the Naranjo score remain unknown in daily clinical practice [92]. For example, in patients with allopurinol-induced SJS/TEN, the drug is not usually readministered, a placebo is not given, and there is no known toxic concentration of allopurinol in the serum. As a result, suspected reactions to allopurinol are often classified as “probable” or “possible.” This may not be helpful in deciding whether allopurinol should be discontinued, especially when other drugs that cause similar reactions are used concurrently. This is a commonly encountered situation in clinical practice.

In addition to causality assessment tools, clinical and laboratory tests, such as oral provocation and patch testing, have been used to identify the offending drug. Although the oral provocation test is considered the gold standard for other drug reactions, it cannot be used for severe reactions such as SJS/TEN. Patch testing has been successfully used to identify the cause of severe skin reactions, such as acute generalized exanthematous pustulosis (AGEP) and DRESS; however, there is no standard preparation for performing the test. Newer in vitro tests, such as lymphocyte transformation tests (LTTs) and cytokine assays, seem promising, although they can identify the causative drug in 21%–56% and 50%–78% of patients, respectively [4]. Currently, a combination of causality assessment tools and clinical tests can help practitioners judiciously identify causative drugs.

Nearly all the patients in this review received supportive care, including fluid and electrolyte replacement, nutritional support, analgesia, and antibiotic therapy. In addition to supportive modalities, systemic immunomodulating treatments, such as corticosteroids and IVIG, were frequently used.

Systemic corticosteroids are the most widely investigated drugs for the management of SJS/TEN. The results of meta-analyses on the use of corticosteroids in SJS/TEN are controversial. While some of these studies failed to show survival benefits with the use of corticosteroids [93], others suggested improved survival [94, 95]. Unfortunately, studies conducted on corticosteroids do not have a uniform methodology. The dose and schedule of drug administration, specific corticosteroid agents used, study population, and time to start steroids after the onset of symptoms are the most important confounding factors in clinical studies, which can partly explain the different results observed in the meta-analyses.

Similar discrepancies have also been observed in studies on IVIG in patients with SJS/TEN. Although the use of IVIG has been associated with the interruption of disease progression [96] and reduced time to mucocutaneous healing [97], it has failed to show survival benefits in several studies [98, 99]. Notably, trials that used high-dose IVIG, defined as a total dose > 2 g/kg body weight, have shown reduced mortality in SJS/TEN patients [100, 101]. The different doses and regimens of IVIG and the different compositions of the available products may explain these inconsistent findings.

Less studied agents, such as cyclosporine and TNF-α inhibitors, have been associated with reduced mortality in patients with SJS/TEN. Plasma exchange, which removes drugs, metabolites, and cytokines, is a promising intervention that can be performed daily or every other day. In addition, several combinations of the abovementioned interventions with various beneficial effects have been studied in patients with SJS/TEN [4].

There were 21 deaths in the study population. The distribution was as follows: 4 of 28 patients (14.3%) with SJS, 15 of 55 patients (27.3%) with TEN, and 2 of 6 patients (33.3%) with SJS/TEN. These mortality rates are higher than those reported in the US [102]. There are two possible explanations. First, the patients included in this systematic review were from various countries with different levels of care than those in the US. Second, the US study gathered information on patients admitted between 2009 and 2012, whereas the patients in our study were reported from 1970 when the care of patients was not of current quality.

Another important issue in the interpretation of mortality rates is the role of underlying disorders, which may complicate patients’ clinical condition. Except for two patients, all patients who died in our study had at least one (average of 2.15) chronic medical condition, including hypertension, diabetes mellitus, dyslipidemia, heart failure, chronic kidney disease, chronic liver disease, atrial fibrillation, stroke, and chronic obstructive pulmonary disease (data not shown).

There are at least two areas for further research in the field of allopurinol-induced, or more generally, drug-induced, SJS/TEN. In the first step, a more discriminative causality assessment tool should be developed and validated to help practitioners identify the causative agent(s) in SJS/TEN in a timely manner. Next, the relative efficacy and safety of treatment strategies, including corticosteroids, IVIG, plasma exchange, cyclosporine, and TNF-α inhibitors, as well as their various dosages and regimens, should be investigated in multicenter prospective clinical trials.

The findings of this systematic review have at least two limitations that should be addressed. First, as mentioned above, many drug-induced adverse reactions are not reported because more severe reactions are more likely to be reported. Therefore, the analysis of the study patients, particularly quantitative variables, may not completely match the clinical picture of allopurinol-induced SJS/TEN. Second, the patients were not uniformly reported, and there were unreported or missing data for some patients.

5. Conclusion

Although the prevalence of gout is higher in men, the reported cases of allopurinol-induced SJS/TEN were similar between men and women, indicating possible reporting bias. In approximately 50% of patients who experienced SJS/TEN, the dose increment rate was > 100 mg/day every week. The median time to the onset of the reaction was 16 days after the initiation of allopurinol, with a shorter time (8.5 days) in patients with prior skin reactions. Corticosteroids, IVIG, cyclosporine, and plasma exchange, either alone or in combination, have been successfully used in several patients. Finally, nearly all patients who died of allopurinol-induced SJS/TEN had underlying chronic medical conditions.

Conflicts of Interest

The authors declare no conflicts of interest.

Funding

No funding was received for this research.

Acknowledgments

The research council of the Alborz University of Medical Sciences supported this systematic review. The authors would also like to thank Dr. Maryam Daei for her valuable contributions to this work.

Supporting Information

Supporting Table 1. Search strategy of the study; Supporting Table 2. Results of the quality assessment of case report studies; Supporting Table 3. Results of the quality assessment of case series studies; Supporting Figure 1. Distribution of the number of SJS/TEN cases based on the duration of allopurinol use.

Open Research

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Supporting Information

References

1 Allopurinol [package Insert], Camber Pharmaceuticals, Inc. (2024) .
Google Scholar
2 Yang C.-Y., Chen C.-H., Deng S.-T. et al., Allopurinol Use and Risk of Fatal Hypersensitivity Reactions: A Nationwide Population-Based Study in Taiwan, JAMA Internal Medicine. (2015) 175, no. 9, 1550–1557, https://doi.org/10.1001/jamainternmed.2015.3536, 2-s2.0-84941197601.
10.1001/jamainternmed.2015.3536
PubMed Web of Science® Google Scholar
3 Yaseen W., Auguste B., and Zipursky J., Allopurinol Hypersensitivity Syndrome, Canadian Medical Association Journal. (2023) 195, no. 13, https://doi.org/10.1503/cmaj.221575.
10.1503/cmaj.221575
Web of Science® Google Scholar
4 Chang H. C., Wang T. J., Lin M. H., and Chen T. J., A Review of the Systemic Treatment of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis, Biomedicines. (2022) 10, no. 9, https://doi.org/10.3390/biomedicines10092105.
10.3390/biomedicines10092105
Web of Science® Google Scholar
5 Page M. J., McKenzie J. E., Bossuyt P. M. et al., The PRISMA 2020 Statement: an Updated Guideline for Reporting Systematic Reviews, BMJ. (2021) 372, https://doi.org/10.1136/bmj.n71.
10.1136/bmj.n71
Google Scholar
6 Fouchard N., Bertocchi M., Roujeau J.-C., Revuz J., Wolkenstein P., and Bastuji-Garin S., SCORTEN: A Severity-Of-Illness Score for Toxic Epidermal Necrolysis, Journal of Investigative Dermatology. (2000) 115, no. 2, 149–153, https://doi.org/10.1046/j.1523-1747.2000.00061.x, 2-s2.0-0033889176.
10.1046/j.1523-1747.2000.00061.x
PubMed Web of Science® Google Scholar
7 Naranjo C. A., Busto U., Sellers E. M. et al., A Method for Estimating the Probability of Adverse Drug Reactions, Clinical Pharmacology and Therapeutics (St. Louis). (1981) 30, no. 2, 239–245, https://doi.org/10.1038/clpt.1981.154, 2-s2.0-0019799332.
10.1038/clpt.1981.154
CAS PubMed Web of Science® Google Scholar
8 Moola S., Munn Z., Tufanaru C. et al., E. Aromataris and Z. Munn, Chapter 7: Systematic Reviews of Etiology and Risk, JBI Manual for Evidence Synthesis, 2020, JBI, https://synthesismanual.jbi.global.
10.46658/JBIMES-20-08
Google Scholar
9 Munn Z., Barker T. H., Moola S. et al., Methodological Quality of Case Series Studies: an Introduction to the JBI Critical Appraisal Tool, JBI Evidence Synthesis. (2020) 18, no. 10, 2127–2133, https://doi.org/10.11124/JBISRIR-D-19-00099, 2-s2.0-85072583874.
10.11124/JBISRIR-D-19-00099
PubMed Web of Science® Google Scholar
10 Kantor G. L., Toxic Epidermal Necrolysis, Azotemia, and Death after Allopurinol Therapy, JAMA. (1970) 212, no. 3, 478–479, https://doi.org/10.1001/jama.1970.03170160066019, 2-s2.0-0014956072.
10.1001/jama.1970.03170160066019
CAS PubMed Web of Science® Google Scholar
11 Stratigos J. D., Bartsokas S. K., and Capetanakis J., Further Experiences of Toxic Epidermal Necrolysis Incriminating Allopurinol, Pyrazolone and Derivatives, British Journal of Dermatology. (1972) 86, no. 6, 564–567, https://doi.org/10.1111/j.1365-2133.1972.tb05070.x, 2-s2.0-0015354650.
10.1111/j.1365-2133.1972.tb05070.x
CAS PubMed Web of Science® Google Scholar
12 Ellman M. H., Fretzin D. F., and Olson W., Toxic Epidermal Necrolysis Associated with Allopurinol Administration, Archives of Dermatology. (1975) 111, no. 8, 986–990, https://doi.org/10.1001/archderm.1975.01630200046002, 2-s2.0-0016679571.
10.1001/archderm.1975.01630200046002
CAS PubMed Web of Science® Google Scholar
13 Chan H. L., Ku G., and Khoo O. T., Allopurinol Associated Hypersensitivity Reactions: Cutaneous and Renal Manifestations, Australian & New Zealand Journal of Medicine. (1977) 7, no. 5, 518–522, https://doi.org/10.1111/j.1445-5994.1977.tb03375.x, 2-s2.0-0017668584.
10.1111/j.1445-5994.1977.tb03375.x
CAS PubMed Web of Science® Google Scholar
14 Bennett T. O., Sugar J., and Sahgal S., Ocular Manifestations of Toxic Epidermal Necrolysis Associated with Allopurinol Use, Archives of Ophthalmology. (1977) 95, no. 8, 1362–1364, https://doi.org/10.1001/archopht.1977.04450080072005, 2-s2.0-0017722257.
10.1001/archopht.1977.04450080072005
CAS PubMed Web of Science® Google Scholar
15 Assaad D., From L., Ricciatti D., and Shapero H., Toxic Epidermal Necrolysis in Stevens Johnson Syndrome, Canadian Medical Association Journal. (1978) 118, no. 2, 154–156.
CAS PubMed Web of Science® Google Scholar
16 Lang P. G., Severe Hypersensitivity Reactions to Allopurinol, Southern Medical Journal. (1979) 72, no. 11, 1361–1368, https://doi.org/10.1097/00007611-197911000-00004, 2-s2.0-0018595189.
10.1097/00007611-197911000-00004
PubMed Web of Science® Google Scholar
17 Marra L. M. and Wunderle R. C., Oral Presentation of Toxic Epidermal Necrolysis, Journal of Oral and Maxillofacial Surgery. (1982) 40, no. 1, 59–61, https://doi.org/10.1016/s0278-2391(82)80020-7, 2-s2.0-0019974264.
10.1016/S0278-2391(82)80020-7
CAS PubMed Web of Science® Google Scholar
18 Davies P. and Ryan D. W., Stevens-Johnson Syndrome Managed in the Clinitron Bed, Intensive Care Medicine. (1983) 9, no. 2, 87–89, https://doi.org/10.1007/bf01699263, 2-s2.0-0020957294.
10.1007/BF01699263
CAS PubMed Web of Science® Google Scholar
19 Vinciullo C., Allopurinol Hypersensitivity: A Potentially Life Threatening Reaction, Australasian Journal of Dermatology. (1984) 25, no. 2, 59–67, https://doi.org/10.1111/j.1440-0960.1984.tb00628.x, 2-s2.0-0021685122.
10.1111/j.1440-0960.1984.tb00628.x
CAS PubMed Google Scholar
20 Pennell D. J., Nunan T. O., O’Doherty M. J., and Croft D. N., Fatal Stevens-Johnson Syndrome in a Patient on Captopril and Allopurinol, The Lancet. (1984) 1, no. 8374, https://doi.org/10.1016/s0140-6736(84)91807-5, 2-s2.0-0021345170.
10.1016/s0140-6736(84)91807-5
PubMed Web of Science® Google Scholar
21 Dan M., Jedwab M., Peled M., and Shibolet S., Allopurinol-induced Toxic Epidermal Necrolysis, International Journal of Dermatology. (1984) 23, no. 2, 142–144, https://doi.org/10.1111/j.1365-4362.1984.tb05689.x, 2-s2.0-0021329393.
10.1111/j.1365-4362.1984.tb05689.x
CAS PubMed Web of Science® Google Scholar
22 Edwards R. and Ridder M., Stevens-Johnson Syndrome: A Multisystem Case, Dimensions Of Critical Care Nursing: DCCN. (1985) 4, no. 6, 335–348.
10.1097/00003465-198511000-00004
CAS PubMed Google Scholar
23 Renwick I. G., Asymptomatic Hyperuricemia and Allopurinol Induced Toxic Epidermal Necrolysis, British Medical Journal. (1985) 291, no. 6493, https://doi.org/10.1136/bmj.291.6493.485, 2-s2.0-0022428067.
10.1136/bmj.291.6493.485
PubMed Web of Science® Google Scholar
24 Aubock J. and Fritsch P., Asymptomatic Hyperuricaemia and Allopurinol Induced Toxic Epidermal Necrolysis, British Medical Journal. (1985) 290, no. 6486, 1969–1970, https://doi.org/10.1136/bmj.290.6486.1969, 2-s2.0-0021859790.
10.1136/bmj.290.6486.1969
CAS PubMed Web of Science® Google Scholar
25 Sakellariou G., Koukoudis P., Karpouzas J. et al., Plasma Exchange (PE) Treatment in Drug-Induced Toxic Epidermal Necrolysis (TEN), The International Journal of Artificial Organs. (1991) 14, no. 10, 634–638, https://doi.org/10.1177/039139889101401006.
10.1177/039139889101401006
CAS PubMed Web of Science® Google Scholar
26 Heng M. C. Y. and Allen S. G., Efficacy of Cyclophosphamide in Toxic Epidermal Necrolysis: Clinical and Pathophysiologic Aspects, Journal of the American Academy of Dermatology. (1991) 25, no. 5, 778–786, https://doi.org/10.1016/s0190-9622(08)80969-3, 2-s2.0-0026010494.
10.1016/S0190-9622(08)80969-3
CAS PubMed Web of Science® Google Scholar
27 Ashworth L. E., Allopurinol-Induced Stevens-Johnson Syndrome, Journal of Pharmacy Practice. (1992) 5, no. 2, ix–x, https://doi.org/10.1177/089719009200500202, 2-s2.0-84970122892.
10.1177/089719009200500202
Google Scholar
28 Alfandari S., Beuscart C., Senneville E., Mouton Y., and Delaporte E., Toxic Epidermal Necrolysis in a Patient Suffering from Acquired Immune Deficiency Syndrome, Infection. (1994) 22, no. 5, https://doi.org/10.1007/bf01715552, 2-s2.0-0028134903.
10.1007/BF01715552
PubMed Web of Science® Google Scholar
29 Halevy S., Cohen A. D., and Livni E., The Diagnostic Role of the In Vitro Drug-Induced Interferon-Gamma Release Test in Stevens-Johnson Syndrome, International Journal of Dermatology. (1999) 38, no. 11, 835–840, https://doi.org/10.1046/j.1365-4362.1999.00792.x, 2-s2.0-0032711344.
10.1046/j.1365-4362.1999.00792.x
CAS PubMed Web of Science® Google Scholar
30 Bashir S., Shah S. M., and Babar I., Allopurinol Induced Stevens-Johnson Syndrome: a Case Report, Journal of Pakistan Medical Association. (2000) 50, no. 6, 207–209.
CAS PubMed Google Scholar
31 Zakrzewski J. L., Lentini G., Such U. et al., Toxic Epidermal Necrolysis: Differential Diagnosis of an Epidermolytic Dermopathy in a Hematopoietic Stem Cell Transplant Recipient, Bone Marrow Transplantation. (2002) 30, no. 5, 331–333, https://doi.org/10.1038/sj.bmt.1703624, 2-s2.0-0036739312.
10.1038/sj.bmt.1703624
CAS PubMed Web of Science® Google Scholar
32 Yeung C. K., Lam L. K., and Chan H. H., The Timing of Intravenous Immunoglobulin Therapy in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis, Clinical and Experimental Dermatology. (2005) 30, no. 5, 600–602, https://doi.org/10.1111/j.1365-2230.2005.01863.x, 2-s2.0-23044452819.
10.1111/j.1365-2230.2005.01863.x
CAS PubMed Web of Science® Google Scholar
33 Kakeda M., Tohyama M., Iwasaki J., Hashimoto K., and Mizutani H., A Case of Histopathologically Typical Toxic Epidermal Necrolysis Despite No Visible Blisters or Erosive Lesions, The Journal of Dermatology. (2005) 32, no. 8, 654–660, https://doi.org/10.1111/j.1346-8138.2005.tb00817.x, 2-s2.0-25144439071.
10.1111/j.1346-8138.2005.tb00817.x
CAS PubMed Web of Science® Google Scholar
34 Saxena R. and Loghmanee F., Fatal Drug Reaction Due to Allopurinol Therapy in a 72-Year-Old Man, Archives of Pathology & Laboratory Medicine. (2005) 129, no. 8, e183–e184, https://doi.org/10.5858/2005-129-e183-fdrdta.
10.5858/2005-129-e183-FDRDTA
PubMed Google Scholar
35 Stenton S. B., Dalen D., and Wilbur K., Myocardial Infarction Associated with Intravenous Immune Globulin, The Annals of Pharmacotherapy. (2005) 39, no. 12, 2114–2118, https://doi.org/10.1345/aph.1g104, 2-s2.0-28544452976.
10.1345/aph.1G104
PubMed Web of Science® Google Scholar
36 Paquet P., Jacob E., Quatresooz P., Jacquemin D., and Piérard G. E., Delayed Reepithelialization and Scarring Deregulation Following Drug-Induced Toxic Epidermal Necrolysis, Burns. (2007) 33, no. 1, 100–104, https://doi.org/10.1016/j.burns.2006.04.031, 2-s2.0-33846046024.
10.1016/j.burns.2006.04.031
CAS PubMed Web of Science® Google Scholar
37 Dainichi T., Uchi H., Moroi Y., and Furue M., Stevens-Johnson Syndrome, Drug-Induced Hypersensitivity Syndrome and Toxic Epidermal Necrolysis Caused by Allopurinol in Patients with a Common HLA Allele: What Causes the Diversity?, Dermatology. (2007) 215, no. 1, 86–88, https://doi.org/10.1159/000102045, 2-s2.0-34250888038.
10.1159/000102045
PubMed Web of Science® Google Scholar
38 Kemen C., Lemke J., Hoeger P. H. et al., Human Leukocyte Antigen-Related Risk Factors for Toxic Epidermal Necrosis, The Pediatric Infectious Disease Journal. (2009) 28, no. 6, https://doi.org/10.1097/inf.0b013e31819f3610, 2-s2.0-67649518992.
10.1097/INF.0b013e31819f3610
PubMed Web of Science® Google Scholar
39 Hsieh H.-J., Chan A. L. F., and Lin S.-J., Stevens-Johnson Syndrome Induced by Combination of Imatinib and Allopurinol, Chemotherapy. (2009) 55, no. 4, 197–199, https://doi.org/10.1159/000218097, 2-s2.0-65549097342.
10.1159/000218097
CAS PubMed Web of Science® Google Scholar
40 Ventura F., Fracasso T., Leoncini A., Gentile R., and De Stefano F., Death Caused by Toxic Epidermal Necrolysis (Lyell Syndrome), Journal of Forensic Sciences. (2010) 55, no. 3, 839–841, https://doi.org/10.1111/j.1556-4029.2010.01338.x, 2-s2.0-77951099846.
10.1111/j.1556-4029.2010.01338.x
CAS PubMed Web of Science® Google Scholar
41 Hanken I., Schimmer M., and Sander C. A., Basic Measures and Systemic Medical Treatment of Patients with Toxic Epidermal Necrolysis, JDDG: Journal der Deutschen Dermatologischen Gesellschaft. (2010) 8, no. 5, 341–346, https://doi.org/10.1111/j.1610-0387.2009.07289.x, 2-s2.0-77951781323.
10.1111/j.1610-0387.2009.07289.x
PubMed Web of Science® Google Scholar
42 Fernando S. L. and Broadfoot A. J., Prevention of Severe Cutaneous Adverse Drug Reactions: The Emerging Value of Pharmacogenetic Screening, Canadian Medical Association Journal. (2010) 182, no. 5, 476–480, https://doi.org/10.1503/cmaj.090401, 2-s2.0-77950878238.
10.1503/cmaj.090401
PubMed Web of Science® Google Scholar
43 Kim T., Lee T., Bae Y. et al., Severe Pneumonia Caused by Combined Infection with Pneumocystis Jiroveci, Parainfluenza Virus Type 3, Cytomegalovirus, and Aspergillus fumigatus in a Patient with Stevens-Johnson Syndrome/toxic Epidermal Necrolysis, Acta Dermato-Venereologica. (2010) 90, no. 6, 625–629, https://doi.org/10.2340/00015555-0977, 2-s2.0-78649715687.
10.2340/00015555-0977
PubMed Google Scholar
44 Ranu H., Jiang J., and Ming P. S., A Case Series of Allopurinol-Induced Toxic Epidermal Necrolysis, Indian Journal of Dermatology. (2011) 56, no. 1, 74–76, https://doi.org/10.4103/0019-5154.77557.
10.4103/0019-5154.77557
PubMed Google Scholar
45 Comparin C., Hans Filho G., Takita L. C., Costa N. C. W., Nascimento R. A. F., and Nanni L. O. C., Treatment of Toxic Epidermal Necrolysis with Intravenous Immunoglobulin: a Series of Three Cases, Anais Brasileiros de Dermatologia. (2012) 87, no. 3, 477–481, https://doi.org/10.1590/s0365-05962012000300022, 2-s2.0-84863099516.
10.1590/S0365-05962012000300022
PubMed Web of Science® Google Scholar
46 Lee H. Y., Philippidou M., Marcus R., Walsh S., and Creamer D., Sequential Stevens-Johnson Syndrome and Photo-Recall Phenomenon, British Journal of Dermatology. (2012) 166, no. 5, 1145–1146, https://doi.org/10.1111/j.1365-2133.2011.10734.x, 2-s2.0-84862791126.
10.1111/j.1365-2133.2011.10734.x
CAS PubMed Web of Science® Google Scholar
47 Kamal T., Elnikety S., Mashaly H., and Casha J., Acute Compartment Syndrome of the Forearm as a Rare Complication of Toxic Epidermal Necrolysis: A Case Report, Journal of Medical Case Reports. (2012) 6, no. 1, https://doi.org/10.1186/1752-1947-6-84, 2-s2.0-84858431939.
10.1186/1752-1947-6-84
PubMed Google Scholar
48 Sawicki J. and Ellis A. K., Stevens-Johnson Syndrome: A Review of 14 Adult Cases with One Fatal Outcome, Annals of Allergy, Asthma, & Immunology. (2013) 110, no. 3, 207–209.e1, https://doi.org/10.1016/j.anai.2012.12.017, 2-s2.0-84875134032.
10.1016/j.anai.2012.12.017
PubMed Web of Science® Google Scholar
49 Lee M.-H. H., Stocker S. L., Williams K. M., and Day R. O., HLA-B∗5801 Should Be Used to Screen for Risk of Stevens-Johnson Syndrome in Family Members of Han Chinese Patients Commencing Allopurinol Therapy, Journal of Rheumatology. (2013) 40, no. 1, 96.2–7, https://doi.org/10.3899/jrheum.120803, 2-s2.0-84871880477.
10.3899/jrheum.120803
Google Scholar
50 Watanabe Y., Matsukura S., Isoda Y., Morita A., Aihara M., and Kambara T., A Case of Toxic Epidermal Necrolysis Induced by Allopurinol With Human Herpesvirus-6 Reactivation, Acta Dermato-Venereologica. (2013) 93, no. 6, 731–732, https://doi.org/10.2340/00015555-1610, 2-s2.0-84886376614.
10.2340/00015555-1610
PubMed Web of Science® Google Scholar
51 Caldarola G., Sollena P., Peris K., and De Simone C., Human Leukocyte Antigen-B^∗58:01 Allele in a Familial Case of Stevens-Johnson Syndrome Induced by Allopurinol, The Journal of Dermatology. (2015) 42, no. 7, 753–754, https://doi.org/10.1111/1346-8138.12894, 2-s2.0-84934436283.
10.1111/1346-8138.12894
CAS PubMed Web of Science® Google Scholar
52 Villano J. H. and Lovell E. O., Mixed Signals: Toxic Epidermal Necrolysis, The American Journal of Medicine. (2015) 128, no. 3, 254–256, https://doi.org/10.1016/j.amjmed.2014.11.004, 2-s2.0-84924178929.
10.1016/j.amjmed.2014.11.004
PubMed Web of Science® Google Scholar
53 Paik S., Sen S., Das J., Saha B., and Tripathi S. K., Allopurinol Induced Stevens-Johnson Syndrome: A Case Report, Journal of Clinical and Diagnostic Research. (2015) 9, no. 2, WJ01–WJ2, https://doi.org/10.7860/JCDR/2015/11786.5558, 2-s2.0-84922248467.
10.7860/JCDR/2015/11786.5558
PubMed Google Scholar
54 Rodgers B. K. and Kumar A. B., Rapidly Progressing Severe Cutaneous Adverse Reaction with Acute Kidney Injury after Drug Exposure: An Uncommon Presentation, American Journal of Therapeutics. (2016) 23, no. 3, e916–e919, https://doi.org/10.1097/mjt.0000000000000070, 2-s2.0-84900351651.
10.1097/MJT.0000000000000070
PubMed Web of Science® Google Scholar
55 Casagranda A., Suppa M., Dehavay F., and del Marmol V., Overlapping DRESS and Stevens-Johnson Syndrome: Case Report and Review of the Literature, Case Reports in Dermatology. (2017) 9, no. 2, 1–7, https://doi.org/10.1159/000475802, 2-s2.0-85019096382.
10.1159/000475802
PubMed Web of Science® Google Scholar
56 Banerjee B. and Chowdhury S. K., Allopurinol Induced Toxic Epidermal Necrolysis, International Journal of Pharmaceutical Sciences and Research. (2017) 8, no. 4, 1842–1845.
Google Scholar
57 Brown C. S., Defazio J. R., An G. et al., Toxic Epidermal Necrolysis with Gastrointestinal Involvement: A Case Report and Review of the Literature, Journal of Burn Care and Research. (2017) 38, no. 1, e450–e455, https://doi.org/10.1097/bcr.0000000000000336, 2-s2.0-84964038468.
10.1097/BCR.0000000000000336
PubMed Web of Science® Google Scholar
58 Wallenborn J. and Fischer M., Intensive Care in a Patient with Toxic Epidermal Necrolysis, Case Reports in Critical Care. (2017) 2017, 1–4, https://doi.org/10.1155/2017/3246196.
10.1155/2017/3246196
Google Scholar
59 Irfan M., Azfar N. A., Malik L. M., and Rashid T., Plasmapheresis: An Effective Treatment in Patients of Toxic Epidermal Necrolysis: Case Report of Two Patients, Journal of Pakistan Association of Dermatologists. (2017) 27, no. 2, 173–176.
Google Scholar
60 Wang F., Ma Z., Wu X., and Liu L., Allopurinol-induced Toxic Epidermal Necrolysis Featuring Almost 60% Skin Detachment, Medicine. (2019) 98, no. 25, https://doi.org/10.1097/md.0000000000016078, 2-s2.0-85068561152.
10.1097/md.0000000000016078
Web of Science® Google Scholar
61 Buenrostro-Rubio I., Silva-Villaseñor J. A., Hatami-Blechner A. W. et al., Allopurinol-Induced Toxic Epidermal Necrolysis, Drug Saf Case Rep. (2019) 6, no. 1, https://doi.org/10.1007/s40800-019-0101-z.
10.1007/s40800-019-0101-z
PubMed Google Scholar
62 Claytor J. D., Herfarth H. H., and Weaver K. N., Colonic Involvement of Stevens-Johnson Syndrome/toxic Epidermal Necrolysis: A Rare Cause of Gastrointestinal Bleeding, ACG Case Reports Journal. (2019) 6, no. 10, https://doi.org/10.14309/crj.0000000000000242.
10.14309/crj.0000000000000242
PubMed Google Scholar
63 Chhabra M. and Gaur A., Allopurinol-induced Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis: A Case Report, Asian Journal of Pharmaceutical and Clinical Research. (2019) 12, no. 2, 5–7, https://doi.org/10.22159/ajpcr.2019.v12i2.29448.
10.22159/ajpcr.2019.v12i2.29448
Google Scholar
64 Ponzo M. G., Miliszewski M., Kirchhof M. G., Keown P. A., and Dutz J. P., HLA-B^∗58:01 Genotyping to Prevent Cases of DRESS and SJS/TEN in East Asians Treated with Allopurinol—A Canadian Missed Opportunity, Journal of Cutaneous Medicine and Surgery. (2019) 23, no. 6, 595–601, https://doi.org/10.1177/1203475419867599, 2-s2.0-85071110244.
10.1177/1203475419867599
PubMed Google Scholar
65 Gupta S. S., Sabharwal N., Patti R., and Kupfer Y., Allopurinol-Induced Stevens-Johnson Syndrome, The American Journal of the Medical Sciences. (2019) 357, no. 4, 348–351, https://doi.org/10.1016/j.amjms.2018.11.018, 2-s2.0-85059692247.
10.1016/j.amjms.2018.11.018
PubMed Web of Science® Google Scholar
66 Bozca B. C., Irican C. M., and Karakaş A. A., Three Toxic Epidermal Necrolysis Cases Treated with Cyclosporine and a Review of the Literature, Dermatologic Therapy. (2020) 33, no. 6, https://doi.org/10.1111/dth.14435.
10.1111/dth.14435
PubMed Web of Science® Google Scholar
67 Xiong H., Liu G., Xiao J. et al., Recurrence of Stevens-Johnson Syndrome/toxic Epidermal Necrolysis Induced by Allopurinol and Piroxicam, European Journal of Dermatology. (2020) 30, no. 5, 620–621, https://doi.org/10.1684/ejd.2020.3857.
10.1684/ejd.2020.3857
CAS PubMed Web of Science® Google Scholar
68 Gopan A., Anukrishna V. P., Janeendran D., Subhash A., Thomas J., and Reghu R., Allopurinol Induced Stevens-Johnson Syndrome, International Journal of Research in Pharmacy and Science. (2021) 12, no. 1, 829–831, https://doi.org/10.26452/ijrps.v12i1.4189.
10.26452/ijrps.v12i1.4189
Google Scholar
69 Lavu A., Thiriveedi S., Thomas L., Khera K., Saravu K., and Rao M., Clinical Utility of HLA-B^∗58:01 Genotyping to Prevent Allopurinol-Induced SJS/TEN, Hospital Pharmacy. (2021) 56, no. 6, 660–663, https://doi.org/10.1177/0018578720934972.
10.1177/0018578720934972
PubMed Google Scholar
70 Srivastava B., Bhardwaj R., Khanchandani R., Ansari Z. M., and Belwal G., Rifampicin- A Nd Allopurinol-Induced Stevens-Johnson Syndrome: A Case Series, Indian Journal of Physiology & Pharmacology. (2021) 65, no. 1, 51–54, https://doi.org/10.25259/ijpp_386_2020.
10.25259/IJPP_386_2020
Google Scholar
71 Hoyer D., Atti C., Nuding S., Vogt A., Sedding D. G., and Schott A., Toxic Epidermal Necrolysis Caused by Allopurinol: A Serious but Still Underestimated Adverse Reaction, Am J Case Rep. (2021) 22, no. 1, https://doi.org/10.12659/ajcr.932921.
10.12659/AJCR.932921
PubMed Web of Science® Google Scholar
72 Ikediobi O. and Schneider J. A., Pharmacogenomics of Allopurinol and Sulfamethoxazole/Trimethoprim: Case Series and Review of the Literature, Journal of Personalized Medicine. (2021) 11, no. 2, 71–79, https://doi.org/10.3390/jpm11020071.
10.3390/jpm11020071
PubMed Web of Science® Google Scholar
73 Ferdiana A., Fachiroh J., Oktarina D. A. M. et al., Allopurinol-Induced Stevens-Johnson Syndrome in Javanese Men with Positive HLA-B^∗58:01, Frontiers in Genetics. (2022) 13, https://doi.org/10.3389/fgene.2022.839154.
10.3389/fgene.2022.839154
PubMed Google Scholar
74 Manciuc C., Lacatusu G. A., Vata A., Sapaniuc C., Arteni C. M., and Petrariu F. D., Concomitance or Consequence? Stevens-Johnson Syndrome in COVID-19: A Case Report, Experimental and Therapeutic Medicine. (2022) 23, no. 4, https://doi.org/10.3892/etm.2022.11182.
10.3892/etm.2022.11182
Google Scholar
75 Zeller F. K., Bader P. R., Nägeli M. C., Buehler P. K., and Schuepbach R. A., Severe Toxic Epidermal Necrolysis and Drug Reaction with Eosinophilia and Systemic Symptoms Overlap Syndrome Treated with Benralizumab: A Case Report, Case Reports in Dermatology. (2022) 14, no. 2, 203–209, https://doi.org/10.1159/000525752.
10.1159/000525752
PubMed Web of Science® Google Scholar
76 Reyes-Ramos A. R., Preclaro I. A. C., Castillo M. M. S., and Basco S. E. S., Stevens-Johnson Syndrome in an Adult Filipino Male Positive for HLA-B^∗38:16 and B^∗58:17, Associated with Allopurinol: A Case Report, The Journal of Clinical Pharmacology. (2023) 63, no. 6, 742–744, https://doi.org/10.1002/jcph.2213.
10.1002/jcph.2213
CAS PubMed Web of Science® Google Scholar
77 Anis T. R. and Meher J., Allopurinol-Induced Stevens-Johnson Syndrome (SJS), Clinical Pharmacology: Advances and Applications. (2023) 15, 99–105, https://doi.org/10.2147/cpaa.s427714.
10.2147/CPAA.S427714
PubMed Web of Science® Google Scholar
78 Zhu Y., Pandya B. J., and Choi H. K., Prevalence of Gout and Hyperuricemia in the US General Population: the National Health and Nutrition Examination Survey 2007-2008, Arthritis & Rheumatism. (2011) 63, no. 10, 3136–3141, https://doi.org/10.1002/art.30520, 2-s2.0-80053497428.
10.1002/art.30520
PubMed Web of Science® Google Scholar
79 Brabete A. C., Greaves L., Maximos M., Huber E., Li A., and Lê M. L., A Sex- and Gender-Based Analysis of Adverse Drug Reactions: A Scoping Review of Pharmacovigilance Databases, Pharmaceuticals. (2022) 15, no. 3, https://doi.org/10.3390/ph15030298.
10.3390/ph15030298
Web of Science® Google Scholar
80 Stamp L. K., Taylor W. J., Jones P. B. et al., Starting Dose Is a Risk Factor for Allopurinol Hypersensitivity Syndrome: a Proposed Safe Starting Dose of Allopurinol, Arthritis & Rheumatism. (2012) 64, no. 8, 2529–2536, https://doi.org/10.1002/art.34488, 2-s2.0-84864486646.
10.1002/art.34488
CAS PubMed Web of Science® Google Scholar
81 Stamp L. K. and Barclay M. L., How to Prevent Allopurinol Hypersensitivity Reactions?, Rheumatology. (2017) 57, no. suppl_1, i35–i41, https://doi.org/10.1093/rheumatology/kex422, 2-s2.0-85047730100.
10.1093/rheumatology/kex422
Google Scholar
82 FitzGerald J. D., Dalbeth N., Mikuls T. et al., 2020 American College of Rheumatology Guideline for the Management of Gout, Arthritis Care & Research. (2020) 72, no. 6, 744–760, https://doi.org/10.1002/acr.24180.
10.1002/acr.24180
PubMed Web of Science® Google Scholar
83 Lee E. Y., Knox C., and Phillips E. J., Worldwide Prevalence of Antibiotic-Associated Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Systematic Review and Meta-Analysis, JAMA Dermatology. (2023) 159, no. 4, 384–392, https://doi.org/10.1001/jamadermatol.2022.6378.
10.1001/jamadermatol.2022.6378
PubMed Web of Science® Google Scholar
84 Pejčić A. V., Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Associated with the Use of Macrolide Antibiotics: a Review of Published Cases, International Journal of Dermatology. (2021) 60, no. 1, 12–24, https://doi.org/10.1111/ijd.15144.
10.1111/ijd.15144
PubMed Web of Science® Google Scholar
85 Milosavljević M. N., Pejčić A. V., and Milosavljević J. Z., A Review of Published Cases of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Associated with the Use of Acetaminophen, Cutaneous and Ocular Toxicology. (2021) 40, no. 3, 280–292, https://doi.org/10.1080/15569527.2021.1942896.
10.1080/15569527.2021.1942896
CAS PubMed Web of Science® Google Scholar
86 Mockenhaupt M., Epidemiology of Cutaneous Adverse Drug Reactions, Allergologie select. (2017) 1, no. 1, 96–108, https://doi.org/10.5414/alx01508e.
10.5414/ALX01508E
CAS PubMed Google Scholar
87 Abe J., Umetsu R., Mataki K. et al., Analysis of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Using the Japanese Adverse Drug Event Report Database, Journal of Pharmaceutical Health Care and Sciences. (2016) 2, no. 1, https://doi.org/10.1186/s40780-016-0048-5.
10.1186/s40780-016-0048-5
PubMed Google Scholar
88 Mahajan V., Manvi S., Mehta K. S. et al., The Clinical Characteristics, Putative Drugs, and Optimal Management of 62 Patients with Stevens-Johnson Syndrome And/or Toxic Epidermal Necrolysis: A Retrospective Observational Study, Indian Dermatology Online Journal. (2022) 13, no. 1, 23–31, https://doi.org/10.4103/idoj.idoj_530_21.
10.4103/idoj.idoj_530_21
PubMed Web of Science® Google Scholar
89 Wang L., Varghese S., Bassir F. et al., Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Systematic Review of PubMed/MEDLINE Case Reports from 1980 to 2020, Frontiers of Medicine. (2022) 9, https://doi.org/10.3389/fmed.2022.949520.
10.3389/fmed.2022.949520
Google Scholar
90 Dobry A. S., Himed S., Waters M., and Kaffenberger B. H., Scoring Assessments in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis, Frontiers of Medicine. (2022) 9, https://doi.org/10.3389/fmed.2022.883121.
10.3389/fmed.2022.883121
Google Scholar
91 Sassolas B., Haddad C., Mockenhaupt M. et al., ALDEN, an Algorithm for Assessment of Drug Causality in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Comparison with Case-Control Analysis, Clinical Pharmacology & Therapeutics. (2010) 88, no. 1, 60–68, https://doi.org/10.1038/clpt.2009.252, 2-s2.0-77953811466.
10.1038/clpt.2009.252
CAS PubMed Web of Science® Google Scholar
92 Murali M., Suppes S. L., Feldman K., and Goldman J. L., Utilization of the Naranjo Scale to Evaluate Adverse Drug Reactions at a Free-Standing Children’s Hospital, PLoS One. (2021) 16, no. 1, https://doi.org/10.1371/journal.pone.0245368.
10.1371/journal.pone.0245368
Web of Science® Google Scholar
93 Ye L. P., Zhang C., and Zhu Q. X., The Effect of Intravenous Immunoglobulin Combined with Corticosteroid on the Progression of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Meta-Analysis, PLoS One. (2016) 11, no. 11, https://doi.org/10.1371/journal.pone.0167120, 2-s2.0-85000997362.
10.1371/journal.pone.0167120
Web of Science® Google Scholar
94 Houschyar K. S., Tapking C., Borrelli M. R. et al., Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: a Systematic Review and Meta-Analysis, Journal of Wound Care. (2021) 30, no. 12, 1012–1019, https://doi.org/10.12968/jowc.2021.30.12.1012.
10.12968/jowc.2021.30.12.1012
PubMed Web of Science® Google Scholar
95 Zimmermann S., Sekula P., Venhoff M. et al., Systemic Immunomodulating Therapies for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Systematic Review and Meta-Analysis, JAMA Dermatology. (2017) 153, no. 6, 514–522, https://doi.org/10.1001/jamadermatol.2016.5668, 2-s2.0-85020701308.
10.1001/jamadermatol.2016.5668
PubMed Web of Science® Google Scholar
96 Viard I., Wehrli P., Bullani R. et al., Inhibition of Toxic Epidermal Necrolysis by Blockade of CD95 with Human Intravenous Immunoglobulin, Science. (1998) 282, no. 5388, 490–493, https://doi.org/10.1126/science.282.5388.490, 2-s2.0-0032538505.
10.1126/science.282.5388.490
CAS PubMed Web of Science® Google Scholar
97 Prins C., Vittorio C., Padilla R. S. et al., Effect of High-Dose Intravenous Immunoglobulin Therapy in Stevens-Johnson Syndrome: a Retrospective, Multicenter Study, Dermatology. (2003) 207, no. 1, 96–99, https://doi.org/10.1159/000070957, 2-s2.0-0142090517.
10.1159/000070957
CAS PubMed Web of Science® Google Scholar
98 Firoz B. F., Henning J. S., Zarzabal L. A., and Pollock B. H., Toxic Epidermal Necrolysis: Five Years of Treatment Experience from a Burn Unit, Journal of the American Academy of Dermatology. (2012) 67, no. 4, 630–635, https://doi.org/10.1016/j.jaad.2011.12.014, 2-s2.0-84866416260.
10.1016/j.jaad.2011.12.014
PubMed Web of Science® Google Scholar
99 Wolf R. and Davidovici B., Severe Cutaneous Adverse Drug Reactions: Who Should Treat, where and How?: Facts and Controversies, Clinics in Dermatology. (2010) 28, no. 3, 344–348, https://doi.org/10.1016/j.clindermatol.2009.06.020, 2-s2.0-77953592420.
10.1016/j.clindermatol.2009.06.020
PubMed Web of Science® Google Scholar
100 Prins C., Kerdel F. A., Padilla R. S. et al., Treatment of Toxic Epidermal Necrolysis with High-Dose Intravenous Immunoglobulins: Multicenter Retrospective Analysis of 48 Consecutive Cases, Archives of Dermatology. (2003) 139, no. 1, 26–32, https://doi.org/10.1001/archderm.139.1.26, 2-s2.0-2442583225.
10.1001/archderm.139.1.26
CAS PubMed Web of Science® Google Scholar
101 Trent J. T., Kirsner R. S., Romanelli P., and Kerdel F. A., Analysis of Intravenous Immunoglobulin for the Treatment of Toxic Epidermal Necrolysis Using SCORTEN: The University of Miami Experience, Archives of Dermatology. (2003) 139, no. 1, 39–43, https://doi.org/10.1001/archderm.139.1.39, 2-s2.0-0037231873.
10.1001/archderm.139.1.39
CAS PubMed Web of Science® Google Scholar
102 Hsu D. Y., Brieva J., Silverberg N. B., and Silverberg J. I., Morbidity and Mortality of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in United States Adults, Journal of Investigative Dermatology. (2016) 136, no. 7, 1387–1397, https://doi.org/10.1016/j.jid.2016.03.023, 2-s2.0-84992523193.
10.1016/j.jid.2016.03.023
CAS PubMed Web of Science® Google Scholar

All articles

Allopurinol-Induced Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis: A Systematic Review of Case Reports and Case Series

Abstract

1. Introduction