Albendazole and Stevens–Johnson syndrome: A cause

Aakash Gupta; Balachandra S Ankad; Priyanka Jaju

doi:10.4103/CDR.CDR_40_18

CASE REPORT

Year : 2020 | Volume : 4 | Issue : 1 | Page : 53-56

Albendazole and Stevens–Johnson syndrome: A cause

Aakash Gupta, Balachandra S Ankad, Priyanka Jaju
Department of Dermatology, S. Nijalingappa Medical College and HSK Hospital, Bagalkot, Karnataka, India

Date of Submission	19-Oct-2018
Date of Decision	29-Dec-2018
Date of Acceptance	03-Feb-2019
Date of Web Publication	06-Jan-2020

Correspondence Address:
Aakash Gupta
Department of Dermatology, S. Nijalingappa Medical College and HSK Hospital, Bagalkot, Karnataka
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/CDR.CDR_40_18

Abstract

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) represent severe reactions in the skin and the mucous membranes, most commonly caused by drugs. An adult female developed erythematous and dusky red lesions over the body 5 days after oral albendazole. Atypical target lesions sparing the scalp were seen on day 2 of admission with positive Nikolsky sign. A clinical diagnosis of SJS (with 12.1% predicted mortality) was made which correlated with biopsy. The patient responded well to intravenous dexamethasone and oral cyclosporine. The report highlights the drug, albendazole, as a sole factor causing SJS/TEN and warrants further evaluation and subsequently control measures.

Keywords: Albendazole, drug reaction, Stevens–Johnson syndrome

How to cite this article:
Gupta A, Ankad BS, Jaju P. Albendazole and Stevens–Johnson syndrome: A cause. Clin Dermatol Rev 2020;4:53-6

How to cite this URL:
Gupta A, Ankad BS, Jaju P. Albendazole and Stevens–Johnson syndrome: A cause. Clin Dermatol Rev [serial online] 2020 [cited 2022 Jan 25];4:53-6. Available from: https://www.cdriadvlkn.org/text.asp?2020/4/1/53/275246

Introduction

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) represent severe reactions in the skin and the mucous membranes caused by drugs. The two terms share same phenotype in the same spectrum where SJS is limited to 10% body surface area (BSA), and TEN represents >30% BSA involvement. Both the conditions are characterized by blistering and epithelial sloughing.

In 1922, Stevens and Johnson first reported the syndrome in two boys, who presented with fever, erosive stomatitis, severe ocular inflammation, and widespread eruptions over the body including mucosa.^[1]

Initially, the cutaneous lesions were similar to that of erythema multiforme (EM) and hence SJS was thought to be a severe form of EM. Later, Lyell reported six patients with extensive epidermal loss, resembling scalded skin, along with marked systemic involvement and termed it TEN.^[2] Along the years, it was recognized that extensive SJS could cause TEN. In 1993, physician experts suggested that SJS is a part of TEN spectrum and should not be classified along with EM. A new spectrum of dermatoses called SJS/TEN has been proposed with drugs as a causative factors.^[3] The overall SJS/TEN mortality is about 22%; in SJS <10% of patients die from the acute illness, while in TEN the predicted mortality is approximately 30%.^[4] Literature review suggests that albendazole inducing SJS is a very rare phenomenon.^[5] Here, we describe SJS caused by a commonly used drug albendazole.

Case Report

A middle-aged female presented to the outpatient department of a tertiary care hospital in Karnataka. She presented with discrete to confluent erythematous macule all over the body with mucosal erosions, fever, and easy fatigability of 2 days' duration. There was a rapid progression to STS/TEN overlap within 3 days [Figure 1], [Figure 2], [Figure 3]. Initially, the lesions were erythematous and dusky red. Atypical target lesions sparing the scalp were seen on Day 2 of admission with positive Nikolsky sign. Hemorrhagic crusts were seen on vermillion border and marked conjunctival congestion was seen. Her SpO₂ was 100% on room air, total count was normal except a mild increase in neutrophils. Chest radiograph, renal function test, serum glucose level, and serum bicarbonates were within the normal limits. Systemic examination of the patient revealed no abnormality.

Figure 1: Few well-defined hemorrhagic papules with erythematous base (on admission)

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Figure 2: The same patient after 3 days of admission. Epidermal keratinization is clinically evident

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Figure 3: Multiple ill-defined dusky lesions over the back after 3 days. Back at admission (inset)

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There was a history of taking albendazole 5 days before the onset of symptoms. The skin biopsy showed epidermal necrosis, basal vacuolar change, and epidermal and dermal lymphocytic infiltrate [Figure 4]. A diagnosis of SJS was made based on clinical and histopathological features. Dermoscopy revealed erythematous base containing islands of necrosis [Figure 5]. The SCORE of TEN (SCORTEN) score was two in this patient at diagnosis, with predicted mortality of 12.1%.^[6],[7] The patient responded well to intravenous dexamethasone and oral cyclosporine.

Figure 4: Biopsy showing epidermal necrosis, basal vacuolar change, epidermal and dermal lymphocytic infiltrate (×10 view). Inset apoptotic keratinocytes (×40 view)

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Figure 5: Dermoscopy of lesion showing necrotic patches over erythematous base

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Discussion

The incidence of SJS/TEN is approximately 1–2 cases per million per year.^[8],[9],[10] Although SJS and TEN can occur in any age group, the elderly are commonly affected with female being twice as commonly affected.^[11]

SJS/TEN is mainly caused by drugs, with a culprit drug being demonstrated in around 85% of cases.^[11] Theoretically any medication can cause SJS but allopurinol, carbamazepine, lamotrigine, nevirapine, oxicam, phenobarbital, phenytoin, sulfamethoxazole, and sulfasalazine have a higher association and are responsible for one-half of all cases.^[12],[13] HLA-B1502 and HLA-B5801 association has also been demonstrated in susceptible individuals.^[14],[15] To find the culprit drug, the European SCAR Study was designed to demonstrate the time latency from the beginning of drug administration and onset of adverse events.^[16]

It is believed that SJS is hypersensitivity reaction caused by drug-induced cytotoxic T lymphocytes activating immune reactants such as tumor necrosis factor-α, interferon-γ, and inducible nitric oxide synthase which causes keratinocyte damage directly or through activation of FAS ligands, perforin, granzyme, and granulysin leading to apoptosis.^{[16],[17],[18],[19]}

As soon as a diagnosis of SJS/TEN has been made, discontinuation of the culprit drug is an essential and immediate intervention; this maneuver decreases the risk of death.^[20]

SCORTEN was developed by Bastuji-Garin et al. to predict mortality in patients suffering from SJS/TEN. SCORTEN is calculated at admission and includes age, presence of malignancy, heart rate, epidermal detachment, serum urea, serum glucose, and serum bicarbonate levels. One point is given for each parameter up to a maximum score of 7 [Table 1]. The mortality is predicted on the total score in the patient which ranges from 1.2% to 98.5% [Table 2].^[4],[7],[21]

Table 1: SCORTEN criteria

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Table 2: SCORTEN: Severity of illness score for toxic epidermal necrolysis

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An algorithm, termed ALgorithm of Drug causality in Epidermal Necrolysis (ALDEN), has been developed to help define drug causality in SJS/TEN. It is used as a retrospective measure of drug causality. It includes parameters such as (a) delay from the initial drug component intake to the onset of reaction (index day), (b) drug present in the body on index day, (c) prechallenge/rechallenge, (d) dechallenge, (e) type of drug (notoriety) and other causes. The scores given in ALDEN scores range from −12 to +10. The scores correspond to <0: very unlikely; 0–1: unlikely; 2–3: possible; 4–5: probable; and ≥6: very probable.^[6] The ALDEN score, in this case, was found to be 2; hence, there is a possibility that albendazole may cause SJS. Naranjo algorithm for the causal association was 5,^[22] indicating the probability of albendazole in causing such reaction. Rechallenge test was not done in the present case.

The development of SJS has been reported in a patient following intake of metronidazole along with mebendazole.^[16],[23] Albendazole (P02CA03)^[24] belongs to a similar category as mebendazole in the anti-helminthic spectra, and its association as a drug causing SJS should be kept as a possibility.

It is well known that perforin-granzyme and granulysin-mediated immunological response is implicated in the pathogenesis of SJS. Recently, granulysin has been proposed as a marker for early diagnosis of SJS.^[25] The mortality in SJS is significantly reduced when patients are given systemic corticosteroids along with cyclosporine.^[26]

Conclusion

SJS is a life-threatening disorder with drugs being attributed in most of the cases. To the best of our knowledge, only a few cases of SJS/TEN due to albendazole have been reported.^{[5],[27],[28]} More studies are warranted to prove this causal association.

Declaration of patient consent

The informed consent was obtained for participation in the study and publication of data and images for research and educational purposes.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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