INTRODUCTION
Stevens–Johnson syndrome (SJS) is an acute, rare, and potentially fatal skin reaction that involves loss of skin, and in some cases, mucosal membranes with systemic symptoms.[1] Medications are causative in over 80% of cases.[1]
Here, we present a case series on sertraline, a selective serotonin reuptake inhibitor (SSRI) being the causative agent behind SJS.
CASE SERIES
A 63-year-old female homemaker presented to us with the complaints of fever, cough, and rhinitis for the past 7 days. Over 2 days, it was associated with rash which was all over the face, trunk, and limbs [Figure 1]. It was erythematous, targetoid, purpuric macules and large painful erosions with flaccid bullae. Dermatological opinion was sought. The Nikolsky’s sign was found to be positive. Histological examination of a skin biopsy showed total necrosis of the epidermis. The serology for HIV 1 and 2, hepatitis, and herpes virus was found to be negative. The patient was diagnosed to be in major depression 3 years back and was placed on escitalopram 10 mg initially. Then, over the course of 2 months, the dose was increased to 20 mg. The depressive symptoms were reduced, and she was well-maintained on the drug. She had another exacerbation of the symptoms for the past 3 weeks after defaulting medications for the past 3 months. The patient was started on sertraline 50 mg at night 7 days back. The patient had no other comorbidities, and complete blood count revealed neutropenia and lymphocytosis. Rest all blood investigations were within the normal limits. Reverse transcription–polymerase chain reaction (RT-PCR) for COVID-19 was also negative. The patient was managed with corticosteroids, and sertraline was held. After 2 weeks, her cutaneous symptoms reduced, and she was started on escitalopram 15 mg and subsequently increased to 20 mg over 15 days. She was well-maintained in the follow-up visits. Hence, a diagnosis of Stevens–Johnson Syndrome was made, and the agent causing it was sertraline.
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Figure 1: SJS type lesion on the back
In our second case, a 55-year-old male presented to us with upper respiratory tract infection and fever for 3 days. It was associated with erythematous rash over the face and limbs [Figure 2]. On examination, targetoid macules were found, and the Nikolsky’s sign was positive. It was associated with mucosal lesions over the pharynx. Skin biopsy was taken from the lesions, which showed epidermal necrosis. Complete blood count showed lymphocytosis and eosinophilia. The patient was diagnosed with dysthymia and was taking tablet nortriptyline at a dosage of 100 mg for the past 3 years. The patient defaulted the same for the past 2 months. He was started on sertraline at a dosage of 50 mg at night 2 weeks back, following the return of depressive symptoms. He is a known diabetic on antidiabetic regimen. His Glycated Haemoglobin (Hba1c) and both fasting and postprandial blood sugar levels were within the normal limits. His serology for HIV, hepatitis B surface antigen (HbsAg), and herpes virus was negative. RT-PCR for COVID-19 was also negative. He was managed with methylprednisolone, and sertraline was stopped. His mucocutaneous condition improved in a week, and he was started on amitriptyline 50 mg and was well-maintained in follow-ups.
Figure 2: SJS type lesions on the trunk
In the third case, a 72-year-old female presented with high-grade fever and cough for the past 5 days. It was associated with rash over the face, limbs, and trunks that emerged 2 days following fever. The rashes were erythematous and macular with annular features. The Nikolsky’s sign was positive, and histology revealed necrosis of the epidermal layer. The patient was diagnosed with major depressive disorder with anxious distress 7 years back and was tried on amitriptyline 100 mg initially and then on dosulepin 100 mg. She responded well to both, but defaulted for the past 1 year. There was relapse of symptoms 1 month back, and thus, she was put on sertraline 50 mg 10 days back. She had no other comorbidities. Complete blood count showed eosinophilia, and other blood investigations were normal. Her serology profile that included HIV 1 and 2, HbsAg, and herpes virus was negative. RT-PCR for COVID-19 was also negative. She was managed with corticosteroids, and sertraline was withheld. Her mucocutaneous symptoms reduced, and she was started on escitalopram 10 mg. She was well-maintained in ward for 7 days, and dosage was increased to 20 mg during discharge, but she defaulted follow-ups till then.
DISCUSSION
In the literature, we have found many cases of anticonvulsant, notably lamotrigine-induced SJS.[2,3] Case reports of SSRI-induced SJS are less, and in one article, lamotrigine-fluoxetine combination led to SJS.[4] Coming to sertraline, we could only find one reported case.[5]
SJS is rare and occurs unpredictably that involves drug-specific CD8+ cytotoxic lymphocytes, the Fas-Fas ligand (FasL) pathway of apoptosis, granule-mediated exocytosis, and tumor necrosis factor-alpha (TNF-α) pathway.[6] Granulysin, found in the cytotoxic granules, is the main cause of keratinocyte apoptosis. Fas–FasL, expressed on the activated cytotoxic T-cells, can also destroy keratinocytes through the production of intracellular caspases. Cytotoxic T-cells exocytose perforin and granzyme B, which create channels in the target cell membrane activating the caspases. TNF-α, nitrous oxide induced by TNF-α, and interferon (IFN)-alpha may stimulate caspases.[7]
Lamotrigine has more action on such immune pathways that involve CD4 and CD8 cells compared to other psychotropics.[8] Antidepressants appear, in general, tend to reduce pro-inflammatory factor levels, particularly C-reactive protein, TNF-α, interleukin (IL)-1β, and IL-6, but still can also increase their level triggering the release of cascades involving IFNs and complement system.[9]
In our case series, all of the patients were using different brands of sertraline and had an age of above 50 years. This goes in sync with the single reported case on sertraline and SJS, but no such age-related association could be established.[5] In order to identify the culprit drug (s), it is important to consider the chronology of administration of the drug and the reported ability of the drug to induce SJS/TEN. The chronology of administration of a culprit drug, or time between first administration and development of SJS/TEN, is between 1 and 4 weeks in the majority of cases, which is in our case series too.[10]
Thus, sertraline, which is considered to be safe in psychiatric practice, can lead to such dangerous and fatal event. Hence, while prescribing it, we should monitor the patient for such complications.
Ethical concerns
Due consent was taken from the patients regarding sharing their details anonymously.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
It was self-funded.
Conflicts of interest
There are no conflicts of interest.
REFERENCES
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