Case history:
A 58 year old female patient presented to dermatology out-patient department (OPD) with chief complaints of
Rash over entire body including her face and mouth since 6 days [Figure1]
Peeling of skin over both upper limbs and both lower limbs, trunk and back since 5 days[Figure2] [Figure3]
On further eliciting the history, the patient mentioned that she had been taking sustained release tablet of aceclofenac 200 mg, over the counter, since 14 days for complaint of bilateral knee joint pain from a local pharmacy near her home. About 8 days before the admission to our hospital, she took two tablets of aceclofenac 200 mg sustained release at the gap of 5-6 hours. About 3-4 hours of taking the second tablet, she had an episode of fever which was sudden onset, progressed to high grade and was associated with burning sensations all over the body, nausea, malaise and arthalgia. The episode of fever was abated on giving paracetamol 500 mg by the family members. She also developed a rash which first appeared over her fingers of hands, spread to both upper limbs along with the trunk. The rash further progressed to her face including oral mucosa and around both eyes, both lower limbs and finally spread to the entire body. The next day, there was peeling of skin on the rashes at her face including areas around both eyes [Figure 1], upper limbs [Figure 2] and lower limbs, trunk and both back [Figure 3]. The relatives took the patient to a local private practitioner where the symptoms of the patient could not be alleviated and the lesions continued to progress. She was referred to the dermatology OPD of our hospital where she was admitted subsequently. There was no history of burn injury, diarrhoea, haematuria, photophobia or burning micturition. The patient had no history of similar complaints in the past. She was a known case of hypothyroidism since 12 years for which she was taking tablet levothyroxine 25 mcg once daily and hypertension since 10 years for which she is taking amlodipine 5 mg once daily. The patient had taken second dose of Covishield dose against Covid-19, 6 months back. She did not experience any hypersensitivity reaction back then. The patient had regularly been taking over the counter diclofenac sodium for knee joint pain for the last 5 years, at a local pharmacy near her home. There was no history of similar complaints in the family.
General examination revealed normal rate of pulse, respiration, normal blood pressure and temperature with no pallor, icterus, cyanosis, clubbing or lymphadenopathy. No significant finding was noticed during systemic examination. Findings of local/dermatological examination were as follows
as per rule of 9, approximately 40% of body surface area was involved in desquamation.
Laboratory investigations revealed that Liver function tests, random blood sugar, urine protein were withing normal limits. Complete blood count revealed haemoglobin at 8 g/dl while other parameters were within normal limits. There was increase in serum urea and serum creatinine levels. [serum urea:50 mg/dl; serum creatinine: 1.5 mg/dl]
SCORTEN score came out to be 3
a diagnosis of TEN secondary to aceclofenac consumption was made on the basis of history and clinical examination.
The patient was treated with intravenous fluids, multivitamins, corticosteroids, oral anti-fungals. Liquid paraffin was applied locally on the lesions. Wound care was done on the lesions for 5 days. Normal saline soaks were applied on the lips. Antibiotic prophylaxis was given to prevent any further infection of lesions.
The patient was hospitalised for seven days. There was marked improvement in her symptoms. The spread of the skin lesions was stopped, older skin lesions healed and there were no new lesions occurring.
WHO-UMC causality assessment7 came out to be “probable” category as there was;
Discussion: TEN is a rare, acute, serious and potentially life-threatening cutaneous disorder associated with extensive erythema, necrosis blistering and detachment of epidermis and mucous membranes. Medications are causative in over 80% of cases of TEN.8
The underlying pathophysiology of TEN is not completely understood. It is considered to be cytotoxic t cell mediated human leukocyte antigen dependent drug hypersensitivity. At least 200 drugs have been reported to be associated with SJS/TEN. Drug can elicit cytotoxic T-cell response by several mechanisms; drug or drug metabolite may act as hapten or pro-hapten, may directly interact with HLA protein, may alter the specificity of HLA or may bind directly with T-cell receptor which can eventually lead to T-cell activation. Upon activation, stimulated cytotoxic CD-8+ cells kill autologous target cells. Extensive apoptosis, sloughing and necrosis in keratinocytes and mucosal cells is brought about by cascade release of cytokines or chemokines including perforin/granzyme, Fas-FasL, TNF-α and granulysin.9
Besides strong association of SJS/TEN with certain HLA alleles, genetic variation in drug metabolising enzymes and rug transporters that play important role in pharmacokinetics of drugs also appears to be involved in pathogenesis of SJS/TEN. Viral and bacterial infections, malignancies, vaccination too can interact complexly with immune system and increase the risk of developing SJS/TEN.9
The most common acute complication is septicaemia.8 In the long term, many internal organ systems outside of the eyes and skin maybe affected in SJS/TEN, including the pulmonary, gastrointestinal/hepatic, oral, otorhinolaryngologic, gynaecologic, genitourinary and renal systems.10
Management recommended by expert group involves prompt withdrawal of culprit drug, meticulous supportive care and judicious and early use of corticosteroids with or without cyclosporine.11 The reported mortality rate of TEN is approximately 30%.12
Ten can occur in all age groups, the mean age in TEN induced by NSAIDs is more than in SJS (57.7 ± 3.6 v/s 4.8 ± 2.6 years). In general, female sex appears to be more vulnerable to TEN. The most common group of NSAIDs involved in SCARs are reported to be proprionic acid derivatives, acetaminophen, acetic acid derivatives and salicylic acid. The mean time to symptom onset is reported to be 12.1 ± 3.8 days for TEN induced by NSAIDs.13 The time of symptoms onset in previous case report of aceclofenac induced TEN is around 24 hours after taking 100 mg tablet of aceclofenac6 but in our case the patient was exposed to aceclofenac over 14 days. In the previous report, aceclofenac induced TEN proved to be fatal6 while in our case, the patient showed improvement and was discharged after seven days.
Drug induced Ten is potentially life threatening disorder. Early detection and prompt treatment is crucial for better outcome. Aceclofenac can induce TEN in susceptible individuals.
Acknowledgments: NIL
Conflict of Interest: No conflict of interest
Funding: not applicable