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
- Presence of generalised purpuric macules on face, inside the mouth, on
both upper limbs, the entire trunk and on both lower limbs
- Presence of desquamation of skin over purpuric macules over both upper
limbs, back, both heels and face causing superficial erosions
- Presence of oral aphthae
- Lips showing superficial erosions with crusting
- Crusting on bilateral perioral area
- Bilateral conjunctivae showed erythema
- presence of erosions on vaginal mucosa
- scalp was spared
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
- age > 40 years,
- epidermal detachment > 30%,
- blood urea > 28 mg/dl
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;
- Positive temporal association between drug intake and occurrence of
skin lesions
- No other pathophysiological explanation of the skin lesions
- Positive De-challenge test as the skin lesions stopped spreading after
the withdrawal of the drug
- Re-challenge was not done
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