Paracetamol Induced Toxic Epidermal Necrolysis: A Case Report

Introduction

The dermatologic condition named Toxic epidermal necrolysis (TEN) is characterised by extensive erythema, necrosis, and bullous detachment of the epidermis and mucous membranes. This condition can be fatal with exfoliation that can lead to sepsis and/or death.¹

This condition was first described in 1939 and a Scottish dermatologist Alan Lyell coined the term toxic epidermal necrolysis (TEN) in 1956 to describe an uncommon but severe condition, also known as Lyell’s disease.

TEN is frequently identified by broad blisters that appear as macules and/or flat atypical targets whenever there is a significant separation of the skin and mucous membrane, which is accompanied by full-thickness epidermal necrosis.

Additionally, severe, episodic, acute mucocutaneous reactions are observed which are most often brought on by medications and seldom by infections.² The illness is self-limiting, but has a high incidence of morbidity (10–70) and many potential sequelae due to scarring.¹

Erythema multiforme (EM) can occur in rare and severe forms, including Stevens-Johnson syndrome (SJS). It can occur as a result of negative hypersensitive reaction to medications, which can cause potentially lethal skin and mucosal eruptions. It is regarded as a less serious variation of toxic epidermal necrolysis (TEN). The extent of epidermal detachment, which accounts for 30% of the body surface area is the only distinction from SJS-TEN which shows just 10 to 30%.³

Due to its affordability and ease of use, paracetamol is one of the most commonly used analgesic and antipyretic. Despite being considered to be very safe, adverse effects such as cutaneous hypersensitivity reactions have been reported. Few cases of SJS and TEN linked to paracetamol use have been reported in the past.⁴

Case Report

A 40 year old male patient presented to the hospital with multiple grouped vesicles and bullae with erosions of skin all over the body since three days. The patient had fever associated with chills four days before and took medication for sore throat on the same day. Patient presented with burning sensation in eyes along with watering of eyes. He had disturbed sleep secondary to burning sensation. The patient developed erosions in the oral cavity since two days and also erosions in genitalia along with burning sensation during micturition since one day. Patient gave a history of developing two similar episodes of reaction one year and also three years ago. Patient took medication for upper respiratory tract infection, after which he was apparently normal for three days, before developing itching all over the body. Initially during this episode, patient consumed paracetamol orally for fever. After developing itching, patient consumed cetirizine for relief. Following this, a sudden, progressive onset of itching developed on upper limbs, lower limbs, trunk followed by multiple blisters formation over upper limbs, lower limbs, trunk and genitals. Patient gave a history of alcohol consumption twice a week.

In laboratory findings, complete blood count results were as follows - white blood cells 15000 mm (neutrophils: 88.8%, lymphocytes: 9.4%, monocyte: 1.3%, eosinophil: 0.3%, basophil: 0.2%), haemoglobin 16.8 g/dL, platelet: 394*10/uL. Hepatic enzymes, blood urea nitrogen and serum creatinine were within normal range. Patient was managed with Inj. Dexamthasone 2 cc, Inj. Pantop 40 mg, Inj. Ceftriaxone 1 g and Calamine lotion (OD), Soframycin cream (OD), Liquid paraffin (CD) for topical application on affected areas of the skin. The lesions resolved with a faint lingering hyperpigmentation after 15 days of the above mentioned treatment. Skin biopsy was performed on a lesion on right arm, oral provocation test was not conducted and patch test was done which was positive.

Discussion

SJS is a rare, severe, mucocutaneous blistering illness that manifests suddenly and unpredictably resulting in significant morbidity. TEN is the name given for its more severe variant. SJS used to be regarded as an EM major, but due to its severity, the presence of constitutional symptoms, atypical target lesions with a propensity to confluence, a positive Nikolsky’s sign, the involvement of several mucosal sites, and lasting sequelae, it is now considered as a separate entity from EM.

Three clinical criteria, including the pattern of individual skin lesions, the distribution of lesions, and the degree of epidermal detachment, allow SJS to be distinguished from other skin disorders. SJS results in extensive ulcerative lesions in the oral cavity. About 30% of patients experience prodromal symptoms, which typically appear one to three weeks after beginning a new medication and lasts for one to two weeks. These symptoms include flu-like symptoms, sore throat, headache, arthralgia, myalgia, fever, and other rashes.

In a small number of cases, ocular alterations such as dry eyes that match those of mucous membrane pemphigoid may be noticed. There could be urethritis and vulvar ulcers. The eye, genital, skin, and mouth ulcers were present.

Although various causes including drug induced infections, malignant illnesses, and transplant rejection have been suggested as SJS risk factors, majority of them were attributed to side effects to drugs. Nonsteroidal anti-inflammatory drugs (NSAIDs), antipsychotics, antibiotics, allopurinol, and anticonvulsants are the most popular medications.³

In the present case report, the patient complained of wet eyes and burning sensation in the eyes. He had trouble sleeping because of the burning sensation. The patient developed erosions in the oral cavity since two days, as well as erosions in the genitalia and burning sensation during micturition since one day. Patient’s medical history revealed that he had previously experienced two episodes of similar reaction after taking medication for an upper respiratory tract infection, one year and also three years ago. The patient appeared to be normal three days prior, but after taking Paracetamol for his fever, he started to experience itching all over his body. To reduce itching, patient used cetirizine. Following this, a sudden, progressive onset of itching with multiple blisters on upper and lower limbs was observed and the itching spread to the trunk.

There is no widely established, unquestionably successful, or targeted treatment for SJS/TEN other than confirmative care. The major therapeutic activity in TEN is early detection of the drug reaction and withdrawal of the substance. Because confirmative care is an essential component of its therapeutic strategy and as it may be a life-threatening condition, acid-base and metabolic balance regulation, fluid and electrolyte replacement, glucose management, and topical skin treatment comprises the initial management. Mouthwashes are used to treat oral lesions. With the use of topical anaesthetics, patient can drink fluids and experience less discomfort. Any exposed skin can be covered with sterile cloths impregnated with paraffin or saline.

The patient’s full recovery in the present case can be attributed to the prompt and successful management of inflammation with systemic steroid therapy and the appropriate topical care of the scouring regions. According to past research, systemic steroids, antibiotics, and adjunct therapies were used to treat majority of the TEN patients. Careful handling, nutritional support, aggressive fluid & electrolyte control, and pain management are required. The cornerstone for the treatment could be the importance of sterile wound care. A sterile dressing should be applied often to necrotic tissues. A variety of biological and artificial compounds were used for wound dressing with varying degrees of success. It is important to note that individuals with a history of SJS or an unfavourable skin reaction to Paracetamol should not consume the medicine again, and a complete medical history should be collected before any prescriptions are issued.

The condition of the patient improved after the intake of Paracetamol was stopped. Thus drug withdrawal is the first line of treatment for medication-induced TEN. The early and prompt treatment of the patient with general antibiotics and steroids, as well as the acceptable topical care of the scouring regions with inseminated paraffin sterile dressings, could be considered as probable reasons for his complete recovery. Therefore, in conclusion, knowledge of medications that cause significant drug reactions like TEN/SJS can help doctors prevent these conditions with judicious use of medications and appropriate handling of the situations.

Conclusion

From the present case report, we may infer that Paracetamol could be the most likely cause for the incident as the patient did not report having taken any other medications prior to the incident. The confirmatory patch test conducted also came positive for Paracetamol and Paracetamol has been known to cause similar reactions in the past. Thus, it is imperative for doctors to be aware of serious unfavourable hypersensitivity reactions that can occur even with medications that are generally believed to be safe, such as Paracetamol.