Drug-induced eruptions manifest in various forms and are triggered by medications like antimicrobials, antiepileptics, or NSAIDs. Maculopapular skin eruptions are the most common skin reactions to antimicrobials, whose presentations vary from mild skin irritation to severe diseases such as Stevens-Johnson Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN). 

SJS is a mucocutaneous illness which is associated with significant morbidity and mortality[4]. In SJS, they are commonly characterized by erythematous macules and hemorrhagic erosions of the mucous membranes[7]. The global incidence of drug-induced SJS is around 77% and among them, the antimicrobial Sulphonamide induced SJS is most common[5, 15]. The incidence in children is rarer than in adults[6].

Levine GA (2015) stated that with a 45.8% global usage, Co-amoxiclav is one of the most commonly prescribed antibiotics. This drug is also one of the five drugs that cause severe cutaneous adverse reactions (SCARs) and is known to cause maculopapular rashes, which is a mild and common cutaneous Adverse Drug Reaction (ADR)[8, 9]. Such reactions are commonly immune mediated and also occur in about 10 per cent of individuals treated with beta-lactams. Although they frequently cause mild cutaneous reactions, the progression to SJS due to Co-amoxiclav is uncommon and rare with a reported incidence of 1 per million people per year[1]. In this case report, we describe a case of SJS that was induced by Co-amoxiclav in a 13-year-old male child.

A 13-year-old child, a resident of Marathwada region, presented with a history of fever and sore throat to a local physician and was prescribed Tablet Co-amoxiclav - Amoxicillin (250mg) & Clavulanic acid (125mg) twice a day and Tablet Paracetamol (250mg) three times a day. On day 3, after starting the medications, the patient began to develop an erythematous maculopapular rash with central blisters initially over his four limbs. Then it spread all over his chest and back and gradually involved 70% of his total body area on day 5. This was then followed by the appearance of oral lesions, bilateral conjunctival congestion, and genital mucosa involvement on day 6. On the same day, he reported to the casualty of tertiary care Government Medical College & Hospital of Maharashtra and was advised to discontinue all previous medications and to get hospitalized. 

On the day of hospitalization, general examination showed the child was well-built, nourished, conscious, and oriented. His vitals were normal, and a systemic examination showed no abnormal deficit. Cutaneous examination shows multiple well-defined bullae throughout the body. There were well defined post inflammatory hyperpigmentation over the back. The lips had well-defined, crusted, and bleeding erosions, and the patient experienced difficulty in opening his mouth. Bilateral conjunctival congestion was present and the genital mucosa was involved ([Fig. 1] & [Fig. 2]). There was a history of a similar episode one year back, characterized by identical lesions and similar extent of body surface area involvement, after consumption of unknown tablets orally, and was managed by a local practitioner after hospital admission.

Throughout his hospital stay for 9 days, the patient received intravenous steroids, antibiotics, intravenous fluids, antifungals, and other treatment according to standard hospital protocol[8]. Topical care involved saline soaks, chlorhexidine mouth wash, antibiotic cream, and moisturizing lotion applied all over the body and genitals. The inability of patient to open his mouth slowly disappeared as the healing of the erosion cured, and he could take oral feed. By day 8 of hospitalization, repeat photographs of the patient was taken ([Fig. 3] & [Fig. 4]).

Lab tests revealed an initial count of White Blood Cell (WBC) was 13,000 cells/cm³, and it steadily decreased to 8,200 cells/cm³ over the course of the hospital stay. The Liver Function Tests (LFT) and Renal Function Tests (RFT) were in normal range. HCV test was negative. The child recovered subsequently and was discharged on day 9 of hospitalization. 

The patient provided written informed assent and the patient’s parent also provided informed written consent for this manuscript and photograph to be published. Institutional Ethics Committee approval was obtained.

The event showed a reasonable temporal relationship with drug intake, and the clinical response to drug withdrawal was appropriate, with no rechallenge been done. Given that the patient had previously tolerated paracetamol without any similar reaction, the adverse drug reaction was decided as “probable” using the WHO causality assessment scale[11]. The Naranjo Adverse Drug Reaction Probability Scale was also used as an assessment of causality criterion of the suspected ADR. The total score in the evaluation was "7", and it was determined that the causality of the ADR due to Co-amoxiclav was “probable”[10] ([Table. 1]). 

As part of the Pharmacovigilance Program of India (PvPI), this case was reported to the Indian Pharmacopoeia Commission via the VigiFlow platform through AMC (ADR Monitoring Centers). Reporting ADRs to national centers like PvPI and to the WHO is essential for enhancing overall drug safety[12].

For prognostic purposes in SJS/TEN patients, a validated mathematical tool known as SCORTEN (severity-of-illness score for toxic epidermal necrolysis) was used. This score predicted a mortality of 3.2%[13] ([Table. 2]). The SCORTEN score on the day of admission was 3.2%, with only one prognostic parameter positive (epidermal detachment >10%). Repeat assessment on day 3 showed no change in the score. At the time of discharge, the score had reduced to 0%, correlating with complete healing of all cutaneous lesions. Early identification of SJS, discontinuation of triggering medicine, and prompt initiation of supportive therapy had improved the prognosis in this patient. Early detections and interventions such as issuing drug alert cards to patients can aid in preventing future re-exposure and reactions, thus decreasing the mortality and improving the chances for survival[14].

Though Co-amoxiclav is considered among one of the safe antimicrobial used and very commonly used antimicrobial among all age groups, it can show a serious, life threatening ADR like SJS, very rarely. We have reported SJS related to Co-amoxiclav, which is very rare (1 per million). It further highlights the importance of attentive ADR observation and its management, the need for pharmacogenetics interventions and proactive pharmacovigilance of all drugs, even they are traditionally considered safe.

Thanks to my professors and fellow residents for their support. I express extreme gratitude to Dr. Rajkumar (Junior Resident, Dept. of Skin & VDRL) for his continued assistance in this research.