Abstract

Steven Johnson’s Syndrome (SJS) is a life-threatening mucocutaneous reaction characterized by skin detachment and blistering. SJS is most commonly triggered by medications, characterized by extensive necrosis and detachment of the epidermis. This case report delves into a rare adverse drug reaction involving Losartan, an angiotensin II receptor antagonist, and hydrochlorothiazide which is a diuretic commonly used for hypertension. A 72-year-old female developed Steven Johnson Syndrome (SJS) after administration of a Losartan-Hydrochlorothiazide combination., the patient’s past medication history showed that she was on Tab. Amlodipine 5mg for a long period and developed pedal edema for this reason they visited the nearby clinic. Later, Tab. Amlodipine 5 mg was changed to Tab. Repace H (Losartan 50 mg + Hydrochlorothiazide 12.5 mg). During the initiation of Tab. Repace H, due to an increase in itching, redness, blistering, and breathing difficulty, was then hospitalized at a tertiary care hospital, where Tab. Losartan H was withdrawn, and treated symptomatically. Management involved a multidrug approach, including intravenous corticosteroids, antibiotics, and topical antimicrobials. The incidence of Losartan-induced SJS is rare, with an estimated annual occurrence of 1-6 per million persons. This case underscores the importance of vigilance in prescribing antihypertensive medications, especially in older individuals, as SJS can be potentially life-threatening. The study challenges previous assertions about drugs with low SJS risk, highlighting the need for ongoing research and clinician awareness.

Keywords

Introduction

Fig 6: Occurance of peeling and appearance of new skin on the toes after treatment

DISCUSSION

In this documented case, a 72-year-old female patient was admitted with complaints of fever, erythema, and severe peeling of skin on the mouth, genital area, palm, and sole. Itchy rashes over the body, cheeks, inside mouth, and buccal mucosa for 3 days. From the patient reconciliation, it was found that the patient was on Tab. losartan H for the past 4 days. It was later diagnosed as Tab. losartan-H induced Steven Johnsons Syndrome by the physician, as the patient developed rashes after the introduction of this medication.  The FDA has approved losartan for the treatment of several illnesses, including diabetic nephropathy and hypertension. ARBs have a reputation for being Reno-protective in those with type 2 diabetes. Losartan prevents angiotensin II-induced cardiac remodeling in hypertension with left ventricular hypertrophy(5).  Hydrochlorothiazide belongs to a class of medications called diuretics also known as water pills. It is used alone or in combination with other medications to treat high blood pressure. The recommended dose for treating fluid retention is 25 to 100 milligrams daily as a single or divided dose and the recommended dose for treating hypertension is 12.5 - 50 milligrams per oral once daily(6).  Steven Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are blistering eruptions that are rare but severe and life-threatening. They are considered to be variants of the same disorder and are often discussed together as SJS/TEN. Onset occurs within 7 to 14 days after drug exposure. Patients are presented with generalized tender/ painful bullous formation over the body with fever, headache, and respiratory symptoms leading to rapid clinical deterioration. Lesions show rapid confluence and spread, resulting in extensive epidermal detachment and sloughing. This may result in marked fluid loss, hypotension, electrolyte imbalances, and secondary infections(7).  The incidence of SJS, SJS/TEN-overlap, and TEN combined between 1991 and 1995 was estimated to be 1.53-1.89 per one million people annually based on a population-based registry in Germany. According to Maja Mockenhaupt's research, 40% of patients older than 40 also had a higher risk of developing SJS, which is consistent with the 72-year-old patient in our instance(8). A similar case report of SJS was reported by Gikku Mariyam Varghese et.al in which the management of treatment was an immediate withdrawal of the offending agent followed by supportive care. Our study also supports it. Garcia-Doval et al., reports that; earlier the drug is withdrawn, the better the prognosis, while exposure to drugs with longer half-lives increases the risk of death.  The management of SJS with corticosteroids is controversial. If steroids are to be taken, they should be started in the early stages and evenly tapered. Corticosteroids with antibiotics have shown an appreciable improvement in a similar case. In this case, Inj methyl prednisone 40 mg IV BD was given for 7 days and was further tapered to 20 mg BD for 5 days. Gradually 10 mg and 5 mg for consecutive 5 days.  It is necessary to monitor for infection, and if a clinical suspicion develops, anti-infective medicine should be begun empirically until culture and sensitivity results are obtained. Antibiotic Inj. Cefglobe (Cefperazone + Sulbactam) 1.5 gm, IV BD for 7 days was given here to the patient. Erythema and lesions were calmed down upon the use of topical antimicrobials such as Metrogyl DC (Metronidazole) ointment, candid ointment, liquid paraffin, Moisturex soft cream, Momate cream, T-bact ointment, DK gel for genitals. Mucositis was healed with syrup Mucain gel. Causality assessment for the ADR was done by using Naranjo adverse reaction probability scale and the score was found to be 8, this indicates that the reaction was probable.  Maja Mockenhaupt's study, reports that drugs with the least risk for SJS/TEN are Beta-blockers, ACE-inhibitors, Calcium channel blockers, Thiazide diuretics (with Sulfonamide structure), Sulfonylurea anti-diabetics (with Sulfonamide structure), Insulin and NSAIDs (propionic acid type i.e., ibuprofen) but our study contradicts with his statement.

CONCLUSION

This case report, reports the fact that severe hypersensitivity reactions can occur with Losartan - Hydrochlorothiazide combination which is a rare adverse drug reaction. SJS can be a possibly dangerous and life-threatening condition. A thorough history of drug use along with a physical examination showing signs of skin and mucous membrane involvement should raise serious suspicions about the illness. Therefore, clinicians must be more cautious while prescribing drugs which belongs to these classes.

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