Cutaneous adverse drug reactions (CADRs) are among the most common manifestations of drug-induced toxicity, ranging from mild, self-limiting rashes to severe, life-threatening conditions such as Stevens–Johnson syndrome and toxic epidermal necrolysis (1). They are a significant cause of morbidity and occasionally mortality in hospitalized patients, contributing to increased length of stay and healthcare costs (2,3).

The risk of CADRs is strongly associated with polypharmacy, which is increasingly prevalent in modern clinical practice, especially among elderly patients and those with multiple comorbidities (4,5). The simultaneous administration of several medications raises the probability of drug–drug interactions, altered pharmacokinetics, and cumulative toxicities (6). Hospitalized patients are particularly vulnerable due to the frequent use of antimicrobials, anticonvulsants, antiretrovirals, and nonsteroidal anti-inflammatory drugs, which are well-known triggers of CADRs (7,8).

Previous studies have reported CADR prevalence rates in hospitalized patients ranging from 2% to 10%, with variation based on prescribing patterns, population characteristics, and diagnostic criteria (9).

The present prospective observational study was designed to evaluate the prevalence, clinical patterns, and severity of CADRs among hospitalized patients exposed to polypharmacy. This study aims to contribute to the growing body of evidence that can support safer prescribing practices and strengthen institutional pharmacovigilance frameworks.

Study Design and Setting

This was a prospective observational study conducted in the dermatology and general medicine wards of a tertiary care teaching hospital over a period of 12 months (June 2023–May 2024).

Study Population

A total of 620 hospitalized patients aged ≥18 years and receiving polypharmacy (defined as ≥5 concurrent medications) were included. Patients with pre-existing dermatological conditions that could confound diagnosis of CADRs, those unwilling to participate, and those admitted for less than 48 hours were excluded.

Data Collection

All enrolled patients were followed during their hospital stay. Detailed demographic and clinical information, including age, sex, comorbidities, number and class of drugs prescribed, and duration of therapy, was recorded. Patients were examined daily for the occurrence of cutaneous reactions. Any suspected CADR was confirmed by a dermatologist through clinical examination and supported, when necessary, by relevant investigations (e.g., skin biopsy, laboratory tests).

Assessment of Causality and Severity

The relationship between the suspected drug and the reaction was assessed using the World Health Organization–Uppsala Monitoring Centre (WHO-UMC) causality scale. Reactions were categorized as certain, probable, possible, or unlikely. Severity was graded using the Modified Hartwig and Siegel scale, classifying cases into mild, moderate, or severe. Preventability was also assessed using the Schumock and Thornton criteria.

Data Analysis

All data were entered into Microsoft Excel and analyzed using SPSS version 25.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics were applied for prevalence, demographic distribution, and clinical patterns. Categorical variables were expressed as frequencies and percentages, while continuous variables were presented as mean ± standard deviation. Chi-square test was applied to assess associations, and a p-value <0.05 was considered statistically significant

Prevalence of CADRs

Out of 620 hospitalized patients receiving polypharmacy, 58 developed CADRs, giving an overall prevalence of 9.3%. Among them, 35 were male (60.3%) and 23 were female (39.7%). The highest incidence was observed in the age group 41–60 years (46.5%), followed by 21–40 years (31.0%) (Table 1).

Table 1. Demographic distribution of patients with CADRs (n=58)

Clinical Pattern of CADRs

The most frequently observed reactions were maculopapular rash (41.3%), fixed drug eruption (20.6%), and urticaria (18.9%). Severe forms such as Stevens–Johnson syndrome and exfoliative dermatitis were reported in 3.4% and 1.7% of cases, respectively (Table 2).

Table 2. Clinical patterns of CADRs

Drug Classes Implicated

Antimicrobials were the most common causative group (39.6%), followed by anticonvulsants (22.4%) and NSAIDs (19.0%). Other classes included antiretrovirals and antitubercular drugs (Table 3).

Table 3. Drug classes associated with CADRs

Causality and Severity Assessment

According to the WHO-UMC causality scale, 62.0% of reactions were “probable,” while 31.0% were “possible” and 7.0% were “certain.” Most CADRs (72.4%) were mild to moderate in severity, while 5 cases (8.6%) were classified as severe, requiring drug withdrawal and intensive supportive care (Table 4).

Table 4. Causality and severity of CADRs

Summary of Findings

Overall, the prevalence of CADRs among hospitalized patients on polypharmacy was 9.3%. The most common clinical pattern was maculopapular rash, and antimicrobials were the leading causative agents. Majority of reactions were categorized as probable in causality and mild-to-moderate in severity, though a small proportion progressed to severe forms requiring hospitalization and drug withdrawal (Tables 1–4).

In the present study, the prevalence of cutaneous adverse drug reactions (CADRs) among hospitalized patients receiving polypharmacy was 9.3%, which is consistent with earlier reports ranging between 2% and 10% in inpatient settings (1,2). The observed rate underscores the heightened susceptibility of patients exposed to multiple medications to dermatological toxicities.

Demographic patterns in this study showed a higher occurrence among middle-aged adults (41–60 years), aligning with earlier findings where CADRs were more frequent in adults than in pediatric or geriatric groups (3,4). A slight male predominance was noted, though gender distribution has varied across studies (5).

Clinical manifestations revealed maculopapular rash, fixed drug eruption, and urticaria as the leading presentations, corroborating evidence from previous prospective analyses in Indian and Western cohorts (6,7). Severe forms such as Stevens–Johnson syndrome, though less common, remain clinically significant due to their high morbidity and mortality risk (8,9).

Drug classes implicated included antimicrobials, anticonvulsants, and NSAIDs, similar to other pharmacovigilance studies that consistently identify these agents as common offenders (10,11). Antitubercular and antiretroviral drugs also contributed, reflecting prescribing patterns in tertiary care hospitals where infectious diseases are common (12).

Causality assessment using the WHO-UMC scale showed most reactions as “probable,” comparable to studies that highlight the difficulty in establishing certainty due to polypharmacy and confounding comorbidities (13). Severity assessment demonstrated that the majority of reactions were mild to moderate, but a notable fraction required discontinuation of the offending drug, similar to earlier observations (14).

The findings emphasize the need for proactive pharmacovigilance, particularly in hospitalized patients with complex medication regimens. Rational prescribing, periodic medication review, and prompt dermatological consultation can reduce the clinical and economic burden of CADRs (15).

This prospective study demonstrates that cutaneous adverse drug reactions are relatively common in hospitalized patients receiving polypharmacy, with a prevalence of 9.3%. Antimicrobials, anticonvulsants, and NSAIDs were the leading culprits, and maculopapular rashes were the most frequent clinical presentation. While most reactions were mild to moderate, a notable minority required drug withdrawal and intensive care. These findings emphasize the importance of vigilant monitoring, rational prescribing, and early dermatological involvement to reduce the burden of CADRs in hospital settings.

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