Indian Journal of Paediatric Dermatology

: 2021  |  Volume : 22  |  Issue : 1  |  Page : 37--42

Clinical Spectrum of Cutaneous Adverse Drug Reactions in Pediatric Population in East Coast of Andhra Pradesh: An Observational Study

VV V Satyanarayana, Suruthi Purushothaman, Bonu Chandipriya 
 Department of Dermatology, Venereology and Leprology, Rangaraya Medical College, Kakinada, Andhra Pradesh, India

Correspondence Address:
Suruthi Purushothaman
House No. 168, Subbiah Nagar, Thattanchavady, Puducherry - 605 009


Context: Cutaneous adverse drug reaction (CADR) among pediatric population is underappreciated and often misdiagnosed in clinical settings. Furthermore, epidemiologic data on only cutaneous adverse reactions among this population are limited. Aim: The aim of this study is to analyze the CADRs with reference to the pattern, causative drugs, its subgroup analysis, and other clinical characteristics among children. Settings and Design: This was an observational, hospital-based study over a period of 12 months. Materials and Methods: The CADRs occurring and referred to the inpatient and outpatient department of dermatology were actively monitored and the collected reports were analyzed for CADR pattern, drug groups, clinicodemographic profile, and severity of adverse drug reaction (ADR). Statistical Analysis Used: Data were documented in Microsoft Excel and analyzed using SPSS Version 20.0. Results: A total of 33 CADRs were documented. Most of the ADRs (40%) occurred between the age of 11 and 15 years. Antimicrobials comprised the major group of drugs causing ADRs (42.4%). Maculopapular rash (54.5%) and urticaria (15.2%) were the most common type of ADR. A single case of death due to anticonvulsant-induced toxic epidermal necrolysis had been observed in the study period. There were more occurrences of ADRs with multiple drugs compared to single-drug therapy. About 80% of reactions were of mild to moderate. Conclusion: Knowledge of the pattern and the offending drug helps in better diagnosis, management, reduced complications in this population, and also helps in preventing recurrences, thereby helps in promoting the safe use of drugs, which can overall impact the quality of health care among children positively.

How to cite this article:
Satyanarayana VV, Purushothaman S, Chandipriya B. Clinical Spectrum of Cutaneous Adverse Drug Reactions in Pediatric Population in East Coast of Andhra Pradesh: An Observational Study.Indian J Paediatr Dermatol 2021;22:37-42

How to cite this URL:
Satyanarayana VV, Purushothaman S, Chandipriya B. Clinical Spectrum of Cutaneous Adverse Drug Reactions in Pediatric Population in East Coast of Andhra Pradesh: An Observational Study. Indian J Paediatr Dermatol [serial online] 2021 [cited 2021 Jan 19 ];22:37-42
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Full Text


The World Health Organization (WHO) describes an adverse drug reaction (ADR) as “Noxious and unintended response to a drug occurring at doses used in man for prophylaxis, diagnosis, or therapy of a disease or for physiological function modification.[1]” ADRs are classified into two classes according to whether it is a predictable side effect related to the pharmacologic action of a drug or if it is an idiosyncratic reactions Type A (augmented) and Type B (bizarre), respectively.[2]

Cutaneous adverse drug reactions (CADRs) represent 35%–36% of any ADRs reported in children, only being surpassed by gastrointestinal ADRs (39%).[3] Incidence in hospitalized children is 2%–3%.[4] Therefore, the dermatologist plays an essential role in the team management of these patients. Children are more susceptible than adults to drug dosage errors because of their smaller body size.[5] Moreover, ADRs can mimic many other childhood eruptions, especially viral exanthems, which present as a maculopapular rash, making it a challenge to differentiate from a CADR.[6] Most CADRs are mild and resolve on withdrawing the causative drug. The most common forms of CADRs are maculopapular exanthems and urticarial reactions which have excellent prognosis.[7] Severe CADRs endangering patient's life are Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis, and drug reaction with eosinophilia and systemic symptoms (DRESS).[8]

While there is a general impression that children are at a lower risk for ADRs than adults, a number of factors pertinent to pediatric therapy place certain groups of children at a high risk for adverse events associated with therapy. Information on the frequency, severity, and class of drugs most frequently involved in cutaneous adverse reactions in the pediatric population group is of particular interest because premarketing clinical trials are done mostly in adults. The safety profile of a drug thus marketed with its testing done on adults can vary significantly when used in children. An active drug surveillance system is needed to capture risk. Thus, the aim of the present study was to determine the age, gender pattern, clinical characteristics, drug implicated, and severity of drug-induced CADRs in pediatric patients in East Coast Andhra Pradesh. Literature search revealed limited studies on only cutaneous reaction among children and no data regarding CADRs in our community. Data obtained in the study will help in determining the specific pattern and drugs implicated and also in predicting the serious CADRs early so that pediatric morbidity and mortality due to CADRs can be either avoided or reduced.

 Materials and Methods

This observational study was conducted between June 2018 and May 2019 after obtaining clearance from the Institutional Ethics Committee (IEC/RMC/2018/574A dated on May 28, 2018) of Rangaraya Medical College, Kakinada. The pharmacovigilance center of the institute of pediatric patients with CADRs who attended the Dermatology, Venereology, and Leprology (DVL) outpatient department (OPD), antiretroviral testing center, or those referred from other departments to DVL were actively evaluated by the postgraduate and details collected with standardized Central Drugs Standard Control Organization suspected ADR reporting form[9] after proper oral informed consent and fulfilling inclusion and exclusion criteria. The study was also explained to the pharmacovigilance center of the institute and collected data were informed and cross-checked every fortnightly through either direct or telephonic conversation. Data collected from the participants were age, sex, implicated class of drug/drugs, indication for use, time gap between drug intake and onset of skin eruption, distribution and duration of the rash, previous similar experiences with the same or different class of drug, presence of comorbidities or interacting diseases, and improvement in cutaneous eruption on stopping the drug. A detailed general, cutaneous, and mucosal examination was performed and noted. The WHO causality definitions which classify ADRs into “certain,” “probable,” “possible,” “unlikely,” “unclassified,” or “unclassifiable” were used to assess the suspected offending drug.[10]

Sample size calculation

Sample size was estimated as 81 calculated with the formula: Z2 P (1 – p)/d2.

Estimated prevalence (p) of pediatric CADRs as 30% with the previous studies.

Absolute error (d) as 10%.

Because the study was limited to 1-year period and comparing previous CADR data in the institute, final sample size was limited to <40 and we observed 33 CADRs at the end of the present study.

Outcome variables were pattern of CADRs (presenting features, morphology, lag period, causative drugs and their pharmacological groups, and severity of the reactions). All data were entered into Microsoft Excel and descriptive analysis was done using IBM SPSS Version 20.0 statistics software package, India. Data analyzed were expressed as frequency and percentage.

Rechallenge was avoided for the ethical reasons.

Inclusion criteria

The following criteria were included in the study:

Children below or aging 15 yearsChildren presenting to DVL OPD or referred from other departments with suspected drug-related CADRsParents or caretaker willing to consent for the study.

Exclusion criteria

Patients not willing to participate in the studyPatients who developed drug reactions following intake of Ayurveda, homeopathic, and indigenous medicines were excluded from the study.


Of the total 362 CADRs, 33 (9.11%) CADR cases were reported in pediatric age group between 3 months and 15 years. Among them, 23 (70%) were boys and 10 (30%) were girls with boy-girl ratio of 2.3:1. The most common age group among reported CADRs in pediatric population were between 11 and 15 years contributing to 13 (40%) cases followed by 12 (36%) cases between 6 and 10 years and 8 (24%) cases between 0 and 6 years. Polypharmacy accounted for around two-third cases of the ADRs received. [Figure 1] shows the frequency of drug groups in the causation of CADRs in the study.{Figure 1}

Antimicrobial agents were the most common drug group involved in 14 (42.4%) children in the reported CADRs followed by antiretroviral therapy (ART) (11 [33.3%]), anticonvulsants (5 [15.15%]), and nonsteroidal anti-inflammatory drugs (NSAIDs) (3 [9.09%]).

Commonly associated antimicrobial agents were ceftriaxone, metronidazole, and cotrimoxazole, among antiretrovirals, most common was abacavir, and phenytoin was the most common implicated anticonvulsants [Table 1].{Table 1}

The common CADRs reported were mild type. [Figure 2] describes the morphological pattern of CADRs observed in the study. The most common pattern observed was maculopapular rash [Figure 3] in 18 (54.5%) children and the most common drug implicated was abacavir followed by urticaria in 5 (15.2%) children and angioedema [Figure 4] in 3 (9.0%) children.{Figure 2}{Figure 3}{Figure 4}

Severe CADRs such as SJS [Figure 5] TEN [Figure 6] and fixed drug eruption (FDE) were observed in seven children and the most common drug implicated was phenytoin [Table 1]. Deaths were seen in 1 case (3.22%) due to TEN (1 case – phenytoin).{Figure 5}{Figure 6}

The average duration of intake of drug and appearance of CADRs is 1 h–25 days. Longest duration was for anticonvulsant drugs (25 days) followed by antiretroviral drug (12.6 days) and the shortest was for antibiotics (1 h).


Cutaneous drug eruptions in the pediatric population are of important public health concern. In the present times, incidence of adverse drug events, morbidity and mortality in the pediatric population, and the overall reports of the drug related events are considerably high. According to studies conducted in outpatients, it is estimated that 2.5% of children who are treated with a drug and up to 12% of children treated with an antibiotic will experience a CADR.[11] Similarly, in the present study, antimicrobials were the most commonly implicated drug which is similar to that of the study done in 2014 at All India Institute of Medical Sciences, Jodhpur,[12] which can be due to the widespread and probably injudicious use of antimicrobials in the setup.

Common CADR pattern in children is five types, exanthematous cutaneous eruption, acute urticarial reaction, FDE, photosensitivity reaction, and serum sickness-like reaction.[13]

The most common pattern observed was maculopapular rash followed by urticarial, which is similar to that of previous studies. The maculopapular rash is characterized by raised, erythematous macules and papules initially originating on the trunk, and further spreading to the limbs and similar clinical features may be induced by viruses and related immunological mechanisms.[14] Some of our patients (five patients with maculopapular eruption) had been diagnosed initially with viral exanthem in different centers, therefore, clear discrimination of both conditions is very important.

Severity scale (Modified Hartwig and Siegel Scale) indicated that about 80% of the cases were mild to moderate in severity. Severe drug reactions include TEN, SJS, DRESS, and drug-induced hypersensitivity syndrome. Death was reported in a single case of a 9-year-old male child started on phenytoin for epilepsy and 15 days later presented with TEN involving 90% of body surface area with oral mucosa and conjunctival involvement.

Chatterjee et al.[15] noted in a study in an outpatient-based setting that the incidence of CADR was 2.66%, whereas in the present study, it is high 9.11% which may be due to regular referral from other departments and antiretroviral centers and female children constituted 61.16% of the total which is not consistent with the present study where males over numbered which matches with the pediatric gender distribution in this zone, indicating that gender does not have much association with CADR. The literature suggests both preponderance of male[16],[17] and female[18],[19] association with CADRs. Common offenders were antimicrobials (34.10%), anticonvulsants (32.88%), and anti-inflammatory drugs (21.51%), and it is in consistent with the previous studies.[17],[19],[20] Among antimicrobials, CADRs due to cephalosporins and antiretroviral drugs were more frequent than cotrimoxazole[18],[21] and penicillins[20] in contrast to earlier studies. Among NSAIDs, diclofenac was the most frequent implicated drug as compared to paracetamol, aspirin,[18] and mefenamic acid[20] in earlier studies. This could be due to the widespread use of diclofenac as analgesic in our setup.

The morphological skin reaction variants in the study by Chatterjee et al.[15] were urticaria (27.19%), fixed drug rashes (25.16%), and macular and morbilliform eruptions (25.43%), whereas in the present study, maculopapular rash (54.5%), over numbered urticaria (15.2%), and FDE common drugs found to cause cutaneous reactions in a study by Raksha and Marfatia[22] were NSAIDs (21%) followed by the sulfa group (14%), whereas Pudukadan and Thappa[18] in their study have reported cotrimoxazole (22.25%) followed by dapsone (17.7%) as the most common offenders. In our study, the most common culprit drug group is antimicrobial agents 42.4% and the most common drug is ceftriaxone (16.7%) followed by ART 33.3%, anticonvulsants 15.15%, and NSAIDs 9.09%.

The risk of adverse reaction directly correlates with the number of drugs taken and the age of the patient.

Fixed-dose regimens were the main culprit drugs causing CADRs mainly ART drugs such as abacavir/lamivudine/nevirapine regimen followed by tenofovir/lamivudine/efavirenz regimen. In the present study, antiretroviral contributed to the second most common drugs implicated which can be attributed to the higher prevalence of childhood retroviral infection in the particular zone.[23]

Nonsevere types of cutaneous drug reactions require only symptomatic treatment with antihistamines and bland emollients mainly along with drug withdrawal. Severe CADRs such as SJS/TEN/DRESS/DISH require inpatient care. Fluid electrolyte balance and systemic corticosteroids, cyclosporine, or intravenous immunoglobulin are the mainstay of therapy along with supportive care in severe CADRs. Systemic corticosteroids in TEN are controversial. Eye care with lubricants in TEN/SJS is important.[24]

This study also highlights the high prevalence of CADRs due to antiretroviral drug as pediatric retroviral infection is comparatively high in the community[23] and immunologically suppressed children are more risky for developing adverse reactions. The present study has few limitations. Being a single-centered study from Southeast India, the results cannot be extrapolated to other hospitals from a different setting. Over the period of 1 year, CADR profile due to various drugs was monitored and the final sample size was reached. Although we monitored all CADRs, there is a possibility of cases being missed out due to patient's interhospital transfer, against medical advice, etc. Hence, our study may not reflect the actual burden of CADRs. Since it is an observational study, we could not follow-up patients for temporal relationship to assess causality and preventability. Thus, we recommend further research and multicentric study to explore other aspects of CADRs.


Timely diagnosis of the condition and identification of the offending drug and its omission form the cornerstone of management to prevent serious outcomes. A high index of suspicion should be maintained to make a rapid diagnosis and in managing children with severe CADRs to prevent morbidity and mortality.

Parents and caretakers should be educated properly regarding the drug class implicated for the specific cutaneous reaction and should be counseled to carry ADR card with them whenever approaching health-care system to prevent reexposure.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published, and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


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