RESEARCH ARTICLE

Cutaneous adverse drug reactions in a tertiary care hospital: An observational study

Baijayanti Rath, Manas Ranjan Naik, Bhabagrahi Rath, Renuka Bhoi *, Jai Prakash

^a Department of Pharmacology, VIMSAR, Burla, Odisha, India

^b Indian Pharmacopoeia Commission, Ghaziabad, U.P., India

Introduction

An adverse drug reaction (ADR) is defined as any response to a drug that is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis or therapy of disease, or modification of physiological function (Pirmohamed et al., 2004). The burden of ADRs is high and accounts for considerable morbidity, mortality, and extra cost. Cutaneous adverse drug reactions (CADRs) are one of the most common ADRs caused by drugs causing a lot of morbidity and mortality (Patel et al., 2008). The incidence of ADRs globally varies with studies that show incidences ranging from as low as 0.15% to as high as 30% (Nandha et al., 2011). The overall incidence of CADRs in developed countries is 1-3%, while that in the developing countries is reported to be higher between 2% and 5% (Lazarou et al., 1998). Changes in drug metabolism drug interactions, oxidative stress, and various cytokines are the various factors that cause cutaneous adverse drug reactions. Indian reports on ADR monitoring have been very few. This may be because ADR monitoring is still developing in India. Pharmacovigilance (PvPI) is the pharmacological science that deals with the detection, assessment, understanding, and prevention of adverse effects and promotes the safe use of drugs (Gruchalla et al., 2000). In 2005, the national pharmacovigilance program (NPP) was introduced by the Ministry of Health and Family Welfare further, which was revised in July 2010. This program is monitored by the central drugs standard control organization (CDSCO), New Delhi (Roujeau et al., 1994; Ajayi et al., 2000). The pharmacovigilance program of India plays a vital role in improving the safety of medicines in the Indian population. Under PvPI, various regional ADR monitoring centers (AMCs) have been established at various medical institutions throughout the country. This study aims to evaluate the patterns of CADRs, the causative drugs along with causality and severity assessment.

Methods

A total number of 50 patients with cutaneous adverse drug reactions who were included in our last study attended skin OPD, VIMSAR Burla, from June 2018 to September 2018. This study analyzed all antimicrobial drug-related individual case safety reports (ICSRs) reported at AMC, VIMSAR Burla. Causality assessment of ADRs was done by using the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) causality assessment scale as certain, probable, possible, unlikely, unclassified, and unassessable/unclassifiable (Hartwig et al., 1992). The severity of ADRs was assessed by the modified Hartwig and Siegel scale (Chatterjee et al., 2006). The study was approved by the institutional ethics committee. Descriptive statistics were used to analyze the data and values are expressed in numbers and percentages.

Results

During the study, a total of 50 patients with cutaneous adverse drug reactions were studied. The most common age group is 21-40 years with a male to female ratio of 44% and 56% as presented in Table 1. In the age group 21-40 years, CADRs are found most common. Fixed drug eruption was the most common type of drug reaction (44%). This was followed by a maculopapular rash (24%) and Stevens-Johnson syndrome (16%), as presented in Table 2. Other types of drug reactions like DRESS syndrome (10%), bullous eruption (4%), drug-induced lupus erythematosus (2%) were seen in this study. From Table 3, it was inferred that NSAIDs were the most offending drugs (32%), followed by antitubercular drugs (16%) and ofloxacin (14%), ornidazole (12%), antiretroviral drugs (8%), with the least by fosphenytoin, ciprofloxacin eye drop, bicalutamide, ceftazidime, and vecuronium at 2% each.

Among individual drugs within NSAIDs, paracetamol (87.5%), ibuprofen (6.25%), and aspirin (6.25%) were responsible for fixed drug eruptions, as presented in Table 4. Causality assessment using the WHO-UMC scale (n=50) showed that 8% of ICSRs could be assessed as certain and 24% could be assessed as probable. Most (60%) ICSRs were assessed as possible, as presented in Table 5.

Severity assessment of ADRs by the modified Hartwig and Siegel's severity scale (n=50) indicated that most reactions were of mild-to-moderate severity, with one case (ofloxacin) assessed as severe on the severity scale, as presented in Table 6.

Discussion

In previous studies, maculopapular rash, exanthematous eruptions, urticaria, and erythema multiforme are the most common clinical types of drug reactions. Fixed drug eruptions were the most common drug reaction (44%) in our study, which was very close to the result by Saha et al. (Saha et al., 2012), followed by a maculopapular rash (24%). This is in contrast to the study done by Tejashwani et al. (Tejashwani et al., 2018), where the most common CADRs were maculopapular rash (16.66%) and fixed drug eruptions were only 13.33%. The demographic data shows the age group of 21-40 years and males (56%) were most commonly affected. In the present study, NSAIDs were the drug class most commonly associated with ADRs. Paracetamol (87.5%) was the commonest NSAID responsible for fixed drug eruptions. Antitubercular drugs were responsible for 16% of the CADRs. There were 8 cases of Stevens-Johnson syndrome associated with antibacterial drugs, which often required immediate cessation of treatment. The severity analysis by the modified Hartwig-Siegel scale showed that most of the reactions were moderate (46%), with only one case reaction assessed as severe, i.e. with ofloxacin, where the patient required intensive medical care. Similar results have been obtained from previous studies (Padmavathi et al., 2013).

Conclusions

The pattern of cutaneous adverse drug reactions is variable among previous studies. In this study, NSAIDs were commonly associated with dermatological reactions. Fixed drug eruption was followed by maculopapular rash as the most common presentations. The second most common drug of concern was antitubercular drugs. Most of the CADRs were attributed to antibacterial drugs like ofloxacin and ornidazole, and other drugs like antiretrovirals and antimalarials like artesunate. Most of the reactions were moderately severe. Causality assessment was certain and probable for 18.9% and 41.5% of the reactions, respectively, and reactions were serious in 33.96% (95% confidence interval 21.21-46.71%).

Conflict of Interest

There is no conflict of interest between the authors.

References

1. Ajayi, F. O., Sun, H., Perry, J. (2000). Adverse drug reactions: a review of relevant factors. Journal of Clinical Pharmacology, 40(10), 1093-1101.
2. Chatterjee, S., Ghosh, A. P., Barbhuiya, J., Dey, S. K. (2006). Adverse cutaneous drug reaction: A one year survey at a dermatology outpatient clinic of a tertiary care hospital. Indian Journal of Pharmacology, 38(6), 429.
3. Chattopadhyay, C., Chakrabarti, N. (2012). A cross-sectional study of cutaneous drug reactions in a private dental college and government medical college in eastern India. Nigerian Journal of Clinical Practice, 15(2), 194-198.
4. Gruchalla, R. (2000). Understanding drug allergies. The Journal of Allergy and Clinical Immunology, 105(6 Pt 2), S637-S644.
5. Hartwig, S. C., Siegel, J., Schneider, P. J. (1992). Preventability and severity assessment in reporting adverse drug reactions. American Journal of Hospital Pharmacy, 49(9), 2229-2232.
6. Lazarou, J., Pomeranz, B. H., Corey, P. N. (1998). Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA, 279(15), 1200-1205.
7. Nandha, R., Gupta, A., Hashmi, A. (2011). Cutaneous adverse drug reactions in a tertiary care teaching hospital: A North Indian perspective. International Journal of Applied and Basic Medical Research, 1(1), 50-53.
8. Patel, R. M., Marfatia, Y. S. (2008). Clinical study of cutaneous drug eruptions in 200 patients. Indian Journal of Dermatology, Venereology and Leprology, 74(4), 430.
9. Pirmohamed, M., James, S., Meakin, S., Green, C., Scott, A. K., Walley, T. J., Farrar, K., Park, B. K., Breckenridge, A. M. (2004). Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ, 329(7456), 15-19.
10. Roujeau, J. C., Stern, R. S. (1994). Severe adverse cutaneous reactions to drugs. The New England Journal of Medicine, 331(19), 1272-1285.
11. [UNVERIFIED-S], P., [UNVERIFIED-K], M., [UNVERIFIED-S], A. (2013). Causality, severity and preventability assessment of adverse cutaneous drug reaction: a prospective observational study in a tertiary care hospital. Journal of Clinical and Diagnostic Research (JCDR), 7(12), 2765-2767.
12. Saha, A., Das, N. K., Hazra, A., Gharami, R. C., Chowdhury, S. N., Datta, P. K. (2012). Cutaneous adverse drug reaction profile in a tertiary care outpatient setting in eastern India. Indian Journal of Pharmacology, 44(6), 792-797.
13. Tejashwani, , Patel, D., Bhupati, N. (2018). An observational study of cutaneous adverse drug reactions in a tertiary hospital. International Journal of Research in Dermatology, 4(2), 254-258.

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