|Year : 2019 | Volume
| Issue : 2 | Page : 89-93
Assessment of cutaneous adverse drug reactions in a tertiary care hospital
Juny Sebastian, Madhan Ramesh, Chanchal Anandhy Mahin, Linda Jose, Vijayalaxmi Nagappa Sirasgi, Adhirai Raveendran
Department of Pharmacy Practice, JSS College of Pharmacy, JSS Academy of Higher Education and Research (JSSAHER), Mysuru, Karnataka, India
|Date of Web Publication||16-Dec-2019|
Dr. Madhan Ramesh
Department of Pharmacy Practice, JSS College of Pharmacy, JSSAHER, Sri Shivarathreeshwara Nagar, Mysuru - 570 015, Karnataka
Source of Support: None, Conflict of Interest: None
Introduction: Cutaneous adverse drug reactions (CADRs) are one of the significant clinical problems not only in dermatology practice but also in any areas where drug is involved. Aim: The aim of this study was to determine the incidence, pattern, predictors, and direct cost associated with the management of CADRs. Methodology: It was a prospective, observational study which involved both spontaneous reporting and intensive monitoring. Study patients were followed throughout their hospital stay. Where a CADR was detected, all the required data were collected and analyzed. Bivariate regression analysis was used to determine the predictors of CADRs. Results: The incidence of CADRs was 25.01%. Drug classes most commonly implicated in CADRs were antibiotics (29.055%), nonsteroidal anti-inflammatory drugs (17.31%), antineoplastic drugs (11.17%), and antitubercular drugs (10.05%). Majority (66.48%) of the reactions were “probable” in their causality category. Serious CADRs accounted for 1.67%. There was a significant association between the occurrence of CADRs and the use of ≥2 medications, adult patients, and male gender. The total and average costs incurred in the management of CADRs were INR 61,116/- and 734/-, respectively. Conclusion: Among the study population, adults, male gender, and patients receiving ≥2 medications and patients who presented with ≥2 comorbidities were identified as the predictors for the development of CADRs. Hence, it is important to monitor closely the patients with the identified risk factors for the CADRs to minimize the complications associated with the CADRs.
Keywords: Cutaneous adverse drug reactions, inpatients, intensive monitoring, outpatients, spontaneous reporting
|How to cite this article:|
Sebastian J, Ramesh M, Mahin CA, Jose L, Sirasgi VN, Raveendran A. Assessment of cutaneous adverse drug reactions in a tertiary care hospital. Indian J Drugs Dermatol 2019;5:89-93
|How to cite this URL:|
Sebastian J, Ramesh M, Mahin CA, Jose L, Sirasgi VN, Raveendran A. Assessment of cutaneous adverse drug reactions in a tertiary care hospital. Indian J Drugs Dermatol [serial online] 2019 [cited 2020 Jun 3];5:89-93. Available from: http://www.ijdd.in/text.asp?2019/5/2/89/272965
| Introduction|| |
Adverse drug reactions (ADRs) are a major problem in drug therapy. Cutaneous ADRs (CADRs) are the most common ADRs (30%–45%) in recent times. CADRs are described as any “noxious, unintended, morphologic skin changes with or without systemic involvement that develops after local or systemic administration of drugs in dosage commonly used for prevention, diagnosis, or treatment of disease or modification of physiologic function.”, In the United States, the incidence of fatal ADRs is 0.32%, and CADRs account for >30% of all reported ADRs. CADRs affect 2%–3% of all hospitalized patients and 2% of which are considered to be severe. CADRs are responsible for about 2% of hospital admissions, and approximately 2%–7% of these are reported to be severe. In India, CADRs account for 2%–5% of all inpatients (IPs), while it affects 2.6% of outpatients (OPs).
The incidence of ADRs increases with increase in number of drugs, and almost all drugs can cause dermatologic reactions. CADRs can arise as a result of immunologic or nonimmunologic mechanism and can range from minor to severe life-threatening reactions. The most common mild-to-moderate CADRs are rashes, urticaria, pruritus, itching, hypersensitivity reactions, and angioedema, and the severe reactions are alopecia, psoriasis, Stevens–Johnson syndrome (SJS), toxic epidermal necrosis (TEN), and fixed drug eruption (FDE)., Female gender, increasing age, more number of drugs, immunocompromised status, genetic factors, and autoimmune disorders are implicated as risk factors for the development of CADRs.,
The frequency of CADRs in a particular population is influenced by the drug utilization habit, the reaction rates of drugs, and pharmacogenetic traits of the population studied. CADRs are one of the significant problems not only in dermatology practice but also in any area where a drug is involved. The study was designed in this background to assess the CADRs as it is essential to know the information regarding dermatologic reactions to take measures to minimize the complications of CADRs and prevent and manage these reactions.
The main objective of the study was to identify the pattern of CADRs in patients treated at the study site. The study also aimed to determine the incidence, predictors, and the direct cost associated with the management of CADRs.
| Methodology|| |
This prospective and observational study was conducted for a period of 6 months from October 2014 to March 2015. The study site was the Departments of General Medicine, Surgery, Paediatrics, Psychiatry, and Dermatology Wards of JSS Hospital, Mysuru. The study was approved by the Institutional Human Ethical Committee. The study enrolled patients who were admitted and treated in the study site of either gender of any age and who received at least one medication. All the relevant data were collected from the patient case records, treatment charts, laboratory reports, and interviewing patient and his caretakers. All those eligible inpatients were intensively monitored to identify the development of any ADR from the day of admission to the day of discharge. The OP case sheets were reviewed on the day of patient visit to the hospital to detect any ADR. Furthermore, the study considered the spontaneous reporting of ADRs received from health-care professionals working in the study site. On the identification/reporting of a CADR, all the relevant data pertaining to the patient and the CADR were documented in a suitably designed data collection form.
Cutaneous adverse drug reaction assessment
Collected data were further reviewed to confirm the occurrence of CADR, and the collected data were subjected for analysis to determine the incidence, causality (using Naranjo Scale and WHO Probability Scale), predictability, preventability (using Modified Schumock and Thornton Scale), severity (using Modified Hartwig and Siegel scale), seriousness, and outcome of CADRs.
Predictors of cutaneous adverse drug reactions
Gender, age, duration of hospital stay, number of comorbidities, and number of drugs received were the variables that were taken into consideration for identification of predictors. The statistical analysis was performed, and the predicted values were calculated using bivariate regression analysis.
The total direct cost involved in the management of CADRs was assessed considering the cost associated with bed charges, cost of medications and devices, laboratory investigation costs, and consultation fee.
| Results|| |
Of the total 1416 patients (640 OPs and 776 IPs), ADRs were reported in 650 patients (OP = 450 and IP = 200) during the study period. A total of 179 CADRs were identified from 163 patients giving an incidence of 25.07%, while with respect to number of ADRs, the incidence is 27.53%. Most of the CADRs were reported from OPs (n = 86 [54.60%]), and male patient population developed more CADRs (n = 90 [55.21%]). The demographic details of the study population are present in [Table 1].
CADRs were predominant in adults (n = 115 [70.55%]) when compared to pediatrics and geriatrics. SJS, psoriasis, angioedema, urticaria, and FDE were the most common reasons for the admission and thereby the reported serious CADRs. Among the CADRs, 97 were Type A (54.19%) and 82 were Type B (45.81%). It was observed that both in IPs and OPs, rash (31.28%), urticaria (15.08%), FDE (8.93%), alopecia (7.26%), and itching (6.70%) were found to be the most common CADRs. The details of CADRs are present in [Table 2].
In our study, the classes of drugs most commonly implicated in CADRs were antibiotics (n = 52 [29.05%]), nonsteroidal anti-inflammatory drugs (NSAIDs) (n = 31 [17.31%]), and antineoplastic agents (n = 20 [11.17%]), followed by antituberculosis drugs (n = 18 [10.05%]). The most common antibiotics which contributed to CADRs in our study were ceftriaxone (8.37%), amoxicillin (3.35%), and ciprofloxacin (2.79%). Among NSAIDs, paracetamol (7.26%), diclofenac (6.14%), and aspirin (1.67%) were the drugs most commonly implicated in CADRs.
Assessment of cutaneous adverse drug reactions
The causal association between the suspected drugs and the reported CADRs was found to be “probable” in 119 (66.48%) and “possible” in 60 (33.52%) cases. Of the 179 CADRs observed in our study, 84 (46.92%) and 95 (53.08%) CADRs were belonged to “mild” and “moderate” in its severity category, respectively. Of the total CADRs reported, 93 (51.95%) CADRs were “predictable” and 86 (48.04%) were “not predictable.” Only 1.67% of CADRs were serious.
Predictors of cutaneous adverse drug reactions
The findings of the statistical analysis suggest that patients who receive ≥2 medications, adults, male gender, and patients who have ≥2 comorbidities were the predictors for the development of CADRs. The details of the predictors of CADRs in our study population are presented in [Table 3].
Management of cutaneous adverse drug reactions
In the present study, the main line of management of CADRs was the withdrawal of the suspected drug which was observed in 104 (58.10%) cases. No change in the suspected drug was made in 75 (41.89%) cases, as these reactions were mild and do not require any alteration in dose or withdrawal of the suspected drug. Topical treatment was given in 21.48% of cases (15.08% [OP] and 6.40% [IP]) and systemic treatment was given in 38.89% of cases (17.31% [OP] and 21.58% [IP]) to treat the CARD. It was also observed that most of the patients (139 [77.65%]) were recovered from the CADRs, while in 31 cases (17.31%), it was continuing at the end of the study and, in 9 cases (5.02%), the outcome was not known. None of the CADRs were fatal.
Cost assessment due to cutaneous adverse drug reactions
It was observed that the total cost involved in the management of CADRs was Rs. 61116. The average cost involved in the management of CADRs was Rs. 734.04 (range: Rs. 100–900).
| Discussion|| |
Similar to the previously published studies, the present study observed CADRs commonly in male gender and adult age group. There are published studies describing that the CADRs can occur at any age from pediatrics to geriatrics. The common CADRs reported in the study are similar to the study conducted by Raut et al., wherein rash (31.91%) and urticaria (4.25%) were reported to be the commonly occurred CADRs. The severity category of the reported CADRs is also similar to the previous study,, where the reported severity category was mild in 51.06%, moderate in 23.4%, and severe in 25.5% of CADRs. However, some other studies reported more CADRs of moderate and severe category as they observed reactions such as SJS, TEN and FDE., Majority of such reactions were seen in patients enrolled from OP departments as their disease conditions were mild to moderate that can be treated with ambulatory care, whereas patients with severe cutaneous conditions needed hospital admission. Drug classes implicated for CADRs in the present study was antibiotics and NSAIDs similar to previously published studies.,,, However, a study done by Saha et al. found that the major drug classes implicated for the CADRs were sulfonamides and fluoroquinolones. Some of the predictable reactions include rash, angioedema, and alopecia while pruritus, FDE, and psoriasis reaction were not predictable due to the use of multiple drugs which may all contribute to the CADRs. Nonpredictable reactions come under that category, as the CADRs were developed after initiation of appropriate therapy including dose, frequency, route of administration, and duration. The study also observed that none of the CADRs were due to drug–drug interactions, and where required, appropriate monitoring was carried out to prevent the CADRs due to drug–drug interactions.
Causality assessment of the CADRs was found to be similar with the study conducted by Raut et al., wherein most of the reactions had a “probable” causality score, followed by possible causality score as assessed using Naranjo algorithm. CADRs that were found to be serious include angioedema, FDE, and urticaria as these reactions resulted in prolongation of hospitalization.
Predictors of cutaneous adverse drug reactions
The bivariate analysis identified age, gender, number of comorbidities, and number of medications as predictors of CADRs in the study population. Assessment of other factors such as duration of hospital stay was not statistically significant. These findings are similar to the published studies ,,,, which all reported increasing number of drugs administered, age, gender, and number of comorbidities as risk factors for developing CADRs. Increased body mass index, preexisting renal and liver diseases, more than 4 comorbidities, more than 6 drugs, and the history of previous ADRs were listed as predictors for ADR-related hospitalization in a previously published study.
Management of cutaneous adverse drug reactions
The first-line management of any ADR is the withdrawal of the suspected drugs. But, withdrawal of the suspecting agent depends on many factors such as nature and severity of ADRs and availability of the alternate medication which can be used in the particular clinical situation., In this study, CADRs such as urticaria, hypersensitivity reaction, and hyperpigmentation required a suspected drug to be withdrawn, and symptomatic treatment was initiated. In CADRs such as rash and pruritus, the suspected drug was continued as the reaction was mild, and the literature suggests that these reactions subside by itself ,, on the continued use of these drugs. In most of such cases, patients were on chemotherapy, antiretroviral therapy, antitubercular therapy, and receiving treatment for diabetes mellitus or hypertension.
Majority of the patients recovered from the CADRs with the symptomatic therapy and some reactions were continuing by the end of the study, as it was obvious that reaction like psoriasis requires more time to recover completely. CADRs such as urticaria, rash, pruritus, FDE, angioedema, hyperpigmentation, and hypersensitivity reactions warranted the use of topical formulation and systemic formulations such as corticosteroids and antihistamines. CADRs that led to prolongation of hospital stay incurred the maximum cost as found in previous studies by Chan et al. and Qing-Ping et al.
| Conclusion|| |
Although the study identified that the major drug classes implicated for CADRs are antibiotics and NSAIDs, any patients receiving multiple drug therapy are at risk for the development of any cutaneous reaction. Hence, any new symptom following administration of a drug needs to be suspected and investigated for CADRs. The immediate management of any CADRs is the withdrawal of the offending agent, and the reaction resolves after 1 to 2 weeks following withdrawal.
The authors would like to thank the staff and students of the Department of Dermatology and Department of Clinical Pharmacy, JSS Hospital, for their encouragement and support. We would also like to thank Mr. D.H.P Gowda, Assistant Professor at JSS College of Pharmacy, Mysore, for supporting us to perform the statistical analysis.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Patel TK, Thakkar SH, Sharma D. Cutaneous adverse drug reactions in Indian population: A systematic review. Indian Dermatol Online J 2014;5:S76-86.
Sudersan V, Siddiqua S, Aruna D, Manmohan, Ramesh S, Yasmeen N. Cutaneous adverse drug reactions in a tertiary care hospital. Der Pharmacia Lettre 2012;4:408-13.
Raut A, Pawar A, Pankaj M, Srivastava P, Mishra A. Clinical pattern and severity of cutaneous adverse drug reactions. Int J Pharm Pharm Sci 2013;5:612-16.
Ahmad A, Parimalakrishnan S, Mohanta GP, Manna PK, Manavalan R. Incidence of adverse drug reactions with commonly prescribed drugs in tertiary care teaching hospital in India. Int J Res Pharmaceutical Sci 2012;3:79-83.
Son YM, Lee JR, Roh JY. Causality assessment of cutaneous adverse drug reactions. Ann Dermatol 2011;23:432-8.
Noel MV, Sushma M, Guido S. Citaneous adverse drug reactions in hospitalized patinets in a tertiary care center. Indian J Pharmacol 2004;26:292-5.
Saha A, Das NK, Hazra A, Gharami RC, Chowdhury SN, Datta PK, et al.
Cutaneous adverse drug reaction profile in a tertiary care out patient setting in Eastern India. Indian J Pharmacol 2012;44:792-7.
] [Full text]
Sharma R, Dogra D, Dogra N. A study of cutaneous adverse drug reactions at a tertiary center in Jammu, India. Indian Dermatol Online J 2015;6:168-71.
] [Full text]
Shamna M, Dilip C, Ajmal M, Linu Mohan P, Shinu C, Jafer CP, et al.
A prospective study on adverse drug reactions of antibiotics in a tertiary care hospital. Saudi Pharm J 2014;22:303-8.
Amrinder R, Kaur I, Singh J, Kaur T. Monitoring of cutaneous adverse drug reactions in a tertiary care hospital. J Pharmacovigil 2016;4:207.
Ghosh S, Acharya LD, Rao PG. Study and evaluation of the various cutaneous adverse drug reactions in Kasturba hospital, Manipal. Indian J Pharm Sci 2006;68:212-5. [Full text]
Verma R, Vasudevan B, Pragasam V. Severe cutaneous adverse drug reactions. Med J Armed Forces India 2013;69:375-83.
Alomar MJ. Factors affecting the development of adverse drug reactions (Review article). Saudi Pharm J 2014;22:83-94.
Tuchinda P, Chularojanamontri L, Sukakul T, Thanomkitti K, Nitayavardhana S, Jongjarearnprasert K, et al.
Cutaneous adverse drug reactions in the elderly: A retrospective analysis in Thailand. Drugs Aging 2014;31:815-24.
Angamo MT, Curtain CM, Chalmers L, Yilma D, Bereznicki L. Predictors of adverse drug reaction-related hospitalisation in Southwest Ethiopia: A prospective cross-sectional study. PLoS One 2017;12:e0186631.
Sasidharanpillai S, Riyaz N, Khader A, Rajan U, Binitha MP, Sureshan DN, et al.
Severe cutaneous adverse drug reactions: A clinicoepidemiological study. Indian J Dermatol 2015;60:102.
Sharma R, Dogra N, Dogra D. A clinical study of severe cutaneous adverse drug reactions and role of corticosteroids in their management. Indian J Drugs Dermatol 2017;3:20-3. [Full text]
Riedl MA, Casillas AM. Adverse drug reactions: Types and treatment options. Am Fam Physician 2003;68:1781-90.
Chan AL, Lee HY, Ho CH, Cham TM, Lin SJ. Cost evaluation of adverse drug reactions in hospitalized patients in Taiwan: A prospective, descriptive, observational study. Curr Ther Res Clin Exp 2008;69:118-29.
Qing-Ping S, Xiao-Dong J, Feng D, Yan L, Mei-Ling Y, Jin-Xiu Z, et al.
Consequences, measurement, and evaluation of the costs associated with adverse drug reactions among hospitalized patients in China. BMC Health Serv Res 2014;14:73.
[Table 1], [Table 2], [Table 3]