|Year : 2019 | Volume
| Issue : 3 | Page : 77-82
Evaluation of adverse drug reactions in dermatology department of a charitable hospital in India
Murshida Parvin1, Uday Venkat Mateti1, Tonita Mariola Noronha2
1 Department of Pharmacy Practice, NGSM Institute of Pharmaceutical Sciences, Nitte, Mangalore, Karnataka, India
2 Department of Dermatology, K.S. Hegde Medical Academy, Nitte, Justice K.S. Hegde Charitable Hospital, Mangalore, Karnataka, India
|Date of Web Publication||15-Oct-2019|
Dr. Uday Venkat Mateti
Department of Pharmacy Practice, NGSM Institute of Pharmaceutical Sciences, Nitte, Mangalore, Karnataka
Source of Support: None, Conflict of Interest: None
Background: Adverse drug reactions (ADRs) can be confined to either skin or be a part of systemic reaction such as drug hypersensitivity syndrome or toxic epidermal necrolysis. Objective: The objective is to evaluate the incidence, causality, severity, preventability, and risk factors of ADRs in the dermatology department of a charitable hospital in India. Patients and Methods: A prospective observational study was carried out over a period of 8 months in the dermatology department. The WHO and Naranjo's scales evaluated the suspected ADRs for causality assessment, severity by Hartwig and Siegel Scale, and preventability by modified Schumock and Thornton Scale. Results: A total number of 200 eligible patients were enrolled in the study. Out of 200, 18 patients developed ADRs. The incidence of dermatological ADRs in the study was 9%. The most commonly manifested ADRs were Stevens–Johnson syndrome (SJS) (22.2%) followed by skin rashes (16.7%) and others. The maximum number of ADRs were observed with antibiotics (33.5%), followed by antiepileptic drugs (16.7%) and nonsteroidal anti-inflammatory drugs (NSAIDs) (16.7%). According to the WHO and Naranjo's scales, most of the reactions were probable with 61.1% and 55.6%, respectively. Most of the ADRs were moderately severe (66.6%) and were not preventable (55.6%). Conclusions: SJS and rashes were the most commonly observed clinical pattern of ADRs. The most common drug class responsible for ADRs was antibiotics, followed by antiepileptic drug and NSAID's. Dermatological ADRs varied in their causality, severity, and preventability.
Keywords: Adverse drug reaction, Stevens–Johnson syndrome, toxic epidermal necrolysis
|How to cite this article:|
Parvin M, Mateti UV, Noronha TM. Evaluation of adverse drug reactions in dermatology department of a charitable hospital in India. Libyan J Med Sci 2019;3:77-82
|How to cite this URL:|
Parvin M, Mateti UV, Noronha TM. Evaluation of adverse drug reactions in dermatology department of a charitable hospital in India. Libyan J Med Sci [serial online] 2019 [cited 2019 Nov 13];3:77-82. Available from: http://www.ljmsonline.com/text.asp?2019/3/3/77/269229
| Introduction|| |
We know that medicines are beneficial to the human body and are used either to cure or to prevent diseases. Nevertheless, these drugs can also cause certain harmful effects under therapeutic doses. Health-care professionals are required to be aware of these reactions to reduce the burden caused by adverse drug reactions (ADRs) on patients and the society. Drug-induced skin reactions are common and account for 30% of all reported ADRs. It is essential that patients are made aware of his/her sensitivity, as subsequent exposure to the drugs may cause more severe eruption. Skin reactions may occur at any point of time during the course of the treatment., The majority of skin reactions such as exanthematous (75%–95%) and urticaria (5%–6%) were caused due to drug exposure. These drug reactions can be confined to either skin or be a part of systemic reaction such as drug hypersensitivity syndrome or toxic epidermal necrolysis (TEN). Cutaneous drug reactions are thought to be mild to moderate but sometimes can be life-threatening such as Stevens–Johnson syndrome (SJS) and TEN. Pharmacist can act as the key person in health care and drug therapy, who provides information regarding safety and efficacy of drugs. The aim of the study is to evaluate the incidence, causality, severity, preventability, and risk factors of ADRs in the dermatology department of a charitable hospital.
| Patients and Methods|| |
A prospective observational study was carried out over a period of 8 months (from August 2016 to March 2017) at Justice K.S. Hegde Charitable Hospital, Mangaluru. The Institutional Ethics Committee (REF: INST.EC/EC/70/2016–2017) of K.S. Hegde Medical Academy, Mangaluru, India, approved the study. Patient of either gender with more than 18 years and all the patients presenting to the dermatology department were included in the current study. The information includes demographics data such as age, gender, complaints on admission, medical history, medication history, allergies, and prescription given to the patient including drug prescribed, dose, frequency and duration of the treatment was obtained from the patient's clinical records. Details necessary for evaluation regarding previous allergies, concomitant medications, comorbidities, and others were collected. All the prescriptions of the study population were screened for the assessment of ADRs. Identification of ADRs was done based on the regular follow-up of the patients by analyzing the subjective and objective findings. Demographics of the patients were studied to find out the pattern of ADRs. Factors studies were (a) patient characteristics (gender, age, comorbidities, and length of stay) and (b) drug characteristics (number of drugs).
Causality assessment was performed using the WHO-UMC and ADRs were categorized into certain, probable, possible, unlikely, and conditional. Naranjo's causality assessment scale whereby the ADRs were classified into certain, probable, possible, and unlikely to be drug induced depending on the level of association. Depending on the severity, ADRs were classified into mild, moderate, and severe reactions using the criterion developed by Hartwig–Siegel Scale for severity assessment. ADRs were categorized into definitely preventable, probably preventable, and not preventable by using the criteria of Schumock and Thornton Modified Scale.
Frequencies with percentage was used to summarize age groups, gender, number of drugs dispensed, frequency of ADRs, drugs involved in with ADRs and without ADRs, and severity of ADRs. Mean with standard deviation was used to summarize age and length of stay. The Chi-square test was used to find the association between age groups, gender, number of drugs, and length of hospital stay on with and without ADRs. P < 0.05 was considered as statically significant. All the data were analyzed in the SPSS version 16.0 (IBM Corp., Armonk, NY, United States of America).
| Results|| |
A total number of 200 patients were recruited during the study period. Out of 200 patients, 18 patients developed ADRs. The percentage occurrence of ADRs in the study was 9%. In the present study, most of the patients developed ADRs in the age group of 18–30 years (33.3%) followed by other age groups. The mean age group of the patients with and without ADRs was 42.38 ± 17.84 and 38.92 ± 14.76 years, respectively, with P = 0.684. [Table 1] summarized the detailed age-wise distributions of the patients.
Most of the ADRs were developed in female patients (61.1%) than male patients (38.8%). There was no significant difference in gender between patients with ADRs and without ADRs. The gender-wise distributions of the patients are presented in [Table 1]. In this study, 90% of the patients without ADRs had no history of social habits and none of the patients had any history of social habits. [Table 1] summarized the detailed social habits of the patients. Most of the patients had diabetes mellitus (5%), hypertension (4%), and other comorbidities. Details among the patients are presented in [Table 1]. The median number of drugs prescribed per patient with ADRs was 9 and without ADRs was 3, respectively. There were significant differences in number of drugs prescribed between patients with and without ADRs. The detailed information on number of drugs prescribed per patient is summarized in [Table 1].
The most common class of drugs responsible for development of ADRs in this study was antibiotics (33.5%) (ampicillin [5.6%], clindamycin [5.6%], vancomycin [5.6%], tazobactam [11.1%] and meropenem [5.6%]) followed by antiepileptic drug (phenytoin [16.7%]), nonsteroidal anti-inflammatory drugs (NSAIDs) (paracetamol [16.7%]) and other class of drugs are summarized in [Table 2]. SJS (22.2%) was the most commonly observed cutaneous ADR (CADR) seen in 4 patients, followed by rashes (16.7%) in 3 patients, erythema multiforme (5.6%), fixed drug eruption (5.6%), TEN (5.6%), acne vulgaris (5.6%), Drug reaction with eosinophilia and systemic symptoms syndrome (5.6%), maculopapular rash (5.6%), urticarial (5.6%), polymorphic light eruption (5.6%), and others were seen in each one patient. [Table 3] and [Table 4] summarized the clinical patterns of ADRs and the suspected ADRs with drugs. ADRs were classified into three class based on the seriousness of reactions. Out of 18 ADRs, 8 (44.4%) patients required hospitalization, 8 (44.4%) required intervention to prevent permanent damage, and life-threatening ADRs in 2 (11.1%) patients. Out of 18 patients, 7 (38.9%) patients spent in hospital in the range of 15–24 days due to ADRs followed by 0–1 day, 2–7 days, and 8–14 days.
The causality assessment of suspected ADRs was analyzed by using the WHO-UMC and Naranjo's scales. As per the WHO-UMC causality assessment [Table 5], most of the ADRs were probable (61.1%) and possible (38.9%). As per Naranjo's scale [Table 5], most of the ADRs were probable (55.6%) followed by possible (38.9%) and certain (5.6%).
The Hartwig Scale performed the severity assessment of ADRs. Out of 18 ADRs, most ADRs were moderate 11 (66.66%) followed by mild 6 (33.33%). The detailed severity levels of ADRs are presented in [Table 5]. Preventability assessment was performed by using Schumock and Thornton Scale. As per this scale, 44.4% of the reactions were probably preventable and 55.6% were not preventable. [Table 5] summarized the detailed preventability assessment of ADRs. Out of 18 ADRs, in 16 cases drug was withdrawn (88.9%), 1 case dose was altered (5.6%), and in another case no change (5.6%). Out of 18 ADRs, in 17 cases, symptomatic (94.4%) treatment was given, and in only 1, case-specific (5.6%) treatment was given. The treatment outcomes of ADRs (n = 18) was 88.9% of the ADRs were recovered followed by 11.1% continuing in this study. Out of 18 ADRs, in 16 (72.2%) case, dechallenge has been performed and 2 (27.7%) cases dechallenge has not been performed. In all the 16 dechallenged cases, definite improvement of ADRs was observed. In this study, the rechallenge was not performed in any of the cases.
| Discussion|| |
According to the WHO, ADR is defined as “a response to a drug that is noxious and unintended and occurs at doses, used in human for prophylaxis, diagnosis, or therapy of a disease or for modification of physiological function.” It may also result in diminished quality of life, increased physician visits, hospitalizations, and even death. In this study, the incidence of dermatological ADRs was 9%, that is, higher than reported figures from similar studies conducted by Gohel et al. and Suthar and Desai were 3.78% and 7.02%, respectively., The incidence of dermatological ADRs among patients in developed countries ranges from 1% to 3%, whereas in developing countries such as India, it is 2%–5%., The incidence of drug-induced adverse skin reactions was found to be 2%–15% in a dermatology outpatient setting. CADRs are the most frequent of all manifestations of drug sensitivity. They manifest with a varied and diverse morphological pattern ranging from trivial urticaria to severe form gangrene.
In the present study, the occurrence of ADRs was predominance in females; the findings were similar to previous studies,,, where the higher incidence was observed in females as compared to males. In this study, the maximum number of ADRs was developed in the age group 18–30 years which is comparable to the study conducted by Hiware et al., and in contradictory to the study carried out by Chatterjee et al., were the majority of patients in a younger age group (11–20 years).
In the present study, the most common class of drugs responsible for the development of ADRs were antibiotics, followed by antiepileptic drugs and NSAIDs; results that were similar to those observed in other studies., We found that SJS (22.2%) was the most commonly observed CADR seen, followed by rashes and other reactions; findings comparable to a recent study reported by Sasidharanpillai et al., and contradictory to other studies , were the maculopapular rash was the most common ADR.
As per the WHO-UMC causality assessment, we found most of the ADRs were probable (61.1%) and possible (38.9%). These results are comparable to a study carried out by Rajaram et al. were probable (81.25%) and possible (18.75%) of ADRs. Contradictory result was found in a study conducted by Gohel et al., most of the ADRs were possible (54.6%) and probable (36%). As per the Naranjo's scale, most of ADRs were probable (55.6%) followed by possible (38.9%) and certain (5.6%). These results are comparable to the previous study carried out by Murray et al., ADRs were probable (67.30%) and possible (32.69%). Contradictory result was found in the study conducted by Bushra et al., ADRs were probable (97.8%) and certain (2.2%).
In the present study, the Modified Hartwig and Siegel Scale performed severity assessment of ADRs. Most of the ADRs were mild (33.33%) followed by moderate 11 (66.66%). These results are similar to study carried by Rajaram et al., the ADRs were moderate (70%), mild (20.88%), and severe (2.08%). Contradictory result was found in the study carried out by Verma et al., the ADRs were mild (67.6%), moderate (29.4%), and severe (2.9%).
Preventability assessment was performed by using the Schumock and Thornton Scale. As per this scale, 44.4% of the ADRs were probably preventable and 55.6% were not preventable. These results are contrasted with a study carried out by Verma et al., where most of the ADRs were probably preventable (82.5%), according to Gohel et al., most of ADRs were definitely preventable (72.16%). In a study conducted by Gohel et al., there were four different actions taken against suspected drugs which were drug discontinuation, drug replaced, dose reduction, and medication given for the management of ADRs. In the present study, most of the cases were drug withdrawn, followed by dose reduced or altered.
Most of our cases were recovered followed by continuing reactions. Sriram et al. observed consistent results on the outcome of management of ADRs. According to Castro-Pastrana et al., most of the cases were hospitalized followed by required intervention to prevent permanent damage and less cases of life-threatening. In the present study, most of the patients were hospitalized and required intervention to prevent permanent damage, followed by life-threatening of reactions. In the current study, factors including age, gender had no significant association with ADRs whereas; there was significant difference between numbers of drugs with ADRs. The study conducted by Pudukkan D et al., showed significant association with gender and ADRs.
| Conclusions|| |
The study concluded that, dermatological ADRs were common occurrence and it is essential for detection and prevention. Clinical spectrum of CADRs ranging from mild urticaria to serious TEN was observed. SJS and rashes were the most commonly observed clinical patterns of ADRs. The most common drug class responsible for ADRs was antibiotics, followed by antiepileptic drug and NSAID's. Dermatological ADRs was varied in their causality, severity, and preventability. There is a need for the development of a uniform, prospective, well-defined monitoring program to enhance awareness and promote research into the dangerous phenomenon of ADRs on patients and for drugs and patients in general. Health-care professionals should promote in reporting the ADRs to pharmacovigilance centers.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]