Cutaneous Adverse Drug Reactions in a Tertiary Care Teaching

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hospital based prospective observational study carried out in dermatology department over a 5 months period. .... Leffell DJ, editors. Fitzpatrick's dermatology in general medicine. 7th ed. ... [9] Anjaneyan G., Gupta R., Vora R., (2013) Clinical.
Cutaneous Adverse Drug Reactions in a Tertiary Care Teaching Hospital - A Prospective Study Amala Lukose1, *Mamatha K.1, Shyam Prasad A.L.2, Sandra Magdalene1 1Faculty 2Professor,

of Pharmacy, M. S. Ramaiah University of Applied Science, Bengaluru 560054 Department of Dermatology M. S. Ramaiah Medical College and Hospital, Bengaluru 560054 *Contact Author e-mail: [email protected]

Abstract Adverse Drug Reactions (ADRs) are important cause of hospitalization, increased health expenditure and mortality. Cutaneous ADRs (CADRs) are the most frequent ADRs and affect 2-3% of hospitalized patients. The well known risk factors for CADR includes age, sex, previous history of ADRs and environmental factors. The severity of CADRs may vary from mild pruritus to a life threatening Stevens - Johnson Syndrome (SJS). The present study was a hospital based prospective observational study carried out in dermatology department over a 5 months period. The study aims to report and analyze the causality, severity and type of suspected CADRs. During the study period, 250 prescriptions were analyzed and a total of 16 CADRs were identified. Patients in the age group of less than 25 years were found to experience more number of CADRs (50%). Drug classes mostly associated with CADRs were antibiotics (37.5%) followed by corticosteroids (12.5%) and NSAIDs (12.5%).Majority (68.75%) of ADRs were probable and 31.25% of ADRs were possible as per causality assessment by Naranjo`s scale and WHO scale. Severity assessment showed that 93.75% of ADRs were moderate and 6.25% were mild reactions. There were no fatalities reported due to ADR. Suspected ADRs were managed by symptomatic treatment. ADR reporting is an effective tool in increasing the general vigilance among health care professionals and may influence the recommendations for drug use through regulatory authorities. Clinical pharmacists play a vital role in early detection, management, assessment and prevention of ADRs and reporting. Key Words: Cutaneous Adverse Drug reaction, Causality, Severity

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monitoring, and dose reduction or withdrawal plays an important role in management and prevention of severe adverse drug reactions [6]. This study was undertaken to identify, assess causality and severity and report suspected CADRs in patients attending the dermatology department in a tertiary care teaching hospital, Bengaluru.

INTRODUCTION

ADRs account for significant morbidity and mortality in the health care sector and are considered as the fifth leading cause of death among all diseases [1, 2]. Approximately 5-8% of hospitalization worldwide is due to ADRs [1]. Cutaneous adverse drug reactions (CADRs) are defined as noxious, unintended, morphologic skin changes, with or without systemic involvement, that develop after local or systemic administration of drugs in dosages commonly used for prevention, diagnosis, or treatment of diseases or modification of physiologic functions. There is a wide spectrum of CADRs, varying from transient maculopapular rashes to potentially fatal SJS and toxic epidermal necrolysis [3, 4]. CADRs are the commonest ADRs (30-45%) responsible for about 2% of hospital admissions and about 2-7% of these may be severe [1, 2]. In India, CADRs account for 2.5% of all inpatient admissions and 2.6% of outpatient consultation [1].

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This hospital based prospective observational study was conducted in dermatology department of M. S. Ramaiah hospital (MSRH), Bengaluru for a period of 5 months. The study was done in concordance with the Institutional Ethical Committee of the hospital. Inpatients and outpatients of department of dermatology and inpatients referred from the other department for dermatology consultation were included in the study. ICU cases were excluded. Written informed consent was taken from all the subjects enrolled for the study. The data was collected from patient’s case sheets, patient treatment charts, patient admission record, medical notes and nursing notes and documented in a predesigned data collection form and ADR documentation form. The data obtained included patient demographics, type of skin disorder, findings on systemic and cutaneous examination, drugs prescribed, and concomitant disease condition, description of reaction, date and time of onset of reaction, suspected drugs and management of ADRs. The patients were also interviewed regarding their medication history, timings of drug administration, time of onset of reaction and other such details to establish timetemporal relationship between the drug and the

The Central Drugs Standard Control Organization (CDSCO) under the aegis of Govt. of India, Ministry of Health and Family welfare established adverse drug reaction monitoring centers in various tertiary care hospitals all over India under Pharmacovigilance Programme 2010. These hospital-based ADR monitoring programmes aim to identify and quantify the risks associated with the use of drugs in patients. ADR reporting leads to an increased general vigilance and may influence the recommendations for drug use through regulatory authorities [5]. Early recognition of various morphological patterns, recognition of offending drug, subsequent

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MATERIAL AND METHODS

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reaction. The clinician’s opinion was taken to identify the offending drug and also during the assessment of causality of the reaction. A thorough literature survey was done to obtain incidence of similar ADR for the suspected drugs. The causality assessment were done by using WHO probability scale and Naranjo’s scale while Wills and Brown classification was used to classify ADRs into different types. Severity of ADRs was assessed by using Hartwig scale [7].

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Table 1. Suspected drugs and its adverse reactions Suspected drug

Adverse Reactions

Trimethoprim and Contact dermatitis sulfamethoxazole Methoxsalen

Erythema

Nimesulide and

RESULTS AND DISCUSSION

Maculopapular rash A total of 250 cases were analyzed during the study period and 16 CADRs were identified. Females are considered to be more predisposed to experience ADRs compared to males but, in our study male preponderance (68.75%) was seen (Fig.1). A similar kind of male dominance was also seen in the study conducted by Raut A et al [8].

Age and gender distribution 35.00%

31.30%

31.30% Male Female

30.00% 25.00% 20.00%

Paracetamol Cetrimide and Irritant contact dermatitis Chlorhexidine Ciprofloxacin

Fixed drug eruption

Cefixime

Maculopapular rash

Levofloxacin

Maculopapular rash

Prednisolone

Striae

Betamethasone

Folliculitis

Ibuprofen and

18.80%

Maculopapular rash Paracetamol

15.00% 10.00%

6.20%

Clopidogrel and

6.20%

Ecchymotic patches

5.00%

Aspirin

0.00% 0-25

26-50 Age group

>50

Cefotaxime

Erythema

Fusidic acid and Contact dermatitis Fig. 1 Age and gender distribution of patients with ADR In our study, ADRs were experienced more commonly in the age group of less than 25 years in both the genders. A study conducted by Anjaneyan G et al9 also had similar kind of results wherein the patients commonly affected with ADRs belonged to age group between 21 to 30 years. Maculopapular rash and contact dermatitis were the two most common adverse reactions in our study population. A study conducted by Chatterjee et al showed that urticaria and fixed drug rashes were the most common morphological reactions [10]. Factors like time of drug exposure, time of reaction, discontinuation/drug withdrawal, and patient’s history of similar reaction to suspected drug and other predisposing factors are to be analyzed to obtain causal relationship between ADRs and suspected drug [11].

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Betamethasone Minoxidil

Contact dermatitis

Isopropyl alcohol, Methanol, Buterol

Erythema

and Toluene

The causality assessment by Naranjo’s scale showed that 68.75% of reactions were probable and 31.25% were possible. Assessment using WHO probability scale showed that 11 ADRs were probable and 5 were possible ADRS which is consistent with the results of the study conducted by Verma R et al [1].

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Table 2: Classes of suspected drugs

Naranjo's Causality 68.75%

70%

Drug classes

Frequency

Percentage

Antibiotic

6

37.5

Corticosteroids

2

12.5

NSAIDs

2

12.5

Demelanizing agent

1

6.25

30%

Vasodilator

1

6.25

20%

Antibiotic and

1

6.25

Anticoagulant

1

6.25

Anti-infective

1

6.25

Antiseptic

1

6.25

60% 50% 40%

31.25%

steroid

0%

10% 0%

Definite

Probable

Possible

4.

Fig. 2 Causality assessment of ADR by Naranjo’s scale In the present study, severity assessment by Hartwig scale showed 93.75% as moderate ADRs and 6.25% as mild ADRs, which is in contrast to the study conducted by J Ratan et al [6], where in 78.8% of the ADRs were mild and 21.2% were moderate. Assessment using Wills and Brown classification in our study revealed predominance of type H (82.4%) reactions over type A (17.6%) reactions (Fig. 3). Drug classes most commonly associated with ADRs were antibiotics (29.4%) followed by corticosteroids (23.5%) and NSAIDs (11.8%). These results were similar to a study conducted by Raut A et al [8]. In our study there were no fatalities reported due to ADRs. Suspected ADRs were managed by symptomatic treatment using antihistamines, corticosteroids, moisturizer, emollient and skin protective. In all patients who experienced ADRs, drug withdrawal was done as a part of management.

CONCLUSION Cutaneous ADRs differ in their severity, appearance, onset, potential sequelae and underlying immunopathologic mechanisms. Classes of drugs such as antibiotics and steroids are most often implicated. Thorough history taking about the drug and associated reactions, detailed examination of skin and various systems could play a major role in early diagnosis of the CADR. Depending on the nature of drug eruption, symptomatic treatment can be given by using antihistamines, corticosteroids, moisturizers and emollients. Awareness regarding ADRs and its consequences among patients and health care professionals is important in prevention of potential ADRs. Clinical pharmacist plays a vital role in early detection, management, assessment and prevention of ADRs and reporting.

REFERENCE [1] Verma R., Tiwari S., Gupta C.M., Verma N., (2014) Cutaneous Adverse Drug Reactions - A Study of Clinical Patterns, Causality, Severity & Preventability, IOSR Journal of Dental and Medical Sciences.,13(7). pp,102-109.

Hartwig scale 6%

[2] Verma C.R., Vasudevan L.C., Pragasam V., (2013) Severe Cutaneous Adverse Drug Reactions, Medical Journal Armed Forces India.,69, pp.375-383.

Mild 94%

Moderate

[3] Shear N.H., Knowles S.R., Shapiro L. (2008) Cutaneous reactions to drugs. In: Wolff K., Goldsmith L.A., Katz SI, Gilchrest BA, Paller AS, Leffell DJ, editors. Fitzpatrick's dermatology in general medicine. 7th ed. New York: McGraw-Hill; pp. 355–362.

Fig. 3 Severity assessment of ADRs by Hartwig scale

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[4] James W.D, Berger T.G., Elston D.M., (2006) Contact Dermatitis and Drug Eruptions. Andrews' disease of the skin. 10th ed. Philadelphia: WB Saunders; pp. 115–138.

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[5] Dhasmana D.C., Seth V, Mishra K.C., (2002) Voluntary Adverse Drug Reaction Reporting in a Tertiary Care Teaching Hospital. Indian Journal of Pharmacology. 34, pp.204-205. [6] Ratan J, Lihite , Lahkar M.A., (2013) Study on Cutaneous Adverse Drug Reactions in ADR Monitoring Centre of Tertiary Care Hospital, Guwahati, Journal of Applied Pharmaceutical Science., 3(03), pp.078-081. [7] Srinivasan R., Ramya G., (2011) Adverse Drug Reaction-causality Assessment, International Journal of Research in Pharmacy and Chemistry, 1(3), pp.602-612. [8] Raut A., Pawar A., Pankaj M., Srivastava P., Mishra A., (2013) Clinical Pattern and Severity of Cutaneous Adverse Drug Reactions, Int J Pharm Pharm Sci., 5(2), pp.612-616. [9] Anjaneyan G., Gupta R., Vora R., (2013) Clinical Study of Adverse Cutaneous Drug Reactions at a Rural Based Tertiary Care in Gujarat. Natl J. Physiol Pharm Pharmacol. 3(2), pp.129-136. [10] Chatterjee S., Ghosh A.P., Barbhuiya J., Dey S.K., (2006) Adverse Cutaneous Drug Reactions: A One Year Survey at a Dermatology Outpatient Clinic of a Tertiary Care Hospital. Indian J Pharmacol., 38, pp.429–431. [11] Gosh S., Leelavathi D., Acharya I., Padma GM., (2006) Study and Evaluation of Various Cutaneous Adverse Drug Reactions in Kasturba hospital, Manipal, Indian J. Pharm. Sci., 68(2), pp.212-215.

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