JOURNAL OF EVIDENCE BASED MEDICINE AND HEALTHCARE

Table of Contents

2019 Month : August Volume : 6 Issue : 31 Page : 2113-2116

CLINICO-EPIDEMIOLOGICAL STUDY OF CUTANEOUS ADVERSE DRUG REACTIONS: A HOSPITAL-BASED STUDY

Satyendra Kumar Sharma1, Tanmay Padhi2

1. Resident, Department of Dermatology, VSS Institute of Medical Sciences and Research (VIMSAR), Burla, Sambalpur, Odisha.
2. Associate Professor, Department of Dermatology, VSS Institute of Medical Sciences and Research (VIMSAR), Burla, Sambalpur, Odisha.

 Corresponding Author:
Dr. Tanmay Padhi,
Department of Dermatology,
VSS Institute of Medical Sciences and Research (VIMSAR),
Burla, Sambalpur, Odisha.
E-mail: padhitanmay@gmail.com
DOI: 10.18410/jebmh/2019/430

ABSTRACT
BACKGROUND
Cutaneous drug reactions are the most common adverse reactions attributed to drugs. They often mimic or cause common cutaneous reaction patterns such as bullous disorders, lichen planus, psoriasis, eczema etc.,

METHODS
It was a hospital based cross sectional study including 140 clinically diagnosed cases of Cutaneous Adverse Drug Reaction (CADR). Demographic details, clinical patterns, types of drugs and causality assessment were studied in each one of them.

RESULTS
Most common age group to have CADR was 21-40 years. The male to female ratio was 2.25:1. Fixed Drug Eruption including the bullous variant was the commonest, seen in 45.71% patients and followed by maculopapular rash in 17.14% and Stevens Johnson Syndrome (SJS) in 11.42%. The commonest offending group of drug as a whole was Antimicrobials (54.3%) followed by Non-Steroidal Anti Inflammatory Drugs (NSAID) (37.85%) and Antiepileptics (5.71%).

CONCLUSIONS
CADR commonly presents as Fixed Drug Eruption or maculopapular lesions and commonly implicated drugs are Antimicrobials, NSAIDs and Anti-Epileptics.

KEYWORDS
CADR, Causality Assessment, Drug Reaction, Fixed Drug Eruption

How to cite this article

Sharma SK, Padhi T. Clinico-epidemiological study of cutaneous adverse drug reactions: a hospital-based study. J. Evid. Based Med. Healthc. 2019; 6(31), 2113-2116. DOI: 10.18410/jebmh/2019/430

BACKGROUND

Cutaneous adverse drug reaction (CADR) is any unwanted change in the structure or function of the skin, its appendages or mucous membranes and its all adverse events related to drug eruption, regardless of the aetiology.1 CADR includes pigmentary changes, maculopapular drug eruption, Stevens Johnson syndrome (SJS), Toxic epidermal necrolysis (TEN) & Drug hypersensitivity syndrome (DHS). In spite of being a common problem, not many Indian studies exist on the profile of CADR and there is a paucity of data on CADR from Western Odisha. With this background, we decided to conduct the study with an objective to find out the clinical pattern of drug reactions, to know about nature of the offending drug (self-medication or prescribed), to evaluate mortality and morbidity associated with drugs, to educate the patients, to avoid self-intake of drugs and re-intake of offending drugs.

We wanted to identify the common drugs causing CADR among the study population. We also wanted to find out the clinical spectrum of CADR and determine the epidemiological profile of CADR patients.

 

METHODS

The study was conducted from October 2016 to October 2018 and included 140 clinically diagnosed patients of CADR attending OPD of Dept. of Skin & VD as well as inpatient in different department of VIMSAR, Burla. Due approval was taken from the Institutional Ethics Committee before proceeding for the study.

Patients presenting with visible skin lesions suspected to be drug related and relevant history of drug intake were included in our study whereas lesions due to other disease (e.g., viral exanthems, rash of rickettsial infections, collagen vascular disease) on closer examination were excluded. All cases were studied in detail with respect to history of drug intake, type of drug, route of intake. time gap between intake of drug and appearance of lesions, clinical spectrum of cutaneous lesions. Causality assessment was done, and cases were classified into different groups as per WHO.

 

RESULTS

Table 1 shows demographic detail of patients. Males outnumbered females and maximum number of cases belong to 21 to 40 years. Out of 140 cases, 69 (43.2%) had 

obtained the drugs without prescription. Table 2 shows Reaction time, it is the time taken for the reaction to appear since the last exposure of the suspected drug. This was found to be 1 to 10 days in 123(87.85%) patient. Reaction time of 1 day was common in cases of FDE and urticaria, and ranged from 2 weeks to 3 weeks in case of drug hypersensitivity syndrome, Stevens Johnson syndrome, Toxic epidermal necrolysis. Table 3 shows FDE and its bullous variant (45.71%) was the commonest type of drug reaction followed by maculopapular drug reaction (17.14%). Severe forms of drug reaction like SJS, SJS-TEN overlap, TEN, Dapsone Hypersensitivity Syndrome (DHS) and exfoliative dermatitis (ED) were seen very less number of cases. Table 4 shows that most of the CADRs were attributed to NSAIDS 53(37.85%) followed by Antibiotics 52(37.14%). Table 5 shows Severe adverse cutaneous reaction and causative agents. SJS was the commonest followed by DHS and TEN. Among the antiepileptics, carbamazepine was the most common offending agent responsible for 4(50%) cases followed by phenytoin in 2 (25%) and oxcarbazepine and fosphenytoin in one each. When the causality assessment was considered, majority belonged to possible group (105) followed by probable/likely group in 35. No one belonged to the certain, unlikely, conditional and unclassifiable groups.

 

Characteristic

Number

Percentage

Gender

 

 

Male

97

69.29

Female

43

30.71

Age Distribution (in Years)

 

 

<10

12

8.57

11-20

12

8.57

21-30

42

30

31-40

27

19.29

41-50

18

12.86

51-60

18

12.86

61-70

71-80

7

4

5

2.86

Residence

 

 

Rural

117

86.59

Urban

23

13.40

Socioeconomic Status

 

 

Upper

04

1.03

Upper-middle

03

5.15

Lower-middle

43

14.43

Upper-lower

35

22.68

Lower

55

56.70

Table 1. Demographic Details

 

Duration (in Days)

No. of Cases

Percentage (%)

1-10

123

87.85

11-20

7

5

21-30

6

4.28

31-60

2

1.42

>60

2

1.42

Total

140

100

Table 2. Time in Days or Onset of Reaction

 

Serial No.

Types of Reaction

No. of Cases

Percentage (%)

1.

Fixed drug eruption

59

42.14

2.

Bullous FDE

5

3.57

3.

Maculopapular drug reaction

24

17.14

4.

Stevens Johnson syndrome

16

11.42

5.

SJS-TEN overlap

1

0.71

6.

Toxic epidermal necrolysis

2

1.42

7.

Erythema multiforme

4

2.85

8.

Urticaria

7

5.00

9.

Dapsone hypersensitivity

4

2.85

10.

Mucositis

1

0.71

11.

Bullous drug reaction

6

4.28

12.

Lichenoid dermatitis

7

5.00

13.

Exfoliative dermatitis

1

0.71

14.

Drug induced VASCULITIS

3

2.14

 

Total

140

100

Table 3. Clinical Spectrum of CADR

 

Sl.

No.

Drug

No. of

Patients

Percentage (%) from

Total No. of Cases (n=140)

1.

Antibiotics

52

37.14

2.

Antiepileptics

8

5.71

3.

Antifungal

1

0.71

4.

Antiviral

2

1.42

5.

Antimalarial

1

0.71

6.

Antiprotozoal

5

3.57

7.

Antitussive

2

1.42

8.

ART (nevirapine)

3

2.14

9.

ATT

12

8.57

10.

Ayurvedic

1

0.71

11.

NSAIDS

53

37.85

 

Total

140

100

Table 4. Drug Sub-Types Responsible for CADR

ART (Antiretroviral Therapy), ATT (Antitubercular Therapy), NSAIDS (Non-steroidal Anti-inflammatory Drugs).

 

Sl.

No.

Drug

SJS

SJS-TEN

Overlap

TEN

DHS

1.

Aceclofenac

2

 

1

 

2.

Acyclovir

1

     

3.

ATT

1

     

4.

Carbamazepine

3

     

5.

Cefpodoxime

1

     

6.

Diclofenac

   

1

 

7.

Nevirapine

2

     

8.

Nitrofurantoin

 

1

   

9.

Ofloxacin +Ornidazole

1

 

 

 

10.

Paracetamol

2

     

11.

Phenytoin

2

     

12.

Sulfadoxine

1

     

13.

dapsone

     

4

 

Total no. of Cases

16

1

2

4

Table 5. Drugs Responsible for Severe Forms of CADR

 

Causality Assessment

No. of Patients

Certain

0

Probable/likely

35

Possible

105

Unlikely

0

Conditional/unclassified

0

Unassessable/unclassifiable

0

Table 6. WHO-UMC Causality Assessment

 

DISCUSSION

Of the various cutaneous ADRs, Fixed Drug Eruption including the bullous variant was the commonest, seen in 64 (45.71%) patients, similar to the findings of study by Chatterjee et al,2 Patel et al,3 Qayoom et al,4 but in contrast to Chattopadhyay et al,5 Jha et al,6 Saha et al,7 Hiware et al8 and Jhaj et al.9 Maculopapular Rash followed this in 24(17.14%), followed by SJS in 16 (11.42%). Fifteen cases of FDE and three cases of its bullous variant were caused by Fixed dose combination of ofloxacin and ornidazole.bMale preponderance was seen with a M: F ratio of 2.25: 1.This was similar to the findings by Sharma et al10 and Patel et al.3 However studies by Chattopadhyay et al,5 Nandha et al,11 Sehgal et al12 and Pudukadan et al.13 showed an equal or a female preponderance. Higher male proportion in our study could be because of medical seeking behavior of males.

The age group of patients ranged from 2 years to 80 years, with maximum cases (30%) occurring within the 21-30 years age group. This was similar to the findings of Sharma et al,10 Jha et al,6 Nayak et al1 and Noel et al.14 Pediatric and geriatric age group showed a decreased incidence which was in concurrence with Sehgal S et al.12 Adverse reactions to drugs increase with age.13 This may be due to the increased use of medications by the elderly, increased potential for drug-drug interactions, and altered drug handling by the body. CADR was seen with oral routes of administration in majority of cases (n=133) and only 7 cases developed CADR through parenteral route which was similar to the findings of Qayoom et al4 and Ratnam et al15 and in contrast to Saha et al.7

Reaction time ranged from 1 day to 80 days with shortest time for FDE (4-5 hours) and longest for lichenoid dermatitis (80 days).In our study it was commonly seen to be within 1-10 days in 87.85% cases. Saha et al,7 Sharma et al10 and Pudukadan et al.13 also had similar findings. Serious cutaneous adverse reaction (SCARs) was seen in 23 (16.42%) cases. It included SJS in 16 cases, DHS in 4 cases, TEN in 2 cases and SJS-TEN overlap in 1 case. This was lower than the findings by Saha et al,7 and much higher than Jha et al6 and Hiware et al.8 The frequency seen in various studies ranged from 7-25% Pudukadan et al.13 Noel et al.14 Patel et al.3 Sehgal et al.12 and Jhaj et al.9 The common offending group of drugs for SJS in our study were aceclofenac, nevirapine, paracetamol, carbamazepine (two cases each),which is in contrast to the findings of Noel et al and Patel et al.

Erythema mutiforme was seen in 4 (2.85%) caused by NSAIDs and antibiotics in 2 cases each. Urticaria was seen with 7 cases (5%), caused by NSAIDs and antibiotics in 4 and 3 cases respectively. The commonest offending group of drugs as a whole was Antimicrobials (54.3%) followed by NSAIDs (37.85%) and Antiepileptics (5.71%). Antimicrobials were the leading offending group causing CADR in earlier studies conducted by Patel et al,3 Jha et al,6 Hiware et al,8 Jhaj et al,9 Chattopadhyay et al,5 Chatterjee et al2 and Qayoom et al.4 Antimicrobials comprised of antibiotics (68.42%) followed by ATT (15.79%), ART nevirapine (3.94%), Antiprotozoals like nitroimidazoles including metronidazole(3.94%) & ornidazole (2.63%),antiviral acyclovir (2.63%) and antifungals (1.31%) . However, When individual drugs were considered, the most common drug responsible was paracetamol (17.85%) followed by Fixed dose combination of a fluoroquinolones with nitroimidazole (ofloxacin + ornidazole) (14.28%) and Aceclofenac in 10% of cases. This could be attributed to the easy availability of these drugs as over the counter (OTC) products. Antiepileptics were responsible for 5.71% of the reaction, most common agents amongst them being Carbamazepine followed by phenytoin which was similar to the findings of Patel et al.3 Only 4 (2.85%) of patients were HIV patients. This is actually much lower than what was reported in other studies,16,17 which emphasised the fact that HIV is a risk factor to develop ADR. Low incidence in our study may be due to underreporting.

Most of the patients in our study belonged to lower socioeconomic status (39.3%), which was similar to the findings of study done by Jayanthi et al.18 Most of the patients attending the outpatient/inpatient department of our hospital belonged to low socioeconomic status, that’s why in our study low socioeconomic group patients were more in number as compared to other socioeconomic groups. The causality profile of CADR of our study population was categorized as per WHO-UMC case causality assessment criteria. Among 140 subjects of CADRs the majority belonged to “possible” group (105) followed by “probable or likely” group (35).No one belonged to “certain”, “unlikely”, “conditional” and “unclassifiable” groups. All these findings were similar to those of Saha et al.7

 

CONCLUSIONS

CADR presents in a wide spectrum of dermatological manifestations including fixed drug eruptions, maculopapular eruptions and Stevens Johnson syndrome. Antimicrobials, NSAIDs and anti-epileptics are the commonly implicated agents and in most of the cases, they appear within 10 days of intake of the drug. Self-medication and availability of drugs without prescription significantly influence the incidence of CADRs.

 

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