|Year : 2023 | Volume
| Issue : 1 | Page : 28-33
Clinical patterns of cutaneous adverse drug reactions in tertiary care centre of central India: A cross-sectional study
Rakesh P Roge1, Jayesh Ishwardas Mukhi2, Sudhir M Mamidwar2, Pallavi Rupkumar Rokade2, Bhagyashree Babanrao Supekar2
1 Civil Hospital Bhandara, Bhandara, India
2 Department of Dermatology, Venereology and Leprology, Government Medical College & Hospital, Nagpur, Maharashtra, India
|Date of Submission||18-May-2023|
|Date of Decision||19-Jul-2023|
|Date of Acceptance||20-Jul-2023|
|Date of Web Publication||24-Aug-2023|
Jayesh Ishwardas Mukhi
Department of Dermatology, Venereology and Leprology, TB Campus, Government Medical College & Hospital, Nagpur 440003, Maharashtra
Source of Support: None, Conflict of Interest: None
Introduction: Cutaneous adverse drug reactions (CADRs) are the most common adverse reactions attributed to drugs in which any type of skin reaction can be mimicked, induced, or aggravated. Aim and Objectives: To study the morphological patterns of various types of CADRs. Materials and Methods: It was a descriptive cross-sectional study carried out from November 2017 to September 2019, where medical records of diagnosed cases of CADRs were analyzed in a predesigned proforma with respect to demographic data, clinical features, treatment history (topical and oral), offending drug, temporal association with a skin eruption, investigations, and treatment outcome. Statistical analysis was done using mean, median, and proportion. Results: A total of 180 patients with CADRs were enrolled. There was a male preponderance with the mean age being 32.9 ± 2.9 years. The most common CADR reported was fixed drug eruption (n = 77). Steven Johnson syndrome was the most common (n = 7) severe cutaneous adverse reaction. The mean duration of latency was 6.2 (±8.61 days). Antimicrobial drugs accounted for most of the benign as well as severe CADRs (41.4%). Among all cases, 43.9% of patients had mild CADR and 16.7% had severe CADR. Causality assessment using the Naranjo adverse drug reaction probability scale, 70% had a possible association, 18.3% probable and 11.7% had a doubtful association. Conclusion: Early identification of CADR is important to reduce morbidity and mortality. Patient education is required to avoid self-administration of drugs and re-administration of the same offending drugs to prevent further morbidity. Immediate withdrawal of the culprit drug/drugs with adequate management can be lifesaving.
Keywords: Acneiform eruption, Central India, cutaneous adverse drug reaction, fixed drug eruption
|How to cite this article:|
Roge RP, Mukhi JI, Mamidwar SM, Rokade PR, Supekar BB. Clinical patterns of cutaneous adverse drug reactions in tertiary care centre of central India: A cross-sectional study. Indian J Drugs Dermatol 2023;9:28-33
|How to cite this URL:|
Roge RP, Mukhi JI, Mamidwar SM, Rokade PR, Supekar BB. Clinical patterns of cutaneous adverse drug reactions in tertiary care centre of central India: A cross-sectional study. Indian J Drugs Dermatol [serial online] 2023 [cited 2023 Sep 23];9:28-33. Available from: https://www.ijdd.in/text.asp?2023/9/1/28/384288
| Introduction|| |
Adverse drug reactions (ADRs) are an important cause of morbidity, hospitalization, increased health expenditure, and even death. The overall incidence of CADRs in developed countries is 1%–3%, while the incidence in developing countries is thought to be higher between 2% and 5%. The incidence of cutaneous reaction increases with the number of drugs taken. Clinical patterns of cutaneous adverse drug reactions (CADR) ranges from maculopapular rash to potentially fatal toxic epidermal necrolysis. CADRs are not defined only to skin and mucosa but can also involve multiple organ systems. Many a time, CADRs are trivial and benign but it is essential to diagnose the condition and find out the culprit drug to avoid a life-threatening reaction in the future. Hence, all physicians should have a detailed knowledge of such CADRs, the common offending drugs, and prognostic indicators to handle such reactions appropriately.
| Materials and Methods|| |
It was a cross-sectional descriptive study conducted over two years from November 2017 to October 2019. After obtaining institutional ethical clearance, all patients of cutaneous ADR irrespective of age and sex and those attending dermatology department were enrolled in the study. Whereas, those who were not willing to participate, those who could not recall the name of the suspected medicines consumed, and those whose lesions turned out to be disease-related (e.g., viral exanthems, rash of rickettsial infections, and collagen vascular disease) on closer examination were excluded. Case records of patients were evaluated with respect to age, gender, family history, past history, duration of illness, treatment history (topical and oral), offending drug, site of onset, progression of lesion, clinical patterns, distribution of rash, temporal association with skin eruption and associated systemic involvement and biopsy was performed in doubtful cases. Diagnosis of CADR was based on a detailed general, physical, and cutaneous examination regarding morphology, pattern, distribution of eruption and a mucosal examination was performed. All CADRs were reported to the pharmaco-vigilance program of India. Causality was assessed using the Naranjo probability scale. Statistical analysis was done using mean, median, and proportion.
| Results|| |
In our study, 180 patients with CADRs were enrolled. There was male preponderance (M:F = 1.3:1) [Chart 1]. The most common age group affected was 31–40 years (n = 50, 27.8%) with the mean age of all patients being 32.9 ± 2.9 years (range 2–67 years). The most associated complaint was a burning sensation (n = 54, 30%), followed by an asymptomatic (n = 45, 25%). Out of all CADR, 43.9% were mild CADR, whereas 16.7% were severe CADR. The most common CADR reported was fixed drug eruption (FDE) (n = 77) [Figure 1] followed by acneiform eruption (n = 29). While the least common were exfoliative dermatitis (n = 1) and AGEP (n = 1) [[Figure 2]A–D]. Very rare CADRs observed were Itraconazole-induced maculopapular rash (n = 1), chloroquine-induced lichenoid eruption (n = 1) and gefitinib-induced papulopustules and/or paronychia, regulatory abnormalities of hair growth, itching dryness due to EGFR inhibitors complex (n = 2) [Figure 3]. Amongst all SCARs, Steven Johnson syndrome (SJS) [[Figure 4]A–D] was the most common (n = 7). The duration of latency for CADR ranged between 12 h to 59 days with a mean duration being 6.2 (±8.61, 1–14 days). In our study, the mean lag period for urticaria to appear was the lowest (0.5 days) and hyperpigmentation had a maximum lag period (n = 59) [Table 1]. Only 18.3% of patients had a previous similar history of CADR. Exclusive cutaneous and mucosal involvement was observed in 64.4% and 5% of cases, whereas concomitant mucosal involvement was reported in 28.9% of cases. Antimicrobial drugs accounted for most of the benign CADRs (41.4%) of which amoxicillin (n = 13) and cotrimoxazole (n = 12) were responsible for most of the CADRs. Second most common offending drug for CADR belonged to non steroidal anti-inflammatory drug (NSAIDs) (23.1%) group, followed by anti-epileptics (4.9%), while the offending drug was unknown in 13.3% of cases, as depicted in [Table 2]. Among all SCARs, dapsone (n = 8) was the most common culprit drug, followed by cefixime (n = 4). Amoxicillin was most commonly responsible for FDE (%) (n = 8) and maculopapular drug rash (n = 3), while co-trimoxazole was the most common drug responsible for urticaria cases (n = 5). Systemic steroids (n = 8), and Anti Kochs therapy drugs (n = 8) were the most common drugs, causing acneiform eruption. Amongst all cases, 43.9% of patients had mild CADR and 16.7% had severe CADR. 80.5% of patients had taken drugs prescribed by a physician and 19.4% of patients had taken over-the-counter (OTC) drugs. Skin (64.4%) was the predominant site of involvement, followed by skin with mucosa (28.8%) and mucosa only (5.0%). Abnormalities in biochemical parameters were seen predominantly in patients with severe cutaneous adverse reaction as eosinophilia (4.4%), deranged liver function test (2.8%), renal with liver involvement (2.2%), liver involvement with eosinophilia (1.7%), and only renal involvement (1.1%). Causality assessment using the Naranjo ADR probability scale, 70% had a possible association, 18.3% probable and 11.7% had a doubtful association. Steven Johnson syndrome (28%) was the most common severe cutaneous adverse drug reaction and antimicrobials were the most common cause of severe cutaneous adverse drug reactions, as depicted in in [Table 2]. 1.6% of patients worsened and died and 98.3% of the patient improved and cured.
|Figure 1: Bullous fixed drug eruption over the forearm in a 30-year-old male after consumption of Ofloxacin|
Click here to view
|Figure 2: (A and B): Exfoliative dermatitis in a 62-year-old male after consumption of dapsone. (C and D) AGEP in a 23-year-old male after consuming cefixime|
Click here to view
|Figure 3: Papulopustules and/or paronychia, regulatory abnormalities of hair growth, itching dryness due to EGFR inhibitors complex in a 52-year-old male after consumption of gefitinib|
Click here to view
|Figure 4: (A–D) Toxic epidermal necrolysis in a 42-year-old female after consumption of phenytoin. (A and B) Steven Johnson syndrome in a 36-year-old male after consuming ofloxacin (C and D)|
Click here to view
| Discussion|| |
Approximately 3% of all disabling injuries during hospitalization are drug reactions and complications of drug therapy are the most common type of adverse event in hospitalized patients. In our study, 104 were males and 76 were females with a ratio of 1.3:1. This was in concordance with studies conducted by Anjaneyan et al. and Patel et al. whereas Pudukadan and Thappa and Abanti et al. showed female preponderance. The mean age of our cases was 32.9 (± 2.9; 2–67 years). This result was found to be similar to the results of the studies conducted by Pudukadan and Thappa and Abanti et al. The most common presenting symptom was a burning sensation with rash in 54 (30%) patients followed by an asymptomatic rash in 45 (25%) patients. Similar results were reported in the study conducted by Pudukadan and Thappa where symptomatic rash (56.7%) and in Anjaneyan et al. where itching (37%) was the most common presentation, followed by a rash (18%) and swelling (15%). The mean duration of latency in our study was 6.25 days (±3.6; 0.16–90 days). Most of the cases (n = 97) had developed a rash after 48 hours after taking the incriminated drug. This result was found to be similar to the study, conducted by Abanti et al. SCARs accounted for 13.8% of total CADRs in our study, which was similar to findings by Sharma and Sethuraman. In our study among the SCARs, SJS (7/180) was the most common followed by dapsone hypersensitivity syndrome (6/180). SJS (5/150) was reported to be the most common by Sharma et al. which is similar to our study. In our study, out of 180 patients, a history of similar cutaneous reactions was present in 18.3% of patients. In the study done by Patel et al. history of CADRs was present in 18.92% of patients which is similar to our study. Antimicrobial group of drugs were most commonly reported with an incidence of CADR followed by NSAIDs. Pudukadan et al. and Abanti et al. have also reported that antimicrobials were the common culprit drugs followed by anti-epileptics and NSAIDs., Amoxicillin was the most common antimicrobial causing CADRs in our study, responsible for about 7.2% of cases. Patel et al. recorded cephalosporin (3.75%) as the most common antimicrobial drug responsible. In our study, 80.5% of patients had taken drugs prescribed by a physician and 19.4% of patients had taken OTC drugs. This is in concordance with the study by Abanti et al. where physician-prescribed drugs constituted 88.7% and OTC drugs 11.3%. Cutaneous drug reactions due to OTC drug constitutes a significant proportion and steps should be taken to prevent patients from going for OTC medications by proper counseling of patients and strict rules to be laid down for pharmacies regarding drug distribution. The most common site of involvement was the skin (64.4%) followed by skin with mucous membranes (28.8%), mucous membranes (5.0%) and only palm and sole (1.6%). In a study conducted by Sehgal et al., palmoplantar involvement was seen in 2.5% of cases and oral and ocular involvement in 13.7% of cases. We reported that 98.3% of the patients were improved and cured. A study conducted by Nandha et al. showed 71.42% of patients were cured, 27.47% improved and 1.11% died which is similar to our study. According to the causality assessment using Naranjo adverse drug reaction probability scale, 126 (70%) had a possible association, 33 (18.3%) had a probable association and 21 (11.7%) had a doubtful association. Sharma and Sethuraman recorded that 116 (77.3%) had a probable association, 19 (12.6%) had a highly probable, and 15 (1%) had a possible association with the drug which is not concordant with our study due to subjective error. According to the University of Virginia Health System Adverse Drug Reaction Reporting Program, in our study, the most common grade of severity was mild in 43.8% followed by moderate in 39.4% and severe in 16.6% of patients. This result was almost similar to the study conducted by Pudukadan and Thappa.
| Conclusion|| |
We report FDE being the most common CADR and anti-microbial group of drugs (amoxicillin) as a common culprit drug in the causation of cutaneous adverse reaction in our dermatology setting. Early identification of CADR is important to reduce morbidity and mortality. Patient education is required to avoid self-administration of drugs and re-administration of the same offending drugs to prevent further morbidity. To the best of our knowledge, this is the first study from central India exploring the clinical patterns of CADRs.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Dimri D, Raina RS, Thapliyal S, Thawani V Retrospective analysis of pattern of cutaneous adverse drug reactions in tertiary hospital of Pauri Garhwal. J Clin Diagn Res 2016;10:FC01-6.
Nayak S, Acharjya B Adverse cutaneous drug reaction. Indian J Dermatol 2008;53:2-8.
Anjaneyan G, Gupta R, Vora RV Clinical study of adverse cutaneous drug reactions at a rural based tertiary care centre in Gujarat. Natl J Physiol Pharm Pharmacol 2013;3:129-36.
Patel RM, Marfatia YS Clinical study of cutaneous drug eruptions in 200 patients. Indian J Dermatol Venereol Leprol 2008;74:430.
Pudukadan D, Thappa DM Adverse cutaneous drug reactions: Clinical pattern and causative agents in a tertiary care center in South India. Indian J Dermatol Venereal Leprol 2004;70:20-4.
Abanti S, Das NK, Hazra A, Gharami RC, Chowdhury SN, Datta PK Cutaneous adverse drug reaction profile in a tertiary care out patient setting in Eastern India. Indian J Pharmacol 2012;44:792-7.
Sharma VK, Sethuraman G Adverse cutaneous reactions to drugs: An overview. J Postgrad Med 1996;42:15-22.
Patel TK, Thakkar SH, Sharma D Cutaneous adverse drug reactions in Indian population: A systematic review. Indian Dermatol Online J 2014;5:S76-86.
Sehgal S, Balachandran C, Shenoi SD Clinical study of cutaneous drug reactions in 80 patients. Indian J Dermatol Venereol Leprol 2003;69:6-7.
Nandha R, Gupta A, Hashmi A Cutaneous adverse drug reactions in a tertiary care teaching hospital: A North Indian perspective. Int J Appl Basic Med Res 2011;1:50-3.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2]