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E-IJD® - ORIGINAL ARTICLE |
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| Year : 2021 | Volume
: 66
| Issue : 4 | Page : 445 |
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| A Study of Cutaneous Adverse Drug Reactions and their Association with Autoimmune Diseases at a Tertiary Centre in South-West Rajasthan, India |
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Shweta Rana1, Kalpana Gupta1, Nidheesh Agarwal1, Ahamed Noor Mqnsoon Ahamed2
1 Department of Dermatology, Geetanjali Medical College and Hospital, Udaipur, India
2 Department of Pharmacy, Geetanjali Medical College and Hospital, Udaipur, India
| Date of Web Publication | 17-Sep-2021 |
Correspondence Address:
Kalpana Gupta
Department of Dermatology, Geetanjali Medical College and Hospital, Udaipur
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ijd.IJD_261_17
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 Abstract | | |
Background: Cutaneous adverse drug reactions (CADRs) comprise about 30% of all adverse drug reactions and observed in 2–3% of hospitalized patients by wide variety of offending agents. Aims: To study the clinical patterns, causative drugs and their association with autoimmune diseases in CADR patients. Materials and Methods: A total of 174 CADR patients who presented to the dermatology OPD over a period of 18 months (1 July 2015 to 31 Dec 2016) were considered for the study. Detailed history, clinical examination, hematological, and biochemical investigations were recorded. The venereal disease research laboratory test, HIV (ELISA), and histopathological examination were done wherever indicated. Results: The mean age of the patients with cutaneous drug eruptions was 40.2 years. Most of them (31.0%) were in the age group of 41–50 years. There were 93 (53.4%) males and 81 (46.5%) females with the M:F ratio of 1.5:1. The most common eruption observed was maculopapular rash in 33.3% followed by fixed drug eruption (17.2%) and lichenoid dermatitis' (11.5%). The drugs most commonly responsible for CADRs were antimicrobials (n = 68, 39%) with fixed dose combination of fluoroquinolones with nitroimidazoles (n = 42). We also noticed that a total of 42 patients out of 174 had comorbities in the form of diabetes (n = 27, 15.5%), hypothyroidism (n = 9, 5.1%), rheumatoid arthritis (n = 3, 1.7%), vitiligo (n = 2, 1.1%), and SLE (n = 1, 0.5%). Conclusion: Cutaneous ADR patterns and the drugs causing various reactions are changing every year, which may be because of the introduction of newer molecules and changing trends in the use of drugs. In our study, a significant relation of CADRs with autoimmune diseases (P value = 0.004) was also observed.
Keywords: Adverse drug reaction, diabetes, hypothyoidism
How to cite this article:
Rana S, Gupta K, Agarwal N, Mqnsoon Ahamed AN. A Study of Cutaneous Adverse Drug Reactions and their Association with Autoimmune Diseases at a Tertiary Centre in South-West Rajasthan, India. Indian J Dermatol 2021;66:445 |
How to cite this URL:
Rana S, Gupta K, Agarwal N, Mqnsoon Ahamed AN. A Study of Cutaneous Adverse Drug Reactions and their Association with Autoimmune Diseases at a Tertiary Centre in South-West Rajasthan, India. Indian J Dermatol [serial online] 2021 [cited 2023 Mar 28];66:445. Available from: https://www.e-ijd.org/text.asp?2021/66/4/445/326115 |
| Introduction | |  |
Adverse drug reaction is an appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product, which predicts hazard from future administration and warrants prevention or specific treatment, or alteration of the dosage regimen, or withdrawal of the product.[1],[2],[3] Unfortunately, Indian clinico-epidemiological studies of CADRs are limited as majority of them are mild and self-limiting on drug withdrawal, and therefore underreported.[4]
Cutaneous adverse drug reactions (CADRs) comprises about 30% of all adverse drug reactions and observed in 2–3% of hospitalized patients.[5] Fortunately, only about 2% of adverse cutaneous reactions are fatal.[6]
There is a wide spectrum of cutaneous adverse drug reactions varying from transient maculopapular rash to fatal toxic epidermal necrolysis (TEN). Indiscriminate use of drugs and increase in elderly population (which usually requires management by polypharmacy) are among the many factors which have led to an increase in the menace of CADRs. This study was therefore planned to evaluate the patterns of CADRs and their relation with autoimmune diseases if any at a tertiary center in south-west Rajasthan.
This prospective observational study was designed to evaluate: Demographic profile of patients developing cutaneous adverse drug reactions. Clinical pattern of cutaneous adverse drug reactions and the causative drugs. Association of CADRs with autoimmune diseases.
| Materials and Methods | | |
The study was conducted in the Dermatology department of a tertiary care center in southwest Rajasthan after the approval of institutional ethical committee. All patients of suspected cutaneous adverse drug reactions who presented to the dermatology OPD over a period of 18 months (1 July 2015 to 31 Dec 2016) were considered for the study. A detailed history (for drugs taken, their doses, frequency, skin lesions, associated prodromal symptoms, incubation period, any previous and present systemic illness, and improvement in symptoms on withdrawal of the suspected drug) was recorded, thorough clinical examination was performed and routine investigations were done in all cases. Cutaneous reactions because of errors in dosage and where the drugs taken were unknown, homeopathic, or ayurvedic, and patients with incomplete history were excluded. They were then classified ascertain/probable/possible/unlikely/unclassified/unclassifiable cases of drug reaction, as per WHO definitions.[3] Only probable and possible cases based on causality assessment were included in the study. If more than one drug was suspected to be responsible, the most likely causative agent was considered.
All CADR patients were given appropriate treatment with antihistamines, topical, and oral steroids and other drugs, depending upon the severity of CADR and hospitalized when necessary.
At the end of the study, the data was analyzed, and inferences were drawn using Chi-square test.
| Results | | |
A total of 234 patients with suspected CADRs were observed and considered for the study. They were then assessed according to WHO-UMC causality assessment and graded as certain, probable, possible, unlikely, unclassified, and unclassifiable. Out of the 234 patients, 67 (38.5%) patients were graded under probable category followed by possible (n = 107, 61.4%), unlikely (n = 11, 6.3%), unclassified (n = 30, 17.2%), unclassifiable (n = 19, 10.9%) [Figure 1]. None of the cases could be classified as certain CADR, as drug re-challenge was not performed. A total of 174 patients graded as probable (n = 67) and possible (n = 107) were included in the study. | Figure 1: Categorical representation of patients according to WHO -UMC causality scale
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There were 93 (53.4%) males and 81 (46.5%) females with the MF ratio of 1.5:1.
The age of patients ranged from 10 to 65 years (mean age = 40.2 years). Maximum number of patients (n = 54, 31.0%) were in the age group of 41–50 years, followed by 21–30 years (n = 42, 24.1%), 31–40 years (n = 30, 17.2%), 51–60 years (n = 27, 15.5%) and minimum patients were seen in the age group below 10 years and above 60 years [Figure 2].
Among various clinical patterns, maculopapular rash was the most common (n = 58, 33.%), followed by fixed drug eruption (n = 30, 17.2%), lichenoid dermatitis (n = 20, 11.5%), erythema multiforme (n = 16, 9.2%), acneiform eruptions (n = 11, 6.3%), exfoliative dermatitis (n = 7, 4.1%), SJS/TEN (n = 5, 2.9%), and others (n = 27, 15.5%) which comprised of icthyosis, xerosis, generalized pruritus, pityriasisrosea like rash and vasculitis [Figure 3].
The drugs most commonly responsible for CADRs were antimicrobials (n = 68, 39%) with fixed dose combination of fluoroquinolones with nitroimidazoles (n = 42) topping the list followed by fluoroquinolones alone, beta-lactams and sulphonanamides, analgesics (n = 30, 17%), antiepileptics (n = 21, 12%), antitubercular drugs (n = 12, 7%), and miscellaneous (n = 43, 25%) [Figure 4].
The time interval between the onset of drug intake and the manifestation of CADR ranged from 8 h (in a patient of pruritus) to 7 weeks (in a patient of lichenoid dermatitis) [Figure 5]. | Figure 5: Ofloxacin and ornidazole combination induced maculopapular rash
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Deranged renal and liver function tests were seen in 34 patients (19.5%) [Figure 6],[Figure 7],[Figure 8]. Ten patients (5.7%) had other abnormal biochemical values [Figure 9]. Eosinophilia (absolute eosinophil count >500 cells/mm3)[7] was seen in 36 patients (20.6%). Seven patients had HIV and four were VDRL positive [Figure 10].
Systemic complications like altered liver and renal function tests, septicaemia, ocular involvement, pneumonia, acute renal failure were seen in three out of five patients of SJS/TEN, however all patients survived. One patient of SJS had vitiligo.
We also noticed that a total of 42 patients out of 174 had comorbities in the form of diabetes (n = 27, 15.5%), hypothyroidism (n = 9, 5.1%), rheumatoid arthritis (n = 3, 1.7%), vitiligo (n = 2, 1.1%), and SLE (n = 1, 0.5%).
| Discussion | | |
Cutaneous adverse drug reactions are among the most common diagnosis in dermatology clinics and dermatologists have a subjective (susceptible to bias) idea about the common culprit drugs and the clinical patterns of CADRs associated with them, therefore objective evaluation using causality assessment is necessary before labelling a patient to be that of CADR and distinguish them from the other similarly presenting dermatoses. Hutchison described causality assessment as a "method for eliciting a state of information about a particular drug-event connection as input and delivering as output a degree of belief about the truth of the proposition that the drug caused the event to occur."[8]
In our study, a total of 174 CADR patients classified on the basis of WHO-UMC causality assessment scale were studied out of which 93 were males and 81 were females and various morphological patterns of ACDRs were noted.
The age group of the patients ranged from 10 to 65 years. Maximum number of patients belonged to the age group of 41–50 years. Another Indian studies also found out that CADRs were more common in elderly accounting to the fact of polypharmacy.[9] CADRs were noticed more in the males in our study as well as in the study of James et al.,[10] the reason being that our tertiary care hospital is situated in rural tribal area where females tend to neglect their skin problems. However, most studies claim female preponderance.[6],[11],[12]
Eosinophilia was noticed in 20.6% patients in our study while it was quite high in a study conducted by Pudukadan D et al. (42.2%).[13]
CADRs vary in their pattern of morphology and distribution. In our study, maculopapular rash was the most common drug eruption (33.3%) followed by FDE (17.2%) which is in keeping with the other Indian and international studies,[5],[14],[15],[16] while in few studies FDE topped the list.[17],[18],[19] Lichenoid dermatitis formed a substantial part of CADRs in our study accounting for 11.5% of patients mostly seen in the patients taking antihypertensives and antitubercular drugs.
Antimicrobials were the most common group of drugs implicated (39%) followed by NSAIDS (17.2%), antiepileptics (phenytoin and carbemazepine)(12.1%), antitubercular (isoniazid)(7%), and miscellaneous drugs (25%). Antimicrobials are implicated as the most common offending group of drugs in other studies also.[14],[20],[21] Among the antibiotic group, fixed dose combination of fluoroquinolones with nitroimidazoles was found to be the offending drug followed by fluoroquinolones alone, beta-lactams, and sulphonamides. Among the NSAIDS, Ibuprofen was the most common drug implicated.
Among the FDE patients, NSAIDS (diclofenac, Ibuprofen, paracetamol) were the most common drug implicated followed by antibiotics (fluoroquinolones). Five cases of FDE were seen with fluconazole which is in accordance with two more studies.[22],[23]
Severe cutaneous adverse reactions (SCAR) accounted for 2.9% of all the patients which is quite low as compared to the study conducted by Neol et al.[24]
Maculopapular rash was most commonly noticed with antimicrobials (ampicillin, ofloxacin, and ciprofloxacin) in our study which was in conformity with Jhaj et al.[25] Antiepileptics (carbamazepine, phenytoin) were the most common drug found responsible for SCAR followed by antibiotics like ofloxacin. Similar finding was noticed by Sasidharan et al.[26]
Isoniazid was implicated to cause maximum number of acneiform eruptions. Miscellaneous group of drugs included antihypertensives, diuretics, antifungals (fluconazole), PPIs (omeprazole and pantoprazole), and corticosteroids.
Other than the above findings, we also noticed that patients having diabetes mellitus type I, hypothyroidism, rheumatoid arthritis, vitiligo, and SLE formed a bulk of 42 patients out of 174 (P value = 0.004). Most of the diabetic patients were on oral antibiotics and antifungals for pyoderma and fungal infections (tinea and candidiasis) which made them more susceptible to develop adverse drug reactions. Most common adverse drug reaction pattern seen in these patients were lichenoid dermatitis, pruritus, and FDE. Two more studies observed that immunosuppressed and autoimmune patients are more susceptible to develop adverse cutaneous drug reactions.[1],[2]
| Conclusion | | |
CADRs are potentially avoidable causes for seeking medical care. Not warning a patient about potential adverse effects, prescribing the offending drug to a previously sensitized patient or prescribing a cross-reactive medication makes them a common reason for litigation. Moreover with the introduction of new drugs in the market, and the changing spectrum of drugs preferred for use by clinicians, a continuous monitoring of the patterns of CADRs in each region of the country is important. Such epidemiological data shall prove to be of great assistance to dermatologists in managing CADRs on a day to day basis. In our study, we also noticed that significant number of CADR patient had association with certain autoimmune conditions (P value = 0.004), though multiple studies on large scale in every region of the country are required to support this data.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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