A study of fixed-drug reactions at a rural-based tertiary care center, Gujarat

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Author Details : Nishit Surti, Trusha Patel, Aishni Shah, Dhruv Patel, Rita Vora*

Volume : 5, Issue : 1, Year : 2019

Article Page : 85-88

https://doi.org/10.18231/2581-4729.2019.0018

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Abstract

Abstract

Introduction: Nowadays, due to the widespread availability of various drugs, adverse cutaneous drug reactions (ACDRs) have become very common. One type of ACDR that dermatologists encounter frequently these days is Fixed-drug reaction (FDR). FDR is a characteristic type of adverse cutaneous reaction, which occurs at the same site whenever a particular drug is taken. That is why there is a need to identify the drugs causing FDR and to counsel the patients properly to avoid recurrence.

Aim and Objective: The aim and objective was to study the demographic details, clinical patterns, and the culprit drugs causing FDR.

Setting and Design: We have conducted a cross-sectional, observational study.

Materials and Methods: We have conducted an observational cross-sectional study from April 2010 to March 2018 at the Department of Dermatology, Venereology and Leprology at Shree Krishna Hospital, Pramukhswami Medical College, Karamsad, Gujarat, after taking approval from the research ethical committee of our hospital. All patients coming to the skin out patient department who were diagnosed clinically as FDRs were included in the study, irrespective of age and sex. In every case, a detailed history was elicited and proper clinical examination was carried out and it was recorded in a proforma. The data collected was analyzed using proportions, frequencies and chi-square test. All the patients were counseled and given a list of drugs causing FDR to avoid recurrence.

Results: In our study, we enrolled 78 patients of FDR in which there were 43 (55.12%) males and 35 (44.88%) females. In these patients, the most frequent condition for which the offending drug was taken was fever (in 18 [23.08%] patients), while the most common complaint after intake of offending drug was pigmented patch (in 32 [41.03%] patients) followed by mucosal lesions (in 20 [25.64%] patients). Overall, antimicrobials (31 [39.74%]) were the most common group of drugs which caused FDR followed by nonsteroidal anti-inflammatory drugs (28 [35.90%]). Considering a single molecule, diclofenac (16 [20.51%]) was the most common drug causing FDR followed by metronidazole (6 [7.69%]) and then cotrimoxazole, fluconazole and ciprofloxacin (5 [6.41%]) each.

Conclusion: Among ACDRs encountered in dermatology patients, FDRs form an important part. Antimicrobials are the most common group while diclofenac is the most common drug causing FDR.

Keywords: Fixed-drug reaction, Adverse cutaneous drug reactions, Antimicrobials, NSAIDS.

Introduction

Discussion

In outpatients and inpatients, the prevalence of ACDR has been reported to be 1% and 2%–5%, respectively.^[8] There are two types of ADRs: The majority (nearly 95%) are those which are dose dependent and predictable from the primary and secondary drug pharmacology known as Type A (augmented) reactions; while others are idiosyncratic, unpredictable from drug pharmacology and determined by patient-specific susceptibility factors, known as Type B (bizarre) reactions.^[9] According to most of the studies, FDR is the second or third common ACDR.^[10] and among all ACDRs, FDRs range from 16% to 21%. The real percentage may be more than these values because ACDRs are under reported due to increased selling of over-the-counter drugs. FDR has is associated with HLA-B22.^[11],^[12] The exact mechanism of FDR occurrence is not yet understood, but it is hypothesized that the active and quiescent lesions are caused due to a cell-mediated process. The culprit drug acts as a hapten, which creates an inflammatory response by binding preferentially to the basal keratinocytes. This causes the keratinocytes to release cytokines such as TNF-alpha, which upregulate the expression of intercellular adhesion molecule-1 (ICAM-1). ICAM-1 stimulates the CD8+ effector/memory T-cells. Whenever the culprit drug is re-introduced in the body, these CD8+ effector/memory T-cells produce a large amount of interferon-gamma and TNF-alpha, causing tissue damage and reactivation of the

lesions.^[13],^[14] FDR can occur at any age. In our study, majority of patients belonged to 21–30 years age group, which correlates with other studies. In this study, antimicrobials (31 [39.74%]) were the most common group of drugs causing FDR, followed by NSAIDs (28 [35.90%]), antifungals drugs (12 [15.38%]), antiepileptics (2 [2.56]) and antitubercular drugs (3 [3.85%] each), and antiretroviral drugs and antispasmodics ([1.28%] each). In study by Ghosh et al. antibiotics were found to be the most frequent cause of adverse cutaneous reactions, thus showing similar results, although antiepileptics were second common cause.^[15] In a study by Raksha et al., NSAIDs caused 21% of the FDR followed by sulfa drugs with 14%.^[16] In our study, diclofenac was found to be most commonly associated with FDR (16 [20.51%]) followed by metronidazole (6 [7.69%] cases), and then cotrimoxazole, fluconazole and ciprofloxacin 5 (6.41%) each. In studies by Singh et al. and Shrivastava et al, cotrimoxazole was found to be the most common antimicrobial as the cause of FDR.^[17],^[18]A study by Pudukadan and Thappa showed that the most common culprit drugs were cotrimoxazole in 22.25% of patients followed by dapsone in 17.7% of patients.^[19] In our study, when two or more drugs were thought to have caused the FDR, the most likely drug was noted and it was confirmed when the symptoms reduced on withdrawing the drug. There are many methods to find out the offending drug such as intradermal tests, provocation tests or skin prick tests but they are of limited use as they need expertise, time consuming and may even cause life-threatening ADRs that may raise ethical issues. Fortunately, there is an in vivo challenge test called the drug patch test, which is easy to perform and can be used to detect ACDRs.^[20] Patch testing was first used by Alanko et al. for determining the causative drugs in FDR.^[21] In ACDRs, patch testing is the investigation of choice and it is useful in FDRs caused by NSAIDs.^[20] Patch testing for contact dermatitis and drug test has the same basic principle and methodology. Patch testing is usually performed on a previously affected skin to avoid false-negative result.^[22] For patch testing, petrolatum, water, or alcohol can be used as vehicles in which 1-10% of pure drug form should be used. Drugs causing most of the reactions are anticonvulsants (carbamazepine, phenobarbitone, phenytoin or lamotrigine), betalactam antibiotics (amoxicillin and ampicillin), NSAIDs and sulfonamides. If the patch test results are negative, oral provocation test has been found to be the only reliable method to spot the offending drug. In our study, the only limitation is that no objective test was conducted to confirm the culprit drug and instead of mentioning all the drugs taken by the patient, only that drug which was most likely to cause drug reaction was recorded.

Conclusion

Among all ACDRs, FDR is an important type, which is seen very often nowadays because a wide array of drugs is available. The primary factor responsible for drug reactions are unmonitored selling of over the counter (OTC) medications. The main drugs causing FDR include antibiotics, analgesics, and antiepileptics. In order to reduce the cases of ACDR, we must focus on reporting of maximum cases and their monitoring. Patients should also be counseled about drug reactions and should be given drug list of that respective ACDR to avoid recurrence. Hence, this study highlights the importance of a sustained combined effort needed on part of the pharmacists, physicians as well as the public to effectively monitor the rampant use of over the counter medication as well as prescribed drugs to curtail the drug reactions which can potentially occur, and prevent them at a grassroot level.

Conflict of Interest: None.

References

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How to cite : Surti N , Patel T, Shah A, Patel D, Vora R, A study of fixed-drug reactions at a rural-based tertiary care center, Gujarat. IP Indian J Clin Exp Dermatol 2019;5(1):85-88

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