Common drugs causing allergy in patients attending a tertiary care centre in South Kerala

INTRODUCTION

As per WHO, Adverse drug reaction is ‘any noxious change which is suspected to be due to a drug, occurs at doses normally used in man, requires treatment or decrease in dose or indicates caution in the future use of the same drug’.¹ An adverse drug reaction (ADR) is an unintended reaction to a drug that occurs at doses used for prevention, diagnosis, or treatment.² ADRs are common and affects between 15 and 25% of patients; serious reactions occur in 7–13% of patients.^3,4 Drug allergy affects the quality of life of the patient, lead to delayed treatment, unnecessary investigations, increased morbidity and even death.² Furthermore, identification of drug allergy and the drug causing it is challenging. The skin is the organ most frequently and prominently affected by drug-induced allergic reactions. The most common cutaneous manifestation is generalized maculopapular rash, which is characterized by an erythematous lesion that appear within days to three weeks after drug exposure. Drug allergic reactions can be either immediate or late reactions. Immediate reactions occur 1 to 6 hours following drug intake whereas late reaction occurs several hours to days later. Reactions can be either mild or life-threatening anaphylactic reaction.

Aim

Aim was to determine the common drugs causing allergic reactions in patients referred for drug allergy testing.

METHODS

A hospital based descriptive study with convenient sampling methodology was adopted. All patients those who attended the outpatient department of respiratory medicine of SUT academy of medical sciences from 01/02/2019 to 31/01/2020 was included in the study. It included patients referred from other departments like general medicine, general surgery, orthopaedics, gynaecology and obstetrics for drug allergy testing who had previous history of drug allergy.

Inclusion criteria

All indicated patients above the age of 10 years.

Exclusion criteria

Patients who required testing for only one or two group of drugs.

Scientific research committee and institutional ethical committee approval was obtained. After getting informed written consent each person was enrolled into the study. A detailed history of all drugs taken by the patient, including dates of administration, drug formulation, dosage and route of administration, clinical symptoms and their timing and duration in relation to drug exposure, as well as previous and subsequent drug exposures and reactions was taken

An intradermal test was done with the common drugs. Twenty-four drugs were selected for the sensitivity study. It included antibiotics, analgesics, anaesthetic agents and other common drugs. Patients were directed to stop taking antihistamines and corticosteroids 72 hours prior the test.

Intradermal testing

The drugs are injected into the volar aspect of the fore arm with an insulin syringe and a wheal of around 3mm is made. Histamine is used as positive control and normal saline is used as negative control. Patient is observed for 20 minutes and the wheal is measured with a scale. A wheal with diameter more than double that of the negative control is considered as positive. A wheal measuring double that of negative control is considered as doubtful and less that that is considered as negative.

Data was entered into the Microsoft excel sheets. Data of the study participants, reactions by the causative drugs were extracted and summarized by absolute numbers, percentages and means.

RESULTS

The study subjects included 14 males and 86 females. The age of the study participants ranged from 18 to 84. The mean age was 46 years with a Standard deviation of 15.54. There were no patients under the paediatric age group. 25 % of patients were of age 60 years and above (Table 1).

The reaction pattern of the study subjects is summarised in Table 2. Out of the 100 study subjects, 20% of study subjects showed positive reaction for diclophenac. 19% of study subjects showed positive reaction for ampicillin and paracetamol. 15% showed positive reaction for ketorolac. Ciprofloxacin (11%) and ranitidine (10%) followed next in case of positive reactions.

Metronidazole, glycopyrrolate and deriphyllin showed negative reaction in all study subjects. 99% of the study subjects showed negative reactions for amikacin, bupivacaine, lignocaine and propofol where as 98% showed negative reaction for midazolam.

DISCUSSION

Drug hypersensitivity reactions are most common in patients over 50 years of age and 63–70% of patients suspected of having an allergic reaction to the drugs are women5. Anaphylaxis by all causes is reported more frequently in adult females than males. This difference surfaces after puberty, suggesting that sex hormones may be involved.^6,7 In a study done by Rajan et al in Trivandrum, 56% of cases of ADR was reported in females and 44% in males with, male-female ratio of 0.78.⁸ A study done in a teaching hospital in India showed similar result; out of the total cases reported females were more compared to males.⁹ In our study 86% of patients reported for intradermal test were females and 25% were of age 60 years and above.

Non-steroidal anti-inflammatory drugs (NSAIDs) and antimicrobials were the two groups which showed positive reactions in most of the patients in this study. Among antibiotics, β-lactams and fluroquinolones were prominent. In a systematic review of ADR in Indian population by Thejus et al, the major causative drug groups were antimicrobials (45.46%), NSAIDs (20.87%) and anti-epileptic drugs (14.57%). Commonly implicated drugs were sulfa (13.32%), β-lactams (8.96%) and carbamazepine (6.65%).¹⁰ A study done by Rajan et al found out that, among the distribution of different classes of drugs causing ADR, immunoglobulin was the most common class of drugs (55.3%) followed by vaccines (16.9%). Other common class of drugs reported were due to antibacterial (7.8%), and antiepileptic (7.5%)8. In a study done by Suh DC et al showed that antibacterial, and antiepileptic were shown as most implicated drug classes.¹¹ According to the study done by Sharma S et al, the most common drug group responsible for causing CADRs was antibiotics (47.58%) followed by non‑steroidal anti‑inflammatory drugs (16.13%) and anticonvulsants (13.71%).¹²

CONCLUSION

Adults including elderly persons were the majority with positive skin test results with drugs. NSAIDs and antimicrobials showed reactions in most of the patients. The drugs which were commonly prescribed by the medical practitioners were found to be more prone for allergic reactions. Since the reactions can sometimes be fatal, it is important to know the drugs prone for ADR through intradermal testing. Prevention of future reactions is an essential part of patient management.

Recommendations: The patient should be provided with written information about which drugs are to be avoided. Those drugs should be noted in the hospital records. The mainstay of treatment for drug allergy is avoidance of the offending drug. When available, alternative medications with unrelated chemical structures should be substituted.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: The study was approved by the Institutional Ethics Committee

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