European Journal of Cardiovascular Medicine

Tuberculosis remains a significant health challenge, particularly in resource-limited settings. While ATT is critical for management, it is also associated with a spectrum of adverse drug reactions, particularly involving the skin, which can significantly affect patient adherence, quality of life, and treatment success rates¹.The cutaneous adverse effects can range from mild pruritus and rashes to

severe manifestations like exfoliative dermatitis, drug reactions with eosinophilia and systemic symptoms (DRESS) Stevens-Johnson syndrome

(SJS), toxic epidermal necrolysis (TEN), and CADRs, can have serious implications on treatment continuity and patient safety².The exact incidence of CADRs associated with anti-tubercular drugs varies widely depending upon factors like genetic predisposition, age, sex, nutritional status, comorbid conditions like HIV or diabetes, and polypharmacy. Studies have reported that up to one-fourth of patients on first-line anti-tubercular therapy may experience some form of CADR, highlighting the clinical relevance of this issue³. ATT related CADR  cases have steadily been reported in the literature^4,5,6,7 and an increase in the reported number of ATT associated DRESS cases has been observed over the past few years⁴. CADRs can affect compliance and prognosis This study evaluates the prevalence, clinical profile, and risk factors of CADRs in patients on ATT

Study Design and Population:                                                                                     

This prospective observational study was conducted in the Department of Respiratory Medicine and the Department of Dermatology, Venereology and Leprosy (DVL) in Government Medical College and Hospital, Nizamabad, Telangana, India. The objective of this study was to evaluate the cutaneous adverse effects associated with first-line anti-tubercular drugs in patients diagnosed with tuberculosis. It included 50 hospitalized TB patients, aged between 19-80 years who developed CADRs during ATT course. These patients were initiated on anti-tubercular therapy (ATT) as per the National Tuberculosis Elimination Programme (NTEP) guidelines after obtaining written informed consent.

Inclusion Criteria

• Patients with confirmed clinical or/and microbiological diagnosis of TB.
• Treatment-naïve individuals starting first-line ATT.
• Patients willing to participate in the study and provide informed consent.

Exclusion Criteria

• Patients with known dermatologic conditions prior to ATT initiation.
• Patients previously treated with ATT.
• Pregnant or lactating women.
• Patients who deny informed consent or not willing to participate in the study.

Data Collection:

Fixed-dose combination (FDC) comprising of anti-tubercular drugs such as isoniazid, rifampicin, pyrazinamide, and ethambutol during the intensive phase (first 2 months), followed by isoniazid and rifampicin during the continuation phase (next 4 months) were administered to the study patients. Second line ATT drugs were used in patients who could not tolerate first line ATT. Dosages were adjusted according to body weight as per standard treatment guidelines.

A baseline assessment was conducted,and patients were monitored with monthlyfollowups for six months or until their therapy was completed. Comprehensive 

demographic information, medical history, underlying conditions, and initial

biochemical assessments were documented. At every followup visit or whenever symptoms arose, all patients were thoroughly assessed for any cutaneous adverse drug reactions (CADRs). All observed CADRs were quickly recorded, noting the type of skin rash (e.g., maculopapular rash, urticaria, exfoliative dermatitis, SJS-TEN, etc.), rash severity, time of rash onset following therapy initiation, and the drug(s) thought to be implicated. In instances of significant reactions, adjustments to treatment or discontinuation of the drug were implemented as needed.

Statistical Analysis:
Descriptive statistics were used to present the frequency of CADRs and implicated risk factors

Demographic and Clinical Characteristics

• Total population: 50 patients (23 males, 27 females).

• Age range: 19-80 years (Mean: 50 years).

• TB type: 30 patients (60%) had pulmonary TB, and 20 patients (40%) had extra-pulmonary TB.

Risk Factors for CADRs

• Elderly age: 24 patients (48%)

• Polypharmacy: 13 patients (26%)

• Pre-existing renal disease: 4 patients (8%)

• Diabetes mellitus: 6 patients (12%)

• Smoking and alcohol consumption: 15 (30%) and 14 (28%) patients, respectively.

Clinical Manifestations

• Most Common Rash Types:

• Maculopapular rashes (42%)

• Urticarial rashes (18%)

• Lichenoid drug rashes (12%)

• Severe Reactions:

• DRESS syndrome: 26%

• Exfoliative dermatitis: 12%

• AGEP: 8%

Systemic Involvement

• Eosinophilia: 40 patients (80%)

• Transient Hepatitis: 19 patients (38%)

• Renal Dysfunction: 4 patients (8%)

Drug Analysis

• Most Commonly Implicated Drugs:

• Ethambutol: 46%

• Pyrazinamide: 20%

• Isoniazid: 18%

• Rifampicin: 16%

• Streptomycin: 8%

• Levofloxacin: 6%

Key findings are summarized below:

Gender Distribution

Tb Types

Drug Distribution

Rash Types

Systemic Involvement

The findings underscore the substantial burden of CADRs among TB patients receiving ATT.  Maculopapular rash(42%), Urticarial rash (18%), lichenoid drug rash(12%) were predominant These observations are largely consistent with those of Sharma et al. (2020)8,who reported maculopapular rash as the predominant manifestation (40%),and ethambutol(46%) was the most frequently implicated drug. Sharma et al. (2020)¹⁵  also found ethambutol to be the most frequent offenders in skin-related ADRs.Systemic manifestations such as eosinophilia (80%) and hepatic involvement (38%) were common. Recognizing risk factors like age and polypharmacy can guide preventive strategies.

CADRs are a significant cause of morbidity in ATT patients⁹. Any of the drugs used in ATT regimen can potentially cause CADRs¹⁰. Hence the patients need to be thoroughly counselled regarding the risk of CADRs prior to the initiation of therapy. The treating physicians must have high index of suspicion regarding the same.Timely diagnosis, avoidance of culprit drugs, and consideration of patient-specific risks can improve outcomes. Continued pharmacovigilance and personalized treatment protocols are essential.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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