Allergy Asthma Immunol Res.  2019 Jan;11(1):90-103. 10.4168/aair.2019.11.1.90.

Prevalence and Clinical Features of Drug Reactions With Eosinophilia and Systemic Symptoms Syndrome Caused by Antituberculosis Drugs: A Retrospective Cohort Study

• Jung HY
• Park S
• Shin B
• Lee JH
• Lee SJ
• Lee MK
• Lee WY
• Yong SJ
• Kim SH

• KMID: 2426788
• DOI: http://doi.org/10.4168/aair.2019.11.1.90

Abstract

PURPOSE
Although there have been reported cases of drug reactions with eosinophilia and systemic symptoms (DRESS) syndrome caused by antituberculosis drugs, there has been no research to examine its prevalence. This study assessed the prevalence and clinical characteristics of DRESS syndrome caused by antituberculosis drugs.
METHODS
The electronic medical records of a cohort consisting of adult patients diagnosed with tuberculosis between July 2006 and June 2010 were reviewed and retrospectively inspected. We searched the surveillance system for adverse drug reactions and the electronic medical records to identify patients who reported severe cutaneous adverse reactions to antituberculosis drugs. These patients were then re-assessed using a European Registry of Severe Cutaneous Adverse Reactions to Drugs and Collection of Biological Samples (RegiSCAR) scoring system. Clinical characteristics, including the symptoms and latency of DRESS syndrome, the therapeutic dosage and period of steroids, and the final duration of tuberculosis therapy, were examined.
RESULTS
Of the 1,253 adult patients with tuberculosis receiving antituberculosis drugs, 15 were identified as potential cases of DRESS syndrome (prevalence of 1.2%). Ethambutol was the most frequently used drug (53.5%), followed by rifampicin (26.7%), pyrazinamide (20.0%), streptomycin (13.3%), and isoniazid (6.7%). The median latency after day 1 of antituberculosis medication was 42 days. The median daily dose of steroids, expressed in prednisone-equivalent units, was 33-mg/day, and the median dosing period was 14 days. The duration of tuberculosis treatment was 76 days longer than the standard treatment period of 180 days. There was a significant difference in the peak eosinophil counts of DRESS syndrome patients according to RegiSCAR scores. Moreover, there was a significant quantitative correlation between the RegiSCAR score and peak eosinophil count. A negative correlation was also found between the RegiSCAR score and latency.
CONCLUSIONS
This study confirmed the prevalence of DRESS syndrome in a cohort of adult patients with tuberculosis.

Keyword

Adverse drug reaction; drug hypersensitivity syndrome; antituberculosis; prevalence

MeSH Terms

Adult
Cohort Studies*
Drug Hypersensitivity Syndrome
Drug-Related Side Effects and Adverse Reactions
Electronic Health Records
Eosinophilia*
Eosinophils
Ethambutol
Humans
Isoniazid
Prevalence*
Pyrazinamide
Retrospective Studies*
Rifampin
Steroids
Streptomycin
Tuberculosis
Ethambutol
Isoniazid
Pyrazinamide
Rifampin
Steroids
Streptomycin

Figure

• 

  Fig. 1 This flow diagram shows that, among the ≥ 19-year-old patients who were receiving antituberculosis drugs who also required hospitalization for generalized skin rash, those who met the DRESS syndrome criteria were selected as the study subjects. DRESS, drug reactions with eosinophilia and systemic symptoms; AST, aspartate aminotransferase; ALT, alanine aminotransferase; SCAR, severe cutaneous adverse reactions.

• 

  Fig. 2 Skin symptoms of DRESS syndrome vary and include the following: disuse infiltrative maculopapules, exfoliation, facial edema and urticaria. (A) Diffuse erythematous papules and plaques on the right forearm and dorsum of hand (patient #8). (B) Diffuse scaly eczematous lesions on the face (patient #13). DRESS, drug reactions with eosinophilia and systemic symptoms.

• 

  Fig. 3 Enlarged lymph nodes were coincidently observed by chest and abdominopelvic computed tomography scanning, which was initially conducted to detect the cause of fever in the patient. (A) Multiple lymph node enlargement in both axillary areas are demonstrated. (B) Bilateral inguinal lymphadenopathy in a reactive patient (patient #8).

• 

  Fig. 4 This figure shows the prevalence rate of DRESS syndrome along with the causative antituberculosis drug. DRESS, drug reactions with eosinophilia and systemic symptoms.

• 

  Fig. 5 This figure shows the result of a patch test conducted with the antituberculosis drugs (INH, EMB, RFP, PZA and SM). The patch test was conducted 8 weeks after completion of tuberculosis treatment and was found to be EMB - and SM-positive (patient #13). INH, isoniazid; EMB, ethambutol; RFP, rifampicin; PZA, pyrazinamide; SM, streptomycin.

• 

  Fig. 6 This figure shows the correlation between the RegiSCAR score and the peak eosinophil counts as well as the latent period. (A) Positive correlation between RegiSCAR scores and peak eosinophil counts. (B) Negative correlation between the RegiSCAR scores and the latent period. RegiSCAR, European Registry of Severe Cutaneous Adverse Reactions to Drugs and Collection of Biological Samples.

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