Allergy Asthma Respir Dis AARD Allergy, Asthma & Respiratory Disease 2288-0402 2288-0410 The Korean Academy of Pediatric Allergy and Respiratory Disease; The Korean Academy of Asthma, Allergy and Clinical Immunology 10.4168/aard.2015.3.4.297 Case Report Successful readministration of second-line antituberculous agents in a patient with near-fatal drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome Moon Sung Do 1 2 Won Ha Kyung 1 2 Cho Jae-Young 1 Kang Min-Koo 1 2 Kim Ju-Young 1 2 3 Park Han-Ki 1 2 3 Kim Sujeong 4 http://orcid.org/0000-0002-2317-4201 Kang Hye-Ryun 1 2 3 Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul National University College of Medicine, Seoul, Korea. Regional Pharmacovigilance Center, Seoul National University Hospital, Seoul, Korea. Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea. Correspondence to: Hye-Ryun Kang. Division of Allergy and Clinical Immunology, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea. Tel: +82-2-2072-0820, Fax: +82-2-742-3291, helenmed@snu.ac.kr 07 2015 28 07 2015 3 4 297 301 09 04 2015 08 06 2015 17 06 2015 © 2015 The Korean Academy of Pediatric Allergy and Respiratory Disease; The Korean Academy of Asthma, Allergy and Clinical Immunology 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/).

For the treatment of multidrug-resistant (MDR) tuberculosis, maintenance of appropriate antituberculous agents is essential because of its low cure rate and high dropout rate. Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe drug-induced systemic hypersensitivity response resulting in cessation of causative agents. In cases of second-line antituberculous agent-induced DRESS, it is extremely difficult to find other replacement medications to cure MDR tuberculosis. A 53-year-old male who had taken the second-line antituberculous agents (cycloserine, streptomycin, p-aminosalicylic acid, and prothionamide) as well as pyrazinamide for 5 weeks experienced DRESS syndrome accompanying hepatic coma. His symptoms improved with discontinuation of antituberculous agents and administration of high-dose methylprednisolone for 1 month. To resume the antituberculous medication, second-line antituberculous agents were administered one by one using a rapid desensitization protocol. While kanamycin, levofloxacin, and cycloserine were successfully readministered, p-aminosalicylic acid- and prothionamide-induced cutaneous hypersensitivity symptoms were relatively mild compared to previous reactions. Herein, we report a case of successfully treated MDR tuberculosis having a history of fatal DRESS syndrome to antituberculous agents using the rapid desensitization protocol.

 Drug hypersensitivity syndrome Antitubercular agents Immunologic desensitization Ministry of Food and Drug Safety

This study was supported by a grant from Ministry of Food and Drug Safety to operation of the Regional Pharmacovigilance Center in 2015.

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Day PZA SM CS PAS PTH LVFX KM AC Remarks
0 ● ● ● ● ● ● PZA was already started 4 months ago.
27 ● ● ● ● ● ● Fever on day 27, maculopapular rash on day 37
31 □ □ ● ● ● □ Clinical improvement after discontinuation of PZA, SM, and LVFX
36 ● ● ● ● Fever on the next day of PZA readministration
37 □ ● ● ● Maculopapular rash and azotemia despite discontinuation of PZA
42 □ □ □ Generalized maculopapular rash and hepatic encephalopathy despite discontinuation of CS, PAS, PTH
43-71 Administration of systemic steroid
74 ● Severe generalized erythema and urticaria
79 ▲
81 ▲
83 △ Pruritus, erythema, and urticaria
107 ▲
119 △ Erythema urticaria on both arms
134 ●

● , administration of full dose; □ , discontinuation; ▲ , administration with desensitization protocol; △ , hypersensitivity reaction despite administration with desensitization protocol; PZA, pyrazinamide; SM, streptomycin; CS, cycloserine; PAS, p-aminosalicylic acid; PTH, prothionamide; LVFX, levofloxacin; KM, kanamycin; AC, amoxicillin clavulanate.

 Intravenous rapid desensitization protocol for kanamycin (target dose: 1,000 mg)
Step Concentration (mg/mL) Rate (mL/hr) Time (min) Administrated dose (mg) Cumulative dose (mg)
1 0.0491 5 15 0.0614 0.0614
2 0.0491 10 15 0.1228 0.1841
3 0.0491 20 15 0.2455 0.4297
4 0.0491 40 15 0.4910 0.9207
5 0.0491 80 15 0.9821 1.9027
6 0.0491 160 6.3 0.8225 2.7252
7 0.4955 15 15 2.4775 5.2027
8 0.4955 40 15 4.9550 10.1577
9 0.4955 80 15 9.9099 20.0676
10 0.4955 160 5.6 7.4324 27.5000
11 5.0 20 15 25 52.5
12 5.0 40 15 50 102.5
13 5.0 80 133.4 897.5 1,000

1:100 solution for steps 1-6: 5.5 mL of 1:10 solution was added to normal saline 50 mL (0.0491 mg/mL); 1:10 solution for steps 7-10: 5.5 mL of 1:1 solution was added to normal saline 50 mL (0.4955 mg/mL); 1:1 solution for steps 11-13: Kanamycin 1,000 mg in normal saline 200 mL (5.0 mg/mL).

 Oral rapid desensitization protocol for prothionamide (target dose: 250 mg twice a day)
Step Time from start (hr) Administered dose (mg) Cumulative dose (mg)
1 0 0.025 0.025
2 1 0.050 0.075
3 2 0.125 0.2
4 3 0.25 0.45
5 4 0.5 0.95
6 5 1.0 1.95
7 6 2.0 3.95
8 7 3.75 7.7
9 8 7.5 15.2
10 9 15 30.2
11 10 30 60.2
12 11 62.5 122.7
13 12 125 247.7
14 13 250 497.7

1:10 solution for steps 1-6: 5.5 mL of 1:1 solution was added to 5% dextrose water 50 mL (0.248 mg/mL); 1:1 solution for steps 7-11 prothionamide 125 mg in 5% dextrose water 50 mL (2.5 mg/mL). Tablets were used for steps 12-14.

 Oral rapid desensitization protocol for cycloserine (target dose: 500 mg twice a day)
Step Time from start (hr) Administered dose (mg) Cumulative dose (mg)
1 0 0.05 0.05
2 1 0.10 0.15
3 2 0.25 0.4
4 3 0.5 0.9
5 4 1.0 1.9
6 5 2.0 3.9
7 6 4.0 7.9
8 7 7.5 15.4
9 8 15.0 30.4
10 9 30.0 60.4
11 10 60.0 120.4
12 11 125 245.4
13 12 250 495.4
14 13 500 995.4

1:10 solution for steps 1-6: 2.0 mL of 1:1 solution was added to 5% dextrose water 18 mL (0.5 mg/mL); 1:1 solution for steps 7-12 cycloserine 250 mg in 5% dextrose water 50 mL (5.0 mg/mL). Tablets were used for steps 13-15.