Hypersensitivity reaction and tolerance induction to ethambutol

As ethambutol was the optimal choice for this MAC treatment, a second attempt was

done with the 12th step protocol, three different solutions2,3, with slower increments

than usual, and pre-medication with hydroxyzine and 20mg of oral prednisone. The

first 400mg were tolerated and she was put on 400mg everyday during 8 days,

augmented to 800mg in the second week and to 1200mg in the third week, without

adverse reactions.

Bibliography:

1-Rodrigues Carvalho S, Silva I, Leiria-Pinto P, Rosado-Pinto J. Rapid oral tolerance induction to isoniazid and pyrazinamide and controlled administration of ethambutol:

clinical case. Allergol Immunopathol 2009;37(6):336-8.

2-Castells M, Tennant NM, Sloane DE, Hsu FI, Barrett NA, Hong DI et al. Hypersensitivity reactions to chemotherapy: outcomes and safety of rapid desensitization in 413

cases. J Allergy Clin Immunol 2008;122:574–580

3- Cernadas JR et al. General considerations on rapid desensitization for drug hypersensitivity - a consensus statement. Allergy 2010 Nov;65(11):1357-66.

Josefina R Cernadas1, Natacha Santos1, Claudia Pinto2, Mariana Castells3 1Servico de Imunoalergologia, Centro Hospitalar São João, E.P.E., Porto Portugal 2Servico de Pneumologia, Centro Hospitalar Tras-os-Montes e Alto Douro, E.P.E. Vila Real, Portugal 3Department of Medicine, Division of Rheumatology, Immunology, and Allergy, Brigham and Women’s Hospital, Boston, U.S.A.

66 years old woman followed in the Pulmonology Department of

Centro Hospitalar São João for bronchiectasis.

Atypical mycobacteriosis by Mycobacterium kansasii.

Completed 18 months of rifampicin, ethambutol and isoniazid

without adverse reactions.

2008

2006

2 sputum cultures with Mycobacterium avium complex (MAC)

Started streptomycin (2 months), rifampicin, ethambutol and

clarithromycin.

Two month before finishing treatment:

Facial erythema, angioedema of the neck and upper limbs followed

by pruritic scaling maculo-papular exanthema in the neck, trunk,

upper and lower limbs, associated with mild dyspnoea with no

hemodynamic changes. Treated with intravenous anti-histaminic and

corticosteroid, all medication was stopped.

MAC identification in cultures persisted.

Rifampicin and clarithromycin was prescribed for 1 month

followed by a controlled intake of a 400mg tablet of

ethambutol with oral hydroxyzine pre-medication.

3 hours after ethambutol intake she had a similar reaction.

2010

Referred to the Drug Allergy Clinic

Skin tests with ethambutol

Solutions of 1mg/mL and 10mg/mL prepared by the hospital’s pharmacy were used for

skin testing and for the smaller initial dosages

Because of clinical history and reproducibility of the reactions,

an hypersensitivity reaction to ethambutol was assumed and a

a 2 day tolerance induction protocol was started, adapted from

previous literature reports1

Day

Time (min)

Dose (mg)

Cumulative dose (mg)

1

0 0,10 0,10 45 0,50 0,60 90 1,00 1,60

135 2,00 3,60 180 4,00 7,60 225 8,00 15,60 270 16,00 31,60

Day

Time (min)

Dose (mg)

Cumulative dose (mg)

2

0 16 47,60 45 32 79,60 90 50 129,60

135 100 229,60 180 200 429,60 225 400 829,60 270 400 1229,60

The patient had a cutaneous reaction and the procedure was

adjusted to achieve the needed 1200mg dose in four days,

without success.

Solution (mg/mL)

Time (min)

Dose (mL)

Dose (mg)

Cumulative dose (mg)

0,01

0 1 0,01 0,01 30 2 0,02 0,03 60 4 0,04 0,07 90 8 0,08 0,13

0,1

120 1 0,1 0,23 150 2 0,2 0,43 180 4 0,4 0,83 210 8 0,8 1,63

1 240 1 1 2,63 270 10 10 12,63

10 300 10 100 112,63 330 30 300 412,63

1 week 1 week

Comments:

Ethambutol is a bacteriostatic antimycobacterial drug with ocular toxicity as the main side effect. Hypersensitivity reactions to

ethambutol are rare and definite causal relationship is usually difficult to determine. Our patient had reproducible hypersensitivity

reactions with ethambutol and two different tolerance induction protocols needed to be performed until tolerance was reached.

doubtful results