The Internet Journal of Pharmacology
Rapid Oral Desensitisation To Isoniazide
Josefina Rodrigues, André Moreira, Joćo Fonseca, Isabel Camões,
Marianela Vaz: Rapid Oral Desensitisation To Isoniazide. The Internet
Journal of Pharmacology. 2004. Volume 3 Number 1.
Tuberculosis remains the leading
cause of death world-wide from any infectious agent and the
alarming increase in the annual incidence of new cases has been
described as a global emergency with figures of 10 million
infected and 3.5 million deaths projected for the year 2005 (
1 ). Adverse reactions to anti-tuberculosis drugs occur
in about 5% of treated patients and can be responsible for
cessation or switching the therapy( 2 , 3 ).
This is of particularly concern in systemic disease, in which
allergic reactions to Isoniazide (INZ) make desensitisation
necessary. We present a case report of rapid oral desensitisation
We report the case of a 40-year-old man, without history of atopic
diseases, antibiotic hypersensitivity or previous treatment with
antituberculous medications. He was admitted to the hospital for
persistent fever and had diagnosis of intestinal tuberculosis made by
laparotomy. He began a regimen of INZ 300mg/day, Rifampicine (RIF) 600
mg/day, Pirazinamide (PZM) 1500 mg/day and Ethambutol (ETB) 700 mg/day
without any reaction and was kept on a free tyramine and histamine food
On the 13th day of therapy, 30 minutes after INZ, RIF and
ETB he develops acute pruriginous urticarial rash in head, trunk and
legs without angioedema or dyspnea, which resolved with endovenous
prednisolone and intramuscular hidroxizine. On that day he didn't took
PZM. On the next day, he doesn't make INZ, takes RIF and ETB on the
morning without reactions and has a similar reaction after PZM, which
was made on early afternoon. On the next day he was challenged with 150
mg INZ with elicitation of the same reaction. Because he had persistent
fever we were not able to check for hypertermia after challenge. After
that until desensitisation, the patient was kept on a regimen of RIF and
ETB without any reactions.
We performed prick and intradermal tests with INZ which were negative
suggesting a non-IgE mediated reaction or that a metabolite from INZ was
the responsible for the reaction. We concluded by allergic sensitisation
to INZ and probably to PZM and after informed consent performed a
desensitisation protocol (Table 1) to INZ.
Table 1: Oral INZ desensitisation protocol
As far as we know this is the first reported case of sensitisation to
both INZ and PZM. There's a report ( 4 ) from a patient with
INZ occupational asthma with positive skin prick test to INZ suggesting
an IgE mediated reaction, which was not our case. Hypersensitivity
reactions with cutaneous manifestations may occur with PZM, however only
in less than 1% of treated patients ( 3 ). Christine Holland
et al ( 5 ) has proposed a desensitisation protocol for INZ
and RIF in a patient sensitised to both drugs. We could not desensitise
the patient to PZM, after the procedure to INZ, because he did not agree
on a second challenge with PZM. After desensitisation the patient was
able to tolerate 300 mg/day of INZ without complaints and was kept on a
free PZM protocol treatment.
André Moreira, email@example.com
Unidade de Imunoalergologia,
H S Joćo
Al Prof Hernāni Monteiro, 4200 Porto
1. WHO Report on the Tuberculosis Epidemic 1996 .
World Health Organisation Publications . 1996.
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J Allergy Clin Immunol 1984;74:209-224.
3. Girling DJ. Adverse effects of antituberculosis
drugs. Drugs 1982;23:56-74.
4. Asai, S., Shimoda T, and Fujihara, K. Occupational
aasthma caused by isonicotinic acid hydrazide inhalation. J Allergy Clin
Immunol 1987; 80, 578-582.
5. Holland CL, Malasky C, Ogunkoya A, Bielory L. Rapid
oral desensitization to isoniazid and rifampin. Chest