Skin reactions

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    All TB drugs
     

    Skin reactions such as itch and skin rash may be hypersensitivity reactions due to any TB drug. General signs of hypersensitivity such as fever, dizziness, vomiting and headache may also occur.
    Skin reactions usually appear early during treatment, often in the first month, but rarely during the first week. Most skin reactions are mild or moderate. Severe cutaneous adverse reactions such as Stevens-Johnson and Lyell syndromes, and DRESS (drug reaction with eosinophilia and systemic symptoms) may occasionally occur, particularly if administration of the TB drug continues after first signs of hypersensitivity appear.

    Minor skin reactions

    • Simple itching: symptomatic treatment (e.g. antihistamine) without interrupting or modifying the TB treatment.
    • Localised, mild skin rash, with or without itching:
      • Rule out other possible causes unrelated to TB drugs (e.g. scabies, contact dermatitis).
      • If no obvious other cause, stop all TB drugs.
      • Give symptomatic treatment (an antihistamine, no corticosteroids except in emergencies) and wait for disappearance of symptoms.
      • Once the reaction has resolved, try to determine which drug caused the reaction (see re-challenge of TB drugs below).

    Major skin reactions

    • Stop all TB drugs.
    • In the event of anaphylaxis, manage according to standard emergency protocol (epinephrine, etc.).
    • For generalised rash, a parenteral corticosteroid may be needed.
    • Once the reaction has resolved, try to determine which TB drug caused the reaction (see "Rechallenge of TB drugs" below).
    • Never re-introduce any drug resulting in Stevens-Johnson or Lyell syndromes, DRESS or anaphylaxis.

    Rechallenge of TB drugs

    Each TB drug can be reinstated as a "challenge" (a test-dose). Introduce one drug at a time, starting with the drugs least likely to have caused the reaction.

     

    Give the drugs in a setting where a health care provider can respond to any severe allergic reaction.

     

    If a test-dose of any drug causes a reaction, discontinue this drug, unless it is deemed essential to the regimen (in this case, desensitisation can be considered). 

     

    • First-­line TB drugs
      Start with isoniazid over 3 days then add rifampicin over 3 days, etc.

    Drug

    Likelihood

    Test-dose 1

    Test-dose 2

    Test-dose 3

    H

    Least likely

    50 mg

    Full dose

    Full dose

    R

    Least likely

    75 mg

    300 mg

    Full dose

    Z

    Likely

    250 mg

    1000 mg

    Full dose

    E

    Likely

    100 mg

    500 mg

    Full dose

     

    Note: if the initial reaction to treatment is severe, a weaker test-dose should be used (approximately 1/10th of the dose indicated for test-dose 1).

     

    • Second-­line TB drugs
      Start with the most important drug in a regimen unless there is suspicion that it is the cause of the reaction. Restart each TB drug one after the other, starting at about 1/10th of the dose on Day 1, half-dose on Day 2 and full dose on Day 3.