What is the management plan for a patient with an allergy to tuberculosis (TB) serum?

Management of Tuberculosis Serum Allergy

For patients with an allergy to tuberculosis serum (PPD), alternative testing methods should be used, and if treatment is needed, a desensitization protocol or alternative regimens should be implemented.

Alternative Testing Methods for TB

• Interferon-gamma release assays (IGRAs) are recommended as the primary alternative to tuberculin skin testing for patients with known allergies to PPD 1
• IGRAs do not contain the components of PPD that typically cause allergic reactions and are therefore safer for patients with PPD allergies 1
• If a patient has a history of an allergic reaction to PPD, avoid repeat tuberculin skin testing due to risk of severe reactions 2

Types of Allergic Reactions to TB Serum

• Immediate-type hypersensitivity reactions (occurring within minutes to hours) are the most concerning and require special management 3
• Delayed-type hypersensitivity (DTH) is the normal immune response to tuberculin in infected individuals and should not be confused with an allergic reaction 2
• Severe reactions may include anaphylaxis, urticaria, or angioedema 4

Management Algorithm for Patients Requiring TB Treatment with PPD Allergy

Step 1: Risk Assessment

• Determine the severity of the previous allergic reaction to PPD 4
• Evaluate the patient's need for TB treatment (active TB vs. latent TB infection) 1
• Consider HIV status, as HIV-infected patients may have altered immune responses 2

Step 2: For Patients with Latent TB Infection

• If treatment is indicated for LTBI in a patient with PPD allergy:
  • Consider rifampin monotherapy for 4 months as the preferred regimen (avoids other potentially cross-reactive medications) 1
  • Alternative: isoniazid plus rifapentine for 3 months if no cross-reactivity concerns exist 1

Step 3: For Patients with Active TB Disease

• For patients with active TB requiring first-line drugs:
  • Implement a sequential reintroduction protocol for first-line drugs 3
  • Start with the least likely culprit drug at a low dose and gradually increase 4, 3
  • Monitor closely for signs of allergic reaction during reintroduction 4

Step 4: Desensitization Protocol

• For patients who require a medication to which they are allergic:
  • Begin with 6-8 step desensitization protocol under medical supervision 3
  • Start with 1/1000 of the therapeutic dose and gradually increase 3
  • Complete the protocol in a monitored setting with emergency medications available 3
  • Success rates for desensitization protocols are high (>90% in some studies) 3

Management of Hepatotoxicity During TB Treatment

• If hepatotoxicity develops during treatment:
  • Suspend treatment until liver function normalizes 5
  • Reintroduce drugs sequentially, starting with isoniazid at 50 mg/day, increasing to 300 mg/day after 2-3 days 5
  • Add rifampicin at 75 mg/day after 2-3 days without reaction, then gradually increase to full dose 5
  • Finally add pyrazinamide at 250 mg/day and increase to full dose 5

Special Considerations

• Female sex has been identified as a risk factor for immediate-type hypersensitivity reactions to TB medications (odds ratio 4.085) 3
• Patients with HIV co-infection have higher rates of T-cell mediated hypersensitivity reactions to anti-TB drugs 4
• Multiple drug sensitization can occur, making management more complex 4

Pitfalls and Caveats

• Do not confuse anergy (lack of DTH response) with allergy to PPD 2
• Never restart a drug that has caused a severe cutaneous adverse reaction (Stevens-Johnson syndrome or toxic epidermal necrolysis) 2
• Skin tests and patch tests for TB drug allergies have limited predictive value and should be performed only by allergy specialists 4
• Always report TB cases to local health departments, even when managing allergic reactions 1