What causes chilliness in a leprosy patient undergoing treatment with antibiotics such as rifampicin and dapsone?

Chilliness in Leprosy Patients During Treatment

Direct Answer

The feeling of chilliness in a leprosy patient undergoing treatment with rifampicin and dapsone is most commonly caused by rifabutin or rifampicin-induced "flu syndrome," characterized by episodes of fever, chills, headache, dizziness, and bone pain, particularly when the drug is taken irregularly or after a drug-free interval. 1

Primary Mechanism: Rifampin-Induced Flu Syndrome

Rifampicin is the most likely culprit for chilliness during leprosy treatment. The FDA drug label explicitly identifies a "flu syndrome" as a recognized adverse reaction to rifampicin, which includes:

• Episodes of fever and chills 1
• Headache and dizziness 1
• Bone pain 1
• Shortness of breath and wheezing 1

This flu syndrome is particularly likely to occur when rifampicin is taken irregularly by the patient or when daily administration is resumed after a drug-free interval. 1 This pattern is critical to recognize in clinical practice, as poor adherence or interrupted treatment schedules can trigger these symptoms.

Alternative Consideration: Dapsone Syndrome

While less common, dapsone can cause a hypersensitivity syndrome that includes fever, malaise, and systemic symptoms. 2 However, dapsone syndrome typically presents with:

• Fever and malaise 2
• Nausea and anorexia 2
• Lymphadenopathy 2
• Hepatitis 2
• Exfoliative dermatitis 2

If chilliness is accompanied by rash, lymph node enlargement, or jaundice, dapsone syndrome should be considered. 2 This is a more severe hypersensitivity reaction requiring immediate drug discontinuation.

Drug Interaction Effects

Rifampicin induces the metabolism of dapsone, which decreases dapsone's plasma half-life and may alter the clinical presentation of adverse effects. 3 This enzyme induction occurs through upregulation of hepatic cytochrome P450 enzymes, particularly CYP3A4. 3 However, this interaction primarily affects drug efficacy rather than causing chilliness directly.

Clinical Approach to Evaluation

When a leprosy patient reports chilliness during treatment, assess for:

• Pattern of medication adherence: Irregular dosing or recent resumption after interruption strongly suggests rifampicin flu syndrome 1
• Associated symptoms: Isolated chills with fever points to rifampicin; chills with rash, lymphadenopathy, or jaundice suggests dapsone syndrome 2
• Timing of symptom onset: Early reactions (within days to weeks) are more consistent with drug hypersensitivity 4
• Presence of other systemic symptoms: Headache, bone pain, and shortness of breath support rifampicin flu syndrome 1

Management Strategy

For rifampicin-induced flu syndrome with chilliness:

• Ensure strict adherence to daily dosing without interruptions 1
• Avoid intermittent or irregular dosing schedules 1
• Provide symptomatic relief with antipyretics if needed
• Continue treatment if symptoms are mild and self-limiting 1

If dapsone syndrome is suspected (chilliness plus rash, lymphadenopathy, or hepatitis):

• Immediately stop all medications 5
• Monitor liver function tests until normalized 5
• Sequentially reintroduce drugs one by one to identify the offending agent 5
• Start with isoniazid at 50 mg/day, then rifampicin at 75 mg/day, then dapsone last 5

Critical Pitfalls to Avoid

Do not dismiss chilliness as a minor complaint without assessing medication adherence patterns. 1 Irregular rifampicin dosing is a preventable cause of flu syndrome that can be corrected with patient education.

Do not continue rifampicin at the same dose if severe flu syndrome develops with shock-like symptoms or significant respiratory compromise. 1 While rare, these severe reactions require immediate medical attention.

Do not assume all fever and chills in leprosy patients are due to medications. Consider leprosy reactions (Type 1 or Type 2 reversal reactions) as alternative diagnoses, particularly if occurring 6-12 months into treatment. 4