What is the approach to managing a patient with DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) syndrome due to anti-tuberculosis (anti-TB) medication?

Management of DRESS Syndrome Due to Anti-TB Medications

Immediately discontinue all anti-tuberculosis medications when DRESS syndrome is suspected, initiate systemic corticosteroids (methylprednisolone 0.5-1 mg/kg IV or equivalent), provide supportive care with dermatology consultation, and transition to alternative TB regimens once the patient stabilizes. 1, 2, 3

Immediate Recognition and Discontinuation

Clinical Diagnosis

• Suspect DRESS when a patient on anti-TB therapy presents with the triad of fever, diffuse skin rash (often exfoliative erythematous macules with or without target lesions), and eosinophilia, typically occurring 2-8 weeks after starting treatment. 2, 4, 5
• Check complete blood count with differential (expect eosinophilia averaging 16.7%), comprehensive metabolic panel (liver and kidney involvement are most common), and liver function tests immediately. 2, 3, 4
• All first-line anti-TB drugs can cause DRESS, but rifampicin is most frequently implicated (84.2% of cases), followed by isoniazid (68.4%) and pyrazinamide (26.3%). 4, 5

Immediate Drug Withdrawal

• Stop all anti-TB medications immediately—do not attempt to identify the specific culprit drug initially, as this delays definitive management and worsens outcomes. 2, 3, 4
• Permanent discontinuation of the causative medication is imperative; avoid re-exposure to prevent potentially fatal recurrence. 2

Acute Management and Supportive Care

Corticosteroid Therapy

• Administer IV methylprednisolone 0.5-1 mg/kg (or oral equivalent) and continue for at least 4 weeks with gradual taper, as DRESS requires prolonged immunosuppression due to its T-cell mediated mechanism. 1, 2
• Convert to oral corticosteroids once clinical response is evident, but taper slowly over at least 4 weeks to prevent relapse. 1
• Monitor eosinophil counts as a useful marker of disease progression and treatment response. 6

Dermatology and Multidisciplinary Care

• Consult dermatology immediately for skin biopsy confirmation and management guidance. 1, 2
• Apply topical emollients, petrolatum-based products, and high-strength topical corticosteroids to affected skin. 1
• Administer oral antihistamines for symptomatic relief of pruritus. 1
• For severe cases with extensive skin involvement (>30% body surface area), consider admission to burn unit or ICU with wound care services. 1

Additional Immunosuppression for Severe Cases

• Consider intravenous immunoglobulin (IVIG) or cyclosporine for severe or corticosteroid-unresponsive cases, particularly those with multi-organ failure. 1, 6
• One case series reported successful use of IVIG in combination with corticosteroids for severe anti-TB DRESS. 6

Infection Prevention During Immunosuppression

Critical Monitoring

• Be vigilant for secondary infections during corticosteroid treatment, as methicillin-resistant Staphylococcus aureus (MRSA) and other opportunistic infections can complicate management. 6
• Contrary to initial concerns, tuberculosis progression does not typically occur under corticosteroid treatment for DRESS, even in patients with advanced TB. 3
• Monitor for signs of osteomyelitis, septic arthritis, or other deep-seated infections, particularly with indwelling catheters. 6

Alternative TB Treatment Regimens

Transition to Second-Line Therapy

• Once the patient stabilizes (typically 4 weeks after drug discontinuation), initiate alternative anti-TB regimens that exclude the causative drugs. 2, 3
• The most commonly used alternative regimens include levofloxacin (or moxifloxacin), ethambutol, streptomycin, and cycloserine. 2, 3
• Continue non-hepatotoxic drugs (ethambutol 15-20 mg/kg daily, streptomycin, fluoroquinolones) during the acute phase if the patient has infectious TB or is clinically unwell. 7

Specific Alternative Regimens

• If rifampicin must be excluded: treat with isoniazid, ethambutol, and a fluoroquinolone for at least 12 months. 7
• If isoniazid must be excluded: treat with rifampicin and ethambutol for 9 months, supplemented with a fluoroquinolone for the initial 2 months. 7
• If pyrazinamide must be excluded: treat with rifampicin and isoniazid for 9 months total, supplemented with ethambutol for the initial 2 months. 7

Desensitization Protocols (Controversial)

When to Consider Desensitization

• Desensitization may be attempted in select cases where alternative regimens are inadequate, but this carries significant risk and should only be performed under expert TB consultation with close monitoring. 5
• A recent protocol from Peru reported 72.2% success rate with desensitization/re-desensitization, but this requires specialized expertise and infrastructure. 5
• Skin testing can be performed to identify the specific culprit drug, though discrepancies between skin tests and clinical reactions have been reported. 4

Contraindications to Desensitization

• Never attempt desensitization in patients who experienced multi-organ failure, severe hepatotoxicity, or life-threatening manifestations of DRESS. 3, 6
• The mortality rate of anti-TB DRESS is approximately 8%, with deaths primarily occurring in patients with severe liver involvement. 2, 3

Long-Term Monitoring and Follow-Up

Resolution Timeline

• Expect cutaneous eruptions to resolve within 4 weeks of drug discontinuation and corticosteroid initiation. 2
• Eosinophilia and transaminitis may continue to worsen initially despite drug discontinuation, necessitating continued corticosteroid therapy. 2
• Follow-up at 1 month to confirm complete resolution of rash and normalization of laboratory values. 2

Consultation Requirements

• Consult TB experts for all cases of anti-TB DRESS to optimize second-line treatment regimens and ensure adequate TB control while managing the drug reaction. 7, 3
• Expert consultation is mandatory when treatment options are limited or when considering desensitization protocols. 7

Critical Pitfalls to Avoid

• Do not prematurely reintroduce anti-TB drugs before complete resolution of DRESS (minimum 4 weeks), as this can trigger severe recurrence. 2, 4
• Never add a single drug to a failing regimen, as this creates monotherapy and risks developing drug resistance. 7
• Do not use prophylactic corticosteroids or antihistamines when initiating anti-TB therapy, as this has not proven effective and may mask early DRESS symptoms. 1
• Avoid concurrent hepatotoxic medications (acetaminophen, alcohol, lipid-lowering agents) during TB treatment in high-risk patients. 7