What is the management approach for an adult patient with a history of tuberculosis (TB) who presents with septic and distributive shock secondary to erythroderma and acute liver failure due to anti-tuberculosis (anti-TB) medications?

Management of Septic and Distributive Shock Secondary to Anti-TB Drug-Induced Erythroderma and Acute Liver Failure

Immediately discontinue all hepatotoxic anti-TB drugs (isoniazid, rifampicin, and pyrazinamide) and initiate aggressive hemodynamic resuscitation with vasopressors while transitioning to non-hepatotoxic TB therapy with ethambutol plus a fluoroquinolone and/or injectable agent.

Immediate Resuscitation and Drug Discontinuation

Stop all hepatotoxic TB medications immediately when acute liver failure develops, as continuing these drugs carries devastating mortality risk without liver transplantation 1, 2. The combination of isoniazid, rifampicin, and pyrazinamide exposes patients to fulminant hepatic failure, which is often fatal 3, 2.

Hemodynamic Support for Septic Shock

• Initiate epinephrine infusion at 0.05-2 mcg/kg/min titrated to achieve adequate mean arterial pressure, adjusting every 10-15 minutes in increments of 0.05-0.2 mcg/kg/min 4
• Dilute 1 mg epinephrine in 1,000 mL of 5% dextrose to produce 1 mcg/mL concentration, administered through a large vein 4
• After hemodynamic stabilization, wean incrementally over 12-24 hours 4

Critical Pitfall

The presence of both erythroderma and acute liver failure suggests severe drug hypersensitivity reaction (DRESS syndrome), which carries high mortality. Do not attempt sequential drug reintroduction in this acute setting—this protocol is only for stable patients after complete recovery 1.

Transition to Non-Hepatotoxic TB Regimen

Switch immediately to ethambutol plus a fluoroquinolone (levofloxacin or moxifloxacin) and/or an injectable agent (streptomycin, amikacin, kanamycin, or capreomycin) to maintain TB treatment while avoiding further hepatotoxicity 5, 1.

• Use at least two to three new drugs to prevent acquired resistance—never add a single drug to a failing or interrupted regimen 5
• For seriously ill patients with infectious TB, continue treatment with non-hepatotoxic alternatives rather than stopping all TB therapy 1
• Plan for 12-18 months of treatment when using regimens without both isoniazid and pyrazinamide 1

Monitoring Requirements

• Monitor renal function closely when using injectable agents or ethambutol, as these are renally excreted and toxic in renal insufficiency 5, 6
• Assess visual acuity before and during ethambutol therapy; patients must stop immediately if visual symptoms occur 7
• Check serum drug levels for aminoglycosides to avoid toxicity, keeping levels below 4 mg/L 5

Management of Acute Liver Failure

Consider urgent liver transplantation consultation if the patient develops fulminant hepatic failure with progressive coagulopathy, encephalopathy, or rising bilirubin despite drug discontinuation 3. Literature review shows that in anti-TB drug-induced fulminant hepatic failure, discontinuation of toxic drugs and orthotopic liver transplantation are the definitive treatments 3.

• Exclude other causes of liver injury including viral hepatitis and biliary tract disease before attributing all hepatotoxicity to TB drugs 1
• Monitor for irreversible hepatic damage even after transplantation, as some patients experience continued deterioration 3

Management of Erythroderma

Address the distributive shock component from erythroderma with:

• Aggressive fluid resuscitation and temperature regulation
• Skin barrier protection to prevent secondary infection
• High-protein nutrition to compensate for protein loss through damaged skin

Long-Term TB Treatment Strategy

Do not attempt to reintroduce hepatotoxic drugs (isoniazid, rifampicin, pyrazinamide) in patients who developed fulminant hepatic failure, as recurrence carries extremely poor prognosis 1, 2.

• Continue the non-hepatotoxic regimen (ethambutol, fluoroquinolone, injectable agent) for extended duration of 12-18 months depending on disease extent 1
• Ensure directly observed therapy (DOT) to maximize adherence with the prolonged alternative regimen 5
• Obtain drug susceptibility testing to guide optimal drug selection 5

Critical Consideration

The mortality risk from untreated TB must be balanced against the risk of continued hepatotoxic therapy. In this case of established fulminant hepatic failure with septic shock, the hepatotoxic drugs pose immediate life-threatening risk and must be stopped, while TB treatment continues with safer alternatives 1, 3, 2.