Fatal acute hepatitis after sequential treatment with levofloxacin, doxycycline, and naproxen in a patient presenting with acute Mycoplasma pneumoniae infection.
BACKGROUND
The diagnosis of drug-induced liver injury relies on comprehensive clinical assessments due to the absence of an established biomarker or pathognomonic features of liver histology. However, prompt recognition of a culprit drug as the cause of liver injury is the most important aspect in the management of hepatotoxicity.


METHODS
A 63-year-old white male (85 kg) was admitted because of community-acquired pneumonia with associated pericarditis and subclinical hepatitis, subsequently related to acute Mycoplasma pneumoniae infection (diagnostic positive immuno-globulin M enzyme immunoassay, on hospital days 5 and 20). The patient had received cisplatin and radiotherapy from March to May 2006, as treatment for pharyngolaryngeal squamous cell carcinoma T3N0M0 without subsequent evidence of localized or meta-static recurrent disease (last oncologic consultation, May 17, 2007). He reported alcohol ingestion until March 2006 but no known liver disease, blood transfusion, or exposure to mushrooms or industrial cleaning solvents. Results of serologic tests for viral and nonviral infectious hepatitis, iron and copper studies, and tests for autoantibodies were normal or negative. The patient became initially asymptomatic and fever disappeared following sequential treatment with levo-floxacin (500 mg BID), doxycycline (100 mg BID), and naproxen (500 mg TID). However, on hospital day 10 jaundice and a significant elevation (alanine aminotransferase, 1577 U/L; aspartate amino-transferase, 1754 U/L; alkaline phosphatase, 189 U/L) of serum transaminases appeared. Despite the discontinuation of all medication, the patient gradually deteriorated and died 27 days after admission due to acute fulminant hepatic failure. Autopsy revealed massive hepatic necrosis, inflammatory changes with presence of eosinophils, and cholestasis. An objective causality assessment scale (Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale) suggested that each of the 3 drugs could "probably" (score = 6) be related to the patient's fulminant hepatitis. The Naranjo Adverse Drug Reactions Probability Scale assessment for the same drugs indicated a "possible" causal relation (score = 2).


CONCLUSIONS
We report a case of lethal hepatitis possibly/probably associated with levofloxacin, doxy-cycline, and naproxen in a patient with acute M pneumoniae infection.
Carrascosa
Miguel F
MF
Internal Medicine Department, Hospital of Laredo, Cantabria, Spain. mcarrascosa@hlrd.scsalud.es
Lucena
María Isabel
MI
Andrade
Raúl J
RJ
Caviedes
José Ramón S
JR
Lavín
Antonio C
AC
Mones
Juan C
JC
Rivero
Andrea P
AP
Serrano
Vicente B
VB
D000208:Acute Disease; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D004318:Doxycycline / Q000009:adverse effects* / Q000627:therapeutic use; D017809:Fatal Outcome; D006505:Hepatitis / Q000150:complications; D006801:Humans; D064704:Levofloxacin; D017114:Liver Failure, Acute / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000009:adverse effects* / Q000627:therapeutic use; D015242:Ofloxacin / Q000009:adverse effects* / Q000627:therapeutic use; D010493:Pericarditis / Q000150:complications; D011019:Pneumonia, Mycoplasma / Q000150:complications / Q000188:drug therapy*
D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D009288:Naproxen; D064704:Levofloxacin; D015242:Ofloxacin; D004318:Doxycycline