Aseptic meningitis, hepatitis and cholestasis induced by trimethoprim/ sulfamethoxazole: A case report

This is the first report of a young patient with both aseptic meningitis and drug-induced liver injury caused by TMP/SMX. Drug-induced aseptic meningitis and cholestatic hepatitis constitute a considerable diagnostic challenge to clinicians. In addition to a thorough evaluation of infectious causes, clinicians should be aware of drug-induced aseptic meningitis and cholestatic hepatitis.

A 2.5-year-old girl was admitted to hospital due to suspicion of meningitis.
  • Intravenous administration of aciclovir and trimethoprim-sulfamethoxazole (TMP/SMX)prophylaxis
  • CSF culture and PCR on mumps virus, enterovirus, parechovirus, herpes simplex and varicella zoster virus; negative
  • Blood culture; negative
  • Antinuclear antibodies; negative


  • Conjugated hyperbilirubinaemia: total 76µmol/L; conjugated bilirubin: 74 µmol/L; AST: 332 U/L; ALT: 358 U/L
  • Ultrasound of liver and gallbladder; normal
  • Serology on EBV, CMV, Hepatitis A, B, C and E, Bartonella Henselae, Borrelia Burgdoferi; negative
  • IgA, IgG and IgM; normal
  • ASMA, AMA, ANCA, anti-LKM-1, anti-DNA antibodies; negative
  • Drug induced aseptic meningitis is a diagnosis of exclusion, made after infectious causes have been ruled out. Many cases remain unrecognized, since it constitutes a diagnostic challenge.
  • TMP/SMX is the most commonly observed antimicrobial drug causing aseptic meningitis.
  • Two possible pathogenic mechanism proposed are:
    • Drug would form a hapten conjugation with a CSF or meningeal protein, being a type II or type III hypersensitivity reaction

    • Type IV hypersensitivity, using the T-cell by reversibly binding to the Human Leukocyte Antigen (HLA) on its receptor.

Clinicians should be aware of the possible severe consequences of (prolonged) TMP/SMX use and have a high index of suspicion of drug-induced aseptic meningitis in cases with symptoms of meningitis and negative CSF culture, especially in the combination with liver injury.


WBC: White blood cells; CRP: C-reactive protein; CSF: Cerebrospinal fluid; PCR: Polymerase chain reaction; AST: Aspartate transaminase; ALT: Alanine transaminase; EBV: Epstein-Barr virus; CMV:  Cytomegalovirus; ASMA: Anti-smooth muscle antibody; AMA: Antimitochondrial antibody; ANCA: Antineutrophil cytoplasmic antibodies; LKM-1: Liver kidney microsome type 1 antibody; TMP/SMX: Trimethoprim-sulfamethoxazole

    1.    Van Asperdt JAA, De Moor RA. Aseptic meningitis, hepatitis and cholestasis induced by trimethoprim/sulfamethoxazole: a case report. BMC Pediatrics.
    2021;21:345. Available at:

MAT-IN-2201306 V1.0 06/22