S KUO1, A GRAVER1, G KIRKLAND1, R YU1
1 Royal Hobart Hospital, Hobart, Tasmania
Background: Thrombotic microangiopathy (TMA) can result from multiple pathologies including thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome (HUS). Autoimmune diseases such as Systemic Lupus Erythematosus (SLE) can cause secondary HUS. Eculizumab (anti-C5 monoclonal antibody) is approved for treatment of atypical HUS (aHUS) and has been reported as treatment for TMA secondary to SLE.
Case Report: A 66-year-old female presented with new onset congestive cardiac failure secondary to malignant hypertension. Abnormal pathology results on initial testing included haemoglobin 94 g/L, platelets 44 /nL, and creatinine 143 µmol/L.
Blood film suggested TMA, prompting plasmapheresis commencement; this was discontinued with confirmation of adequate ADAMTS13 activity (153%). Subsequent testing identified positive anti-antinuclear antibody (640 speckled) and extractable nuclear antigens (anti-SSA and anti-SSB), but negative anti-double stranded DNA. Testing for shiga toxin-producing Escherichia coli was negative. Eculizumab was therefore commenced as treatment for aHUS. Interestingly, C3, and more so C4, were low.
Eculizumab failed to produce any clinical improvement, so a renal biopsy was performed. Light microscopy demonstrated TMA; immunofluorescence was non-specific (positive IgM, IgA, C1q and lambda light chain; negative IgG and kappa light chain) and electron microscopy showed deposits consistent with Lupus nephritis. Treatment was consequently changed to conventional Lupus nephritis therapy, which resulted in rapid achievement and maintenance of clinical remission.
Conclusion: SLE can present as TMA, and should be considered a differential in patients diagnosed with aHUS but unresponsive to Eculizumab. Renal biopsy remains an important diagnostic tool in these patients.