Case

A 3-year-old girl presented to the Emergency Department with the chief complaint of brown macrohematuria for 2 weeks. Her past medical history revealed scarlet fever and mild upper respiratory tract infections 2 months earlier, and no recent trauma or travel was reported. She had no familiarity for rheumatological disease, and her parents were unrelated. The first clinical examination was unremarkable, including the absence of fever, arthralgia, or skin rash. The patient presented with normal growth and development and up-to-date vaccinations. Abdominal ultrasound reported bilateral kidney hyperechogenicity with a preserved cortico-medullary differentiation, and chest radiography was normal. Initial blood and urinary tests are summarized in Table 1 and mainly revealed a non-hemolytic anemia associated with thrombocytopenia, positive direct Coombs test, hypergammaglobulinemia, and high ESR:CRP ratio. Kidney function was normal, and urinalysis revealed hematuria associated with proteinuria. Furthermore, a persistent activation of the classical complement pathway was noticed in association with a low CH50 and the presence of anti-C1q and anti-C3b antibodies.

Table 1 Laboratory tests at referral

After 3 days, the patient presented malar rash, palatal petechiae, and peripheral edema associated with a rapid worsening of anemia and thrombocytopenia.

Autoimmune screen revealed high titer of ANA, anti-dsDNA, ENA, and p-ANCA with anti-platelet, anti-beta2GP1, and anti-phosphatidylserine antibodies associated with LAC positivity but no anti-complement factor B (CFB) and anti-complement factor H (CFH) autoantibodies.

Questions

  1. 1.

    Which major diagnoses must be considered in this context?

  2. 2.

    What further investigations would you perform for the work-up of your main hypothesis?

  3. 3.

    If the main hypothesis is confirmed, which treatment regimen could you consider?