Case Quiz (June 2019)
A 4-year-old boy, who presented with fever of 3 days’ duration and an episode of generalized tonic-clonic seizure that lasted approximately 4 minutes. He had post-ictal drowsiness for 12 minutes. There were no other associated symptoms. Six weeks prior to the presentation he was brought to a general practitioner for fever and skin rashes over his face and upper limbs. He was treated with orally administered paracetamol and cefuroxime axetil. Subsequently, the fever resolved but the skin rashes persisted. On admission, he was diagnosed as having simple febrile seizure and eczema herpeticum. At 13 months of age he was diagnosed as having single gene deletion α-thalassemia trait (αα/ −α4.2), and remained asymptomatic since diagnosis. His parents were non-consanguineous. His mother is 35-years old and has α-thalassemia trait. There was history of right ear infection a year before and that had resolved with treatment. He has history of allergy and intermittently was on orally administered desloratadine. There was no other significant past medical history, and he was not on any other medicine prior to the recent presentation. His immunization status was up to date, and developmentally he was normal.
On admission, a physical examination revealed Glasgow Coma Scale of 15/15, blood pressure 95/50 mmHg, pulse rate 120/minute, and temperature 38.1 °C. He was febrile, pale, with no jaundice, and he had “shotty” cervical lymph nodes. The results of examinations of his throat, tonsils, and ears were normal. Some maculopapular rashes with scaly and crusted areas were noted on his left cheek, both arms and knees, and trunk area. There was hepatosplenomegaly of 4 cm and 3 cm, respectively. There were no bleeding tendencies or neurologic deficit noted.
Laboratory findings showed hypochromic microcytic anemia, thrombocytopenia, reticulocytosis, raised serum LDH and impaired kidney function tests.A peripheral blood smear showed significant fragmented red cells, spherocytes, and polychromasia. Serial investigation results showed persistent anemia and thrombocytopenia. Direct and indirect Coombs tests were negative. Tests for liver functions and coagulation profile were normal. Tests for Epstein–Barr virus IgM was negative while Epstein–Barr virus IgG was positive. Immunological profile revealed: positive ANA speckled pattern, negative anti-double-stranded DNA, negative anti cardiolipin IgM, normal C3 and C4, normal factor H, D and B and high ESR (115 mm/hour) .
A diagnostic test was done.
Case Answer (June 2019)
Acquired TTP with secondary ADAMTS13 deficiency. ADAMTS13 assay confirmed the diagnosis in this very young boy with microangiopathic hemolytic anemia (MAHA) and elevated LDH.TTP is diagnosed when the classic pentad of fever, MAHA, thrombocytopenia, neurologic manifestation, and elevated creatinine are present. However, not all signs are observed at initial presentation and the disease varies in severity.
In acquired TTP, antibodies toward ADAMTS13 may develop idiopathically or in association with another autoimmune condition or connective tissue disease
TPlasma exchange and immunosuprressive therapy are the mainstay of treatment for acquired TTP, to remove the autoantibody against ADAMTS13 and the ultra-large vWF, while replacing the missing protease in the patient
