A 9-year-old male, Hispanic, presented to the pediatric emergency department with abdominal pain and fever of 14 days of evolution. Maternal family contact 5 weeks ago RT-PCR SARS-CoV-2 positive and the patient's serological test for SARS-CoV-2 antibodies at hospital admission was positive (IgG). He had no previous hospitalizations, no reports of illnesses or surgical interventions and complete immunizations. Vital functions on admission were heart rate 120 beats/minute, respiratory rate 22/minute, temperature 38°C, weight 30 kg, height 128 cm. On clinical examination, there was the pallor of the skin and mucous membranes, chapped lips, macular erythematous lesions symmetrically distributed on the neck, forehead, and groin area. The abdomen was painful to palpation in the mesogastrium. Her labs showed hemoglobin 11 g/dL, leukocytes 18.9 x 103/uL, platelets 528 x 103/uL, C-reactive protein 4.6 mg/dL, normal coagulation profile, fibrinogen 488 mg/dL, lactate dehydrogenase 1317 U/L, D-dimer 1.6 mg/L, complement C3 and C4 normal, urea 18 mg/dL, creatinine 0.4 mg/dL, albumin 3.7 g/dL, triglycerides 130 mg/dL, creatine kinase 25 mg/dL, ferritin 538 ng/mL, serum electrolytes with normal values and the urine test showed hematuria. Abdominal ultrasound showed hepatomegaly and echocardiography without alterations. He received exogenous human immunoglobulin 2gr/kg/day, acetylsalicylic acid 3mg/kg/day for 7 days, prednisone 2mg/kg/day for 5 days for the probable multisystemic inflammatory syndrome. On the second day of treatment, she was afebrile and on the fourth day the erythematous lesions decreased, there was an absence of hematuria and a decrease in acute phase reactants, with the indication for discharge home. Five days after discharge, abdominal pain and fever persisted, hemoglobin 11.3 g/dL, leukocytes 10 x 103/uL, eosinophils 1305/uL, absolute neutrophil count 5321/uL, lymphocytes 2710/uL, platelets 606 x 103/uL, c-reactive protein 8.2 mg/dL, fibrinogen 664 mg/dL, dimer D 2 ug/mL, ferritin 1030 ng/mL, lactate dehydrogenase 890 U/L, coagulation profile, urea, creatinine, and serum electrolytes were normal. Immunological tests were performed: negative antinuclear antibodies (ANA), negative anti-dsDNA, negative anti-neutrophil cytoplasmic antibodies (ANCA), negative anti-cyclic citrullinated peptide antibodies (anti-CCP), negative rheumatoid factor, negative lupus antibody and negative antiphospholipid profile, negative IgG antibodies against Toxocara. He received treatment with methylprednisolone at a dose of 2mg/kg/day for 7 days and then at a dose of 30mg/kg for 3 days, then prednisone 2mg/kg/day for 15 days. During his hospitalization he presented a decrease of abdominal pain and absence of fever, being discharged with the indication of controls by rheumatology.
He was readmitted to the pediatric emergency room 4 months later, with 12 days of evolution characterized by fever, abdominal pain, and generalized edema. On admission, he presented a heart rate of 140 beats/minute, respiratory rate 29/minute, blood pressure (p90-95). He presented edema of the face, genitals, hands, and feet. The skin was cold, turgid with erythematous macular lesions of urticariform appearance (positive dermographism) associated with diffuse hematic crusts and fine desquamation on face, neck, thorax, arms, and legs. Examinations found hemoglobin 11.6 gr/dL; platelet count 170 x 103/uL; prothrombin time (PT) 13.1 sec, INR 1.1; activated partial thromboplastin time (aPTT) 34 sec, fibrinogen 432 mg/dL, urea 16 mg/dL, creatinine 0.34 mg/dL, D-dimer 4.32 mg/L, lactate dehydrogenase 1862 U/L, serum calcium 7.2mg/dL, complement C3 120mg/dL, C4 28mg/dL, and hemoglobinuria. He was transferred to the dermatology department due to the dermatological lesions described. Three days later the dermal lesions increased (Fig. 1), a skin biopsy of the lesions was performed describing acute spongiotic dermatitis with intraepidermal vesicles and numerous necrotic keratinocytes in the epidermis, associated with superficial and deep perivascular and perianexial inflammatory infiltrate with numerous eosinophils and extravasation of red cells. The histochemical study with Periodic Acid Schiff and Alcian Blue was negative. He presented oligoanuria and generalized tonic-clonic seizure associated with desaturation 86% (fiO2 21%) on three occasions. Due to unstable hemodynamic compromise, it was decided to perform endotracheal intubation and transfer him to the Pediatric Intensive Care Unit (PICU) for ventilatory and hemodynamic management. In PICU hemoglobin 10.6 g/dl, schistocytes 6+/field (blood), positive direct coombs test, leukocytes 13.4 x 103/uL, platelets 19 x103/uL, haptoglobin not detectable, triglycerides 280 mg/dL, ferritin 3442 ng/mL, lactate dehydrogenase 1862 U/L, D-dimer 4 mg/L, complement C3 120 mg/dL and C4 28mg/dL, creatinine 1,23 mg/dL), creatine kinase 248mg/dL, erythrocyte sedimentation rate 19 sec and ADAMTS13 activity in 54% (RV: 40–130%) after transfusion support of blood products. Flow cytometry showed decreased T lymphocytes, CD4 + lymphocytes, CD8 + lymphocytes, increased CD4/CD8 ratio for age, and decreased NK cell count. The Viral load for Epstein Barr virus, Cytomegalovirus, and Parvovirus B19 was negative.
Renal ultrasound showed left kidney with asymmetry concerning the contralateral one and in the Doppler study, there was a decrease in the wave depth suggesting left renal hypoperfusion. With the clinical and laboratory manifestations described, the patient was diagnosed with TTP. The PLASMIC score was 7 (Table 1). He received fresh frozen plasma, renal replacement therapy, methylprednisolone cycles, human immunoglobulin, and rituximab (Table 1). Due to the persistence of severe thrombocytopenia, it was decided to initiate PEX receiving 14 sessions, before the plasma exchange, she received platelet transfusion to compensate for the platelet deficit, with poor response. During his stay in the PICU, he presented deterioration of the sensorium and intracerebral hemorrhage (after one month of the last PEX session) was found in the tomography. The patient had an unfavorable evolution and fatal outcome in the second month of hospitalization. The genetic panel of sequence analysis and deletion/duplication test of 13 genes (ADAMTS13, C3, CD46, CD55, CD59, CFB, CFH, CFI, DGKE, INF2, MMACHC, PLG, THBD) for atypical hemolytic uremic syndrome and thrombotic microangiopathy were negative.