Case Quiz (August 2017)
A 12-year-old boy with Sickle cell anemia (SCA) was referred with suspected nephrotic syndrome. SCA was diagnosed when he was 9 months old. Since he was 3 years old, the patient has suffered from frequent vaso-occlusive crises causing rapid onset pain episodes, accompanied by local tenderness and swelling mostly over the lumbosacral spine, femur, iliac crest, tibia, and shoulder. The patient has never experienced recurrent or acute abdominal pain indistinguishable from acute surgical abdomen, chest pain, or arthritis. He had no family history of familial Mediterranean fever.
Hypertransfusion was started when he was 2 years old. The baseline Hb prior to hypertransfusion was 5.0 g/dl. Transfusions were given frequently for hyperhemolytic reactions due to alloimmunization, but occasionally for unremitting vaso-occlusive crises.
When he was 12 years old, the frequency of blood transfusion increased to every 20 days because of hyperhemolytic reactions, so splenectomy and cholecystectomy for cholelithiasis were done. He was immunized against pneumococcus and penicillin for prophylaxis was also given post-splenectomy. However, the frequency of sickle cell crises did not decrease. After splenectomy, no transfusion was needed.
On admission, the patient was pale and anxious and physical examination revealed the following: BP 110/80 mmHg, HR 96/min, RR 22/ min, and temperature 36.8°C. The liver tip was palpated 3 cm below the right costal margin. A transverse incision scar of the previous laparotomy was noticed over the entire abdomen. There were pitting edemas on the lower extremities. Periorbital edema and ascites were noted.
Results of laboratory investigations were as follows: urinalysis showed 4+ proteinuria, 3+ blood, and a 24-h sample proteinuria 1,892 mg/day (67 mg/m2 per h). Urine osmolarity was 409 Osm/kg, Hb 10.2 g/dl, Hct 32.1%, platelet count (Plt) 908,000/mm3, white blood cell count (WBC) 19,500/mm3, MCV 79.5 fl, ferritin 4,855 ng/ml, and ESR 92 mm/h. Direct Coomb’s test was positive. Serum amyloid A (SAA) level was 2.78 mg/l (reference range: 0–6.4 mg/l). Molecular analysis revealed that the patient had HbSS. Serum total cholesterol was 376 μg/dl, triglycerides 182 μg/dl, total protein 4.2 g/dl, and albumin 2.0 g/dl. Serum electrolytes, liver enzymes, C3 and C4 levels were within the normal range. Antinuclear antibody and anti-double stranded DNA were negative. Hepatitis B surface antigen (HBsAg) was negative, anti-hepatitis B surface antibody (HBsAb) 1,631 IU/ml, anti-hepatitis A virus (HAV) IgG 50 IU/ml, and anti-HAV IgM was negative. Echocardiography and telecardiogram were normal.
Renal biopsy was diagnostic.
Case Answer (August 2017)
Amyloidosis in patients with sickle cell anemia.
Membranoproliferative glomerulonephritis and focal segmental glomerulosclerosis accounted for most cases of nephrotic syndrome in SCA patients. However,
Familial Mediterranean fever is the most common cause of secondary amyloidosis in childhood. On the other hand, our patient has never suffered from acute surgical abdomen-like pain, recurrent fever attacks, peritonitis, synovitis or pleuritis, or erysipelas-like erythema, but bone pain over the lumbosacral spine and lower extremities. He does not have a family history of FMF or amyloidosis and any detected FMF mutation.
Possible explanations for Amyloidosis in patient with SCA:
1. frequent sickle cell crises are likely to provoke recurrent acute inflammation, leading to repeated stimulation of acute phase responses (serum amyloid A) and development of a predisposition to generation and deposition of amyloid protein.
2. Iron overload or HTF protocol might also have effects on the deposition of AA amyloid in this case.
