R. P. Warrier

Poland's syndrome and Wilms tumor: an unusual association.

Polands syndrome, a rare congenital disorder with pectoralis muscular girdle defect, have been reported in association with lymphoreticular malignancies in the past. Childhood solid tumors in association with this congenital anomaly have not been reported so far. We describe this rare association of Polands syndrome and Wilms tumor. Due to the possibility of increased risk of leukemogenesis in patients with Polands syndrome, chemo-radiation therapy of Wilms tumor in our patient may increase the risk of secondary leukemia. Therapeutic modification of primary cancer in these patients may be necessary with careful long-term follow-up for early detection and treatment of secondary cancer.

Focal Segmental Glomerulosclerosis in Children With Acute Lymphocytic Leukemia: Case Reports and Review of Literature

Purpose: To report the occurrence of focal segmental glomerulosclerosis (FSGS) in children with acute lymphocytic leukemia (ALL), discuss pathogenesis and problems in management. Patients and Methods: Progressive renal dysfunction developed in two adolescent black girls with high-risk ALL who underwent renal biopsies that were consistent with FSGS. In both patients, no known etiologic factors, such as systemic lupus erythematosus. poststreptococcal glomerulonephritis. sickle cell anemia, or acquired immunodeficiency syndrome, were evident. FSGS induced by Adriamycin (Pharmacia & Upjohn. Columbus. OH) has been observed experimentally in rats. The patients had received anthracyclines and methotrexate. a known nephrotoxic chemotherapeutic agent. Results: One patient progressed to chronic renal failure and required prolonged dialysis followed by renal transplantation, though the leukemia remained in remission. The other patient is also in remission and on maintenance treatment for leukemia. She has persistent proteinuria and is currently undergoing a trial of high-dose steroid therapy. Conclusion: The combination of FSGS with leukemia poses a management challenge to the clinician in terms of further treatment with potentially nephrotoxic drugs, complications of nephrotic syndrome (including infections), and timing of renal transplantation. Future studies should address whether FSGS represents a glomerular response to anthracycline-induced injury in susceptible black persons.

Effects of iron deficiency on the secretion of interleukin‐10 by mitogen‐activated and non‐activated murine spleen cells

Interleukin (IL)‐10 plays crucial regulatory roles in immune responses by inhibiting the secretion of several cytokines (IL‐2, IL‐12, interferon‐gamma (IFN‐γ)) and lymphocyte proliferation. Iron deficiency, a public health problem for children, alters these immune responses. To determine whether these changes are related to altered IL‐10 secretion, we measured IL‐10 in 24 and 48 h supernatant of spleen cell cultures from iron deficient (ID), control (C), pairfed (PF), and ID mice fed the control diet (iron repletion) for 3 (R3) and 14 (R14) days (d, n = 12/group). Mean levels of hemoglobin, hematocrit, and liver iron stores varied as follows: C ≈ PF ≈ R14 > R3 > ID (P < 0.01). Mean baseline IL‐10 levels of ID mice tended to be higher than those of other groups (P > 0.05, ANOVA). Mean IL‐10 levels secreted by concanavalin A (Con A) and antibody raised against cluster of differentiation molecule 3 (anti‐CD3)‐treated cells (±background) were lower in ID than in C (48 h) and iron replete mice (P < 0.05). Underfeeding also reduced IL‐10 secretion by anti‐CD3‐treated cells (48 h, P < 0.05). Lymphocyte proliferative responses to anti‐CD3 ± anti‐CD28 antibodies were lower in ID than in C and PF mice, and they were corrected by iron repletion (P < 0.05). IL‐10 levels negatively correlated with indicators of iron status (r ≤ −0.285) and lymphocyte proliferation (r ≤ −0.379 [r ≤ −0.743 for ID mice]), but positively correlated with IFN‐γ levels (r ≤ 0.47; P < 0.05). Data suggest that iron deficiency has a generalized deleterious effect on cells that secrete both cytokines. Reduced IL‐10 secretion by activated cells does not overcome the inhibition of lymphocyte proliferation due to other factors of T cell activation that are regulated by iron. J. Cell. Biochem. 90: 278–286, 2003.

Immunotactoid glomerulopathy in sickle cell anemia

Abstract A 12-year-old African American male with homozygous sickle cell disease (SCD) was admitted with insidious onset of periorbital and scrotal edema. The initial evaluation failed to reveal any underlying monoclonal gammopathy, or cryoglobulinemia, or other systemic causes for the renal disease. A percutaneous renal biopsy was consistent with immunotactoid glomerulopathy (ITG), which is rare in children and is characterized histologically by fibrillar deposits in the glomeruli. Children can present with symptoms of nephrotic syndrome and progress to end stage renal disease. Our patient was treated with an ACE inhibitor and is currently free of edema and with normal renal function on follow-up at 1 year. Immunotactoid glomerulopathy should be considered in the differential diagnosis of nephrotic syndrome in children with sickle cell disease. Renal biopsy is indicated in children with sickle cell disease and nephrotic syndrome and ITG should be considered as potential cause. Although there is no effective treatment for this condition, ACE inhibitors can decrease the proteinuria and possibly delay the progression to end stage renal disease. The side effects related to the use of ACE inhibitors should be monitored. These include renal impairment, hyperkalemia, anemia, neutropenia, and angioedema. Since we have a short follow-up in our patient, the role and safety of ACE inhibitors in the management of ITG need further evaluation.

Acute Perforative Appendicitis During Preoperative Chemotherapy for Wilms Tumor

Infectious complications are not uncommon in children undergoing treatment for cancer. Abdominal pain, especially right lower quadrant pain secondary to appendiceal and cecal inflammation, is a major concern in immunocompromised hosts and a potential source of sepsis. The authors report the case of a child who developed acute perforative appendicitis requiring appendectomy while on preoperative chemotherapy for Wilms tumor, stage IV, favorable histology. Problems related to diagnosis and management of acute abdominal pain and infection in an immunocompromised child with an abdominal mass are discussed along with a review of the literature.

Acute lymphocytic leukemia after fulminant varicella associated with severe neutropenia.

Acute lymphocytic leukemia developed within 3 weeks after a fulminant case of varicella complicated by pneumococcal sepsis and severe bone marrow suppression in a child treated with filgrastim (human granulocyte colony-stimulating factor).

Acute Onset of Anemia After IV Immunoglobulin

A previously healthy 6-year-old boy was diagnosed to have bacterial meningitis and was treated for 6 days with intravenous (IV) ceftriaxone. His spinal fluid culture was negative. He developed difficulty in walking and vision loss and was diagnosed to have optic neuritis by the ophthalmologist. Consults by a neurologist followed by repeat spinal tap were consistent with a demyelinating process. Magnetic resonance imaging revealed multifocal areas of subcortical patchy T2/FLAIR signal hyperintensity with associated enhancement of the optic nerves. An electroencephalogram showed generalized slowing, indicative of diffuse encephalopathy. He was diagnosed to have acute disseminated encephalomyelitis (ADEM) and started on high-dose methylprednisolone burst with taper and IV immunoglobulin (IV IgG) 2 g/kg over 2 days. Within 48 hours after the infusion, his urine became very dark, and he appeared pale but not jaundiced. He continued to be active, with no evidence of impending failure. He had developed a grade 2/6 ejection systolic murmur best heard in the left second parasternal space. The liver was palpable 2 cm below the costal margin but nontender. The spleen was not palpable. He did not have joint swelling, skin rash, or edema. As regards to the laboratory investigations, hemoglobin (Hb) was noted to have decreased from 11.9 g/dl at admission 2 days earlier to 7.9 g/dl. Reticulocyte count was 2.6%, and mean corpuscular volume, mean corpuscular hemoglobin concentraction and red blood cell distribution width were normal. Peripheral smear showed normocytic, normochromic anemia with occasional spherocytes and polychromasia, indicating the possibility of hemolysis with an active marrow. Urinalysis was negative for red blood cells (RBCs) and blood. A direct Coombs was weakly reactive. The antibody was eluted from the RBCs and identified as passive anti-IgG anti-A and anti-B. The patient’s blood group was AB, and the indirect Coombs was negative. The specific batch of IV IgG was checked and revealed high anti-A and anti-B titers.

Leukocytosis in an Infant With Down Syndrome

A newborn female with Down syndrome initially presented to the neonatal intensive care unit with difficulty feeding, failure to thrive, and respiratory difficulty that required oxygen supplementation. She also had atrioventricular canal defect that was diagnosed prenatally. On physical examination, she had hepatosplenomegaly, as well as dysmorphic features typical of Down syndrome phenotype. Hemoglobin was 16.9, platelet count was 276 000, and white blood cells (WBC) count was 62 400 with the smear showing myelocytes, promyelocytes, and myeloblasts. WBC went as high as 80 000 with blast count as high as 44% and platelets as high as 771 000. Subsequent peripheral smear showed blasts, promyelocytes, metamyelocytes, and macrocytosis of red blood cells with normal platelets. The patient’s liver enzymes, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase were mildly elevated. Abdominal ultrasound revealed mild hepatosplenomegaly, minimal ascites, and gallbladder wall thickening. Further investigation with genetic and molecular biologic workup confirmed trisomy 21 as a somatic mutation and revealed GATA-1 mutation. The patient was negative for JAK2 V617 mutation. On flow cytometry, blasts were positive for CD34, CD117, HLADR, CD4, CD71, and CD9. Markers for megakaryocytic differentiation, CD41 and CD61, were partially expressed. Fluorescence in situ hybridization studies were inconclusive and attempts at obtaining additional genetic markers, specifically RUNX1, were unsuccessful.

Nephroblastoma and end-stage renal failure with bilateral cystic kidneys.

A child of 10 years 5 months presenting with chronic renal failure had bilateral cystic kidneys. Biopsy of a right lower-pole solid mass revealed nephroblastoma. At bilateral nephrectomy, both kidneys were both replaced by variable-sized cysts with a unifocal nephroblastoma on the right. Renal failure with nephroblastoma is uncommon and is usually either a manifestation of the Drash syndrome or a complication of chemotherapy. The need to assess both kidneys in a child with any other renal abnormality in addition to a renal mass should always be considered.