Helen S. Maurer

Epstein-Barr virus-induced diseases in boys with the X-linked lymphoproliferative syndrome (XLP): Update on studies of the registry

Analyses of 100 subjects with the X-linked lymphoproliferative syndrome (XLP) in 25 kindreds revealed four major interrelated phenotypes: infectious mononucleosis, malignant B-cell lymphoma, aplastic anemia, and hypogammaglobulinemia. Eighty-one of the patients died. Two male subjects were asymptomatic but showed immunodeficiency to Epstein-Barr virus (EBV). Seventy-five subjects had the infectious mononucleosis phenotype and concurrently, 17 subjects of this group had aplastic anemia. All subjects with aplastic anemia died within a week. Aplastic anemia did not accompany hypogammaglobulinemia or malignant lymphoma phenotypes. Hypogammaglobulinemia had been detected before infectious mononucleosis in three subjects, after infectious mononucleosis in five subjects, and was not associated with infectious mononucleosis in 11 boys with hypogammaglobulinemia. In nine subjects infectious mononucleosis appeared to have evolved into malignant lymphoma; however, the majority of patients with malignant lymphoma showed no obvious antecedent infectious mononucleosis. One subject had infectious mononucleosis following recurrent malignant lymphoma. Twenty-six of 35 lymphomas were in the terminal ileum. Results of immunologic and virologic studies of 15 survivors revealed combined variable immunodeficiency and deficient antibody responses to EBV-specific antigens. Mothers of boys with XLP exhibited abnormally elevated titers of antibodies of EBV. Subjects of both sexes with phenotypes of XLP should be investigated for immunodeficiency to EBV. Persons with inherited or acquired immunodeficiency may be vulnerable to life-threatening EBV-induced diseases.

Histiocytosis X: A seven-year experience at a children's hospital

Thirty-two patients with histiocytosis X were evaluated and treated at Childrens Memorial Hospital, Chicago, during the years 1978 to 1984. Twelve patients (38%) had solitary or multifocal bone lesions, three (9%) had bone lesions and diabetes insipidus, and seventeen (53%) had cutaneous and/or multisystem involvement. Age at diagnosis ranged from 2 days to 15 years. Fifteen patients were 2 years of age or younger at the time of diagnosis. Sixteen patients (50%) had skin infiltrates, of whom,seven (43%) had cutaneous lesions documented at birth. Cutaneous lesions included vesicopustules, erythematous papules, nodules, eczematous dermatitis, granulomatous ulcerative lesions, petechiae, and hemorrhagic lesions. Xanthomas and nail dystrophy were not observed. The therapeutic regimen chosen was based on extent of involvement and location of infiltrates. Only two of the thirtytwo patients died; both had multisystem disease.Thirty-two patients with histiocytosis X were evaluated and treated at Childrens Memorial Hospital, Chicago, during the years 1978 to 1984. Twelve patients (38%) had solitary or multifocal bone lesions, three (9%) had bone lesions and diabetes insipidus, and seventeen (53%) had cutaneous and/or multisystem involvement. Age at diagnosis ranged from 2 days to 15 years. Fifteen patients were 2 years of age or younger at the time of diagnosis. Sixteen patients (50%) had skin infiltrates, of whom seven (43%) had cutaneous lesions documented at birth. Cutaneous lesions included vesicopustules, erythematous papules, nodules, eczematous dermatitis, granulomatous ulcerative lesions, petechiae, and hemorrhagic lesions. Xanthomas and nail dystrophy were not observed. The therapeutic regimen chosen was based on extent of involvement and location of infiltrates. Only two of the thirty-two patients died; both had multisystem disease.

X-Linked Lymphoproliferative Syndrome Registry report

Immune deficiency, especially to the Epstein-Barr virus, and increased susceptibility to fatal infectious mononucleosis, acquired agammoglobulinemia, and lymphoma are the cardinal features of the X-linked lymphoproliferative syndrome. Since the establishment of the XLP Registry in September, 1978, 59 affected males in seven unrelated kindreds were comprehensively studied. A spectrum of lymphoproliferative phenotypes was observed. Thirty-four patients (57%) died from infectious mononucleosis, eight (14%) had fatal infectious mononucleosis with lymphoma (immunoblastic sarcoma), nine (15%) had depressed immunity following EBV infection, and eight (14%) developed lymphoma. Several patients with XLP lacked EBV antibodies despite infection by EBV. The results of this study suggest that EBV can be an oncogenic agent in patients who are immune deficient with XLP.

Subclassification of Acute Lymphoblastic Leukaemia in Children: Analysis of the Reproducibility of Morphological Criteria and Prognostic Implications

. Stained smears of aspirated bone marrow obtained at time of diagnosis from 223 children with acute leukaemia were reviewed independently by three observers in a double‐blind fashion in order to assess the reproducibility and clinical significance of the French—American—British Cooperative Group Classification. In 170 cases of acute lymphoblastic leukaemia (ALL), triple agreement of 69.4% was reached in the subclassification into L1, L2 and L3 types. The closest degree of agreement between two observers was 86.8%.

A New Familial Disorder with Abnormal Erythrocyte Morphology and Increased Permeability of the Erythrocytes to Sodium and Potassium

Extract: A newborn infant of Philippine parents was found to have a morphological abnormality of his erythrocytes consisting of an elliptical shape of the cells and one or more transverse slitlike areas of decreased density. These changes were also present in erythrocytes of the patients father, a half-sister of the father, and four of the patients six siblings. None of the affected family members had anemia or evidence of abnormal hemolysis, and erythrocyte survival by the radiochromium method was normal in three of the individuals studied. Erythrocytes from the affected family members had an increased degree of autohemolysis after incubation for 48 hr, but this was prevented almost entirely by addition of glucose. Glucose consumption in vitro by erythrocytes of the propositus occurred at a rate approximately 60% greater than that of normal controls. The intracellular sodium concentration of the erythrocytes was not different from that of erythrocytes from normal individuals, but a moderate decrease in intracellular potassium was found. When washed cells were incubated in a glucosefree medium, sodium gain and potassium loss were significantly greater than from cells of normal controls. When compared with normal values, efflux of radiosodium was increased during incubation of cells in glucose-containing medium. Erythrocytes from the affected individuals had decreased osmotic fragility, and osmometric measurements indicated a lesser degree of cell swelling in hypotonic solutions than occurred with cells from normal controls.Speculation: The findings in this family demonstrate that increased erythrocyte cation permeability need not be associated with an accelerated rate of hemolysis. In these individuals the absence of hemolytic disease may reflect a capacity of the erythrocytes to compensate for increased cation permeability by an elevated rate of glycolysis-linked ion transport. This compensatory process would appear to be virtually unaffected by interaction of the erythrocytes of these individuals with the spleen.

H. INFLUENZA B IMMUNIZATION OF CHILDREN WITH SICKLE CELL DISEASES

H. flu B vaccine is recommended for children 1.5-6 yrs with sickle cell anemia but the adequacy of their response is unknown. We immunized 55 children age 1.5-5.6 yrs (mean 3.6) with sickle cell syndromes, ss, sc or s-thal using two vaccines alternately, single blind (25 patients PRP; 30 PRP-D). The vaccine groups were similar in age, sickle diagnoses and vaccine-to-post-serum interval (28-57 days, mean 40). Coded pre and post sera were tested by radioimmunoassay for ug/ml of anti-PRP antibody.The geometric mean titer (GMT) for the entire group of children rose 48 fold from 0.126 (PRP, 0.158; PRP-D, 0.104) to 6.16 (PRP, 2.45 or 16 fold vs. PRP-D, 12.88 or 123 fold; p=.006, p=.001 for fold rise difference). A total of 34 children (16 PRP; 18 PRP-D) with pre titers <0.125 rose 80 fold from a GMT of 0.045 (PRP, 0.046; PRP-D, 0.044) to 3.60 (PRP, 1.35 or 30 fold vs. PRP-D, 8.51 or 195 fold; p=.019, p=.025 for rise). Eighty-eight, 68 and 28% of PRP children and 100, 97 and 60% of PRP-D children achieved titers of≥0.1, ≥1.0 and≥5.0 respectively. Only 5% or 16% of the total group ended up with possibly inadequate titers <0.1 or<:1.0 respectively.Thus both vaccines were immunogenic in most sickle cell children and are likely to protect. However, PRP-D appears to be more immunogenic than PRP in our population at 1-2 mos after vaccination.