Search

Sir .—Rao et al 1 reported the case of a child with immune thrombocytopenic purpura (ITP) in whom unusual aseptic meningitis, with greater than 0.90 neutrophils in cerebrospinal fluid, developed within 36 hours of intravenous immune globulin (IVIG) administration. Although the authors stated that "all reported cases of aseptic meningitis occurred in patients with immune thrombocytopenic purpura," it was also observed in adults 2 with ITP who were given different preparations of IVIG in different doses. Although bacterial and viral cultures of cerebrospinal fluid remained negative in those cases (including the authors' patient), this unusual aseptic meningitis could be related to a causative agent (including chemicals) that is not yet known, since the cerebrospinal fluid findings do not fit those of pseudotumor cerebri. Since the prognosis of acute childhood ITP is very favorable, and, when required, the platelet count can be raised above 150×10 9 /L within 3 days in

The mainstain therapy in polymyositis is corticosteroids and immunosupressive drugs. We report 2 cases of severe refractory polymyositis with dramatic response with the association of plasma exchange and intravenous gammaglobulin despite the failure of these therapies isolated prescribed in one case.

Excerpt To the Editor:The otherwise excellent review article by Berkman and colleagues (1) on the uses of intravenous gammaglobulin contains an astonishing misstatement regarding Kawasaki disease t...

In a patient with idiopathic thrombocytopenic purpura (ITP), the hemostatic control is considerably troublesome. When a tooth extraction is required in such a case, platelet rich plasma and/or fresh whole blood transfusion has been usually practiced. Though oral surgical treatmant has become convenient with this therapy, serious problems such as a new production of antibodies against platelet happens. Since these antibodies invalidate the effect of transfusiontherapy in lethal bleeding, its use must be deliberate. So we are looking forward to a more suitable method in minor treatments of oral surgery or dentistry.It was revealed by Imbach et al. in 1981 that high-dose intravenous gammaglobulin therapy was able to increase the number of platelets in ITP. Thereafter the usefulness of this therapy has been ascertained at various clinics and it is considered a new treatment for ITP. By this time no important side effects through this therapy are reported. We consider this therapy is also very useful on our clinics.We have recently experienced two cases of tooth extraction with this therapy in a patient with ITP and obtained good results. From these experiences we have come to the conclusion that systematic oral or dental care is most imprtant in a patient with ITP or hemorrhagic diathesis.

KANOH, T., OHNO, T., HARADA, S. and FUJII, H. An Unsuccessful Attempt to Isolate Human Immunodeficiency Virus (HIV) from Patients with Primary Immunodeficiency Diseases. Tohoku J. exp. Med., 1987, 152 (4), 391-395 -Isolation of the human immunodeficiency virus (HIV) was performed in 5 seronegative patients with primary immunodeficiency diseases (IDDs) who had no or little ability to produce antibodies and received a large amount of intravenous gammaglobulin (IVG) for a long period. In this study cultured cells were considered to be infected if the following 2 criteria were met: (1) They produced revers etranscriptase (RT) activity in the supernatant fluid and (2) expressed viral antigens. Under experimental conditions, virus was demonstrated by both RT activity and viral antigen expression detectable by immunofluorescence technique in lymphocyte cultures from 2 seropositive patients with acquired immunodeficiency syndrome-related complex who were examined as controls. There was no evidence of HIV infection in cultures of lymphocytes from all of the 5 patients with primary IDDs and from 2 healthy subjects. The above patients did not show the extremely low numbers of target T4+ cells, which make isolation of the virus in lymphocytes difficult. The present results suggest that current methods of IVG preparation either remove or inactivate HIV.

High-dose intravenous gammaglobulin (IVIgG) was given to 12 children and adults with chronic idiopathic thrombocytopenic purpura (ITP) to avoid splenectomy or because they either failed to respond to or required maintenance with high doses of steroids and/or immunosuppressives. The average platelet count increase to initial therapy was 239,500/microliters (range 23,000–790,000). A concomitant IgG Fc receptor blockade, measured by IgG-sensitized 51Cr-labeled autologous erythrocytes, was seen in 11 of 11 patients tested, both splenectomized and not splenectomized, lasting 3–4 wk. Six or more months after treatment, 2 children are in remission, 2 children and 2 adults are stable requiring no therapy with platelet counts of approximately 50,000 and 30,000, respectively, 3 children require maintenance IVIgG therapy at 2–10-wk intervals, and 1 child and 2 adults have become refractory to further IVIgG. Splenectomy was not performed in 4 children. Two adults were able to discontinue daily prednisone. The 3 patients who became unresponsive to Swiss Red Cross gamma-globulin (IgSRK) therapy did so in conjunction with a markedly elevated platelet-associated IgG and IgM. Serum IgM increased an average of 103 mg/dl after the IVIgG infusions. No significant side effects were seen.

A patient with adrenoleukodystrophy was successfully treated by means of intravenous gammaglobulin injections. The clinical symptoms, especially visual loss, were apparently relieved and no neurological deterioration was observed during a 18-month period following the start of the gammaglobulin treatment.

Ten patients with idiopathic thrombocytopenic purpura (ITP) were studied before and following a rise in circulating platelets subsequent to infusions of intravenous gammaglobulin (400 mg/kg/day x 5 days). We quantitated the amount of circulating IgG capable of binding to normal donor platelets in vitro using an 125I-monoclonal anti-human IgG assay, as well as the amount of IgG associated with the patients' platelets before and following therapy. We found no evidence for a decrease in platelet-specific IgG antibodies in these patients undergoing an acute response to therapy. These data suggest that the short-term efficacy of intravenous gammaglobulin is due to effects other than a substantive reduction in platelet reactive antibodies, such as the alteration of IgG-coated platelet destruction.

I N 1890 the first Nobellaureate, von Behring, recognized antibodies in serum to diphtheria toxin and introduced passive immune prophylaxis against the disease. About 60 years later, the potential of this treatment became apparent when Bruton,1 and Good and Varco,z and Barandun et al used gammaglobulin (IgG) to successfully treat infections in children with X-linked infantile agammaglobulinemia. This treatment was quickly extended to other patients as treatment and as prophylaxis. For the next 30 years, most physicians used a standard dose of 100 to 200 mg/kg of IgG every 4 weeks for immune replacement. This dose did not raise the plasma concentration of IgG to normallevels, but higher doses could not be used because the preparation could only be given by intramuscular injection. In the late 1970s, safe and effective IgG preparations that could be administered intravenously (IV) became available. The ability to give the preparation IV meant that very high doses of IgG could be given, and this led to the recognition that IgG could act as an "immune suppressant." As will be discussed, intravenous gammaglobulin (IV IgG) has provided insights into the role of IgG in both physiological and pathological cell clearance. In this review, we will summarize the various preparations of IgG that can be given IV and the efficacy of IV IgG as an immune replacement and an immune suppressant, and we will discuss the adverse effects of IV IgG.

l. Woerner S J, Abildgaard CF, French BN. Intracranial hemorrhage in children with idiopathic thrombocytopenie purpura. Pediatrics 1981;67:453-60. 2. Zerella JT, Martin LW, Lampkin BC. Emergency splenectomy for idiopathic thromboeytopenic purpura in children. J Pediatr Surg 1978;13:243-6. 3. Sartorius JA. Steroid treatment of idiopathic thromboeytopenic purpura in children: Preliminary results of a randomized cooperative study. Am J Pediatr Hematol Oncol 1984;6: 165-9. 4. McWilliams NB, Maurer H. Acute idiopathic thrombocytopenic purpura in children. Am J Hematol 1979;7:87-96. 4a. Buchanan GR, Holtkamp cA. Prednisone therapy for children with newly diagnosed idiopathic thrombocytopenic purpura: A randomized clinical trial. Am J Pediatr Hematol Oncol 1984;6:355-61. 5. lmbach P, d'Apuzzo V, Hirt A, et al. High-dose intravenous gammaglobulin for idiopathic thrombocytopenic purpura in childhood. Lancet 1981;1:1228-31. 6. Bussel JB, Goldman A, Imbaeh P, Schulmau I, Hilgartner MW. Treatmeflt of acute idiopathic thrombocytopenia of childhood with intravenous infusions of gammaglobulin. J PEDIATR 1985;106:886-90. 11.

Testicular volumes of adolescents. J PEDIATR 1982;100:1010. 3. Lambert B. The frequency of mumps and mumps orchitis, and the consequences for sexuality and fertility. Acta Genet [Suppl] 1951;2:1. 4. Rundle AT, Sylvester PE. Measurement of testicular volume: its application to assessment of maturation and its use in diagnosis of hypogonadism. Arch Dis Child 1962;37:514. 5. Hurxthal LM. Hypogenitalism during the time of puberty. JAMA 1948;136:12. 6. Cassorla FG, Golden SM, Jonsonbaugh RE, et al. Testicular volume during early infancy. J PEDIATR 1981;99:742. 7. Takihara H , Sakatoky J, Fujji M, et al. Significance of testicular size measurement in andrology. I. A new orchidometer and its clinical application. Fertil Steril 1983;39:836. 8. Schonfeld WA, Bebe GW. Normal growth and variation in male genitalia from birth to maturity. J Urol 1942;48:759. 9. Schonfeld WA. Primary and secondary sexual characteristics. Am J Dis Child 1943;65:535. 10. Prader A. Testicular size: assessment and clinical importance. Triangle 1966;7:240. 11. Marshall WA, Falkner F, Tanner JM, eds. Human growth. New York: Plenum, 1978:150.

Fourteen adults with idiopathic thrombocytopenic purpura suffered a relapse after treatment with steroids, vinca alkaloids, or intravenous gammaglobulin. Splenic sequestration of platelets labelled with 111In-oxine was assessed, and the patients then underwent splenectomy. During follow up of four to 47 months (mean 20.7) none of the patients required further treatment, including three of 14 who showed partial relapses. Splenic sequestration patterns did not predict relapses, but an unexpected finding was that patients who relapsed had significantly smaller spleens. It is concluded that splenectomy is beneficial in most adult patients with idiopathic thrombocytopenic purpura and that radiological techniques to measure the size of the spleen may be useful in predicting which patients may relapse.

A 22-year-old woman with severe idiopathic thrombocytopenic purpura, complicating pregnancy, was unresponsive to high-dose corticosteroids and three separate infusions of high-dose intravenous immunoglobulin using the conventional schedule of 400 mg/kg/d for five days. A dramatic albeit transient, elevation of her platelet count followed a six day course of very high dose immunoglobulin (1000 mg/kg/d) thus allowing elective lower segment cesarean section to be performed without complications and with the delivery of a live, female infant. Two months later a further course of very high dose gammaglobulin was again effective in raising the patient's platelet count prior to elective splenectomy. No adverse reactions were seen to either infusion.

Intravenous gammaglobulin was compared with the standard British intramuscular preparation in patients with hypogammaglobulinaemia and chronic bronchitis. Five patients were given six months' treatment with the weekly intramuscular preparation and six months' treatment with intravenous gammaglobulin given once every 18 days. During the trial they recorded symptoms of infection, absence from work, and sputum volume; lung function tests were performed during the intravenous treatment. The half life of the intravenous IgG and changes in serum IgG and C1q concentrations were also measured in seven other patients who received intravenous gammaglobulin every two weeks for 12 weeks. IgG concentrations, sputum volume, and infection scores were significantly better during intravenous treatment and there were no adverse effects from the intravenous gammaglobulin. These five patients were significantly more healthy when they received an intravenous gammaglobulin preparation, probably because the intravenous preparation increased serum IgG concentrations. Although longer studies are needed, intravenous gammaglobulin should be considered for patients with severe chest disease and those who cannot tolerate intramuscular injections.

Intravenous gammaglobulin (IVGG) can improve the clinical course of several immune-mediated diseases. We report the first results of such treatment in eight patients with severe Guillain-Barre syndrome (GBS). We observed that IVGG was beneficial in at least some of the patients with severe GBS. These results should be confirmed in a randomized trial.

An infant with severe, isoimmune thrombocytopenia secondary to maternal anti-Pla 1 immunisation was treated successfully by intravenous gammaglobulin (400 mg/kg per day for five days). This treatment compared with Pla 1 negative platelet transfusions is discussed.

A neonate with isoimmune neonatal neutropenia (INN) was treated with intravenous gammaglobulin. The neutrophil count increased significantly with the therapy. Intravenous gammaglobulin is a safe and effective regimen for INN.

The immunologic status of a patient with disseminated cryptococcosis and no underlying predisposing factor was evaluated. The proportions and numbers of T cells, T cell subsets, B cells and proliferative responses to mitogens and soluble antigens, including cryptococcal antigen, were comparable to those in healthy control subjects; however, the patient had moderately severe hypogammaglobulinemia. The patient continues to do well clinically with intravenous gammaglobulin and antifungal therapy. This study suggests that antibodies might also play a role in the defense against cryptococcal antigen.

phase radioimmunoassay for platelet-associated immunoglobulin G. J Lab Clin Med 101:392, 1983. 5. Singer DB: Postsplenectomy sepsis. In Rosenberg HS, Bolande RP, editors: Perspectives in pediatric pathology, vol 1. Chicago, 1973, Year Book Medical Publishers, p 285. 6. Venetz U, Willi P, Hirt A, lmbach P, Wagner HP: Chronic idiopathic thrombocytopenic purpura in childhood. Helv Paediatr Acta 37:27, 1982. 7. Fehr J, Hofmann V, Kappeler V: Transient reversal of thrombocytopenia in idiopathic thrombocytopenic purpura by high-dose intravenous gammaglobulin. N Engl J Med 306:1254, 1982. 8. Picozzi V J, Roeske WR, Greger WP: F~ te of therapy failures in adult idiopathic thrombocytopenic purpura. Am J Med 69:690, 1980. 9. Lammi AT, Lovric VA: Idopathic thrombocytopenic purpura: An epidemiologic study. J PEDIATR 83:31, 1973. 10. Williams W J, Beutler E, Erslev A J, Rundles RW, editors: Hematology. New York, 1972, McGraw-Hill. II. Cohen P, Gardner FH: The thrombocytopenic effect of sustained high-dosage prednisone therapy in thrombocytopenic purpura. N Engl J Med 265:611, 1961.

This work was supported in part by a grant-in-aid from the Japan Medical Research Foundation and by Scientific Research Grants (project No. 57770632) from the Ministry of Education, Science and Culture of Japan.

We report our preliminary experience of high-dose intravenous gammaglobulin in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) selected for inefficacy or severe side effects of steroid and immunosuppressive treatment. Our treatment proved safe and effective, reversing the disability of CIDP, the improvement being temporally related to the commencement of intravenous high-dose gammaglobulin. The possible mechanisms of action are discussed.

Seven children with chronic or intermittent and six with acute idiopathic thrombocytopenic purpura (ITP) were treated with large intravenous doses of polyvalent, intact immunoglobulin (Ig). In all patients the platelet count rose sharply within 5 days, but the initial response and the subsequent course varied from patient to patient. Among children with chronic ITP the initial response was more marked in splenectomised than in non-splenectomised patients. Among those with acute ITP the two who remained Ig dependent had a smaller initial response than the four patients who required no maintenance treatment. During the 90-110 days of observation five of six patients with chronic ITP could be maintained with Ig alone. No untoward effects of Ig therapy were observed.

Retroviruses related to human T-lymphotropic virus III/lymphadenopathy-associated virus (HTLV-III/LAV) have been isolated from peripheralblood mononuclear cells of two patients with "common variable" hypogammaglobulinaemia who were being treated with intravenous gammaglobulin. One has had three different opportunistic infections. In both patients hypogammaglobulinaemia developed within 6 years of a longlasting undiagnosed viral-like illness in adolescence, and it is suggested that the virus causing that illness also gave rise to the hypogammaglobulinaemia. However, iatrogenic infection from intravenous gammaglobulin cannot be ruled out.

Excerpt To the editor: Recently, Mintzer and coworkers (1) reported the cases of three patients with immune thrombocytopenia, Kaposi's sarcoma, and the acquired immunodeficiency syndrome. Two of th...