Treatment of hypogammaglobulinaemia with intravenous immunoglobulin, 1973-93

AIMS: To review the results of long term high dose intravenous immunoglobulin treatment. METHODS: 162 treatment years in 18 patients with hypogammaglobulinaemia who received intravenous immunoglobulin treatment between 1973 and 1993 were reviewed. RESULTS: A mean dose of 0.42 g/kg immunoglobulin resulted in a mean trough IgG concentration on the 23.5th centile for age. The subjects enjoyed a good standard of health. Infection rates were similar to the general paediatric population and a similar pattern of infections occurred. There were only 0.06 episodes of pneumonia and 0.11 hospital admissions per year of treatment. The development of chronic pulmonary disease was significantly related to trough IgG concentrations less than the 10th centile (p < 0.009), however, this developed in only two children after the start of treatment. All children had normal growth parameters. Adverse reactions to immunoglobulin infusions reduced from 9.1% to 0.8% after the introduction of low pH modified intravenous immunoglobulin in 1986. Although minor, transient increases in liver transaminase values were common; none of the 11 patients tested by hepatitis C polymerase chain reaction were positive. CONCLUSION: Children with hypogammaglobulinaemia who are receiving replacement treatment grow normally and have an infection rate similar to that of non-immunodeficient children. No evidence of transmission of hepatitis C virus by the Commonwealth Serum Laboratories immunoglobulin was found.     

Treatment of Crohn disease with intravenous immunoglobulin

In a 14.5 year old girl with Crohn's disease a complete remission was achieved with intravenous immunoglobulins. Earlier treatment with various therapeutical regimens had been unsuccessful. During the next two relapses the same prompt positive response was reproducible, whereas in the third the dose of immunoglobulin had to be doubled.     

Treatment of Kimura disease with intravenous immunoglobulin

Kimura disease is an uncommon chronic inflammatory condition of unknown etiology and is characterized by painless subcutaneous nodules, usually affecting the head and neck, eosinophilia, and markedly elevated immunoglobulin E levels. Several reports have described the main modalities of treatment; both corticosteroids and surgery have provided good results, but occasionally corticosteroids cannot be tapered as the disease flares up. We report here the case of an 8-year-old boy diagnosed with Kimura disease who was successfully treated with 1 dose of intravenous immunoglobulin as a steroid-sparing agent.     

Immunomodulation, part III: intravenous immunoglobulin

Intravenous immunoglobulin therapy does not appear to be efficacious in the prevention of neonatal sepsis. The value of a 3-4 percent reduction in sepsis or any serious infection without a reduction in mortality must be weighed against the cost of the therapy. The efficacy of IVIG therapy in the treatment of neonatal sepsis remains uncertain. The results of the ongoing International Neonatal Immunotherapy Study should provide definitive answers regarding the effectiveness of this therapy. Long-term follow-up and cost (length of stay) are important components of this study. Ohlsson and Lacy recommend studies evaluating the effectiveness of IVIG preparations with high concentrations of antibodies to common unit- or geography-specific pathogens. The cost-effectiveness of the production and use of such products should be included in study designs. Part IV of this series will explore the use of the amino acid glutamine as an immunomodulating agent in neonates.     

Supply, use, and abuse of intravenous immunoglobulin

Intravenous immunoglobulin is used as a replacement therapy in primary immunodeficiency diseases as well as an immunomodulatory agent in a variety of autoimmune and inflammatory disorders. The mechanisms of intravenous immunoglobulin action are complex and, for some disorders, not well understood. This paper reviews the recent literature and discusses approved, new, and controversial indications for intravenous immunoglobulin therapy, with special emphasis on its mechanism of action.     

Treatment of hyperkalaemia with intravenous salbutamol.

Thirteen children with hyperkalaemia were treated by intravenous infusions of salbutamol, 4 micrograms/kg over 20 minutes. Reductions in the mean (SD) plasma potassium concentrations, of 1.48 (0.5) and 1.64 (0.5) mmol/l were obtained at 40 and 120 minutes, respectively, after completion of the infusions. No side effects were noted.     

Transfusion related acute lung injury with intravenous immunoglobulin

This case report describes transfusion related acute lung injury with the use of intravenous immunoglobulin in a child with Guillain barre syndrome.     

Opsonic activity in serum from septic infants treated with intravenous immunoglobulin.

Thirteen infants with staphylococcal sepsis and reduced opsonic activity received infusions of acid treated immunoglobulin together with antibiotics. Opsonic activity (using Staphylococcus aureus (type 42D) as the test organism), haemolytic activity of complement, and concentrations of complement C3 and IgG were measured in serum prepared before and after three days of treatment with immunoglobulin at a dose of 250-300 mg/kg/day. There was increased ingestion of S aureus by normal human granulocytes in the presence of fresh serum prepared after infusion of immunoglobulin and significantly increased opsonic activity of heat inactivated serum after treatment with immunoglobulin. The haemolytic activity of complement and concentrations of complement C3 were not influenced, and serum concentrations of IgG increased as the result of receiving a total of 800-900 mg/kg immunoglobulin over a period of three days. This study shows that administration of acid treated IgG to septic infants leads to functionally increased opsonisation.     

Treatment of severe pertussis: a study of the safety and pharmacology of intravenous pertussis immunoglobulin.

BACKGROUND: Pertussis in infants is often severe, resulting in complications and prolonged hospitalization. Treatment is limited to supportive care. Antibiotics do not significantly alter the course of the disease. Therapies directed at pertussis toxin, a major virulence factor of Bordetella pertussis, might be beneficial. This study examines the safety and pharmacology of intravenous pertussis immunoglobulin (P-IGIV), which has high levels of pertussis toxin antibodies. METHODS: P-IGIV was prepared as a 4% IgG solution from the pooled plasma from donors immunized with inactivated pertussis toxoid. The IgG pertussis toxin antibody concentration of 733 microg/ml is >7-fold higher than contained in conventional intravenous immunoglobulin products. Children with presumptive pertussis were allocated to one of three treatment doses of P-IGIV. RESULTS: Twenty-six of 30 enrolled children had confirmed pertussis. There were no adverse events associated with P-IGIV except one patient who had transient hypotension that responded to an infusion rate decrease. P-IGIV doses of 1500, 750 and 250 mg/kg achieved > or =4-fold, 3-fold and >2-fold rises in peak geometric mean titers of pertussis toxin IgG antibodies, respectively. P-IGIV exhibited a half-life of 38.4 days and a volume of distribution of 87.8 ml/kg. All three treatment groups showed declines in lymphocytosis (P < 0.05) and paroxysmal coughing by the third day after P-IGIV infusion compared with preinfusion values. CONCLUSION: P-IGIV is safe and achieves high pertussis toxin antibody titers in infants. This study provides data for a prospective, controlled trial of P-IGIV.     

Early treatment with intravenous immunoglobulin in patients with Kawasaki disease

OBJECTIVES: To determine if a shorter interval between Kawasaki disease (KD) treatment with intravenous immunoglobulin (IVIG) and fever onset results in increased treatment failures, need for adjunctive therapy, or development of coronary artery lesions. STUDY DESIGN: Patients with KD (n = 178; 89 matched pairs) diagnosed between 1987 and 1999 were included in this case-control study. All patients had fever plus at least 4 of the 5 clinical criteria for KD. Eighty-nine patients who received IVIG at day 5 or earlier were matched to patients diagnosed within 4 weeks and given IVIG at days 6 to 9 of fever. Compiled data from a detailed chart review included demographics, clinical features, fever duration, investigations, disease course, and response to therapy. Differences between matched case and control pairs were analyzed by means oft tests and McNemar tests. RESULTS: No demographic differences were noted between the two groups. Patients treated on day 5 or less of fever had a shorter total fever duration (5.2 +/- 1.9 days vs 8.0 +/- 1.8 days, P <.0001), longer fever after IVIG treatment (1.5 +/- 1.9 days vs 0.8 +/- 1.3 days, P =.008), and less coronary artery ectasia at 1 year after KD onset (4% vs 16%, P =.02). There was no significant difference between cases and control patients in the number of patients with KD recrudescence, need for repeat courses of IVIG, need for corticosteroids, length of hospitalization, or development of coronary artery aneurysms within the first 3 months. Patients who were treated on day 5 or less of fever had higher levels of serum albumin (36 +/- 5 g/L vs 33 +/- 5 g/L, P <.01) and serum ALT (115 +/- 155 U/L vs 46 +/- 49 U/L, P <.001) as well as a lower platelet count (354 +/- 131 vs 403 +/- 166, P =.02) than did control patients during the acute phase. CONCLUSIONS: Early treatment of KD resulted in less coronary ectasia at 1 year after KD onset but was not associated with a quicker resolution of fever, an increased number of treatment failures, an increased need for adjunctive therapy, length of hospitalization, nor development of coronary artery lesions. In children with fever and classic clinical and laboratory findings of KD, treatment with IVIG on or before 5 days of fever resulted in better coronary outcomes and decreased the total length of time of clinical symptoms.