Sasson Lavi

Increased susceptibility to mycoplasma infection in patients with hypogammaglobulinemia

The incidence and morbidity of Mycoplasma infections were examined in a group of 23 patients with hypogammaglobulinemia. Among this group of patients, 18 had one or more episodes of acute respiratory illness during which Ureaplasma urealyticum, Mycoplasma orale, or Mycoplasma pneumoniae were isolated from sputum. Resolution only followed institution of specific antibiotic therapy and elimination of the Mycoplasma. In addition to respiratory illness, U. urealyticum was isolated from the urine of two patients with urinary tract infection and from an area of cellulitis in another patient. M. pneumoniae was isolated from the joint of a patient with arthritis. In six patients with chronic lung disease, Mycoplasma was frequently isolated and clinical improvement, albeit transient, coincided with negative Mycoplasma culture results. These findings emphasize the unique susceptibility to Mycoplasma infection in patients with hypogammaglobulinemia.

Kawasaki disease: Review of risk factors for coronary aneurysms

Between June 1, 1979, and May 31, 1984, at The Hospital for Sick Children in Toronto, Kawasaki disease was diagnosed in 163 patients (112 boys, 51 girls, P less than 0.001). Fifteen percent of the children had coronary artery aneurysms. Prior to diagnosis, 24% had been given low doses of aspirin, and 50% acetaminophen. Children with coronary aneurysms had significantly higher temperature during days 10 to 13 of the disease. The febrile phase of the disease was also significantly longer in these children. Coronary artery involvement occurred with equal frequency in boys and girls. There was no significantly greater incidence of coronary artery involvement in infants younger than 1 year of age than in older children. Duration of fever (greater than or equal to 14 days vs less than 14 days) was equally as predictive of the eventual occurrence of coronary aneurysms as the modified Asai score.

Benefit of intravenous IgG replacement in hypogammaglobulinemic patients with chronic sinopulmonary disease

Seven patients with hypogammaglobulinemia and chronic sinopulmonary infections were treated with a preparation of intravenous gammaglobulin. In order to maintain levels of serum IgG at greater than 500 to 750 mg/dl four weeks after infusion, 0.6 g/kg was administered every month. Stable serum levels were achieved after three to eight months. After six to 12 months of this regimen, there was significant reduction in acute infections requiring hospitalization, amelioration of clinical and radiographic evidence of chronic maxillary sinusitis, and improvement in pulmonary symptoms and pulmonary function test results. The administration of increased amounts of IgG intravenously is of benefit in patients with chronic sinopulmonary infections.

Corticosteroids for prevention of adverse reactions to intravenous immune serum globulin infusions in hypogammaglobulinemic patients

Severe adverse reactions to intravenous immune serum globulin occurred repeatedly in four of 10 hypogammaglobulinemic patients. Treatment-limiting symptoms included fever, chills, headache, hypertension, and chest pain. Pretreatment of patients with hydrocortisone immediately prior to infusion prevented subsequent adverse reactions and permitted these patients to receive immune serum globulin intravenously.

Corticosteroids―salicylate interaction in a case of juvenile rheumatoid arthritis

In an 11-year-old child with juvenile rheumatoid arthritis (JRA), the addition of prednisone caused a significant decrease in salicylate serum con-centrations. A pharmacokinetic assessment suggested that these changes were not the result of altered compliance or impaired absorption of salicylate but rather an increase in salicylate clearance induced by the corticosieroid.

Combined immunodeficiency and atopy caused by a dominant negative mutation in caspase activation and recruitment domain family member 11 (CARD11)

Background Combined immunodeficiency (CID) is a T‐cell defect frequently presenting with recurrent infections, as well as associated immune dysregulation manifesting as autoimmunity or allergic inflammation. Objective We sought to identify the genetic aberration in 4 related patients with CID, early‐onset asthma, eczema, and food allergies, as well as autoimmunity. Methods We performed whole‐exome sequencing, followed by Sanger confirmation, assessment of the genetic variant effect on cell signaling, and evaluation of the resultant immune function. Results A heterozygous novel c.C88T 1‐bp substitution resulting in amino acid change R30W in caspase activation and recruitment domain family member 11 (CARD11) was identified by using whole‐exome sequencing and segregated perfectly to family members with severe atopy only but was not found in healthy subjects. We demonstrate that the R30W mutation results in loss of function while also exerting a dominant negative effect on wild‐type CARD11. The CARD11 defect altered the classical nuclear factor &kgr;B pathway, resulting in poor in vitro T‐cell responses to mitogens and antigens caused by reduced secretion of IFN‐&ggr; and IL‐2. Conclusion Unlike patients with biallelic mutations in CARD11 causing severe CID, the R30W defect results in a less profound yet prominent susceptibility to infections, as well as multiorgan atopy and autoimmunity.

775 PROBABLE EFFICACY OF HIGH DOSE SALICYLATE IN REDUCING CORONARY INVOLVEMENT IN KAWASAKI DISEASE

Although acetylsalicylic acid (ASA) is the most widely used drug in Kawasaki disease because of its anti-inflammatory and antiplatelet effect, a previous study failed to show efficacy of ASA 30 mg/kg/day in reducing coronary involvement in this disease. We have recently documented erratic and often reduced absorption of ASA in Kawasaki disease such that 30 mg/kg/day could not be assumed to yield therapeutic concentrations. In the present study the efficacy of high dose salicylates in reducing the coronary features of Kawasaki disease was assessed in 36 children who received ASA 80-180 mg/kg/day, and 18 who did not receive high dose salicylates during the febrile phase of the disease and whose fever was controlled mainly with acetaminophen. The two groups were comparable with respect to age and body weight. In the ASA-treated group the dose was adjusted to achieve a concentration ≥ 20 mg/dl. There were significantly more cases of coronary disease in the non-treated group (50%) than in the salicylate-treated group (16.6%) (P=0.014). Due to impaired absorption of ASA during the febrile phase of the disease salicylate serum concentrations achieved per given dose were on average 50% those observed during the non-febrile phase. Despite the difficulty in achieving therapeutic concentrations of salicylate during the febrile phase of Kawasaki disease even with doses as high as 100 mg/kg/day, this dose appears to reduce coronary artery involvement.