ro13-9904 and Immunologic-Deficiency-Syndromes

Hypogammaglobulinemia develops in 3 to 6% of patients with thymoma and this association is commonly referred to as thymoma with immunodeficiency (formerly Good syndrome). Recurrent infections with encapsulated bacteria and opportunistic infections associated with disorders of both humoral and cell mediated immunity frequently occur in this rare primary, adult-onset immunodeficiency. We report a case of thymoma with immunodeficiency complicated by disseminated herpes simplex virus (HSV) infection and review five additional cases of HSV-related infections reported since 1966 in patients presenting with thymoma with immunodeficiency. Patients presented with epiglottitis, keratitis, recurrent genital herpes, ulcerative dermatitis, and acute hepatitis. Four of the six cases had a fatal outcome, two of which were directly attributable to HSV infection. Since the risk of invasive opportunistic infections is high and the presentation atypical, lymphocyte count and total serum immunoglobulin should be measured regularly in all patients presenting with thymoma with immunodeficiency.

Topics: Adult; Aged; Ceftriaxone; Fatal Outcome; Female; Herpes Simplex; Humans; Immunoglobulins; Immunologic Deficiency Syndromes; Male; Middle Aged; Thymoma; Thymus Neoplasms

About 2% of childhood episodes of invasive pneumococcal disease (IPD) are recurrent, and most remain unexplained.. To report two cases of otherwise healthy, unrelated children with recurrent IPD as the only clinical infectious manifestation of an inherited disorder in nuclear factor-kappaB(NF-kappaB)-dependent immunity.. One child carried two germline mutations in IRAK4, and had impaired cellular responses to interleukin (IL)1 receptor and toll-like receptor (TLR) stimulation. The other child carried a hemizygous mutation in NEMO, associated with a broader impairment of NF-kappaB activation, with an impaired cellular response to IL-1R, TLR and tumour necrosis factor receptor stimulation. The two patients shared a narrow clinical phenotype, associated with two related but different genotypes.. Otherwise healthy children with recurrent IPD should be explored for underlying primary immunodeficiencies affecting the IRAK4-dependent and NEMO-dependent signalling pathways.

Topics: Anti-Bacterial Agents; Antibody Formation; Ceftriaxone; Child; Child, Preschool; DNA, Complementary; Exons; Humans; I-kappa B Kinase; Immunologic Deficiency Syndromes; Interleukin-1; Interleukin-1 Receptor-Associated Kinases; Introns; Male; NF-kappa B; Pneumococcal Infections; Pneumococcal Vaccines; Polymerase Chain Reaction; Recurrence; Signal Transduction; Streptococcus pneumoniae

We compared the bactericidal efficacies of various antimicrobial agents and combinations thereof in experimentally induced Nocardia asteroides pneumonia in immunocompromised mice. Cortisone acetate treatment, which produced impaired cell-mediated immune function, was followed by nasal inoculation of 5 x 10(4) CFU of N. asteroides into each mouse. Therapy was begun 24 h after inoculation and continued for the next 96 h. Dosages of antimicrobial agents resulted in concentrations approximating levels in human serum. Animals from each of nine treatment groups were sacrificed every 24 h. The pulmonary tissue obtained was homogenized and quantitatively cultured. Results were calculated to indicate the number of CFU per gram of lung tissue. Amikacin and imipenem were the two most effective single agents studied. Sulfadiazine and ciprofloxacin were ineffective, and ceftriaxone reduced bacterial counts modestly. Combination therapy did not enhance the bactericidal activities of the agents tested. We conclude that amikacin and imipenem, as well as select broad-spectrum cephalosporins, represent therapy superior to the sulfonamides in this experimental model and may represent alternative treatment for patients who cannot tolerate sulfa agents (e.g., human immunodeficiency virus-infected patients) or who fail primary treatment.

Topics: Amikacin; Animals; Anti-Bacterial Agents; Ceftriaxone; Ciprofloxacin; Cortisone; Female; Humans; Imipenem; Immunity, Cellular; Immunologic Deficiency Syndromes; Lung Diseases; Mice; Nocardia asteroides; Nocardia Infections; Sulfadiazine