Conditions: JOB's Syndrome Hyper-IgE Recurrent Infection Syndrome Immune Deficiency
Keywords: Hyper-IgE Recurrent Infection Syndrome Ranitidine Therapy Job's Syndrome Cross-Over Study Double-Blind Placebo Controlled Hyper-IgE Syndrome Job Syndrome Immune Deficiency
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 16
Healthy volunteers: no

Brief summary:
This study will examine the safety and effectiveness of ranitidine (Zantac) in patients with Hyper-IgE recurrent infection syndrome, a disease characterized by recurrent infections of the ears, sinuses, lungs and skin, and abnormal levels of the antibody immunoglobulin E (IgE).

Patients age 2 and older who have Hyper-IgE recurrent infection syndrome and who have had chronic or frequent infections in the last 12 months may be eligible for this study.

Participants are randomly assigned to take ranitidine or placebo in pill or liquid form twice a day for 12 months. In addition to treatment, patients undergo the following procedures during visits scheduled on day 0 of the study (baseline) and at 3, 12, 15 and 24 months. Evaluations at 6, 9, 18 and 21 months are by telephone.

* Medical history and physical examination - baseline and 3 and 24 months.
* Clinical severity score - baseline and 3, 6, 9, 12, 15, 18, 21 and 24 months.
* Dermatology exam - baseline and 3, 12, 15 and 24 months.
* Pulmonary function test - baseline and 12 and 24 months.
* Chest CT - baseline and 12 and 24 months.
* Quality of life assessment - baseline and 3, 12, 15 and 24 months.
* Pregnancy testing - baseline and 3, 12, 15 and 24 months.
* HIV test - baseline and 12 and 24 months.
* Contraception evaluation - baseline and 3, 6, 9, 12, 15, 18, 21 and 24 months.
* Missed school/work days assessment - baseline and 3, 12, 15 and 24 months.
* Medication adherence - baseline and 3, 6, 9, 12, 15, 18, 21 and 24 months.

In addition to the above procedures, participants who are not enrolled in study 00-I-0159 have a baseline scoliosis series and genetic consult.

Detailed description:
Hyper-immunoglobulin E (IgE) syndrome (HIES) is a rare primary immunodeficiency characterized by eczema, recurrent skin and lung infections, elevated serum IgE, and multiple connective tissue and skeletal abnormalities. The autosomal dominant form of HIES is caused primarily by a mutation in the STAT3 gene. Patients with HIES produce IgE antibodies specific for Candida albicans and Staphylococcus aureus, two of the common pathogens in this population. We hypothesize that the presence of pathogen-specific IgE, combined with continuous exposure to these ubiquitous agents, leads to chronic IgE-mediated histamine release from basophils and mast cells, with subsequent pathogen-specific immune tolerance and an increase in pathogen-specific T regulatory cells. We plan to test this hypothesis through clinical and immunologic evaluation of HIES patients before, during, and after histamine-2 receptor (H2) blocker therapy with ranitidine through a prospective, placebo-controlled crossover study. We chose this therapy because histamine has been shown to stimulate interleukin-10 (IL-10), a major down regulatory cytokine, through the H2 receptor, and clinical improvement has been observed in several patients treated with H2 blockers. Laboratory studies will include determinations of pathogen-specific immunoglobulin G4 (IgG4):IgE ratios, basophil activation, IL-10 producing regulatory T-cells, cellular proliferative responses to staphylococcal and candidal antigens, and functional testing of regulatory T-cells. Clinical evaluations will include comprehensive history and physical examination, dermatologic evaluation, genetic evaluation for clinical severity scoring of HIES, pulmonary function tests, and chest computerized tomography (CT) examination. Through this study, we will further our understanding of the immunologic abnormalities of HIES and determine whether a larger prospective, double-blind trial of H2 blockade as adjunctive therapy for HIES is indicated.

Arms:
arm 1: Patients took placebo for 12 months and then ranitidine for 12 months arm 2: Ranitidine for one year followed by placebo for one year

Interventions: intervention 1: Ranitidine intervention 2: Placebo
Intervention descriptions: intervention 1: Double blinded, randomized placebo controlled crossover study. Patients received 12 months of placebo and 12 months of treatment medication (ranitidine). intervention 2: None

Protocol document: