Effect of Ranitidine on Hyper-IgE Recurrent Infection (Job's) Syndrome

• INCLUSION CRITERIA:

  1. Male and female patients with the diagnosis of Hyper IgE Recurrent Infection (Job) syndrome. Mutations in the STAT3 gene account for the majority, if not all cases of HIES. However as the full genetics of HIES remains unknown, we will use clinical criteria, including the expert opinion of the investigators, as well as a score greater than 40 by the diagnostic scoring system used in protocol 00-I-0159.
  2. A chronic (greater than 4 weeks duration) infection or greater than 2 acute infections within the last 12 months. Acute infections can include but are not limited to: pneumonia, abscesses, sinusitis, skin infections, mucocutaneous candidiasis and ear infections. Chronic infections include continuous or intermittent symptoms despite appropriate therapeutic interventions for at least 4 weeks, including but not limited to chronic lung infiltrates with productive cough, chronic ear drainage despite topical therapy, chronic or intermittent drainage from a single abscess site, and/or chronic signs of sinusitis on sinus CT scan.
  3. Patients aged 2 years and above. There is no upper age limit. We are excluding children less than 2 years of age, as we do not expect them to meet the first inclusion criterion, having a score high enough to be diagnosed with HIES.
  4. Patients have to be at their own personal clinical baseline for at least 2 weeks duration. Patients will not start the study medication during an acute exacerbation of and infection.
  5. The patient or the patient's guardian will be willing and capable of providing informed consent after initial counseling by clinical staff. Separate consent forms for all interventional procedures will be obtained after explanation of the specific procedure.
  6. Patients must agree to have blood stored for future studies of the immune system and/or other medical conditions.
  7. Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
  8. Patients may be concurrently enrolled on other protocols as long as the Principal Investigator (PI) is informed.

EXCLUSION CRITERIA:

1. Pregnancy. Ranitidine is pregnancy class B, and likely safe in pregnancy, but as this has not been studied, pregnant patients will be excluded. In addition, hormonal changes that occur during pregnancy may affect the skin manifestations and frequency of infection.
2. Hypersensitivity to ranitidine or any of the ingredients in ranitidine.
3. Pre-existing medications or conditions for which the investigators judge that ranitidine should not be given.
4. Patient or investigators unwilling to stop baseline H2 receptor antagonist therapy (over the counter or prescription) such as Tagamet (Cimetidine), Pepcid (Famotidine), and Axid (Nizatidine). H2 receptor antagonist therapy must be stopped for 3 months prior to study initiation. Patients who are receiving H2 receptor antagonist therapy for gastritis, acid reflux, or peptic ulcer disease will be offered changing their regimen to a proton pump inhibitor or other non-H2 receptor antagonist therapy to allow for study enrollment (3 months after stopping the H2 receptor antagonist).
5. Patients under the age of 2 years
6. Patients with HIV, receiving chemotherapy or who have a malignancy.
7. Any condition that in the judgment of the investigator would place the subject at undue risk or compromise the results or interpretation of the study.