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Delayed-type Hypersensitivity Follow-up

  • Author: Harumi Jyonouchi, MD; Chief Editor: Russell W Steele, MD  more...
 
Updated: Dec 03, 2015
 

Further Inpatient Care

Consider patients with most T-cell disorders for stem cell transplantation, usually by bone marrow transplantation using a HLA-matched related or unrelated donor.

Only a few cases of bone marrow transplantation (BMT) have been reported in patients with mutations in the interferon (IFN)-γ and interleukin (IL)-12/IL-23 signaling pathways with rather unfavorable results. Intact T-cell functions other than IFN-γ/IL-12/IL-23 axis increases the risk of graft rejection and concurrent NTM infection usually present at the time of BMT increase the risk of post-BMT complications.[19, 20]

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Deterrence/Prevention

Patients in whom immunodeficiency causing impaired CMI is suspected should never receive the BCG or smallpox vaccine. Similarly, live vaccines (MMR and varicella) are contraindicated, although this vaccine is not administered until age 1 year, by which time most T-cell disorders have been diagnosed. Guidelines regarding the administration of the MMR vaccine have been updated.[21]

Patients with IFNGR1, IFNGR2, STAT-1, IL12P40, or IL12RB1 mutations are advised to receive prophylaxis against NTM using rifabutin and clarithromycin.

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Complications

Antigens that are currently available for DTH skin testing are not associated with significant morbidity and do not cause mortality.

Experimental animal models of immunodeficiency with absent DTH reactivity suggest that other infections may also occur in the absence of effective CMI. These infections include L monocytogenes, L pneumophila, T gondii, and Leishmania species.

In humans with idiopathic disseminated BCG or with mutations in the IFN-γ signaling pathway, the risk of contracting nontyphus Salmonella infections increases.

One report describes severe infections with viruses (eg, respiratory syncytial virus [RSV], parainfluenza virus, herpes simplex virus (HSV), cytomegalovirus [CMV], and varicella-zoster virus [VZV]) in a patient with an IFN-γ signaling pathway defect.

Some patients with IFNGR1 mutations have good antibody responses to HSV, CMV, VZV, and Epstein-Barr virus (EBV) without clinical infection, suggesting that their host response to these viruses is intact.

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Prognosis

Adequate nourishment and discontinuation of drug therapy can reverse anergy caused by malnutrition and immunosuppression by immunomodulating agents, respectively.

As noted in Mortality/Morbidity, severe mutations in IFNGR1, IFNGR2, STAT-1,IL12P40, and IL12RB1 lead to lethal disseminated infections with NTM. Mutations in the IFN-γ signaling pathway that cause milder clinical infections are described; many of these patients benefit from exogenous IFN-γ therapy.

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Patient Education

 

Regarding IFNGR1, IFNGR2, STAT-1, IL12P40, and IL12RB1 mutations, inform families about the risks of infection so that appropriate steps to avoid exposure to infection are instituted.

  • Families should be aware that BCG and live viral vaccines are contraindicated.
  • Genetic counseling is an essential as a part of medical care for the family. Inform parents of the 1 out of 4 risk for affected infants in autosomal recessive gene mutations. Mutations in the intracytoplasmic domain of IFNGR1 result in autosomal dominant transmission.
  • If hematopoietic stem cell transplant (HSCT) is considered as a therapeutic option, an adequate informed consent from for HSCT must include the high risk for life-threatening infection during the preparative immunosuppressive regimen in addition to the risk for failure to engraft and graft versus host disease (GVHD). Although successful complete immune reconstitution from HSCT can be obtained using fully HLA matched related and unrelated donors, patients may not engraft or may experience GVHD post-transplant. Other forms of stem cell reconstitution that can be offered include cord blood cell transplantation. Gene therapy is expected to be an option in the future.

The Immune Deficiency Foundation is an important resource for education and for support for patients and families with any primary immunodeficiency disease. The current address is 40 W. Chesapeake Ave, Suite 308, Towson, MD 21204. Some states have local chapters.

The Jeffrey Modell Foundation at 747 Third Avenue, New York, NY 10017 provides support and raises funds.

For excellent patient education resources, visit eMedicineHealth's Allergies Center.

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Contributor Information and Disclosures
Author

Harumi Jyonouchi, MD Faculty, Division of Allergy/Immunology and Infectious Diseases, Department of Pediatrics, Saint Peter's University Hospital

Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology and Medicine, Society for Pediatric Research, Society for Mucosal Immunology

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Russell W Steele, MD Clinical Professor, Tulane University School of Medicine; Staff Physician, Ochsner Clinic Foundation

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, Southern Medical Association

Disclosure: Nothing to disclose.

Additional Contributors

Terry W Chin, MD, PhD Associate Clinical Professor, Department of Pediatrics, University of California, Irvine, School of Medicine; Associate Director, Cystic Fibrosis Center, Attending Staff Physician, Department of Pediatric Pulmonology, Allergy, and Immunology, Memorial Miller Children's Hospital

Terry W Chin, MD, PhD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Allergy, Asthma and Immunology, American College of Chest Physicians, American Federation for Clinical Research, American Thoracic Society, California Society of Allergy, Asthma and Immunology, California Thoracic Society, Clinical Immunology Society, Los Angeles Pediatric Society, Western Society for Pediatric Research

Disclosure: Nothing to disclose.

Acknowledgements

John Wilson Georgitis, MD Consulting Staff, Lafayette Allergy Services

John Wilson Georgitis, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association for the Advancement of Science, American College of Chest Physicians, American Lung Association, American Medical Writers Association, and American Thoracic Society

Disclosure: Nothing to disclose.

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