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.^{[22, 23]}

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.^[24]

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

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.

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.

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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