Table 4.

Treatment of Manifestations in Individuals with X-Linked Hyper IgM Syndrome

Manifestation/
Concern		TreatmentConsiderations/Other
Recurrent
infections
  • Immunoglobulin replacement w/intravenous or subcutaneous immunoglobulin starting at diagnosis
    Initial dosing for IgG replacement: 0.4-0.6 g/kg every 3-4 wks for IV, or ≥100 mg/kg dose weekly for subcutaneous Ig.
    Titrate IgG levels as for primary antibody deficiency syndromes.
  • Prophylactic antibiotics against opportunistic infections incl P jirovecii
  • Institute appropriate antimicrobial therapy for acute infections.
  • Aggressively evaluate pulmonary infections (incl use of diagnostic bronchoalveolar lavage) to define specific etiology.
  • Prevention of infections 1
Discussion re prophylactic use of azithromycin or nitazoxanide for all affected individuals for prevention of Crypstosporidium is ongoing. While not standard of care, it should be considered for those living in / traveling to an area w/↑ Cryptosporidium rates.
Immunodeficiency Only current curative treatment is HSCT, preferably at age <10 yrs.Modified conditioning regimens may be needed in those w/preexisting liver disease, & hepatic transplant along w/HSCT may be required.
Chronic
neutropenia 		Recombinant GCSF
Malnutrition &
poor growth 		Total parenteral nutrition & consultation w/clinical dietary nutritionist may be required to optimize caloric intake.
Sclerosing
cholangitis 		Some males w/end-stage sclerosing cholangitis have been treated successfully w/orthotopic liver transplantation closely assoc w/allogeneic bone marrow transplantation. Infectious etiologies need to be pursued & treated prior to transplantation.
Autoimmune
disorders 		Treatment of autoimmune disorders usually involves judicious use of immunosuppressants tailored to individual's diagnosis.
Cancer Treatment should follow standard protocols/therapies for individual cancers in conjunction w/immunologist.

GCSF = granulocyte colony-stimulating factor; HSCT = hematopoietic stem-cell transplantation; P = Pneumocystis

1.

The following methods are used to prevent infection:
Antibiotic prophylaxis. Prophylaxis for pneumonia secondary to Pneumocystis jirovecii (PJP) is indicated for all children with HIGM1 due to the high risk of developing PJP during the first two years of life. There is no standard-of-care approach established for length of PJP prophylaxis. However, individuals with HIGM1 who develop PJP after age two years should continue prophylaxis for life or until after HSCT transplant when normal immune function is established. Typical prophylaxis is trimethoprim-sulfamethoxazole orally, pentamidine by intravenous or inhalation therapy, dapsone, and atovaquone.
Immunoglobulin (either subcutaneous or intravenous). Immunoglobulin replacement should be considered at the time of diagnosis, as individuals with HIGM1 cannot generate antibodies to encapsulated bacteria naturally and are at risk for overwhelming infection from these organisms. IgG replacement is a highly purified blood derivative (a combination of many specific antimicrobial antibodies) that is typically given every three to four weeks or can be given subcutaneously, usually on a weekly basis.
Additional antibiotic prophylaxis should be evaluated on a case-by-case basis with ongoing questions regarding Cryptosporidum prophylaxis not yet being standardized.
Routine childhood immunizations (killed vaccines) may be safely administered but do not preclude the need for immunoglobulin replacement. Live vaccines (e.g., rotavirus, MMR, varicella, live attenuated polio, and BCG) should not be given to individuals with HIGM1.
Only boiled and/or filtered water should be ingested. Avoid swimming in non-chlorinated pools. Avoid swimming in lakes and ponds. Children should avoid water parks and farm animals.

From: X-Linked Hyper IgM Syndrome

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