Standard of Care Treatment and Your Care Team

Because DAVID syndrome affects both the immune and endocrine systems, managing it requires a coordinated approach. While the combination of these conditions is rare, the treatments for each part—adrenal insufficiency and antibody deficiency—are well-established and effective ^[1][2].

Endocrine Management: Replacing Cortisol

The hallmark of the endocrine side of DAVID syndrome is ACTH deficiency, which means the body cannot make enough cortisol (the “stress hormone”). This causes central (secondary) adrenal insufficiency. While central adrenal insufficiency usually does not affect the salt-regulating hormone aldosterone like primary adrenal insufficiency does, this does not lessen the risk of a life-threatening adrenal crisis.

• Daily Replacement: The standard treatment is daily hydrocortisone, a short-acting medication that replaces what the body is missing ^[3]. Because cortisol levels naturally fluctuate throughout the day, the dose is usually divided into two or three parts ^[4].
• Stress Dosing: During times of “physiological stress”—such as a fever, a serious illness, or surgery—the body requires more cortisol. You must manually increase the dose according to a specific, written Adrenal Insufficiency Action Plan provided by your endocrinologist ^[5][6].
• Emergency Injection: If your child is vomiting and cannot keep their oral medication down, or if they show signs of an adrenal crisis, an immediate intramuscular (IM) injection of hydrocortisone is required to save their life ^[7][8]. Your written plan will specify exactly when and how to use this.

Immunology Management: Boosting Defenses

To address the hypogammaglobulinemia (low antibodies), the goal is to provide the immune “armor” your child’s body isn’t building.

• Immunoglobulin Replacement Therapy (IgRT): This involves regular infusions of antibodies (IgG) collected from healthy donors.
  • IVIG (Intravenous): Given through a vein, usually once every 3 to 4 weeks in a clinic or hospital ^[9].
  • SCIG (Subcutaneous): Given under the skin, often weekly. This can frequently be done at home by parents after training ^[9][10].
• Antibiotic Prophylaxis: For some children who continue to have infections despite immunoglobulin therapy, doctors may prescribe a low-dose “preventative” antibiotic to take daily ^[11][12].
• Monitoring: Your immunologist will monitor “trough levels” (the lowest level of IgG in the blood before the next dose) and adjust the amount based on how well your child is fighting off infections ^[13][14]. Note that not every child with NFKB2-related antibody dysfunction needs IgRT; decisions are highly individualized.

Vaccines and Immunizations

Vaccine management requires a patient-specific plan from your immunologist.

• Inactivated Vaccines: These are generally recommended, though the body’s antibody response to them may be reduced ^[15].
• Live Vaccines: Live-virus vaccines (like MMR or Varicella) may be contraindicated or require individualized review by the immunology team.
• IgRT Interference: If your child receives IVIG/SCIG, the donor antibodies can interfere with the timing and interpretation of some live-virus vaccines.
• Never start, stop, or defer vaccines based solely on this guide. Always obtain a formal vaccine plan from your immunologist.

Comprehensive Pituitary Care

The NFKB2 mutation can sometimes affect other hormones over time.

• Growth and Thyroid: While ACTH is the most common deficiency in DAVID syndrome, some children also develop Growth Hormone (GH) or Thyroid-Stimulating Hormone (TSH) deficiencies ^[1][15].
• Sequential Testing: Because these issues can emerge years after the initial diagnosis, your care team will perform regular blood work and monitor your child’s growth charts closely ^[16].

Building and Vetting Your Care Team

Your child’s “medical home” should be anchored by a Pediatric Endocrinologist and a Pediatric Immunologist who are willing to talk to each other. Because infections (the domain of the immunologist) trigger the need for stress dosing (the domain of the endocrinologist), these two specialists must be in sync.

When meeting with specialists, consider asking:

1. “How many patients with adrenal insufficiency or CVID do you currently manage?”
2. “What is your preferred method for communicating with the other specialists on my child’s team?”
3. “Can you provide a written, customized Adrenal Action Plan that specifically addresses how to handle infections and vomiting?” ^[8]

A Genetic Counselor is also a vital team member to help you understand the NFKB2 mutation and what it means for other family members ^[17]. Coordinating this “village” of specialists ensures that both the immune and hormone systems are protected simultaneously.