Primary Immune Deficiency (PID)

PID is a class of inherited disorders of the immune system that predispose individuals to an increased rate and severity of infection, immune dysregulation with autoimmune disease and malignancy. A high rate of comorbidities can occur with PID, including pulmonary diseases, rheumatological diseases, and autoimmune disease.

Infections occurs in various part of the body, usually the skin, sinuses, throat, ears, lungs, brain or spinal cord, urinary or intestinal tracts

These infections are characteristically repetitious, difficult to treat or unusually severe.

There are more than 450 primary immunodeficiencies recognized by the International Union of Immunological Societies.  There are approximately 500,000 people affected in the United States as estimated by NIH.

• Typical infections include those of the sinuses, ears, and lungs
• Infections can lead to lung damage and shorten lifespan

PID, particularly CVID, is also associated with

• Immune dysregulation and autoimmune disease

• Autoimmune complications contribute to morbidity/mortality
• Autoimmune hematologic complications often present as Immune Thrombocytopenia Purpura (ITP) and Autoimmune Hemolytic Anemia (AIHA)

• Malignancy

PID is underdiagnosed and often has a long interval to diagnosis

• PID; frequently go undetected in the primary care setting as the presentations may be perceived as routine infections
• The time to diagnosis following symptom onset is on average 12.4 years

Primary Therapy - Immunoglobulin

• Ig therapy (IV or SC) is required for patients with PID characterized by impaired antibody production, usually accompanied by recurrent or unusually severe infection
• Mandatory for patients with severe PIDs that directly impact B-cell function and antibody production
• Increasingly seen as important in other PIDs in which antibody or B-cell dysfunction is implicated but may not be as apparent in conventional testing

Secondary/Supportive Measures

• Antibiotics
• Corticosteroids
• Bronchodilators/Steroidal inhalants
• Antivirals
  
  

Patients receiving Ig therapy should have regular monitoring of IgG trough levels, blood cell counts, and serum chemistry

Indication

Principle	Principle Rationale
Indications	IVIg therapy is indicated as replacement therapy for patients with PID characterized by absent or deficient antibody production. This is an FDA-approved indication for IVIg, for which all currently available products are licensed.
Diagnosis	There are a large number of PID diagnoses for which IVIg is indicated and recommended. Many have low total levels of IgG, but some have a normal level with documented specific antibody deficiency.;
Frequency of  IVIg treatment	IVIg is indicated as continuous replacement therapy for primary immunodeficiency. Treatment should not be interrupted once a definitive diagnosis has been established.
Dose	IVIg is indicated for patients with primary immunodeficiency at a starting dose of 400 to 600 mg/kg every 3 to 4 weeks. Less frequent treatment, or use of lower doses, is not substantiated by clinical data.
IgG trough levels	IgG trough levels can be useful in some diagnoses to guide care but are NOT useful in many and should NOT be a consideration in access to IVIg therapy
Site of Care	The decision to infuse IVIg in a hospital, hospital outpatient, community office, or home based setting must be based upon clinical characteristics of the patient.
Route	Route of immunoglobulin administration must be based upon patient characteristics. The majority of patients are appropriate for intravenous and a subset are appropriate for subcutaneous therapy.
Product	IVIg is not a generic drug and IVIg products are not interchangeable. A specific IVIg product needs to be matched to patient characteristics to protect patient safety. A change of IVIg product should occur only with the active participation of the prescribing physician.

^{Table adapted from the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma & Immunology
(www.aaaai.org/practice-resources/practice-tools/ivig-toolkit.aspx).}