Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

primary hypogammaglobulinemia

1st line – referral to specialist center for immunoglobulin replacement therapy

Back
ACUTE
|
primary hypogammaglobulinemia
|
significantly reduced total IgG
1st line – 

referral to specialist center for immunoglobulin replacement therapy

If primary antibody deficiency syndromes causing marked reduction (<2 standard deviations below the mean) in IgG levels are suspected, patients should be referred to specialist centers for further investigations and definitive treatment.

If primary antibody deficiency syndromes (including combined variable immunodeficiency, X-linked agammaglobulinemia, autosomal-recessive agammaglobulinemias, and immunoglobulin class-switch recombination defects) are suspected, immunoglobulin replacement therapy should be started.

Evidence suggests achieving IgG levels >500 mg/dL reduces infection frequency, and levels >800 to 900 mg/dL may further improve respiratory outcomes.[42][43][44] In most cases of primary antibody deficiency, treatment with immunoglobulin replacement is lifelong.

Subcutaneous immunoglobulin is therapeutically equivalent to intravenous immunoglobulin (usually given weekly, with the same total dose as when given intravenously) and can be considered as an alternative.[34][35] Furthermore, there is evidence that patients receiving subcutaneous immunoglobulin at home may have improved health-related quality of life compared with patients administered immunoglobulin replacement therapy in a hospital setting.[40][41]

Dose should be titrated according to the IgG trough level, which is patient-specific (taken immediately before the next infusion).

A scoring system has been proposed to help guide decisions on immunoglobulin replacement, which might help with borderline cases in adults.[60]

Primary options

immune globulin (human): children: consult specialist for guidance on dose; adults: 400-600 mg/kg intravenously every 3-4 weeks

Consider – therapeutic/prophylactic antibiotic therapy

Back
ACUTE
|
primary hypogammaglobulinemia
|
significantly reduced total IgG
Consider – 

therapeutic/prophylactic antibiotic therapy

Treatment recommended for SOME patients in selected patient group

It is widely accepted that antibiotic use for acute infection in hypogammaglobulinemia is beneficial. Exact antibiotic regimens are developed based on local policy, individual microbiologic susceptibility, and patient characteristics.

Appropriate therapeutic antibiotics should be started promptly in patients with acute bacterial infection. These are ideally bactericidal rather than bacteriostatic. Most physicians advocate prolonged courses (at least 10-14 days), although evidence supporting this is limited.

Prophylactic antibiotics can also be considered if infections are frequent despite immunoglobulin therapy.[8] Prophylaxis is usually considered if there are >2 or 3 mild infections per year or at least one severe infection per year, but this has not been clearly defined.

Consider – management of bronchiectasis: chest physical therapy ± surgery

Back
ACUTE
|
primary hypogammaglobulinemia
|
significantly reduced total IgG
Consider – 

management of bronchiectasis: chest physical therapy ± surgery

Treatment recommended for SOME patients in selected patient group

Chest physical therapy is indicated in established bronchiectasis.

Surgery may be necessary for localized areas of bronchiectasis.

1st line – therapeutic/prophylactic antibiotic therapy

Back
ACUTE
|
primary hypogammaglobulinemia
|
reduced IgA/IgG subclass/specific antibody production
1st line – 

therapeutic/prophylactic antibiotic therapy

Primary immunodeficiency diseases with normal total IgG but reduced specific components are often less severe than those with reduced total IgG. For example, IgA or IgG subclass deficiency may not require any treatment. If symptomatic, they can usually be managed with antibiotics alone.

It is widely accepted that antibiotic use for acute infection in hypogammaglobulinemia is beneficial. Exact antibiotic regimens are developed based on local policy, individual microbiologic susceptibility, and patient characteristics.

Appropriate therapeutic antibiotics should be started promptly in patients with acute bacterial infection. These are ideally bactericidal rather than bacteriostatic. Most physicians advocate prolonged courses (at least 10-14 days), although evidence supporting this is limited.

Prophylactic antibiotics can also be considered if infections are frequent despite immunoglobulin therapy.[8] Prophylaxis is usually considered if there are >2 or 3 mild infections per year or at least one severe infection per year, but this has not been clearly defined.

Consider – referral to specialist center for replacement immunoglobulin therapy

Back
ACUTE
|
primary hypogammaglobulinemia
|
reduced IgA/IgG subclass/specific antibody production
Consider – 

referral to specialist center for replacement immunoglobulin therapy

Treatment recommended for SOME patients in selected patient group

Referral to appropriate specialist centers may be necessary for further investigations and definitive treatment.

Immunoglobulin replacement may be considered in cases of impaired specific antibody production where there is severe disease or complications.

If immunoglobulin replacement is commenced, it is worth stopping antibiotic therapy (preferably in the spring in temperate countries) after a period of time to re-evaluate immunologic status.

Evidence suggests achieving IgG levels >500 mg/dL reduces infection frequency, and levels >800 to 900 mg/dL may further improve respiratory outcomes.[42][43][44] In most cases of primary antibody deficiency, treatment with immunoglobulin replacement is lifelong.

Subcutaneous immunoglobulin is therapeutically equivalent to intravenous immunoglobulin (usually given weekly, with the same total dose as when given intravenously) and can be considered as an alternative.[34][35]

Furthermore, there is evidence that patients receiving subcutaneous immunoglobulin at home may have improved health-related quality of life compared with patients administered immunoglobulin replacement therapy in a hospital setting.[40][41]

Dose should be titrated according to the IgG trough level, which is patient-specific (taken immediately before the next infusion).

Primary options

immune globulin (human): children: consult specialist for guidance on dose; adults: 400-600 mg/kg intravenously every 3-4 weeks

Consider – management of bronchiectasis: chest physical therapy ± surgery

Back
ACUTE
|
primary hypogammaglobulinemia
|
reduced IgA/IgG subclass/specific antibody production
Consider – 

management of bronchiectasis: chest physical therapy ± surgery

Treatment recommended for SOME patients in selected patient group

Chest physical therapy is indicated in established bronchiectasis.

Surgery may be necessary for localized areas of bronchiectasis.

1st line – urgent referral to specialist center

Back
ACUTE
|
primary hypogammaglobulinemia
|
severe combined immunodeficiency (SCID)
1st line – 

urgent referral to specialist center

SCID is a medical emergency.

Patients should be referred to specialist centers for confirmed diagnosis and treatment as soon as it is suspected. It may be suspected with low absolute lymphocyte counts and low immunoglobulins.

Plus – hematopoietic stem cell transplantation or gene therapy

Back
ACUTE
|
primary hypogammaglobulinemia
|
severe combined immunodeficiency (SCID)
Plus – 

hematopoietic stem cell transplantation or gene therapy

Treatment recommended for ALL patients in selected patient group

Specialist treatment should be undertaken as quickly as possible. Outcomes are better with earlier diagnosis and intervention. Definitive treatment includes hematopoietic stem cell transplantation.

Gene therapy is an emerging technology that has also been used in X-linked SCID and adenosine deaminase-deficient SCID.

Plus – immunoglobulin replacement therapy ± PEG-ADA replacement

Back
ACUTE
|
primary hypogammaglobulinemia
|
severe combined immunodeficiency (SCID)
Plus – 

immunoglobulin replacement therapy ± PEG-ADA replacement

Treatment recommended for ALL patients in selected patient group

Immunoglobulin replacement therapy is given while awaiting definitive treatment. Dose should be titrated according to the IgG trough level, which is patient-specific (taken immediately before the next infusion).

Polyethylene glycol-modified adenosine deaminase (PEG-ADA) replacement can also be considered in ADA-deficient SCID.[25]

Primary options

immune globulin (human): children: consult specialist for guidance on dose; adults: 400-600 mg/kg intravenously every 3-4 weeks

Consider – therapeutic/prophylactic antibiotic therapy

Back
ACUTE
|
primary hypogammaglobulinemia
|
severe combined immunodeficiency (SCID)
Consider – 

therapeutic/prophylactic antibiotic therapy

Treatment recommended for SOME patients in selected patient group

It is widely accepted that antibiotic use for acute infection in hypogammaglobulinemia is beneficial. Exact antibiotic regimens are developed based on local policy, individual microbiologic susceptibility, and patient characteristics.

Appropriate therapeutic antibiotics should be started promptly in patients with acute bacterial infection. These are ideally bactericidal rather than bacteriostatic. Most physicians advocate prolonged courses (at least 10-14 days), although evidence supporting this is limited.

Prophylactic antibiotics can also be considered if infections are frequent despite immunoglobulin therapy.[8] Prophylaxis is usually considered if there are >2 or 3 mild infections per year or at least one severe infection per year, but this has not been clearly defined.

Consider – management of bronchiectasis: chest physical therapy ± surgery

Back
ACUTE
|
primary hypogammaglobulinemia
|
severe combined immunodeficiency (SCID)
Consider – 

management of bronchiectasis: chest physical therapy ± surgery

Treatment recommended for SOME patients in selected patient group

Chest physical therapy is indicated in established bronchiectasis.

Surgery may be necessary for localized areas of bronchiectasis.

1st line – referral to specialist center

Back
ACUTE
|
primary hypogammaglobulinemia
|
non-SCID cellular and antibody deficiency
1st line – 

referral to specialist center

In nonsevere combined immunodeficiencies with both cellular and antibody defects (including common variable immunodeficiency), referral to specialist centers is important for definitive investigation and management.

Plus – hematopoietic stem cell transplantation or gene therapy

Back
ACUTE
|
primary hypogammaglobulinemia
|
non-SCID cellular and antibody deficiency
Plus – 

hematopoietic stem cell transplantation or gene therapy

Treatment recommended for ALL patients in selected patient group

Specific treatment protocols are customized for the various individual diseases. Specialist therapy in the form of hematopoietic stem cell transplantation or gene therapy may be required.

Plus – immunoglobulin replacement therapy

Back
ACUTE
|
primary hypogammaglobulinemia
|
non-SCID cellular and antibody deficiency
Plus – 

immunoglobulin replacement therapy

Treatment recommended for ALL patients in selected patient group

Given while awaiting definitive treatment and after transplant while awaiting B-cell reconstitution.

Dose should be titrated according to the IgG trough level, which is patient-specific (taken immediately before the next infusion).

Primary options

immune globulin (human): children: consult specialist for guidance on dose; adults: 400-600 mg/kg intravenously every 3-4 weeks

Consider – therapeutic/prophylactic antibiotic therapy

Back
ACUTE
|
primary hypogammaglobulinemia
|
non-SCID cellular and antibody deficiency
Consider – 

therapeutic/prophylactic antibiotic therapy

Treatment recommended for SOME patients in selected patient group

It is widely accepted that antibiotic use for acute infection in hypogammaglobulinemia is beneficial. Exact antibiotic regimens are developed based on local policy, individual microbiologic susceptibility, and patient characteristics.

Appropriate therapeutic antibiotics should be started promptly in patients with acute bacterial infection. These are ideally bactericidal rather than bacteriostatic. Most physicians advocate prolonged courses (at least 10-14 days), although evidence supporting this is limited.

Prophylactic antibiotics can also be considered if infections are frequent despite immunoglobulin therapy.[8] Prophylaxis is usually considered if there are >2 or 3 mild infections per year or at least one severe infection per year, but this has not been clearly defined.

Consider – management of bronchiectasis: chest physical therapy ± surgery

Back
ACUTE
|
primary hypogammaglobulinemia
|
non-SCID cellular and antibody deficiency
Consider – 

management of bronchiectasis: chest physical therapy ± surgery

Treatment recommended for SOME patients in selected patient group

Chest physical therapy is indicated in established bronchiectasis.

Surgery may be necessary for localized areas of bronchiectasis.

secondary hypogammaglobulinemia

1st line – treatment of underlying cause

Back
ACUTE
|
secondary hypogammaglobulinemia
1st line – 

treatment of underlying cause

The underlying cause should be treated and medications that might result in hypogammaglobulinemia discontinued if possible.[2]

Secondary hypogammaglobulinemia has various causes related to impaired production or increased loss of immunoglobulins.[3][16]

Impaired production can be associated with hematologic malignancy (e.g., myeloma, leukemia, lymphoma), medication (e.g., rituximab, carbamazepine, phenytoin, antimalarials, disease-modifying antirheumatic drugs, cytotoxic or immunosuppressive therapy), radiation, or malnutrition.[2]

Increased loss of immunoglobulins can be associated with protein-losing enteropathy (e.g., from inflammatory bowel disease, autoimmune enteropathy, intestinal lymphangiectasia), severe nephrotic syndrome (although most patients with nephrotic syndrome have preserved immunoglobulin levels), or intestinal lymphangiectasia.[2]

Consider – replacement immunoglobulin therapy

Back
ACUTE
|
secondary hypogammaglobulinemia
Consider – 

replacement immunoglobulin therapy

Treatment recommended for SOME patients in selected patient group

Guidelines support the use of replacement immunoglobulin in patients with severe or recurrent infections, ineffective antimicrobial treatment, and either proven specific antibody failure or serum IgG level of <400 mg/dL.[2][46][47] 

Replacement immunoglobulin therapy may be considered for hypogammaglobulinemia secondary to hematologic malignancy (B-cell chronic lymphocytic leukemia, non-Hodgkin lymphoma, multiple myeloma, other B-cell tumors) and after hematopoietic stem cell transplantation.[48][49][50][51]

Evidence supporting the use of immunoglobulin replacement in other causes of secondary hypogammaglobulinemia, including following solid organ transplant, is limited.[2][52][53][54] 

Dose should be titrated according to the IgG trough level, which is patient-specific (taken immediately before the next infusion).

Primary options

immune globulin (human): children: consult specialist for guidance on dose; adults: 400-600 mg/kg intravenously every 3-4 weeks

Consider – therapeutic/prophylactic antibiotic therapy

Back
ACUTE
|
secondary hypogammaglobulinemia
Consider – 

therapeutic/prophylactic antibiotic therapy

Treatment recommended for SOME patients in selected patient group

It is widely accepted that antibiotic use for acute infection in hypogammaglobulinemia is beneficial. Exact antibiotic regimens are developed based on local policy, individual microbiologic susceptibility, and patient characteristics.

Appropriate therapeutic antibiotics should be started promptly in patients with acute bacterial infection. These are ideally bactericidal rather than bacteriostatic. Most physicians advocate prolonged courses (at least 10-14 days), although evidence supporting this is limited.

Prophylactic antibiotics can also be considered if infections are frequent despite immunoglobulin therapy.[8] Prophylaxis is usually considered if there are >2 or 3 mild infections per year or at least one severe infection per year, but this has not been clearly defined.

Consider – management of bronchiectasis: chest physical therapy ± surgery

Back
ACUTE
|
secondary hypogammaglobulinemia
Consider – 

management of bronchiectasis: chest physical therapy ± surgery

Treatment recommended for SOME patients in selected patient group

Chest physical therapy is indicated in established bronchiectasis.

Surgery may be necessary for localized areas of bronchiectasis.

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Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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