Complications
Infusion-related reactions include shivering, flushes, headache, nausea, and fatigue. These have reduced considerably in recent years with improvements in manufacturing, although the likelihood is increased with a higher infusion rate and if given at the time of concurrent active infection. The presence of anti-IgA antibodies is thought to be related to anaphylactoid reaction to products with a high IgA content, although this finding is not universal.[39][71] Some authorities advocate measuring anti-IgA antibodies to guide choice of immunoglobulin product, particularly in common variable immunodeficiency patients with undetectable levels of serum IgA, although this practice is not universal.
Viral transmission of hepatitis C causing significant morbidity in affected patients was last reported in 1994.[81] Recognizing the hepatitis C virus, screening blood donors, and changes in the manufacturing process make this extremely unlikely to happen now. Most physicians advocate annual monitoring of hepatitis B surface antigen, and hepatitis B and C polymerase chain reaction for screening. There also remains a theoretical possibility of prion transmission through immunoglobulin products.
Respiratory tract infections (particularly with encapsulated bacteria) are the most common infection in hypogammaglobulinemia; they affect >95% of patients at some stage.[17] Prompt treatment of infection is important, and prophylactic antibiotics may be necessary.
Chronic respiratory disease with bronchiectasis is reported in 17% to 76% of patients due to late diagnosis of common variable immunodeficiency (CVID) and inadequate treatment (may also occur despite adequate immunoglobulin therapy).[29][67][68] Monitoring for pulmonary complications includes serial pulmonary function tests and chest computed tomography (CT) scans. Caution with repeated CT scanning is necessary, as some patients with hypogammaglobulinemia are radiosensitive (e.g., with CVID, ataxia-telangiectasia, and related disorders) and more prone to malignancy with repeated exposure.[69][70] Disease progression is prevented and limited by early detection and adequate treatment of hypogammaglobulinemia, as well as prompt treatment of infection and chest physical therapy as appropriate.
Infectious diarrhea occurs in 5% to 32% of patients, and about 40% of patients with hypogammaglobulinemia have chronic mild diarrhea of unknown cause.[12] Stool samples should be screened for pathogens.
B-cell lymphoid malignancy is the most common associated malignancy, particularly with common variable immunodeficiency (CVID), but the risk is increased in other forms of primary antibody deficiency as well.[18][19]
Patients with primary antibody deficiency have an increased risk of malignancy (estimated between 1.8- and 13-fold increase).[72][73][74] There is no consensus on monitoring for malignancy, although there should be a low threshold for investigation of suspicious symptoms. Certain hypogammaglobulinemias are associated with radiosensitivity (e.g., ataxia-telangiectasia, CVID), and indication for frequent computed tomography scanning should be balanced against potential radiation risk in these conditions.[69][70]
Persistent colonization with Helicobacter pylori may be a risk factor for gastric carcinoma.
Patients with primary antibody deficiency have an increased risk of malignancy (estimated between 1.8- and 13-fold increase).[72][73][74] There is no consensus on monitoring for malignancy, although there should be a low threshold for investigation of suspicious symptoms. Certain hypogammaglobulinemias are associated with radiosensitivity (e.g., ataxia-telangiectasia, common variable immunodeficiency), and indication for frequent computed tomography scanning should be balanced against potential radiation risk in these conditions.[69][70]
Autoimmune cytopenias are relatively common, particularly in common variable immunodeficiency (CVID); the strongest evidence suggests a rate of 11%.[75] In addition, 86% of these patients experienced their first episode of cytopenia before or concurrently with their diagnosis of CVID.[75] Cytopenia can be detected with complete blood count results; treatment follows standard protocols, including the use of corticosteroids.
Autoimmune cytopenias are relatively common, particularly in common variable immunodeficiency (CVID); the strongest evidence suggests a rate of 11%.[75] In addition, 86% of these patients experienced their first episode of cytopenia before or concurrently with their diagnosis of CVID.[75] Cytopenia can be detected with complete blood count results; treatment follows standard protocols, including the use of corticosteroids.
Granulomatous infiltration affecting the lungs has been reported in 8% to 22% of patients with common variable immunodeficiency (CVID) and is associated with a significantly poor prognosis.[17][76] The presence of splenomegaly may be a risk factor for the development of granulomatous lymphocytic interstitial lung disease in patients with CVID.[77][78] Other organs, including liver, lymph nodes, skin, kidneys, eyes, and nervous system, can also be affected. Etiology is unclear, although it is speculated that T-cell dysregulation or human herpes virus 8/cytomegalovirus infection might be responsible. Ideal treatment is unknown, although corticosteroids have been used as well as other immunosuppressants and biologic agents, including tumor necrosis factor-alpha inhibitors.
Patients with hypogammaglobulinemia (particularly in X-linked agammaglobulinemia) are more prone to enteroviral meningoencephalitis.[79] This has become less frequent. Treatment is with high doses of intravenous immunoglobulin (to maintain trough levels >700 mg/dL).[54] Intrathecal immunoglobulin has been used in the past.
Susceptibility to mycoplasma arthritis is increased in hypogammaglobulinemia.[80] This resolves with appropriate antibiotics and immunoglobulin replacement. More rarely, autoimmune joint disease and vasculitides have also been reported.
Celiac-like enteropathy is a less frequently reported gastrointestinal complication than infectious diarrhea. Etiology is less clear than with infectious complications, although it may be related to immune dysregulation. Gastrointestinal evaluation should be considered for unexplained gastrointestinal symptoms, but serologic testing (e.g., celiac antibodies) is not helpful, as it is likely to be negative as a consequence of the hypogammaglobulinemia.
Inflammatory bowel disease is a less frequently reported gastrointestinal complication than infectious diarrhea. Etiology is less clear than with infectious complications, although it may be related to immune dysregulation.
Inflammatory bowel disease is a less frequently reported gastrointestinal complication than infectious diarrhea. Etiology is less clear than with infectious complications, although it may be related to immune dysregulation.
Pernicious anemia is a less frequently reported gastrointestinal complication than infectious diarrhea. Etiology is less clear than with infectious complications, although it may be related to immune dysregulation. Gastrointestinal evaluation should be considered for unexplained gastrointestinal symptoms, but serologic testing (e.g., gastric parietal cell and intrinsic factor antibodies) is not helpful, as it is likely to be negative as a consequence of the hypogammaglobulinemia.
Mucosal nodules are a less frequently reported gastrointestinal complication than infectious diarrhea. Etiology is less clear than with infectious complications, although it may be related to immune dysregulation.
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