A flowchart illustrates the process of CG screening and downstream testing for patients. The flowchart starts with an LFT performed for a patient in a primary or secondary care setting. A note advises that if performed in a secondary care setting, consider prior use of intravenous fluids in the surgical, medical, or intensive care settings, which may temporarily lower the CG result. A second note advises considering comorbidities and treatments which may influence the CG result. The flowchart then checks CG levels, which branch into low or high. If CG levels are low, a red-bordered alert advises that low calculated globulin may represent antibody deficiency, and recommends considering immunoglobulin measurement if there is a history of infections, and noting if the patient has repeated low CG. The pathway then asks whether the patient presents with features suggestive of immunodeficiency, such as an appropriate infection history. If yes, check Ig levels plus or minus SPEP. If Igs are low, evaluate infection burden and consider vaccine responses. If IgG is less than 4 g per L and, or, or the patient has a significant infection burden, consider seeking advice or referral to an immunologist or hematologist. If CG levels are high, check Ig levels plus SPEP. This branches into two pathways. If paraproteins are present, possible causes include lymphoproliferative diseases such as myeloma, lymphoma, and Waldenstrom Macroglobulinemia, and plasma cell decreases, leading to evaluating for possible SID and then considering referral to hematology. If a polyclonal antibody increase is present, possible causes include viral infections, liver diseases, autoimmune diseases, and sarcoidosis, leading to a recommendation to consider further evaluation.
Flowchart to guide CG screening and downstream testing (10, 16, 17, 52, 55, 56, 57). aCommon manifestations of immunodeficiency include infections, inflammation, autoimmunity, and allergy. bComorbidities may include nephrotic syndrome, hepatic insufficiency, hyperlipoproteinemia, metastatic malignancy, and iron deficiency anemia. Treatments may include plasma exchange and FcRn inhibitors. cLow and high CG action/cut-off levels range from <18 to 23 g/L and >33 g/L, respectively. Low CG levels may be indicative of a primary or secondary antibody deficiency; high CG levels may indicate lymphoproliferative disease, e.g., myeloma, viral infections, or autoimmune diseases (17). dSerial low CG results may improve sensitivity and specificity for non-transient reductions in Ig. CT, computed tomography; IgG, immunoglobulin G; SPEP, serum protein electrophoresis; CG, calculated globulin; FcRn, neonatal Fc receptor; Ig, immunoglobulin; LFT, liver function test; SID, secondary immunodeficiency.