Table 3.

Common causes of PHGG divided by CRP

High CRP (>30  mg/L)Variable CRPLow CRP (<30  mg/L)
• Infection
• Malignancy
• Vasculitis
• Autoinflammatory
• Hematologic (CD, ECD)
Note: PHGG in these conditions is typically driven by IL-6 and other inflammatory cytokines. 
• Autoimmune (Sjӧgren syndrome, sarcoidosis)
• Iatrogenic (IVIG)
• Hematologic (lymphoma, RDD) 
• Liver disease
• IgG4-RD
• Immune deficiency (ALPS, dysgammaglobulinemias)
• Graves disease
Note: PHGG in these conditions is generally from immune dysregulation other than IL-6 signaling. In liver disease, loss of portal filtering and increased exposure to enteric antigens are implicated. 
High CRP (>30  mg/L)Variable CRPLow CRP (<30  mg/L)
• Infection
• Malignancy
• Vasculitis
• Autoinflammatory
• Hematologic (CD, ECD)
Note: PHGG in these conditions is typically driven by IL-6 and other inflammatory cytokines. 
• Autoimmune (Sjӧgren syndrome, sarcoidosis)
• Iatrogenic (IVIG)
• Hematologic (lymphoma, RDD) 
• Liver disease
• IgG4-RD
• Immune deficiency (ALPS, dysgammaglobulinemias)
• Graves disease
Note: PHGG in these conditions is generally from immune dysregulation other than IL-6 signaling. In liver disease, loss of portal filtering and increased exposure to enteric antigens are implicated. 

CRP is a surrogate for systemic inflammation and is the “rule of thumb” with many individual exceptions. For example, a patient with an inflammatory condition may have received corticosteroids suppressing their CRP, or a patient with a condition such as IgG4-RD may have a concomitant infection driving up the CRP.

ALPS, autoimmune lymphoproliferative syndrome.

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