Table 1.

Features of proliferative vs fibrotic IgG4-RD

ProliferativeFibrotic
Clinical Involvement of specific organs
Symptoms are from tumefactive swelling of organs and organ dysfunction
Chronic, relapsing and remitting 
Involvement of body regions rather than distinct organs
Contiguous spread and architectural distortion
Progressive disease
Chronic, long-standing disease (median time to diagnosis >6 months) 
Organ involvement Lacrimal and major salivary glands
Lymph nodes
Orbits and sinuses
Lungs and airways
Vasculature (aorta, coronary arteries)
Pancreas and hepatobiliary system
Kidneys 
Retroperitoneum/aortitis
Mediastinum
Abdominal mesenteritis
Thyroid
Meninges 
Laboratory High serum IgG4 (especially Asian patients)
Frequent elevation in IgE
Eosinophilia
Hypocomplementemia
CRP and erythrocyte sedimentation rate are low or modestly elevated in most cases 
Normal or slightly elevated serum IgG4 and IgE
Normal complement
CRP and erythrocyte sedimentation rate are low in most cases but elevated in the subset with active aortitis 
Radiology CT scan neck to pelvis sufficient for most
If lacrimal swelling → CT head as well to assess for orbital involvement 
For fibrotic disease, FDG-PET may be helpful to rule out histiocytosis (bone involvement) or lymphoma/metastatic cancer.
FAPI-PET is an emerging tool for assessing fibrotic disease. 
Pathology Dense lymphoplasmacytic infiltrate with many IgG4+ plasma cells
Scattered eosinophils
Storiform fibrosis
Obliterative phlebitis rare 
Scant lymphoplasmacytic infiltrate with scattered IgG4+ plasma cells
Storiform fibrosis predominant
Obliterative phlebitis predominant 
Treatment Typically responsive to glucocorticoids and B-cell depletion Glucocorticoids and B-cell depletion halt progression, but fibrosis is often not reversible. 
ProliferativeFibrotic
Clinical Involvement of specific organs
Symptoms are from tumefactive swelling of organs and organ dysfunction
Chronic, relapsing and remitting 
Involvement of body regions rather than distinct organs
Contiguous spread and architectural distortion
Progressive disease
Chronic, long-standing disease (median time to diagnosis >6 months) 
Organ involvement Lacrimal and major salivary glands
Lymph nodes
Orbits and sinuses
Lungs and airways
Vasculature (aorta, coronary arteries)
Pancreas and hepatobiliary system
Kidneys 
Retroperitoneum/aortitis
Mediastinum
Abdominal mesenteritis
Thyroid
Meninges 
Laboratory High serum IgG4 (especially Asian patients)
Frequent elevation in IgE
Eosinophilia
Hypocomplementemia
CRP and erythrocyte sedimentation rate are low or modestly elevated in most cases 
Normal or slightly elevated serum IgG4 and IgE
Normal complement
CRP and erythrocyte sedimentation rate are low in most cases but elevated in the subset with active aortitis 
Radiology CT scan neck to pelvis sufficient for most
If lacrimal swelling → CT head as well to assess for orbital involvement 
For fibrotic disease, FDG-PET may be helpful to rule out histiocytosis (bone involvement) or lymphoma/metastatic cancer.
FAPI-PET is an emerging tool for assessing fibrotic disease. 
Pathology Dense lymphoplasmacytic infiltrate with many IgG4+ plasma cells
Scattered eosinophils
Storiform fibrosis
Obliterative phlebitis rare 
Scant lymphoplasmacytic infiltrate with scattered IgG4+ plasma cells
Storiform fibrosis predominant
Obliterative phlebitis predominant 
Treatment Typically responsive to glucocorticoids and B-cell depletion Glucocorticoids and B-cell depletion halt progression, but fibrosis is often not reversible. 

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