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[Conditions](https://durgical.com/en/conditions/) · [Rheumatology](https://durgical.com/en/conditions/)

# IgG4-related disease

An immune disease that causes tumour-like swelling and scarring of glands and organs such as the pancreas, salivary glands and tear glands.

Updated 2026-11-01

## Structures involved

Tap one to see what it is and open it in 3D.

- [Parotid gland](https://durgical.com/en/anatomy/parotid-gland/)
- [Submandibular gland](https://durgical.com/en/anatomy/submandibular-gland/)
- [Lacrimal gland](https://durgical.com/en/anatomy/lacrimal-gland/)
- [Thyroid gland](https://durgical.com/en/anatomy/thyroid-gland/)
- [Neck lymph nodes](https://durgical.com/en/anatomy/lymph-nodes-of-neck/)
- [Sublingual gland](https://durgical.com/en/anatomy/sublingual-gland/)
- [Pancreas](https://durgical.com/en/anatomy/pancreas/)
- [Common bile duct](https://durgical.com/en/anatomy/bile-duct/)
- [Abdominal aorta](https://durgical.com/en/anatomy/abdominal-aorta/)

## Why it happens

- [Fibrosis in organs: TGF-β and the myofibroblast](https://durgical.com/en/general-pathology/fibrosis-in-organs-tgf-and-the-myofibroblast/)
- [Chronic inflammation: causes, cells and features](https://durgical.com/en/general-pathology/chronic-inflammation-causes-cells-and-features/)
- [Immunoglobulins (antibodies)](https://durgical.com/en/biochemistry/enzymes/immunoglobulins/)
- [Pancreas: acini and islets](https://durgical.com/en/histology/pancreas-acini-and-islets/)

## What it is

A chronic immune-mediated fibroinflammatory condition that forms tumour-like masses in one or several organs. Biopsy shows a dense infiltrate of IgG4-positive plasma cells, storiform fibrosis and obliterative phlebitis. Common sites are the pancreas (type 1 autoimmune pancreatitis), bile ducts, salivary and lacrimal glands, orbit, retroperitoneum, aorta and [kidneys](https://durgical.com/en/anatomy/kidney/).

## Who gets it

Rare and probably underdiagnosed. It mainly affects middle-aged and older men; [head and neck](https://durgical.com/en/anatomy/region/head-and-neck/) forms are more balanced between sexes. Most data come from Japan, Europe and the United States, and Latin American case series are growing as awareness increases.

## Causes

- Cause unknown; immune-mediated with activated B cells, plasmablasts and CD4 cytotoxic T cells
- Possible autoantigens and genetic susceptibility
- Allergic (atopic) background in many patients

## Risk factors

- Male sex
- Age over 50
- History of allergy or asthma

## Pathophysiology

Cytotoxic CD4 T cells and activated B cells sustain inflammation and stimulate fibroblasts, producing storiform (cartwheel) fibrosis and occlusion of veins. Organs enlarge painlessly and later scar, which can cause loss of function (exocrine and endocrine pancreatic failure, obstructed bile ducts or [ureters](https://durgical.com/en/anatomy/ureter/)). The high IgG4 level reflects the process but is probably not itself the cause of damage.

## Symptoms and signs

- Painless bilateral swelling of the submandibular, parotid or lacrimal glands (formerly Mikulicz disease)
- Painless obstructive jaundice and weight loss (autoimmune pancreatitis or sclerosing cholangitis)
- Proptosis or swelling around the eyes
- Back or flank pain from retroperitoneal fibrosis
- Enlarged lymph nodes
- New diabetes or fatty stools from pancreatic insufficiency

## Red flags

- Painless jaundice in an older adult (must exclude pancreatic cancer or cholangiocarcinoma)
- Rising creatinine with hydronephrosis (ureteric obstruction from retroperitoneal fibrosis)
- Visual loss or diplopia from orbital disease
- Aortic aneurysm or aortitis on imaging

## Diagnosis

**Clinical**
Based on typical organ involvement, imaging, serum IgG4 and above all histology, using the 2019 ACR/EULAR classification criteria. Cancer, lymphoma and other mimics must be excluded.

**Tests**
Serum IgG4 is raised in most but is neither sensitive nor specific; eosinophilia, raised IgE and low complement may be present. Biopsy shows a lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis and obliterative phlebitis. [Liver](https://durgical.com/en/anatomy/liver/) tests, glucose, lipase and creatinine to assess organ function.

**Imaging**
CT or MRI showing a diffusely enlarged «sausage-shaped» [pancreas](https://durgical.com/en/anatomy/pancreas/) with a capsule-like rim, [bile duct](https://durgical.com/en/anatomy/bile-duct/) strictures, enlarged glands or periaortic soft tissue; ultrasound for salivary glands; PET-CT to map disease extent.

## Differential diagnosis

- Pancreatic cancer and cholangiocarcinoma
- Primary sclerosing cholangitis
- Sjögren disease
- Lymphoma
- Sarcoidosis
- Granulomatosis with polyangiitis

## Goal of treatment

Control inflammation before irreversible fibrosis develops, relieve obstruction and preserve organ function.

## Treatment

**Medical**
Systemic corticosteroids are first-line and usually produce a rapid response, which also supports the diagnosis; they are tapered over months.

**Medical**
Rituximab or steroid-sparing drugs (azathioprine, mycophenolate) for relapses or steroid dependence; biliary stenting when obstruction does not resolve; insulin or pancreatic enzymes when the pancreas has failed.

**Follow-up**
Long-term follow-up with serum IgG4, imaging and organ function tests, since relapses are common; monitoring for glucose, bone and infection side effects of steroids.

## Complications

- Pancreatic exocrine and endocrine insufficiency (diabetes)
- Biliary cirrhosis from chronic bile duct strictures
- Hydronephrosis and kidney failure
- Aortic aneurysm or dissection
- Relapse in the same or new organs

## Prognosis

Responds well to corticosteroids in most patients, but relapse is common when they are reduced. Early treatment prevents permanent fibrosis; late disease may leave organ damage even when inflammation is controlled.

## Test yourself

Think of the answer, then tap the question to see it.

## What are the three key histological features of IgG4-related disease?

Dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis and obliterative phlebitis.

## Which type of autoimmune pancreatitis belongs to IgG4-related disease?

Type 1 autoimmune pancreatitis.

## What is the first-line treatment?

Systemic corticosteroids.

## Why is a raised serum IgG4 alone not enough for the diagnosis?

It is neither sensitive nor specific; cancer, lymphoma and other mimics must be excluded, ideally with biopsy.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/conditions/igg4-related-disease/)

## Related conditions

- [Chronic pancreatitis](https://durgical.com/en/conditions/chronic-pancreatitis/)
- [Pancreatic cancer](https://durgical.com/en/conditions/pancreatic-cancer/)
- [Primary sclerosing cholangitis](https://durgical.com/en/conditions/primary-sclerosing-cholangitis/)
- [Cholangiocarcinoma (bile duct cancer)](https://durgical.com/en/conditions/cholangiocarcinoma/)
- [Sjögren disease](https://durgical.com/en/conditions/sjogren-disease/)
- [Sialolithiasis (salivary stones)](https://durgical.com/en/conditions/sialolithiasis/)
- [Acute suppurative sialadenitis (bacterial parotitis)](https://durgical.com/en/conditions/acute-suppurative-sialadenitis/)
- [Thyroiditis (subacute, painless and postpartum)](https://durgical.com/en/conditions/thyroiditis/)
- [Sarcoidosis](https://durgical.com/en/conditions/sarcoidosis/)
- [Non-Hodgkin lymphoma](https://durgical.com/en/conditions/non-hodgkin-lymphoma/)
- [Granulomatosis with polyangiitis](https://durgical.com/en/conditions/granulomatosis-with-polyangiitis/)
- [Thyroid eye disease (Graves orbitopathy)](https://durgical.com/en/conditions/thyroid-eye-disease/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [IgG4-related disease](https://dermnetnz.org/topics/igg4-related-disease) (DermNet, 2026).

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Source: https://durgical.com/en/conditions/igg4-related-disease/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/igg4-related-disease/