IgG4-related diseases! How to tell?

50-year-old Uncle Li (pseudonym) went to the local hospital for a physical examination a month ago, and during the physical examination, ultrasound found "thickened bile ducts and obvious lumps in the pancreas"
.

After getting this result, Uncle Li and his family were a little worried, and re-examined the abdominal CT again and found that "the pancreas is massed, and the tumor cannot be ruled out", and the doctor in the local hospital also recommended to go to a large hospital for treatment as soon as possible, and the family's mood fell to the bottom
.

"This matter cannot be delayed!" Uncle Li's children immediately took him to Run Run Shaw Hospital affiliated to Zhejiang University School of Medicine, and the doctor asked whether the patient had recent symptoms such as weight loss, jaundice, abdominal pain, whether the stool was formed, and whether it was regular.

The doctor arranged blood drawing and puncture examination for him according to the situation, and finally found that Uncle Li's pancreatic "mass" was considered to be an "IgG4-related disease", which is an immune system disease, not a tumor! Subsequently, Uncle Li was transferred to the rheumatology and immunology department for treatment
.

What are IgG4-related diseases?

Presumably when you see this name

It was also the same as Uncle Li at that time

Full of question marks, right?

IgG4-related diseases

What is the disease?

IgG4-related disease (IgG4-RD) is a newly defined immune-mediated chronic inflammatory disease with fibrosis in recent years
.

The disease can affect multiple parts of the body, and the vast majority of patients have elevated
serum IgG4 levels.

The exact etiology and pathogenesis of IgG4-RD remain unclear
.
Studies have shown that potentially relevant factors include genetics, environment, especially microbial infection and molecular mimicry, autoantibodies, innate immunity and adaptive immunity
.

IgG4-RD is more common in middle-aged and elderly people, with a male-to-female ratio of about 8:3
.
There is no epidemiological data in China, and the prevalence of IgG4-RD reported in Japan is (0.
28~1.
08)/100,000
.

Although this disease is a benign inflammatory disease, a small number of patients have a tendency to self-heal, but most patients have a gradual progression trend, which can lead to dysfunction of important organs, so it should not be taken lightly
.
IgG4-RD

What are the symptoms?

IgG4-RD is often chronic, occult or subacute, with markedly elevated serum IgG4 levels and mass-like lesions being the most common clinical manifestations
.

The systemic symptoms of the disease are not prominent, fever is rare, and some patients will have fatigue and weight loss
.
Allergic diseases are common, such as allergic rhinitis, asthma, eczema, urticaria, etc
.

IgG4-RD can affect multiple organs and tissues throughout the body, and the onset of symptoms and clinical manifestations are varied
.
The clinical features of the main organs affected are as follows:

01 Salivary glands

Large sialadenitis is most common in IgG4-RD and typically presents with bilateral or unilateral painless enlargement of the submandibular, parotid gland, or sublingual glands, hard texture on palpation, and may be accompanied by dry mouth
.
The initial symptoms are not obvious, it is easy to be ignored, and when the organ enlargement is obvious, it is easy to be misdiagnosed as a tumor
.

02 Orbital lesions

Lacrimal gland involvement is common, manifested as unilateral or bilateral painless lacrimal gland enlargement, and patients may have a foreign body sensation and eye discomfort; Ophthalmic muscle lesions can be manifested as thickening of the eye muscles, and in severe cases, eyeball protrusion, blurred vision, double vision, etc.
may occur; Intraorbital inflammatory pseudoneoplasia can compress the optic nerve and may present with decreased vision or as exophthalmos
.

03 Pancreas

One
of the most commonly affected internal organs.
It usually begins with painless obstructive jaundice, some patients have epigastric pain, steatorrhea and weight loss, and a few can present as new-onset diabetes
.
Typical radiographic findings are diffuse pancreatic enlargement; Focal lesions may also occur, similar to tumor-like masses, and are easily confused
with pancreatic malignancy.

04 Biliary tract

The main clinical manifestations are abnormal liver function and obstructive jaundice dominated by elevated cholangioenzymes
.

05 Retroperitoneal tissue

The main clinical manifestations are pain or discomfort in the lower back and abdomen, and edema
of the lower extremities.

06 Thoracic organs

Patients may be asymptomatic or present with cough, asthma, shortness of breath, chest tightness, or chest pain
.
07 Urinary system

Renal parenchymal involvement is mainly manifested as tubulointerstitial nephritis, and a small number of patients have glomerular lesions dominated by proteinuria, which can cause acute or chronic renal insufficiency
in severe cases.
Imaging manifestations include renal parenchymal mass or multiple cortical nodules, diffuse enlargement of the kidney, renal pelvis mass, and thickening of the renal pelvis or ureteral wall
.
Prostate involvement is mainly manifested as an enlarged prostate, resulting in symptoms such as difficulty urinating and frequent urination
.

08 Endocrine system

The most commonly affected organ is the thyroid gland, called IgG4-associated sclerosing thyroiditis, which presents as diffuse enlargement, hardening, or a localized mass of the thyroid gland
.
There is pain, local swelling, dysphagia, hoarseness, and dyspnea due to compression of the trachea
.
In the vast majority of patients, hypothyroidism, antithyroid antibodies can be detected in serum, and histopathological biopsy can confirm the diagnosis
.

09 lymph nodes

Lymphadenopathy is common in IgG4-RD and can occur in more than half of patients, presenting with superficial or deep lymphadenopathy; Superficial lymphadenopathy is painless with well-defined
boundaries.

10 Cardiovascular system

Uncommon, but cardiovascular involvement can affect prognosis
.

Based on the above characteristics, do you think that this small immune disease is somewhat incredible, not only can imitate tumors vividly, but also imitate tumors in many parts of the body! Carelessness puts patients in panic and puts doctors in a dilemma
.

IgG4-related diseases

How is it diagnosed?

The clinical presentation of IgG4-RD is complex and diverse, sometimes difficult to distinguish from tumors, infections, and other immune disorders, and diagnosis requires a combination of clinical history, serology, imaging, and histopathological features
.

There are a variety of clinical diseases similar to the histopathological manifestations of IgG4-RD, which require differential diagnosis, such as chronic inflammation, tumors, infections, other autoimmune diseases (systemic vasculitis), multicenter Castleman disease, Rosai-Dorfman disease, inflammatory myofibroblastoma, etc.
, which can mimic IgG4-RD and cause misdiagnosis
.

IgG4-related diseases

How is it treated?

The overall goal of treatment is to control inflammation in the lesion, restore organ function, and maintain disease remission
.
Early treatment prevents irreversible organ damage
caused by inflammation and fibrosis.

The principles of treatment are as follows:

● Patients with symptoms and progressive disease activities need to be treated; Patients with asymptomatic visceral involvement who are assessed for progressive disease also require prompt treatment
.

● If important organs are affected and the lesions are active, such as pancreas, biliary tract, kidney, lung, retroperitoneal fibrosis, aortitis, central nervous system, etc.
, timely treatment can prevent organ damage and improve prognosis
.

● A small number of patients with asymptomatic lymphadenopathy or mild superficial gland enlargement and slow disease progression, such as IgG4-related tear adenitis, submandibular adenitis, and lymphadenopathy, can be closely observed and followed
.
Aggressive treatment
should be given once symptoms develop or activity accelerates.

● Treatment of IgG4-RD is divided into two phases
: induction of remission and maintenance therapy.
Current therapeutic products for IgG4-RD include glucocorticoids, traditional immunosuppressants, and biologics
.
Other adjuvant therapies include obstructive site tube drainage and surgery
.

IgG4-RD

What is the prognosis?

The disease has been known for a short time, and there are no data
on long-term survival.

Overall, the response to hormone therapy is relatively good, if there is no irreversible damage to important organs, the long-term prognosis is good, and the prognosis of patients with important organ damage and dysfunction is related to the degree of organ damage, such as pancreas, kidney, lung, hypertrophic dura meningitis or pituitary inflammation
.

This disease is currently incurable and easy to recur, so it is necessary to regularly follow up and monitor the condition under the guidance of rheumatologists, which is particularly important
to improve the prognosis.