IgG4-associated Autoimmune Diseases: Causes, Symptoms & Treatment

IgG4-associated autoimmune diseases are a group of diseases in which the immune system attacks the body’s own tissues. The diseases are categorized as systemic diseases and can affect multiple organ systems simultaneously or sequentially. In the meantime, the administration of glucocorticoids has become common for the symptomatic treatment of these previously incurable diseases.

What are IgG4-associated autoimmune diseases?

The human immune system recognizes pathogens and other foreign bodies that have invaded the human body. The cells of the immune system attack the foreign bodies after identification in order to eliminate them and thus protect the organism. In autoimmune diseases, the immune system falsely recognizes the body’s own tissues as foreign and attacks healthy cells of its own organism. The so-called IgG4-associated diseases are a group of autoimmune diseases. They are systemic diseases that can, in principle, be directed against all tissues and organs of the body. IgG4-associated autoimmune diseases cause severe swelling and fibrotization and arise in an immune-mediated manner. The group is composed of chronic diseases with proliferation of antibody-producing IgG4-positive plasma cells. The clinical picture of IgG4-associated autoimmune diseases may differ significantly from case to case. IgG4-associated diseases are most common in East Asia and preferentially affect men between middle and advanced age. Sometimes the best-known IgG4-associated disease is IgG4-associated pancreatitis or autoimmune pancreatitis type 1.

Causes

As with all other immune diseases, the cause of IG4-associated immune diseases has been controversial. Meanwhile, many researchers assume an independent mechanism of development. According to scientists, the so-called “cross-talk” between the innate and the acquired immune system is disturbed in patients with this group of diseases. The so-called Th2 response of the defense system seems to play a central role in the pathogenesis of the diseases. The reaction activates regulatory T lymphocytes and stimulates the formation of transforming growth factor ß and interleukin 10. These substances in turn stimulate the body to produce IgG4. The triggering mechanism for the Th2 response is as yet unknown. Some authors speak of autoantigens, while others discuss infectious agents. According to current findings, autoantibodies against prohibitin are present in the majority of all patients. This association argues for a purely autoimmune genesis of most IgG4-RD group. However, not every IgG4 patient is affected by autoimmune disease. Better stated, it remains largely unclear whether IgG4 proliferation is causative for disease development or occurs as an epiphenomenon after disease development.

Symptoms, complaints, and signs

Symptoms of IgG4-associated autoimmune disease vary from case to case and depend primarily on the exact disease. Apparently, IgG4-RD often manifest in different organs or tissue systems at the same time or in quick succession. For this reason, they are referred to as systemic diseases. The degree of organic dysfunction depends on the individual case. In principle, enlargement or swelling of affected organs and tissues represents the common feature of all IgG4-associated autoimmune diseases. In most diseases of the group, severe scarring occurs in the sense of sclerosis of the tissue. Compression of excretory ducts has been observed especially in diseases such as Miculicz syndrome, sclerosing cholangitis, and Ormond disease. This phenomenon entails congestion of secretions, often associated with secondary symptoms. More than a dozen different diseases are now classified as IG4-associated autoimmune diseases. In some diseases from the group, mild pain symptomatology may occur in the affected tissues.

Diagnosis and disease course

As part of the diagnostic process, organic examinations of various organs and tissues of the body must be performed to detect IgG4-associated diseases. Only when several organ systems are affected, for example, combined when the lungs, kidneys, liver, or pancreas are affected, can we speak of an IgG4-associated disease.Laboratory values and imaging are part of standard diagnostics. Histology is also required in most cases. The prognosis for patients with IgG4-associated autoimmune diseases is relatively unfavorable due to susceptibility to secondary diseases. Apparently, diseases of the group make the risk of tuberculosis and cancer increase. Chronicity of IgG4-associated diseases is also associated with poor prognosis. Regularly affected tissues may take irreversible damage. This circumstance is particularly unfavorable when organs are affected.

Complications

IgG4-associated autoimmune diseases can cause serious damage and complications to organs, which can also be life-threatening for the patient. This can limit the life expectancy if no immediate treatment of the disease occurs. However, it is not possible to predict which organs will be affected and how the symptoms will manifest themselves. In most cases, however, there is an enlargement of the organs and thus pain. They can also swell and lead to scars. Not infrequently, there is also damage to the patient’s skeleton and stabbing pain. The affected person generally feels ill and suffers from low resilience. The muscles often ache and there are restrictions in movement. In most cases, treatment of IgG4-associated autoimmune diseases is only symptomatic, as causative treatment is not possible. In this case, the patient is administered medication and no further complications occur. However, complications can then arise if organs have been irreversibly damaged. In this case, death occurs or transplantation is necessary to keep the patient alive.

When should you go to the doctor?

Swelling on the body and diffuse skin changes should be presented to a physician. If there is a feeling of tightness inside the body, if the skin abnormalities spread further, or if malaise sets in, a physician is needed to clarify the symptoms. In case of dysfunction of individual systems or a general feeling of illness, a visit to the doctor is necessary. If acute situations occur, such as a loss of consciousness, an emergency physician must be called. First aid measures are necessary to ensure the survival of the patient until the doctor arrives. In the event of pain, a drop in performance level, concentration problems, dizziness or sleep disturbances, a doctor must be consulted. If gait unsteadiness, headaches, bleeding, stomach problems, diarrhea or constipation occur, a physician should be consulted. If cramps set in or mental abnormalities are noticed, a doctor should be consulted. Problems with urination, breathing disorders or intermittent breathing, should be examined and treated. If the affected person suffers from disturbances in mobility, joint problems or strong changes in weight, a doctor should be consulted. If there are changes in heart rhythm, high blood pressure or circulatory problems, a follow-up visit to a physician is necessary. Repeated vomiting, nausea and sputum are considered unusual and should be examined by a physician. If there is no cold, a doctor should be consulted as soon as the complaints persist for several days.

Treatment and therapy

Causative treatment sometimes does not exist for patients with IgG4-associated autoimmune disease, because the cause has not yet been conclusively determined. Therefore, therapy is exclusively symptomatic. In other words, diseases of this group are not curable up to the present time. Experience has shown that glucocorticoids have been used for symptomatic treatment of patients with IgG4-associated diseases. If there is intolerance to steroids or a steroid-refractory course occurs, rituximab can be administered. The drug rapidly leads to improvement in clinical and histologic findings. The B cells in the patient’s tissues decrease. The same is true for IgG4 levels in the serum of the affected person. It is important to have an actual confirmed diagnosis before administering any medication. Especially lymphoma diseases have to be excluded by differential diagnosis before starting therapy. Other therapy options have not yet been documented.Especially in IgG4-associated autoimmune pancreatitis, excellent response to glucocorticoids has been reported in a large proportion of all cases. Irreversible damage to organs may need to be compensated with organ transplantation.

Outlook and prognosis

IgG4-associated autoimmune diseases are incurable according to current scientific and medical knowledge. Therefore, the prognosis is described as unfavorable. Nevertheless, there are therapeutic approaches that provide relief of individual symptoms and thus contribute to an improvement in the quality of life. The chronic course of the disease has a strong impact on the person affected. In addition to various dysfunctions and pain, there is also the threat of life-threatening progressions. If organs are affected, the prognosis deteriorates significantly. Life expectancy is usually shortened in these patients, as irreparable damage occurs. Alternatively, organ transplants can be performed as a life-prolonging measure. If a donor organ is available, this path is often chosen. The surgical procedure is associated with risks and side effects. If no complications occur and the donor organ is accepted by the organism, the patient normally experiences an improvement in health. If the operation is unsuccessful, symptoms increase and the general condition is severely weakened. In the case of organ enlargement, severe pain is common. As a result, the patient must undergo long-term therapy. As soon as the treatment is discontinued, there is a regression of the complaints. A permanent relief is currently not possible, because so far no exact cause for the development of the autoimmune disease could be found. Treatment of the individually occurring symptoms is the focus of medical care.

Prevention

The causes and detailed pathogenesis for IgG4-associated diseases have not yet been conclusively elucidated. As long as the causes of the diseases remain unclear, there will be no promising avenues for prevention. This relationship characterizes not only IgG-associated autoimmune diseases but applies to nearly all autoimmune diseases to date.

Follow-up

IgG4-associated autoimmune diseases can only be treated to a limited extent during follow-up. For preventive care, as with almost all autoimmune diseases, there are only a few broad guidelines. Doctors first recommend an anti-inflammatory diet with foods that strengthen the body. This is followed by a healthy lifestyle with sufficient exercise. The focus is on patients being mindful of themselves and their lifestyle. Exercise reduces the risk of inflammation and at the same time improves the patient’s own body image. Avoiding certain foods reduces the risk of inflammation. For example, animal foods such as meat can have a harmful effect. Very sugary foods and arachidonic acid, which is found in red meat, for example, promote inflammation. That’s why sufferers should limit their consumption of meat and refined sugar. Legumes, vegetables, nuts, fruit and linseed oil, for example, are suitable as anti-inflammatories. Omega-3 fatty acids and many spices also provide a stronger immune system. Those affected can exchange information directly in self-help groups or participate in an online forum. Here they meet with understanding and get used to their new life situation. This communication helps in coping with the immune disease on a daily basis.

Here’s what you can do yourself

In various self-help groups or forums on the Internet, affected people exchange information. The often long road to diagnosis is a burden. Each sufferer must find his own way in dealing with the changed life situation. Sharing experiences and recognizing parallels are positive aspects of coping. Many patients are helped by an anti-inflammatory diet. Numerous foods have a positive effect on inflammatory processes in the body. Quality of life increases through a healthy lifestyle. In addition to diet, this also includes mindful treatment of oneself. Sport also has an anti-inflammatory effect and increases well-being. A first step is to avoid foods that increase inflammation. Meat and animal foods contain arachidonic acid. This fatty acid promotes inflammation, as does refined sugar.Vegetables, legumes, fruits, nuts, berries, linseed oil and rapeseed oil, on the contrary, have an inhibitory effect. The occurrence of inflammatory processes and chronic inflammation is reduced by eating tomatoes, cherries, papaya, blueberries, pomegranate seeds or pomegranate juice, pineapple, spinach, carrots, watermelon, white cabbage, lamb’s lettuce and omega-3 fatty acids, such as in wild salmon. Spices such as turmeric, ginger, chili, oregano and cinnamon also show health-promoting effects. So do garlic and onions. Poultry offers an alternative to red meat. This also applies to fatty sausage. Sugar can be replaced with honey, agave syrup or raw cane sugar.