IgG4-Related Disease

What is IgG4-Related Disease?

IgG4-related disease is a multi-organ condition in which inflammation and fibrosis, often forming tumor-like masses, develop in the body for reasons that are not yet known.^[1] It is also called IgG4-related sclerosing disease, and it was recognized as a single disease only in the early 2000s.^{[2, 3]}

Because it can look like cancer, infection or other inflammatory diseases, it is often mistaken for something else. For a condition like this, we ask that you are under a physician's care for it and that your treating team knows you are receiving complementary care.

Common symptoms

Symptoms depend on which organs are involved, and the pancreas, kidneys, orbital tissues, salivary glands and retroperitoneum are among the most common sites.^[1] Typical problems include swollen salivary glands or lymph nodes, puffiness around the eyes, jaundice, abdominal pain, and dry mouth or dry eyes. Fatigue and weight loss can occur too.^[3]

The disease can develop slowly. It can cause serious organ damage, including organ failure, if it is not recognized.^{[3, 4]}

Causes and risk factors

The cause is unknown.^[1] The immune system is clearly involved: B cells and certain T cells appear to drive the tissue injury, which is why drugs that deplete B cells work well in many patients.^[5]

Most reports describe middle-aged and older adults. Other risk factors are not well established.^[4]

How it is diagnosed and treated conventionally

Diagnosis depends mainly on biopsy findings, together with imaging, blood tests and the pattern of organs involved. Elevated serum IgG4 is common but is not reliable enough to diagnose the disease alone.^{[3, 6]} Classification criteria published by the American College of Rheumatology and EULAR help doctors recognize it.^[6]

Glucocorticoids such as prednisone usually work quickly, and a prolonged course is often needed because the disease relapses in most people.^[3] Long-term steroid use is a concern in a disease of middle-aged and older adults, so doctors are studying steroid-sparing options, including B-cell-targeted drugs.^{[4, 6]} Treatment is directed by a rheumatologist or another specialist for the affected organ.

Why IgG4-Related Disease calls for a whole-person approach

Because the disease can involve several organs and its treatment can last for years, the person living with it deals with more than a single diagnosis. Symptoms of the disease, side effects of long treatment and the strain of a rare, often misunderstood illness can all affect daily life.^{[3, 4]}

The clinic's supportive care is aimed at those day-to-day problems. It does not target the immune process itself, and no study has shown that it does.

Immune activity and fibrosis

The disease is driven by immune cells that promote scarring in tissue, and the amount of fibrosis helps determine how well immune-suppressing treatment works.^{[2, 5]} This is the part of the disease that your specialist manages.

Treatment burden

Steroids and other immune-suppressing drugs are effective but have costs, and doctors are actively looking for ways to need less steroid.^[4] Anything we offer must fit around these medicines and never replace them.

Dryness and glandular symptoms

When the salivary and tear glands are involved, dry mouth can affect eating, speaking, sleep and dental health. Dry mouth is also a common problem in other autoimmune conditions, which is why most of the supportive research below comes from them.^[7]

Sleep, stress and fatigue

Chronic illness, steroid treatment and uncertainty about the future can disturb sleep and raise stress. Sleep and stress are the symptom areas where the research on acupuncture and some herbs is most developed, although none of it was done in people with this disease.^{[8, 9]}

Acupuncture as supportive care in IgG4-Related Disease

What the research shows

We found no clinical trials of acupuncture in IgG4-related disease. Acupuncture has not been shown to affect the disease process, to shrink masses or to lower IgG4 levels.

Research in related conditions gives limited guidance on symptoms. A review of 10 trials of acupuncture for dry mouth, in conditions including Sjögren's syndrome and after radiation, rated the quality as low and found the results inconclusive.^[7] A review of non-drug treatments for Sjögren's syndrome found only 5 small trials, including one of acupuncture for dry mouth, all at high risk of bias.^[10] In cancer patients with dry mouth from radiation, a systematic review of 8 trials, with 3 pooled in a meta-analysis, found that acupuncture improved reported dry-mouth symptoms but not measured saliva flow. All trials had a high risk of bias and the evidence was low quality.^[11]

For sleep, a review of 24 trials, 15 of which were pooled in a meta-analysis, found that acupuncture improved insomnia scores compared with medication, with benefit appearing after about three weeks of treatment. Results varied a great deal between trials.^[8] A broad review of acupuncture meta-analyses found evidence of a positive effect for chronic pain and cancer-related fatigue among a small number of conditions, but these are different conditions from the one on this page.^[12]

How acupuncture may work

For this disease, no mechanism has been tested. In general, researchers propose that acupuncture influences how the nervous system processes pain and stress, and may affect saliva production through nerve pathways. These are proposed explanations, not settled facts, and the dry-mouth trials above did not show consistent changes in measured saliva flow.^{[7, 11]}

What treatment involves

Treatment uses fine, sterile, single-use needles, with sessions usually lasting about 20 to 40 minutes. A course of several visits is followed by reassessment of whether it is helping with the symptom you want to address, such as sleep or dry mouth.

In prospective studies, about 9 in 100 patients had a minor reaction such as bleeding, soreness or redness at a needle site, and serious events occurred in about 1 in 10,000 patients.^[13] Tell the practitioner first if you have a bleeding disorder, take blood thinners, are pregnant, or have a pacemaker (relevant to electroacupuncture). Also tell us if you take steroids or other immune-suppressing medicine, because you may be more prone to infection, and about any low blood counts.

Ayurvedic medicine as supportive care in IgG4-Related Disease

The Ayurvedic view

Ayurveda has no classical name for IgG4-related disease. A practitioner would instead describe a person's overall constitution and the symptoms in traditional terms, such as imbalance of the doshas or weak digestion (agni). These are traditional frameworks for choosing supportive care, not biomedical diagnoses.

Therapies that may be used

Care is individual and is limited here to gentle measures:

• Diet and daily routine, such as regular meals and consistent sleep and waking times
• Stress-reducing practices such as breathing exercises and relaxation
• Warm oil massage for comfort, where appropriate
• Individually prescribed herbs, only after review of your medicines

Panchakarma, the traditional cleansing program, is not appropriate during pregnancy, acute illness or frailty. Because IgG4-related disease involves organ damage and often immune-suppressing medicines, we would not use it unless your treating physicians agree that it is medically sensible. Ayurvedic products also vary in quality, and one study found detectable lead, mercury or arsenic in about one fifth of those bought online.^[14]

What the research shows

We found no clinical trials or systematic reviews of Ayurvedic medicine for IgG4-related disease. Any benefit for the disease itself is unknown.

For stress and sleep in general, meta-analyses of placebo-controlled trials of ashwagandha (Withania somnifera) reported lower anxiety and stress scores and better sleep measures. The larger analysis (12 trials) rated the certainty as low, and both noted large differences between trials and called for more or larger studies.^{[9, 15]} None of these trials enrolled people with IgG4-related disease. Ashwagandha is also traditionally described as affecting the immune system, so whether it is suitable for someone with an immune-mediated disease on immune-suppressing treatment is a question for your physician.

Herbal medicine as supportive care in IgG4-Related Disease

Herbs and formulas that have been studied

No herbs or formulas have been tested in clinical trials for IgG4-related disease in the studies we found. The closest research is on Sjögren's syndrome, another immune-mediated condition that affects the salivary and tear glands. Chinese herbal products studied there include total glucosides of paeony, tripterygium glycosides and a number of proprietary formulas.^[16]

What the research shows

A network meta-analysis of 66 trials (5,052 participants) in Sjögren's syndrome found that Chinese herbal medicine added to conventional drugs did better than conventional drugs alone on measures such as inflammation markers, IgG and dry-eye tests.^[16] These results come from a different disease and cannot be assumed to apply to IgG4-related disease.

For the disease itself, there is no evidence. Herbs should not be used to try to treat the disease or to lessen the need for immune-suppressing drugs.

Safety and herb-drug interactions

Herbs are active substances and can interact with medicines. A literature review described cases in which St John's wort lowered blood levels of ciclosporin and tacrolimus, with organ rejection in some cases. It also described bleeding when warfarin was combined with danshen or ginkgo.^[17] Anyone taking steroids, azathioprine, methotrexate, rituximab or other immune-suppressing medicines needs a practitioner and prescriber to review each herb first.

Herbal and dietary supplements account for about 20% of drug-induced liver injury cases in the United States, and the liver can already be affected in this disease.^[18] Tripterygium products, used in Chinese medicine for autoimmune disease, are potent and should not be used without specialist supervision.

About one fifth of Ayurvedic medicines bought online contained detectable lead, mercury or arsenic.^[14] Any herb should come from a tested source. Tell us if you are pregnant or breastfeeding or have liver or kidney disease. Kidney involvement is a known feature of IgG4-related disease.^[1]

Translating traditional medicine into modern biological language

This is interpretation, not equivalence. Chinese medicine would describe patterns such as dryness, stagnation of qi and blood, or dampness with phlegm accumulating in tissue. Ayurveda would speak of dosha imbalance or accumulated ama. Researchers study different things: B cells, T cells and fibrosis in this disease.^[5]

We are not aware of any research linking these traditional patterns to the biology of IgG4-related disease. What the traditions offer is a way to organize individual symptoms such as dryness, poor sleep or stress for supportive care.

How this care fits with your medical care

The clinic's role is complementary. We do not diagnose IgG4-related disease or manage the disease, prescribe or change medicines, or replace your rheumatologist or other specialists. Do not stop or change prescribed steroids or other medicines without your prescriber.

Please bring your diagnosis, recent test results and imaging reports, and a full list of medicines and supplements. Tell us about your specialist team so we can make sure the supportive care fits with theirs. If you take immune-suppressing medicine, ask your physician whether acupuncture needs special precautions for you.

When to seek urgent medical care

Some symptoms in this disease can signal organ damage or a treatment complication and need prompt medical evaluation.^{[3, 4]}

• Yellowing of the skin or eyes, dark urine or pale stools
• Severe or worsening abdominal or back pain
• Much less urine, new swelling of the legs or face
• Fever or other signs of infection while on immune-suppressing medicine
• Sudden vision changes, eye pain, or rapidly worsening swelling around the eyes
• Shortness of breath, cough that is new or worsening, or chest pain

For emergencies, call 911 or go to the nearest emergency department.