IgG4-related disease

IgG4-related disease is immune-mediated, meaning that an immune system gone awry is the origin, rather than any infection or injury. Why it does so is not yet understood; the effect is inflammation in one organ or more, which with time can set into firm swellings and end as scar tissue.

The condition takes its name from IgG4, one of the antibodies that every healthy immune system makes and carries in the blood. Many people with the condition have a raised IgG4 level, which is how it came to be named, but the antibody is best understood as a marker linked to the condition rather than a straightforward test for it. That level, as the section on diagnosis makes plain, is never enough by itself.

It is not a common condition, and those it affects are mostly in middle age or beyond. Men are affected more often than women, most markedly when the disease is in the kidneys, the pancreas or the tissue at the back of the abdomen; in the eyes or the salivary glands the two sexes are affected about equally. Children are only rarely affected.

What stands out about IgG4-related disease is how many places it can turn up. The list of possible sites is long: the tear and salivary glands, the tissue behind the eye, the pancreas and bile ducts, the kidneys, the lungs, the thyroid, the lining around the brain, and the tissue at the back of the abdomen that surrounds the aorta, the body's main blood vessel. For some, one organ alone is involved. For others it is several, either together or in succession as the years go by.

Blood vessel walls can be inflamed too, the aorta's included, which is one reason the condition is sometimes grouped with the vasculitis family. Where a vessel is involved, scans of it join both the initial assessment and the follow-up.

Scans cannot always tell a firm inflammatory swelling from a tumour, so a good many people first hear of IgG4-related disease while being checked for a cancer, or because an organ has stopped doing its job. That can be hard to hear at first, but the distinction is usually clear, and neither the treatment nor the outlook of cancer applies to you.

The condition can progress without symptoms. Many people have little to notice for months or even years, and damage can build slowly inside an organ while they feel reasonably well, which is why a firm diagnosis matters.

Symptoms, when there are any, take their shape from the organ concerned. Common patterns include painless swelling of the salivary or tear glands, felt as a fullness around the jaw or the eyes; jaundice, a yellowing of the skin or eyes, if the pancreas or the bile ducts are affected; discomfort in the back or abdomen, or difficulty with the flow of urine, when the tissue around the aorta and the kidneys is involved; breathlessness when the lungs are affected; and headaches when the lining around the brain is inflamed. An eye, or both, can be pushed forward, and tiredness, a poor appetite and weight loss are often there as well. Because the picture varies so widely, the assessment looks across the organs the condition can reach, not the first symptom alone.

IgG4-related disease has no single deciding test. Four things are brought together instead: the organs involved, the blood tests, the imaging and, in most cases, a biopsy.

It is the biopsy that usually matters most, a small piece of the affected tissue examined under the microscope. What the microscope shows is the blend of inflammation and scarring particular to this condition, and it helps to set aside other explanations, cancer among them. Blood tests measure the IgG4 level, which can support the diagnosis but has to be read with care: some people without the condition have a raised level, and some who genuinely have it do not, so the level is never taken as the answer by itself. Imaging, whether CT, MRI or at times PET, shows the organs affected and the extent of the involvement, and repeating it later is how the response to treatment is judged.

The condition can pass for others, cancer and Sjögren's syndrome among them, so specialists arrive at the diagnosis by taking everything together rather than leaning on one result. In the UK the case is often reviewed by a team with regular experience of the condition, and a good proportion of those assessed for it prove to have a different diagnosis.

Three things are asked of treatment: an end to the inflammation, no more scarring in the organs, and after that a quiet condition kept so with the least medicine that will do it.

Treatment opens with a course of steroid tablets, usually prednisolone, to which the condition nearly always responds. The drawback is that the condition commonly comes back as the dose is reduced or after the steroids stop, which is why treatment usually reaches beyond steroids alone. A second, steroid-sparing medicine that calms the immune system is often added, which lets the steroid be cut back, methotrexate, azathioprine or mycophenolate among the choices; our guide to steroids in rheumatology goes into how a steroid course is run and why it is never ended abruptly.

When control is proving difficult, or relapses keep coming, rituximab, a biologic treatment, frequently works very well. B cells, the immune cells behind the IgG4 antibody and much of the inflammation, are what it depletes, and many of the problems of long-term steroids can then be avoided. In England the NHS funds it for a small, carefully selected group: people whose disease has come back and who either have not responded to the medicines above or cannot take them because of side effects or other medical reasons, with the decision resting with a specialist team rather than any one doctor. Newer treatment is arriving: in the United States, inebilizumab, a targeted therapy that clears B cells, was licensed for this condition in April 2025 after it cut the risk of a flare by 87 per cent compared with a steroid course alone. What is available varies from one country to another and changes over time; ask your specialist what is on offer here.

Follow-up continues over the years, because the condition can flare after a long quiet spell. For anyone whose IgG4 level was raised at diagnosis, repeat measurements are a genuinely useful guide: a clear and sustained rise often signals that the inflammation is stirring again, and prompts a search for where it has returned. Even so, the level is not the whole story: it can stay somewhat raised while you are doing well, so scans are used alongside it to show what is actually happening inside an organ. The whole point of that follow-up is to catch returning inflammation early, before it does damage, and it goes a long way to explaining why the outlook today is good.

Since IgG4-related disease can affect several organs, more than one specialist is usually needed, working as a team. Who holds the overall plan depends on where the disease sits: a rheumatologist may coordinate the assessment and the immune-calming treatment, or, where the pancreas or the bile ducts lead, a specialist in those organs may, and the organ specialists, whether for the kidneys, the eyes, the glands or elsewhere, join as and when they are needed. When the tissue around the aorta is involved, imaging of the vessel itself is part of the plan. Dr Borukhson practises within a world-renowned tertiary centre, with ready access to consultant colleagues in the other specialties this condition may call on. Where it helps, she can bring those specialists in directly, and particularly complex cases can go to a multidisciplinary team meeting (MDT) with minimal delay. Whenever more than one kind of expertise is needed, the strands of your care can be drawn together and decisions reached promptly.

What helps most is ordinary routine. Take the medicines exactly as prescribed; steroid tablets in particular must never be stopped suddenly. Attend the appointments, blood tests and scans even when you feel perfectly well, because the inflammation can be quietly active even so. The treatments damp down the immune system, so keep the vaccinations your team advises up to date, and a fever, a suspected infection, or contact with measles, chickenpox or shingles is a same-day matter, as the next section says.

Keep a note of any symptom that is new or has come back, and tell the team promptly when something has returned, as the next section says; the note is for the pattern between visits, because the disease can travel from organ to organ, and what happens over months says more to your team than a single visit can.

Most of what IgG4-related disease does can be brought to a routine review; a few things cannot wait.

Treat any of these as a 999 or A&E emergency: call 999 and do not drive yourself to A&E.

• Severe illness with suspected sepsis: a high fever with shaking, confusion, rapid breathing, or feeling dramatically worse over hours
• With a fever or feeling unwell, a rash that does not fade when you press it, a stiff neck with eyes that cannot bear bright light, or skin, lips or tongue turning blue, grey, pale or blotchy, since these can be signs of meningitis or sepsis; on black or brown skin the rash and the change of colour may be easier to see on the palms of the hands or the soles of the feet
• Sudden severe pain in the abdomen or back, since the aorta itself can be inflamed
• Chest pain that is crushing, tight or like a pressure, that spreads to an arm, the jaw, the neck, the stomach or the back, that comes with breathlessness, sweating, feeling sick or feeling light-headed, or that came on suddenly and does not go away
• Breathlessness that is severe, with gasping, choking or no breath to get words out; or coughing up blood
• Palpitations happening now that do not stop, or that come with chest pain, breathlessness, feeling faint or fainting, since a heart whose muscle or rhythm is affected has to be checked at once
• A blackout, since bleeding from a weakened stretch of the aorta can be behind it
• Sudden weakness or numbness on one side, a drooping face or difficulty speaking, a sudden severe headache, sudden confusion or a seizure, or sudden loss of vision, any of which can be a stroke, even if it stops after a short time, and in IgG4-related disease can also come from inflammation of the lining around the brain
• An eye that suddenly and completely loses its sight
• Lips, mouth, throat or tongue that suddenly swell, a throat that feels tight, very fast breathing or a struggle to breathe or to swallow, skin, tongue or lips turning blue, grey or pale (on black or brown skin this may be easier to see on the palms of the hands or the soles of the feet), becoming suddenly very confused, drowsy or dizzy, or fainting and not being able to be woken, since this can be a severe allergic reaction, anaphylaxis, which can follow a dose of any medicine
• Vomiting blood, or bleeding from the back passage that is heavy or will not stop, most of all with faintness, confusion or pain in the abdomen, or vomit that is black or dark brown, since a stomach ulcer on prednisolone can bleed
• Thoughts of harming yourself or ending your life, which steroids can bring on

Any of these needs an assessment that is urgent, on the same day, from your GP, your rheumatology team or NHS 111:

• A fever, or feeling generally unwell, on immunosuppressant, biologic or steroid treatment, since an infection has to be treated early
• New chest pain, new palpitations, or breathlessness that is new or getting worse; palpitations happening now that do not stop, or that come with chest pain, breathlessness, feeling faint or fainting, belong to the first list
• A persistent dry cough with a fever, with new breathlessness, or that is worsening over hours to days
• A headache that is new and persistent, or that keeps getting worse, with none of the signs above, since the lining around the brain can be inflamed
• A new red, painful eye, or sight that has blurred, dimmed or changed, which needs an eye casualty or urgent eye clinic the same day, since the tissue around and behind the eye can be inflamed and swelling there can press on the nerve of sight
• Marked swelling of the face or ankles, or frothy or bloody urine, since the kidney tissue itself can be inflamed
• Yellowing of the skin or the eyes that has appeared quickly, since inflammation in the pancreas or the bile ducts can block the flow of bile
• Passing much less urine than usual, or none at all, since the tubes that drain the kidneys can be squeezed by the inflamed tissue
• A marked change in mood or behaviour, confusion, or seeing or hearing things that are not there, on steroid treatment, since prednisolone can do this, the more so the higher the dose; confusion that comes on suddenly is a 999 or A&E emergency, as the first list says
• Unusual thirst or hunger, passing urine more often, or feeling sleepy or confused, on steroids, or swelling of the arms or legs, bruising or bleeding that is not normal, black or dark red stools, severe stomach pain, severe back pain, a severe upset stomach, being sick, or very bad dizziness, since each can be a steroid effect that needs checking without delay; pain in the abdomen or back that comes on suddenly and severely is a 999 or A&E emergency, as the first list says
• Contact with measles, chickenpox or shingles, since these infections can be severe on steroids and a medicine to protect you may be needed
• Being near someone with measles, chickenpox or shingles, while you take a medicine that weakens the immune system, since measles and chickenpox can be dangerous when the immune system is weakened, and you can catch chickenpox from someone with shingles if you have never had chickenpox; NHS 111 can tell you what to do that day

A persistent dry cough on its own, or breathlessness that has drifted slowly, over weeks or months, is something to tell your team promptly, without waiting for a routine slot. If the symptoms that first led to your diagnosis come back, if a new swelling appears, or if an affected organ seems to be working differently, let your rheumatology or specialist team know promptly rather than saving it for the next planned appointment: these can be signs of returning inflammation, which is easier to treat early. A fever that persists with no explanation, in someone not on immunosuppressant, biologic or steroid treatment, is likewise one to get medical advice on promptly, from your GP, or your rheumatology or specialist team. Settled symptoms, questions about your medicines and the quiet stretches between scans belong to the planned reviews. If you cannot tell how urgent something is, asking is never a mistake.

Being uncommon, and starting with symptoms that are quiet or easily blamed on something else, IgG4-related disease is often diagnosed late, at times only when a suspected cancer is being looked into. The outcome turns on timing: recognise the pattern and confirm the diagnosis before an organ has come to lasting harm, and treatment usually works. Kept under proper review, the condition can be held in check, and most people manage it well over the long term. If you have an unexplained swelling, an organ that is misbehaving for no clear reason, or a diagnosis made elsewhere that needs following, a specialist assessment can make sense of the whole and put in place the treatment and monitoring that protect your organs over the long term.

My IgG4 blood level is raised. Does that mean I have the disease?

Not on its own. Everyone has some IgG4 in their blood; it is one of the normal antibodies, and a raised level is one clue among several. A high level turns up in some people who do not have the condition, and a normal one in some who do, which is why the test alone can neither prove the diagnosis nor exclude it. So the blood test never makes the diagnosis by itself; that rests on your symptoms, your scans and, in most cases, a small sample of the affected tissue, taken together.

IgG4-related disease and cancer: are they the same thing?

No. The condition is inflammatory, not cancerous. The mix-up happens because, on a scan, a firm swelling in an organ and a tumour can look alike, and it is quite often a hunt for a suspected cancer that brings the condition to light. Separating the two matters, and what usually decides it is a sample of the tissue, interpreted with everything else that is known. Once it is clear which one you have, the outlook changes entirely: medicines that calm the immune system generally work well.

What does treatment for IgG4-related disease involve?

The starting point is a course of steroid tablets, prednisolone as a rule, and nearly everyone responds to them. The inflammation tends to creep back as the steroid is reduced or stopped, so a second medicine that calms the immune system, such as methotrexate, azathioprine or mycophenolate, is commonly added to hold the steroid dose down. If the disease will not come under control, or comes back time after time, rituximab, a biologic treatment that thins out the immune cells behind the condition, often proves highly effective.

Can it return after treatment?

Yes, it can, and that is exactly why you are followed up. Treatment usually settles it well, yet it can flare again, at times after a long quiet stretch, and stopping treatment altogether commonly brings it back. The reviews, blood tests and scans exist to catch any return early, so that it is treated before harm is done. With that ongoing care, many people keep the condition quiet over the long term.

Will more than one specialist be involved in my care?

Usually several. A rheumatologist may hold the overall plan and the treatment that calms the immune system, or a liver or pancreas specialist may lead when the pancreas or the bile ducts are the main site; the organ specialists, for the kidneys, the eyes or the glands, come in for the parts that concern them. Because it is uncommon, a centre that sees the condition regularly sometimes shares in the care. One plan then covers all the organs involved.