Immunotherapy-related arthritis

Checkpoint inhibitors, the immunotherapies behind this condition, take off some of the brakes that normally restrain the immune system, so that it goes after cancer cells harder. Freed in this way, the immune system can occasionally turn on healthy tissue as well, the lining of the joints included, and inflame it. This belongs to a group of side effects called immune-related, and the joint trouble comes from the stirred-up immune system, not from the cancer.

It can happen to anyone having these medicines. Every type of checkpoint inhibitor has been linked with joint and other rheumatic side effects; they turn up most often when two of these medicines are combined, and then tend to be at their most severe. They may start within weeks or not until months have passed, sometimes once treatment has stopped. That outside cause is what sets it apart from rheumatoid arthritis, which has none so clear.

The joint symptoms can differ from person to person. You may notice:

• Joints that ache, swell and stiffen, one alone or several together
• Stiffness that is at its worst in the morning
• Stiffness and aching around the shoulders and hips, much like polymyalgia rheumatica
• Symptoms that begin part-way through treatment, or now and then after it has finished

Other immune side effects can come with the joints, in the bowel, the skin, the lungs, the liver, the kidneys or the glands that make hormones, and some can turn serious quickly: the seek-help section below lists them with the route for each.

Your history of immunotherapy is the starting point, together with the way the joint symptoms behave, an examination and suitable tests. It matters that the cancer treatment is recognised as the cause, and the assessment also checks that some other cause is not being overlooked.

Ultrasound can help to confirm joint inflammation and to judge accurately how much there is. Point-of-care ultrasound is part of the consultation with Dr Borukhson, so the scan can often be done without a second trip. The ultrasound clinic page gives a fuller account of the scan itself.

The treatment must quieten the joints and ease the symptoms without disrupting your cancer care, so the two are always weighed together. How strong it needs to be depends on how severe the inflammation is: it runs from simple painkillers to a steroid, and methotrexate or a similar disease-modifying medicine, or now and then a biological medicine, may be added if the symptoms persist. Methotrexate damps down the immune system, so it can make an infection likelier. Immunotherapy can often carry on, though severe symptoms sometimes lead to a pause, a step the oncology team decides together with the rheumatologist. A joint that gives particular trouble may be helped by an ultrasound-guided injection. You, your oncologist and your rheumatologist decide on the plan together.

Your cancer and rheumatology teams manage this with you, and there is a good deal you can do each day as well. Gentle movement within what feels comfortable eases stiffness and keeps the joints working; mix busier days with quieter ones, rest a flaring joint, and try warmth for stiffness. Jot down the joints involved and any change in them, and bring the notes to your appointments.

Go to every follow-up visit: each one lets the plan be fitted to where your cancer treatment and your symptoms now stand. Many people get good control with the two teams sharing the care, and the joints often settle once their treatment is well under way or has finished.

If you are having immunotherapy, or have had it, your cancer team will have given you a 24-hour number for the acute oncology service. It is the first call for the second list below, contact with measles, chickenpox or shingles included, except where a line names its own place, as the hot joint with a fever and the eye do. Short of the signs in the lists below, joints that become painful, swollen or stiff, or worse than they were, with nothing else wrong, are also for your cancer team through that number, during treatment or after it, without waiting for your next routine appointment, so that the cause can be pinned down early. The lists below take the rest in order of urgency.

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
• 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
• Chest pain of any kind that is new, during or after immunotherapy, since these treatments can, rarely, inflame the heart
• 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 the heart's rhythm can be disturbed when checkpoint inhibitors inflame it
• Muscle weakness with difficulty swallowing, speaking or breathing, or with drooping eyelids or double vision, since checkpoint inhibitors can inflame the muscles, and often the heart with them, in a way that can threaten life
• 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
• An eye that suddenly and completely loses its sight
• Sudden severe pain in the abdomen or back, since the pancreas can react to prednisolone
• 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, through the 24-hour acute oncology number your cancer team gave you, or NHS 111 if you cannot get through:

• A fever, or feeling generally unwell, on immunosuppressant, biologic or steroid treatment, since an infection has to be treated early; during or after immunotherapy a fever can also mean an immune side effect, so it belongs here with or without other treatment
• Joint pain, swelling or stiffness so severe that it stops you moving about or getting through the day, since severe inflammation needs treating without delay and can change the plan for your cancer treatment; a joint that will take no weight at all, or that cannot be moved, is a 999 or A&E emergency, as the hot-joint lines below say
• A joint that is hot and swollen, with a fever or feeling unwell, since an infected joint has to be ruled out at once, at A&E or through NHS 111
• A joint that has become hot and very swollen suddenly, or is worsening quickly, even without a fever, since an infected joint does not always announce itself with one; a joint that will take no weight at all, or that cannot be moved, is a 999 or A&E emergency, whether or not there is a fever
• New palpitations, or breathlessness that is new or getting worse, since checkpoint inhibitors can inflame the lungs and, more rarely, the heart; palpitations happening now that do not stop, or that come with chest pain, breathlessness, feeling faint or fainting, belong to the first list; a cough that does not go away, new wheezing, or swollen feet and ankles need the same-day call too
• Diarrhoea four or more times a day or during the night, blood or mucus in your poo, uncomfortable cramps or severe pain in the tummy, or a stoma more active than usual, since these treatments can inflame the bowel, which can quickly become serious; on prednisolone, pain in the abdomen or back that comes on suddenly and severely belongs to the first list
• A rash that is spreading, or skin that blisters or peels, since a severe skin reaction has to be treated in hospital
• Yellowing of the skin or eyes, dark urine, pain on the right side of the tummy, feeling very sleepy, or losing your appetite, since the liver can be inflamed
• Blood in your urine, passing less urine than usual, or needing to pass urine often or with discomfort, since these treatments can, though not commonly, inflame the kidneys
• Weakness, numbness or tingling in the arms, legs or face, a drooping eyelid or double vision, a headache that does not get better, drowsiness or confusion, problems with moving or speaking, or pain elsewhere in the body with no clear cause, since these treatments can, rarely, affect the nerves, the muscles and the brain; weakness or numbness that comes on suddenly on one side, speech that suddenly fails, or confusion that comes on suddenly can be a stroke, and weakness with trouble swallowing, speaking or breathing, or with drooping eyelids or double vision, can mean the muscles are badly inflamed, both 999 or A&E emergencies in the first list, as is new chest pain of any kind
• Feeling more tired than usual, dizziness, or weight that changes without explanation, since these treatments can affect the glands that make hormones
• 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, as does an eye that light hurts; double vision or a drooping eyelid goes to the 24-hour number, as the line on weakness and numbness says
• 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

Any other new symptom during or after immunotherapy is worth a call to the 24-hour number the same day too, or to NHS 111 if you cannot get through, since immune side effects can reach almost any part of the body and are easier to treat early. If you cannot tell how urgent something is, asking is never a mistake.

This arthritis sits where rheumatology and cancer care overlap, so an assessment made hand in hand with your oncology team serves you best. If you are having, or have had, immunotherapy and your joints have become painful or swollen, a prompt specialist review is worthwhile, once your cancer team knows, whether they arrange it or you book it directly.

How is joint pain traced back to immunotherapy?

By putting together the immunotherapy you have had, the way the joint symptoms behave, an examination and the tests that fit. Recognising that the cancer medicine is behind it is important, as is making sure no other cause is overlooked. A point-of-care ultrasound scan helps to show accurately how much inflammation a joint holds, and Dr Borukhson can often do it at the same visit.

Will treating it mean stopping my cancer treatment?

Often not. The aim is to calm the joints and ease the symptoms while protecting your cancer care, and the two have to be weighed together. Many people can carry on with their immunotherapy, though severe symptoms sometimes lead to a pause, a decision your oncology team makes with the rheumatologist, not one taken on the joints alone. Where one joint gives most of the trouble, an injection guided by ultrasound may help. You, Dr Borukhson and your cancer team settle the plan together.

Is it the same as rheumatoid arthritis?

It can look much the same, with pain, swelling and stiffness that is worse in the morning, but its cause sets it apart: the immune system has been stirred up by the cancer medicine, so the arthritis has an outside trigger instead of arising by itself. It can start part-way through a course of treatment, or now and then after the course is over. Knowing the trigger changes how it is assessed and treated, which is why the rheumatologist and the oncology team work on it together.

I have new joint pain on immunotherapy. Who should I tell, and how quickly?

Chest pain of any kind that is new, a joint that will take no weight at all or cannot be moved, and breathlessness that is severe, with gasping, choking or no breath to get words out, are a 999 or A&E emergency, and so is anything in the first list under When to seek help. Call 999 and do not drive yourself to A&E. If none of those signs applies, ring the 24-hour number the same day, or NHS 111 if you cannot get through, for joints so painful or stiff that you cannot get through the day, or for a fever, feeling unwell or any other new symptom, such as diarrhoea, a rash, a cough or breathlessness; a joint that is hot and swollen with a fever goes to A&E or NHS 111, and a red, painful eye or a change in sight to an eye casualty or urgent eye clinic, though double vision or a drooping eyelid goes to the 24-hour number, as the second list says. Short of those signs, tell your cancer team when joints become painful, swollen or stiff, or worse than they were, during treatment or after it, without waiting for your next appointment; the 24-hour number they gave you is the way to reach them, and a rheumatology assessment is worth having.

What happens over time?

It varies a great deal between people, and depends on which joints are inflamed, how the inflammation answers treatment and the course of your cancer care. With treatment that suits your situation and is planned with your oncologist, many people get good control of the joints. Since this arthritis straddles rheumatology and cancer medicine, it is reviewed regularly alongside your oncologist, and the plan moves with your treatment and your symptoms.