When Cancer Immunotherapy Affects the Joints and Muscles
Cancer immunotherapy has transformed the treatment of many cancers. Immune checkpoint inhibitors help the immune system recognise and attack cancer cells, but this increased immune activity can occasionally affect healthy tissues as well.
The resulting complications are known as immune-related adverse events, often abbreviated to irAEs. They may affect almost any organ, including the skin, bowel, lungs, liver, hormone-producing glands, nervous system, heart, joints and muscles.
Most people receiving immunotherapy will not develop a serious rheumatological complication. However, new joint pain, swelling, stiffness or muscle weakness should be reported because some symptoms require investigation and treatment.
The aim is not simply to suppress every ache or abnormal blood result. It is to establish whether symptoms represent immune-related inflammation, another effect of cancer treatment, an unrelated musculoskeletal problem or, occasionally, a complication of the cancer itself.
Which cancer treatments are involved?
The rheumatological complications discussed here are most closely associated with immune checkpoint inhibitors. These include drugs that target PD-1, PD-L1 or CTLA-4, such as pembrolizumab, nivolumab, atezolizumab, durvalumab and ipilimumab.
This is not an exhaustive list, and checkpoint inhibitors are sometimes used in combination.
“Immunotherapy” is a broad term covering several different forms of cancer treatment. Targeted therapies, hormone treatments and conventional chemotherapy can also cause joint or muscle symptoms, but often through different mechanisms. Knowing the exact cancer treatment is therefore an important part of the assessment.
Why can immunotherapy cause inflammation?
Immune checkpoints normally help prevent excessive immune activity. Cancer cells can exploit these checkpoints to avoid being attacked.
Checkpoint inhibitors block these signals, allowing immune cells to respond more effectively against cancer. In some people, however, the activated immune system also begins to inflame healthy tissues.
This does not always produce a condition identical to rheumatoid arthritis, polymyalgia rheumatica or another established rheumatic disease. Immunotherapy-related syndromes can resemble these conditions without meeting their usual diagnostic or classification criteria. Autoantibody tests may also be negative despite genuine inflammation.
Inflammatory arthritis
Inflammatory arthritis is one of the better-recognised rheumatological complications of checkpoint inhibitor treatment.
It may cause pain, swelling and stiffness in the small joints of the hands and wrists, or affect larger joints such as the knees, ankles and shoulders. Some people develop inflammation in only one or two joints, while others have a pattern resembling rheumatoid arthritis or a spondyloarthritis.
Morning stiffness may last for a prolonged period, and joints can become visibly swollen. Symptoms may interfere with walking, dressing, gripping objects or carrying out ordinary daily activities.
Blood tests for rheumatoid factor and anti-CCP antibodies are often negative. This does not exclude an immunotherapy-related inflammatory arthritis. Examination and, where appropriate, ultrasound or MRI may provide more useful evidence of active inflammation.
Polymyalgia-like symptoms
Checkpoint inhibitors can cause a syndrome resembling polymyalgia rheumatica, usually involving pain and stiffness around the shoulders, neck and hips.
People may struggle to lift their arms, turn in bed, dress or stand from a chair. Symptoms are often worse in the morning or after rest.
The presentation does not always behave exactly like conventional polymyalgia rheumatica. Inflammatory markers may be normal, and some patients have additional joint inflammation or other immune-related complications.
A new headache, scalp tenderness, jaw pain when chewing or any visual disturbance requires urgent assessment because these can be symptoms of giant cell arteritis. Although uncommon, delayed treatment of giant cell arteritis can threaten sight.
Myositis: an important cause of muscle weakness
Myositis means inflammation of muscle. It is much less common than general muscle aching, but it is potentially serious and needs to be recognised quickly.
The important symptom is usually genuine weakness rather than pain alone. Someone may find it increasingly difficult to rise from a chair, climb stairs, lift their arms, hold their head up or carry out tasks that were previously straightforward.
Checkpoint inhibitor-associated myositis can overlap with inflammation of the heart muscle or with a myasthenia-like neurological syndrome. This overlap can affect breathing, swallowing, the eyelids or eye movements and may become life-threatening.
Urgent medical assessment is needed for:
New or rapidly progressive muscle weakness
Difficulty swallowing, speaking or breathing
Drooping eyelids or double vision
Chest pain, palpitations, fainting or unexplained breathlessness
Difficulty holding the head upright
These symptoms should be reported immediately to the oncology team or the hospital’s 24-hour cancer treatment advice line. Depending on their severity, emergency assessment may be required.
Other rheumatological complications
Checkpoint inhibitors can produce a wide range of less common inflammatory presentations.
Some people develop very dry eyes or a dry mouth resembling Sjögren’s disease. Others may develop inflammation of blood vessels, sarcoid-like disease, inflammation around tendons or joints, or features resembling a connective-tissue disease.
Immunotherapy can also trigger a flare of a pre-existing autoimmune or inflammatory condition. For example, someone with established rheumatoid arthritis, psoriasis, polymyalgia rheumatica or inflammatory bowel disease may notice renewed disease activity.
New symptoms do not necessarily mean that cancer immunotherapy must be stopped. They do mean that the situation should be assessed carefully.
When can symptoms begin?
Immune-related adverse events can occur early in treatment, after several cycles or months later. Occasionally, symptoms begin or persist after checkpoint inhibitor treatment has finished.
Inflammatory arthritis can become a longer-term condition in some patients, even after the original treatment has been stopped. This differs from certain other immune-related adverse events that may settle more completely after treatment.
Patients should therefore continue to report new inflammatory symptoms after immunotherapy has ended, particularly if their oncology team has advised them to remain alert to delayed side effects.
Not every ache is caused by immune-related inflammation
Joint and muscle symptoms are common, particularly during cancer treatment, but not all of them represent a rheumatological irAE.
Possible alternative explanations include osteoarthritis, tendon problems, gout, infection, thyroid or other hormonal abnormalities, medication effects, deconditioning and ordinary mechanical pain. Cancer itself can sometimes cause musculoskeletal symptoms through bone involvement, paraneoplastic syndromes or other complications.
A hot, acutely swollen joint may be caused by infection or crystal arthritis and may need urgent aspiration. New back or bone pain may require investigation for causes unrelated to inflammatory arthritis.
Fatigue and muscle aching can also occur when checkpoint inhibitors affect the thyroid, pituitary or adrenal glands. These hormonal complications require a different form of treatment.
The timing of the symptoms is helpful, but timing alone does not establish the diagnosis.
How are symptoms assessed?
Assessment begins with identifying the exact cancer treatment, when it was started and whether symptoms appeared in relation to treatment cycles. It is also important to understand the underlying cancer, other medication, previous rheumatic conditions and any immune-related problems affecting other organs.
Examination may look for joint swelling, restriction of movement, tendon inflammation, muscle weakness, rashes, vascular abnormalities and neurological signs.
Blood tests are selected according to the clinical presentation. These may include inflammatory markers, blood count, kidney and liver function, thyroid testing and creatine kinase, or CK, when muscle inflammation is suspected. Rheumatoid factor, anti-CCP antibodies, ANA and other immune tests may be helpful in selected cases, but broad antibody testing without a clear clinical question can be misleading.
If myositis is suspected, further assessment may include cardiac tests because muscle inflammation can occasionally occur alongside myocarditis. Neurological investigation may also be required when there are swallowing problems, eyelid weakness, double vision or breathing symptoms.
Ultrasound or MRI can help identify inflammation when the examination is uncertain. A hot or substantially swollen joint may need aspiration to exclude infection or crystal arthritis.
How are rheumatological side effects treated?
Treatment depends on the severity of the symptoms, which tissues are affected and how the cancer is responding to immunotherapy.
Mild symptoms may sometimes be managed with pain relief, an anti-inflammatory medicine if it is safe for that individual, or a local steroid injection. Anti-inflammatory medicines are not suitable for everyone, particularly people with kidney disease, stomach ulceration, cardiovascular problems or certain interactions with other medication.
More active inflammation may require corticosteroids. The dose and route depend on whether the problem is limited joint inflammation, widespread arthritis, significant muscle disease or involvement of another organ.
If arthritis persists, returns whenever steroids are reduced or requires prolonged steroid treatment, a conventional disease-modifying antirheumatic drug may be considered. In selected severe or resistant cases, biological treatment may be appropriate.
The purpose of rheumatology involvement is to control inflammation while avoiding unnecessary immunosuppression and, wherever possible, allowing effective cancer treatment to continue.
Patients should not start leftover steroids, change their steroid dose or stop immunotherapy without speaking to their treating team.
Does immunotherapy have to be stopped?
Not necessarily.
The decision to continue, pause or permanently stop a checkpoint inhibitor is made jointly with the oncology team. It depends on the severity of the adverse event, whether other organs are involved, how quickly symptoms improve, the response of the cancer and the available alternative cancer treatments.
Mild or moderate joint inflammation can sometimes be treated while immunotherapy continues. Severe myositis, myocarditis, neurological overlap or other major organ complications may require immunotherapy to be withheld and urgent treatment to begin.
If immunotherapy has been paused, the question of restarting it is considered individually. There is no single answer that applies to every patient.
What if you already have an autoimmune disease?
A pre-existing autoimmune disease does not automatically rule out checkpoint inhibitor treatment. However, there may be a greater risk of a flare or of developing another immune-related complication.
Where possible, it is helpful for the oncology and rheumatology teams to review the existing diagnosis, current disease activity and medication before immunotherapy begins. Treatment may need to be adjusted, but stopping established medication without a coordinated plan can also cause harm.
The balance between controlling autoimmune disease and treating cancer is individual and should be discussed openly with the patient.
When should you contact your oncology team?
New or worsening joint swelling, prolonged stiffness, muscle weakness or significant limitation of movement should be reported promptly. Do not wait for a routine oncology appointment if symptoms are progressing.
Contact the oncology team urgently for a hot swollen joint accompanied by fever or feeling unwell, rapidly increasing weakness, difficulty swallowing or breathing, drooping eyelids, double vision, chest symptoms or new visual disturbance.
It is particularly important to use the hospital’s cancer treatment advice line because the team needs to consider complications affecting organs outside the musculoskeletal system as well.
The role of the rheumatologist
A rheumatologist can help establish whether symptoms represent immune-related inflammation, a flare of an existing disease or an unrelated musculoskeletal problem.
This may involve confirming objective inflammation, excluding important alternatives and selecting treatment that controls symptoms with the least necessary immunosuppression. Close communication with oncology is essential because rheumatological decisions cannot be separated from the cancer treatment plan.
If musculoskeletal symptoms persist after oncology assessment, or the diagnosis and treatment plan remain unclear, a rheumatology review familiar with immune-related adverse events may help. This should be coordinated with your oncology team. Information about private rheumatology appointments is available here.
The bottom line
Immune checkpoint inhibitors can cause inflammatory arthritis, polymyalgia-like symptoms, myositis and other rheumatological complications. Many of these problems can be treated effectively, and developing joint symptoms does not automatically mean that cancer immunotherapy must stop.
However, true muscle weakness, swallowing or breathing difficulty, drooping eyelids, double vision, chest symptoms and visual disturbance require urgent attention.
The safest approach is early reporting, careful assessment and coordinated decision-making between the patient, oncology team and rheumatologist. This allows inflammation to be treated while keeping the priorities of cancer care firmly at the centre of the plan.
Related reading
Morning Stiffness and Swollen Joints: Could This Be Inflammatory Arthritis?
DMARDs Explained: Methotrexate, Hydroxychloroquine and Other Treatments
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Please note, these posts are for general information only and do not constitute medical advice. Dr Singh would encourage you to speak to your healthcare professional to be assessed and managed for your specific symptoms.