Relationships between rheumatic disease and cancer

• Fortunately, it's not common, but malignant cancerous diseases (cancer) have an increased incidence in certain rheumatic diseases (please read more below)
• Some immunosuppressive, anti-rheumatic drugs can also increase the risk of cancer
• Cancer disease can cause rheumatic pain and inflammation
• Cancer treatment with different medications can trigger rheumatic symptoms and illness.
  • In particular, this is relevant to the new Check Point inhibitors: Please see separate page here (in Danish)

Symptoms of cancer difficult to recognize

Among people with rheumatic disease, it can sometimes be difficult to recognize the symptoms of cancer. Systemic (autoimmune) rheumatic diseases in themselves cause lethargy, night sweats, fever, muscle weakness, decreased appetite and weight loss. These are symptoms that also occur in cancer (B symptoms). Also rashes, joints- and muscle aches can be related to both cancer and rheumatic disease. If symptoms persist, a more thorough assessment with medical examinations and blood and urine samples is required.

Studies by suspected cancer (a selection)

• Blood tests
• Lung and chest CT (thoracic)
• CT stomach area and pelvic (abdomen)
• Mammography and gynecological examination in women
• Stool samples
• PET / CT if the investigation does not lead
• The investigations are considered repeated if there is still suspicion of cancer

Rheumatic diseases (diagnoses) associated with cancer

Myositis / dermatomyositis

Myositis with typical skin changes (dermatomyositis, DM). Increased incidence also at Myositis type IMNM. With DM, there is a clearly increased risk of cancer (approximately 25% are diagnosed with cancer) in adults, most often with a onset in the same year as the rheumatic disease is diagnosed or in the following 2-3 years. About 2/3 of cancer cases are cancer of the cervix, lungs, ovaries, pancreas, bladder og stomach. Risk factors are high age at disease start (no increased cancer risk among children with DM (Juvenil DM)), Certain antibodies (blood sample): p-155 / 140 / TIF-Ƴ, NXP-2. Warning signs are new symptoms that can not be explained by muscle disease. (Reference: Dobloug C, 2015). Myositis is differenciated from muscle weakness by Myastenia gravis which can be triggered by cancer in thymus.

Rheumatoid arthritis (arthritis)

Approximately doubled the risk of lymphoma (Lymphoma, most often non-Hodgkin's lymphoma). Risk factors are high arthritis activity over many years, powerful immunosuppressive drugs and Felty's syndrome. Warning symptoms are rapid deterioration of otherwise long-term stable disease.

Sjögren's syndrome

It is increased incidence of non-Hodgkin's lymphoma. Risk during life is calculated to be 5-10%. Risk factors are high disease activity measured by frequent swelling of the large salivary glands (Glandula parotis), purpura (Vasculitis) in the skin and blood samples with low Complement C4. Warning symptoms are increasing general symptoms and changes in blood tests.

Systemic Lupus Erythematosus (SLE)

Slightly increased cancer risk, but without increased mortality observed. The frequency of Lymphoma, especially aggressive diffuse large cell B-cell lymphoma are increased. High disease activity, long-term disease and immunosuppressive treatment are risk factors. Warning symptoms include low white blood cells counts, swollen lymph nodes and enlarged spleen.

Systemic Sclerosis

There are various research results, but the risk can be 1,5 - 5,1 times increased lung cancer og non-Hodgkin's lymphoma. Also, some risk of esophageal cancer) may be expected, probably due to increased gastric acid reflux (Barett's oesophagus) over time. Warning symptoms are increasing lung problems with new CT lung changes, skin ulcers that do not grow and increase swallowing problems.

Overlapping symptoms

In the case of cancer, scleroderma-like symptoms, often with overlap with myositis and other connective tissue diseases, may occur (pseudo-scleroderma) (Reference: Frich L, 2019).

Bekhterev's disease (ankylosing spondylitis) has not increased cancer risk

Psoriasis arthritis (psoriasis arthritis): No increased cancer risk

Granulomatosis with polyangiitis (GPA / Wegener's granulomatosis)

• Skin cancer (non-melanoma type) may be increased during the first 2 year after diagnosis

Polymyalgia rheumatism: No increased cancer risk. If the onset symptoms are uncharacteristic, further investigation will still be recommended. However, polymyalgia rheumatica and similar muscle pain are a not uncommon side effect of cancer treatment with checkpoint inhibitors (please read more below under "Rheumatic complications of cancer treatment"

Temporalis arteritis (giant cell arteritis) No increased cancer risk. If the initial symptoms are non-typical for the disease, further investigation will be recommended

Medications against rheumatic disease and cancer

The indication for each drug must be evaluated against the risk of adverse effects on individual basis. Age, gender, family cases with cancer, prior chemotherapy or radiation therapy, many X-ray examinations and smoking should be included in the assessment.

People who have or have had cancer

Must be considered individually. Although the individual drugs do not show an increased risk of cancer development, immunosuppressive anti-rheumatic drugs may theoretically contribute to increased risk of proliferation or recurrence of known cancer. If one is in doubt, it is recommended that rheumatologist and cancer specialist make an individual patient assessment.

NSAIDs og cortisone: These drugs do not increase cancer risk

Azathioprine (Imurel) can derive from data for treatment of Rheumatoid arthritis over time cause an increased risk of lymphoma. Data for SLE are too sparse to draw a conclusion.

Cyclophosphamide (Sendoxane) leads to increased risk of Lymphoma, Leukemia og urinary bladder cancer. However, data is based on long-term use with tablets. Modern anti-rheumatic treatment in the form of intravenous dosing over less than 6 months indicates little or no increased risk.

Hydrochlorochloroquine (Plaquenil) does not result in increased cancer risk

Methotrexate (Ebetrex, Metex, Methotrexate) have not shown an increased risk of cancer

Sulfasalazine (Salazopyrin) does not result in increased cancer risk

Biological drugs

Abatacept (Orensia): Too few observations to draw conclusions

Rituximab (MabThera): Data from more than 5000 patient-years with treatment do not indicate increased cancer risk, but non-melanoma skin cancer has not been evaluated.

TNF inhibitors (Infliximab, adalimumab, etanercept, cerulizumab, golimumab) do not seem to lead to increased cancer risk, but observation time is still somewhat short for sure conclusions.

Tocilizumab (RoActemra): Too few observations to draw conclusions

Literature

• Turesson C, 2012

Rheumatism in cancer

1. Rheumatic pain in direct tumor growth towards joints

• Leukemia
• Lymphoma
• Multiple myeloma (plasmacytoma)
• Skeletal metastases
• Carcinogenic arthritis (see below)

2. Rheumatic symptoms caused by cancer / Paraneoplastic (para-malignancy) rheumatic syndromes

   • Carcinomatic polyartritis results in swollen joints and arthritis, most often in knees and ankles without abnormal rheumatoid antibodies (RF, CCP / ACPA). The joint symptoms usually occur up to one year before cancer is detected and is most commonly associated in women with breast cancer og lung cancer in men
   • Gout can be triggered during cancer treatment (tumor tissue dies) and cause sudden pain with severe joint inflammation
   • Hypertrophic arthropathy Clubbing is a thickening around the fingers outer joints and curvature of the nails. Also symptoms in the skeleton in the arms and legs. Symptoms of the fingers also occur in benign chronic lung or heart disease
   • Remitting Sero-Negative Symmetric Synovitis with Pitting Edema (RS3PE) is usually a benign rheumatic disease that quickly causes swelling of the hands of the elderly. The symptoms respond quickly to Prednisone. However, the condition may also occur by an underlying cancer. Typical symptom is then poor response to Prednisolone treatment.
   • Palmar fasciitis og polyarthritis-syndrome is characterized by increasing contracture (contraction) on the palm surface in both hands. This means that fingers can not be stretched out completely and hard connective tissue (fibrosis) may be observed in the palms. The syndrome can precede tumor disease, most often ovarian cancer in women. Treatment of underlying cancer usually improves the symptoms, while anti-rheumatoid treatment has little effect
   • Raynaud's phenomenon ("corpse fingers")
   • Myositis (muscle inflammation) in the form of dermatomyositis in adults is associated with cancer in 25% of cases. Dermatomyositis is described elsewhere on this page
   • Lambert-Eaton syndrome results in myasthenia resembeling disease with weak muscles in the legs and arms. Lung cancer has been detected at 50-70% of cases
   • Vasculitis diseases in the form of Leukocytoclastic vasculitis, Henoch-Schönlein Purpura (IgA Vasculitis) in older men and Polyarteritis nodosa (PAN) may in some cases be triggered by underlying cancer

3. Rheumatic complications in cancer treatment

   • After chemotherapy may not be joints- and muscle aches with stiffness mostly in the morning occur. Symptoms usually go over by themselves during the first year. Treatment of symptoms with NSAIDs (Ibux, Voltaren and others) can help
   • Aromatase inhibitors which is used as part of the treatment by hormone receptor positive breast cancer may cause joint pain
   • Immunological checkpoint inhibitors
     • However, they increase the risk of autoimmune disease as Rheumatoid arthritis (RA) og Polymyalgia rheumatica (PMR) (Reference: Belkhir R, 2017)
     • Please see separate page about checkpoint inhibitors and rheumatic disease here (in Danish)
   • BCG treatment against urinary bladder cancer can cause joint pain and arthritis (arthritis), usually 2-4 weeks after treatment. Knees and ankles are most often attacked. The symptoms usually last for 6 months
   • Raynaud's phenomenon may occur after chemotherapy treatment with bleomycin, vinblastine, vincristine og cisplatin (against Lymphoma, testicular cancer and others)
   • Scleroderma / Systemic Sclerosis -like skin changes (with Raynaud's and hard skin) may also occur after bleomycin treatment.
   • Graft-versus-host disease (GVHD) may occur after transplant, including Bone marrow transplant (HMAS). Raynaud's phenomenon is not typical
   • Granulocyte and granulocyte macrophage colony stimulating factor (G-CSF / GM-CSF) used as a supplement for some chemotherapy. The treatment may lead to acute, symmetrical arthritis in multiple joints. Symptoms usually occur within a few days after the end of treatment.
   • Interferon alpha (INF alpha) and interferon gamma (INF gamma) against lymphoproliferative cancer (Lymphoma, Leukemia and others) may trigger transient Systemic lupus (SLE)- similar symptoms. Relapse of Hepatitis C infection can cause joint pain og Rheumatoid arthritis like symptoms
   • Interleukin-2 which is used among other things against metastatic Malignant melanoma (Skin cancer) and kidney cancer may trigger Psoriasis arthritis, Ankylosing spondylitis, Rheumatoid arthritis, Myositis and other rheumatic diseases. Usually, symptoms ease when treatment is completed

Literature

• Alias ​​A, 2012
• Grans Compendium in Rheumatology

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