Cancer and rheumatic disease 4.5/5 (10)

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Definition

Cancers are malignant diseases which, at the onset of the disease, cause symptoms from the locomotor system, connective tissue and blood vessels, so that cancer and rheumatic disease can be difficult to distinguish from each other in some cases. In addition, rheumatic diseases are rarely associated with an increased incidence of cancer. Certain drugs used in cancer treatment can also cause rheumatic side effects. When a tumor or metastases is located in the skeleton, near Iedd or in the surrounding connective tissue, pain, stiffness and reduced mobility from joints or muscles can be among the main symptoms.

Symptoms

Among people with rheumatic disease, it can sometimes be difficult to recognize the symptoms of cancer. Systemic (autoimmune) the rheumatic diseases in themselves cause lassitude, night sweats, fever, muscle weakness, reduced appetite, altered bowel function, cough, heavy breathing on exertion and weight loss, which is also seen in cancer diseases.

Cancer and rheumatism
Symptoms of rheumatic disease can sometimes resemble cancer, so that cancer and rheumatic disease can be difficult to distinguish.

Also rash, back pain, 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.

On rare occasions, cancerous tumors can grow into joints, so that pain and swelling are mistaken for primary rheumatic disease. In addition, bone pain can be seen in Leukemia, Lymphoma, multiple myeloma (plasmacytoma) og metastases.

Examinations

A minimum investigation in case of suspected cancer may include:

Disease history may include mapping risk factors such as hereditary predisposition, environmental factors such as smoking, previous chemotherapy or long-term use of immunosuppressive drugs or previous cancer.

Clinical examination of the head and neck, lymph nodes, skin, breasts, rectum and prostate.

Laboratory investigations may include lowering reaction (SR), CRP, blood percentage (hemoglobin), white blood cells (leukocytes) with differential counts, platelets (thrombocytes), liver enzymes such as ALT, AST, gamma-GT and LD, kidney function tests (creatinine), pancreatic amylase / lipase, muscle enzymes (creatine kinase, CK), blood sugar, metabolic hormones (TSH, f-T4), protein electrophoresis. In regards to Rheumatoid arthritis is anti-CCP useful, similarly for ANA in connective tissue disorders and ANCA in certain types of vasculitis (ANCA vasculitis). Urine sting.

Imaging. CT -lungs (thorax), -stomach area (abdomen) and pelvis, mammography of women.

Other. If the investigation does not disprove the suspicion, a more specific investigation is indicated. This may include MRI, PET / CT, endoscopies (gastrointestinal-lung) and tumor markers in blood samples. It is important that not much time is wasted, so that referral to a special department (packaging process) may be relevant.

Rheumatic diseases and cancer risk

Ankylosing spondylitis) does not have an increased cancer risk.

Eosinophilic fasciitisBlood cancers and solid tumors are seen somewhat more often than expected (reference; Haddad H, Hematol Oncol Stem Cell Ter, 2014).

Hypertrophic arthropathy "Clubbing" is thickening around the outer joints of the fingers and curvature of the nails. Also problems from skeleton in arms and legs. The symptoms in the fingers also occur with benign, chronic lung or heart disease (reference: Sarkar M, 2012).

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 (reference: Jain AS, 2013).

Myositis / dermatomyositis in adults. In the case of muscle inflammation (myositis) with concomitant typical changes in the skin (dermatomyositis, DM), cancer is detected in 7-14% of adults, which is more often than expected. The cancer is most often detected in the same year as the rheumatic disease is diagnosed, but there is an increased risk also in the following 2-3 years. About 2/3 of cancer cases are made up of cancer of the cervix, lungs, ovaries, pancreas, bladder og stomach. Risk factors are high age at disease onset, antibody (blood test): p-155/140/TIF-Ƴ, NXP-2. One should be aware of new symptoms that cannot be explained based on the muscle disease (reference: Dobloug C, 2015). Children with dermatomyositis do not have an increased risk of cancer. Myositis is distinguished from muscle weakness by Myastenia gravis which can be triggered by tumor i thymus (reference: Sieb JP, 2014).

Lambert-Eaton syndrome results in myasthenia -similar disease picture with failing muscle power in the legs and arms. Lung cancer is the most common underlying cancer type (reference; Kesner VG, 2018).

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 (ovarian cancer) in women. Treatment of underlying cancer most often improves the symptoms, while anti-rheumatic treatment has little effect (reference: Kajikawa H, 2018). However, there are also cases without another underlying disease (idiopathic palmar and polyarthritis syndrome).

Panniculitis: Acute inflammation of fatty tissue (panniculitis) can be pancreatic disease, including cancer in some cases. Arthritis and nodules under the skin are often seen at the same time. Other cancers can also be associated with panniculitis (reference; Buragina G, 2019).

Polymyalgia rheumatica (PMR): There is no increased risk of cancer, but people with PMR are also at risk for cancer. If the initial symptoms of PMR are uncharacteristic, further investigation is also recommended for cancer (reference: Myklebust G, 2002). However, polymyalgia rheumatica-like muscle pain is a possible side effect of cancer treatment with checkpoint inhibitors (reference: Zhou J, 2020).

Psoriasis arthritis (psoriasis arthritis): No increased cancer risk (reference: Vaengebjerg S, 2020).

Raynaud's phenomenon ("corpse fingers") can rarely be an expression of underlying cancer. Suspicion arises from other concurrent symptoms such as weight loss and new night sweats (reference; Lokieni S, 2021).

Rheumatoid arthritis (arthritis). A slightly increased risk of lymphoma has been seen (Lymphoma, most often non-Hodgkin's lymphoma), but not such that special follow-up is recommended without symptoms. Risk factors are high arthritis activity over many years and Felty's syndrome. Many years of use of powerful immunosuppressive drugs can increase the risk of skin cancer. With such drugs, regular sunscreen and other protective measures are therefore recommended (see also section on drugs and cancer above) (References: De Cock D, Vest Practice and Res Clin Rheum, 2018Klein A, Hematol Oncol, 2018).

RS3PE (remitting seronegative symmetrical synovitis with pitting edema)Up to 30% are cancer-associated. Various cancers. The symptoms may respond well to prednisolone, but a poor response should raise the suspicion of an underlying malignancy (reference: Karmacharya P, Clin Exp Rheum, 2016.)

Sjögren's syndrome. Lifetime risk of lymph node cancer in the form of non-Hodgkin's lymphoma is estimated at 5-10%. This is an excess compared to the rest of the population. Risk factors are high disease activity measured by frequent swelling of the major 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 the blood tests (reference: Reksten TR, 2014).

Sweet's syndrome. About. 20% associated with cancer (Iymphoproliferative). All respond to corticosteroids. Most often, acute myelogenous leukemia and other haematological, but also solid tumors occur. Note! They seem to respond to treatment, but very often micrometastases remain (reference; Heath MS, Front Immunol, 2019).

Systemic Lupus Erythematosus (SLE). SLE is not associated with a particularly increased risk of cancer, and no increased mortality from cancer has been demonstrated. Slightly increased incidence of lymph node cancer (Lymphoma, diffuse large cell B-cell lymphoma can still occur with high disease activity, long-term illness and immunosuppressive treatment as risk factors. Warning symptoms are a low white blood cell count, swollen lymph glands and an enlarged spleen (reference: Ladourceur R, 2020).

Systemic Sclerosis. There is probably a slightly increased risk of lung cancer, breast cancer, cervical cancer and skin cancer (reference Szekanecz E, Autoimmunity Rev, 2012), but very few people are affected. Patients with the RNA polymerase III antibody in the blood is disposed. In cancer, scleroderma-like symptoms, often overlapping with myositis and other connective tissue diseases, can occur (pseudo-scleroderma) (Reference: Frich L, 2019).

Gout can be triggered during cancer treatment (tumour-tissue dies) or in related kidney failure and causes sudden pain with severe joint inflammation. Gout as a general risk factor for cancer is debated, but analyzes of large materials may indicate a slightly increased risk for certain forms of cancer (urinary tract, gastrointestinal tract, lung) (reference: Wang W, 2015).

Vasculitis diseases: It is not common, but in some cases with (inflammation of blood vessels (vasculitis) can occur at the same time as cancer. Characteristics can be an unusual vasculitis disease that does not fit the established diagnoses, previous cancer, burning sensation (polyneuropathy), possible itching. Cancer in the lymph nodes and bone marrow (lymphoproliferative and myeloproliferative diseases) is most common. Almost all types of vasculitis have been reported in cancer, but a direct connection is often unclear, because coincidences are also possible. Checkpoint inhibitors used in cancer treatment can trigger vasculitis (reference; Daxini A, Clin Rheum, 2018. Giant cell arteritis (temporal arteritis) is generally not prohibited with increased cancer risk, but the age group (older people) is exposed to both conditions. If the initial symptoms are uncharacteristic, further investigation can therefore be recommended. Literature; Spruce JT. Tidsskr Nor Lægefor, 1997;  Agha A, Curr Rheum Rep 2012.

Medicines and cancer

The indication for each drug against rheumatic disease is always assessed against the risk of side effects in the individual. Age, sex, family history of cancer, previous chemotherapy or radiotherapy, many X-ray examinations (X-ray exposure) and smoking can be taken into account in the assessment. Active rheumatic inflammation over several years can in itself increase the risk of cancer (reference; Simon TA, 2015; Singh N, 2019). By suppressing the rheumatic inflammation, most people will immunosuppressive, anti-rheumatic drugs do not increase the risk (reference: Zappavigna S, 2020). A possible exception is cyclophosphamide (Sendoxan), which is used in the most severe cases of complicated rheumatic disease. An increased incidence of Lymphoma, Leukemia og urinary bladder cancer. However, data are based on long-term use with tablets, while modern anti-rheumatic treatment uses intravenous dosing with a duration of less than 6 months, which suggests less increased risk of cancer. Immunosuppressive drugs such as methotrexate, azathioprine (Imurel), and mycophenolate (CellCept) can contribute to skin cancer if you spend a lot of time in the sun without good protection. This is well documented for people who use the drugs after transplantation (reference: Corchado-Cobos R, 2020). Hydrochlorochloroquine (Plaquenil), sulfasalazine (Salazopyrin), NSAIDs, cortisone/prednisolone or Biological drugs such as abatacept (Orensia), rituximab (MabThera), TNF inhibitors (infliximab, adalimumab, etanercept, cerulizumab, golimumab) or tocilizumab (RoActemra) have not been shown to increase the risk of cancer.

People who have or have had cancer must be assessed individually. Although most drugs against rheumatic disease do not show an increased risk of developing cancer, immunosuppressive drugs can theoretically contribute to an increased risk of the spread or recurrence of known cancer if this has not been cured. If there is any doubt, it is recommended that a rheumatologist and cancer specialist (oncologist) make an individual assessment.

Rheumatic complications in cancer treatment. In the treatment of cancer, drugs are used which in some cases can cause rheumatic side effects. 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 may increase the risk of autoimmune disease such as arthritis/Rheumatoid arthritis (RA) og polymyalgia revmatika (PMR) and similar conditions (Reference: Belkhir R, 2017; Calabrese L, 2020).

BCG treatment against bladder cancer can cause joint pain and joint swelling (reactive arthritis), usually 2-4 weeks after the treatment. Knees and ankles are most often affected. The symptoms usually resolve within 6 months (reference: Freixa M, 2020).

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) is used as a supplement for some chemotherapy. The treatment may lead to acute, symmetrical arthritis in several 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 metastasizing Malignant melanoma (Skin cancer) and kidney cancer may trigger Psoriasis arthritis, Ankylosing spondylitis, Rheumatoid arthritis, Myositis and other rheumatic diseases. Usually, the symptoms subside when the treatment is finished.

Literature


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