Paraneoplastic Syndromes – Symptoms and Causes
Overview
Paraneoplastic syndromes are rare disorders triggered by an abnormal immune system response to cancer in the body. They occur when cancer-fighting antibodies or immune cells mistakenly attack normal cells in the nervous system or other organs.
These conditions can affect various body systems and often appear before cancer is diagnosed. Some patients develop symptoms months or even years before their underlying cancer is discovered.
Symptoms
Paraneoplastic syndromes produce a wide range of symptoms that vary based on which body systems are affected. These symptoms often appear before cancer is diagnosed and can sometimes be more serious than the cancer itself.
Neurological symptoms may include difficulty walking, loss of fine motor skills, slurred speech, memory problems, seizures, vision changes, and sleep disorders. These symptoms happen when the immune system attacks parts of the nervous system.
Endocrine-related symptoms might involve unexplained weight loss, excessive thirst, frequent urination, and blood sugar changes. Some patients experience weakness, high blood pressure, or electrolyte imbalances due to hormone disruptions.
Skin manifestations can include itching, redness, skin thickening, or unusual darkening of the skin. Some people develop a distinctive rash called dermatomyositis, which appears as a purplish-red rash on the eyelids, face, neck, chest, and shoulders.
Blood abnormalities are common and may cause:
- Unexplained anemia
- Excessive blood clotting
- Bleeding problems
- Easy bruising
Joint and muscle problems often develop, with symptoms like:
- Muscle weakness (especially in the hips and shoulders)
- Joint pain and swelling
- Morning stiffness
- Difficulty climbing stairs or getting up from chairs
Kidney function changes may lead to protein in urine, decreased urine output, and swelling in the legs and ankles. Some patients experience unexpected fevers, night sweats, and a general feeling of illness that doesn’t improve with standard treatments.
Types of Paraneoplastic Syndromes
Paraneoplastic syndromes occur when cancer cells trigger abnormal immune system responses that affect parts of the body beyond the tumor. These conditions vary based on which body systems they affect.
Neurological Syndromes
These affect the nervous system and may appear before cancer is diagnosed. Common types include:
- Limbic Encephalitis: Causes memory problems, seizures, and confusion.
- Cerebellar Degeneration: Leads to trouble with balance and coordination.
- Lambert-Eaton Syndrome: Creates muscle weakness, especially in the legs.
Most neurological paraneoplastic syndromes are linked to small cell lung cancer, though they can occur with other cancers too.
Endocrine Syndromes
These syndromes involve hormone imbalances when tumors release hormones or hormone-like substances:
| Syndrome | Common Features | Associated Cancers |
|---|---|---|
| Cushing’s Syndrome | Weight gain, high blood pressure, diabetes | Small cell lung cancer, adrenal tumors |
| Hypercalcemia | Confusion, kidney stones, bone pain | Lung cancer, breast cancer, multiple myeloma |
| SIADH | Low sodium levels, headache, confusion | Small cell lung cancer |
Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) is particularly common with lung cancers.
Hematological Syndromes
These affect blood cells and clotting:
- Anemia: Low red blood cell count causing fatigue.
- Thrombocytosis: Excess platelets increasing clotting risk.
- Leukemoid reaction: Abnormally high white blood cell counts.
Cutaneous Syndromes
These cause skin changes and may include:
- Dermatomyositis: Purple rash on eyelids and muscles, with muscle weakness.
- Acanthosis nigricans: Dark, velvety skin patches in body folds.
- Sweet’s syndrome: Painful red bumps, fever, and joint pain.
These skin conditions often improve when the underlying cancer is treated.
Rheumatologic Syndromes
These affect joints and connective tissues. They include hypertrophic osteoarthropathy (clubbing of fingers and painful joints) and polymyalgia rheumatica (muscle pain and stiffness in shoulders and hips).
When to See a Doctor
Contact your healthcare provider if you notice unexplained symptoms that don’t improve, especially if they develop rapidly or affect your nervous system. Seek immediate medical care for severe symptoms like difficulty walking, seizures, vision problems, or sudden confusion.
Medical attention is particularly important if you’ve been diagnosed with cancer and develop new symptoms. Even if your cancer is in remission, tell your doctor about new health issues that arise.
Causes
Paraneoplastic syndromes develop when cancer cells trigger an immune system response. This happens when cancer cells produce substances like hormones or proteins that aren’t normally made by these cells.
The body sees these substances as foreign and mounts an immune response.
The immune system creates antibodies to fight these unusual substances. Unfortunately, these antibodies can mistakenly attack normal cells in the nervous system, muscles, joints, or other body parts. This “friendly fire” causes the symptoms of paraneoplastic syndromes.
Certain cancers are more likely to cause paraneoplastic syndromes:
- Small cell lung cancer
- Breast cancer
- Ovarian cancer
- Lymphomas
- Thymomas
The risk factors for developing paraneoplastic syndromes include:
- Having one of the cancers listed above
- Advanced age
- Genetic factors that affect immune response
- History of autoimmune disorders
Sometimes paraneoplastic symptoms appear before cancer is diagnosed. In fact, these symptoms might lead doctors to discover a previously unknown cancer.
This happens because the immune system is very sensitive and can detect cancer cells before they show up on imaging tests.
Risk Factors
Several factors may increase a person’s chance of developing paraneoplastic syndromes.
The most significant risk factor is having cancer, particularly certain types such as small cell lung cancer, breast cancer, ovarian cancer, and lymphomas. People over age 50 face higher risks as cancer rates increase with age.
Smoking habits strongly influence risk levels, especially for lung cancer-related paraneoplastic syndromes. A family history of cancer or autoimmune disorders may also play a role in susceptibility.
Certain medical conditions can increase vulnerability. Patients with compromised immune systems, whether from disease or medications, might experience altered immune responses that contribute to paraneoplastic syndrome development.
Gender differences exist for specific types. For example, Lambert-Eaton myasthenic syndrome occurs more frequently in men, while ovarian cancer-related paraneoplastic disorders naturally affect only women.
Previous autoimmune conditions may predispose someone to developing these syndromes when cancer appears. The body’s immune response to cancer can sometimes trigger these unexpected complications.
