What is Hypergammaglobulinemia (Polyclonal Gammopathy)?
Hypergammaglobulinemia (also known as polyclonal gammopathy) is a condition where your body produces too many kinds of specific proteins (called immunoglobulins) that are made by cells in the blood, known as plasma cells. This is often linked to liver disease, autoimmune disorders (conditions where your immune system attacks your own body), and some types of cancers. It can also occur during acute (short-term) or chronic (long-term) inflammation, which is the body’s response to injury or illness.
It’s important to understand that hypergammaglobulinemia is generally a mild condition that doesn’t generally develop into an obvious form of cancer. This is unlike something known as monoclonal gammopathy of undetermined significance (MGUS), another condition that results in an overproduction of a specific type of protein.
What Causes Hypergammaglobulinemia (Polyclonal Gammopathy)?
The exact cause of hypergammaglobulinemia, also known as polyclonal gammopathy, is still unknown. However, it has been observed that this condition is associated with a variety of different disorders. In particular, liver disease is the most common cause related to hypergammaglobulinemia.
There are also other causes worth noting. Autoimmune conditions like Sjögren syndrome, blood disorders such as idiopathic neutropenia, non-blood related cancers, infections like the human immunodeficiency virus, IgG4-related disease (a condition where the immune system attacks healthy tissues), and certain medical treatments like intravenous immunoglobulin therapy can all play a role in causing hypergammaglobulinemia.
Risk Factors and Frequency for Hypergammaglobulinemia (Polyclonal Gammopathy)
Hypergammaglobulinemia, also known as polyclonal gammopathy, isn’t very common. This condition typically affects older individuals, with the average age being 58 years old. There’s also roughly an equal number of men and women who get this disease. Some research suggests that it is notably prevalent among African American and black populations.
- Hypergammaglobulinemia, or polyclonal gammopathy, is not common.
- It mainly occurs in older people, with the average age of patients being 58.
- Both men and women are equally likely to have this condition.
- It appears to be more common among African American and black populations.
Signs and Symptoms of Hypergammaglobulinemia (Polyclonal Gammopathy)
Hypergammaglobulinemia, also known as polyclonal gammopathy, does not directly cause symptoms. Instead, the symptoms a patient experiences are typically connected to an underlying disorder causing the hypergammaglobulinemia. When diagnosing a patient with this condition, doctors should consider a number of factors based on the patient’s history and physical examination:
- Signs of chronic liver disease
- Fever or any signs of infection
- Travel and exposure history
- Enlarged lymph nodes
- Skin lesions
- Arthritis
- Swelling of tear, salivary, and parotid glands
- An enlarged liver or spleen
- Symptoms related to hyperviscosity syndrome (a condition where the blood becomes too “thick” or “sticky”)
- Previous treatment with intravenous immunoglobulin
- A family history of immune system disorders
Testing for Hypergammaglobulinemia (Polyclonal Gammopathy)
Hypergammaglobulinemia, also known as polyclonal gammopathy, occurs when there is an increase in various types of immunoglobulins in your blood. Immunoglobulins are proteins that help your body fight off infections. The presence of hypergammaglobulinemia can be identified through a diagnostic tool called Serum protein electrophoresis. This tool detects a large and wide increase in the gamma region of the test, indicating that there are more immunoglobulins in your blood than usual.
If hypergammaglobulinemia is identified, and the cause is clear based on your symptoms and medical history, then no further investigation is typically needed. However, if the cause isn’t obvious, your doctor may run additional tests to figure out what’s causing the rise in immunoglobulins. These might include a complete blood count, tests for inflammation, liver enzyme tests, antibody tests, tests for specific viruses such as hepatitis or HIV, imaging tests for disease in the liver or other organs, or bone marrow biopsy in cases where a blood disorder or lymphoma is suspected.
There are five types of immunoglobulins: IgM, IgG, IgA, IgD, and IgE, and a rise in specific types can help narrow down the cause of hypergammaglobulinemia. For example, things like acute infections and a condition known as hyper-IgM syndrome can cause increased levels of IgM. Conditions such as liver cirrhosis, a disease affecting your veins called IgA vasculitis, autoimmune diseases like rheumatoid arthritis and celiac disease, and AIDS can cause a rise in IgA levels. Increased levels of IgE are usually due to allergic conditions, lymphoma, a condition known as hyper-IgE syndrome, and atopic diseases. Conditions associated with an increase in IgG levels include liver disease, autoimmune disease, vasculitis, infection, blood diseases, a condition known as IgG4-related disease, immunodeficiency, and administration of intravenous immunoglobulins treatment.
Treatment Options for Hypergammaglobulinemia (Polyclonal Gammopathy)
Hypergammaglobulinemia is a condition where you have too many gamma globulins, which are types of proteins made by the immune system. When hypergammaglobulinemia occurs, it’s usually because of some underlying illness. The best way to treat hypergammaglobulinemia is to treat the original condition. Most of the time, if you treat the root cause, the excessive gamma globulins will go away.
Sometimes, hypergammaglobulinemia can lead to other problems like “hyperviscosity syndrome.” In these cases, your doctor will usually prescribe steroids and a procedure called plasmapheresis, where some of your blood is removed, treated, and returned to your body.
In some cases, hypergammaglobulinemia is associated with a condition known as IgG4-related disease. To treat this, physicians usually recommend steroids or a drug called rituximab. About 80% of patients respond well to steroids. But rituximab seems to be more effective, with about 95% of patients responding positively to it. In such cases, your doctor will first try to get the disease under control with rituximab. Once the disease is in a stable state, you may be given lower doses of the steroid or other steroids to prevent any potential side effects from long-term use of strong steroids.
The doctors will then keep you under close observation and regularly check your blood levels. Despite this, some patients experience a relapse within a year and may need another round of treatment with rituximab.
For severe chronic inflammation from certain conditions like hidradenitis suppurativa and Castleman disease, you’ll likely undergo treatment with the drugs anakinra and siltuximab respectively.
If hypergammaglobulinemia is due to a condition called Sjogren’s Syndrome, it often doesn’t require specific treatment. Instead, your doctor will monitor you regularly to make sure there aren’t any changes or new complications.
Remember, each condition and person are different. These are general descriptions and your healthcare team will provide a treatment tailored to your specific situation.
What else can Hypergammaglobulinemia (Polyclonal Gammopathy) be?
If you’ve been diagnosed with ‘hypergammaglobulinemia (polyclonal gammopathy),’ it means there’s too much of a particular protein in your blood. This condition could be caused by various diseases. Here are some possible causes categorized into several groups:
Liver Disease
- Autoimmune hepatitis
- Viral hepatitis
- Ethanol-induced liver injury
- Primary biliary cirrhosis (PBC) or Primary sclerosing cholangitis (PSC)
- Cryptogenic cirrhosis
- Primary hemochromatosis
- Alpha1-Antitrypsin deficiency (A1AT deficiency)
Connective Tissue Disease
- Sjogren syndrome
- Systemic lupus erythematosus (SLE)
- Rheumatoid arthritis (RA)
- Mixed connective tissue disease (MCTD)
- Overlap syndrome
- Familial Mediterranean fever (FMF)
- Benign hypergammaglobulinemic purpura of Waldenstrom
Lymphoproliferative Disorders
- Pseudo-lymphoma
- Malignant lymphoma
- Castleman disease (a group of uncommon lymphoproliferative disorders)
Myelodysplastic syndromes
Nonhematologic Malignancy
- Gastric carcinoma
- Hepatocellular carcinoma
- Lung cancer
- Renal cell carcinoma
- Chondrosarcoma
- Ovarian cancer
Infections
- Subacute bacterial endocarditis
- Whipple disease
- Brucellosis
- Lyme disease
- Renal abscess
- Cystic fibrosis
Neurologic Conditions
- Acquired chronic dysimmune demyelinating polyneuropathy
- Chronic progressive sensory ataxic neuropathy
- HTLV-1–associated myelopathy
Diseases associated with abnormal Immune System
- Graves disease
- Chronic ulcerative colitis
- Sarcoidosis
- Chronic autoimmune pancreatitis
- Hyperimmunoglobulinemia D and periodic fever syndrome
Other Hematologic Conditions
- Idiopathic thrombocytopenic purpura (ITP)
- Idiopathic neutropenia
- Severe hemophilia A
Miscellaneous Conditions
- Cardiac myxoma
- Asbestos exposure
- Lymphoid interstitial pneumonia (LIP)
- Cryptogenic organizing pneumonitis (COP)
Understanding the root cause of your condition is important. Each of these diseases needs a different approach in terms of treatment. If you are diagnosed with ‘hypergammaglobulinemia (polyclonal gammopathy),’ your doctor will consider all these potential causes to find the best treatment method for you.
What to expect with Hypergammaglobulinemia (Polyclonal Gammopathy)
‘Hypergammaglobulinemia (polyclonal gammopathy)’ is a condition where there are too many antibodies in the blood, and most cases tend to get better after treating the original cause of the condition. Unfortunately, it’s not possible to predict the outcomes for each patient accurately. However, certain factors can suggest how well a patient may recover. These factors include their age, the type of disease they have, the concentration of a protein called serum albumin in their blood, and the number of platelets, which are cells that help the blood to clot.
Possible Complications When Diagnosed with Hypergammaglobulinemia (Polyclonal Gammopathy)
People with a condition known as ‘hypergammaglobulinemia (polyclonal gammopathy)’ have an increased chance of getting other infections. There have also been cases where this condition is linked to ‘hyperviscosity syndrome,’ a medical issue where the blood becomes too thick.
Common Issues:
- Increased chances of further infections
- Potential association with ‘hyperviscosity syndrome’
Preventing Hypergammaglobulinemia (Polyclonal Gammopathy)
Teaching the patient is a crucial part of handling hypergammaglobulinemia (also known as polyclonal gammopathy). Hypergammaglobulinemia is a condition where you have an excess of immunoglobulins, which are proteins that help fight off infections, in your blood. It’s important to know that this condition is not cancerous. One important way to manage this condition is to regularly check the proteins in your blood through a test called serum protein electrophoresis. Also, when the patient is actively involved in making decisions about their medical care, they are more likely to follow through with the plan.
