Anemia and joint pain

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The Link Between Rheumatoid Arthritis and Anemia

Why Do People With Rheumatoid Arthritis Develop Anemia?

The most common type of anemia in people with RA is the anemia of inflammation, explains Sioban Keel, MD, an associate professor of medicine in the division of hematology at the University of Washington School of Medicine in Seattle. “Anemia can occur in people who have ongoing inflammation in their body, including rheumatoid arthritis and inflammatory bowel diseases like Crohn’s disease and ulcerative colitis,” she says.

The inflammation from RA interferes with the body’s ability to recycle the iron in our blood and absorb iron from food, which can lead to anemia, says Dr. Keel.

Medications commonly used to manage RA, sometimes including non-steroidal anti-inflammatory drugs (NSAIDs) and steroids (also called corticosteroids), may also trigger anemia through a different mechanism of chronic blood loss. These drugs, especially the NSAIDs, can cause chronic irritation and bleeding of the stomach lining, according to the National Institute of Diabetes and Digestive and Kidney Diseases. This blood loss may be slow and not immediately noticeable, but over time, it can lead to anemia.

How Is RA-Related Anemia Treated?

Talk to your doctor if you’re experiencing symptoms of anemia like those noted above, or if you feel that your other RA symptoms aren’t under control. They will want to rule out non-RA related causes of anemia before recommending treatment, or changing your arthritis treatment plan if your medications could be contributing to anemia.

When it comes to treatment, iron therapy given by mouth or intravenously is often beneficial for people who have both RA and anemia and who have low blood levels of iron.

Powerful antacids, often given to people taking NSAIDs to protect their stomach lining, can diminish the absorption of iron from the intestines. This may lead to the need for intravenous rather than oral iron.

Typically, says Dr. Keel, the treatment for RA-related anemia is to treat the inflammation caused by the RA. And managing the inflammation and swollen joints associated with RA should help alleviate your anemia and its symptoms.

In chronically active RA inflammation, your doctor may ultimately recommend that you replace NSAIDs or steroids with one of the disease-modifying anti-rheumatic drugs (DMARDs), which are effective in remitting RA inflammation. An effective RA treatment regimen will improve both your joint symptoms and anemia, and you’ll feel better all around.

Does Rheumatoid Arthritis Cause Anemia? What to Know About This Common Blood Disorder

Anemia is a condition that develops when your blood is short on red blood cells or hemoglobin — an iron-rich protein that allows red blood cells to carry oxygen from your lungs to the rest of your body. With your body can’t circulate enough oxygen, it can leave you feeling tired and weak. Anemia is the most common blood disorder; according to the National Heart, Lung, and Blood Institute, it affects more than 3 million Americans.

So what does anemia have to do with rheumatoid arthritis (RA) and other forms of inflammatory arthritis?

A lot, actually. A research review published in the American Journal of Medicine found anemia can occur in up to 60 percent of RA patients. Other research shows anemia affects about half of people with lupus; mild cases of anemia may be seen in psoriatic arthritis.

What Causes Anemia in People with Inflammatory Arthritis?

There are many different forms of anemia and each has its own cause.

Anemia of Chronic Disease

One type — called anemia of chronic disease, or ACD — is a major cause of anemia in people with RA. In one study of 225 RA patients, ACD accounted for 77 percent of the observed anemia. It’s also the most common form of anemia in lupus patients.

Also called anemia of inflammation, ACD affects people who have conditions that cause inflammation, such as infections, cancer, chronic kidney disease, and autoimmune diseases (like RA or lupus).

With ACD, you may have normal or sometimes increased amounts of iron stores in your body tissue, but a low level of iron in your blood. Chronic inflammation may prevent your body from using the stored iron to create new red blood cells, which leads to anemia. Inflammation can also affect the way your body produces a specific hormone called erythropoietin, which controls the production of red blood cells. A 2008 study of 111 patients with early RA reported the prevalence of ACD to be 25 percent during the first year of disease.

Getting inflammation under control with medication is the best way to treat this kind of anemia.

Iron Deficiency Anemia

Iron deficiency anemia — the most common type of anemia — also occurs in people with inflammatory arthritis. It is caused by a shortage of iron in both body tissues and blood. Your bone marrow needs iron to make hemoglobin; without adequate iron, your body can’t produce enough hemoglobin for red blood cells.

Iron deficiency anemia often occurs because of blood loss. In people with inflammatory arthritis, taking nonsteroidal anti-inflammatory drugs (NSAIDs) — used to relieve pain and help reduce inflammation — can cause ulcers or gastritis, which may lead to gastrointestinal bleeding, and in turn, iron-deficiency anemia.

It’s critical to be aware of gastrointestinal complications if you’re using NSAIDs, especially at a high dose or for an extended period of time. Read more about GI warning signs and how to protect yourself.

How Other Medications Affect Anemia in Arthritis

Aside from NSAIDs, other medications may lead to forms of anemia as well.

Some disease-modifying anti-rheumatic drugs (DMARDs) — like methotrexate (Rheumatrex, Trexall, Otrexup, Rasuvo), sulfasalazine (Azulfidine), and leflunomide (Arava) — used to treat RA have been associated with aplastic anemia. This rare, but serious, form of anemia occurs when there’s damage to your bone marrow and your body stops producing enough new blood cells. Loss of bone marrow caused by certain drugs used to treat lupus (such as azathioprine or cyclophosphamide) can also reduce red blood cell production, according to the Lupus Foundation of America.

Different types of anemia are treated in different ways. Your doctor will need to determine the cause of your anemia in order to figure out next steps.

What Are the Symptoms of Anemia?

RA-related anemia is typically mild and develops slowly, causing few or no symptoms. Feeling tired or weak or having fatigue is a common sign of anemia, but this also occurs as part of normal disease activity in inflammatory arthritis. If you have fatigue from your chronic disease, it can be hard to tell if you might also have anemia. This is why routine blood testing at the doctor to detect anemia (more on this below) is important.

If your anemia becomes more severe, however, the lack of oxygen in your blood can cause more telltale signs of anemia, such as:

  • Pale skin
  • Irregular heartbeats
  • Feeling faint, dizzy, or light-headed
  • Shortness of breath
  • Cold hands and feet
  • Headache
  • Chest pain

How Is Anemia Diagnosed?

Anemia can be detected during routine bloodwork at doctor visits. Any abnormalities in the following could indicate anemia:

  • Number of red blood cells
  • Levels of hemoglobin in your blood
  • Number of developing red blood cells (called reticulocytes)
  • Size, shape, and color of red blood cells for any irregularity
  • Amount of iron in your blood
  • Amount of iron stored in your body

Your doctor can also pick up on certain signs of anemia while performing a physical exam, such as while listening to your heart or lungs and pressing on your abdomen.

How Is Anemia Treated?

Managing your inflammatory arthritis is step one if you have ACD. Reducing inflammation in the body can help alleviate both joint symptoms and anemia, and improve your overall well-being.

If you have low iron levels contributing to your anemia, your doctor may suggest taking iron supplements and making changes to your diet. In some cases, adjustments may be made to your RA meds. If you suspect you have anemia, talk to your doctor, who can determine the safest steps for you.

If symptoms of anemia become severe, your doctor may consider doing a blood transfusion or injections of a synthetic hormone called erythropoietin, which may help stimulate red blood cell production.

Treating anemia is critical to not only help you feel better from symptoms like fatigue, but also to prevent serious health complications, such as heart problems like an irregular heartbeat or heart failure.

Keep Reading

  • Arthritis Fatigue: 7 Tips to Help You Cope
  • 12 Healthy Habits for Inflammatory Arthritis Worth Adding to Your Daily Routine
  • Common Questions About Taking Methotrexate for Rheumatoid Arthritis

Iron deficiency

What is anaemia?

Anaemia (American spelling, anemia) is a deficiency of red blood cells. It can occur either through the reduced production or an increased loss of red blood cells.

Three essential elements must be present to produce red blood cells: iron, vitamin B12 and folic acid. The most common cause of anaemia is iron deficiency, affecting more than 2 billion people worldwide.

What is iron-deficiency anaemia?

The estimated prevalence of iron deficiency worldwide is double that of iron deficiency anaemia. Iron deficiency anaemia occurs when there is insufficient iron to create red blood cells

Who gets iron deficiency?

The main groups at risk of iron deficiency and iron-deficiency anaemia are pre-school children, adolescents, pregnant and young women, which are times of increased physiological need for iron.

What causes iron deficiency?

In people living in developing countries, iron deficiency tends to be due to insufficient dietary iron intake or to blood loss from intestinal worm colonisation. In high-income countries, iron deficiency may result from a vegetarian diet, chronic blood loss, or malabsorption.

  • Diet-related iron deficiency
    • Malnutrition — poverty, premature babies (milk is a poor source of iron), young children who are picky eaters
    • Strict vegetarian and vegan diets
    • Cereal-based diets — decreases iron bioavailability, as phytates in grains reduce iron absorption
  • Blood loss
    • Heavy menstruation (periods)
    • Gastrointestinal bleeding — from peptic ulcer, polyps or cancer, may occur over a long period
    • Excessive blood donation
  • Gastrointestinal iron deficiency
    • Malabsorption
    • Crohn disease
    • Helicobacter infection or atrophic gastritis, which may also lead to B12 deficiency
    • Intestinal parasitic infections, such as hookworm or tapeworm
  • Medication-related iron-deficiency
    • Aspirin and non-steroidal anti-inflammatory drugs — cause gastritis
    • Proton pump inhibitors – may impair iron absorption
  • Other conditions
    • Pregnancy
    • Bleeding disorders, such as von Willebrand disease
    • End-stage renal failure — a combination of blood loss from dialysis and low erythropoietin levels (a hormone that stimulates red blood cell production)
    • Congestive cardiac failure — possibly due to subclinical inflammation and impaired iron absorption
    • Myelodysplasia — bone marrow disease which can present with anaemia
    • Intravascular haemolysis (rare) as in paroxysmal nocturnal haemoglobinuria

What are the clinical features of iron deficiency?

The signs and symptoms of an iron deficiency depend on whether the patient is anaemic, and if so, how fast the anaemia develops. In cases where anaemia develops slowly, the patient can often tolerate extremely low concentrations of red blood cells (< 100 g/L) for some weeks before developing any symptoms. The first symptoms to appear are due to low delivery of oxygen to tissues, and may include:

  • Lethargy
  • Weakness
  • Poor concentration
  • Shortness of breath
  • Palpitations.

Skin signs of iron deficiency anaemia

Skin signs of anaemia are often subtle and may include:

  • Paleness of skin, palm creases and conjunctiva
  • Angular cheilitis, painful cracks at the corners of the mouth
  • Atrophic glossitis, loss of tongue papillae (smooth, shiny tongue)
  • Pruritus and dry skin
  • Nail disorders, including koilonychia
  • Dry and brittle hair
  • Increased hair shedding (telogen effluvium) resulting in diffuse alopecia.
Cutaneous signs of iron deficiency

Systemic symptoms of iron deficiency anaemia

Other characteristic manifestations of iron deficiency anaemia may include:

  • Pica — an appetite for clay, dirt, paper or starch
  • Pagophagia — a pica for ice, considered quite specific for iron deficiency. Responds rapidly to iron replacement.
  • Beeturia — excretion of red urine with the consumption of beets. In people with normal iron levels, ferric ions decolourise betalain (the red pigment in beets). In iron-deficient states, there are inadequate amounts of iron to decolourise this pigment.
  • Restless legs syndrome — marked discomfort in the legs occurring at rest that is relieved by movement.

Iron deficiency may also predispose to bacterial and fungal infections such as impetigo, boils and candidiasis.

What tests should be done?

Full blood count

A full, or complete, blood count (FBC, CBC) is essential to detect anaemia. Iron deficiency can be present when blood count indices are normal.

If anaemia is due to iron deficiency, the cells are smaller and contain less haemoglobin resulting in lowered red blood cell count or haematocrit, mean corpuscular volume (MCV) and mean cell haemoglobin concentration (MCH). Reticulocyte haemoglobin content (Ret-Hb), which tends to be low in iron deficiency anaemia, can be used to monitor response to iron replacement. Red cell distribution width (RDW) can reveal mixed iron and vitamin B12 deficiency as this results in red cells of variable size.

Ferritin

Ferritin is a measure of iron stores and is the most sensitive and specific test for iron deficiency. Low levels of ferritin less than 15 μg/ml are diagnostic of iron deficiency. Levels higher than 40 μg/ml in a healthy person are considered optimal.

Normal or high levels of ferritin do not exclude iron deficiency, because ferritin acts as an acute phase reactant. Levels are higher in the presence of chronic inflammation (eg, rheumatoid arthritis) when erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) are elevated. In the context of inflammation, significantly higher cut-off values for ferritin are used (eg, 100 μg/ml) and are more predictive of iron deficiency. Ferritin is also more elevated in patients with chronic kidney disease and heart failure.

Other iron tests

In iron deficiency:

  • Serum iron is reduced — be aware that serum iron can be very variable, fluctuating through the day, and serum iron is not useful in assessing iron stores
  • Iron binding capacity is increased — a measure of the capacity of iron to bind with transferrin (an iron transporter)
  • Transferrin saturation is reduced
  • Soluble transferrin receptor (sTfR) is reduced – this reflects total body stores, except if there is a disease of the bone marrow. sTfR is an expensive test. It is useful at discriminating iron deficiency in difficult cases, for instance, in patients with chronic renal failure or chronic inflammation like rheumatoid arthritis. It is unchanged in anaemia of chronic disease.

Retest iron status after three months of iron supplementation.

Older patients sometimes have unexplained iron deficiency anaemia. If bowel investigation is negative, bone marrow examination may be considered in undifferentiated cases.

What is the treatment for iron deficiency?

Once iron deficiency has been established, the underlying cause should be investigated and managed (correct/control GI bleeding or menstrual blood loss, eg, with the levonorgestrel-releasing intrauterine device or tranexamic acid for a woman with heavy periods). Most people with iron deficiency anaemia will need iron replacement therapy to correct the anaemia and replenish iron stores. The benefit of treating iron deficiency without anaemia is still uncertain. Specific groups of patients like those with cardiovascular disease (with heart failure or angina) should receive red blood cell transfusions which will correct both hypoxia (low oxygen) and the iron deficiency.

Increase dietary iron

Red meat contains haem iron, which is readily absorbed. Non-haem iron sources may need the help of vitamin C in the form of fresh fruit or tablets.

Many manufactured foods contain iron, so it is essential to read the labels.

Calcium (in milk products) and tannin in tea, coffee and red wine, reduce the absorption of non-haem iron, so these should be taken several hours before a meal. Conversely, vitamin C (ascorbic acid) enhances the absorption of iron when they are taken together.

Oral iron

Iron supplementation is safe in pregnancy, infants, children and adults. It can be used in iron deficiency anaemia and anaemia of chronic disease.

Iron preparations come in the form of tablets, oral liquids and injection. Oral preparations are most commonly used.

Oral iron preparations from reputable sources include:

  • Ferrous fumarate 33% elemental iron
  • Ferrous sulfate 20% elemental iron
  • Ferrous gluconate 12% elemental iron

Enteric-coated and slow-release formulations are less well absorbed, but better tolerated. Taking iron with vitamin C (ascorbic acid) may increase its absorption and help replenish iron stores more quickly. Lower dose preparations are less effective.

In anaemic patients, once haemoglobin levels are corrected to within the normal range, iron replacement should be continued for a further three months to replenish iron stores. Aim for serum ferritin levels over 50 μg/ml.

Iron absorption is reduced in the presence of gastrointestinal disease (atrophic gastritis, infection with Helicobacter pylori, coeliac disease, inflammatory bowel disease), chronic kidney disease and inflammatory conditions.

Interactions with iron

Iron may interfere with the absorption of some medications, including:

  • Doxycycline
  • Fluoroquinolones
  • Mycophenolate mofetil
  • Penicillamine
  • Thyroid hormones.

Iron absorption is decreased by calcium, tannins (in tea and red wine) and plant phytates (in cereals). Iron should be taken at a different time of day.

Iron infusions

Intravenous infusions are used in patients that cannot tolerate oral supplementation, or where iron losses exceed the daily amount that can be absorbed orally. Intravenous iron is also essential in the management of anaemia in patients with chronic kidney disease that are receiving dialysis and treatment with erythropoiesis-stimulating agents (agents to stimulate red blood cell production). Parenteral iron in patients with heart failure has led to improvements in physical performance, symptoms and quality of life.

The most commonly used intravenous preparation is iron polymaltose, which is infused over several hours. Other intravenous preparations include low molecular weight iron dextran, iron carboxymaltose, iron sucrose and ferric gluconate complex.

Side effects of iron replacement

Adherence to recommended oral iron replacement therapy may be poor with some patients as iron preparations are associated with a high incidence of side effects. These include nausea, constipation, diarrhoea and black stools. To reduce this:

  • Take the iron preparation after meals — but iron absorption is reduced
  • Wait 30 minutes before lying down
  • Divide the dose and take it twice daily
  • Take it alternate days, which is better tolerated
  • If treatment is not urgent, start with one tablet twice weekly and gradually increase the dose as tolerated
  • Start with doses containing under 30 mg of elemental iron.

Intravenous iron polymaltose may cause infusion reactions such as headache, nausea and muscle pains. Severe allergic reactions including anaphylaxis have been reported. Delayed reactions include fever and joint pain. Extravasation is rare but may lead to persistent brown discolouration of affected skin.

Intramuscular injections of iron are now rarely used. They may result in long-lasting brown staining (siderosis), pain, haematoma and sterile abscesses. Improvement in iron staining has been reported following treatment with Q-switched ruby and Nd:YAG laser.

Siderosis from iron injection

What is the outcome for iron deficiency anaemia?

Most patients with uncomplicated iron deficiency anaemia should experience:

  • Rapid resolution of pagophagia
  • Improved feeling of well-being within the first few days of treatment
  • Increase in reticulocyte count (red blood cell precursors) and haemoglobin concentration within a week
  • Slow recovery of tongue papillae, skin, nails and hair.

In those who do not respond to treatment, alternative diagnoses need to be considered, for example, B12 or folate deficiencies, myelodysplastic syndrome (bone marrow abnormalities) and inherited anaemias.

Psoriatic Arthritis

What is psoriatic arthritis?

Psoriatic arthritis is a type of arthritis linked with psoriasis, a chronic skin and nail disease. Psoriasis causes red, scaly rashes and thick, pitted fingernails. Psoriatic arthritis is similar to rheumatoid arthritis (RA) in symptoms and joint swelling (inflammation). But it tends to affect fewer joints than RA. And it does not make the typical RA antibodies. The arthritis of psoriatic arthritis comes in 5 forms:

  • Arthritis that affects the small joints in the fingers, toes, or both
  • Asymmetrical arthritis of the joints in the hands and feet
  • Symmetrical polyarthritis, which is similar to RA
  • Arthritis mutilans, a rare type of arthritis that destroys and deforms joints
  • Psoriatic spondylitis, arthritis of the lower back (sacroiliac sac) and the spine

What causes psoriatic arthritis?

Doctors don’t know what causes psoriatic arthritis. But factors such as immunity, genes, and the environment may play a role.

What are the symptoms of psoriatic arthritis?

The psoriasis symptoms may start before or after the arthritis. Psoriasis causes red, scaly rashes and thick, pitted fingernails. About 3 in 20 to 3 in 10 people with psoriasis may develop psoriatic arthritis. Symptoms of psoriatic arthritis may include:

  • Inflamed, swollen, and painful joints, often in the fingers and toes
  • Deformed joints from chronic inflammation

The symptoms of psoriatic arthritis can look like other health conditions. Make sure to see your healthcare provider for a diagnosis.

How is psoriatic arthritis diagnosed?

Psoriatic arthritis is easier to confirm if you already have psoriasis. If you don’t have the skin symptoms, diagnosis is more difficult. The process starts with a health history and a physical exam. Your healthcare provider will ask about your symptoms. You may have blood tests to check the following:

  • Erythrocyte sedimentation rate (ESR or sed rate). This test looks at how quickly red blood cells fall to the bottom of a test tube. When swelling and inflammation are present, the blood’s proteins clump together and become heavier than normal. They fall and settle faster at the bottom of the test tube. The faster the blood cells fall, the more severe the inflammation.
  • Uric acid. High blood uric acid levels can be seen in psoriatic arthritis but are not used for diagnosis or monitoring.
  • Imaging. X-rays, CT scans, ultrasound, MRI, and skin biopsies may all be used to help diagnosis.

How is psoriatic arthritis treated?

Treatment will depend on your symptoms, age, and general health. It will also depend on the severity of your condition.

Both the skin condition and the joint inflammation are treated. Early diagnosis and treatment helps prevent joint damage. Some medicines used to treat psoriatic arthritis include:

  • Nonsteroidal anti-inflammatory medicines (NSAIDs) to ease symptoms
  • Corticosteroids for inflammation
  • Immunosuppressive medicines such as methotrexate to reduce inflammation if NSAIDs don’t work
  • Biologic medicines to ease inflammation
  • Vitamins and minerals such as calcium and vitamin D to slow bone deformation

Other treatment may include:

  • Exercise
  • Heat and cold
  • Occupational therapy to help you do your daily activities
  • Physical therapy to help your muscle and joint function
  • Management of psoriasis skin rash
  • Splints
  • Surgery to repair or replace a damaged joint. This is usually not needed until years after diagnosis.
  • Ultraviolet light treatment (UVB or PUVA)

What are the possible complications of psoriatic arthritis?

The condition may damage joints enough to change your activity level. Lack of activity can lead to stiff joints and muscle weakness. Psoriatic arthritis can also cause tiredness (fatigue) and low red blood cell count (anemia). You are more likely to develop:

  • Diabetes
  • High blood pressure
  • High cholesterol
  • Obesity

Living with Psoriatic Arthritis

There is no cure for psoriatic arthritis. But you can reduce your symptoms by sticking to your treatment plan. Manage pain with medicine, acupuncture, and meditation. Get enough exercise. Good exercises include yoga, swimming, walking, and bicycling. Work with a physical or occupational therapist. He or she can suggest devices to help you in your daily tasks.

When should I call my healthcare provider?

Let your healthcare provider know if your symptoms get worse or you have new symptoms.

Key Points about Psoriatic Arthritis

  • Psoriatic arthritis is a form of arthritis with a skin rash.
  • Psoriasis is a chronic skin and nail disease. It causes red, scaly rashes and thick, pitted fingernails. The rash may come before or after the arthritis symptoms.
  • Psoriatic arthritis causes inflamed, swollen, and painful joints. It happens most often in the fingers and toes. It can lead to deformed joints.
  • Treatment may include medicines, heat and cold, splints, exercise, physical therapy, and surgery.

Next steps

Tips to help you get the most from a visit to your healthcare provider:

  • Know the reason for your visit and what you want to happen.
  • Before your visit, write down questions you want answered.
  • Bring someone with you to help you ask questions and remember what your provider tells you.
  • At the visit, write down the name of a new diagnosis, and any new medicines, treatments, or tests. Also write down any new instructions your provider gives you.
  • Know why a new medicine or treatment is prescribed, and how it will help you. Also know what the side effects are.
  • Ask if your condition can be treated in other ways.
  • Know why a test or procedure is recommended and what the results could mean.
  • Know what to expect if you do not take the medicine or have the test or procedure.
  • If you have a follow-up appointment, write down the date, time, and purpose for that visit.
  • Know how you can contact your healthcare provider if you have questions.

Signs and Symptoms

In the early stages of myeloma, some patients have no signs or symptoms of the disease. It is sometimes detected before symptoms appear, when results of laboratory tests done as part of a routine medical examination show abnormalities in the blood and/or urine. When symptoms are present, the most common ones are bone pain and fatigue.

Doctors sometimes refer to the acronym, CRAB, to describe signs of myeloma. The letters stand for

  • C – Calcium elevation (high levels of calcium in the blood; also known as “hypercalcemia”)
  • R- Renal insufficiency (poor function of the kidneys that may be due to a reduction in blood-flow to the kidneys)
  • A – Anemia (low red blood cell counts)
  • B – Bone abnormalities (lesions).

Patients with one or more of these CRAB criteria are considered to have disease that requires therapy. Those who do not exhibit any of these criteria are said to have “smoldering” or “asymptomatic myeloma,” and these patients may be followed with a watch-and-wait approach.

Some other symptoms of myeloma include​:

  • Bone pain and/or skeletal fractures. Bone pain is the most common early symptom of myeloma. Bones are constantly in a process of remodeling, maintaining a balance between bone destruction and formation. Myeloma causes an imbalance, with greater bone destruction and less new bone formation. This may result in bone thinning (osteoporosis) or holes in the bones (lytic lesions). Bones may break easily from activities as simple as coughing. The damage is most commonly found in the back or ribs, but it can occur in any bone. The pain is usually constant and made worse by movement. Bone lesions are present in
    about 80 percent of myeloma patients, most commonly in the spine and pelvis, but could affect any bone. Bone lesions are not usually found in joints.
  • Fatigue and weakness as a result of low red blood cell counts (anemia). Myeloma patients may fatigue more easily and feel weak. They may also have a pale complexion from anemia.
  • Frequent infections due to a weakened immune system. Myeloma patients may experience repeated infections because the antibodies they need to fight invading viruses, bacteria or other disease agents are not made efficiently or in adequate numbers. A urinary tract, bronchial, lung, skin or other type of infection may be the first sign of the disease. In addition, recurrent infections may complicate the course of the disease.

Other signs and symptoms include:

  • Damage to kidneys from high levels of antibodies (proteins). The patient’s urine may look foamy and the patient’s legs may swell.
  • Numbness, tingling, burning or pain in the hands or feet (caused by a condition called “peripheral neuropathy”).
  • Some patients have high levels of calcium, which can cause increased confusion, increased blood pressure, nausea/vomiting, constipation and excessive thirst.
  • In rare cases, patients can have hyperviscosity syndrome, when the blood thickens. Symptoms of hyperviscosity syndrome are abnormal bleeding, headaches, chest pain, decreased alertness or shortness of breath.
  • Some patients can have amyloidosis, a condition in which the abnormal myeloma protein is deposited in various tissues in the body, causing damage.

If you experience by any of the above symptoms, see your doctor. Sometimes, you may have no symptoms. In this case, your doctor may first detect the disease as a result of a lab test or an X-ray taken for another reason.

Related Links

  • Download or order The Leukemia & Lymphoma Society’s free booklet, Myeloma.

Iron Deficiency

What Is It?

Published: March, 2019

Iron deficiency is an abnormally low level of iron in the body.

Iron is an essential mineral found in red meat and certain fruits and vegetables. In the body, iron is needed to form myoglobin, a protein in muscle cells, and it is essential for certain enzymes that drive the body’s chemical reactions. In the bone marrow, iron is used to make hemoglobin, the oxygen-carrying chemical inside the body’s red blood cells. If iron levels fall too low, it causes iron deficiency anemia. When this happens, red blood cells become smaller than normal and contain less hemoglobin.

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How is hemochromatosis diagnosed?

Most patients with hemochromatosis are diagnosed between the ages of 30 and 50; and about 75% have no symptoms. Hemochromatosis is discovered when elevated levels of iron in the blood are found as part of routine blood testing; or when blood iron levels are measured as in screening studies in family members of patients with hereditary hemochromatosis. Some patients are diagnosed as having hemochromatosis when their doctors perform blood iron levels as part of the evaluation for abnormal elevations in blood levels of liver enzymes, AST and ALT. However, symptoms of skin bronzing or hyperpigmentation (about 70% eventually develop this symptom), diabetes, liver disease, arthropathy, hypogonadism, cardiomyopathy, and impotence or no menstrual periods (amenorrhea) may be present and may suggest that additional screening tests such as transferrin saturation and other blood and liver tests be ordered.

Blood iron tests

There are several blood tests that reflect the amount of iron in the body; ferritin level, iron level, total iron binding capacity (TIBC), and transferrin saturation.

Ferritin is a blood protein whose levels correlate with the amount of iron stored in the body. Blood ferritin levels usually are low in patients with iron deficiency anemia, and are high in patients with hemochromatosis and other conditions that cause an increase in body iron levels. Since ferritin also can be elevated in certain infections like viral hepatitis and other inflammatory conditions in the body, an elevated ferritin level alone is not sufficient to accurately diagnose hemochromatosis.

Serum iron, TIBC, and transferrin saturation are often performed together. Serum iron is the measure of the amount of iron in serum (the liquid portion of the blood). TIBC is a measure of the total amount of iron that can be carried in serum by transferrin, a protein that carries iron in serum from one part of the body to another. Transferrin saturation is a number calculated by dividing serum iron by TIBC – it is a number that reflects what percentage of the transferrin that is being used to transport iron. In healthy individuals the transferrin saturation is between 20% and 45%. In patients with iron deficiency anemia, the serum iron and transferrin saturation are abnormally low; and in patients with hereditary hemochromatosis the serum iron and transferrin saturation may be abnormally high. Consequently, if transferrin saturation is about 45% or higher, the presence of mutations C282Y or H63D should be examined to confirm the diagnosis of hereditary hemochromatosis.

Since serum iron can be elevated by eating and can fluctuate during the day, serum iron measurements should be done fasting, usually in the morning before breakfast.

Liver biopsy

The most accurate test for diagnosing hemochromatosis used to be the measurement of the iron content of liver tissue obtained by a biopsy. A liver biopsy involves the removal of a sample of liver tissue for analysis and is usually performed with a needle under local anesthesia. After numbing the skin and the underlying tissues, the doctor inserts the needle into the liver through the right lower rib cage, sometimes under ultrasound guidance. The tissue obtained by the needle is studied under a microscope for signs of active liver disease, fibrosis and cirrhosis (permanent scarring), and iron content (usually significantly elevated in hemochromatosis).

The liver biopsy also has prognostic value because it determines whether the patient already has irreversible advanced cirrhosis. Patients with hemochromatosis who have a normal liver biopsy have longevity similar to other healthy adults if adequately treated, while patients with cirrhosis as a result of hemochromatosis have significantly reduced longevity. Furthermore, the risks of cirrhotic patients developing liver cancer (hepatocellular carcinoma) are substantially higher than normal subjects, even with adequate treatment of the iron overload with phlebotomy. However, with the newer genetic testing, this invasive technique should be used only under certain conditions and is used infrequently.

Genetic Tests

The gene for hereditary hemochromatosis was identified in 1996. The gene is referred to as the HFE gene. Hereditary hemochromatosis is associated in most patients with two mutations of the HFE gene; C282Y and H63D. Currently, most investigators consider detection of these genes as diagnosis of heriditary hemochromatosis.

A C282Y homozygote is a person who has inherited one mutated C282Y gene from each parent. A C282Y homozygote is considered at considerable risk for developing iron overload disease. However, not every C282Y homozygote develops iron overload.

A C282Y/H63D compound heterozygote is a person who has inherited one mutated C282Y gene from one parent and a second mutated H63D gene from the other parent. Most compound heterozygotes have normal iron levels though some can develop mild to moderate iron overload.

A C282Y heterozygote is a person who has inherited one mutated C282Y gene from one parent and a second normal HFE gene from the other parent. Children born of two C282Y heterozygotes have a 25% chance of being a C282Y homozygote and, therefore, will be at risk of developing hemochromatosis. A C282Y heterozygote does not develop iron overload.

An algorithm for diagnosing hereditary hemochromatosis is as follows:

  1. Adults suspected of having hereditary hemochromatosis (for example, adult, first-degree relatives of a patient with hereditary hemochromatosis) are evaluated by measurements of fasting serum iron, TIBC, transferrin saturation and ferritin.
  2. Patients with elevated serum iron, ferritin, and transferrin saturation of greater than 45% are evaluated by genetic testing
  3. Patients with transferrin saturation greater than 45% who are C282Y homozygotes have hemochromatosis and, therefore, should be treated with therapeutic phlebotomy (see below).

Who should undergo liver biopsy?

Not all patients with hemochromatosis need to undergo liver biopsy. The purpose of liver biopsy is to identify those patients with cirrhosis and to exclude other possible liver diseases. (Patients with hemochromatosis and cirrhosis are at increased risk of complications, especially liver cancer.)

Young patients (<40 years of age) who are C282Y homozygotes with normal liver blood tests and serum ferritin levels <1000 ng/ml have a very low risk of having cirrhosis of the liver. Therefore, these patients can be treated with therapeutic phlebotomy without a liver biopsy. Their prognosis is excellent with adequate treatment.

Older patients (>40 years of age) who have serum ferritin levels >1000 ng/ml, and have abnormally elevated liver blood tests may already have developed cirrhosis. Doctors may recommend liver biopsies in these patients provided that it is safe for them to undergo liver biopsy.

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