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Rheumatoid Arthritis and AIHA: Understanding the Connection

Posted on September 01, 2022
Medically reviewed by
Ariel D. Teitel, M.D., M.B.A.
Article written by
Jane Chung, PharmD, RPh

Autoimmune hemolytic anemia (AIHA) can occur on its own (known as primary or idiopathic AIHA), or it can be caused by other diseases (known as secondary AIHA).

Some conditions that can cause secondary AIHA include autoimmune disorders like rheumatoid arthritis (RA) as well as blood cancers such as leukemia and certain infections.

Other autoimmune diseases that have been linked to AIHA include:

  • Hashimoto’s disease
  • Sjögren’s syndrome
  • Systemic lupus erythematosus (also called SLE or lupus)
  • Thyroid disease
  • Ulcerative colitis

How Rheumatoid Arthritis Is Related to AIHA

Individuals with RA commonly develop anemia. Anemia occurs when the blood doesn’t have enough healthy red blood cells (RBCs). An estimated 33 percent to 60 percent of people with RA have mild anemia.

There is not a lot of scientific evidence directly linking RA and AIHA. In fact, AIHA, in general, is rarely seen in people living with RA.

However, rheumatologic conditions are considered risk factors for warm AIHA. There are case reports of people living with both conditions, but the process by which RA can cause AIHA is not well understood at this time.

How To Treat AIHA If You Also Have Rheumatoid Arthritis

About 70 percent to 80 percent of people with AIHA will show only short-term symptoms and mild anemia. In these cases, AIHA may resolve on its own without any medical treatments.

If RA is the underlying cause of AIHA, then treating RA is the best way to treat AIHA.

Steroids and Nonsteroidal Anti-Inflammatory Drugs

Doctors may prescribe nonsteroidal anti-inflammatory drugs (NSAIDs) and/or low-dose corticosteroids (also called glucocorticoids) to help decrease swelling and pain.

Aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), and celecoxib (Celebrex) are some examples of NSAIDs. Steroids used to treat RA include prednisone, dexamethasone, and methylprednisolone.

Disease-Modifying Antirheumatic Drugs

RA treatment options start with disease-modifying antirheumatic drugs (DMARDs). These medications help relieve symptoms and slow down the progression of joint damage. Common DMARDs include:

  • Methotrexate (Rheumatrex, Trexall, Otrexup, Rasuvo)
  • Leflunomide (Arava)
  • Hydroxychloroquine (Plaquenil)
  • Sulfasalazine (Azulfidine)
  • Azathioprine (Azasan, Imuran)

Another type of DMARD is a class of drugs known as Janus kinase (JAK) inhibitors. This type of medication is given to those who cannot be treated with methotrexate alone. JAK inhibitors include tofacitinib (Xeljanz) and baricitinib (Olumiant).

Biologic Drugs

People with more serious RA may require the addition of biologic treatments. These medications block the immune system from sending chemical signals that lead to inflammation and damage to the joints and tissues. Examples include:

  • Abatacept (Orencia)
  • Adalimumab (Humira)
  • Certolizumab (Cimzia)
  • Etanercept (Enbrel)
  • Golimumab (Simponi)
  • Infliximab (Remicade)
  • Rituximab (Rituxan)

These biologics are often given with methotrexate, as combining medications is more helpful than using one drug by itself.

One of these biologic drugs stands out the most as a dual treatment for RA and AIHA. Rituximab is a monoclonal antibody approved by the U.S. Food and Drug Administration (FDA) to treat several conditions, including RA. However, it has numerous off-label uses as well — one of them is AIHA.

Rituximab is the preferred therapy for people with different types of AIHA, including warm autoimmune hemolytic anemia and cold agglutinin disease. In the case of warm autoimmune hemolytic anemia, rituximab is used in people who did not respond to steroid treatment, known as refractory AIHA.

Complications That May Occur If You Have Both Conditions

AIHA is a condition involving the destruction of RBCs. Complications (unexpected medical problems that occur during a disease) can arise due to this destruction, known as hemolysis. The resulting lack of RBCs can also cause complications.

AIHA that is caused by RA will also be associated with complications of RA.

Complications From Hemolysis and Anemia

When RBCs are destroyed by hemolysis, symptoms of anemia can develop. These symptoms include fatigue, shortness of breath, and palpitations.

Skin complications, although rare, can occur in people with AIHA. These complications are seen more often in those with cold autoimmune hemolytic anemia. The lack of red blood cell flow can cause the extremities to feel numb, painful, and cold. The skin may also become discolored. In severe cases, anemia can lead to the death of skin cells. Treating skin complications involves avoiding cold temperatures and keeping extremities, especially the hands and feet, warm.

When the body is constantly undergoing hemolysis, it tries to compensate for this loss of RBCs by producing more. The process of creating new RBCs requires vitamin B9, also known as folate. Folate deficiency can occur due to this increased demand. As a result, folate supplementation is recommended for the duration of AIHA.

AIHA is associated with an increased risk of venous thromboembolism (VTE). This term refers to blood clots in the veins. The prevalence (how common something is) of VTE in people living with AIHA is up to 27 percent.

Over time, continuous and uncontrolled hemolysis can lead to short-term kidney injury. When RBCs are destroyed, the broken-down cell parts need to be cleared through the kidneys. In AIHA, the degraded cell parts can start accumulating, causing stress and damage to the kidneys.

Complications From Underlying Rheumatoid Arthritis

RA is associated with complications such as osteoporosis and carpal tunnel syndrome, as well as heart and lung problems.

Osteoporosis occurs when the bones weaken, making them more prone to fracture. RA itself can increase the risk of osteoporosis. This condition is also an unfortunate side effect of corticosteroids, which are used to treat RA.

If RA affects the wrist, the inflammation in this area can compress the nerves used by the hand and fingers. This can cause carpal tunnel syndrome.

RA may lead to hardened and blocked arteries, causing heart problems. Parts of the heart can also become inflamed.

People living with RA are at an increased risk of developing pulmonary (lung) complications. Constant inflammation in the airway as a result of a dysfunctional immune response in RA can cause airway diseases. In addition, using medications that suppress the immune system (immunosuppressives) can result in lung infections. Methotrexate, a widely used DMARD for RA, can also be toxic to the lungs.

Communicate With Your Doctor

If you have questions about your treatment, or if you believe your treatment plan isn’t working, talk to your health care team. Make sure to attend follow-up appointments with your doctor.

Talk With Others Who Understand

On myAIHAteam, the social network for people with autoimmune hemolytic anemia and their loved ones, members come together to ask questions, give advice, and share their stories with others who understand life with AIHA.

Are you living with AIHA and RA? Share your experience in the comments below, or start a conversation by posting on your Activities page.

All updates must be accompanied by text or a picture.
Ariel D. Teitel, M.D., M.B.A. is the clinical associate professor of medicine at the NYU Langone Medical Center in New York. Review provided by VeriMed Healthcare Network. Learn more about him here.
Jane Chung, PharmD, RPh earned a Bachelor of Science in Pharmacy Studies and a Doctor of Pharmacy from Northeastern University in Boston, MA. Learn more about her here.

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