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Is Prurigo Nodularis an Autoimmune Disease?

Medically reviewed by Raj Chovatiya, MD, PhD, MSCI
Written by Emily Wagner, M.S.
Posted on February 2, 2024

Researching prurigo nodularis (PN) can be confusing because various websites offer conflicting information. Some sources suggest that PN is an autoimmune disease, while others say it’s not. Sorting through these details can make it difficult to understand your condition.

Many doctors and researchers agree that PN is not an autoimmune disease. Instead, they believe it’s caused by dysregulation or miscommunication between your immune system, skin cells, and nerves.

In this article, we’ll discuss why prurigo nodularis (also called nodular prurigo) isn’t universally considered an autoimmune disease. We’ll also cover other immune-mediated conditions — conditions involving abnormal immune system responses — that PN is related to.

By working with your dermatologist and sticking to your treatment plan, you can better control your PN and other health conditions. Keeping your PN symptoms under control can also help you improve your quality of life.

What Are Autoimmune Diseases?

Autoimmune diseases are conditions in which your immune system attacks your body’s own healthy cells. Specifically, your immune system mistakes certain patterns as harmful. Your body then creates autoantibodies, a type of specialized protein. These autoantibodies tag your tissues for destruction, leading to troublesome symptoms.

Examples of autoimmune diseases include:

  • Rheumatoid arthritis — Affects your joints
  • Multiple sclerosis — Affects your brain and spinal cord
  • Type 1 diabetes — Affects your pancreas (the organ that makes insulin)

Some skin conditions like psoriasis and dermatomyositis are also autoimmune diseases. However, doctors and researchers haven’t figured out whether PN is an autoimmune disease. Instead, they think PN may be due to immune dysregulation — miscommunication between your skin, immune system, and nerve cells.

Prurigo Nodularis Is Considered an Immune-Mediated Disease

PN is a skin condition that causes intense itching or pruritus. When you pick at, rub, or scratch your skin, it creates hard lumps, known as nodules and papules. These lumps release inflammatory chemicals known as cytokines that make your skin even itchier than before. The more you itch, the more cytokines your skin releases. This creates a vicious “itch-scratch cycle” that’s hard to break.

Nodules from scratching may appear as pink or reddish, hard lumps on lighter skin tones. On brown and black skin tones, the nodules may appear darker. (CC BY-NC-ND 3.0 NZ/DermNet)


PN is considered an inflammatory skin condition but not an autoimmune disease. This is because the immune system doesn’t attack healthy cells in PN. Researchers haven’t found any autoantibodies that play a role in PN.

Instead, many immune cells release cytokines and create inflammation. For example, mast cells release histamines, which are responsible for causing itchy skin with allergies. Other immune cells, known as T cells, also release chemicals that cause itching in other skin diseases.

Prurigo Nodularis Is Related to Other Immune-Mediated Diseases

Even though PN isn’t considered an autoimmune disease, it does seem to be related to other diseases that lead to immune system dysfunction. Many studies have found connections between PN and other immune-mediated or autoimmune diseases. When you have two conditions or diseases at the same time, they’re known as comorbidities.

Doctors and researchers believe that cytokines play a key role. This is because many of the cytokines involved in PN are also found in other diseases. For example, interleukin (IL)-31 causes itchy skin in PN. Researchers also believe IL-31 plays a role in dermatomyositis, an autoimmune disease that affects connective tissues.

Researchers from Korea followed 3,591 people with PN, looking for related autoimmune diseases. The authors found that people with PN are twice as likely to develop systemic lupus erythematosus (the most common type of lupus), an autoimmune disease that affects the skin, joints, and kidneys.

The authors also reported that people with PN were more likely to have:

  • Crohn’s disease — An autoimmune disease affecting the digestive tract
  • Hashimoto’s thyroiditis — An autoimmune thyroid disease
  • Atopic dermatitis (the most common type of eczema) — A skin condition associated with dry, itchy skin

Another study found that PN is associated with psoriasis. Like PN, psoriasis is an immune-mediated condition that causes inflammation.

Biologics for Treating Prurigo Nodularis

Biologics are lab-made proteins used to treat a variety of diseases. Monoclonal antibody drugs are commonly used in treating autoimmune diseases to reduce inflammation and control immune system function. They’re given as subcutaneous (underneath the skin) intravenous infusions or injections. Doctors have been using biologics to treat autoimmune diseases for several years.

Dupilumab (Dupixent) was first approved by the U.S. Food and Drug Administration (FDA) in 2017 for treating atopic dermatitis. It works by blocking inflammatory molecules in the skin. Since then, dupilumab has also been approved for treating PN, asthma, and other inflammatory conditions.

Another biologic drug known as nemolizumab is currently in clinical trials. Phase 3 trials results published in October, 2023 showed that nemolizumab significantly reduced itching and improved skin clearance in people with moderate to severe prurigo nodularis. Researchers have found that the drug has a good safety profile and was well-tolerated. Common side effects include injection site reactions, headache, and worsening of atopic dermatitis. The drug is not currently approved by the FDA.

Dupilumab Has Helped People With Prurigo Nodularis Achieve Remission

Dupilumab is the first FDA-approved treatment for PN in adults. The approval was based on two clinical trials (large studies) looking at whether dupilumab was safe and effective for treating PN.

The study participants received either dupilumab or a placebo (saline solution) every two weeks for 24 weeks total. The investigators — doctors and researchers running the study — measured the participants’ itch scores and number of nodules.

After 24 weeks, the investigators found that dupilumab treatment helped 60 percent of participants improve their skin itching scores. On the other hand, only 18.4 percent of participants taking the placebo improved their scores. This finding means that dupilumab treatment was effective for treating PN.

Another study from China found that dupilumab treatment helped people reach remission, meaning they had skin clearance and no symptoms. The authors reported that after 16 weeks of treatment:

  • 45.3 percent of participants experienced complete remission
  • 43.8 percent had partial remission
  • 10.9 percent had no remission

The most common side effects of the drug, according to the FDA, include injection site reactions, common cold, muscle pain, diarrhea, and throat pain.

These studies all show promising results for treating PN with dupilumab. However, we don’t yet know how long the effects last. Over time, investigators will need to run longer studies to find out whether dupilumab helps treat PN symptoms in the long term.

Discuss Prurigo Nodularis Treatment and Other Health Concerns With Your Doctor

If you’re living with an underlying condition or one related to PN, it’s important to get proper treatment. These conditions may be making your PN symptoms worse. By better controlling underlying conditions, you can stop the itch-scratch cycle, improve your PN symptoms, and prevent them from returning.

Many anti-inflammatory treatments used for PN also treat other autoimmune diseases. You can work closely with your dermatologist or another health care provider to find what combination of treatments works best for you.

Examples of therapies used for treating PN include:

  • Corticosteroids
  • Creams and lotions to relieve itchiness and pain
  • Phototherapy with ultraviolet (UV) light
  • Antihistamines like diphenhydramine (Benadryl)
  • Immunosuppressive medications like methotrexate (Trexall) and cyclosporine (Gengraf)
  • Immunomodulatory drugs like thalidomide (Revlimid)
  • Antiseizure medications like gabapentin (Neurontin)

Talk With Others Who Understand

MyPrurigoTeam is the social network for people with prurigo nodularis and their loved ones. On MyPrurigoTeam, more than 2,000 members come together to ask questions, give advice, and share their stories with others who understand life with PN.

Do you have more questions about why prurigo nodularis isn’t considered an autoimmune disease? Share them in a comment below or on your Activities page.

References
  1. A Review of the Current Management and Burden of Prurigo Nodularis in the United States — American Journal of Managed Care
  2. Autoimmune Disorders — Mount Sinai
  3. Prurigo Nodularis — Yale Medicine
  4. Chronic Nodular Prurigo: An Update on the Pathogenesis and Treatment — International Journal of Molecular Sciences
  5. Pruritus in Autoimmune Connective Tissue Diseases — Annals of Translational Medicine
  6. Epidemiology, Comorbidities, and Prescription Patterns of Korean Prurigo Nodularis Patients: A Multi-Institution Study — Journal of Clinical Medicine
  7. Crohn’s Disease — Johns Hopkins Medicine
  8. Hashimoto’s Thyroiditis — Johns Hopkins Medicine
  9. Atopic Dermatitis (Eczema) — Mayo Clinic
  10. Real-World Prevalence of Prurigo Nodularis and Burden of Associated Diseases — Journal of Investigative Dermatology
  11. About Psoriasis — National Psoriasis Foundation
  12. Overview: Biologic and Advanced Therapies for Autoimmune Conditions — Guy’s and St Thomas’ NHS Foundation Trust
  13. Biologics — National Psoriasis Foundation
  14. Surgery in the Age of Biologics — Gastroenterology Report
  15. Dupilumab: First Global Approval — Drugs
  16. Trial of Nemolizumab in Moderate-to-Severe Prurigo Nodularis — The New England Journal of Medicine
  17. Phase 3 Trial of Nemolizumab in Patients With Prurigo Nodularis — The New England Journal of Medicine
  18. Nemolizumab — DermNet
  19. FDA Approves First Treatment for Prurigo Nodularis — U.S. Food & Drug Administration
  20. Dupilumab in Patients With Prurigo Nodularis: Two Randomized, Double-Blind, Placebo-Controlled Phase 3 Trials — Nature Medicine
  21. Dupilumab for the Treatment of Prurigo Nodularis: A Systematic Review — Frontiers in Immunology
  22. Prurigo Nodularis: Diagnosis and Treatment — American Academy of Dermatology Association
    Posted on February 2, 2024
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    Raj Chovatiya, MD, PhD, MSCI is an assistant professor of dermatology at Northwestern University Feinberg School of Medicine in Chicago, Illinois. Learn more about him here.
    Emily Wagner, M.S. holds a Master of Science in biomedical sciences with a focus in pharmacology. She is passionate about immunology, cancer biology, and molecular biology. Learn more about her here.

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