National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Simple cryoglobulinemia


Other Names:
Cryoglobulinemia type 1
Categories:
Simple cryoglobulinemia occurs when the body makes an abnormal immune system protein called a cryoglobulin. At temperatures less than 98.6 degrees Fahrenheit (normal body temperature), cryoglobulins become solid or gel-like and can block blood vessels. This causes a variety of health problems. Many people with cryoglobulins will not experience any symptoms. If symptoms occur, they may include skin ulcers, purple skin spots (purpura), numbness in the fingers and toes (Raynaud's phenomenon), joint pain, and kidney problems. The underlying cause is unknown. Simple cryoglobulinemia is typically associated with immune system cancers, such as multiple myeloma or non-Hodgkin lymphoma. It is diagnosed based on the results of a clinical exam and the presence of cryoglobulins in the blood. Treatment varies based on the severity of symptoms and any underlying conditions.[1][2][3][4]
Last updated: 6/16/2020
The following list includes the most common signs and symptoms in people with simple cryoglobulinemia. These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

Signs and symptoms may include:[4]
  • Purple spots and patches on the skin (purpura)
  • Skin ulcers
  • Nerve damage (peripheral neuropathy)
  • Numbness or tingling of the fingers and/or toes (Raynaud's phenomenon)
  • Joint pain and swelling (arthralgia)
  • Kidney problems
The severity of the symptoms can be difficult to predict, and may depend on underlying conditions. People who have kidney and nervous system involvement tend to have more severe disease. In rare cases, symptoms of simple cryoglobulinemia can be life-threatening.[2][4]
Last updated: 6/16/2020
The cause of simple cryoglobulinemia is unknown. It occurs mainly in people with cancers of the immune system, such as multiple myeloma and non-Hodgkin's lymphoma.[4]

In some cases, cryoglobulinemia occurs in someone with no underlying health condition. In these cases, it is known as essential or idiopathic cryoglobulinemia.[1]  
Last updated: 6/16/2020
Simple cryoglobulinemia can be diagnosed based on a clinical history and exam, the symptoms, and testing to look for cryoglobulins in the blood. People found to have cryoglobulinemia are often tested for underlying immune system disorders.[1][2]
Last updated: 6/16/2020
The treatment for simple cryoglobulinemia is focused on the underlying disease and managing the symptoms. Treatment options include medications that suppress the immune system and chemotherapy.[2][4]

Specialists involved in the care of someone with simple cryoglobulinemia may include:
  • Dermatologist
  • Neurologist
  • Kidney specialist 
  • Liver specialist
  • Hematologist
Last updated: 6/16/2020
The number of people with simple cryoglobulinemia is unknown, but it is thought to be rare.[2]
Last updated: 6/16/2020

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Simple cryoglobulinemia. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Social Networking Websites

  • RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
  • The Vasculitis Foundation provides information about Simple cryoglobulinemia.

In-Depth Information

  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • How does cryoglobulinemia affect the lungs? What are the symptoms? How is the lung involvement diagnosed? How does it affect the skin. Is vasculitis painful? See answer

  • Has any correlation been found between cryoglobulinemia and protein S deficiency? See answer


  1. Roccatello D, Saadoun D, Ramos-Casals M, et al. Cryoglobulinaemia. Nat Rev Dis Primers. 2018; 4(1):11. https://pubmed.ncbi.nlm.nih.gov/30072738.
  2. Ramos-Casals M, Stone JH, Cid MC, Bosch X. The cryoglobulinaemias. Lancet. 2012; 379(9813):348-360. https://pubmed.ncbi.nlm.nih.gov/21868085.
  3. Ghetie D, Mehraban N, Sibley CH. Cold hard facts of cryoglobulinemia: updates on clinical features and treatment advances. Rheum Dis Clin North Am. 2015; 41(1):93-108. https://pubmed.ncbi.nlm.nih.gov/25399942.
  4. Sidana S, Rajkumar SV, Dispenzieri A, et al. Clinical presentation and outcomes of patients with type 1 monoclonal cryoglobulinemia. Am J Hematol. 2017; 92(7):668-673. https://pubmed.ncbi.nlm.nih.gov/28370486.