Rare Rheumatology News

Disease Profile

Simple cryoglobulinemia

Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.


US Estimated

Europe Estimated

Age of onset





Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.


Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.


dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.


recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.


Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.


Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.


Not applicable


Other names (AKA)

Cryoglobulinemia type 1


Immune System Diseases


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]


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]


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]


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]


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


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).

      Learn more

      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.


          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.

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