Materiały źródłowe

• #1 Mayo Clinic Health Library – Cryoglobulinemia | Swiss Medical Network

  https://www.swissmedical.net/it/healtcare-library/con-20371235

  Cryoglobulinemia is a family of rare conditions, called vasculitis. […] It’s not clear what causes cryoglobulinemia. It’s been linked to: […] Hepatitis C is the most common infection linked to cryoglobulinemia. Others include hepatitis B, HIV, Epstein-Barr, toxoplasmosis and malaria. […] Some cancers of the blood, such as multiple myeloma, Waldenstrom macroglobulinemia and chronic lymphocytic leukemia, can cause cryoglobulinemia. […] Disease in which the immune system attacks healthy tissues by mistake, called autoimmune, increases the risk of getting cryoglobulinemia. Examples are lupus, rheumatoid arthritis and Sjogren syndrome.

• #1 Cryoglobulinemia: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/329255-overview

  Cryoglobulinemia may be classified based on cryoglobulin composition with the Brouet classification, which is as follows: Type I cryoglobulinemia, or simple cryoglobulinemia, is the result of a monoclonal immunoglobulin, usually immunoglobulin M (IgM) or, less frequently, immunoglobulin G (IgG), immunoglobulin A (IgA), or light chains. […] Types II and III cryoglobulinemia (mixed cryoglobulinemia) contain rheumatoid factors (RFs), which are usually IgM and, rarely, IgG or IgA. These RFs form complexes with the fragment, crystallizable (Fc) portion of polyclonal IgG. The actual RF may be monoclonal (in type II cryoglobulinemia) or polyclonal (in type III cryoglobulinemia) immunoglobulin. Types II and III cryoglobulinemia represent 80% of all cryoglobulins. […] Cryoglobulinemia may also be classified based on the association of the syndrome with an underlying disease. Cryoglobulinemia without an associated disease has been known as essential, or idiopathic, cryoglobulinemia. However, the discovery of a close association between hepatitis C virus (HCV) and mixed cryoglobulinemia has cast doubt on the existence of essential, or idiopathic, cryoglobulinemia.

• #1 Cryoglobulinemia | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/20147

  Cryoglobulin is normally present in healthy individuals at low levels. Experts theorize that these levels indicate the existence of immune complexes actively working to clear this protein by immunoglobulins with RF activity. […] The prime risk factor for cryoglobulinemia is drug use, as 90% of cases of cryoglobulinemic vasculitis are associated with HCV infections. The formation of hepatitis C IgG and IgM RF causes the immune complex formation and complement activation, leading to blood vessel inflammation. Other infectious ethologies include Hepatitis B, Cytomegalovirus, Epstein Barr virus, Parvovirus (B19), Candida, Visceral Leishmaniasis, Coxiella burnetii, and Pyogenic bacterial infections. […] In addition, cryoglobulinemia is also associated with monoclonal gammopathies (such as multiple myeloma, Waldenstrm macroglobulinemia, or MGUS), monoclonal gammopathies of renal significance, and connective tissue diseases (such as SLE and Sjgren syndrome). Lymphoproliferative disorders (e.g. Diffuse Large B-cell lymphoma) are also involved.

• #1 Cryoglobulinemia : Johns Hopkins Vasculitis Center

  https://www.hopkinsvasculitis.org/types-vasculitis/cryoglobulinemia/

  The name literally means cold antibody in the blood, which refers to the chemical properties of the antibodies that cause this disease: cryoglobulins are antibodies that precipitate under cold conditions. Drug use is a prime risk factor for cryoglobulinemia because more than 90% of cases of cryoglobulinemic vasculitis are associated with hepatitis C infections. Hepatitis C is acquired by injection drug use (needlesharing), tainted blood products, and (probably rarely), sexual transmission. […] It is now evident that most patients diagnosed with type II or type III mixed essential cryoglobulinemia have the disease as an immune response to chronic hepatitis C infection. The role of hepatitis C virus is suggested by finding that the cryoglobulins in these patients are enriched with antihepatitis C antibody and hepatitis C RNA. Moreover, antviral therapy can remit the disease in some patients.

• #1 Cryoglobulinemia: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/329255-overview

  Disease associations vary with the type of cryoglobulinemia, as follows: Type I is observed in lymphoproliferative disorders (eg, multiple myeloma, Waldenstrm macroglobulinemia). Types II and III are observed in chronic inflammatory diseases such as chronic liver disease, infections (chronic HCV infection), and coexistent connective-tissue diseases (SLE, Sjgren syndrome). Mixed cryoglobulinemia is rarely associated with lymphoproliferative disorders. […] Infections associated with cryoglobulinemia include the following: Viral – Hepatitis A, B, and C (see Differentials); HIV; Epstein-Barr virus (EBV); cytomegalovirus (CMV); adenovirus; chikungunya; COVID-19. […] Other disorders associated with cryoglobulinemia include the following: Autoimmune diseases – SLE, rheumatoid arthritis, Sjgren syndrome; Vasculitis – Polyarteritis nodosa (especially hepatitis B associated), Henoch-Schnlein purpura; Lymphoproliferative disorders – Waldenstrm macroglobulinemia, multiple myeloma, lymphoma, leukemia (eg, chronic lymphocytic leukemia, hairy cell leukemia); Kidney disease – Proliferative glomerulonephritis; Liver diseases – Hepatitis A, B, and C (30-98% of patients with HCV infection have cryoglobulins, especially type II); cirrhosis. […] Cryoglobulinemia may occur as a familial or idiopathic disorder. Finally, cases have been reported following vaccination (eg, with pneumococcal vaccine, or COVID-19 vaccine).

• #1 How do I Deal with Cryoglobulinemia?

  https://www.iomcworld.com/open-access/how-do-i-deal-with-cryoglobulinemia-111971.html

  Approximately 10% of patients have no discernible reason (termed essential mixed cryoglobulinemia). […] The etiology of cryoglobulins in type I, on the other hand, is tiny blood vessel blockage with a limited inflammatory response. […] For HCV-associated cryoglobulinemia, the mechanism of cryoglobulin pathogenicity is better defined. […] HCV causes clonal B-cell growth, which produces monoclonal IgM molecules that attach to polyclonal IgG molecules, forming an RF. […] Immune complexes are formed when IgM interacts with anti-HCV IgG. […] These immune complexes link to endothelial cells’ C1q receptors, which enhances inflammatory cell recruitment and causes vasculitis.

• #1 Nonviral cryoglobulinemic vasculitis: an updated review for clinical practice

  https://www.oaepublish.com/articles/2574-1209.2023.105

  The presence of cryoglobulinemia, mainly of type II, may also be indicative of an underlying hematological disorder. […] In this sense, B-cell malignancies may include B-cell non-Hodgkins lymphomas such as marginal zone lymphoma, diffuse large B-cell, and follicular lymphoma, as well as lymphoplasmacytic lymphomas.

• #1 Nonviral cryoglobulinemic vasculitis: an updated review for clinical practice

  https://www.oaepublish.com/articles/2574-1209.2023.105

  Within the three major groups of cryoglobulinemia, type I accounts for 10%-22% of all cases, while mixed cryoglobulinemia is responsible for 80%-85%, with type II cryoglobulins being the most frequent type. […] Although the list of diseases associated with the production of cryoglobulins is extensive, in clinical practice, they usually belong to one of three main causative groups, i.e., infections, autoimmune diseases, and B-cell lymphoproliferative disorders. […] The term essential or idiopathic cryoglobulinemia is used to designate a small percentage of cases where an etiologic factor remains unidentified. […] Type I cryoglobulins are always associated with B-cell lymphoproliferative disorders, either with malignant or indolent characteristics. […] According to data from large observational cohort studies, a lymphoproliferative disorder was diagnosed in more than 90% of patients with type I cryoglobulins, with monoclonal gammopathy of undetermined significance (MGUS) identified in 36%-86% of patients, and an overt hematological malignancy found in 20%-64%.

• #1 Cryoglobulinemia – Wikipedia

  https://en.wikipedia.org/wiki/Cryoglobulinemia

  These mixed-protein cryoglobulins are also associated with autoimmune diseases, particularly Sjgren syndrome, less commonly systemic lupus erythematosus and rheumatoid arthritis, and rarely polyarteritis nodosa, systemic sclerosis, temporal arteritis, polymyositis, HenochSchnlein purpura, pemphigus vulgaris, sarcoidosis, inflammatory bowel diseases, and others.

• #1 Cryoglobulinemic Vasculitis – Vasculitis Foundation

  https://vasculitisfoundation.org/education/vasculitis-types/cryoglobulinemic-vasculitis/

  Cryoglobulinemic vasculitis is a rare form of vasculitis, a family of rare disorders characterized by inflammation of the blood vessels, which can restrict blood flow and damage vital organs and tissues. […] The cause of cryoglobulinemic vasculitis is not fully understood. More than 90 percent of cases are associated with chronic hepatitis C virus (HCV) infections, so treating hepatitis is very important. […] Cryoglobulinemic vasculitis is also associated with other underlying inflammatory diseases including lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, and blood cancers such as lymphoma. […] Vasculitis is classified as an autoimmune disorder, a disease that occurs when the body’s natural defense system mistakenly attacks healthy tissue. Factors that may trigger the autoimmune process include genetics, medications, infections, and the environment.

• #1 Triggers, Causes of Cryo and other Facts – Alliance for Cryoglobulinemia

  https://allianceforcryo.org/cryo-odd-diseases-weird-facts/

  One researcher put it this way: “Cryoglobulinemia is the immune systems response to long-standing inflammation….” […] There have been attempts at linking bacterial pneumonia and vaccines for it to connective tissue autoimmune disorders, but it has not been substantiated, and it really looks like it actually triggers an existing autoimmune disorder and not really cause it… all of the facts are not yet in on this one. […] Epstein-Barr virus (infectious mononucleosis) has long been known to sometimes cause cryoglobulinemia, but the association with cryo remains uncertain. […] HIV: There have been reports of HIV patients developing cryo. Once they develop full-blown AIDS, the cryo goes away because the immune system is no longer functioning. […] Vinyl chloride poisoning is known to cause cryoglobulinemia.

• #1 Cryoglobulinemic Vasculitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK556045/

  Cryoglobulins can be detectable in the serum of patients with several inflammatory conditions; however, they do not always lead to the disease. The real mechanism of cryoprecipitation is complicated and still not completely understood. It is sometimes attributed to the intrinsic properties of the Immunoglobulin components. Cryoglobulinemic vasculitis can rarely occur by itself and is usually secondary to other diseases. Brouet classified cryoglobulins into 3 major groups based on the immunoglobulin type: […] Type 1 cryoglobulins comprise monoclonal immunoglobulins, usually IgM, less frequently IgG, IgA, or light chains. Although rare, they are also found in plasma cell dyscrasias like multiple myeloma and monoclonal gammopathy of unknown significance, B cell diseases like Waldenstorms macroglobulinemia, lymphoproliferative diseases like Non-Hodgkin lymphoma and chronic lymphocytic leukemia.

• #1 Cryoglobulinemia | 5-Minute Clinical Consult

  https://www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/816098/all/Cryoglobulinemia

  Exact mechanism of cold insolubility in these cryoproteins is unknown. Hypotheses include reduced concentrations of sialic acid and galactose in the Fc region of Ig as well as steric conformation changes due to temperature variation. […] An underlying lymphoproliferative disorder causes monoclonal B-cell proliferation. […] B-cell hyperactivation or hyperproliferation (from HCV or another chronic inflammatory state) produces Ig with rheumatoid factor activity, which leads to immune complex formation. […] Immune complex deposition and subsequent complement activation causes small vessel damage. […] Chronic immune stimulation or lymphoproliferation resulting in the increased production of CGs […] Immune complex formation among CGs with antigens […] Insufficient clearance of CGs and their immune complexes.

• #1 HCV associated mixed cryoglobulinemia vasculitis | Immunopaedia

  https://www.immunopaedia.org.za/clinical-cases/infectious-diseases/i-have-spots-and-my-skin-burns/

  The cause of the presenting condition is Hepatitis C Virus (HCV) associated mixed cryoglobulinemia vasculitis. […] Cryoglobulinemia refers to a condition with circulating cryoglobulins in the serum. Cryoglobulinemia vasculitis refers to small to medium size vessel vasculitis resulting from the pathogenicity of cryoglobulin-containing immune complexes. […] Significant proportions of patients with chronic infection or autoimmune diseases have detectable levels of cryoglobulins in their serum (about 40-65% of HCV infection, 15-20% of HIV infection, 15-25% of autoimmune diseases). […] The mechanism of cryoglobulin pathogenicity is well described for HCV-associated cryoglobulinemia. HCV drives polyclonal B cell expansion, which induces a polyclonal anti-HCV antibody response. […] The rheumatoid factor (anti-IgG IgM) interacts with anti-HCV IgG to form immune complexes.

• #1 HCV associated mixed cryoglobulinemia vasculitis | Immunopaedia

  https://www.immunopaedia.org.za/clinical-cases/infectious-diseases/i-have-spots-and-my-skin-burns/

  The deposits of immune complexes in the kidneys, small blood vessels and other organs promotes inflammatory cell recruitment and causes vasculitis. […] Chronic antigenic stimulation and HCV lymphotropism involved in B cell expansion favour mixed cryoglobulinemia or monoclonal gammopathy of undetermined significance.

• #1 Neuropathies associated with cryoglobulinemia | MedLink Neurology

  https://www.medlink.com/articles/neuropathies-associated-with-cryoglobulinemia

  Cryoglobulinemia may arise in association with an identifiable cause like an infection (mainly hepatitis C virus infection), a lymphoproliferative disorder, or an autoimmune disease (such as Sjgren syndrome). […] Alternatively, cryoglobulinemia may arise without a detectable underlying disease, in which case the term essential cryoglobulinemia is used. […] The majority of cryoglobulins are mixed antigen-antibody complexes that occur in autoimmune or infectious disorders, especially hepatitis C virus infection. […] Cryoglobulinemic vasculitis is caused by deposition of immune complexes containing rheumatoid factor and complement components on the endothelial cells in the setting of exposure to cold temperature that triggers a local inflammatory reaction, including inflammatory cells and cytokines.

• #1 Cryoglobulinemia: Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/13204-cryoglobulinemia

  Cryoglobulinemia affects women more often than men. It also most commonly affects people over the age of 50. […] Left untreated, cryoglobulinemia can cause permanent skin, tissue and organ damage, including: […] Researchers dont know the cause of cryoglobulinemia, so theres no way to prevent it. But staying out of the cold may help prevent some symptoms, including Raynaud’s phenomenon. Its also important to get tested and treated for hepatitis C infection.

• #1 Cryoglobulinemia – MD Searchlight

  https://mdsearchlight.com/blood-disorders/cryoglobulinemia/

  Cryoglobulinemia can be categorized into three main types based on the composition of their immunoglobulins. […] Type II, this, along with type III, falls into the category of mixed cryoglobulinemia, characterized by the presence of different kinds of immunoglobulins. It is often related to autoimmune diseases, cancers, or infections, especially hepatitis C virus (HCV) infection. […] Often, the main factor that increases the risk of having too much cryoglobulin, a condition known as cryoglobulinemia, is drug use. […] Additionally, cryoglobulinemia is also linked to diseases characterized by an overproduction of certain types of proteins, such as multiple myeloma, Waldenstrom macroglobulinemia, or MGUS, and diseases related to the damage of kidneys of unknown origin. […] Cryoglobulinemia is a rare condition, affecting approximately 1 in 100,000 people, with more cases seen in Southern Europe.

• #1 Cryoglobulinemia – MD Searchlight

  https://mdsearchlight.com/blood-disorders/cryoglobulinemia/

  Its more common in people with certain conditions like HIV, Hepatitis C (HCV), and those who have both HIV and HCV. […] Its also associated with autoimmune diseases like lupus (SLE) and Sjgren syndrome, as well as blood cancers like multiple myeloma and lymphoma. […] The most common cause of mixed cryoglobulinemia is Hepatitis C (HCV) infection. […] The severity of the disease guides the treatment approach. […] In severe cases, a procedure called apheresis is often necessary.

• #1 Cryoglobulinemia and Cryoglobulinemic Vasculitis — Vasculitus Ireland — Vasculitis Ireland Awareness (VIA)

  https://www.vasculitis-ia.org/vasculitis-types/cryoglobulinemia-and-cryoglobulinemic-vasculitis

  Essential Cryoglobulinemia: In some cases, cryoglobulinemia may occur without an identifiable underlying cause, termed „essential cryoglobulinemia.” […] Viral Infections: Besides HCV, other viral infections such as hepatitis B virus (HBV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) have also been implicated in the development of cryoglobulinemia and Cryoglobulinemic Vasculitis. […] Genetic Predisposition: Certain genetic factors may predispose individuals to the development of cryoglobulinemia, although the exact genetic mechanisms are not fully understood. […] Environmental Factors: Environmental factors such as cold exposure or certain medications may trigger or exacerbate cryoglobulinemia in susceptible individuals. […] The interplay between these factors and the immune system leads to the production of cryoglobulins and the subsequent inflammatory response in blood vessel walls, resulting in Cryoglobulinemic Vasculitis.

• #1 Clinical and Serological Profiles in Cryoglobulinemia: Analysis of Isotypes and Etiologies

  https://www.mdpi.com/2077-0383/13/20/6069

  Cryoglobulinemia (CG) is marked by abnormal immunoglobulins (Ig) in serum, precipitating at temperatures below 37 °C. The main mechanism contributing to CG is aberrant autoantibody production by plasma cells and B-cell clonal expansion. This process can be facilitated by lymphoproliferative disorders, persistent immune stimulation due to chronic infections, or autoimmune diseases. Consequently, CG is recognized as a condition encompassing a broad spectrum of potential etiologies, diverse pathogenic mechanisms, a wide array of phenotypic manifestations, and a pronounced interplay between infection, autoimmunity, and neoplastic processes. […] The disorder is often recognized by the classic triad of palpable purpura, arthralgia, and asthenia or weakness, present in as many as 80% of patients at disease onset. However, it may manifest with a broad spectrum of symptoms, affecting the skin, joints, nerves, and kidneys, and even the gastrointestinal and central nervous system in rare cases. When we consider and evaluate the various causes of CG, it becomes evident that the various etiologies are associated with distinct clinical presentations.

• #1 Cryoglobulinemia – UF Health

  https://ufhealth.org/conditions-and-treatments/cryoglobulinemia

  Cryoglobulins are antibodies. It is not yet known why they become solid or gel-like at low temperatures in the laboratory. In the body, these antibodies can form immune complexes that can cause inflammation and block blood vessels. This is called cryoglobulinemic vasculitis. This may lead to problems ranging from skin rashes to kidney failure. […] Type I cryoglobulinemia is most often related to cancer of the blood or immune systems. […] Types II and III are most often found in people who have a long-lasting (chronic) inflammatory condition, such as an autoimmune disease or hepatitis C. Most people with the type II form of cryoglobulinemia have a chronic hepatitis C infection. […] Other conditions that may be related to cryoglobulinemia include leukemia, multiple myeloma, primary macroglobulinemia, rheumatoid arthritis, and systemic lupus erythematosus. […] This disorder is due to a cancer of the blood or immune system such as multiple myeloma. Treatment is directed against the abnormal cancer cells that produce the cryoglobulin.

• #1 Cryoglobulinemic vasculitis – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/cryoglobulinemic-vasculitis/

  Cryoglobulinemia can cause cryoglobulinemic vasculitis, however, many patients are asymptomatic. […] Type II and III cryoglobulinemia (i.e., mixed cryoglobulinemia): 90% of cases […] Viral infection: most common etiology (HCV infection in 70-90% of cases) […] Cryoglobulinemic vasculitis is more commonly associated with type II and III cryoglobulinemia than with type I cryoglobulinemia. Type I cryoglobulinemia typically manifests as a hyperviscosity syndrome. […] Cryoglobulinemia is caused by Cold-precipitable immunoglobulins and is commonly associated with the hepatitis C virus. […] Most patients with cryoglobulinemia are asymptomatic; the prevalence of symptomatic cases varies widely (2-50%) across different populations.

• #1 Mixed cryoglobulinemia syndrome: Clinical manifestations and diagnosis – UpToDate

  https://www.uptodate.com/contents/mixed-cryoglobulinemia-syndrome-clinical-manifestations-and-diagnosis

  Cryoglobulins are classified into three types. Type I cryoglobulins are composed of one monoclonal immunoglobulin (Ig; typically IgG or IgM) and are commonly seen in the setting of a lymphoproliferative disease. By contrast, mixed cryoglobulinemia syndrome (MCS) refers to the presence of either type II or type III cryoglobulins circulating in the serum, composed of polyclonal IgG bound to another immunoglobulin with rheumatoid factor activity. In type II cryoglobulinemia, this immunoglobulin with rheumatoid factor activity is monoclonal (usually IgM isotype), whereas in type III cryoglobulinemia, it is polyclonal. Types II and III cryoglobulins account for up to 90 percent of all cryoglobulinemia cases. […] MCS can manifest clinically as a systemic vasculitis with manifestations ranging from purpura, arthralgia, and weakness to more severe neurologic and kidney involvement. Until recently, the most common cause of MCS was hepatitis C virus (HCV), but the introduction of direct-acting antiviral agents has significantly reduced the incidence of HCV-associated cryoglobulinemia. Other infections, lymphoproliferative, and autoimmune disorders have also been associated with the disease. […] The etiology, clinical manifestations, and diagnosis of MCS will be reviewed here. […] Causes of cryoglobulinemia.

• #1 Mixed cryoglobulinemia | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-3-25

  Mixed cryoglobulinemia (MC), type II and type III, refers to the presence of circulating cryoprecipitable immune complexes in the serum and manifests clinically by a classical triad of purpura, weakness and arthralgias. […] The etiopathogenesis of MC is not completely understood. Hepatitis C virus (HCV) infection is suggested to play a causative role, with the contribution of genetic and/or environmental factors. […] A role for hepatitis B virus (HBV) has been firstly investigated; however, HBV viremia is rarely recorded, while anti-HBV antibodies largely varied among different MC patient populations. It can be estimated that HBV can represent a causative factor of MC in less than 5% of individuals. […] Soon after the discovery of hepatitis C virus (HCV) as the major etiologic agent of non-A-non-B chronic hepatitis, a possible role of HCV infection in MC was proposed independently by two pioneering reports showing a significantly higher prevalence of serum anti-HCV antibodies compared to the general population.

• #1 Dysproteinemias Causing Vascular Purpura – Hematology and Oncology – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hematology-and-oncology/bleeding-due-to-abnormal-blood-vessels/dysproteinemias-causing-vascular-purpura

  Cryoglobulinemia produces immunoglobulins that precipitate when plasma is cooled (ie, cryoglobulins) while flowing through the skin and subcutaneous tissues of the extremities. Cryoglobulins may be IgG, IgM, or IgA. Mixed cryoglobulins are usually composed of IgM complexed with a monoclonal or polyclonal IgG. The immune complexes can interfere with normal platelet function and fibrin polymerization. […] Mixed IgM-IgG immune complexes formed in some chronic infectious diseases, most commonly hepatitis C may also behave as cryoglobulins. […] Cryoglobulinemia can also lead to small-vessel vasculitis, which can cause purpura; hyperviscosity and direct vascular trauma can exacerbate. Cryoglobulinemia can manifest with acral hemorrhagic necrosis, palpable purpura, livedo reticularis, and leg ulcers.

• #1

  https://link.springer.com/article/10.1007/BF02909367

  Ninety-three patients with essential mixed cryoglobulinemia have been followed for more than 5 years in 75% of cases; 21 patients died during this period and the mean age at death was 54 years. The most common cause of death was renal failure. […] The cryoglobulin type seems to be an important prognostic factor: in our population the type II/III ratio is 6/7 at diagnosis, while it becomes 2/1 when the patients who died are considered.

• #1 Cryoglobulinemia With Acronecrosis Not Associated With Hepatitis C Infection: A Case Report | Reumatología Clínica

  https://www.reumatologiaclinica.org/en-cryoglobulinemia-with-acronecrosis-not-associated-articulo-S2173574311000827

  Cryoglobulinemia is a rare disease characterized by the production of monoclonal or polyclonal immunoglobulins that precipitate in cold temperature. While this phenomenon can be observed in a large number of disorders, it has been associated with hepatitis C virus infection in more than 90% of cases. […] The association between hepatitis C virus (HCV) and mixed cryoglobulinemia (MC) has been highly evident from the recognition of serological markers for HCV infection, and found in 90% of cases. […] It is known that HCV infection plays an important causal role, but the contribution of genetic factors and/or environmental factors is unknown. […] Essential MC usually has a more aggressive course than those secondary to other diseases, with prevalence of renal, neuropathic and impaired peripheral circulation.

• #1 Essential Mixed Cryoglobulinemia: Symptoms, Treatment

  https://www.medicinenet.com/essential_mixed_cryoglobulinemia/article.htm

  Cryoglobulinemia is a medical condition that is caused by proteins called cryoglobulins, which are present in the blood. […] Cryoglobulins may or may not cause disease. Cryoglobulins can accompany another condition (such as dermatomyositis, multiple myeloma, viral infections, or lymphoma) or be an isolated condition themselves, called cryoglobulinemia. […] Cryoglobulins in the blood (cryoglobulinemia) can cause a variety of problems throughout the body. […] When the cryoglobulin proteins are a mixture of various antibody types, and forming for unknown reasons (essential), the condition is referred to as essential mixed cryoglobulinemia. […] Essential mixed cryoglobulinemia is sometimes associated with hepatitis C virus infection.

• #1 Mixed Cryoglobulinemia Syndrome (MCS) due to untreated hepatitis B with uncommon presentation: case report and literature review | BMC Rheumatology | Full Text

  https://bmcrheumatol.biomedcentral.com/articles/10.1186/s41927-020-00159-y

  The mixed cryoglobulinemia (MC) syndrome is a systemic inflammatory syndrome that causes small-to-medium vessel vasculitis due to cryoglobulin-containing immune complexes most commonly caused by chronic hepatitis C virus (HCV), and rarely by chronic hepatitis B virus (HBV). […] While HBV affects more than 350 million people worldwide, cryoglobulinemic vasculitis can develop in only 1.24% patients infected with hepatitis B virus. […] While reported to have glomerulus, skin, and liver involvement, HBV induced cryoglobulinemia presenting primarily with pulmonary alveolar hemorrhage is rarely documented in literature. […] Type II, and type III cryoglobulins (mixed cryoglobulins) can form immune complexes causing small to medium vessel vasculitis (Cryoglobulinemic vasculitis) in multiple tissues and organs.

• #1 Nonviral cryoglobulinemic vasculitis: an updated review for clinical practice

  https://www.oaepublish.com/articles/2574-1209.2023.105

  Historically, chronic HCV infection was the main cause of mixed cryoglobulinemia, while autoimmune disorders, B-cell lymphoid malignancies, other infectious diseases, and essential cryoglobulinemia accounted for a small fraction of the cases. […] This has changed in recent years, as the use of DAA for the treatment of HCV progressively led to a decline in the occurrence of HCV-related mixed cryoglobulinemia and the rise of autoimmune diseases as the most frequent conditions associated with the onset of cryoV. […] Systemic lupus erythematosus (SLE) and Sjogrens syndrome (SS) are the most frequent systemic autoimmune diseases associated with mixed cryoglobulinemia and cryoV. […] Non HCV-related infectious mixed cryoglobulinemia may be secondary to viruses, bacteria, parasites, or fungus.

• #2 Cryoglobulinemia: Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/13204-cryoglobulinemia

  Cryoglobulinemia is a condition that occurs when abnormal proteins in your blood called cryoglobulins thicken and clump together at cold temperatures. The condition is a type of vasculitis (inflammation of your blood vessels), which can restrict blood flow and cause damage to your skin, nerves, joints, muscles and organs particularly your kidneys. Another name for cryoglobulinemia is cryoglobulinemic vasculitis. […] Researchers dont know the exact cause of cryoglobulinemia. But the condition is a type of vasculitis, which is an autoimmune disease. Autoimmune disorders occur when your bodys immune system attacks healthy tissue. Factors that may trigger this reaction include: […] Cryoglobulinemia can be present alone (idiopathic), but its frequently associated with other diseases, such as:

• #2 Cryoglobulinemia – Wikipedia

  https://en.wikipedia.org/wiki/Cryoglobulinemia

  Cryoglobulinemia is classified into three groups. Type I cryoglobulinemia has only monoclonal proteins, developing in lymphoproliferative disorders. Type II cryoglobulinemia is the most common, occurring when both monoclonal and polyclonal proteins are present in the bloodstream and are linked to Hepatitis C. Type III cryoglobulinemia has only polyclonal proteins and is often linked to autoimmune diseases. […] Currently, most cases of this disease are found to be associated with premalignant, malignant, infectious, or autoimmune disorders that are the known or presumed causes for the production of cryoglobulins. […] The hematological, infectious, and autoimmune diseases underlying type II cryoglobulinemic disease and the infectious and autoimmune diseases underlying type III cryoglobulinemic disease are also critical parts of the disease’s clinical findings.

• #2 Cryoglobulinemic Vasculitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK556045/

  Cryoglobulins can be detectable in the serum of patients with several inflammatory conditions; however, they do not always lead to the disease. The real mechanism of cryoprecipitation is complicated and still not completely understood. It is sometimes attributed to the intrinsic properties of the Immunoglobulin components. Cryoglobulinemic vasculitis can rarely occur by itself and is usually secondary to other diseases. Brouet classified cryoglobulins into 3 major groups based on the immunoglobulin type: […] Type 1 cryoglobulins comprise monoclonal immunoglobulins, usually IgM, less frequently IgG, IgA, or light chains. Although rare, they are also found in plasma cell dyscrasias like multiple myeloma and monoclonal gammopathy of unknown significance, B cell diseases like Waldenstorms macroglobulinemia, lymphoproliferative diseases like Non-Hodgkin lymphoma and chronic lymphocytic leukemia.

• #2 Cryoglobulinemic Vasculitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK556045/

  Type 2 cryoglobulins consist of monoclonal IgM with rheumatoid factor (RF) activity and polyclonal IgG. […] Type 3 cryoglobulins involve polyclonal IgM with RF activity and polyclonal IgG. […] Newer techniques like immunoblotting have helped identify a novel mixed cryoglobulin, which is called type II to III (it is type II cryoglobulin with microheterogeneity) as it has a simultaneous presence of oligoclonal IgM and polyclonal IgG. […] RF activity denotes the binding capacity of IgM to the Fc fragment of IgG. Type 2 and Type 3 are referred to as mixed cryoglobulins. They are commonly associated with infections, autoimmune diseases, and lymphoproliferative disorders: […] Among infections, Hepatitis C is the most common. Other infections include Hepatitis B, Cytomegalovirus, Epstein B virus, Parvovirus B19, HIV, pyogenic bacterial infections, candidiasis, visceral leishmaniasis, and Coxiella burnetii. […] Autoimmune conditions include systemic lupus erythematosus and Sjogren syndrome. […] Lymphoproliferative disorders like diffuse large B cell lymphoma and Non-Hodgkin lymphoma.

• #2 Cryoglobulinemia : Johns Hopkins Vasculitis Center

  https://www.hopkinsvasculitis.org/types-vasculitis/cryoglobulinemia/

  The name literally means cold antibody in the blood, which refers to the chemical properties of the antibodies that cause this disease: cryoglobulins are antibodies that precipitate under cold conditions. Drug use is a prime risk factor for cryoglobulinemia because more than 90% of cases of cryoglobulinemic vasculitis are associated with hepatitis C infections. Hepatitis C is acquired by injection drug use (needlesharing), tainted blood products, and (probably rarely), sexual transmission. […] It is now evident that most patients diagnosed with type II or type III mixed essential cryoglobulinemia have the disease as an immune response to chronic hepatitis C infection. The role of hepatitis C virus is suggested by finding that the cryoglobulins in these patients are enriched with antihepatitis C antibody and hepatitis C RNA. Moreover, antviral therapy can remit the disease in some patients.

• #2 Cryoglobulinemic Vasculitis – Vasculitis Foundation

  https://vasculitisfoundation.org/education/vasculitis-types/cryoglobulinemic-vasculitis/

  Cryoglobulinemic vasculitis is a rare form of vasculitis, a family of rare disorders characterized by inflammation of the blood vessels, which can restrict blood flow and damage vital organs and tissues. […] The cause of cryoglobulinemic vasculitis is not fully understood. More than 90 percent of cases are associated with chronic hepatitis C virus (HCV) infections, so treating hepatitis is very important. […] Cryoglobulinemic vasculitis is also associated with other underlying inflammatory diseases including lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, and blood cancers such as lymphoma. […] Vasculitis is classified as an autoimmune disorder, a disease that occurs when the body’s natural defense system mistakenly attacks healthy tissue. Factors that may trigger the autoimmune process include genetics, medications, infections, and the environment.

• #2 HCV associated mixed cryoglobulinemia vasculitis | Immunopaedia

  https://www.immunopaedia.org.za/clinical-cases/infectious-diseases/i-have-spots-and-my-skin-burns/

  The cause of the presenting condition is Hepatitis C Virus (HCV) associated mixed cryoglobulinemia vasculitis. […] Cryoglobulinemia refers to a condition with circulating cryoglobulins in the serum. Cryoglobulinemia vasculitis refers to small to medium size vessel vasculitis resulting from the pathogenicity of cryoglobulin-containing immune complexes. […] Significant proportions of patients with chronic infection or autoimmune diseases have detectable levels of cryoglobulins in their serum (about 40-65% of HCV infection, 15-20% of HIV infection, 15-25% of autoimmune diseases). […] The mechanism of cryoglobulin pathogenicity is well described for HCV-associated cryoglobulinemia. HCV drives polyclonal B cell expansion, which induces a polyclonal anti-HCV antibody response. […] The rheumatoid factor (anti-IgG IgM) interacts with anti-HCV IgG to form immune complexes.

• #2 Cryoglobulinemia – UF Health

  https://ufhealth.org/conditions-and-treatments/cryoglobulinemia

  Cryoglobulins are antibodies. It is not yet known why they become solid or gel-like at low temperatures in the laboratory. In the body, these antibodies can form immune complexes that can cause inflammation and block blood vessels. This is called cryoglobulinemic vasculitis. This may lead to problems ranging from skin rashes to kidney failure. […] Type I cryoglobulinemia is most often related to cancer of the blood or immune systems. […] Types II and III are most often found in people who have a long-lasting (chronic) inflammatory condition, such as an autoimmune disease or hepatitis C. Most people with the type II form of cryoglobulinemia have a chronic hepatitis C infection. […] Other conditions that may be related to cryoglobulinemia include leukemia, multiple myeloma, primary macroglobulinemia, rheumatoid arthritis, and systemic lupus erythematosus. […] This disorder is due to a cancer of the blood or immune system such as multiple myeloma. Treatment is directed against the abnormal cancer cells that produce the cryoglobulin.

• #2 Nonviral cryoglobulinemic vasculitis: an updated review for clinical practice

  https://www.oaepublish.com/articles/2574-1209.2023.105

  Within the three major groups of cryoglobulinemia, type I accounts for 10%-22% of all cases, while mixed cryoglobulinemia is responsible for 80%-85%, with type II cryoglobulins being the most frequent type. […] Although the list of diseases associated with the production of cryoglobulins is extensive, in clinical practice, they usually belong to one of three main causative groups, i.e., infections, autoimmune diseases, and B-cell lymphoproliferative disorders. […] The term essential or idiopathic cryoglobulinemia is used to designate a small percentage of cases where an etiologic factor remains unidentified. […] Type I cryoglobulins are always associated with B-cell lymphoproliferative disorders, either with malignant or indolent characteristics. […] According to data from large observational cohort studies, a lymphoproliferative disorder was diagnosed in more than 90% of patients with type I cryoglobulins, with monoclonal gammopathy of undetermined significance (MGUS) identified in 36%-86% of patients, and an overt hematological malignancy found in 20%-64%.

• #2 Cryoglobulinemia: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/329255-overview

  Disease associations vary with the type of cryoglobulinemia, as follows: Type I is observed in lymphoproliferative disorders (eg, multiple myeloma, Waldenstrm macroglobulinemia). Types II and III are observed in chronic inflammatory diseases such as chronic liver disease, infections (chronic HCV infection), and coexistent connective-tissue diseases (SLE, Sjgren syndrome). Mixed cryoglobulinemia is rarely associated with lymphoproliferative disorders. […] Infections associated with cryoglobulinemia include the following: Viral – Hepatitis A, B, and C (see Differentials); HIV; Epstein-Barr virus (EBV); cytomegalovirus (CMV); adenovirus; chikungunya; COVID-19. […] Other disorders associated with cryoglobulinemia include the following: Autoimmune diseases – SLE, rheumatoid arthritis, Sjgren syndrome; Vasculitis – Polyarteritis nodosa (especially hepatitis B associated), Henoch-Schnlein purpura; Lymphoproliferative disorders – Waldenstrm macroglobulinemia, multiple myeloma, lymphoma, leukemia (eg, chronic lymphocytic leukemia, hairy cell leukemia); Kidney disease – Proliferative glomerulonephritis; Liver diseases – Hepatitis A, B, and C (30-98% of patients with HCV infection have cryoglobulins, especially type II); cirrhosis. […] Cryoglobulinemia may occur as a familial or idiopathic disorder. Finally, cases have been reported following vaccination (eg, with pneumococcal vaccine, or COVID-19 vaccine).

• #2 Shining a Warm Light on Cryoglobulinemia

  https://www.cancernetwork.com/view/shining-warm-light-cryoglobulinemia

  We recommend screening for cryoglobulinemia in all patients with HCV infection, livedo reticularis, vasculitic cutaneous ulcers, positive rheumatoid factor or rheumatoid vasculitis, membranoproliferative glomerulonephritis, or atypical Waldenstrm macroglobulinemia. […] The finding of a circulating immunoglobulin (Ig) that is precipitated by cooling and redissolved by warming is itself the definition of cryoglobulinemia, but by convention, cryoglobulinemia more typically refers to the infrequent clinical syndrome of cryoglobulinemic vasculitis that manifests with some combination of cutaneous symptoms, neuropathy, renal dysfunction, and/or arthralgias. […] When cryoglobulins are detected in a patient without HCV infection or other apparent etiology, we recommend thorough staging studies to rule out possible lymphoma.

• #2 Clinical and Serological Profiles in Cryoglobulinemia: Analysis of Isotypes and Etiologies

  https://www.mdpi.com/2077-0383/13/20/6069

  Type I CG is usually a serological finding observed during the course of hematological disorders such as monoclonal gammopathy of undetermined significance (MGUS), malignancies of B-cell lineage, mainly multiple myeloma (MM), and Waldenström macroglobulinemia (WM). Conversely, the detection of types II and III MCG is the main laboratory hallmark of cryoglobulinemic vasculitis. Type II CG is predominantly associated with hepatitis-C virus (HCV) infection, although additional causative factors such as other virus infections, rheumatic diseases (RD), and lymphoproliferative disorders are also plausible etiologies. Type III CG arises in the context of RD or secondary to infections, particularly HCV. Overall, MCG results from a B-cell lymphoproliferative process in the context of persistent immune activation triggered by chronic infections, systemic autoimmune diseases, or an unknown origin, with approximately 10% of patients having no identifiable cause, in which case the disorder is recognized as essential cryoglobulinemia. […] Our study underscores a mixed prevalence of CG across disease subgroups, with hepatitis-C virus as the primary factor, followed by rheumatic and hematological disorders. Four clinical and serological profiles of CG were identified based on their etiologies.

• #2 Nonviral cryoglobulinemic vasculitis: an updated review for clinical practice

  https://www.oaepublish.com/articles/2574-1209.2023.105

  Historically, chronic HCV infection was the main cause of mixed cryoglobulinemia, while autoimmune disorders, B-cell lymphoid malignancies, other infectious diseases, and essential cryoglobulinemia accounted for a small fraction of the cases. […] This has changed in recent years, as the use of DAA for the treatment of HCV progressively led to a decline in the occurrence of HCV-related mixed cryoglobulinemia and the rise of autoimmune diseases as the most frequent conditions associated with the onset of cryoV. […] Systemic lupus erythematosus (SLE) and Sjogrens syndrome (SS) are the most frequent systemic autoimmune diseases associated with mixed cryoglobulinemia and cryoV. […] Non HCV-related infectious mixed cryoglobulinemia may be secondary to viruses, bacteria, parasites, or fungus.

• #2 Cryoglobulinemia – Wikipedia

  https://en.wikipedia.org/wiki/Cryoglobulinemia

  These mixed-protein cryoglobulins are also associated with autoimmune diseases, particularly Sjgren syndrome, less commonly systemic lupus erythematosus and rheumatoid arthritis, and rarely polyarteritis nodosa, systemic sclerosis, temporal arteritis, polymyositis, HenochSchnlein purpura, pemphigus vulgaris, sarcoidosis, inflammatory bowel diseases, and others.

• #2 Mixed cryoglobulinemia | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-3-25

  Given the striking association between MC and HCV infection, the term 'essential’ is now referred to a minority of MC patients. […] However, MC is also the result of concomitant genetic and/or environmental factors, which remain largely unknown. […] HCV has been recognized to be both a hepato- and lymphotropic virus, as suggested by the presence of active or latent viral replication in the peripheral lymphocytes of patients with type C hepatitis or MC. […] HCV may exert a chronic stimulus of the immune-system, through different viral proteins such as core protein. […] Chronic stimulation of the lymphatic system exerted through viral epitopes, autoantigen production, and/or molecular mimicry mechanism has been suggested by the presence, in HCV-positive patients, of anti-GOR antibodies, which are cross-reactive autoantibodies directed to both HCV core and a nuclear antigen named GOR.

• #2 Cryoglobulinemia – Wikipedia

  https://en.wikipedia.org/wiki/Cryoglobulinemia

  The particular components involved are a reflection of the disorders that are associated with, and considered to be the cause of, the cryoglobulinemic disease. […] Mixtures of monoclonal or polyclonal IgM, IgG, and/or IgA along with blood complement proteins such as C4 are the cryoglobulins associated with cases of infectious diseases, particularly hepatitis C infection, HIV infection, and Hepatitis C and HIV coinfection, and, less commonly or rarely, with cases of other infectious diseases such as hepatitis B infection, hepatitis A infection, cytomegalovirus infection, EpsteinBarr virus infection, Lyme disease, syphilis, lepromatous leprosy, Q fever, poststreptococcal nephritis, subacute bacterial endocarditis, coccidioidomycosis, malaria, schistosomiasis, echinococcosis, toxoplasmosis, and Kala-azar.

• #2 Neuropathies associated with cryoglobulinemia | MedLink Neurology

  https://www.medlink.com/articles/neuropathies-associated-with-cryoglobulinemia

  Cryoglobulinemia may arise in association with an identifiable cause like an infection (mainly hepatitis C virus infection), a lymphoproliferative disorder, or an autoimmune disease (such as Sjgren syndrome). […] Alternatively, cryoglobulinemia may arise without a detectable underlying disease, in which case the term essential cryoglobulinemia is used. […] The majority of cryoglobulins are mixed antigen-antibody complexes that occur in autoimmune or infectious disorders, especially hepatitis C virus infection. […] Cryoglobulinemic vasculitis is caused by deposition of immune complexes containing rheumatoid factor and complement components on the endothelial cells in the setting of exposure to cold temperature that triggers a local inflammatory reaction, including inflammatory cells and cytokines.

• #2 Clinical and Serological Profiles in Cryoglobulinemia: Analysis of Isotypes and Etiologies

  https://www.mdpi.com/2077-0383/13/20/6069

  Cryoglobulinemia (CG) is marked by abnormal immunoglobulins (Ig) in serum, precipitating at temperatures below 37 °C. The main mechanism contributing to CG is aberrant autoantibody production by plasma cells and B-cell clonal expansion. This process can be facilitated by lymphoproliferative disorders, persistent immune stimulation due to chronic infections, or autoimmune diseases. Consequently, CG is recognized as a condition encompassing a broad spectrum of potential etiologies, diverse pathogenic mechanisms, a wide array of phenotypic manifestations, and a pronounced interplay between infection, autoimmunity, and neoplastic processes. […] The disorder is often recognized by the classic triad of palpable purpura, arthralgia, and asthenia or weakness, present in as many as 80% of patients at disease onset. However, it may manifest with a broad spectrum of symptoms, affecting the skin, joints, nerves, and kidneys, and even the gastrointestinal and central nervous system in rare cases. When we consider and evaluate the various causes of CG, it becomes evident that the various etiologies are associated with distinct clinical presentations.

• #2 Cryoglobulinemia: Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/13204-cryoglobulinemia

  Cryoglobulinemia affects women more often than men. It also most commonly affects people over the age of 50. […] Left untreated, cryoglobulinemia can cause permanent skin, tissue and organ damage, including: […] Researchers dont know the cause of cryoglobulinemia, so theres no way to prevent it. But staying out of the cold may help prevent some symptoms, including Raynaud’s phenomenon. Its also important to get tested and treated for hepatitis C infection.

• #2 Hepatitis C and Cryoglubulinemia: What to Know

  https://www.healthline.com/health/hepatitis-c/cryoglobulinemia-hepatitis-c

  Chronic hepatitis C (hep C) infection can lead to a type of vasculitis called cryoglobulinemia. […] According to the National Organization for Rare Disorders, more than 90% of cases of mixed cryoglobulinemia are associated with hep C. […] Its not clear exactly what triggers cryoglobulinemia. […] There are likely several factors that play a role, such as infections and viruses, including hep C and HIV. […] Mixed cryoglobulinemia affects females three times as often as males. […] Research suggests that HCV-associated mixed cryoglobulinemia increases morbidity and mortality. […] Antiviral drugs are the main treatment for cryoglobulinemia related to hep C.

• #2 Mixed cryoglobulinemia in patients with dual HCV/HIV infection: analysis of cryoprecipitate as a therapeutic decision tool | Nefrología

  https://www.revistanefrologia.com/en-mixed-cryoglobulinemia-in-patients-with-articulo-X2013251408005752

  Infection by the hepatitis C virus (HCV) is the main cause of mixed cryoglobulinemia. However, the human immunodeficiency virus (HIV) also causes cryoglobulinemia. In high-risk people, dual HIV/HCV infection is common. […] Several studies have shown the relationship between HIV and HCV infections, and the role of cryoglobulins in causing renal damage, particularly MPGN. It is unknown whether the higher percentage of cryoglobulinemia found in cases with dual HIV/HCV infection is due to one and/or the other virus. No reference has found in the literature with respects to the concomitant presence of both viral particles in the cryoprecipitate from patients with dual HIV/HCV infection. […] Analysis of the cryoprecipitate is a useful tool for differential diagnosis of cryoglobulinemia in patients with dual HIV/HCV infection. It may also be used as a supplemental test to rule out a diagnosis in patients apparently monoinfected by HIV.

• #2 Cryoglobulinemia – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/870

  Cryoglobulinemia may be asymptomatic or present acutely. […] Mixed cryoglobulinemia (MC) is the most common type, and it is strongly associated with chronic hepatitis C virus (HCV) infection. […] Types II and III (MC) may be associated with infectious (most commonly hepatitis C virus [HCV] infection) or autoimmune disorders. […] Risk factors include hepatitis C virus (HCV) infection, other viral infections, autoimmune disorders, and lymphoproliferative disorders.

• #2

  https://link.springer.com/article/10.1007/BF00945029

  Agnello V (1995) Hypothesis: the etiology of mixed cryoglobulinemia associated with hepatitis C virus infection. Scand J Immunol 421:179 […] Agnello V, Chung RT, Kaplan LM (1992) A role for hepatitis C virus infection in type II cryoglobulinemia. N Engl J Med 327:1490 […] Agnello V, bel G, Zhang QX, Elfahal M, Knight GB (1997) The etiology of mixed cryoglobulinemia: the role of the LDL receptor and apolipoprotein E2. Arthritis Rheum 39:5315 […] Lunel F, Musset L, Cacoub P, Frangeul L, Cresta P, Perrin M, Grippon P, Hoang C, Valla D, Piette JC, Huraux J, Opolon P (1994) Cryoglobulinemia in chronic liver diseases: role of hepatitis C virus and liver damage. Gastroenterology 106:1291 […] Misani R, Bellavita P, Fenili D, Marchesi D, Massazza M, Borelli G, Comotti B, Tanzi E, Scudeller G, Zanetti A (1992) Hepatitis C virus infection in patients with essential mixed cryoglobulinemia. Ann Intern Med 117:573 […] Zignego AL, Ferri C, Giannini C, Monti M, La Civita L, Careccia G, Longombardo G, Lombardini F, Bombardieri S, Gentilini P (1996) Hepatitis C virus genotype analysis in patients with type II mixed cryoglobulinemia. Ann Intern Med 124: 31

• #2 Cryoglobulinaemic vasculitis | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/cryoglobulinaemic-vasculitis?lang=us

  Cryoglobulinaemic vasculitis (CV) is a form of immune mediated primary vasculitis involving small to medium sized vessels. It may involve multiple organs and can have a range of clinical presentations. […] Mixed cryoglobulinaemias (types II and III) are most often associated with chronic inflammatory disorders and infections, such as: hepatitis C infection (most common cause of cryoglobulinaemic vasculitis). […] Type I, on the other hand, is most often related to B cell lymphoproliferative disorders, such as: Waldenstrm’s macroglobulinemia, multiple myeloma, monoclonal gammopathy of undetermined significance. […] Treatment and prognosis depends on the underlying associated condition.

• #2 Cryoglobulinemia is my life but Not my Identity – Alliance for Cryoglobulinemia

  https://allianceforcryo.org/cryoglobulinemia-is-my-life-but-not-my-identity/

  Cryoglobulinemia is an autoimmune blood disorder. Cryoglobulinemia Type I is a primary disease, meaning it exists by itself for no known reason. Mixed Cryoglobulinemia, Types II and III is associated with other autoimmune disorders, some cancers, and most commonly, with Hepatitis C. […] I have Mixed Cryoglobulinemia associated with the Hepatitis C virus I carried for thirty-three years. […] The most common death related directly to Cryoglobulinemia is kidney failure, when the kidneys become clogged with cryoglobulins and can no longer function. […] The reality for those of us with this disease is living with the complete unknown of what to suspect next because what is written in most text books is only observation, derived by those doctors monitoring their Cryoglobulinemic patients.

• #2 Cryoglobulinemia With Acronecrosis Not Associated With Hepatitis C Infection: A Case Report | Reumatología Clínica

  https://www.reumatologiaclinica.org/en-cryoglobulinemia-with-acronecrosis-not-associated-articulo-S2173574311000827

  Despite establishing treatment with glucocorticoids, immunosuppressants, vasodilators and rituximab we did not achieve an effective response, as seen in cases of MC associated with HCV infection, so plasmapheresis sessions were begun, associated with rituximab, which achieved partial control of the disease. […] The particularity of this case is the presentation of one of the few cases of MC associated with no underlying disease (non-HCV), being therefore essential, and as mentioned in other articles, these cases have an abrupt clinical presentation and poor response to conventional therapy.

• #2 Final Diagnosis — Case 593

  https://path.upmc.edu/cases/case593/dx.html

  The incidence of cryoglobulinemia in patients with chronic HCV infection has been variously reported as between 13% and 54%. […] First-line therapy for mixed cryoglobulinemia due to HCV infection is antiviral therapy with pegylated interferon-? and ribavirin. Viral eradication usually produces marked reduction of complications and arrests end organ damage along with the clearance of cryoglobulins.

• #2 Mixed Cryoglobulinemia Syndrome (MCS) due to untreated hepatitis B with uncommon presentation: case report and literature review | BMC Rheumatology | Full Text

  https://bmcrheumatol.biomedcentral.com/articles/10.1186/s41927-020-00159-y

  HCV-associated Cryoglobulinemic vasculitis (CV) is noted in 90-95% of cases, while hepatitis B virus-related Cryoglobulinemic vasculitis occurs in approximately 3% of cases only. […] As there are few reported cases of HBV-related cryoglobulinemic vasculitis, there are still no definitive treatment guidelines issued yet. […] Therefore, HBV-induced MC with moderate to severe manifestations (eg, glomerulonephritis, cutaneous ulcers, progressive neuropathy, diffuse vasculitis including pulmonary and central nervous system vasculitis), similarly to HCV-associated MC, can be treated with antiviral therapy, glucocorticoids, and rituximab. […] Our unique case presented with a rare phenomenon of hemoptysis and alveolar hemorrhage as an initial presentation of cryoglobulinemic vasculitis without renal involvement and in the setting of unusual association with untreated chronic hepatitis B infection. […] Due to the rarity and poor prognosis of pulmonary hemorrhage in mixed cryoglobulinemia, as well as the unusual association with hepatitis B infection, physicians must have a high index of suspicion for the disease to commence early treatment and reduce patient morbidity.

• #2 Cryoglobulins – Testing.com

  https://www.testing.com/tests/cryoglobulins/

  Cryoglobulins are circulating proteins, specifically immunoglobulins (i.e., IgG, IgM, IgA or light chains), that clump together (precipitate) when they are exposed to cold and dissolve when warmed. […] They may be present in small quantities in the blood of some healthy people but are most frequently associated with abnormal protein production and a variety of diseases and conditions. […] The presence of large amounts of cryoglobulins in the blood, called cryoglobulinemia, can cause symptoms such as bruising, rashes, joint pain, weakness, and Raynaud phenomenon – pain, paleness, bluing, numbness, tingling and coldness in the fingers and toes with exposure to cold. […] Cryoglobulins can cause tissue damage that leads to skin ulcers and, in severe cases, to gangrene. […] Most people who have cryoglobulinemia are chronically infected with hepatitis C virus (HCV), although not everyone with HCV (fewer than 3%) will develop cryoglobulinemia.

• #2 Mixed cryoglobulinemia | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-3-25

  Mixed cryoglobulinemia (MC), type II and type III, refers to the presence of circulating cryoprecipitable immune complexes in the serum and manifests clinically by a classical triad of purpura, weakness and arthralgias. […] The etiopathogenesis of MC is not completely understood. Hepatitis C virus (HCV) infection is suggested to play a causative role, with the contribution of genetic and/or environmental factors. […] A role for hepatitis B virus (HBV) has been firstly investigated; however, HBV viremia is rarely recorded, while anti-HBV antibodies largely varied among different MC patient populations. It can be estimated that HBV can represent a causative factor of MC in less than 5% of individuals. […] Soon after the discovery of hepatitis C virus (HCV) as the major etiologic agent of non-A-non-B chronic hepatitis, a possible role of HCV infection in MC was proposed independently by two pioneering reports showing a significantly higher prevalence of serum anti-HCV antibodies compared to the general population.

• #2 Cryoglobulinemia: Causes, symptoms, and treatment

  https://www.medicalnewstoday.com/articles/318686

  Cryoglobulinemia is a disease caused by an abundance of a protein called cryoglobulin in the blood. […] Cryoglobulinemia causes clumps of abnormal proteins in the blood stream that can block blood flow. […] The causes of cryoglobulinemia vary from person to person. Some of the most common causes include: having an abundance of cryoglobulin in the blood, certain blood cell cancers, having a connective tissue disease, having an infection, most often hepatitis C. […] In cases of secondary cryoglobulinemia, treatment involves correcting the underlying condition. When the underlying cause is treated, the symptoms of cryoglobulinemia should improve as well. […] If a doctor determines that the cryoglobulinemia is caused by hepatitis C, the treatment will center on antiviral medication and the person will likely be referred to a liver specialist.

• #2 Mixed cryoglobulinemia syndrome: Clinical manifestations and diagnosis – UpToDate

  https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-the-mixed-cryoglobulinemia-syndrome-essential-mixed-cryoglobulinemia

  Cryoglobulinemia syndrome (MCS) refers to the presence of either type II or type III cryoglobulins circulating in the serum, composed of polyclonal IgG bound to another immunoglobulin with rheumatoid factor activity. […] Until recently, the most common cause of MCS was hepatitis C virus (HCV), but the introduction of direct-acting antiviral agents has significantly reduced the incidence of HCV-associated cryoglobulinemia. […] Other infections, lymphoproliferative, and autoimmune disorders have also been associated with the disease. […] The etiology, clinical manifestations, and diagnosis of MCS will be reviewed here.

• #3 Mixed cryoglobulinemia | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-3-25

  Mixed cryoglobulinemia (MC), type II and type III, refers to the presence of circulating cryoprecipitable immune complexes in the serum and manifests clinically by a classical triad of purpura, weakness and arthralgias. […] The etiopathogenesis of MC is not completely understood. Hepatitis C virus (HCV) infection is suggested to play a causative role, with the contribution of genetic and/or environmental factors. […] A role for hepatitis B virus (HBV) has been firstly investigated; however, HBV viremia is rarely recorded, while anti-HBV antibodies largely varied among different MC patient populations. It can be estimated that HBV can represent a causative factor of MC in less than 5% of individuals. […] Soon after the discovery of hepatitis C virus (HCV) as the major etiologic agent of non-A-non-B chronic hepatitis, a possible role of HCV infection in MC was proposed independently by two pioneering reports showing a significantly higher prevalence of serum anti-HCV antibodies compared to the general population.

• #3 Triggers, Causes of Cryo and other Facts – Alliance for Cryoglobulinemia

  https://allianceforcryo.org/cryo-odd-diseases-weird-facts/

  One researcher put it this way: “Cryoglobulinemia is the immune systems response to long-standing inflammation….” […] There have been attempts at linking bacterial pneumonia and vaccines for it to connective tissue autoimmune disorders, but it has not been substantiated, and it really looks like it actually triggers an existing autoimmune disorder and not really cause it… all of the facts are not yet in on this one. […] Epstein-Barr virus (infectious mononucleosis) has long been known to sometimes cause cryoglobulinemia, but the association with cryo remains uncertain. […] HIV: There have been reports of HIV patients developing cryo. Once they develop full-blown AIDS, the cryo goes away because the immune system is no longer functioning. […] Vinyl chloride poisoning is known to cause cryoglobulinemia.

• #3 Mixed cryoglobulinemia | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-3-25

  Given the striking association between MC and HCV infection, the term 'essential’ is now referred to a minority of MC patients. […] However, MC is also the result of concomitant genetic and/or environmental factors, which remain largely unknown. […] HCV has been recognized to be both a hepato- and lymphotropic virus, as suggested by the presence of active or latent viral replication in the peripheral lymphocytes of patients with type C hepatitis or MC. […] HCV may exert a chronic stimulus of the immune-system, through different viral proteins such as core protein. […] Chronic stimulation of the lymphatic system exerted through viral epitopes, autoantigen production, and/or molecular mimicry mechanism has been suggested by the presence, in HCV-positive patients, of anti-GOR antibodies, which are cross-reactive autoantibodies directed to both HCV core and a nuclear antigen named GOR.

• #3 Cryoglobulinemia and Cryoglobulinaemic Vasculitis – Vasculitis UK

  https://www.vasculitis.org.uk/about-vasculitis/cryoglobulinemia-and-cryoglobulinaemic-vasculitis

  Cryoglobulinemia means cold antibody in the blood and is the presence of abnormal antibodies that are soluble in the blood at body temperature but which precipitate out of the blood at lower temperatures in the laboratory. […] The commonest underlying causes of cryoglobulinaemia are hepatitis C infection, lymphoma and myeloma. The cause of essential cryoglobulinaemia is not known and can only be diagnosed once all the possible underlying causes have been excluded. […] Cryoglobulins and cryoglobulinaemic vasculitis are often caused by underlying diseases including infections and cancers.

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