Cryoglobulinemia

Japanese: クリオグロブリン血症

(6) Cryoglobulinemia In 1933, Wintrobe and Buell et al. first discovered and reported cryoglobulin in serum samples from myeloma patients. Cryoglobulin is a cloudy white precipitate that reversibly coagulates at low temperatures (0 to 4°C), and is mostly a mixture containing Ig. Cryoglobulins are often detected in cases of vasculitis, viral infections, and lymphoproliferative disorders. Brouet et al. classified cryoglobulinemia into three types based on the components of the precipitate. ① Type I: Monoclonal Ig, mainly IgG and IgM. May be associated with myeloma, macroglobulinemia, MGUS, and lymphoproliferative disorders. ② Type II: Shows mixed cryoglobulins. Often consists of monoclonal IgM with antiglobulin activity (rheumatoid factor (RF) activity) and polyclonal IgG. It is often an immune complex formed when IgM reacts with IgG that has been altered in response to antigens such as various viral components of hepatitis C virus or self-proteins. However, there are rare cases in which no underlying disease is found. ③ Type III: Caused by polyclonal Ig. The mechanism of onset is the same as type II, and it is often caused by IgM.
Symptoms of circulatory disorders such as livedo reticularis, Raynaud's phenomenon, urticaria, purpura vascularis, and cyanosis of the extremities appear in cold weather. Type II is often accompanied by glomerulonephritis, and type III is often accompanied by arthralgia.
Symptoms include increased blood Ig, positive RF test, and decreased serum complement levels.
The prognosis varies depending on the underlying disease, but some cases caused by acute infections may improve naturally. Treatment involves avoiding the cold and treating the underlying disease. In cases where vasculitis or nephritis develops, corticosteroids and immunosuppressants may be administered, and plasma exchange or cryofiltration may be performed to remove cryoglobulin. [Takuya Matsunaga]
■ References
Hanamura I, et al: Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantation. Blood, 108: 1724-1732, 2006.
Harada H, et al: Phenotypic difference of normal plasma cells from mature myeloma cells. Blood, 81: 2658-2663, 1993.
Malpas JS, Bergsagel DE, et al: Myeloma, pp1-581, Oxford University Press, Oxford, 1995.

Cryoglobulinemia (rheumatic disease)

[⇨ 14-10-20)-(6)] [Kiyoji Minoda]

Source : Internal Medicine, 10th Edition About Internal Medicine, 10th Edition Information

Japanese:

（6）クリオグロブリン血症
　1933年にWintrobeとBuellらは，骨髄腫症例の血清サンプル中にクリオグロブリン（cryoglobulin）をはじめて発見して報告した．クリオグロブリンは，0～4℃の低温で可逆性に凝固する白濁沈殿物のことで，ほとんどがIgを含む混合物である．クリオグロブリンは，血管炎，ウイルス感染，リンパ増殖性疾患の症例で検出されることが多い．Brouetらは，沈殿物の構成成分に基づき，クリオグロブリン血症を3つの型に分類した．①Ⅰ型：単クローン性IgでIgGとIgMが多い．骨髄腫，マクログロブリン血症，MGUS，リンパ増殖性疾患に伴う場合がある．②Ⅱ型：混合型クリオグロブリンを示すもの．単クローン性で抗グロブリン活性（リウマトイド因子（RF）活性）を有するIgMと多クローン性IgGからなることが多い．C型肝炎ウイルスなどの各種ウイルス成分や自己蛋白が抗原となり反応して変化したIgGにIgMが反応してできた免疫複合体であることが多い．しかし，基礎疾患の認められないものもまれにある．③Ⅲ型：多クローン性Igによるもの．発症機序はⅡ型と同様であり，IgMによる場合が多い．
　寒冷時に網状皮斑，Raynaud現象，じんま疹，血管性紫斑，四肢末端のチアノーゼなどの循環障害の症状を呈する．Ⅱ型では糸球体腎炎，Ⅲ型では関節痛をきたすことが多い．
　血中Igの増加，RF陽性，血清補体価の低下などをきたす．
　予後は基礎疾患により異なるが，急性の感染症によるものは自然軽快するものもある．　治療は寒冷を避け，基礎疾患に対する治療を行うことである．血管炎や腎炎を発症する症例では，副腎皮質ステロイド薬や免疫抑制薬の投与，クリオグロブリン除去を目的とした血漿交換やクリオフィルトレーションを行うこともある．［松永卓也］
■文献
Hanamura I, et al: Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantation. Blood, 108: 1724-1732, 2006.
Harada H, et al: Phenotypic difference of normal plasma cells from mature myeloma cells. Blood, 81: 2658-2663, 1993.
Malpas JS, Bergsagel DE, et al: Myeloma, pp1-581, Oxford University Press, Oxford, 1995.