Ferri Clodoveo
Dipartimento Medicine e Specialità Mediche, Cattedra ed U,O,C, di Reumatologia, Università di Modena & Reggio Emilia, Modena, Italy.
Orphanet J Rare Dis. 2008 Sep 16;3:25. doi: 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. It is considered to be a rare disorder, but its true prevalence remains unknown. The disease is more common in Southern Europe than in Northern Europe or Northern America. The prevalence of 'essential' MC is reported as approximately 1:100,000 (with a female-to-male ratio 3:1), but this term is now used to refer to a minority of MC patients only. MC is characterized by variable organ involvement including skin lesions (orthostatic purpura, ulcers), chronic hepatitis, membranoproliferative glomerulonephritis, peripheral neuropathy, diffuse vasculitis, and, less frequently, interstitial lung involvement and endocrine disorders. Some patients may develop lymphatic and hepatic malignancies, usually as a late complication. MC may be associated with numerous infectious or immunological diseases. When isolated, MC may represent a distinct disease, the so-called 'essential' MC. 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. Moreover, MC may be associated with other infectious agents or immunological disorders, such as human immunodeficiency virus (HIV) infection or primary Sjögren's syndrome. Diagnosis is based on clinical and laboratory findings. Circulating mixed cryoglobulins, low C4 levels and orthostatic skin purpura are the hallmarks of the disease. Leukocytoclastic vasculitis involving medium- and, more often, small-sized blood vessels is the typical pathological finding, easily detectable by means of skin biopsy of recent vasculitic lesions. Differential diagnoses include a wide range of systemic, infectious and neoplastic disorders, mainly autoimmune hepatitis, Sjögren's syndrome, polyarthritis, and B-cell lymphomas. The first-line treatment of MC should focus on eradication of HCV by combined interferon-ribavirin treatment. Pathogenetic treatments (immunosuppressors, corticosteroids, and/or plasmapheresis) should be tailored to each patient according to the progression and severity of the clinical manifestations. Long-term monitoring is recommended in all MC patients to assure timely diagnosis and treatment of the life-threatening complications. The overall prognosis is poorer in patients with renal disease, liver failure, lymphoproliferative disease and malignancies.
II型和III型混合性冷球蛋白血症（MC）是指血清中存在可循环的冷沉淀免疫复合物，临床上表现为紫癜、乏力和关节痛这一典型三联征。它被认为是一种罕见疾病，但其真实患病率仍不清楚。该疾病在南欧比在北欧或北美更常见。据报道，“原发性”MC的患病率约为1:100,000（女性与男性比例为3:1），但现在这个术语仅用于指少数MC患者。MC的特征是器官受累情况各异，包括皮肤病变（直立性紫癜、溃疡）、慢性肝炎、膜增生性肾小球肾炎、周围神经病变、弥漫性血管炎，较少见的还有间质性肺受累和内分泌紊乱。一些患者可能会发生淋巴系统和肝脏恶性肿瘤，通常作为晚期并发症。MC可能与多种感染性或免疫性疾病相关。当MC单独出现时，可能代表一种独特的疾病，即所谓的“原发性”MC。MC的发病机制尚未完全明确。丙型肝炎病毒（HCV）感染被认为起致病作用，同时还有遗传和/或环境因素的影响。此外，MC可能与其他感染因子或免疫性疾病相关，如人类免疫缺陷病毒（HIV）感染或原发性干燥综合征。诊断基于临床和实验室检查结果。循环混合性冷球蛋白、低C4水平和直立性皮肤紫癜是该疾病的标志。累及中、小血管的白细胞破碎性血管炎是典型的病理表现，通过对近期血管炎性病变进行皮肤活检很容易检测到。鉴别诊断包括多种全身性、感染性和肿瘤性疾病，主要有自身免疫性肝炎、干燥综合征、多关节炎和B细胞淋巴瘤。MC的一线治疗应侧重于通过联合干扰素 - 利巴韦林治疗根除HCV。应根据临床表现的进展和严重程度为每位患者量身定制致病治疗（免疫抑制剂、皮质类固醇和/或血浆置换）。建议对所有MC患者进行长期监测，以确保及时诊断和治疗危及生命的并发症。肾病、肝功能衰竭、淋巴增殖性疾病和恶性肿瘤患者的总体预后较差。
