Figure 2 Cutaneous manifestations of mixed cryoglobulinemia (MC). (a) recent onset orthostatic purpura; at this stage the histopathological evaluation shows (b) the classical necrotizing leukocytoclastic vasculitis characterized by diffuse fibrinoid necrosis and disintegrated neutrophil permeation of the vessel walls; (c) symmetrical hyperpigmentation of the skin on the legs after repeated episodes of purpura; both orthostatic purpura and these permanent ochraceous lesions represent the typical skin manifestations of MC; (d) severe vasculitic manifestation; (e) wide skin ulcer, often resistant to treatment..
Orphanet J Rare Dis. 2008 Sep 16; 3:25
Mixed cryoglobulinemia (MC), type II and type III, refers to the presence of circulating cryoprecipitable immune complexes in the serum and manifests .....
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 Sj gren'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, Sj gren'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.
Copyright 2008 Ferri; licensee BioMed Central Ltd.