Cutaneous symptoms include one or more of the following: cold contact-induced urticarial (which may be the first sign of the disease); painful episodes of finger and/or toe arterial spasms termed Raynaud phenomena ; cyanosis , a palpable purpura termed cryofibrinogenemic purpura ), and a lace-like purplish discoloration termed livedo reticularis all of which occur primarily in the lower extremities but some of which may occur in the nose, ears, and buttocks; non-healing painful ulcerations and gangrene of the areas impacted by the cited symptoms. [2] Patients also have a history of cold sensitivity (~25% of cases), arthralgia (14-58%), neuritis (7-19%), myalgia (0-14%); and overt thrombosis of arteries and veins (25-40%) which may on rare occasions involve major arteries such of those of the brain and kidney. [5] [6] [7] Signs of renal involvement ( proteinuria , hematuria , decreased glomerular filtration rate , and/or, rarely, renal failure ) occur in 4-25% of cases. [5] [8] Compared to secondary cryofibrinogemia, primary crygofibrinogenemia has a higher incidence of cutaneous lesions, arthralgia, and cold sensitivity while having a far lower incidence of renal involvement. [5] Patients with secondary cryofibrinogenemia also exhibit signs and symptoms specific to the infectious, malignant, premalignant vasculitis, and autoimmune disorders associated with their disease. [2] While rare, individuals with cryofibrinogenemic disease may experience pathological bleeding due to the consumption of blood clotting factors consequential to the formation of cryofibrinogen precipitates. [2] [5] Diagnosis [ edit ] Suggested diagnostic criteria for cryoglobulinemic disease fall into the following obligatory and additional categories: [5] Obligatory criteria: 1) cold sensitivity; 2) cutaneous symptoms (i.e. urticaria, purpura, Raynaud phenomenon, ulceration/necrosis/gangrene, and/or livedo reticularis); 3) arterial and/or venous thrombotic events; fever; 4) arthralgia/myalgia; 5) neuritis in >1 site; and 6) renal disorder. ... Andrews' Diseases of the Skin: clinical Dermatology . Saunders Elsevier. ISBN 0-7216-2921-0 . : 822 ^ a b c d e f g h i j k l m Grada A, Falanga V (2017). ... Journal of Thrombosis and Haemostasis . 15 (5): 876–888. doi : 10.1111/jth.13655 . PMID 28211264 . ^ Casini A, Sokollik C, Lukowski SW, Lurz E, Rieubland C, de Moerloose P, Neerman-Arbez M (2015).