The clinical features of<unk>  disease can reflect those due not only to the circulation of cryoglobulins but also to any underlying hematological premalignant or malignant disorder, infectious disease, or autoimmune syndrome. The following sections of clinical features focuses on those attributed to the cryoglobulins. Cryoglobulins cause tissue damage by three mechanisms; they can: *a) increase blood viscosity thereby reducing blood flow to tissues to cause the hyperviscosity syndrome (i.e., headache, confusion, blurry or loss of vision, hearing loss, and epistaxis; *b) deposit in small arteries and capillaries thereby plugging these blood vessels and causing infarction and necrosis of tissues including in particular skin (e.g., ears), distal extremities, and kidneys; *c) in type II and type III disease, deposit on the endothelium of blood vessels and activate the blood complement system to form pro-inflammatory elements such as C5a thereby initiating the systemic vascular inflammatory reaction termed<unk>  vasculitis. Essential<unk>  disease The signs and symptoms in the increasingly rare cases of<unk>  disease that cannot be attributed to an underlying disease generally resemble those of patients suffering Type II and III (i.e., mixed)<unk>  disease. Type I<unk>  disease Signs and symptoms due to the cryoglobulins of type I disease reflect the hyperviscosity and deposition of cryoglobulins within the blood vessels which reduce or stop blood perfusion to tissues. These events occur particularly in cases where blood cryoglobulin levels of monoclonal IgM are high in patients with IgM MGUS, smoldering Waldenström's macroglobulinemia, or Waldenström's macroglobulinemia and in uncommon cases where the levels of monoclonal IgA, IgG, free κ light chains, or free λ light chains are extremely high in patients with non-IgM MGUS, non-IgM smoldering multiple myeloma, or multiple myeloma. The interruption of blood flow to neurological tissues can cause symptoms of confusion, headache, hearing loss, and peripheral neuropathy. Interruption of blood flow to other tissues in type I disease can cause cutaneous manifestations of purpura, blue discoloration of the arms or legs (acrocyanosis), necrosis, ulcers, and livedo reticularis; spontaneous nose bleeds, joint pain, membranoproliferative glomerulonephritis; and cardiovascular disturbances such as shortness of breath, inadequate levels of oxygen in the blood (hypoxemia), and congestive heart failure. Types II and III<unk>  disease Types II and III (or mixed or variant)<unk>  disease may also present with symptoms and signs of blood hyperviscosity syndrome and deposition of cryoglobulins within blood vessels but also include those attributable to<unk>  vasculitis. "Meltzer's triad" of palpable purpura, joint pain, and generalized weakness occurs in ≈33% of patients presenting with type II or type III disease. One or more skin lesions including palpable purpura, ulcers, digital gangrene, and areas of necrosis occur in 69-89% of these mixed disease cases (see attached photograph); less common findings include painful peripheral neuropathy (often manifesting as mononeuritis multiplex in 19-44% of cases), kidney disease (primarily membranoproliferative glomerulonephritis (30%), joint pain (28%), and, less commonly, dry eye syndrome, Raynaud phenomenon (i.e., episodic painful reductions in blood flow to the fingers and toes). While the glomerulonephritis occurring in mixed disease appears to be due to inflammatory vasculitis, the glomerulonephritis occurring in type I disease appears due to the interruption of blood flow. The hematological, infectious, and autoimmune diseases underlying type II<unk>  disease and the infectious and autoimmune diseases underlying type III<unk>  disease are also critical parts of the disease's clinical findings.
Cryoglobulinemia
Myoglobinuria
Hemoglobinuria
Hemosiderinuria
Trimethylaminuria
Lipiduria
Pentosuria
Xanthinuria