The symptoms and physical findings of mixed cryoglobulinemia can vary greatly from one individual to another. Many different organ symptoms can be potentially become involved. Some individuals will only exhibit one manifestation of the disorder; others will exhibit symptoms of multiple organ systems.
Most affected individuals develop purplish discoloration of the skin due to bleeding underneath the skin from small blood vessels (purpura). Numerous small lesions the size of pinpricks (petechaie) may develop. Larger lesions or bruising (ecchymoses) can also occur. The lower extremities are most often affected. Purpuric lesions are most common after an affected individual has been standing or sitting for long periods of time (orthostatic purpura). In some cases, open sores (ulceration) and hives (urticarial) may also develop. Loss of tissue (necrosis) on the extremities (e.g. fingers and toes) can also occur.
Although Joint Pain (arthralgia) is very common in individuals with cryoglobulinemia, joint Inflammation (arthritis) occurs far less frequently. Additional nonspecific symptoms are common including mild to severe itching, mild to severe pain, abdominal pain, muscle weakness, Muscle Pain (myalgia), and abnormal enlargement of the lymph nodes (lymphadenopathy). In some cases, abnormal enlargement of the liver and/or spleen (hepatosplenomegaly) may occur.
Cryoglobulinemia can be associated with a kidney (renal) disease known as membranoproliferative glomerulonephritis (MPGN) type I characterized by a specific pattern of injury to the kidney most likely caused by deposition of cryoglobulins in the kidney. MPGN type I can be a severe complication, eventually leading to kidney failure.
Affected individuals may experience damage to the nerves outside the central nervous system (peripheral neuropathy). Peripheral neuropathy is characterized by Numbness or tingling and painful or burning sensations that usually begin in the feet and sometimes the arms. These sensations may worsen at night (nocturnal exacerbation). Peripheral neuropathy may cause muscles Weakness in legs and arms.
Affected individuals may also develop an abnormally dry mouth (xerostomia) and abnormally dry eyes (xerophthalmia), a combination which is sometimes referred to as Sicca syndrome. Numbness and tingling and a lack of blood flow to the fingers/or toes when exposed to cold temperatures (Raynaud’s phenomenon) may also occur. Internal bleeding and abnormal blood clot formation has also been reported.
Chronic Inflammation of the liver (hepatitis) can occur in affected individuals, particularly those with hepatitis C-associated mixed cryoglobulinemia. Chronic hepatitis is often mild or moderate and may not cause any symptoms. Symptoms that can occur include Fatigue and aching muscles or joints. Chronic hepatitis can eventually progress to cause scarring (cirrhosis) of the liver.
Less often, additional symptoms have been reported in individuals with mixed cryoglobulinemia including lung disease, widespread (diffuse) vasculitis, and certain endocrine disorders such as disorders of affecting the thyroid including autoimmune thyroiditis, hypothyroidism and thyroid cancer. Diffuse vasculitis is a severe, potentially life-threatening complication. When the gastrointestinal tract is involved, sudden, severe abdominal Pain (acute abdomen) may be the initial symptom.
Diabetes mellitus type 2 occurs with greater frequency in individuals with hepatitis C infection with and without mixed cryoglobulinemia than it does in the general population. Whether individuals with mixed cryoglobulinemia have a higher risk of developing diabetes is not known. Some individuals with mixed cryoglobulinemia may develop cancer as a late complication of the disorder, specifically a type of B-cell lymphoma or a form of liver cancer known as hepatocellular carcinoma.