What are the symptoms of cryoglobulinemia?

From the Guidelines

Cryoglobulinemia symptoms typically include purpura, weakness, and arthralgias, as well as various visceral organ involvement, including renal, neurological, cardiac, or digestive disease, as reported in a study published in Autoimmunity Reviews in 2017 1. The symptoms of cryoglobulinemia can be diverse and affect multiple organ systems.

• Fatigue, joint pain, skin rashes, and numbness or tingling in the extremities are common symptoms.
• Patients often develop purpura (purple skin lesions) on the lower limbs, which may be accompanied by skin ulcers in severe cases.
• Kidney involvement can cause protein or blood in urine, high blood pressure, and potentially kidney failure.
• Neurological symptoms may include peripheral neuropathy, confusion, or stroke-like symptoms.
• Some patients experience abdominal pain, enlarged liver or spleen, and digestive issues.
• The severity of symptoms varies widely, with some patients having mild symptoms while others develop life-threatening complications.
• Symptoms typically worsen with cold exposure and may improve in warmer environments.
• The condition often accompanies underlying disorders like hepatitis C infection, autoimmune diseases, or certain cancers, so symptoms of these conditions may also be present. A more recent study published in the Journal of Hepatology in 2020 found that direct-acting antiviral (DAA) therapy can induce a complete clinical response in 73% of patients with cryoglobulin-associated vasculitis, with symptoms of purpura cleared from 97% of patients, renal involvement from 91% of patients, arthralgias from 86% of patients, and neuropathy from 77% of patients 1. Therefore, based on the most recent and highest quality evidence, cryoglobulinemia symptoms can be effectively managed with DAA therapy, which can induce a complete clinical response in a significant proportion of patients 1.

From the Research

Symptoms of Cryoglobulinemia

• Fatigue, arthralgia, purpura, ulcers, neuropathy, and/or glomerulonephritis are common symptoms of cryoglobulinemia 2, 3, 4, 5
• The disease mainly involves small to medium-sized blood vessels and causes vasculitis due to cryoglobulin-containing immune complexes 2, 4
• Clinical presentations can range from mild symptoms such as arthralgias, mild palpable purpura, and fatigue to severe vasculitis features with skin necrotic pattern, peripheral neuropathy, and organ involvement 3, 5
• The kidney is the most common organ presentation, and the presence of glomerulonephritis is a key element when considering prognosis 5
• Other symptoms may include:
  • Nociceptive or neuropathic pain 3
  • Weakness 3
  • Leg ulcers 3
  • Widespread vasculitis 3
  • Hyperviscosity syndrome 3
  • Lung, central nervous system, gastrointestinal tract, and heart involvement 5

Types of Cryoglobulinemia

• Cryoglobulinemia is classified into three types (I, II, and III) on the basis of immunoglobulin composition 2, 4
• Type II is characterized by the presence of both polyclonal IgG and monoclonal IgM, while type III is characterized by the presence of polyclonal IgG and polyclonal IgM 5

Predisposing Conditions

• Predisposing conditions include lymphoproliferative disease, autoimmune diseases, and hepatitis C virus (HCV) infection 2, 4, 5
• The identification of HCV infection in most cases previously defined as "essential" represented a cornerstone in understanding the pathogenesis of this condition 5