Essential mixed cryoglobulinemia (EMC) is a rare systemic disorder characterized by the presence of cryoglobulins—immunoglobulins that precipitate at lower temperatures and dissolve upon rewarming—in the blood. It is termed “essential” when no underlying cause, such as hepatitis C virus (HCV), autoimmune diseases, or lymphoproliferative disorders, is identified. EMC involves the deposition of immune complexes in small blood vessels, leading to vasculitis and subsequent organ damage.
Key Features:
Cryoglobulins: Typically type II or III (mixed), involving monoclonal or polyclonal immunoglobulins (often IgM and IgG).

Clinical Triad (Meltzer’s triad, seen in ~25-30% of cases):
Purpura (recurrent, palpable, often on lower extremities)

Arthralgia (joint pain, usually without arthritis)

Weakness (generalized fatigue)

Other Symptoms:
Renal involvement (glomerulonephritis, leading to proteinuria or hematuria)

Peripheral neuropathy (numbness, tingling)

Skin ulcers, Raynaud’s phenomenon

Liver involvement (hepatomegaly or abnormal liver function tests)

Pathophysiology: Immune complex deposition causes small-vessel vasculitis, triggering inflammation and tissue damage.

Diagnosis:
Laboratory Tests:
Serum cryoglobulin detection (blood sample kept at 37°C, then cooled to 4°C for precipitation)

Low complement levels (especially C4)

Rheumatoid factor positivity (common in type II)

Rule out HCV (serology or PCR), as it’s a common secondary cause

Biopsy (if needed): Skin, kidney, or nerve to confirm vasculitis or immune complex deposition.

Exclusion of Secondary Causes: Screen for HCV, HBV, HIV, autoimmune diseases (e.g., SLE, Sjögren’s), and lymphoproliferative disorders.