Dysproteinemias Causing Vascular Purpura

Amyloidosis Amyloidosis Amyloidosis is any of a group of disparate conditions characterized by extracellular deposition of insoluble fibrils composed of misaggregated proteins. These proteins may accumulate locally... read more causes amyloid deposition within vessels in the skin and subcutaneous tissues, which may increase vascular fragility, causing purpura. Purpura typically occurs on the upper extremities in contrast to immune thrombocytopenia Immune Thrombocytopenia (ITP) Immune thrombocytopenia (ITP) is a bleeding disorder usually without anemia or leukopenia. Typically, it is chronic in adults, but it is usually acute and self-limited in children. Spleen size... read more , in which purpura occurs mostly in the lower extremities. Periorbital purpura or a purpuric rash that develops in a nonthrombocytopenic patient after gentle stroking of the skin suggests amyloidosis.

Some patients with amyloidosis have macroglossia (enlarged tongue) and can have amyloid deposits on the shoulders and in the skin.

In some patients, coagulation factor X is adsorbed by amyloid and becomes deficient, but this deficiency is usually not the cause of bleeding.

Most patients have elevated levels of serum free light chains.

The diagnosis of amyloidosis is confirmed by tissue biopsy (eg, Congo red birefringence staining of affected tissue or abdominal fat pad aspirate).

Cryoglobulinemia produces immunoglobulins that precipitate when plasma is cooled (ie, cryoglobulins) while flowing through the skin and subcutaneous tissues of the extremities. Cryoglobulins may be IgG, IgM, or IgA. Mixed cryoglobulins are usually composed of IgM complexed with a monoclonal or polyclonal IgG. The immune complexes can interfere with normal platelet function and fibrin polymerization.

Monoclonal immunoglobulins formed in macroglobulinemia Macroglobulinemia Macroglobulinemia is a malignant plasma cell disorder in which B cells produce excessive amounts of IgM M-proteins. Manifestations may include hyperviscosity, bleeding, recurring infections... read more (lymphoplasmacytic lymphoma) or in multiple myeloma Multiple Myeloma Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include lytic lesions in bones causing... read more occasionally behave as cryoglobulins, as may mixed IgM-IgG immune complexes formed in some chronic infectious diseases, most commonly hepatitis C Hepatitis C, Chronic Hepatitis C is a common cause of chronic hepatitis. It is often asymptomatic until manifestations of chronic liver disease occur. Diagnosis is confirmed by finding positive anti-HCV and positive... read more .

Cryoglobulins can also be idiopathic.

Cryoglobulinemia can also lead to small-vessel vasculitis, which can cause purpura; hyperviscosity and direct vascular trauma can contribute. Cryoglobulinemia can manifest with acral hemorrhagic necrosis, palpable purpura, livedo reticularis, and leg ulcers.

Cryoglobulins can be detected by laboratory testing.

Hypergammaglobulinemic purpura is a vasculitic purpura that primarily affects women. Recurrent crops of small, palpable purpuric lesions develop on the lower legs. These lesions leave small residual brown spots. Many patients have manifestations of an underlying immunologic disorder (eg, Sjögren syndrome Sjögren Syndrome Sjögren syndrome is a relatively common chronic, autoimmune, systemic, inflammatory disorder of unknown cause. It is characterized by dryness of the mouth, eyes, and other mucous membranes ... read more , systemic lupus erythematosus Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more ).

The diagnostic finding is a polyclonal increase in IgG. Skin biopsy may be needed.

Immunoglobulin A–associated vasculitis Immunoglobulin A–Associated Vasculitis (IgAV) Immunoglobulin A–associated vasculitis (formerly called Henoch-Schönlein purpura) is vasculitis that affects primarily small vessels. It occurs most often in children. Common manifestations... read more (Henoch-Schonlein purpura) is an IgA-mediated small-vessel vasculitis that occurs primarily in children. It involves the skin, joints, intestine, and kidneys.

Palpable purpura develops mainly on the lower legs and buttocks. Because of its distribution, it can be confused with erythema nodosum Erythema Nodosum Erythema nodosum is a specific form of panniculitis characterized by tender, red or violet, palpable, subcutaneous nodules on the shins and occasionally other locations. It often occurs with... read more , a reactive inflammatory panniculitis that can occur in patients with a variety of infectious, immunologic, neoplastic, and drug-induced disorders.

Hyperviscosity syndrome Symptoms and Signs Macroglobulinemia is a malignant plasma cell disorder in which B cells produce excessive amounts of IgM M-proteins. Manifestations may include hyperviscosity, bleeding, recurring infections... read more , usually resulting from a markedly elevated plasma IgM concentration, may also result in purpura and other forms of abnormal bleeding (eg, profuse epistaxis) in patients with macroglobulinemia Macroglobulinemia Macroglobulinemia is a malignant plasma cell disorder in which B cells produce excessive amounts of IgM M-proteins. Manifestations may include hyperviscosity, bleeding, recurring infections... read more . Marked elevations of other immunoglobulins (especially IgA and IgG3) can also be associated with a hyperviscosity syndrome.