Superficial thrombophlebitis
Superficial thrombophlebitis
Clinical features Superficial thrombophlebitis is a common disease presenting as painful, erythematous, thickened areas with a cordlike morphology. Most cases involve the lower limbs, particularly below the knees, and there is a predilection for females. Multifocal segmental disease is frequent and recurrent episodes are often seen. The disease is usually associated with hypercoagulable states. Predisposing factors are numerous and include varicose veins, pregnancy, the use of oral contraceptives (particularly those with a higher concentration of estrogen), cancer (mainly breast, colonic, pancreatic, gastric, cholangiocarcinoma, hematological as well as cutaneous), Behçet disease, factor V (Leiden) mutation, essential thrombocythemia, anticardiolipin antibodies, and deficiencies of protein C, protein S, factor XII, antithrombin III, and heparin cofactor 2C.1–18 Superficial thrombophlebitis developing in association with secondary syphilis has been documented.19 Superficial suppurative thrombophlebitis occurs mainly in children and it is caused by a wide variety of microorganisms, mainly bacteria (both aerobic and anaerobic) and, less commonly, fungi.20–24 The most common bacteria isolated include S. aureus, E. coli, and P. aeruginosa.20,21 Candida is by far the most common fungus associated with the disease.
recurrent and tend to great chronicity. Ecchymoses are not a feature.1 Some cases clinically resemble Schamberg purpura.5
Laboratory investigations usually reveal a raised ESR, mild anemia and leukopenia, and polyclonal hypergammaglobulinemia (usually IgG, but sometimes IgM or IgA). Antinuclear antibodies, anti-Ro, anti-La, and rheumatoid factor are present in many patients.1,3,6–8 Platelet levels, coagulation studies, and bone marrow examination are typically normal. Cryoglobulinemia is an occasional feature. There are no known HLA associations and family history is negative.1 Lymphadenopathy and splenomegaly are sometimes a feature.1
It is important to note that hypergammaglobulinemic purpura may be classified into two categories: idiopathic (Waldenström; not to be confused with Waldenström macroglobulinemia) and secondary. In the latter group, patients have a wide variety of conditions, including SLE, polymyositis, Hashimoto thyroiditis, Sjögren syndrome, rheumatoid arthritis, hepatitis, chronic lymphocytic leukemia, monoclonal gammopathies, sarcoidosis, and recurrent infections.1,9–12 The purpura may precede the associated illness for many years. Patients with this disorder, therefore, merit a careful and prolonged follow-up.
Pathogenesis and histologic features Direct immunofluorescence examination of skin lesions reveals IgM and C3 in blood vessel walls.13 Perivascular deposits of IgG and C5b-9 have also been reported.8 Circulating immune complexes, with both IgG and IgM, have also been demonstrated in patients with this disorder.14 It is likely, therefore, that hypergammaglobulinemic purpura is another variant of immune complex-mediated vasculitis, namely, a type III hypersensitivity reaction. The precise etiology, however, remains poorly understood.
Superficial thrombophlebitis may be associated with deep vein thrombosis but the risk of this happening appears to be small unless there are additional risk factors.25–28 The chance of a patient with superficial thrombophlebitis developing pulmonary embolism is low, but it has been documented and the risk appears to be greater in patients with disease affecting the thigh.29,30
Histologic features Superficial thrombophlebitis typically involves veins located in the superficial subcutaneous tissue. Early lesions are characterized by an infiltrate predominantly composed of neutrophils obscuring the vessel walls. The neutrophils are progressively replaced by lymphocytes, histiocytes, and occasional giant cells. An organizing thrombus is initially present and this is followed by recanalization and fibrosis. The infiltrate tends to remain localized and there is very little involvement of the surrounding subcutaneous tissue. Arteries are not affected.
Histologic examination of the purpuric lesions may reveal the typical features of acute leukocytoclastic vasculitis with red cell extravasation.15 Occasionally, however, lymphocytic perivasculitis and hemorrhage is all that is evident, possibly reflecting the result of the timing of the biopsy.8
Differential diagnosis The histologic changes are not specific and other causes of leukocytoclastic vasculitis must be considered.
Hyperimmunoglobulinemia D syndrome/mevalonate kinase deficiency
Clinical features Hyperimmunoglobulinemia D syndrome is a rare autosomal recessive disease due to mutations in the MVK gene, a key enzyme located