From this review of articles it is apparent that no single disease, cause, or mechanism so far could be identified to be responsible for LV. It seems that many different circumstances, systemic and localized, lead to similar morphologic changes. In the ultimate analysis it is the morphologic findings, alone, that is the denominator in common among all patients with LV reported in the literature. Authors have attempt separation of LV from other diseases typified by thrombi in the lumina of blood vessels such as antiphospholipid syndrome, calciphylaxis, monoclonal cryoglobulinemia, protein C or protein S deficiency, Factor V Leiden mutation, etc., but the changes morphologic in such conditions both clinical and in an individual biopsy specimen are often indistinguishable. Our review shows that genetically determined disorders of the coagulation cascade, thrombophilia induced by neoplastic diseases, but also autoantibodies in rheumatologic diseases such as lupus erythematosus can produce the very same signs and symptoms in the skin. Even calciphylaxis and disseminated intravascular coagulation may present themselves with the same appearance both clinical and histopathologic. Therefore, a patient diagnosed with LV clinically and histopathologically needs to be worked up completely in regard to genetic alterations of the coagulation cascade, rheumatologic disorders, and internal malignancies. Morphologic findings alone, do not permit differentiation in most instances.

All these observations confirm what we already suggested based on our review of findings clinical and histopathologic, namely, that LV is a clinicopathologic pattern but not a specific disease. That interpretation explains also, why no single treatment regimen has been identified to be successful in all patients with LV. Medications used with positive results in LV, are antiinflammatory, e.g., topical corticosteroids, [12] systemic corticosteroids, [12, 53] intravenous immunoglobulins, [43] PUVA therapy, [36] and potassium iodide, [52] rheologic, e.g., sulfasalazine, [54] tissue plasminogen activator, [55] low molecular weight heparin, [41] Ketanserin, [26] danazol, [33] prostacyclin analogue (PGI2), [34] pentoxyphylline, [24] ticlopidine, [25] acetylalicylic acid, [25] dipyridamole, [25] phenformin, [15] and 10% dextran hydrolysate, [56] and yilding at vasodilating and oxigenation, e.g., nifedepine [57] and sympathectomy, [12] and hyperbaric oxygen treatment. [42]

It is obvious, that depending on the reason for a state of hypercoagulability, the clinical course as well as the response to treatment may vary considerably in patients who have in common the clinical and histopathologic findings of LV. If an inherited disorder of the coagulation cascade is the reason, the course will be protracted and rheologic treatment alone will improve the condition. If thrombophilia is consequent to thrombocytosis as it occurs together with some malignant neoplastic diseases, rheologic therapy alone may improve the condition but only sufficient treatment of the malignancy will cure it. If antiphospholipid antibodies are increased because a patient has systemic lupus erythematosus, immunosuppressive treatment is needed in addition to rheologic therapy.

Defining LV as a pattern and not as a specific disease also resolves the controversy whether LV is a vasculitis or a vasculopathy. If LV is conceived of as a clinicopathologic pattern, criteria for diagnosis and definition of it must be purely morphologic. According to the 3rd edition of Histologic Diagnosis of Inflammatory Skin Diseases [58], small vessel vasculitis is defined as fibrin in the walls of vessels and/or thrombi in the lumina accompanied by a perivascular infiltrate. Therefore, LV qualifies as a vasculitis in a strictly morphologic sense. There is no doubt, however, that a host of changes precede the clinical manifestation of LV and that various causes may lead to activation of the coagulation cascade followed by formation of thrombi in the lumina of vessels. At a stage when LV is diagnosable clinically and histopathologically it fulfils criteria for a small vessel vasculitis it being typified by thrombi in the lumina of vessels and a perivascular infiltrate.

The situation of LV is akin to that of leukocytoclastic vasculitis (LCV), in which multiple causes lead to formation of antigen-antibody complexes followed by formation of fibrin deposits in the walls of vessels and attraction of neutrophils to the site, which then undergo leukocytoclasia. In both, LV and LCV, the perivascular infiltrates are secondary to preceding events. In LCV, just as in LV, the pathomechanisms are systemic ones, and not just ones restricted to the vessels of the legs. It is not helpful to designate LV a vasculopathy in contradistinction to vasculitis, e.g., LCV, because no clear definition of vasculopathy exists. Literally, vasculopathy means "a disease of the vessels." LV, however, seems to be consequent to various alterations of coagulation which themselves have multiple causes. Designating LV simply as a disease of vessels of the legs is an oversimplification.

It is interesting to note that LV has a predilection for the lower legs. That phenomenon is not unique to LV among diseases of small vessels, LCV also presents most commonly on the lower legs. It seems that orthostatic phenomena including stasis and slow blood flow in postcapillary venules serve as predilecting factors for clinical manifestation of both conditions.