Mesoglycan treatment restores defective fibrinolytic potential in cutaneous necrotizing venulitis.

BACKGROUND

Cutaneous necrotizing venulitis (CNV) is a clinical disorder associated with segmental inflammation and fibrinoid necrosis of the dermal venules. It usually presents clinically as palpable purpura, even sometimes as nodules, bullae, ulcers, and urticarial lesions. This form, when showing as leukocytoclastic vasculitis is apparently characterized by the tissue deposition of circulating immune complexes and by reduced cutaneous (CFA) and plasma (PFA) fibrinolytic activity due to reduced release of plasminogen activator (PA) from the venular endotheliocytes. Reduced CFA and PFA cause large amounts of fibrin deposits in both intra- and perivascular areas, which are able to magnify and self perpetuate the inflammatory processes following immune complex deposition.

METHODS

We have studied both the PFA and CFA potential (the maximum amount of PA released in the skin after certain stimuli) and the deposits of immunoglobulins, C3, and fibrin related antigen, before and after intradermal injection of histamine (a substance able to provoke endothelial release of PA), in three subjects affected by CNV before and 20 days after 10 mg/kg/day I.M. treatment with the fibrinolytic agent mesoglycan.

RESULTS

Cutaneous fibrinolytic activity and CFA potential, reduced prior to treatment, was normal after treatment, while the deposits of immunoglobulins (IgA, IgG and IgM), C3, and fibrin related antigen, detected with direct immune fluorescence (DIF) showed similar findings before and after treatment.

CONCLUSIONS

These data suggest that reduced CFA may play a major role in the pathogenesis of the immunologically mediated injury in CNV. The intraperivascular deposition of fibrin is favored. The fibrinolytic agent mesoglycan seems effective in restoring defective fibrinolysis in patients affected by cutaneous necrotizing venulitis, suggesting that in cases with reduced cutaneous fibrinolytic activity (or potential) the use of a fibrinolytic agent should be considered.