Mesoglycans treatment in cutaneous necrotizing vasculitis

Free communication FC19. Phlebology elevated upper part of the body. The evaluation of FV was done by integrating the velocity of the blood flow in relation to the diameter (FV-D) and the circumference (FV-U) of the vessel. The region of interest was the v.femoralis just distal the junction of the long saphene vein Results: In 189 limbs FV-D and FV-U were determined. In 77 healthy limbs mFV-D = mFV-U = 0.15 Vmin. In 82 limbs with complete varicosis mFVD was 0.44 Ymin and mFV-U = 0.47 Ymin. In incomplete varicosis m FV-D was 0.37 Vmin and mFV-U = 0.40 Vmin. Conclusion: The significant differences of FV data corresponding to the grade of the venous reflux disease show that the method allows a quantification of the disease. FC19-3

Hyperbaric oxygenotherapy in the management of chronic leg ulcers: A comparative study of 36 patients

S. Fromentoux, B. Sassolas, G. Cochard, G. Lair, C. Garcia, H. Cartier, G. Guillet. Chu Brest, 29609, Brest, France Background: Hyperbaric oxygenotherapy has already been described in the treatment of several conditions such as gas gangrene, diabetic foot infection or necrotizing cellulitis. To evaluate its effects on wound healing, we set out a study managed during 18 months for patients suffering of chronic resistant leg ulcers. Material and Methods: 36 patients were randomly included in 2 groups with a repartition of 8 F and 10 M in each. The etiology of the ulcers was veinous in 55% (veinous superficial deficiency or post thrombotic syndrome) mixed in 28% and purely arteritic in 17%. The first group (mean age: 69) received a traditional and adapted local and general therapy; the second group (mean age: 63) received similar local and general therapy in association with hyperbaric oxygenotherapy at 3 ATA during 90 minutes, five time a week for 5 weeks. Evaluation was performed on the size and aspects of ulcers with planimetry. We evaluated the density of capillaries around the ulcers with videomicroscopy at Ja and at the end of treatment. Results: The average duration of leg ulcers was 12 months for patients in group 1 and 20 in group 2. At Jc the total surface of ulcers was 742 cm2 in group 1 and 911 in group 2. The mean decrease of surface of ulcers observed at the end therapy was 21% in group 1 and 61% in group 2 (p < 0.05). Eight patients were healed in a median delay of 9.5 Weeks in group 1. and 10 in a delay of 9.4 W in group 2. The videomicroscopy analysis of capillaries around the ulcer increased in 83% of patients of group 1 and 70% of group 2 (ns). Adverse effect of oxygenotherapy was noted in one patient. Discussion: Our controlled study confirm the benefit of hyperbaric oxygenotherapy as an associated therapy in the healing of chronic leg ulcers. However even if the tolerance of this therapy is favorable, the cost of this treatment must be considered.

FC19-4

S161

Chronic venous hypertension: Immunological alterations as possible pathomechanism for leg ulcers

P Teofoli, 0. De Pita, S. Barduagni, A. Frezzolini, S. Cadoni. I. Ghersetich’, T. Lotti’, S. Secci2. P.L. Vannucchi’. Dept. of Immunodertnatology,ogy, IDI, Rome; ‘Dept. of Dermatology, University of Florence; 311 Unit of Internal Medicine; 2General Surgety, S.M.N. Hospital, Florence, Italy Immune mechanisms involved in the pathogenesis of venous leg ulcers have been suggested. In this study we characterized by immunohistochemistry cytokine production (TN& IFNy, ILlO, IL12). some receptor (IL4R. IL6R) and adhesion molecule (ICAM-1, ELAM) expression in non affected skin from lower limb in 8 patients with chronic venous hypertension (CVH). At the same specimens from saphen vein was excised to perform immunohistochemical evaluation of adhesion molecule and cytokine expression. Sera from brachial and saphen veins were evaluated for soluble adhesion molecules (sELAM, sICAM, sVCAM) and circulating cytokines (sIL2R. TNFo, IL6, IFNy, IL12). Soluble CD30 (sCD30) was also considered as an index of Th2 activation. Our results showed a cellular infiltrate mainly consisting of CD3+ CD4+ T cells. A positive staining for TNFo and IL12 was detected in 5 out of 8 in skin specimens at perivascular sites. ICAM- was the only adhesion molecule to be expressed in all evaluated skin samples, apparently by both endothelial and infiltrating cells. Saphen vein sections evidenced strong ICAMand scanty ELAM-1 expression in 6/S examined samples. Immunoenzimatic evaluation showed no difference between brachial and saphen vein cytokine, soluble receptor and, adhesion molecule levels. Mean serum levels of TNFo and sILR were significantly higher than controls and 3 out of 8 patients showed high amounts of circulating IL6. Soluble adhesion molecules were all detected at significantly high levels respect to normal donors. Our results show an upregulation of adhesion molecules expression and release in unaffected skin biopsies, saphen veins and peripheral blood in all patients affected with CVH probably related to TNFLY production. The high levels of sIL2R account for an activation of T cells and, on the other hand, the low sCD30 and high TNFo serum levels detected suggest a possible Thl lymphocyte involvement in the pathogenesis of tissue damage in CVH patients. FCI 9-5

Mesoglycans treatment in cutaneous necrotizing vasculitis

C. Comacchi, I. Ghersetich, M. Benci, T.M. Lot& Department of Dermatology, University of Florence, Italy Cutaneous necrotizing vasculitis when showing as leukocytoelastic vasculitis is characterized by the tissue deposition of circulating immunecomplexes and reduced cutaneous (CPA) and plasma (PFA) fibrinolytic activity due to reduced release of plasminogen activator (PA) from the venularendotheliocytes. Various surface adhesion molecules (GMP ‘140, ELAM-1; gp90) on the endothelial cells mediate the interaction ofthese cells with neutrophils. In some cases the infiltrate progressively changes from one with a preponderance of neutrophils. to one with a preponderance of lymphocytes, indicative of the dynamic nature of the vasculitic process and supporting the hypothesis

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Free conununicarion FCI 9. Phlebolog~~

of participation of a secondary cell-mediated immune response in the late phase of leukocytoclostic CNV, possibly due to the expression of “not self’ antigens (1). We have studied PFA and CFA potential, deposits of immunoglobulins, C3, ond fibrin related antigen, expression of cell membmne antigens, and adhesion molecules (ELAM-1. ICAM-1. LFA-I) in seven patients affected by CNV before (l&15 hrs after the eruption was first noted) and 20 days after 60 mg/day i-m. treatment with the fibrinolytic agent mesoglycans. 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 by direct immunefluorescence showed similar findings before ond after treatment. Immunohistochemistry evidenced a poor perivoscular infiltrate of CD4+, CDla+ and CD36+ cells. ELAM-1 was strongly expressed and ICAM- I and LFA-1 were modemtely expressed. After treatment the infiltrate disappeared in all patients and the adhesion molecules were no longer expressed. These data suggest that reduction of CFA, which causes mossive fibrin deposition, might be involved in the amplification and self-perpetuation of immunologically mediated injury in CNV. The selectine ELAM-I apparently mediates neutrophil migration at inflammatory sites in the early phase of the leukocytoclastic form of CNV. Mesoglycans treatment seems effective in restoring defective CFA, eliminating the infiltrate, and reducing adhesion molecules expression on endothelial cells in patients affected with CNV. References [I] Lotti, T. Comacchi C, Ghersetich I. Cutaneous necrotizing vasculitis. Int J Dermatol 1996; 35 (7): 457474. FClS-6

Retrograde intravenous pressure infusion ’ (RIPI) of urokinase in leg ulcers secondary to chronic venous hypertension (CVI): A study with cutaneous fibrinolytic activity and direct immunofluorescent techniques @IF)

M. Benci, P. Vannucchi’, C. Comacchi, T.M. Lotti. Depr. of Dermatology I, University of Florence; ‘Dept. of Augiology, Santa Maria Nuova Hospital, Flotwrce, Italy RIP1 is a fibrinolytic therapy for deep thrombosis in the lower legs. The technique is based on the infusion of vasooctive drugs (i.e. Urokinose) in a foot vein after placing a sphygmomanometer on the calf with a pressure higher than the arterial district pressure to achieve a high level of fibrinolytic agents in the skin capillaries to dissolve pericapillary fibrin cuffs. Cutaneous fibrinolytic activity (CFA) was evaluated with autohistogmphic technique and perivascular fibrin deposits were investigated using the DIF tecnique before and after RIP1 treatment with 100,000 UI of Urokinose in ten patients affected by leg ulcers secondary to CVI. The results show increased CFA and some change in the pericapillary fibrin cuffs in the periulcerous skin after the RIP1 treatment.

References [I] Lotti T, Fabbri P. Panconesi E. The pathogenesis of venous ulcers. J Am Acad Dermntol. 16: 877-879. 1987 [2] Lotti T, Benci M. Plasminogen activators, venous leg ulcers and reepithelinlization. Int. J Dermntol 34 (IO): 696-699; 1995 [3] Martin M, Heiming T, Fiebnch BJ et al. Angiology 45: 143-148; 1994

LFClS-7 1 Nodular granulomatous lesion on a non-healing ulcer on leg presenting osteomyelitic reaction M. Benci, C. Comacchi, M. Toni’, P. Poggesi’, G. Fen-ant?, T.M. Lotti. Dept. of Dermatology, Univ. of Florence; ‘Dept. of General Mediciue and Cardiology, Univ. of Florence; ’ “1st. Dermoparico dell’ltn~nnmcolata”, (IDI), Rome, Italy Nonhealing ulcers of the lower leg secondary to chronic venous hypertension caused by post-thrombophlebitic syndrome often involve concurrent causes, such as hereditary healing processes, nutritional deficiencies, infections, malignancies, use of corticosteroid drugs, pyoderma gangrenosum. We report the case of an 82-year old patient affected since the age of 40 with chronic venous hypertension secondary to post thromboblebitic syndrome, varicose veins and ulcers on both lower legs, who presented with a 6 month old nodular ulcemted exophytic neoformation on the edge of an ulcer on the left lower leg. at the gaiter area. The lesion, measuring three cm in diameter, was not painful but bled easily. Radiological examination of the limb showed a wide calcified periostenl reaction and seveml osteal spiculae projecting around and into the nodular lesion Histological examination performed after surgical excision of the lesion showed ulcerated skin with exubemnt granulation tissue and intense chronic inflammation infiltrate in the upper and middle dermn. In the deep dermo the infiltrate surrounded fmgments of compact osteal tissue some with internal calcification. This picture indicated osteal tissue sequestrum secondary to an osteomyelitic process. Immunehistochemicol examination showed a weak positivity for the lA4 and MMF 35 MoAbs, complete negativity for desmin and AEI/AE3 cytokemtin MoAbs. This very particular case shows the possibility of osteomyelitic infection with secondary gmnulomntous reaction in the event of a nodular lesion arising on non-healing ulcer accompanied by other clinical symptoms (l-2) References [I] Lotti T. Ulcere degli arti inferiori: Enciclopedin Medico Italiana, Uses Firenze. 1006-1114. 1989 [2] W. T Lawrence, clinical menagment of nonhealing wounds in: Cohen, Diegelmann, lindblad. Wound healing, Saunders camp. Eds. Philadelphia, 1992

FCI 9-6 Vitamin C and healing of leg ulcers J.N. Jnjoo. All Saints Hospital, Lodge Road, Wiuson Green, Birmingham B18 SSD, England Decreased tissue perfusion due to hyperviscosity and lack of supporting tissue due to Vit C deficiency results in tissue damage and may lead to formation of chronic leg ulcers. Mild deficiency of even o. single nutrient is associated with