FRI0073 Topical nerve growth factor for the treatment of chronic leg ulcers in rheumatoid arthritis. (1st June 2001) - Generini, S
Abstract : Background: Connective tissue diseases and, in particular, rheumatoid arthritis (RA), may provoke a cutaneous vasculitis leading to skin ulceration very difficult to heal. A depletion of neuropeptides from the nerve endings may contribute to the retardation of wound contraction and healing. 1 Nerve Growth Factor (NGF) is a neurotrophic and immunomodulatory factor that, in the skin, contributes to the control of cutaneous morphogenesis, wound healing and inflammation. 2 Objectives: Evaluate the efficacy of topical NGF administration in the treatment of vasculitic ulcers in course of RA and systemic sclerosis (SSc). Methods: Four long lasting RA patients (3 F, 1 M, age 73 ± 8.7; disease duration 17 ± 6.2 yrs) and 4 SSc patients (4 F, age 58.25 ± 5.5; disease duration 12 ± 4.3), were selected. All patients presented vasculitic chronic leg ulcers showing very poor or absent response to systemic and local treatments. Ulcers were treated daily with 50 μg of NGF (0.01% dissolved in saline solution) for 4 weeks and twice a week in the following month. Before the application of NGF, fibrin or scab were mechanically removed. Eventually the lesion was dressed with a hydrocolloid patch (Duoderm, Convatec, England). Size and characteristics of the ulcers were recorded twice a week. Results: During the first 2 weeks of treatment, the 4 patients with RA showed a rapid improvement of leg ulcers (both in size and descriptive parameters such as pain, presence of granulation, absence of inflammation), followed by a slower but progressive reduction of size which lead, in all cases, to healing within 5/8 weeks. In SSc patients, the ulcers showed an amelioration in size and characteristics during the first 2 weeks but, in the following weeks, the healing stopped and went back to the torpid course that characterised the ulcers before the treatment. None of them achieved the healing after 8 weeks. Conclusion: In RA patients treated with NGF, despiteb the chronicity of the disease and of the ulcers, a rapid healing was achieved. In these cases, NGF was able to restore the progressive cascade of events leading to wound healing, perhaps through its promoting activity on keratinocytes proliferation and vascular neoangiogenesis. 4 Topical application of NGF may represent a powerful pharmacological tool that may reduce and/or overcome the development of vasculitic ulcers. References: Engin C, Demirkan F, Ayhan S, Atabay K, Baran NK. Delayed effect of denervation on wound contraction in rat skin. Plast Reconstr Surg. 1996;98:1063–7 Di Marco E, Marchisio PC, Bondanza S, et al . Growth regulated sysnthesis and secretion of biologically active Nerve Growth Factor by human keratinocytes. J Biol Chem. 1991;266:21718–22 Bocchini G, Angeletti PU. The NErve Growth Factor: purification as a 30.000-molecular weight protein. Proc Natl Acad Sci USA 1980;6:451–64 Wilkinson DI, Theeuwes MJ, Farber EM. Nerve Growth Factor increases the mitogenicity of certain growth factors for cultured human keratinocytes: a comparison with epidermal growth factor. Exp Dermatol. 1994;3:239–45