Assessing and Comparing the Effect of Diltiazem Gel Versus Nitroglycerin Ointment in Healing Process of Scleroderma Digital Ulcers.

Introduction:

Systemic sclerosis, also named scleroderma (SSc), is an autoimmune connective tissue disease associated with small vessels vasculopathy and collagen deposition in skin and other internal organs [1, 2]. About 30-60 % of patients with limited and diffused type of scleroderma developed by digital ulcers (DUs) in course of their disease [3]. Depending on the sites of the ulcers, their pathophysiology is differed. The ones on distal parts of the digits are related to ischemic changes based on Raynaud phenomenon, intimal fibroproliferation, and thrombosis; while, the ones on bony prominences are mostly due to microtrauma and following poor vascularization for its healing [4].

These ulcers can affect the quality of life of the patients mostly due to the pain and difficulty in their healing [3]. Accordingly, several therapies have been introduced for improving its healing process. Among them, nitroglycerin ointment was assessed to be an effective topical agent on Raynaud phenomenon; however, there can be found only one study assessing its effect on SSc digital ulcer, which was shown to be non significant [5-7].

Calcium channel blockers (CCB) such as diltiazem are also being used for Raynaud phenomenon in scleroderma patients. Yet, some of their potential side effects such as peripheral edema, hypotension, and headache limit the up titration of these classes of drugs [8]. Moreover, their therapeutic effects on SSc digital ulcers are still being questionable. Only, one clinical trial assessed the effect of nifedipine on ulcer healing, which resulted in non-significant difference compared with placebo[7].

In addition to systemic form of CCBs, topical form of them such as diltiazem gel is also being available. Previous studies introduced this form of diltiazem as a vasodilator, mostly, for treatment of chronic anal fissure [9]. Comparing its effects with topical nitrate for chronic anal fissures showed some controversies. Some studies resulted in no significant difference between them; yet, the study by Ala et al, demonstrated that diltiazem gel has superiority to nitroglycerin ointment [10, 11]. Another survey, in spite of finding non- significant difference between these two agents in treatment of anal fissure, gave priority to diltiazem gel because of headache induced by nitroglycerin ointment [12].