G. Fiori¹, A. Magonio¹, A. Del Rosso¹, O. Sacu¹, F. Braschi¹, L. Amanzi¹, R. Goretti¹, M. L. Conforti¹, A. Pignone¹, M. Matucci Cerinic^1
1Department of Medicine and Surgery, Section of Medicine and Rheumatology, University of Florence, Florence, Italy

Background: Raynaud Phenomenon (RP) is an early manifestation of microvessel involvement in Systemic Sclerosis (SSc). Systemic vasodilating drugs, effective on RP, sometimes are not feasible because frequently cause hypotension, but topical drugs of proven efficacy are not available.
Nitroglicerin plasters are efficacious in RP, but frequent adverse effects, such as local allergies, hand oedema, malaise, headache, greatly reduce their use. In small groups of SSc patients, topic application of nitroglicerin creams was efficacious for RP and have overcome these effects (1).

Objectives: To evaluate the efficacy and safety of nitroglicerin cream topical application on RP in SSc in an open label study.
Methods: 22 patients with RP secondary to SSc (age: 55,1 ±14.5 years; 20 women, 2 men; 5 dSSc, 17 lSsc; RP and disease duration 11±5.8 and 7±3.7 years; at capillaroscopy: early pattern in 5 patients, active and late in 10 and 5 patients, respectively) were enrolled. The patients were washed out from vasodilators for 10 days and, during the study, did not assume contemporarily other vasodilating drugs. At enrolment (T0), all patients presented high RP condition score (RCS) (2) [by Numerical Rating Scale (NRS) 0-10] (8.2±0.7) and hand pain RP-related was present in 15/20 patients (6.1±0.3, by NRS 0-10). In each patient, nitroglicerin cream (2% oil/water emulsion) was given daily on the dorsum of hands and fingers bilaterally for 60 days.
The efficacy was assessed by an auto-evaluation form (all items evaluated by NRS 0-10) after the first application (T1) and after 30 (T2) and 60 days (T3) of therapy as follows: RCS score, onset of effect, RP-related hand pain), duration of the effect, local and systemic adverse effects.

Results: Nitroglicerin cream is safe: 1 patient experienced mild nausea and pruritus (resolved in 2 days) and 7 patients headache (in 6/7 cases mild and resolved in 2 days; in 1 case severe and leading to drop out after 10 days of therapy).
RCS and RP-related pain improved significantly from T0 to T1 (p>0.001 in both the items) and the improvement remained stable at T2 and T3 (T>0.05 in respect to T1 in both cases).
The effects, rapid in their onset and long lasting, were maintained all throughout the duration of the study (see table)

Table:

Effects of nitroglicerin on RP in SSc
	T0	T1	T2	T3	P
RCS score	8.2±0.7	2.6±2.5	2.7±2.7	2.5±2.4	<0.01 *
Effect onset (minutes)		24.5±6.9	25.0±7.0	24.1±7.8	>0.05**
Effect duration (hours)		9.6±2.1	10.10±2.5	10.10±2.4	>0.05**
RP-related hand pain (minutes)	6.1±0.9	1.7±1.5	1.7 ± 1.6	1.6±1.5	<0.01*
*P<0.001; T0 vs T1, T2, T3; **P>0.05 for all comparisons

Conclusion: Our data show that nitroglicerin cream is safe, reduces the intensity and the frequency of RP attacks. Effects are rapid and long lasting. Although the results should be confirmed on wider groups of patients, nitroglicerin cream might be considered as an alternative topical therapy for RP.
References: 1) Anderson ME. Rheumatology 2002; 41: 324-8
2) Merkel PA. Arthritis Rheum 2002; 46: 2410-20