A retrospective clinical analysis of pharmacological modalities used for symptomatic relief of Raynaud's phenomenon in children treated in a UK paediatric rheumatology centre.

SIR, Need for pharmacological treatment of RP depends on symptom severity, patient distress and presence of underlying disease. Many treatment modalities, without gold standard, are reported in adults. Paediatric studies are scarce. Calcium channel blockers (nifedipine or amlodipine) are favoured, but response is variable and adverse events occur. Glyceryl trinitrate (GTN) has been used in adults as topical ointment [1, 2] or patches [3], but to date, no studies document paediatric use. We surveyed treatment outcomes of RP within a secondary/tertiary paediatric rheumatology service in North West England. Retrospective case note analysis using a standardized proforma compared amlodipine, nifedipine and GTN patches for efficacy and tolerability in a clinical setting. Treatment was determined by patient/consultant preference. Children were given standard doses of calcium channel blockers, or 5 mg GTN patch (Deponit , UCH Pharma, Brussels, Belgium), cut into quarters, with 1⁄4 patch on each hand (or arm) foot (or leg), increasing to 1⁄2 patch if needed. In resistant cases, intravenous prostacylin (iloprost) was given. Disease severity was graded as mild for occasional winter symptoms; moderate if associated with pain/ frequent symptoms requiring medical treatment; and severe if symptoms were persistent despite preventive/ treatment measures, with or without digital ulceration. Response to treatment was acknowledged by reduction in symptoms. Adverse events were documented. Of 45 patients, 42 had sufficient data at the time of analysis, treated between 2003 and 2008; of 42 patients, 32 (76%) were females. Age at diagnosis ranged from 1 to 17 (mean 12.4, median 14) years. Thirty-two (76%) out of 42 patients had primary RP. Secondary RP occurred in 10/42 (24%), associated with scleroderma (n1⁄4 3), UCTD (n1⁄4 3), juvenile arthritis (n1⁄4 2), SLE (n1⁄4 1) and tuberous sclerosis (n1⁄4 1). Severity and treatment responses to individual therapies and number of patients suffering from adverse events are shown in Table 1. Twelve (70%) of 17 mild patients required no treatment; three (33%) out of nine patients with severe RP and digital ulceration secondary to SSc failed to respond to oral/topical treatment and required intravenous iloprost. Of 42, 10 (23%) patients received sequential treatments. Eight patients took regular disease-modifying drugs, including MTX (n1⁄4 3), AZA (n1⁄4 1), mycophenolate mofetil (n1⁄4 1), HCQ (n1⁄4 5) and etanercept (n1⁄4 1). As in previous literature [4], RP was most common in teenage girls, with primary RP in 76%. Secondary RP tended to be associated with moderate/severe symptoms: 8/25 (32%) compared with 2/17 (12%) patients in the mild group. No pharmacological agent was uniformly efficacious (Tables 1 and 2). Patients who failed to respond to treatment with one vasodilator achieved control with an alternative drug in some cases, but not others (Table 2). GTN patches were effective and well tolerated in over half of the treated patients. Several reports document usefulness of topical GTN in adult patients [1–3, 5]. GTN ointment has been shown to have a beneficial response in patients with primary and secondary RP [1–5]. Sustained-release GTN patches (applied to the chest wall) were used in a randomized, double-blind placebocontrolled cross-over study involving 42 adults [3]. There was significant reduction in frequency and severity of symptoms during GTN treatment in primary RP (n1⁄4 21; P1⁄4 0.013) and SSc (n1⁄4 21; P1⁄4 0.046). Adverse events (mainly headaches) led to treatment withdrawal in eight (19%) patients. Similarly, in the current study, 3/18 (16%) had adverse events (mainly headaches) leading to discontinuation of GTN patches. A comparable percentage of adverse events was seen with nifedipine (25%) and amlodipine (16%). Although a minority of patients were able to achieve control without adverse events on dose reduction, the majority with significant adverse events chose to stop vasodilator therapy or change to an alternative preparation.