J.D. Kirby

Comparison of intravenous infusions of iloprost and oral nifedipine in treatment of Raynaud's phenomenon in patients with systemic sclerosis: a double blind randomised study.

OBJECTIVE--To compare the long term effects of short term intravenous infusions of iloprost with those of oral nifedipine in patients with Raynauds phenomenon associated with systemic sclerosis. DESIGN--Double blind, placebo controlled, randomised group comparison. SETTING--Dermatology outpatient clinic. PATIENTS--Twenty three patients with Raynauds phenomenon associated with well documented systemic sclerosis (American Rheumatism Association criteria) and with typical abnormalities in fingernail folds on capillaroscopy. INTERVENTIONS--Twelve patients were randomised to receive intravenous infusions of iloprost starting at 0.5 ng/kg/min and increased by 0.5 ng/kg/min every 15 minutes to a maximum of 2.0 ng/kg/min for eight hours on three consecutive days with a further single infusion at week 8. Placebo capsules were given concurrently. Eleven patients were randomised to receive nifedipine, starting at 30 mg daily and increased to 60 mg daily after four weeks for another 12 weeks. Infusions of placebo were given in the same manner as the infusions of iloprost. One patient from each group withdrew because of social reasons and three patients receiving nifedipine withdrew because of side effects. END POINT--Reduction in number, duration, and severity of attacks of Raynauds phenomenon, reduction in number of digital lesions, increase in digital blood flow. MEASUREMENTS AND MAIN RESULTS--Measurements were taken at 0, 4, 8, 12, and 16 weeks. Both regimens produced a reduction in the number, duration, and severity of attacks of Raynauds phenomenon. The mean (SE) number of digital lesions was reduced with iloprost (from 3.5 (1.6) to 0.6 (0.3] and with nifedipine (from 4.3 (0.8) to 1.4 (0.5] after 16 weeks. Hand temperature and digital and microcirculatory blood flow were increased with iloprost but not with nifedipine. CONCLUSION--Both iloprost and nifedipine are beneficial in the treatment of Raynauds phenomenon. With nifedipine, however, side effects are common. Short term infusions of iloprost provide longlasting relief of symptoms, and side effects occur only during the infusions and are dose dependent.

Treatment of vasospastic disease with prostaglandin E1.

Prostaglandin E1, a vasodilator and potent inhibitor of platelet aggregation, was administered to 26 patients with severe vasospastic disease of the hands. Patients tolerated infusions well and reported appreciable symptomatic improvement. Five of eight ischaemic ulcers healed in six weeks. Non-invasive studies of blood flow were used to observe haemodynamic changes during and after infusions. The Doppler-derived radial artery pulsatility index fell from 8.8 +/- 0.6 to 4.6 +/0 0.5 (mean +/- SEM), indicating hand vasodilatation. This fall was maintained 24 hours after infusion (5.9 +/- 0.9), but the index had returned to normal values at two weeks. The amplitude of finger pulse volume recordings increased (5.6 +/- 0.7 mm to 23.8 +/- 3.4 mm) and was raised two and six weeks after infusion (13.5 +/- 2.1 mm). Hand temperature measured by infrared radiometry also increased (27.4 +/- 0.7 degrees C to 31.2 +/- 1.2 degrees C). Intensity of digital vasospasm induced by cold water challenge was not objectively affected by prostaglandin E1 despite an increased finger temperature after infusion. Nevertheless, patients reported less frequent and severe attacks. Prostaglandin E1 given by central venous infusion is a safe new vasoactive agent that can produce appreciable symptomatic improvement by increasing digital perfusion, which may last for several weeks after treatment. Further study will define its mode of action and its place in the management of peripheral vascular disease.

Treatment of Raynaud's phenomenon by intravenous infusion of prostacyclin (PGI2)

Twenty five patients with Raynauds phenomenon due to systemic sclerosis were infused with prostacyclin (PGI2). In 88% of the patients there was objective improvement, monitored by thermography or radiometry.

Circulating testosterone, sex hormone binding globulin and prolactin in women with late onset or persistent acne vulgaris

Serum testosterone, sex hormone binding globulin (SHBG) and prolactin were measured in thirty‐eight women with acne which persisted or started after the age of 18 years. One or more of these levels were abnormal in 76% of patients. Increased testosterone or low SHBG were present alone or in combination in 60% of patients. This group was presumed to have a raised level of non‐protein bound, metabolically‐available testosterone. Hyperprolactinaemia, which was present in 45% of patients, may be important in view of the reported association with increased adrenal androgens. The hormonal abnormalities may be causally related to the acne and a greater understanding of them may lead to better treatment.

Prostaglandin E1 infusions for vascular insufficiency in progressive systemic sclerosis.

Twelve patients with systemic sclerosis (SS) and severe Raynauds phenomenon received infusions of prostaglandin E1 (PGE1) at a dose of 6-10 ng/kg/min, with either saline or 5% dextrose, for 72 hours in a single-blind cross-over study. The infusions were administered intravenously by centrally positioned catheters. Infusions were well tolerated with only mild side effects. Following the PGE1 infusion cold tolerance improved and attacks of Raynauds phenomenon were less frequent, less severe, and shorter in duration. This subjective improvement was maintained for several weeks in most patients, and 2 noted healing of ischaemic ulcers. There was no significant change in objective measurements of hand function after either infusion. However, pain measured on a 10 cm visual analogue scale improved 2.19 cm with PGE1 and only 0.91 cm with normal saline (P less than 0.05). Temperature of the fingers and hands recorded by thermography did not change significantly with saline infusions, but did rise during PGE1 infusions (mean rise 2.0 degrees C at 48 hours, p less than 0.001), and was maintained when measured again 2 weeks later (mean rise 1.56 degrees C, p less 0.001). PGE1 may therefore be suitable treatment for Raynauds phenomenon and the vascular insufficiency of systemic sclerosis and other connective tissue diseases.

Steroid-induced atrophy in an animal and human model

A ratchet‐controlled micrometer screw gauge has been used to measure the changes in skin thickness produced by topical corticosteroids.

Androgen status in women with late onset or persistent acne vulgaris

The androgen status of fifty women with persistent or late onset acne vulgaris has been investigated. Abnormalities of serum androgens and sex hormone binding globulin (SHBG) alone or in combination were present in 52% of the patients. Elevated serum testosterone and low SHBG were the commonest abnormalities found (46%). Raised levels of serum dehydroepiandrosterone (DHA) and DHA sulphate were present in 16% and 12% of patients respectively, but elevation of one or other of these androgens was the sole abnormality in only 6% of patients. Serum prolactin was raised in 18% of patients but there was no correlation between prolactin and androgen levels. There was also no correlation between the androgen levels and the severity, distribution or pattern of acne or the presence of hirsuties or irregular periods. The hormonal abnormalities found in this group of patients with acne are similar to those seen in females with the polycystic ovary syndrome and idiopathic hirsuties.

THE INCIDENCE AND OTHER ASPECTS OF FACTITIOUS WEALING (DERMOGRAPHISM)

Summary.— Using an instrument designed to exert known pressures on the skin, an incidence survey of factitious wealing in the general population has been carried out; 2813 subjects have been tested with a pressure of 4900 g/cm2, and the overall incidence was 4·24% (females, 5·2%; males, 4·34%). The incidence did not vary significantly in the different age groups.

Nifedipine in the treatment of Raynaud's phenomenon in patients with systemic sclerosis

A double‐blind, placebo‐controlled, cross‐over trial of nifedipine 10 mg three times daily for 6 weeks, in 10 patients with Raynauds phenomenon secondary to systemic sclerosis, is reported. A significant reduction in the duration of attacks of Raynauds phenomenon was observed. Nifedipine therapy also reduced the number and severity of attacks of Raynauds phenomenon and the development of new digital ulcers, and increased the digital blood flow, but none of these changes was statistically significant. No alteration in red blood cell deformability or leukocyte chemiluminescence was observed during nifedipine treatment.

Prolonged increase in digital blood flow following iloprost infusion in patients with systemic sclerosis.

Thirteen patients with Raynauds phenomenon secondary to systemic sclerosis received three 8-hour infusions of a synthetic prostacyclin analogue (Iloprost) on consecutive days and were followed-up over a period of 10 weeks during the winter of 1985/86. Six weeks after infusion, digital peripheral vascular resistance had fallen (P less than 0.05) and dicrotic notch proportion of pulse amplitude increased (P less than 0.05). Digital blood flow and pulse amplitude (measured by photoplethymography) were also increased but did not reach statistical significance. The trend of improvement in these blood flow parameters was still evident after 10 weeks. The number of cutaneous lesions (digital ulcers, etc) fell from 26 lesions before infusion to only 7 lesions by the end of the study, confirming the subjective improvement reported by the patients.