[Long-term effects of cyclic therapy with iloprost in systemic sclerosis]. / Effetti a lungo termine della terapia ciclica con iloprost nella sclerosi sistemica.

OBJECTIVE: To assess the long-term effects of cyclic infusion of iloprost, a derivative of prostacyclin, on Raynaud's phenomenon-related symptoms and ischemic ulcers in patients with Systemic Sclerosis (SSc). METHODS: A retrospective analysis of prospectively collected parameters in 59 consecutive SSc patients, followed at one institution, who were treated for a median time of 52 months with iloprost for severe Raynaud's phenomenon and ischemic ulcers. RESULTS: Among the 50 patients with ischemic ulcers at the start of therapy, 35 (70%) did not show lesions at the last observation. Despite therapy, four patients underwent amputations (two of forefoot, two of finger distal phalanges). Compared to the pre-treatment point, we observed: decrease of the Raynaud's phenomenon VAS (p<0.001), and, in patients with diffuse cutaneous involvement, of the modified Rodnan skin thickness score (p=0.002). The Health Assessment Questionnaire was not significantly improved. CONCLUSION: Treatment with cyclic iloprost can control Raynaud's phenomenon-related symptoms and ischemic ulcers in the large majority of patients with SSc. However, a disease-modifying effect of this therapy could not be demonstrated.

Disease-modifying effects of long-term cyclic iloprost therapy in systemic sclerosis. A retrospective analysis and comparison with a control group.

OBJECTIVE: To evaluate the role of iloprost, a derivative of prostacyclin, as a possible disease-modifying agent for systemic sclerosis (SSc). METHODS: Fifty-six consecutive SSc patients treated for a median period of 4 years with cyclic infusions of iloprost for severe Raynaud's phenomenon and ischemic ulcers were compared with 56 control patients matched for age, sex, disease subset and duration. Control patients were also similar to the iloprost group with regard to autoantibody status, the presence of major disease-related organ manifestations at baseline, and the use of other treatments. The evolution of lung function test results, the frequency of major disease-specific complications and the survival of the cohorts were the objects of this analysis. RESULTS: No significant difference was observed between the two groups with regard to changes in lung function tests over time, or the number of patients who presented with the onset of active interstitial lung disease, pulmonary arterial hypertension or scleroderma renal crisis. Survival did not differ between the two groups. CONCLUSION: The evolution of lung function test results, the frequency of major disease-specific complications, and survival did not differ significantly between SSc patients treated with cyclic iloprost and a group of patients matched for sex, age, and disease subset and duration. However, no cases of severe pulmonary arterial hypertension were observed in the patients treated with iloprost, suggesting that studies focusing on the possible preventive action of iloprost on the progression of SSc- associated mild pulmonary arterial hypertension would be warranted.

Intravenous cyclophosphamide for interstitial lung disease associated to systemic sclerosis: results with an 18-month long protocol including a maintenance phase.

OBJECTIVE: Cyclophosphamide (CYC) is generally considered the most promising agent available today for systemic sclerosis (SSc)-related interstitial lung disease (ILD). However, the optimal dosage and length of treatment are still undetermined. Our objective was to evaluate the effect of an 18-month long protocol with intravenous (iv) CYC. METHODS: In a single-centre, prospective, observational study, 13 patients with SSc and active alveolitis were given 8 iv pulses in a 6-months period (CYC 750 mg + 6-methylprednisolone 125 mg every three weeks), as an induction therapy. Patients received maintenance therapy with further cycles at 4 (3 pulses), 6 (3 pulses) and 9 weeks (3 pulses) interval. Total CYC dosage was 12.75 g in an 18-month period. End-points were modifications of lung function test (LFT). RESULTS: During the first 6 months of treatment with CYC an increase in Forced Vital Capacity (FVC; p = 0.005) and in diffusion lung capacity for carbon monoxide (DLCO; p = 0.10) was observed; during the maintenance therapy, there was a stabilization in FVC and a mild, non significant decline in DLCO. Treatment was well tolerated. CONCLUSION: iv CYC can induce an initial improvement in LFT (particularly, in FVC) in the first six months, but no further improvement was observed during the maintenance phase.

Systemic sclerosis therapy with iloprost: a prospective observational study of 30 patients treated for a median of 3 years.

Iloprost is useful in the short-term treatment of severe Raynaud's phenomenon and ischaemic ulcers in patients with systemic sclerosis (SSc), but its long-term effects are largely unknown. The aim of this study was to report long-term outcome (median follow-up 36 months) in a prospective observational study of a cohort of 30 consecutive patients with SSc who received iloprost therapy with maintenance infusions every 3 weeks after an initial cycle of 5 consecutive days. At the end of the observation, compared to the pretreatment point, we observed complete healing of digital ulcers in 19/21 patients (90%), a decrease of the Raynaud's phenomenon visual analogue score from 10/10 (25th-75th percentile 7-10) to 5/10 (4-6.75) ( P <0.001) and, in patients with diffuse cutaneous involvement, of the modified Rodnan skin thickness score from 25.5 (16.5-31.5) to 16 (13.5-20) ( P = 0.02), minimal improvement of the Health Assessment Questionnaire from 0.87 (0.68-1.37) to 0.75 (0.62-1.25), which was neither statistically nor clinically significant. The forced vital capacity was not significantly changed, but the diffusion capacity corrected for the alveolar volume decreased from 71% (54-76.7) of the expected value to 62% (51.5-71) ( P = 0.02). In one patient with limited SSc a positive effect on pulmonary hypertension was observed. Six patients, after a median of 25 months of treatment and healing of digital ulcers, discontinued the therapy; after a median of 10 months ulcers did not recur in five of these six. Other reasons for discontinuation were: tolerability (1), disease progression (normotensive renal crisis: 1), and death due to intracranial haemorrhage (1). This same patient had previously suffered a central retinal vein thrombosis. In conclusion, long-term therapy with iloprost in patients with SSc has a durable effectiveness on ischaemic ulcers and Raynaud's phenomenon, but it is not possible to conclude that the natural history of the disease was modified.

[Update on paraneoplastic hypercalcemia. Our experience in the treatment of hypercalcemic states of patients with advanced breast carcinoma]. / Attualità in tema di ipercalcemia paraneoplastica. La nostra esperienza nel trattamento degli stati ipercalcemici delle pazienti con carcinoma mammario avanzato.

The treatment of hypercalcemia of malignancy is troublesome. Personal experience with breast cancer associated hypercalcemia is presented. Eight patients were hydrated with intravenous administration of saline solution containing high doses of salmon calcitonin and subsequently six were treated with antiblastic polychemotherapy. Calcium level fell to normal in all patients. Hypercalcemia, with or without evidence of metastatic bone disease, may be caused by the production of humoral substance by tumoral tissue. In our experience the first therapeutic stage is the infusion of saline solution containing high doses of calcitonin, while the elective treatment is antiblastic polychemotherapy which, acting on tumour growth, may inhibit the release of humoral mediators of hypercalcemia causing a slower but stable reduction in serum calcium level.