Raynaud's phenomenon and plasma endothelin: correlations with capillaroscopic patterns in systemic sclerosis.

Objective: We evaluated endothelin (ET)-1 plasma levels and some clinical measures in patients with primary Raynaud's phenomenon (PRP), and in patients with systemic sclerosis (SSc) and secondary RP (SRP), in the latter according to their different nailfold videocapillaroscopy (NVC) patterns of microangiopathy (early, active, and late).

Methods: Ninety-nine patients with SSc, 49 with PRP, and 45 control subjects were studied. NVC was performed in all patients to distinguish the pattern of microvascular damage, and the morphological alterations were scored by a semiquantitative rating scale.

Capillaroscopy.

Capillaroscopy is the most reliable way to distinguish between primary and secondary Raynaud's phenomenon (RP) through identification of an early pattern of systemic sclerosis (SSc). The presence of giant capillaries and microhaemorrhages on nailfold videocapillaroscopy (NVC) is sufficient to identify the scleroderma pattern (early), and an increase in these features and the addition of loss of capillaries (active pattern) is followed by neo-angiogenesis, fibrosis and 'desertification' (late pattern). The sensitivity of the American College of Rheumatology's classification criteria for SSc increases from 67% to 99% with the addition of these specific NVC abnormalities.

Use of glucocorticoids and risk of infections.

Glucocorticoids (GC) exert many complex quantitative and qualitative immunosuppressive effects that induce cellular immunodeficiency and consequently might increase host susceptibility to various viral, bacterial, fungal, and parasitic infections. In chronic immune/inflammatory conditions cortisol is secreted at inadequate levels and GC therapy today is devoted in substituting this hormone in adequate doses (low) to compensate just for this; therefore, the correct timing of GC administration, such as given during the turning-on phase of TNF secretion (night), can be of major importance. Consequently, the use of the lowest possible GC dose, at the night time and even for the shortest possible time, should decrease dramatically the risk of infections.

The contribution of capillaroscopy to the differential diagnosis of connective autoimmune diseases.

Raynaud's phenomenon (RP) is one of the earliest clinical hallmarks of microvascular involvement in several connective autoimmune rheumatic diseases. The direct observation of the microvasculature with nailfold videocapillaroscopy (NVC) is useful for an early diagnosis of connective autoimmune diseases (secondary RP) and differentiation from primary (unsymptomatic) RP. Generally, to detect early pathologic capillaroscopic changes, the following parameters are considered: presence of enlarged and giant capillaries, haemorrhages, disorganization of the vascular array, ramified/bushy capillaries and loss of capillaries.

Good clinical response, remission, and predictors of remission in rheumatoid arthritis patients treated with tumor necrosis factor-alpha blockers: the GISEA study.

Objective: To assess the prevalence of good clinical response and remission in rheumatoid arthritis (RA) patients with longstanding disease treated with anti-tumor necrosis factor-alpha (TNF-alpha) drugs at outpatient clinics.

Methods: Retrospective national study of 14 academic tertiary referral rheumatology medical centers. RA patients with a Disease Activity Score (DAS28) > 3.

Estrogens and autoimmune diseases.

Sex hormones are implicated in the immune response, with estrogens as enhancers at least of the humoral immunity and androgens and progesterone (and glucocorticoids) as natural immune-suppressors . Several physiological, pathological, and therapeutic conditions may change the serum estrogen milieu and/or peripheral conversion rate, including the menstrual cycle, pregnancy, postpartum period, menopause, being elderly, chronic stress, altered circadian rhythms, inflammatory cytokines, and use of corticosteroids, oral contraceptives, and steroid hormonal replacements, inducing altered androgen/estrogen ratios and related effects. In particular, cortisol and melatonin circadian rhythms are altered, at least in rheumatoid arthritis (RA), and partially involve sex hormone circadian synthesis and levels as well.

Glucocorticoid effects on adrenal steroids and cytokine responsiveness in polymyalgia rheumatica and elderly onset rheumatoid arthritis.

Polymyalgia rheumatica (PMR) usually exhibits a good clinical response to glucocorticoid (GC) treatment, but early clinical symptoms may create some difficulties in the differential diagnosis with elderly onset rheumatoid arthritis (EORA), particularly in patients complaining of shoulder and pelvic girdle involvement at onset (PMR-like clinical onset) (EORA/PMR). Since neuroendocrine mechanisms seem to play a pathogenetic role in these clinical conditions, the aim of this study was to evaluate hormone and cytokine responsiveness to GC treatment in these patients. Cortisol (CO), dehydroepiandrosterone sulphate (DHEAS), 17-OH-progesterone (PRG), interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) were evaluated at base line, and 1 month after GC treatment (prednisone 10 mg/day), in 14 PMR, 11 EORA/PMR, and 13 EORA patients (mean age 73 +/- 5 years, +/- SD, mean disease duration 3 +/- 2 months, +/- SD).

Circadian rhythms: glucocorticoids and arthritis.

Circadian rhythms are driven by biological clocks and are endogenous in origin. Therefore, circadian changes in the metabolism or secretion of endogenous glucocorticoids are certainly responsible in part for the time-dependent changes observed in the inflammatory response and arthritis. More recently, melatonin (MLT), another circadian hormone that is the secretory product of the pineal gland, has been found implicated in the time-dependent inflammatory reaction with effects opposite those of cortisol.