Evaluation of cutaneous surface parameters in psoriatic patients.

PURPOSE: The purpose of this study was to compare cutaneous surface parameters in lesional and non-lesional skin of psoriatic patients and in corresponding areas of control subjects. METHODS: Sixty-six psoriatic patients (of any grade of severity, with or without arthritis, without any therapy other than systemic biologic drugs) and 28 healthy controls were enrolled in this observational, case-control study. Exclusion criteria were current or past sebo-psoriasis and seborrheic dermatitis, pustular or erithrodermic psoriasis; treatment with immune-suppressive agents, retinoids, or ultraviolet phototherapy in the last 6 months; topical treatment in the last 2 weeks. Corneometry, sebumetry, and pHmetry were evaluated on non-lesional skin of forehead, cheek, chin and volar region of forearm, and on a psoriatic plaque (on elbow or neighboring areas); in controls, the same areas were considered. RESULTS: Corneometry values were significantly lower in psoriatic plaques vs. elbows of controls. Sebumetry showed significantly higher values in non-lesional forearm skin and plaques of psoriatic patients vs. corresponding areas of controls. pH was significantly lower in all areas in psoriasis. No differences were found between patients treated or not with biologics and with or without arthritis. CONCLUSION: Evaluating surface skin parameters in psoriasis is useful to better understand the etiopathogenic mechanism and could suggest new therapeutic approaches.

Clinical management of critically ill patients with Cushing's disease due to ACTH-secreting pituitary macroadenomas: effectiveness of presurgical treatment with pasireotide.

The management of critically ill Cushing's disease (CD) patients is extremely challenging. Pasireotide is indicated for the treatment of CD patients when pituitary surgery is unfeasible or has not been curative, but no data are available about the use of this drug as pre-operative treatment in critically ill patients. We report the effects of presurgical pasireotide therapy in CD patients in whom hypercortisolism caused life-threatening hypokalemia, alkalosis, and cardio-respiratory complications precluding surgical approach. Clinical, biochemical, and radiological data of two critically ill patients with ACTH-secreting pituitary macroadenoma, before and during first-line presurgical pasireotide treatment (600 µg s.c. bid). During the first 21 days of treatment, pasireotide therapy induced a rapid, partial decrease of plasma ACTH, serum cortisol, and urinary free cortisol levels, with the consequent normalization of serum potassium concentration and arterial blood gases parameters, in both the patients. They did not experience unmanageable side effects and underwent endoscopic transsphenoidal surgery after 4 weeks of effective treatment. Pre-operative MRI evaluation did not show pituitary tumor shrinkage. Surgical cure of CD was obtained in the first patient, while debulking allowed the pharmacological control of hypercortisolism in the second case. We suggest that pasireotide can induce a rapid improvement of clinical and metabolic conditions in critically ill CD patients in whom surgical approach is considered hazardous and need to be delayed.

Consensus on the use of the fixed combination calcipotriol/betamethasone dipropionate in the treatment of plaque psoriasis.

Calcipotriol, a vitamin D analogue, and betamethasone dipropionate, a high potency corticosteroid, are complementary agents for the topical treatment of psoriasis vulgaris. Robust evidence on the efficacy and safety of their fixed combination has been provided by randomized, double-blind, controlled clinical trials involving more than 7000 patients with the ointment formulation in psoriasis of the body and more than 4000 patients with the gel formulation in scalp psoriasis. These trials have shown that the fixed combination ointment is more effective and better tolerated, not only than placebo, but also than calcipotriol and tacalcitol monotherapies. In addition, it has proved, in most instances, to be more effective than betamethasone and at least as well tolerated. The same applies to the gel for scalp and body psoriasis. Safety studies have excluded that repeated courses of treatment with the fixed combination for up to one year produce systemic effects. Studies have also shown that the fixed combination treatment improves quality of life to a significantly greater extent than calcipotriol, with the once daily regimen most appreciated by patients, in both active disease and recurrency. Because of the extensive evidence, American and European guidelines recommend the calcipotriol/betamethasone dipropionate fixed combination as first line topical treatment for mild to moderate plaque psoriasis of the body and scalp.

Double blind clinical trial in a series of 115 patients with seborrheic dermatitis: prevention of relapses using a topical modulator of Toll like receptor 2.

AIM: Seborrheic dermatitis is a chronic inflammatory disease aggravated by Malassezia species. Toll-like receptors (TLR) are part of innate immune system that can be activated by yeasts. Previous studies showed that an association of Umbelliferae extract with a lipid (TLR2-Regul™) decreases the IL-8 expression in human skin in contact with M. furfur. The aim of this study was to assess the activity of a topical formulated with TLR2-Regul™ in the prevention of seborrheic dermatitis (SD) relapses. METHODS: Immune-competent SD adult patients were treated for SD (topical imidazoles or steroids). Cleared patients were randomized and received a topical containing TLR2-Regul™ (A) or its vehicle (B). Erythema, scales and pruritus were assessed during two months. RESULTS: The study included 115 patients, mean age 43.4, sex ratio m/f 1.5. At week 4 the relapse rate was 26% (N.=15) in group A and 43% (N.=25) in group B. At W8 the relapse rate was 21% (N.=12) in group A and 40% (N.=23) (P=0.0309). CONCLUSION: In this series of 115 adults with seborrheic dermatitis, patients treated with a topical containing TLR-Regul™ showed a significantly less relapse rate compared with the excipient group (P<0.05). TLR modulation could represent a new therapeutic approach in the prevention of seborrheic dermatitis relapses.

Abnormalities of hypothalamic-pituitary-thyroid axis in patients with primary empty sella.

Primary empty sella (PES) is a very frequent neuroradiological finding in the general population, that can induce hypopituitarism. Some studies focused on the association of PES with GH deficiency (GHD) or hypogonadotropic hypogonadism (HH), while data regarding the involvement of hypothalamic-pituitary-thyroid (HPT) axis, despite sporadic reports of central hypothyroidism, or the occurrence of hypoadrenalism (HA) are scanty. In this study, thyroid function and TSH response to exogenous TRH injection (TRH/TSH) were investigated in 43 patients [10 men and 33 women; aged (mean +/- SD), 48+/-12 yr] with PES: 22 patients had total and 21 partial PES. Forty healthy subjects (9 men and 31 women; aged 46+/-12 yr) were enrolled as a control group. Central hypothyroidism was found only in 2/43 cases, whereas one patient showed primary hypothyroidism. In euthyroid patients, mean serum TSH levels were significantly lower than controls (TSH: 1.0+/-0.7 vs 1.4+/-0.6 mU/l, p<0.01) and 79% of them showed abnormal TRH/TSH responses (TRH test was performed in 34 euthyroid patients: 17 cases with total and 17 cases with partial PES), but mean serum free T4 (FT4) and free T3 (FT3) values were not significantly lower than controls (FT4: 15.9+/-0.4 vs 15.0+/-2.1 pmol/l, p=NS; FT3: 5.3+/-1.2 vs 5.8+/-1.5 pmol/l, p=NS). Moreover, no significant differences were evident in mean serum TSH, FT4 and FT3 between patients with total and partial PES (TSH: 1.1+/-0.7 vs 0.9+/-0.8 mU/l, p=NS; FT4: 16.3+/-2.6 vs 15.7+/-2.2 pmol/l, p=NS; FT3: 5.4+/-1.3 vs 5.2+/-0.8 pmol/l, p=NS) and the TRH/TSH peak was impaired or exaggerated/delayed in 9 and 3 patients with total and in 12 and 3 cases with partial PES. No significant differences in the prevalence of abnormal TRH/TSH responsiveness were found between patients with partial or total PES (chi2=1.6, p=NS). Other impairment of pituitary function was detected in 23/43 patients: GHD was present in 15 cases, HH in 11 and central HA in 5 patients. Isolated or combined hypopituitarism was present in 17 and in 6 patients, respectively. In conclusion, pituitary dysfunction is very frequent in patients with PES, but central hypothyroidism occurs rarely. The entity of arachnoid herniation into the sellar fossa does not play a significant role on the degree of HPT axis dysfunction.

Abnormal responses to vasoactive intestinal peptide and corticotropin releasing hormone during the spontaneous remission of Cushing's disease.

Abnormalities in hypothalamic-pituitary adrenal axis function were demonstrated by measuring plasma adrenocorticotropin abnormal concentrations following Vasoactive Intestinal Peptide (VIP) and Corticotropin Releasing Hormone (CRH) administration during a phase of remission of Cushing's disease in a 45-year-old female patient. When observed 80 days after the first examination, the patient no longer showed cushingoid features and serum cortisol and plasma ACTH were not abnormally high. VIP infusion (75 micrograms during 12 min) induced a significant increase in serum cortisol and ACTH plasma levels with respect to the normal unresponsiveness. Exaggerated plasma ACTH response to CRH (50 micrograms iv) was also observed. We conclude that the study of ACTH and cortisol response to VIP and CRH may be useful in revealing Cushing's disease even during a remission phase of the disorder.