Psoriasis Area Severity Index (PASI) and the Dermatology Life Quality Index (DLQI): the correlation between disease severity and psychological burden in patients treated with biological therapies.

BACKGROUND: Multiple metrics evaluate the efficacy of psoriasis treatment, but interestingly, the correlation between the mostly widely used clinical trial efficacy end point, the physician-rendered Psoriasis Area Severity Index PASI score and, the most widely used quality of life metric, the Dermatology Life Quality Index DLQI, is not always high. OBJECTIVE: To perform a systematic review to determine PASI to DLQI correlation. METHODS: RCTs of biological agents for the treatment of moderate-to-severe psoriasis were reviewed in accordance with PRISMA guidelines. The mean percentage PASI improvement and change in mean DLQI values were recorded and compared for treatment groups from baseline to 10-16 weeks of therapy. RESULTS: A search of the literature yielded 155 sources, of which 13 RCTs met inclusion and exclusion criteria. Percentage of PASI improvement from baseline correlates with DLQI changes with an r(2) value of 0.80 from baseline through weeks 10-16. When grouped by mean percentage reduction in PASI, agents demonstrating >75% mean reduction in PASI demonstrated a mean DLQI improvement over agents that achieved <75%-50% mean reduction in PASI or <50% mean reduction in PASI [minimal clinically important difference (MCID) 3.2]. In addition, a reduction in mean PASI of at least 75%, predicted a mean movement from DLQI band 3 to DLQI band 1, in all nine treatment arms demonstrating such efficacy. CONCLUSIONS: Mean PASI and DLQI correlate predictably in patients with chronic moderate-to-severe plaque psoriasis undergoing treatment with biological agents. A reduction in PASI of at least 75% can translate to significant quality-of-life improvement in patients treated with these therapies.

Cutaneous effects of BRAF inhibitor therapy: a case series.

BACKGROUND: The cutaneous effects of rapidly accelerated fibrosarcoma kinase B (BRAF) inhibitors are not well understood. Squamous cell carcinoma (SCC), keratoacanthoma, and photosensitivity have been described in patients taking BRAF inhibitors. PATIENTS AND METHODS: To characterize the timing and frequency of skin lesions in patients receiving BRAF inhibitor therapy, we utilized a retrospective case review of 53 patients undergoing treatment with BRAF inhibitors for 4-92 weeks of therapy. Patients were evaluated at baseline, and then followed at 4- to 12-week intervals. Charts were retrospectively reviewed, and the morphology and timing of cutaneous events were recorded. RESULTS: Thirty-three of the 53 charts met exclusion/inclusion criteria, 15 were treated with vemurafenib, and 18 were treated with GSK 2118436/GSK 1120212. Of 33 patients treated with BRAF inhibitor, 13 developed photosensitivity (39.4%), 10 developed actinic keratoses (30.3%), 10 developed warts (30.3%), and 6 developed SCC (18.2%). CONCLUSIONS: Multiple cutaneous findings were observed in the 33 patients taking BRAF inhibitors. The previously described association with SCC and photosensitivity was observed in these patients as well. Over half of the observed SCCs were invasive in nature. Photosensitivity continues to be frequent with BRAF inhibitors. Patients taking BRAF inhibitors should have regular full body skin exams. Further studies are necessary to better elucidate the rates of these adverse cutaneous effects.

Mechanics of the carotid artery wall and baroreflex sensitivity after acute ethanol administration in young healthy volunteers.

The effects of ethanol administered orally (300 mg/kg in 250 ml of water) or intravenously (7.5 mg.min(-1).kg(-1) in 250 ml of saline over 40 min) on common carotid haemodynamics, wall mechanics and baroreflex sensitivity were compared with the effects of the intravenous infusion of 250 ml of saline. Ethanol or saline was administered to 10 healthy volunteers after 30 min of supine rest, and measurements were obtained 40 min (median; range 34-46 min) after administration. After ethanol administration, the plasma alcohol level rose from 0 to 0.3+/-0.07 g/l. Mean arterial blood pressure had risen slightly at 20 min, but was normalized by 40 min, the time at which the haemodynamic study was performed. Heart rate decreased after infusion of either saline or alcohol, but was unchanged after oral ethanol administration. Both oral and intravenous ethanol administration were associated with significant decreases in baroreflex sensitivity, carotid shear stress and blood velocity, compared with resting values, while the mean carotid artery diameter was increased, and blood viscosity and mean blood flow were unchanged. No changes were observed in these parameters after saline administration. Ethanol, administered either intravenously or orally, increased the stiffness of the carotid artery and decreased the pulsatility (systo-diastolic changes) of its diameter. A direct, statistically significant correlation was found between the decrease in shear stress and the decrease in baroreflex heart rate control sensitivity after both modes of alcohol administration, while no such correlation was found between the increase in the Peterson elastic modulus and the decrease in carotid diameter pulsatility on the one hand or the decrease in baroreflex sensitivity on the other. In conclusion, reduced shear stress associated with vasodilatation of the carotid artery wall may contribute to the decrease in baroreflex sensitivity observed after acute ethanol administration.