1alpha, 25-Dihydroxy-22-oxacalcitriol (maxacalcitol) is a vitamin D3 analogue which displays approximately 10 times greater efficacy at suppressing keratinocyte proliferation in vitro than calcipotriol and tacalcitol. To determine clinical efficacy, a phase II double-blind, randomized, left vs. right, concentration-response study was performed with once-daily topical maxacalcitol in patients with mild to moderate chronic plaque psoriasis. Primary efficacy parameters were psoriasis severity index (PSI) based on sum of scores for erythema, scaling and induration and investigators' overall assessment of patients' response to therapy at 8 weeks of treatment. One hundred and forty-four patients participated. All concentrations of maxacalcitol ointment (6, 12.5, 25 and 50 microg/g) were significantly more effective at reducing PSI than placebo (P < 0.01), with greatest effect noted for maxacalcitol 25 microg/g. Calcipotriol ointment 50 microg/g once daily as active comparator had a similar effect. Marked improvement or clearance of psoriasis was greatest for maxacalcitol 25 microg/g (55% of subjects) which compared favourably with calcipotriol (46%). Improvement continued throughout the study period, with no plateau at week 8. Investigators' and patients' side preference (secondary efficacy parameters) rated maxacalcitol more effective than placebo and 25 microg/g maxacalcitol better than calcipotriol (P < 0.05 for investigators' assessment). Twelve patients withdrew from the study due to adverse events, of which four were judged to be due to study medication. This study indicates that once-daily maxacalcitol ointment is effective in the management of plaque psoriasis, with greatest effect noted at 25 microg/g. As no response plateau was noted at 8 weeks, these data suggest that further benefit might be obtained if maxacalcitol ointment were applied for longer. Finally, investigators' overall assessment and side preference suggest that maxacalcitol 25 microg/g may be more effective than once-daily calcipotriol.
Background and Methods
Cutaneous squamous cell carcinoma (cSCC) is the commonest skin cancer with metastatic potential, however, reported rates of metastasis varies greatly. All cases of primary cSCC on the Isle of Wight between 2005 and 2014 were identified and retrospectively followed for recurrence and/or metastasis. Primary outcome was to identify the rate of metastasis/recurrence from cSCC. Secondary outcomes included associated risk factors for metastasis/recurrence, death from cSCC, and time from diagnosis of primary cSCC to event.
Results
A total of 1122 patients with 1495 tumors were identified within the study period. A total of 18 metastasized and 40 recurred, an overall incidence of 1.2% and 2.7%, respectively. Eight patients died from their disease.
Conclusions
Risk of metastasis from cSCC in the UK general population is likely to be in the order of 1.2%. Where metastasis occurs this is often within 2 years. Recurrence rates are higher following curette and cautery.
Discussion
If treated adequately both recurrence and metastasis from cSCC is a rare event. Not all cSCC cases need follow‐up instead time should be spent educating patients around signs of recurrence/metastasis then discharged, relieving burden on secondary care. Multi‐disciplinary teaming meetings are expensive and should be limited to complex cases.
All patients taking methotrexate for treatment of psoriasis over the past 5 yr have been reviewed. Thirty-eight patients have had pretreatment liver biopsies and at least 1 repeat liver biopsy. Of the 38, nine (24%) have developed significant liver fibrosis or cirrhosis, and have stopped treatment. The high incidence of fibrosis is attributed to synergism between methotrexate and other hepatotoxic factors, particularly alcohol, the use of a baseline biopsy to identify subsequent changes, and the early detection of fibrosis by sensitive histological techniques.
Ninety female patients with acne were allocated randomly to one of three groups and treated either with Diane, a high dose cyproterone acetate (CPA) regime with ethinyloestradiol, or Minovlar. The same dose of oestrogen was common to all three treatment groups. Patients were assessed every 2 months for 6 months, by grading for severity of the acne, lesion counts and photography, and subjectively using a visual analogue scale. In addition, bacteriological sampling and sebum excretion rate (SER) measurements were performed. The results showed a clinical improvement in all three treatment groups, but a more rapid and complete response was seen in those groups who received CPA. There was also a consistent trend suggesting a more favourable response in those in the high dose CPA group. Although there was a marked reduction in SER in the groups treated with CPA, there was no correlation between reduction in SER and clinical improvement in individuals, nor could a reduction in the surface bacterial population be shown to be a primary event in the success of anti-androgen therapy. We have shown that the addition of CPA to oestrogen adds significantly to the therapeutic effect in acne and that anti-androgen and oestrogen combinations are more effective than standard oestrogen and progestagen contraceptive pills.
Seven patients with porphyria cutanea tarda received a total of ten courses of low-dose oral chloroquine therapy (125 mg chloroquine phosphate twice weekly). Patients were treated for a mean 14.9 months during which time all went into clinical and biochemical remission. Relapse occurred in four patients on a total of six occasions after a mean 17 months. In four patients there was no relapse after a mean 47.3 months. There were no adverse side-effects from the treatment. Low-dose oral chloroquine therapy appears to be a safe, effective and convenient treatment for porphyria cutanea tarda, although relapses may occur requiring further therapy.
The effects of four retinoids, all-trans-retinoic acid (RA), 13-cis-retinoic acid (13-cis-RA), aromatic retinoid, and arotinoid ethyl ester ( arotinoid ) were examined on the skin of the rhino mouse. Rhino mouse skin is characterized by the presence of keratin-containing utricles attached to the epidermis, and subcutaneous cysts, both of which are derived from hair follicles. The utricles were examined in horizontal sheets of epidermis, and in vertical histologic sections. After applications of 0.1 ml of 0.1% RA, 0.1% 13-cis-RA, 0.1% aromatic retinoid, or 0.001% arotinoid in acetone to the dorsal skin for 5 days a week for 2 weeks, there was a reduction of utricle diameter to 45%, 52%, 30%, and 31% of acetone-treated controls, respectively. Histologic examination of the epidermis revealed that a dose-dependent hyperplasia and thickening of the epidermis and the stratum granulosum was induced by the retinoids when given at subtoxic doses, being most marked after arotinoid or RA. The thickness of the walls of the utricles also increased with increasing dose of retinoid, paralleling the changes in the epidermis. After doses of 0.1% RA and 0.001% arotinoid , the utricles resembled the hair follicles of hairless mice. Hyperplasia of the epidermis appears to be a primary effect of retinoids or rhino mouse skin. Hyperproliferation of the utricle wall is accompanied by a reduction in the size of the utricle lumen, preceding eventual differentiation of the utricles to normal-looking pilar units.
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