UVB therapy increases 25(OH) vitamin D syntheses in postmenopausal women with psoriasis

BACKGROUND: Vitamin D3 is produced in the epidermis by ultraviolet (UV) radiation (290-315 nm) of 7-dehydrocholesterol. A similar range of 290-320 nm (broadband UVB) has been successfully used for years to treat psoriasis. The aim of this study was to investigate whether UVB therapy was able to influence vitamin D synthesis in psoriasis patients. METHODS: Twenty-four postmenopausal, white Caucasian women, aged 69 +/- 5.9 (mean +/- SD), with active plaque psoriasis, were treated with broadband UVB two to three times per week for 8-12 weeks. The serum concentrations of calcidiol (25(OH)D3), calcitriol (1,25(OH)2D3), intact parathyroid hormone (PTH), thyroid hormones, osteocalcin, calcium and creatinine were measured before the first and after the last dose of radiation. Bone density was measured using Dual-Energy X-ray Absorptiometry (Hologic Delphi A) at the hip and lumbar spine. RESULTS: Serum levels of 25(OH)D3 increased from 36.8 +/- 17 ng/ml (mean +/- SD) to 59.6 +/- 18.7 ng/ml (P<0.001) after the UVB treatment period. Serum PTH decreased from 62.8 +/- 25.7 ng/l to 48.2 +/- 17.4 ng/l (P<0.001). Secondary hyperparathyroidism (PTH>65 ng/l) was revealed in seven patients (29%) in whom PTH values were suppressed by the UVB therapy. The serum levels of calcitriol, calcium, osteocalcin, thyroid hormones and creatinine were unaltered. CONCLUSION: UVB therapy in elderly psoriatic women improved psoriasis, increased serum 25(OH)D3 synthesis and reduced serum PTH concentrations.     

Topical salicylic acid interferes with UVB therapy for psoriasis.

Salicylic acid has been widely used in the topical treatment of psoriasis. Chemically it is closely related to paraaminobenzoic acid. Following in vitro studies indicating that salicylic acid might exhibit relevant UVB absorption, we found that salicylic acid had a clinically pronounced filter effect when applied prior to UVB exposure. The duration of photoprotection after application was more than 12 h, sometimes exceeding 24 h. In a prospective, randomized, double-blind, left-right comparison study in patients with psoriasis between emollients with and without salicylic acid, salicylic acid was shown to decrease the clearing rate significantly.     

Acitretin plus UVB therapy for psoriasis. Comparisons with placebo plus UVB and acitretin alone.

UVB radiation is beneficial for the treatment of psoriasis vulgaris. Patients with recalcitrant disease, however, are slow to respond to UVB phototherapy with and without the use of coal tars or emollients. Etretinate and, more recently, acitretin have proved useful, but clinical improvement is slow when they are used as monotherapy in plaque psoriasis. Each drug also produces side effects, some of which are dose related. This study was designed to compare results of treatment with UVB combined with either acitretin (50 mg/day) or placebo to determine if psoriasis would respond faster and to less cumulative exposure to UVB and acitretin. The psoriatic disease cleared to a greater degree in patients treated with acitretin-UVB with fewer treatments and smaller amounts of UVB radiation than in patients treated with either placebo-UVB or acitretin alone.     

Narrowband UVB and cream psoralen-UVA combination therapy for plaque-type psoriasis

BACKGROUND: Psoralen-UVA (PUVA) and narrowband UVB (311-nm) therapy are considered to be first-line phototherapies for patients with moderate to severe psoriasis. To reduce side effects as a result of systemic resorption of psoralens, topical PUVA therapies have been developed and proven to be effective in the treatment of psoriasis. OBJECTIVE: We sought to evaluate the combination therapy of narrowband UVB plus cream PUVA on selected psoriatic plaques compared with narrowband UVB or cream PUVA alone. METHODS: A total of 30 patients (Psoriasis Area and Severity Index score of 8-15) were included in the randomized study. The combination therapy consisting of narrowband UVB whole-body irradiation followed by cream PUVA therapy for selected psoriatic plaques was evaluated in 10 patients with chronic plaque-stage psoriasis. For comparison, the therapeutic efficacy, number of treatments, and cumulative UV doses until remission (Psoriasis Area and Severity Index score < 4) of cream PUVA therapy or narrowband UVB alone was determined in 10 patients, respectively. RESULTS: Both monotherapies induced clearance of psoriatic lesions in all patients within 5 to 7 weeks. Mean number of treatments for cream PUVA was 24 +/- 5; for narrowband UVB was 21 +/- 3. The mean cumulative UVA dose was 45.0 +/- 16.3 J/cm(2) and the mean cumulative UVB dose was 17.1 +/- 4.1 J/cm(2). Combination therapy resulted in complete clearance of lesions in all patients after 3 to 4 weeks. Mean number of treatment was 14 +/- 2, mean cumulative UVA dose was 18.7 +/- 4.7 J/cm(2), and mean cumulative UVB dose was 8.2 +/- 3.3 J/cm(2). The number of treatments (P <.001, analysis of variance), UVA dose (P <.001, t test), and UVB dose (P <.001, t test) were significantly reduced compared with both monotherapies. CONCLUSIONS: Our results indicate that a combination therapy of narrowband UVB plus cream PUVA appears to have a significantly higher efficacy compared with either monotherapy. The cumulative UV doses were significantly lower in the combination therapy. We conclude that cream PUVA can be used in addition to narrowband UVB for areas that tend to clear less quickly than the rest of the body.     

Calcipotriol (Dovobet) ointment in combination with UVB therapy for psoriasis treatment

Dovobet is a compounded combination of calcipotriol [also calcipotriene] and betamethasone diproprionate, and is used for psoriasis vulgaris once daily. For this photo case presentation, Dovobet was used once daily in combination with UVB phototherapy 3 times a week. Light therapy was increased by 10% increments at each visit or as tolerated by the patient. Results show the combination of light therapy plus Dovobet may be an effective and convenient option in the treatment of psoriasis.     

DNA repair elicited by UVB during PUVA therapy for psoriasis

Summary The skin of patients receiving psoralen and UVA (PUVA) therapy for psoriasis is exposed to trace amounts of UVB radiation emitted by PUVA irradiators in addition to UVA. DNA repair activity was measured using autoradiography in the uninvolved skin of PUVA-treated patients in order to determine whether 8-methoxypsoralen (8-MOP) plus UVA elicits repair, inhibits the skin repair response to UVB, or protects epidermal-cell DNA from UVB damage by promoting a tan. Epidermal-DNA repair activity was observed in 27 out of 37 patients following the first PUVA treatment. Phototesting with multiples of the initial UV dose elicited a linear increase in repair activity. Glass-filtered radiation failed to stimulate repair, indicating that the reaction was due to UVB, not to 8-MOP plus UVA. The same amount of repair activity was observed in the skin of patients irradiated either before or after 8-MOP ingestion, demonstrating that the drug did not interfere with the response of the skin to UVB. At clearing, however, the repair activity was never greater than that elicited at the initial treatment and was often undetectable despite a tenfold increase in UV exposure. It is proposed that DNA damage should be measured to determine whether epidermal cells are entirely protected from UVB radiation at the completion of therapy.     

Topical calcipotriene in combination with UVB phototherapy for psoriasis

A total of 20 patients with symmetric plaque-type psoriasis were recruited for a controlled, investigator-blinded, right–left study. None of the patients had used any therapy other than emollients for 2 months prior to starting in the trial. All patients had a negative antinuclear antibody. By history, all patients had previously improved upon exposure to sunlight or ultraviolet light. Two symmetrical sites of equal severity were selected as target areas. Each patient was treated on one side with mineral oil twice daily and on the opposite side with calcipotriene 0.005% ointment twice daily. The investigator was blinded as to which site received which topical treatment. Both sides were treated with equal doses of ultraviolet B (UVB) three times weekly in graduated suberythemogenic doses. Ultraviolet B radiation was emitted by a group of 6-ft fluorescent bulbs (Light Sources FS72 T12 UVB HO) in a standard phototherapy unit. The above regimen was continued for a total of 12 weeks. The severity of psoriasis in the target sites was rated by the examiner at baseline and at weekly intervals for the 12 weeks of study. Target sites were rated by severity of erythema, scaling, plaque elevation, and pruritus, with each of these parameters being assigned a score on a four-point scale: 0, clear; 1, mild; 2, moderate; 3, severe. The four scores were added together to arrive at a total severity score for each of the target sites. Statistical analysis was performed using the paired t test, P values less than 0.05 were considered statistically significant. Eleven of the 20 patients (55%) showed a greater decrease in the severity of their psoriasis with UVB plus calcipotriene compared with UVB plus mineral oil. The difference in severity scores between the two groups was statistically significant as early as week 1 (P < 0.05). The difference between the UVB and calcipotriene group versus the UVB and mineral oil group peaked between weeks 3 and 6. The differences then decreased but remained statistically significant through to week 12 (Fig. 1). There were no instances of local cutaneous irritation, but mild photosensitivity occurred symmetrically on both sides in three patients.     

Endocrine factors in pre- and postmenopausal women with hidradenitis suppurativa

The relationship between hidradenitis suppurativa (HS) and hyperandrogenism is largely based on the finding of an increased free androgen index due to a low sex hormone binding globulin (SHBG). As SHBG is now believed to be regulated by factors that influence body weight, and previous studies were not controlled for body weight, we have re-evaluated the androgen status of female patients with HS. We have studied the endocrine status of 66 women with HS. Twenty-three had acne, and 23 were significantly obese (body mass index: BMI >30). There was no relationship between obesity and disease duration. Nineteen of 56 women were hirsute. A premenstrual flare in disease activity was reported by 32 women, but this was not related to menstrual disturbances. No consistent relationship was reported with pregnancy. Eight women with HS were menopausal at presentation, and one developed her disease 6 years after the menopause. Plasma androgens in women with HS were compared with controls matched for BMI and hirsuties. There was no difference between HS and controls. Testosterone and dehydroepiandrosterone sulphate were normal in all subjects with HS. In obese subjects, SHBG was reduced, consistent with BMI-matched controls. We have found no supporting evidence for biochemical hyperandrogenism in women with HS when compared with age-, weight- and hirsuties-matched controls. We report the continuation and primary development of HS in postmenopausal women.     

Risk factors for increased serum creatinine level in patients with psoriasis treated with cyclosporine in a real‐world practice

Nephrotoxicity is a major concern for patients with psoriasis using cyclosporine. Here, we evaluated the impact of intermittent cyclosporine treatment on nephrotoxicity risk among patients with psoriasis in real‐world clinical practice. We retrospectively reviewed 611 patients with psoriasis treated with cyclosporine between January 2013 and January 2017, 398 of whom were considered eligible for analysis. Eighteen (4.5%) patients showed a greater than 25% increase in serum creatinine levels. Age over 60 years (relative risk [RR], 1.6; p = .015), diabetes (RR, 2.3; p < .001), and obesity (RR, 1.7; p = .011) were the significant risk factors of increased serum creatinine levels in patients with psoriasis. There was no significant association of the treatment duration or cumulative dose of cyclosporine with increased serum creatinine levels. In real clinical practice, intermittent cyclosporine use with regular serum creatinine tests can be used to treat psoriasis relatively safely. Age over 60 years, diabetes and obesity are significant risk factors for cyclosporine‐induced nephrotoxicity.     

Potentially modifiable risk factors for adverse pregnancy outcomes in women with psoriasis

Background Data on pregnancy outcomes among women with psoriasis are lacking. However, there are several known comorbidities of psoriasis, including obesity, smoking and depression, each of which increases the risk for negative birth outcomes. Objectives To determine if pregnant women with psoriasis have an excess of potentially modifiable risk factors for adverse pregnancy outcomes. Methods Prospectively collected data from the Organization of Teratology Information Specialists (OTIS) Autoimmune Diseases in Pregnancy Project were analysed to compare the prevalence of selected risk factors between 170 pregnant women with psoriasis and 158 nondiseased controls. Results Women with psoriasis were more likely to be overweight/obese prior to pregnancy (P < 0·0001), to smoke (P < 0·0001), or to have a diagnosis of depression (P = 0·03), and were less likely to have been taking preconceptional vitamin supplements (P = 0·004). After controlling for race/ethnicity and socioeconomic status, women with psoriasis were 2·37 (95% confidence interval 1·45–3·87) times more likely to be overweight/obese as women without psoriasis. Duration of disease, age at onset, measures of disease impact during pregnancy, or use of biologics in pregnancy were not significant predictors of overweight/obesity in the subset of psoriatic women. Conclusions Pregnant women with psoriasis may be at increased risk for adverse pregnancy outcomes due to comorbidities or other health behaviours associated with the disease. These should be taken into consideration during clinical treatment of women with psoriasis who are in their childbearing years.     

The effects of fractional microablative CO2 laser therapy on sexual function in postmenopausal women and women with a history of breast cancer treated with endocrine therapy

Purpose: To examine the outcomes of sexual function in postmenopausal women and women with a history of breast cancer treated with endocrine therapy who were experiencing the symptoms of GSM for which they were treated with fractional microablative CO₂ laser. Materials and Methods: From July 2015 to October 2016, a retrospective chart review of women who underwent fractional microablative CO₂ laser therapy (MonaLisa Touch, DEKA) for GSM was conducted. Several validated questionnaires were used to assess changes in symptoms and sexual function including the Female Sexual Function Index (FSFI), the Wong-Baker Faces Scale (WBFS), and the Female Sexual Distress Scale—Revised (FSDSR). Comparisons of mean symptom scores were described at baseline and six weeks after each treatment. Results: There was a statistically significant improvement in every domain of FSFI, WBFS, and FSDS-R when comparing baseline symptom scores to after treatment three symptom scores for all patients. The secondary outcome was to evaluate the differences, if any, in outcomes of sexual function between postmenopausal women and women with a history of breast cancer treated with endocrine therapy. Both groups had statistically significant improvements in many domains studied. Conclusions: Fractional microablative CO₂ laser therapy (MonaLisa Touch, DEKA) is an effective modality in treating the symptoms of GSM in postmenopausal women and women with a history of breast cancer treated with endocrine therapy.     

Biological therapy in genital psoriasis in women

Genital psoriasis (GenPs) is a frequent manifestation of psoriasis, causing distress, especially in women. We prospectively studied a population of 74 psoriatic women with severe and generalized psoriasis eligible to biologic therapy, to examine which biologic therapy is more effective on GenPs and to study possible associations between PASI severity and GenPs. Overall, 25/74 (34%) had GenPs: 6 received Ixekizumab, 7 Ustekinumab, 8 Adalimumab, 2 Secukinumab, 1 Etanercept, 1 Certolizumab. Therapies were administered based on PASI severity, independently from the presence of GenPs. Side effects, PASI score, sPGA‐G scale for GenPs were recorded at time 0 and after 6 month of therapy. The mean sPGA‐G scale value was 2.8 before treatment. After biologic therapy, all patients except one, improved of at least one point. Mostly, patients treated with anti‐IL17 (Secukinumab, Ixekizumab) and anti‐IL12/23 (Ustekinumab) improved. Mean PASI ranged from 10 to 16.3 before treatment. After 6 months of therapy, 4 anti‐TNFα patients, 6 anti‐IL17 and 1 anti‐IL12/23, reached PASI 90. At time 0, no correlation between PASI and sPGA‐G was visible (Pearson r = 0.10, p = .620). From our data, GenPs apparently responds favorably to IL17A inhibitors, but further studies, based on larger numbers of patients, are needed.     

Risk of Herpes zoster in patients with psoriasis treated with biologic drugs

Background Little is known about the risk of herpes zoster (HZ), among patients with psoriasis treated with biologic drugs. Objective To determine the incidence of HZ in patients with psoriasis and the association between HZ and use of biologic drugs in these patients. Methods The study was performed utilizing the medical database of Clalit Health Services in Israel. The incidence of HZ events was calculated among patients with psoriasis treated with phototherapy, traditional systemic medications and biologic drugs. Incidence rates of HZ events were calculated for each medication, as well as hazard ratios adjusted for age, sex and healthcare utilization burden. Results Among 22 330 psoriasis patients (215 656 person‐years), 1321 HZ cases were diagnosed. The crude incidence rates per 1000 person‐years were 6.0 for UVB phototherapy (95% confidence interval (CI), 0–12.8), 10.1 for PUVΑ (1.3–19.0), 5.4 for acitretin (2.2–8.7), 17.0 for methotrexate (10.6–23.4), 13.9 for etanercept (0.3–27.4), 19.3 for infliximab (0–45.8) and 4.6 for controls (CI, 4.3–5.0). No cases of HZ were seen among patients treated with alefacept, efalizumab or adalimumab. In a multivariate analysis, age, female sex, healthcare utilization pattern and corticosteroid treatment were associated with the time to HZ infection. The association of HZ with infliximab approached statistical significance (Hazard ratio: 1.77, 95% CI: 0.92–3.43), but none of the other biologic drugs were significantly associated with the risk of HZ. Conclusion Among patients with psoriasis, treatment with some biologic drugs was associated with a higher incidence of HZ compared with controls, though the difference was not statistically significant.