Topical 0.25% methotrexate gel in a hydrogel base for palmoplantar psoriasis

Palmoplantar psoriasis (PPP) is a chronic, disfiguring condition, and its management is difficult. The systemic side effects of methotrexate can be avoided if it is effective topically. We studied the efficacy and safety of a recently marketed topical methotrexate (0.25%) preparation in a hydrogel base in patients with palmoplantar lesions. A total of 14 adult patients diagnosed clinically as plaque type of palmoplantar psoriasis (>30% of the palm and/or sole areas involved) were included in the study. Topical methotrexate 0.25% in a hydroxygel base was applied twice daily to the lesions for twelve weeks. The lesions were assessed for degree of erythema, scaling, induration and fissuring (ESIF) and were scored on a severity score of 0-3 (0--clear, 1--mild, 2--moderate, 3--severe) every two weeks. The most severe condition was given 12 points; 0 denoted no disease. The response at the end of the study was graded as minimal if there was up to 25% reduction in the EISF score, mild as 26-50% reduction, moderate improvement as 51-75% reduction in score, and marked improvement as >75% reduction in score. The average age of the 11 male and female patients was 41.5 years (18-57 years) with the duration of the disease varying from 2 months to 15 years. Ten patients had both palmar and plantar lesions; two each had only palmar lesions or plantar lesions. The ESI score at baseline was 5.8 +/- 0.9 for the palms and 6.8 +/- 0.5 for the soles. The scores at the end of the study were 3.5 +/- 0.7 for palms and 4.8 +/- 0.2 for the soles. The average time taken for improvement was at least six weeks. None of the patients had complete clearance of lesions. The drug was well tolerated by all patients. Methotrexate 0.25% in a hydrophilic gel is well tolerated but is not very effective in controlling the lesions of psoriasis on the palms and soles. A higher concentration in a different base with better penetration could possibly provide better results.     

Moderate to severe psoriasis: from topical to biological treatment

Introduction  The simple use of topical corticosteroids in the treatment of severe psoriasis is often inefficient and harmful. The first line of treatment in these cases is based on systemic therapies such as methotrexate, cyclosporin and phototherapy. Later on, biological treatments can be used.
Observations  We present three cases of severe psoriasis that have been treated by topical corticosteroids for a long time and with large doses without success and many side-effects. For each one of them, we have introduced either a systemic or a biological treatment with a good efficacy and tolerance.
Discussion  Psoriasis has a strong impact on the quality of life and is comparable to patients with major diseases like cancer or depression. Patients who have severe psoriasis are for the most part disappointed and dissatisfied from their treatment. In fact, the misuse of topical corticosteroids for prolonged periods of time may induce local or systemic side-effects without any improvement. Although patients are more pleased with systemic treatments, their use is often limited because physicians are anxious from the systemic side-effects that may occur.
Conclusion  Systemic treatments are often used too late. Patients are not pleased from the way they are treated. Accordingly, using these treatments earlier may improve patients' quality of life.     

Topical preparations for the treatment of psoriasis: a systematic review

Summary Background There is clinical uncertainty about the appropriate use of first‐line topical treatments for psoriasis. Objectives To assess the relative effectiveness and tolerability of topical treatments for psoriasis suitable for use both in primary and secondary care. Methods All major medical databases of published literature were searched electronically; references of trial reports and recent reviews were searched; authors and companies were contacted for missing data from published reports. The study selection comprised: (1) randomized placebo‐controlled trials of topical treatments for psoriasis; and (2) randomized head‐to‐head studies of the new vitamin D3 derivative treatments for psoriasis that reported clinical outcome using a Total Severity Score (TSS), Psoriasis Area Severity Index or Investigator Assessment of Global Improvement. Eligibility and validity were assessed and data extracted independently by two authors. Clinical outcomes were pooled using a random effect standardized weighted mean difference (SWMD) metric, including 3380 patients randomized in 41 placebo (vehicle)‐controlled trials and 4898 patients randomized in 28 head‐to‐head studies. Results There was a significant benefit in favour of active treatments against vehicle, SWMD: ?1·06 (95% confidence interval [CI]: ?1·26 to ?0·86), approximately a 2‐point improvement on a 12‐point TSS after 6–8 weeks of treatment. The only significantly different benefit was for very potent corticosteroids: SWMD: ?1·51 (95% CI: ?1·76 to ?1·25), approximately a 3‐point improvement on a 12‐point TSS. Head‐to‐head studies support these findings, except that calcipotriol was estimated to be more effective than dithranol, coal tar and other vitamin D₃ derivatives. Polytherapy, using a potent steroid and calcipotriol, was more effective than calcipotriol alone: SWMD 0·42 (95% CI: 0·12–0·72) approximately a 0·8‐point improvement on a 12‐point TSS. No important differences in withdrawal or reporting of adverse events were identified. Conclusions Trials of short duration neither adequately inform the management of chronic disease nor describe the sequelae of treatment. The evidence base for long‐term care, reflecting the disease pathway, should be improved. Combination therapy with topical vitamin D analogues and steroids, and maintenance therapy following treatment response merit further investigation.     

Topical preparations for the treatment of psoriasis: a systematic review

BACKGROUND: There is clinical uncertainty about the appropriate use of first-line topical treatments for psoriasis. OBJECTIVES: To assess the relative effectiveness and tolerability of topical treatments for psoriasis suitable for use both in primary and secondary care. METHODS: All major medical databases of published literature were searched electronically; references of trial reports and recent reviews were searched; authors and companies were contacted for missing data from published reports. The study selection comprised: (1) randomized placebo-controlled trials of topical treatments for psoriasis; and (2) randomized head-to-head studies of the new vitamin D3 derivative treatments for psoriasis that reported clinical outcome using a Total Severity Score (TSS), Psoriasis Area Severity Index or Investigator Assessment of Global Improvement. Eligibility and validity were assessed and data extracted independently by two authors. Clinical outcomes were pooled using a random effect standardized weighted mean difference (SWMD) metric, including 3380 patients randomized in 41 placebo (vehicle)-controlled trials and 4898 patients randomized in 28 head-to-head studies. RESULTS: There was a significant benefit in favour of active treatments against vehicle, SWMD: -1.06 (95% confidence interval [CI]: -1.26 to -0.86), approximately a 2-point improvement on a 12-point TSS after 6-8 weeks of treatment. The only significantly different benefit was for very potent corticosteroids: SWMD: -1.51 (95% CI: -1.76 to -1.25), approximately a 3-point improvement on a 12-point TSS. Head-to-head studies support these findings, except that calcipotriol was estimated to be more effective than dithranol, coal tar and other vitamin D3 derivatives. Polytherapy, using a potent steroid and calcipotriol, was more effective than calcipotriol alone: SWMD 0.42 (95% CI: 0.12-0.72 ) approximately a 0.8-point improvement on a 12-point TSS. No important differences in withdrawal or reporting of adverse events were identified. CONCLUSIONS: Trials of short duration neither adequately inform the management of chronic disease nor describe the sequelae of treatment. The evidence base for long-term care, reflecting the disease pathway, should be improved. Combination therapy with topical vitamin D analogues and steroids, and maintenance therapy following treatment response merit further investigation.     

A novelliposomal formulation of dithranol for psoriasis: preliminary results

We have prepared a novel, aqueous gel-based, liposome-entrapped formulation of dithranol. Herein, we report preliminary observations on its efficacy, tolerability, and cosmetic acceptability in treating stable plaque psoriasis. Nineteen plaques of psoriasis in nine adult patients were treated for six weeks in a prospective, open-label trial. In five patients, there was total clearance of lesions, with more than 50% subsidence in a further two patients. Significantly, there were no reports of lesional or perilesional irritation, and only one patient showed faint brown staining of the skin, which was completely and rapidly reversible. These preliminary results indicate that our liposomal dithranol gel has potential advantages over presently available preparations of dithranol; these may translate into enhanced acceptance of this useful drug by patients and physicians.     

Treatment of psoriasis with topical agents: Recommendations from a Tuscany Consensus

Psoriasis is a chronic and relapsing inflammatory skin disease, clinically characterized by erythematous and scaly plaques. Treatment approach is mainly driven by disease severity, though several factors should be considered in order to identify the optimal therapeutic choice. Mild psoriasis may be treated with a wide array of topical agents including corticosteroids, vitamin D analogs, keratolytics, and calcipotriol/betamethasone propionate compound. Because guidelines may not provide practical indications regarding the therapeutic approach, the use of topical agents in psoriasis is more individually tailored. In order to homogenize the standard of care, at least in a local setting, we collected the real‐life‐based recommendations for the use of topical therapies from an expert panel, the Tuscany Consensus Group on Psoriasis, representing all leading centers for psoriasis established in Tuscany. With this document, this consensus group sought to define principles guiding the selection of therapeutic agents with straightforward recommendations derived from a real‐life setting.     

Topical 5-aminolaevulinic acid photodynamic therapy for intractable palmoplantar psoriasis

Photodynamic therapy (PDT) has been reported to be useful in treating non-melanoma skin cancers and a variety of benign skin conditions including psoriasis. However, only two reports of palmoplantar pustular psoriasis (PPP) treated with PDT have been reported. We treated three intractable cases of PPP with PDT, using 20% 5-aminolaevulinic acid and a 630+/-50 nm light-emitting diode device. The power density was 30 mW/cm2 and the fluence was 15 J/cm2. After treatment, all cases showed mild to marked improvement. Topical PDT may be an alternative therapy in the treatment of PPP, but further study is necessary to confirm the effectiveness of topical PDT in PPP.     

Topical 8-methoxypsoralen increases the efficacy of narrowband ultraviolet B in psoriasis

Background: A combination of oral psoralen with narrowband ultraviolet B (UVB), defined as 'psoralen-narrowband UVB', was shown to have a superior efficacy than UVB alone and even a comparable efficacy to psoralen and ultraviolet A in psoriasis.
Objective: To find out whether topical psoralen-narrowband UVB provides any additional benefit to narrowband UVB alone in psoriasis.
Methods: Nineteen patients with plaque psoriasis were included. Phototherapy was given three times per week. Two symmetrical lesions were selected as target lesions. In the first 12 sessions of phototherapy, the target lesion on one side was treated with 1% 8-methoxypsoralen (MOP) gel 30 min before UVB radiation whereas the target lesion on the other side served as a control. Target lesion scores were assessed at baseline, third, sixth, ninth and 12th sessions. Side effects were recorded.
Results: Sixteen patients completed the study. Target lesion scores decreased significantly on both sides ( P <0.0001). The mean percentage of decreases was greater on the 8-MOP-applied sides compared with the control sides for all assessments, but the difference was statistically significant only at the ninth session (37.7% vs. 58.6%, P =0.043). Pigmentation was frequently seen in 8-MOP gel-applied lesions.
Conclusion: Topical 8-MOP gel plus narrowband UVB has greater efficacy than narrowband UVB alone in psoriasis.     

Topical calcitriol – studies on local tolerance and systemic safety

Calcitriol 3 μg g⁻¹ ointment (Silkis ointment®, Galderma Laboratories) is a new treatment for psoriasis. Calcitriol is the biologically active metabolite of vitamin D₃. It induces keratinocyte differentiation, inhibits keratinocyte, T-cell and fibroblast proliferation, and inhibits the production of some inflammatory mediators, all contributors to the pathogenesis of psoriasis. Preclinical studies have shown an effect of topical calcitriol on calcium homeostasis at doses higher than those in clinical use. No adverse local events were observed when calcitriol was applied to animal skin. Phase I clinical studies confirmed that calcitriol 3 μg g⁻¹ ointment is well tolerated in humans. These studies have demonstrated that at the minimal effective concentration of 3 μg g⁻¹, calcitriol ointment has no discernible photosensitizing or phototoxic potential and no skin irritant or allergic potential in healthy volunteers. Its low systemic absorption through human skin is unlikely to significantly affect calcium homeostasis. This paper summarizes the findings of the preclinical and early clinical studies that provided the foundation of the later Phase II and III clinical trials on efficacy and safety with topical calcitriol 3 μg g⁻¹ ointment for the treatment of plaque psoriasis.     

Topical antibiotics in pregnancy: A review of safety profiles

Medications should be used with caution in women of childbearing age who are pregnant, or are contemplating pregnancy. Although topical medications are considered safer than oral or parenteral agents, their safety data in pregnancy must be assessed carefully. The available information on medication use in pregnancy is limited, and not always aided by the FDA pregnancy letter category system. Thus, in this article, we aggregate human studies, animal studies, and pharmacokinetics data to provide recommendations on utilizing topical antibiotics in pregnancy.     

Topical corticosteroids for atopic eczema: clinical and cost effectiveness of once-daily vs. more frequent use

BACKGROUND: Topical corticosteroids remain the mainstay of treatment for atopic eczema, yet there is uncertainty over the frequency of their use in terms of clinical and cost effectiveness. OBJECTIVES: To assess the clinical and cost effectiveness of once-daily vs. more frequent use of same-potency topical corticosteroids in atopic eczema. METHODS: A systematic review of the clinical and cost-effectiveness literature was undertaken, together with a cost-minimization analysis. RESULTS: The review identified a sparse literature, comprising one previous systematic review and 10 randomized controlled trials (RCTs). No published cost-effectiveness studies were identified. RCTs were focused on potent topical corticosteroids (eight RCTs), with no trials (RCTs/controlled clinical trials) identified on mild potency products. There was broad heterogeneity in trial methods, and therefore we considered outcomes according to: (i) at least a good response or 50% improvement, and (ii) eczema rated as cleared or controlled. Studies found little difference between once-daily and more frequent use of topical corticosteroids. The literature on moderately potent and potent corticosteroids offered no basis for favouring once-daily or more frequent use, although some significant differences favouring twice-daily treatment were identified. One RCT on very potent products favoured three times daily use on the basis of clinical response, but reported no difference in the numbers with at least a good response. Given the similar outcomes seen in clinical effectiveness a cost-minimization approach was adopted to consider cost effectiveness, in order to identify the least-cost option. However, cost-minimization analysis proved complex due to wide variations in product price, with the relative cost of product comparisons by frequency proving the most important factor in determining the least-cost alternative. CONCLUSIONS: This review has not identified any clear differences in outcomes between once-daily and more frequent application of topical corticosteroids. We would encourage prescribing clinicians to consider the once-daily use of topical corticosteroids when making treatment decisions for patients with atopic eczema. However, we find that the literature on clinical effectiveness is limited and a broader understanding of compliance and phobia associated with topical steroids is needed to inform on this issue.     

Keratoses Following Topical Steroid for Psoriasis

A 42-year-old man with generalized psoriasis developed multiple benign keratoses on psoriatic lesions following topical steroid treatment.     

Compounded topical preparations in plaque psoriasis: Still a place for it in 2018?

Compounded topical preparations (CTP) were used to treat psoriasis until the last century and have disappeared from guidelines. The present authors report two severe psoriasis patients who were treated with CTP. A man had psoriasis with a PASI of 23 and a body surface area (BSA) of 43%. He had been using daily for several weeks a CTP including minoxidil, clobetasol propionate and hydroxyprogesterone formulated in an alcohol based vehicle. A woman suffered from psoriasis with an annular inflammatory pattern and a central healing. The PASI was 20 and the BSA was 30%. She had been using a CTP daily for 4 months including resorcinol, salicylic acid, 0.05% tretinoin cream, bethamethasone dipropionate cream. Until the 1970s, the dermatological textbooks recommended to treat severe psoriasis with CTP. Nowadays, CTP are considered outdated because of the large therapeutic armamentarium. The stability and benefit risks of the CTP used here were not documented. The use of CTP in psoriasis should be regulated and must be evidence based. Strict protocol and stability evaluation for preparations must be confirmed prior to compounding.     

Topical corticosteroid therapy for acute radiation dermatitis: a prospective,randomized, double-blind study

BACKGROUND: Radiation dermatitis is a common side-effect of radiation therapy, but there is no current consensus about its appropriate therapy. OBJECTIVES: To compare treatment with topical 0.1% methylprednisolone vs. 0.5% dexpanthenol in a cohort of patients undergoing fractionated radiation therapy for breast cancer. METHODS: In a randomized, double-blind design, treatment was initiated at the beginning of radiation therapy and continued for 2 weeks after termination of radiation. Outcomes were compared by three different measures: clinical (symptom score), functional (transepidermal water loss, TEWL) and subjective (quality of life, QOL). RESULTS: In a preliminary cohort of untreated patients undergoing radiation therapy, clinical signs and TEWL levels increased progressively during radiation therapy, reaching highest values at 5 and 4 weeks, respectively. Although neither topical treatment reduced the incidence of radiation dermatitis, both delayed the emergence of greatest clinical and TEWL scores until approximately 6 and 5 weeks, respectively. With topical corticosteroids, clinical symptoms and TEWL were less pronounced than with dexpanthenol. Whereas general QOL improved after completion of radiation therapy, skin-related QOL declined. However, the skin-related QOL decline could be at least in part reversed by use of topical corticosteroid vs. dexpanthenol-containing emollient. CONCLUSIONS: We provide evidence that prophylactic and ongoing use of topical therapy with either topical corticosteroid or a dexpanthenol-containing emollient ameliorates, but does not prevent radiation dermatitis. Our data suggest, but do not prove, a benefit of a topical corticosteroid vs. a dexpanthenol-containing emollient. Further controlled studies with larger cohorts will be needed to determine optimal forms of topical therapy for radiation dermatitis.     

Topical anthralin for psoriasis vulgaris: evaluation of 70 Japanese patients

In order to determine the usefulness of anthralin in the treatment of psoriasis, we evaluated the effectiveness of topical anthralin therapy in patients with psoriasis vulgaris in our hospital. Seventy patients with plaque-type psoriasis (58 men and 12 women), aged 17-79 years-old (mean; 47.6 years-old), who were treated at the Department of Dermatology, Tokyo Medical and Dental University, between 1992 and 1999, were retrospectively evaluated. Mean psoriasis activity and severity index (PASI) score before therapy was 24.6. Patients were treated with 0.1-2.0% topical anthralin. Responses were determined by clinical examination. The mean PASI score decreased to 8.7 after three months. The most effective anthralin concentration was 0.4-0.5%. The overall response rate was 85.7%, complete remission was obtained in 21.4%, and partial remission in 64.3%. Ten patients (14.3%) were anthralin-resistant. In all patients who entered complete remission, recurrence was noted within six months after stopping anthralin. Minor skin irritation and pigmentation occurred in most of the patients; however, no severe side effects were noted during the treatment. Our study indicated that anthralin is effective for chronic plaque-type psoriasis.     

Topical and intralesional therapies for alopecia areata

Alopecia areata is a common form of nonscarring alopecia. It affects males and females equally and has no racial predilection. It usually affects the scalp, but any hair-bearing area can be involved. It presents as patchy hair loss, loss of hair on the entire scalp (alopecia totalis), or the whole body (alopecia universalis). The histopathology varies according to the disease stage, but usually a perifollicular lymphocytic infiltrate is seen. The course of the disease and response to treatment are unpredictable. Various therapeutic modalities are used including topical, intralesional, and systemic agents, although none are curative or preventive. This article will review the available topical and intralesional agents that are used in the treatment of alopecia areata and suggest a management approach based on the age of the patient and extent of the disease.