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Background: Anthralin is known for its efficacy in treating psoriasis and acne, possessing poor solubility. Addressing these limitations, the present study endeavors to develop a microemulgel formulation of anthralin aimed at enhancing solubility. Method: The solubility study was performed in various solvents. An o/w (oil-in-water) emulsion was formed using the water titration method, which was optimized by statistical experimental design half-run CCD. The final optimized batch was evaluated for physicochemical and in vitro properties Result: The final optimized batch showed a particle size (PS) of 417 nm, −25.2 mV zeta potential (ZP) and pH 5.8, which remained stable upon centrifugation, heating–cooling and freeze–thawing cycle. Furthermore, microemulsion with Carbopol 943 5% w/v was selected as the gel base for the formation of microemulgel characterized by PS, ZP, pH, and viscosity of 230 nm, −50.6 mV, 6.9 and 14,200 cps, respectively, that ensured it a high enough stability. In silico molecular docking between ligand and protein provides the binding energies validating the interaction. Hence, the in silico study was performed for psoriasis and P. acne proteins. An in vitro antibacterial activity study on Propionibacterium revealed a significant efficiency of the formulation and MTT assay using L929 cell line in the presence of the drug-loaded microemulgel indicated an inhibition of growth proving that formulation has anti-psoriatic activity. Conclusions: Combination therapy with Clindamycin might improve efficacy while reducing antibiotic resistance risks.

Psoriasis is associated with metabolic syndrome and cardiovascular disease. Fatty acid-binding proteins (FABP) have been recognized as predictors of these systemic disorders. The aim of this study was to assess correlations between levels of serum heart and adipocyte fatty acid-binding proteins (FABP3, FABP4) and disease severity, indicators of inflammation or metabolic disturbances, and topical treatment in psoriatic patients. Thirty-seven patients with relapse of plaque-type psoriasis and 16 healthy volunteers were recruited. Blood samples were collected before and after 14 days of therapy. Serum FABP concentrations were examined by enzyme-linked immunosorbent assay for correlation with Psoriasis Area and Severity Index (PASI), body mass index (BMI), inflammatory or metabolic parameters, and treatment used. The median FABP4 serum levels were significantly increased ( p  = 0.038) in psoriatic patients, while FABP3 levels did not differ ( p  = 0.47) compared to the controls. No significant correlations were noted between the proteins and PASI, C-reactive protein (CRP), BMI, or levels of glucose or lipids. FABP3 significantly correlated with white blood count ( p  = 0.03) and aspartate aminotransferase ( p  = 0.04). After topical treatment, there was no significant change in serum FABP3 [11.5 (4.9–30.3) vs. 12.9 (3.5–30.3) ng/ml] ( p  = 0.96), whereas FABP4 was decreased [27,286 (20,344–32,257) vs. 23,034 (18,320–29,874) pg/ml] ( p  = 0.12), losing its basal significance. FABP4 may be a marker of psoriasis, and FABP3 may be associated with inflammation or liver disorders in psoriatic patients. FABP do not appear to be useful for determining disease severity or the effectiveness of antipsoriatic treatment.

Contact immunotherapy with diphenylcyclopropenone (DPCP) and anthralin is considered the treatment option for extensive alopecia areata (AA) unresponsive to DPCP immunotherapy alone. Only one study has described the efficacy of combination therapy; therefore, we investigated whether topical DPCP and anthralin can promote hair regrowth in DPCP-non responders. In this retrospective case-series we analyzed the efficacy and side effects of DPCP with anthralin in AA patients who did not respond to several months of treatment with DPCP alone. Thirty-two DPCP-nonresponsive AA patients were treated with DPCP and anthralin for the average of 8.3 ± 3.8 (3–17) months. During the treatment, 40.62% of patients (13 patients out of 32) had terminal hair regrowth. The mean of hair regrowth rate was 41%; it was mainly as partial hair regrowth (˂ 50%) and 27.27% of cases achieved > 50% terminal hair regrowth. Treatment response strongly related to the duration of combination therapy ( p value ˂ 0.001), but we did not find any relation with other demographic characteristics. The first signs of response to treatment were noticed 2–12 months (5.5 ± 3.4) after initiation of combination therapy while there was a positive correlation among the duration of treatment and percentage of hair regrowth ( p  < 0.001). The most common complication was bullae (25%), and the least frequent side effect was generalized pruritus (3.1%). The combination therapy with DPCP and anthralin could be effective to treat DPCP non-responder AA patients. Additionally, the higher treatment response could be achieved by longer treatment duration.

The purpose of this double-blind randomised parallel-group study was to compare the efficacy and safety of short-contact treatment with dithranol ointment (2%) with its combination with calcipotriol ointment (50 microg/g) in 2 groups of in-patients with chronic plaque psoriasis. The patients of the first group (n = 23) topically applied dithranol once daily for 30 min and the vehicle of calcipotriol twice daily. The patients of the second group (n = 23) used a single topical application of dithranol for 30 min daily and additionally applied calcipotriol twice daily. The extent and the severity of psoriasis were assessed by means of psoriasis area and severity index score (PASI score) before the onset of the 6-week therapy and weekly thereafter. The difference between the two groups with regard to the mean PASI score became statistically significant already after the first week of treatment and remained so until the end of the trial. No significant differences were observed between the two groups with respect to the cutaneous adverse events. These findings indicate that the addition of calcipotriol ointment to short-contact dithranol markedly augments the therapeutic efficacy of the latter in chronic plaque psoriasis and impressively accelerates the response of psoriatic plaques to this well-tolerated regimen.

Background: In the vast majority of psoriatic patients, psoriatic lesions are localised on the body as well as on the scalp. Therefore, safety data on the combined use of calcipotriol in lotion and calcipotriol in ointment are needed. Objective: This study investigated the effect of high-dose treatment with a combination of calcipotriol ointment and scalp solution on calcium metabolism, indices of bone turnover and PASI in patients with extensive psoriasis. Methods: Following a 2-week wash-out period, 88 patients were randomised to 4 weeks of treatment with either calcipotriol ointment/scalp solution (80–100 g/week and 30–50 ml/week, respectively; n = 41) or with a dithranol/tar regimen (n = 47). Patients were seen at weeks 1, 2 and 4 during treatment and 1 week following cessation of treatment. Results: No significant differences at the end of treatment were found between the 2 groups with respect to 24-hour urinary excretion of calcium (expressed as calcium/creatinine ratio), phosphate or pyridinoline, serum concentrations of calcium (albumin corrected), creatinine, phosphate, parathyroid hormone, 25-hydroxyvitamin D 3 , 1,25-dihydroxyvitamin D 3 , osteocalcin, alkaline phosphatase (total and bone-specific iso-enzymes) or 1-collagen telopeptide. At the end of treatment, the psoriasis area and severity index had decreased by 57.4% in the calcipotriol group and by 36.1% in the dithranol/tar group (p = 0.004). Investigators’ and patients’ assessments of overall efficacy also favoured treatment with calcipotriol (p < 0.001). Conclusion: The combined use of calcipotriol ointment/scalp solution did not affect the indices of calcium metabolism or bone turnover and was significantly more effective than dithranol/tar in reducing disease severity and extent in patients with extensive psoriasis.

In the search for the ideal dithranol cream preparation for short-contact treatment of psoriasis, we investigated the clinical efficacy, side effects and patient appreciation of two dithranol cream preparations (cream A and B) in a double-blind left-right comparing study. Dithranol was dissolved at preparation in cream A and dispersed in cream B. Cream A is known to have a shelf life of 1 year, while cream B has a much shorter shelf life (several months). Ten patients with chronic plaque-type psoriasis were treated during 7 weeks in a short-contact regimen. The clinical efficacy was monitored by scoring of erythema, induration, scaling and involved area (PASI); skin irritation was scored visually, and patient appreciation was evaluated by means of a multiple-choice questionnaire. Dispersion of dithranol in a cream was associated with less irritation and less discoloration of the skin, and its efficacy was comparable with that of the cream in which the dithranol was dissolved. As the dispersed dithranol formulation is easier to be manufactured, its quality will be less depending on the pharmacist's experience and equipment, and so more reliable. Besides, it will be less expensive to prepare. We advise to use this formulation for short-contact treatment.

Purpose This work probed the topical delivery and skin-staining properties of a novel co-drug, naproxyl-dithranol (Nap-DTH), which comprises anti-inflammatory (naproxen) and anti-proliferative (dithranol) moieties. Method Freshly excised, full-thickness porcine ear skin was dosed with saturated solutions of the compounds. After 24 h, the skin was recovered and used to prepare comparative depth profiles by the tape-stripping technique and to examine the extent of skin staining. Results Depth profiles showed that Nap-DTH led to a 5-fold increase in drug retention in the skin compared to dithranol. The application of Nap-DTH also demonstrated improved stability, resulting in lower levels of dithranol degradation products in the skin. Furthermore, significantly less naproxen from hydrolysed Nap-DTH permeated into the receptor phase compared to naproxen when applied alone (0.08 ± 0.03 nmol cm⁻² and 180 ± 60 nmol cm⁻², respectively). Moreover, the reduced staining of the skin was very apparent for Nap-DTH compared to dithranol. Conclusions Topical delivery of Nap-DTH not only improves the delivery of naproxen and dithranol, but also reduces unwanted effects of the parent moieties, in particular the skin staining, which is a major issue concerning the use of dithranol.

Treatment of psoriasis with dithranol as monotherapy or dithranol in combination with UVB phototherapy is an effective and safe approach for the management of psoriasis. Recently a new formulation of dithranol embedded in crystalline monoglycerides (Micanol) has become available. It was shown that this formulation combines adequate efficacy with low irritation and staining properties. The aim of the present study was to compare and contrast three treatment schedules with respect to clinical efficacy and tolerability: Micanol monotherapy, Micanol in combination with UVB phototherapy and placebo combined with UVB phototherapy. The study design was a partly open, partly double-blind, randomized, left-right comparison. In total 36 patients were included and 24 body halves were available for each of the three treatments. The combination of Micanol with UVB resulted in clearance of lesions in 54% of the patients (body halves). Combination therapies with Micanol and either of the two other therapies were highly effective. However, with the number of patients investigated, a statistically significant difference between the three therapeutic approaches with respect to efficacy could not be shown. The three treatments resulted in a grosso modo comparable clinical improvement. Severe irritation was observed in 8% and staining of the skin in 29% of the patients treated with the combination therapy Micanol/UVB, which is far less compared to the irritation and staining by the conventional short contact approaches. The efficacy and tolerability of Micanol make this active substance an important tool in the management of psoriasis.

We have studied the cutaneous response to ultraviolet radiation, measured objectively as erythema in a sample of 12 body sites on 15 Northern European subjects with multiple doses of ultraviolet B (UVB). Skin pigmentation and the development of photoadaptation in response to five repeated doses of irradiation at three body sites was also measured. We report striking differences of up to 5-fold at different body sites to the same challenge dose (p<0.001) and demonstrate that for this population, site variation is just as important as between-person variation. Skin color at each body site is a strong predictor of response (p<0.001) and that this cannot be attributed to vascular differences, but instead we believe it reflects site-specific variations in melanin pigmentation. We also observed similar but smaller within-person effects for responses to another inflammatory agent, dithranol (p<0.01). Despite this, we did not find evidence for differences in the development of photoadaptation by body site. These results have clear clinical implications for the practice of phototesting prior to commencing phototherapy, for therapeutic failure in sites such as the legs in patients with psoriasis, and perhaps for melanoma body-site distribution.

According to the patients, improvement of efficacy, long-term safety and improvement of compliance are needed. The topical treatment has been innovated during the last decade. Most important are the introduction of two new classes of treatments: topical vitamin D(3) analogues and the retinoid tazarotene. To what extent, however, have we achieved developments which are in line with the needs as expressed by the patients? Improved efficacy has been realized by successful combinations of topical treatments. In particular, the combinations of dithranol, vitamin D(3) and tazarotene with a topical corticosteroid proved to be very effective with a reduced profile of side-effects. The efficacy of vitamin D(3) analogues and tazarotene is such that the efficacy of a potent corticosteroid (betamethasone-17-valerate) is approached; calcipotriol even showed an efficacy which is at least as good as this corticosteroid. The long-term safety of new compounds has been evaluated for at least 12 months in large studies. Remarkably for corticosteroids such information is available for only 12 weeks. However, intermittent applications of a topical corticosteroid in combination with another topical treatment provide an effective and safe long-term control of psoriasis. Compliance is a conditio sine qua non for an effective topical treatment. Important progress has been made to increase compliance. Short-contact dithranol has been popularized as an ambulatory treatment which is a highly effective approach as a care instruction programme. Formulations which are better from a cosmetical point of view have been developed for various topical treatments. Reduction of the frequency of applications proved to be possible for most treatments. Once daily applications for corticosteroids, vitamin D(3) analogues and retinoids have been developed, and intermittent applications, a few times per week, are possible for corticosteroids, which proved to be very effective with a reduced profile of side-effects, and are also developed for dithranol.