Imsidolimab, an anti-interleukin-36 receptor monoclonal antibody, for the treatment of generalized pustular psoriasis: results from the phase II GALLOP trial.

BACKGROUND: Generalized pustular psoriasis (GPP) is a systemic inflammatory disease that can be severe, debilitating and life threatening. Uncontrolled activation of interleukin (IL)-36 proinflammatory activity may underlie the pathogenesis of GPP. Currently, GPP-specific treatment options are limited. OBJECTIVES: To evaluate the efficacy and safety of the anti-IL-36 receptor antibody imsidolimab in patients with GPP. METHODS: In an open-label, single-arm, multiple-dose study, patients with GPP were treated with imsidolimab to assess clinical efficacy, tolerability and safety. Patients received an intravenous dose of imsidolimab 750 mg on day 1, followed by three subcutaneous doses of imsidolimab 100 mg administered on days 29, 57 and 85. The primary efficacy endpoint was the proportion of patients who achieved a clinical response at weeks 4 and 16 following treatment with imsidolimab, as measured by the Clinical Global Impression scale. RESULTS: Eight patients were enrolled and six completed the study. Responses were observed as early as day 3, most rapidly for pustulation relative to other manifestations of GPP, with continued and consistent improvement across multiple efficacy assessments at day 8, day 29 and through day 113. Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity. No patient discontinued the study owing to a nonserious TEAE. Two patients experienced serious adverse events (SAEs); no deaths were reported. CONCLUSIONS: Imsidolimab demonstrated a rapid and sustained resolution of symptoms and pustular eruptions in patients with GPP. It was generally well tolerated, with an acceptable safety profile, and is advancing to phase III trials. These data support the targeting of IL-36 signalling with a specific antibody - imsidolimab - as a therapeutic option for this severely debilitating condition.

Concentrations of selected acute phase proteins in patients with chronic venous insufficiency treated with Sulodexide. Part 1.

Introduction: Chronic venous insufficiency (CVI) is a widespread and serious social problem. The pathogenesis of the disease is multifactorial and one of the important factors in its development is inflammation. Aim: Assessment of the concentration of selected acute phase proteins: C-reactive protein (CRP) and α1 antitrypsin (AAT) in the blood serum of patients with CVI before and after treatment with Sulodexide. Material and methods: The study was carried out in 88 people, including 39 clinically healthy subjects as the reference group and 49 patients with CVI at various stages of the disease. The concentrations of CRP and AAT were determined. Results: The concentration of CRP in patients before the use of Sulodexide, compared to the results in the reference group, was statistically significantly higher. The concentration decreased significantly after the applied treatment. AAT concentration was significantly (p < 0.05) higher in the group of patients compared to the reference group. After treatment with Sulodexide, AAT concentration decreased in all study groups, which was statistically significant compared to the reference group. Conclusions: Elevated levels of acute phase proteins: CRP and AAT in patients indicate the participation of the inflammatory component in the pathogenesis of CVI. Monitoring levels of acute phase protein, especially AAT, may be useful in tracking the course of the disease, the body's response to treatment, and in making prognosis. Sulodexide, which acts mainly as an anticoagulant and profibrinolytic, also has an anti-inflammatory effect, which may contribute to the inhibition of the development of subsequent stages of CVI.

Strategies for coping with stress in mothers of children with atopic dermatitis - a cross-sectional study.

Introduction: Our previous study showed that the severity of atopic dermatitis (AD) in children significantly correlates with the quality of life and perceived stress in their mothers. Aim: To compare strategies for coping with stress in mothers of children with and without AD, as well as to investigate the relationship between coping strategies of mothers of affected children and AD variables, stress intensity, and quality of life. Material and methods: The study included 88 mothers of children with AD and 57 mothers of children without AD as controls. The severity of skin lesions in children with AD was assessed by the Scoring Atopic Dermatitis (SCORAD) index, and skin itch was evaluated by the Numerical Rating Scale (NRS). All mothers completed the sociodemographic questionnaire (SD), the Perceived Stress Scale (PSS), and the Coping Orientations to Problems Experienced (COPE) scale. Additionally, mothers of children with AD filled out the Family Dermatology Life Quality Index (FDLQI). Results: There were no statistically significant differences in coping strategies between the groups. However, there were significant correlations between the selected coping strategies and AD severity, perceived stress of mothers, and quality of life of the entire family of affected children. Conclusions: Although mothers of children with AD experience higher levels of stress compared with mothers of children without AD, the disease does not change coping strategies. Psychological support for mothers of children with AD should be oriented toward strengthening cognitive coping strategies.

Increased serum levels of interleukin-17 in patients with alopecia areata and non-segmental vitiligo.

Introduction: Alopecia areata (AA) and vitiligo are both skin diseases of autoimmune origin. AA is characterized by patchy hair loss primarily on the scalp but may involve other areas as well, while vitiligo is caused by the destruction of melanocytes and results in the appearance of white patches on any part of the body. Many facts indicate similar pathogenesis of these diseases. Both dermatoses are associated with frequent coexistence of other autoimmune diseases and share common genetic risk factors. Recent data support the theory of the involvement of IL-17 in the pathogenesis of both AA and vitiligo. Aim: To evaluate and compare the serum levels of interleukin (IL)-17 in patients with AA and non-segmental vitiligo (NSV). To assess whether the pattern of serum cytokine concentration can be associated with clinical details and activity of the disease. Material and methods: A cross-sectional study was conducted on 33 patients with AA, 30 patients with NSV, and 30 healthy controls. Serum levels of IL-17 were determined quantitatively by ELISA method. Results: Our analysis identified a systemic inflammatory signature associated with AA and NSV, characterized by elevated levels of IL-17. The levels of IL-17 did not differ significantly between AA patients and NSV patients. Conclusions: Our results show that AA and vitiligo may share common etiopathogenetic pathways, which suggests the potential of developing targeted therapies for both AA and vitiligo treatment. Imbalance of T cell subpopulations and complex systemic cytokine profiles may contribute to the pathogenesis of AA and vitiligo.

Tofacitinib for Psoriatic Arthritis in Patients with an Inadequate Response to TNF Inhibitors.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor that is under investigation for the treatment of psoriatic arthritis. We evaluated tofacitinib in patients with active psoriatic arthritis who had previously had an inadequate response to tumor necrosis factor (TNF) inhibitors. METHODS: In this 6-month randomized, placebo-controlled, double-blind, phase 3 trial, we randomly assigned 395 patients, in a 2:2:1:1 ratio, to four regimens: 5 mg of tofacitinib administered orally twice daily (132 patients); 10 mg of tofacitinib twice daily (132 patients); placebo, with a switch to 5 mg of tofacitinib twice daily at 3 months (66 patients); or placebo, with a switch to 10 mg of tofacitinib twice daily at 3 months (65 patients). Data from the patients who received placebo during the first 3 months of the trial were pooled. The primary end points were the percentage of patients who had at least 20% improvement according to the criteria of the American College of Rheumatology (ACR20 response) and the change from baseline score on the Health Assessment Questionnaire-Disability Index (HAQ-DI; scores range from 0 to 3, with higher scores indicating greater disability) at the month 3 analysis. RESULTS: At 3 months, the rates of ACR20 response were 50% with the 5-mg dose of tofacitinib and 47% with the 10-mg dose, as compared with 24% with placebo (P<0.001 for both comparisons); the corresponding mean changes from baseline in HAQ-DI score were -0.39 and -0.35, as compared with -0.14 (P<0.001 for both comparisons). Serious adverse events occurred in 4% of the patients who received the 5-mg dose of tofacitinib continuously and in 6% who received the 10-mg dose continuously. Over the course of 6 months, there were four serious infections, three herpes zoster infections, one myocardial infarction, and one ischemic stroke among the patients who received tofacitinib continuously. Elevations of aspartate and alanine aminotransferase concentrations of three or more times the upper limit of the normal range occurred in more patients who received tofacitinib continuously than in patients who received placebo followed by tofacitinib. CONCLUSIONS: In this trial involving patients with active psoriatic arthritis who had had an inadequate response to TNF inhibitors, tofacitinib was more effective than placebo over 3 months in reducing disease activity. Adverse events were more frequent with tofacitinib than with placebo. (Funded by Pfizer; OPAL Beyond ClinicalTrials.gov number, NCT01882439 .).

Paraoxonase-1 and other factors related to oxidative stress in psoriasis.

INTRODUCTION: Psoriasis is considered as a risk factor for atherosclerosis and contributes to myocardial infarction, ischemic heart disease and brain stroke. AIM: To estimate the atherogenic potential of psoriasis by analysing antioxidative and prooxidative factors (paraoxonase-1, α-tocopherol, uric acid, homocysteine), compare levels of these parameters between groups of psoriatic patients and healthy individuals as well as to analyse the impact of psoriasis severity and duration on the factors under the study and to define correlation between the marked factors and patients' lifestyles, body mass index (BMI) and abdominal circumference. MATERIAL AND METHODS: The investigated group consisted of 66 patients with psoriasis vulgaris, while the control group comprised 30 persons. Both groups were comparable as regards their age, sex and BMI as well as abdominal circumference. RESULTS: A significantly lower activity of paraoxonase-1 (p < 0.001), level of tocopherol (p < 0.05) and significantly higher concentration of homocysteine (p < 0.01), uric acid (p < 0.05) were found in patients with psoriasis as compared to the reference group. A higher homocysteine level occurs in patients with a negative family history of psoriasis (p < 0.05). In the group of patients with psoriasis and metabolic syndrome, the uric acid level was significantly higher (p < 0.05). Concentration of uric acid correlated negatively with the abdominal circumference value (p < 0.001). CONCLUSIONS: Psoriasis promotes arteriosclerosis development by decreasing the levels of antiatherogenic and increasing the levels of proatherogenic agents. Adverse changes in psoriatic patients involve activity of paraoxonase-1, levels of α-tocopherol, uric acid, homocysteine as compared to healthy individuals selected by their age, BMI and abdominal circumference value.

Atopic dermatitis. Interdisciplinary diagnostic and therapeutic recommendations of the Polish Dermatological Society, Polish Society of Allergology, Polish Pediatric Society and Polish Society of Family Medicine. Part I. Prophylaxis, topical treatment and phototherapy.

Atopic dermatitis is a chronic and recurrent inflammatory dermatosis with concomitant intensive pruritus, and is diagnosed both in children and adults. Atopic dermatitis-patients are predisposed to have bacterial, viral and fungal skin infections; they also suffer from an increased risk of developing food allergies (especially, at an infantile age), allergic rhinitis, or bronchial asthma (a so-called atopic march). Currently, an increasing atopic dermatitis incidence constitutes a serious medical problem that regards not only dermatology and allergology, but also paediatrics, and family medicine. The basis for atopic dermatitis treatment and prophylaxis is restoration of epidermal barrier functions by means of tailored emollients. Atopic dermatitis therapies should effectively eliminate clinical symptoms of the disease, prevent exacerbations as well as complications, and improve patients' quality of life.

Atopic dermatitis. Interdisciplinary diagnostic and therapeutic recommendations of the Polish Dermatological Society, Polish Society of Allergology, Polish Pediatric Society and Polish Society of Family Medicine. Part II. Systemic treatment and new therapeutic methods.

The treatment goal in atopic dermatitis is eliminating clinical symptoms of the disease, preventing exacerbations and complications, as well as improving patients' quality of life. In cases of severe atopic dermatitis and lack of response it is recommended to introduce systemic therapy. Patients ofter require multi-specialist consultations, and occasionally hospitalization. It is not recommended to use acupuncture, acupressure, bioresonance, homeopathy, or Chinese herbs in the treatment of atopic dermatitis.

Serum concentrations of selected proinflammatory cytokines in children with alopecia areata.

INTRODUCTION: Alopecia areata (AA) is considered an autoimmune disorder characterized by patchy loss of hair from the scalp and other body parts. Many patients develop the disease in childhood. AIM: To answer the question whether abnormal production of some proinflammatory cytokines (IL-2, IL-6, IL-15, IL-17A and IFNγ) in children with AA may facilitate the development or progression of the disease. MATERIAL AND METHODS: The study group consisted of 42 children with AA, the control group - 37 healthy children. Peripheral venous blood samples were collected from patients with AA and healthy controls and the concentrations of serum cytokines, namely IL-2, IL-6, IL-15, IL-17A, IFN-γ were determined quantitatively by ELISA method. RESULTS: The serum IL-6, IL-15, IL-17A and IFNγ levels were significantly increased in patients with AA compared with control subjects (p < 0.05). The serum IL-15 level was found to be increased when the total duration of AA was increased (q = 0.30; p = 0.05). The serum cytokine level of IL-17A was found to be decreased when duration of the current episode was longer than 2 years (p < 0.05), but the correlation between IL-17A serum level and duration of the current episode was not confirmed in the Spearman test (q = -0.06; p = 0.68). The serum IL-17A level was found to be significantly decreased when the thyroiditis was present (q = -2.378; p < 0.05). CONCLUSIONS: The increased levels of serum IL-6, IL-15, IL-17A and IFNγ in children suggest imbalance in the serum proinflammatory cytokines production in AA.

Lesions on the back of hands and female gender predispose to stigmatization in patients with psoriasis.

BACKGROUND: Psoriasis vulgaris is characterized by disfiguring and stigmatizing skin lesions. The links among lesions distribution, severity, and stigmatization remain unclear. OBJECTIVE: We sought to investigate if the involvement of visible and sensitive areas is linked to stigmatization. METHODS: In all, 115 patients with psoriasis vulgaris were assessed for disease severity, skin lesions distribution, itch, and stigmatization using the Feelings of Stigmatization Questionnaire. Quality of life was assessed with the Dermatology Life Quality Index and the World Health Organization Quality of Life-BREF. RESULTS: The localization of psoriatic lesions on the back of hands was related to higher stigmatization levels (P = .011, total score of the Feelings of Stigmatization Questionnaire), but not the involvement of nails, the palms, the face, or the genital area nor overall disease severity. All patients reported some level of stigmatization, regardless of the localization of lesions and type of psoriasis. Higher levels of stigmatization characterized patients who claimed not to be able to hide their lesions by clothing (P = .025), women (P = .001), and the unemployed (P = .004). Stigmatization was the strongest predictor of quality of life impairment. LIMITATIONS: Only hospitalized patients were included. CONCLUSIONS: Psoriatic lesions on the back of hands are debilitating and warrant effective treatment. Special attention should be paid to female patients, who are more sensitive to stigmatization.

Prevention of Flares in Children with Atopic Dermatitis with Regular Use of an Emollient Containing Glycerol and Paraffin: A Randomized Controlled Study.

BACKGROUND/OBJECTIVES: Emollients are part of the standard treatment for atopic dermatitis (AD), although there is limited evidence that regular use of emollients as management therapy reduces the frequency of flares and corticosteroid consumption. The objective of this study was to evaluate the benefit of emollient use in the management of mild to moderate AD in children by assessing the ability of two different emollients (particularly V0034CR) to prevent flares and to reduce the use of corticosteroids. METHODS: In this randomized, open-label study, patients with a current flare were treated with a potent topical corticosteroid. After flare resolution, patients were centrally randomized to V0034CR emollient, reference emollient, or no emollient (1:1:1 ratio) for 12 weeks. New flares were medically assessed before being treated with a moderately potent corticosteroid. RESULTS: A total of 335 children 2 to 6 years of age were randomized. At 12 weeks, the percentage of patients with one or more flares was statistically significantly lower with V0034CR (35.1%) than without emollient (67.6%; p < 0.001). Fewer patients treated with V0034CR required any corticosteroids or immunosuppressants (23.6%) than patients with no emollient (43.3%) at 12 weeks. The difference was significant at all time points (p = 0.002). Patients treated with emollients had a longer time to first flare, fewer flares, higher complete remission rates, less corticosteroid consumption, lower Investigator Global Assessment scores, and lower Scoring Atopic Dermatitis scores than those who were not. V0034CR was well tolerated, with no specific safety concerns. CONCLUSION: Regular emollient use in children with mild to moderate AD reduces flares and corticosteroid consumption.

Efficacy of Tofacitinib for the Treatment of Moderate-to-Severe Chronic Plaque Psoriasis in Patient Subgroups from Two Randomised Phase 3 Trials.

BACKGROUND: Tofacitinib is a Janus kinase inhibitor being investigated for the treatment of moderate-to-severe plaque psoriasis. We report efficacy of tofacitinib in patient subgroups based on pooled data from two Phase 3 trials (NCT01276639, NCT01309737).
OBJECTIVES: To assess consistency of treatment effects of tofacitinib versus placebo in subgroups defined by baseline characteristics, and to ascertain whether baseline characteristics are of value in optimizing tofacitinib use.
METHODS: Pooled data from the two trials were used to evaluate ≥75% reduction in PASI from baseline (PASI75 response) in subgroups defined by age, age at psoriasis onset, gender, race, geographical region, weight, body mass index, diabetes, metabolic syndrome, tobacco/alcohol use, psoriatic arthritis, disease activity, and prior therapy.
RESULTS: Week 16 PASI75 response rates (N=1843) were 43%, 59% and 9% with tofacitinib 5 and 10mg twice daily (BID) and placebo, respectively (each P<0.0001 versus placebo). Tofacitinib 5 and 10mg BID were effective regardless of baseline characteristics. Across subgroups, tofacitinib generally produced greater response rates with the 10 versus 5mg BID dosage. Lower absolute response rates were seen in heavier patients and patients with prior biologic experience.
CONCLUSIONS: Both tofacitinib dosages demonstrated consistent efficacy versus placebo across subgroups. Lower response rates were seen in heavier patients and those with prior biologic experience. Tofacitinib 10mg BID resulted in a substantial proportion of responders regardless of baseline characteristics.

J Drugs Dermatol. 2016;15(5):568-580.

Presence of selected metabolic syndrome components in patients with psoriasis vulgaris.

INTRODUCTION: Recent studies have suggested a strong association between psoriasis and obesity, dyslipidemia, hypertension, resistance to insulin and metabolic syndrome. AIM: To assess the prevalence of selected metabolic syndrome components in patients with psoriasis and the effect of the abnormalities on the disease activity. MATERIAL AND METHODS: Two hundred and forty-six patients diagnosed with psoriasis and 75 healthy individuals as controls were included in the study. Psoriasis activity was evaluated by the Psoriasis Area and Severity Index (PASI). RESULTS: There was a statistically significant difference in triglyceride concentration between psoriasis patients and controls (p = 0.00001), which was not found for high-density lipoprotein (HDL) concentration. Mean values of serum glucose level in patients with psoriasis were significantly higher than in controls (p = 0.046). Further statistical analysis of the obtained results showed significantly higher systolic blood pressure in the psoriasis patients than in the controls (p = 0.0001), but there was no statistically significant difference in diastolic blood pressure between the investigated groups (p > 0.05). CONCLUSIONS: Higher prevalence of metabolic syndrome components was observed in patients with psoriasis than in the general population.

The effect of clary sage oil on staphylococci responsible for wound infections.

INTRODUCTION: The spreading of bacterial antibiotic resistance among clinical strains of pathogenic bacteria has made investigators to search for other active antibacterial agents which could provide a valuable complement to the existing therapies. AIM: To determine the antibacterial activity of clary sage oil (Salvia sclarea L.) against Staphylococcus clinical strains which were isolated from patients with wound infections. MATERIAL AND METHODS: A comprehensive evaluation of Staphylococcus clinical strain resistance to antibiotics was performed. The constituents of clary sage oil were assayed by GC-FID-MS analysis. The minimal inhibitory concentration (MIC) of the tested essential oil against staphylococci by the micro-dilution broth method was determined. RESULTS: The clary sage oil was active against Staphylococcus aureus, S. epidermidis and S. xylosus with MIC values ranging from 3.75 to 7.00 µl/ml. CONCLUSIONS: The results of the in vitro tests encourage to use formulations containing sage oil as the active natural antimicrobial agent. Because of its antimicrobial properties clary sage oil may be applied to treat wounds and skin infections.

Sturge-Weber syndrome type II treated with PDL 595 nm laser.

Sturge-Weber syndrome (SWS) is rare congenital disorder presenting facial port-wine stains (PWS) eye abnormalities and cerebrovascular malformations. The frequency of SWS is estimated at 1 in 50 000. Cerebrovascular abnormalities can be responsible for seizures, hemiparesis, mental retardation and ophthalmologic abnormalities cause intraocular pressure, glaucoma. Etiopathogenesis of SWS remains elusive. We present a case of a 7-year-old girl with SWS type II. A port-wine stain involves the upper right part of half face and has been associated with glaucoma of both eyes. In the Department of Dermatology in 2009-2012 we performed 23 procedures within 2 months. We have been using PDL laser at wavelength 595 nm and very good cosmetic results were achieved. Given positive treatment effects, the laser therapy of port-wine stains is a method of selection. Port-wine stains in the course of SWS requires a large number of laser treatment.

Role of primary and secondary prevention in atopic dermatitis.

Atopic dermatitis (AD) is a serious epidemiological problem in industrialized countries. The incidence of AD has increased considerably over the last 30 years. Atopic dermatitis is a chronic, recurrent, inflammatory skin disease accompanied by strong itching. It is characterized by typical features depending on age. The parents of children suffering from AD must be prepared to change their lifestyle. They should avoid factors which can promote skin lesions and apply appropriate, regular skin care. The article describes primary prevention of AD as well as prophylactic measures to avoid skin eczema. It presents the role of infections, vaccinations, breastfeeding and the influence of domestic animals, house renovation and moulds on development of AD. The article also describes the significance of the epidermal barrier, skin colonization by microbial agents, pruritus, stress, food and inhalant allergy among people who suffer from AD.

Amorolfine vs. ciclopirox - lacquers for the treatment of onychomycosis.

Amorolfine 5% and ciclopirox 8% nail lacquers are commonly used in topical treatment of onychomycosis. These formulations may be used alone or in combination with oral antifungal agents. Amorolfine and ciclopirox are valuable therapeutic options, however, their usage in monotherapy should be limited. Proper amorolfine and ciclopirox penetration through the nail plate is provided by transungual drug delivery systems. Although amorolfine and ciclopirox have a different mode of action, they both exhibit a broad antifungal activity. The use of antifungal nail lacquers in combination with oral agents, such as terbinafine and itraconazole, improves efficacy of antifungal therapy.

Topical calcineurin inhibitors in dermatology. Part I: Properties, method and effectiveness of drug use.

Topical calcineurin inhibitors (TCI) are a relatively new class of drugs used in dermatology. There are two drug forms available - tacrolimus 0.03% or 0.1% ointment and 1.0% pimecrolimus cream. The drugs act by inhibiting synthesis of proinflammatory cytokines. The only approved indication for using TCI is treatment of atopic dermatitis. The TCI may be used as an alternative therapy to corticosteroids. Tacrolimus is used to treat moderate-to-severe atopic dermatitis, pimecrolimus - mild-to-moderate atopic dermatitis. Topical calcineurin inhibitors do not cause skin atrophy and the drug absorption through the skin is minimal. The TCI have been well-studied, their efficacy was evaluated in a number of vast, long-term studies. The anti-inflammatory potency of tacrolimus ointment is similar to a corticosteroid with moderate activity, while the latter is clearly more active than pimecrolimus cream. Topical calcineurin inhibitors significantly relieve pruritus in atopic eczema.

A 6-year-old boy with Sulzberger and Garbe dermatosis: a case report and literature review.

Sulzberger-Garbe disease was described in 1937. Not more than a hundred of cases of the disease have been reported in the literature. Despite a quite specific picture, there are no features that could undeniably be attributed to this particular disease entity. Discoid exudative and lichenoid lesions are main lesions in this dermatosis. The disease is associated with severe pruritus. The lesions are located on the trunk and extremities as well as the genitals. Eosinophilia is frequently found in the course of the disease. Sulzberger-Garbe dermatosis has been diagnosed mainly in middle-aged males of Jewish origin but it can occur in both sexes at any age. Good therapeutic response to systemic corticosteroids has been observed. It is still controversial whether the disease should be classified as an independent clinical entity.