Water Extract Influence of Stachytarpheta jamaicensis (L.) Vahl Leaves to Prevent Psoriasis Severity in Animal Model

Psoriasis is an autoimmune disease that is characterized by the appearance of lesions on the skin. The current treatment aims to control the symptoms. The efficacy of Stachytarpheta jamaicensis (L.) Vahl’s for autoimmune rheumatoid arthritis and systemic lupus erythematosus has been tested in animal models. The aim of this research was to evaluate the effect of the water extract of S. jamaicensis leaves on psoriasis model animal (male Balb/c mice) induced topically by imiquimod. The water extract of S. jamaicensis leaves is made by boiling. The animal was divided into groups: normal, control, methotrexate 0.2 mg/kgBW, the extract (doses 25, 50 and 100 mg/kgBW). The measured parameters were the Psoriasis Area and Severity Index (PASI) score and skin histopathology. The results showed that all doses of the extract could reduce the PASI score when compared to the control group. Histological results showed that there was a decrease in keratin growth in test animals that were given the extract. Extracts at doses of 25 and 50 mg/kgBW can reduce the thickening of keratin in the epidermis of the back and ears. It can be concluded that the water extract of S. jamaicensis leaf has the most effective activity to prevent psoriasis recurrence in the dose range of 25 and 50 mg/kgBW.Keywords: Psoriasis, Stachytarpheta jamaicensis leaf water extract, PASI, keratin, imiquimod

HMGB-1 in Psoriasis

Psoriasis is a multifactorial pathology linked to systemic inflammation. Enhanced keratinocytes proliferation and a minor maturation state of the cells are typical features. Perivascular T cells, dendritic cells, macrophages, and neutrophilic granulocytes are part of the scenario completed by apoptosis dysregulation. Several proinflammatory mediators, alarmins and growth factors are increased too, both in the skin and the patients’ blood. HMGB1 is important as an alarmin in several inflammatory conditions. Released after cellular damage, HMGB1 acts as a danger signal. Several studies have considered its role in psoriasis pathogenesis. We evaluated its level in psoriasis and the potential of the alarmin blockade through standard therapies, biological treatments and using monoclonal antibodies. PV patients were shown to have significantly increased levels of HMGB1 both in lesional skin and in serum, which were linked, in some cases, to other pro-inflammatory markers and alarmins. In most cases these parameters were correlated with PASI score. Data demonstrated that blocking HMGB1 is effective in ameliorating psoriasis. Focusing on this approach could be valuable in terms of a therapeutic option for counteracting immune-related diseases in a way unthinkable until few years ago.

Physician-reported Clinical Unmet Needs, Burden and Treatment Patterns of Paediatric Psoriasis Patients: a US and EU Real-world Evidence Study

This study is a retrospective analysis using data collected from the Adelphi Paediatric Psoriasis Disease-Specific Programme cross-sectional survey. Despite being treated for their psoriasis, a substantial proportion of paediatric patients presented with moderate (18.3%) or severe (1.3%) disease at sampling; 42.9% and 92.0% had a body surface area (BSA) of >10%, and 38.8% and 100.0% had a Psoriasis Area Severity Index (PASI) score >10, respectively. Overall, 69.9% of patients had only ever been treated with a topical therapy for their psoriasis. For patients with moderate or severe disease at sampling, 16.3% and 14.4% were currently receiving conventional systemics or biologic therapy, respectively. There is a clinical unmet need in this paediatric population; a considerable percentage of patients still experienced moderate or severe disease and persistent psoriasis symptoms, with numerous body areas affected. A significant proportion of patients were undertreated, which may explain the high burden of disease observed.

Development and In Vitro/In Vivo Evaluation of pH-Sensitive Polymeric Nanoparticles Loaded Hydrogel for the Management of Psoriasis

Methotrexate (MTX), the gold standard against psoriasis, poses severe problems when administered systemically viz increased toxicity, poor solubility and adverse reactions. Hence, a topical formulation of MTX for the management of psoriasis can be an effective approach. The present study aimed to develop an MTX based nanoparticle-loaded chitosan hydrogel for evaluating its potential efficacy in an imiquimod-induced psoriatic mice model. MTX-NPs loaded hydrogel was prepared and optimized using the o/w emulsion solvent evaporation method. Particle size, zeta potential, entrapment efficiency, in vitro drug release, ex vivo permeation, skin irritation and deposition studies were performed. Psoriatic Area and Severity Index (PASI) score/histopathological examinations were conducted to check the antipsoriatic potential of MTX-NPs loaded hydrogel using an imiquimod (IMQ)-induced psoriatic model. Optimized MTX-NPs showed a particle size of 256.4 ± 2.17 nm and encapsulation efficiency of 86 ± 0.03%. MTX-NPs loaded hydrogel displayed a 73 ± 1.21% sustained drug release in 48 h. Ex vivo permeation study showed only 19.95 ± 1.04 µg/cm2 of drug permeated though skin in 24 h, while epidermis retained 81.33% of the drug. A significant decrease in PASI score with improvement to normalcy of mice skin was observed. The developed MTX-NPs hydrogel displayed negligible signs of mild hyperkeratosis and parakeratosis, while histopathological studies showed healing signs of mice skin. So, the MTX-NPs loaded hydrogel can be a promising delivery system against psoriasis.

The Effect of Three-Month Vitamin D Supplementation on the Levels of Homocysteine Metabolism Markers and Inflammatory Cytokines in Sera of Psoriatic Patients

Psoriasis is an autoimmune and inflammatory skin disease. Psoriatic patients express higher levels of plasma homocysteine (Hcy) concentration and pro-inflammatory mediators than healthy people; this is frequently associated with vitamin D deficiency. The aim of this clinical study was to investigate the effects of high doses of vitamin D supplementation on the parameters of Hcy metabolism and cytokines in sera of psoriatic patients. This prospective study was conducted on 40 psoriatic patients who had the vitamin D deficiency. All patients received vitamin D 5000 IU/day for three months. Clinical and biochemical measurements were taken at baseline and at follow up (3 months). The results showed that the severity of clinical features, measured by the psoriasis area severity index (PASI) score, were considerably improved in patients after vitamin D supplementation. After vitamin D supplementation, most of the patients (n = 25 or 62.5%) had mild clinical form (p < 0.001). After twelve weeks of intervention period, there were significant increases in vitamin D and B12 serum levels in comparison to the levels that had been measured at the beginning of the study (56.77 ± 14.66 nmol/L and 301.08 ± 95.02 pg/mL vs. 103.85 ± 32.20 nmol/L and 362.81 ± 118.56 pg/mL, respectively; p < 0.001). Moreover, serum levels of Hcy and folate were significantly lower at the end of the study in comparison with the initial levels (12.45 ± 1.92 µmol/L and 8.01 ± 3.88 mg/mL vs. 10.38 ± 1.66 µmol/L and 6.27 ± 2.60 mg/mL, respectively). High doses of vitamin D supplementation led to a significant decrease in pro-inflammatory cytokines (IFN-ɤ, TNF-α, IL-1β, IL-6, IL-8, and IL-17) and high-sensitivity C-reactive protein (hsCRP), whereas the production of anti-inflammatory cytokines (IL-10, IL-5) was up-regulated. In conclusion, supplementation with high doses of vitamin D could be one of the possible preventive and therapeutic measures to reduce systemic inflammation in psoriatic patients.

Frequency of Dyslipidemia in patients with Psoriasis and Association with Disease Severity

Background: Psoriasis is a recurrent disfiguring skin disease, associated with abnormal lipid metabolism and with high occurrence of cardiovascular complications. This linked to the extent of disease, as it is often seen in those patients who have larger body areas involved with psoriasis. Objective: To estimate frequency of dyslipidemia in psoriatic patients and to determine the frequency of dyslipidemia in psoriatic patients based on the severity of disease. Study Design: Cross-sectional study Place and Duration of Study: Department of Dermatology, Fauji Foundation Hospital Rawalpindi from 1stMarch 2017 to 30th September 2017. Methodology: One hundred and fifty cases were enrolled. All cases were enrolled and 3ml of blood was collected following 12 hrs of fasting for determination of lipid profile. Blood sample was sent to the Hospital laboratory and reports were verified by senior pathologists. Severity of psoriasis was determined according to PASI score. Results: Age of participants was between 18-60 years with mean 38.88±12.26 years and 29 (19.33%) male and 121 (80.67%) female cases. According to severity of disease, 50 (33.3%) cases had mild, 70 (46.7%) had moderate and 30(20%) cases had severe Psoriasis. The mean cholesterol, triglycerides (TG), low density lipoprotein (LDL) and high density lipoprotein (HDL) was 12.91 ± 2.17, 8.93 ± 2.90, 5.0 ± 2.28 and 1.98 ± 0.31 respectively. There were 100(66.7%) cases who had dyslipidemia and 50(33.3%) had normal lipid profile. Conclusion: Frequency of dyslipidemia is very high and is associated with severity of psoriasis. Keywords: Psoriasis, Dyslipidemia, Lipid profile and Cardiovascular disease.

The Effect of Systemic Methotrexate and Cyclosporine Combination Therapy inPsoriasis Vulgaris Patients in Bandung, Indonesia

Background: Methotrexate (MTX) and cyclosporine have been used as effective systemic mono-therapy for psoriasis. Several factors are considered to switch monotherapy to combination therapy because monotherapy is no longer effective and has higher side effects. Hence,clinicians have avoided systemic therapy combinations due to its toxicity. However, some studies showed that this combination therapy could be usedeffectively for psoriasis patients. Purpose: This study aimed to analyze the efficacy and adverse effects of systemic MTX and cyclosporine combination therapy in Indonesian psoriasis vulgaris patients. Methods: The retrospective study assessed the effectiveness of 3 monthsmono-therapyand combination therapy of systemic MTX and cyclosporine in psoriasisvulgaris patients from 2016–2017 in Dermatology Clinic, Dr. Hasan Sadikin Hospital, Bandung, West Java, Indonesia. Result: Psoriasis area and severity index (PASI) score 90 were achieved in the group MTX (50%) and cyclosporine group (50%), while none in the combination group.However, eight patients (50%) in group MTX and cyclosporine reached the primary endpoint of PASI 50. One patient in cyclosporine group had adverse effects on kidney profiles. Nonetheless, other patients had no biochemical changes. But, there was no significant difference in the change of PASI between each group (p=0.102). Conclusion: We propose that combination therapy of MTX and cyclosporine is relatively safe and efficacious in treating Indonesian psoriasis vulgaris patients. This combination treatment isas effective as MTX or cyclosporinemono-therapy.

Study of The Relationship Between Psoriasis of Different Clinical Varieties and Osteoporosis

Background Psoriasis is considered as a systemic disease since it is an inflammatory skin disorder associated with increased level of many inflammatory cytokines, which can result in many comorbidities. It was hypothesized that there is an association between psoriasis and osteoporosis and many studies investigated this association, but the majority of them focused on the association between psoriatic arthritis and osteoporosis, while this study excluded psoriatic arthritis and investigated the association between psoriasis of different clinical varieties and osteoporosis. Objective to assess the associated relationship between psoriasis and osteoporosis in psoriatic patients of different clinical varieties, by measuring the prevalence of osteoporosis in a sample of these patients. Subjects and methods Our cross-sectional study included 42 psoriatic male and female patients with non specific ages, 48% of them were males (20 patients) and 52% of them were females (22 patients), and it excluded any patients with endocrinal disorders, chronic renal failure, liver cell failure, other chronic inflammatory disoredres, malabsorption, history of alcohol misuse, history of intake of steroids for longer than 6 months, pregnant women and psoriatic arthritis. All patients were subjected to a questionnaire for detailed history taking, complete general and dermatological examinations, evaluation of psoriasis severity by Psoriasis Area and Severity Index (PASI) score and bone mineral density (BMD) measurement using the DEXA method of the lumbar spine (L1L4) and femoral neck. Results The prevalence of osteoporosis among psoriatic patients was (9.5%), (10%) in males and (9%) in females, which was lower than the prevalence of osteoporosis in the population. While the prevalence of osteopenia was 50%, (45%) in males and (54.5%) in females, which was higher than the prevalence of osteopenia in the population. Additionally this study showed a statistically significant negative correlation between the age of the patients and BMD, and a highly significant positive correlation between the BMI of the patients and BMD, while there were non significant negative correlations between both (duration of psoriasis and PASI score) and BMD, and no significant correlations between clinical variants of psoriasis and BMD. Conclusion Psoriasis is associated with a decrease in the bone mineral density more in males, with higher incidence of osteopenia rather than osteoporosis. The decrease in BMD increases with increasing age, duration of psoriasis and PASI score, decreases with increasing BMI, while the clinical variants of psoriasis didn’t seem to affect the BMD of psoriatic patients.

Ultrasound in Evaluation of Subclinical Enthesitis of Extensor Digitorum Tendon and Nail Unit Changes in Psoriasis

Background Subclinical inflammation at entheseal level has been detected in patients with psoriasis without previous history of arthropathy or Psoriatic arthritis (PsA). Ultrasound (US) is a valid and sensitive tool for the assessment of inflammatory involvement at entheseal level in PsA patients. Objective To detect subclinical arthritis or enthesitis at distal interphalangeal (DIP) fingers and nail unit changes in psoriatic patient for early detection of PsA Patients and Methods This study included 30 adult psoriatic patients and 30 healthy matched controls. All underwent history, clinical examination, Psoriasis Area and Severity Index (PASI), Nail Psoriasis Severity Index (NAPSI) score calculation and musculoskeletal US both grey and power Doppler (PD) assessed at enthesis of extensor digitorum tendon insertion at distal phalanx, DIP joints from 2nd to 5th finger bilaterally examined for detection of synovitis and over the nail for morpho-structural evaluation. Results Patient’s ages ranged from 18-65 years and controls 20-60 years (mean ±SD 45.07 ± 13.52, 38.37 ± 11.96 respectively), male to female ratio 1:2. DIP joint affection in the form of synovial hypertrophy and effusion with PD was found in 13.3% of cases. Enthesophyte with PD in 56.7% of cases. On comparison between NAPSI score by clinical examination versus US examination, the sensitivity of US was 100%, all cases clinically positive by NAPSI were positively affected by US (20 cases). Also 30% of cases were negative by NAPSI and were positive by US (7cases). Three cases were negative by both NAPSI and US. A significant positive correlation was observed between disease duration and NAPSI Score (r = 0.429, pvalue&lt;0.05), similarly between presence of enthesophyte with PD and PASI Score (r = 0.547, pvalue&lt;0.02). Conclusion Detection of subclinical enthesopathy at DIP joint by ultrasound is not infrequent, so it is an important tool for examining enthesis in psoriatic patients. The presence of a high PASI score and long disease duration could be considered as predictive parameters for the presence of psoriatic enthesitis ongoing to arthritis.

Measurement of Serum Elafin Protein in Psoriasis Vulgaris Patients Before and After Narrowband Ultraviolet (NB-UVB) Therapy

Background Psoriasis is a common immune-mediated disease of the skin, mostly characterized by red, scaly, sharply demarcated, indurated plaques. The immunopathogenesis of psoriasis is not fully understood as it is the result of a complex interaction between genetic, environmental and immunological factors. Furthermore, a large body of evidence has identified a dysregulated interplay between keratinocytes and infiltrating immune cells underlying cutaneous inflammation in psoriasis. Cytokines and other soluble factors such as antimicrobial peptides (AMPs) secreted by resident or infiltrating cells are essential elements in this process of cell-cell communication. Objective To measure serum level of elafin protein using ELISA technique in psoriasis vulgaris patients before and after narrowband ultraviolet therapy and detect its correlation with psoriasis severity. Subjects and Methods Sixty subjects; 30 patients with psoriasis vulgaris and 30 age and sex matched apparent healthy controls were included. Each patient was subjected to a detailed history taking and examination beside calculation of PASI score before and after treatment. Blood samples were also taken from all subjects to assess serum Elafin level by ELISA technique before and after treatment. NB-UVB treatment sessions were given for the patients group three times per week for 3 months. Results There was a highly significant correlation between serum Elafin level and PASI scores among patients with psoriasis before and after treatment, which indicates that serum Elafin level could be used as a diagnostic marker for psoriasis severity and a prognostic marker for different psoriatic treatments. Conclusion In conclusion measurement of serum Elafin protein level could be considered as a diagnostic and prognostic marker for psoriasis activity and a useful tool for evaluating the efficacy of treatment.