STELARA® (ustekinumab) experienced significant improvements in signs and symptoms of Psoriatic Arhtritis, according to new findings presented today from a Janssen Research & Development, LLC, (Janssen)-sponsored investigational study.  Data from the 615-patient Phase 3 trial presented at the European League Against Rheumatism (EULAR) Annual Congress showed patients receiving STELARA 45 mg and 90 mg achieved the primary endpoint of the study, a significant reduction in arthritis signs and symptoms at week 24.  Investigators reported STELARA-treated patients also achieved significant improvements in physical function, including dactylitis and enthesitis (two common manifestations of psoriatic arthritis which cause pain and swelling), as well as in plaque psoriasis.  STELARA is currently being investigated in a Phase 3 program for the treatment of active psoriatic arthritis and is approved for the treatment of moderate to severe plaque psoriasis in 65 countries.  The EULAR press committee has selected the STELARA psoriatic arthritis study findings to be presented during the official EULAR press conference occurring Friday, June 8 from 9:00-9:45 CEST, which will take place in the Press Centre, Hall 6.3 at the congress.   

"Some 15 percent of patients living with psoriasis of the skin will develop psoriatic arthritis.  This is a challenging disease that causes great distress for those afflicted, for which we currently have too few treatment options. These new findings showing the efficacy of STELARA in improving the joint symptoms of the disease are therefore important for rheumatologists and dermatologists," said Iain B. McInnes, Ph.D., Professor, Experimental Medicine and Rheumatology, Director of the Institute of Infection, Immunity, and Inflammation, University of Glasgow, Scotland, and study investigator.  "We look forward to additional data from the Phase 3 psoriatic arthritis clinical development program to allow us to more fully assess the efficacy and safety of STELARA in the treatment of this complex inflammatory disease."

In the Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled trial of Ustekinumab, a Fully Human anti-IL-12/23p40 Monoclonal Antibody, Administered Subcutaneously, in Subjects with Active Psoriatic Arthritis (PSUMMIT I) study, patients with active psoriatic arthritis, despite treatment with disease-modifying antirheumatic drugs (DMARDs) and/or nonsteroidal anti-inflammatory drugs (NSAIDs), were randomized to receive subcutaneous STELARA 45 mg or 90 mg or placebo at weeks 0, 4 and then every 12 weeks.  At week 24 of the trial, 42 percent and 50 percent of patients receiving STELARA 45 mg and 90 mg, respectively, achieved at least a 20 percent improvement in signs and symptoms according to American College of Rheumatology (ACR) criteria (ACR 20), the primary endpoint, compared with 23 percent of patients receiving placebo (P < 0.001).  ACR responses were greater with STELARA than placebo regardless of methotrexate use.  As measured by the ACR response criteria, significantly higher proportion of patients in the STELARA 45 mg and 90 mg groups also achieved approximately 50 percent improvement in signs and symptoms (ACR 50) and approximately 70 percent improvement in signs and symptoms (ACR 70) versus patients receiving placebo (P < 0.001 for all comparisons). 

Study participants receiving STELARA achieved clinically relevant improvements in physical function, as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI) and enthesitis (inflammation of the entheses, the sites where tendons or ligaments attach to bone) and dactylitis (inflammation of the finger or toe) scores.  Changes from baseline in HAQ-DI at week 24 were significantly greater in the STELARA groups, and significantly greater proportions of STELARA-treated patients had a clinically meaningful change from baseline in HAQ-DI (defined as a change of at least 0.3) compared with patients in the placebo group.  Among study participants affected with enthesitis (n=425) or dactylitis (n=286) at baseline, significantly greater improvements in symptoms were observed in patients receiving STELARA 45 mg or 90 mg than in patients receiving placebo based on median percent changes in the enthesitis score (-42.9 and -50.0 versus 0.0, respectively) and the dactylitis score (-75.0 and -70.8 vs. 0.0) [P < 0.001].

"These data provide important new insights into the efficacy of STELARA in the treatment of psoriatic arthritis across multiple disease measures," said Alice B. Gottlieb, M.D., Ph.D., Dermatologist-in-Chief and Chair of Dermatology, Tufts Medical Center, Harvey B. Ansell Professor of Dermatology, Tufts University School of Medicine, and study investigator.  "For physicians who treat patients living with active psoriatic arthritis, the potential of STELARA, an IL-12/23 monoclonal antibody, for the treatment of this chronic, inflammatory disease is a promising development."

PSUMMIT I also assessed the efficacy of STELARA in the treatment of moderate to severe plaque psoriasis.  Of 440 patients with at least three percent body surface involvement at the start of the study, 57 percent of patients receiving STELARA 45 mg and 62 percent of patients receiving STELARA 90 mg achieved at least a 75 percent improvement in psoriasis as measured by the Psoriasis Area Severity Index (PASI 75) score at week 24, compared with 11.0 percent of patients receiving placebo (P < 0.001).

Patients in the STELARA groups also reported statistically significant improvements in EULAR/Disease Activity Score (DAS) 28 C-reactive protein (CRP) responses.  At week 24, 66 percent and 68 percent of patients receiving STELARA 45 mg and 90 mg, respectively, reported EULAR/DAS-CRP response compared with 34 percent of placebo patients (P < 0.001).  The DAS 28 is a measure of disease activity in patients with arthritis that is calculated by assessing the number of tender and swollen joints (out of a total of 28), inflammation and the patient's assessment of global health.  CRP is a type of protein produced in the liver and expressed during episodes of acute inflammation associated with arthritic conditions.

Treatment with STELARA was generally well-tolerated with similar proportions of patients experiencing at least one adverse event (AE) through week 16, the placebo-controlled period, among those receiving STELARA (42 percent) and placebo (42 percent).  Serious AEs were reported in two percent of STELARA-treated patients and two percent of patients receiving placebo.  No malignancies, cases of tuberculosis, serious infections, opportunistic infections, major adverse cardiovascular events (MACE) or deaths occurred through the placebo-controlled portion, week 16 of the study; one stroke occurred in the STELARA 45 mg group after the placebo-controlled period.

Source: prnewswire.com

UPDATE:
SUMMIT II report: https://psoriasisclub.org/showthread.php?tid=1057

Ustekinumab (Stelara)  proved effective for the clearance of palmoplantar psoriasis in an open-label pilot study, but only at the higher 90-mg dose reserved under current labeling for psoriasis patients weighing at least 100 kg.

"Higher or more frequent dosing may be required to achieve clinical clearance in patients with palmoplantar psoriasis compared to current recommendations for plaque-type psoriasis," said Dr. Shiu-Chung Au of Tufts Medical Center, Boston.

Dr. Au presented an open-label, 24-week study of 20 patients with moderate to severe palmoplantar psoriasis that was refractory to topical corticosteroids. Dosing of ustekinumab (Stelara) was as for plaque-type psoriasis: The 11 patients weighing less than 100 kg received 45 mg subcutaneously at weeks 0, 4, and 16, whereas the 9 patients weighing 100 kg or more received 90 mg on the same schedule.

The primary study end point was a Palm-Sole PGA (Physician’s Global Assessment) score of 0 or 1 at week 16. The average baseline score on this 0-5 measure of induration, erythema, and scaling was 4. The primary end point was achieved in 1 of 11 patients on the 45-mg dose, compared with 6 of 9 on the 90-mg dose. Of 20 patients, 12 improved at least 2 points on the Palm-Sole PGA at week 16.

In addition, significant improvements were documented with respect to the secondary end points for pain and quality of life. The mean pain score on a 100-point visual analog scale improved from 51 at week 0 to 29 at week 16, and held steady with a score of 30 at 24 weeks. Moreover, the mean score on the Dermatology Life Quality Index improved from 13.9 at baseline to 6.05 at week 16 and to 6.18 at week 24.

Ustekinumab was well tolerated with no serious adverse events.

Palmoplantar psoriasis is an uncommon variant of psoriasis that constitutes a therapeutic challenge, noted Dr. Au. It can be disfiguring and disabling, even though affected patients don’t necessarily have a large area of body surface involvement. The condition is characterized by fissures and sterile inflammatory pustules, in addition to classic well-demarcated psoriasis plaques. Affected patients experience considerable skin pain, often accompanied by a burning sensation. Some patients are unable to walk.

Clinically, palmoplantar psoriasis can look like other diseases, including palmoplantar pustulosis, dyshidrotic eczema, tinea pedis, and contact dermatitis, he explained. To help eliminate other possible diagnoses in the differential diagnosis, participants in the ustekinumab study had to have at least one classic psoriasis plaque somewhere other than the palms and soles.

Current treatment of palmoplantar psoriasis has been unsatisfactory, noted Dr. Au. No standard therapy is recognized, which was the impetus for studying ustekinumab. Future studies will look at employing the 90-mg dose in patients who weigh less than 100 kg and/or administering the 45-mg dose more frequently than the current standard every 3 months, he added.

Source: skinandallergynews.com

Following on from this January thread Erectile Dysfunction and Psoriasis a new study here is some more information from a study in Taiwan.

Quote:Men with psoriasis are at an increased risk for sexual dysfunction, research suggests.

This risk was greater in elderly men compared with their younger counterparts, report investigators.

The study, led by Yun-Ting Chang (Taipei Veterans General Hospital, Taiwan), suggests "physicians should pay attention to the impact of psoriasis on psychosocial and sexual health, especially in old-age patients."

Individuals with psoriasis frequently have other medical conditions, including arthritis, cardiovascular diseases, metabolic syndrome, and psychiatric illnesses.

Sexual activity is known to be impaired in some individuals with severe psoriasis, a finding that has been attributed to physical disfigurement, cardiovascular disease, and psychological problems.

Published in the Journal of Sexual Medicine, the latest study included 12,300 male patients with newly diagnosed psoriasis and 61,500 controls from a national health insurance database.

Of these patients, 1812 experienced some form of sexual dysfunction during the 7-year follow-up period, including 373 men with psoriasis and 1439 without psoriasis. The most common sexual dysfunction observed was erectile dysfunction (ED).

This translated into a 27% higher risk for sexual dysfunction in men with the chronic inflammatory skin condition when compared with men without psoriasis.

When patients were stratified by age, the risk for sexual dysfunction was not significant in men 40 years of age and younger. However, men with psoriasis who were aged 41-60 years had a 32% increased risk for developing sexual dysfunction and men older than 60 years had a 42% higher risk for sexual dysfunction compared with men without psoriasis.

The risk of sexual dysfunction was not significantly elevated in men being treated with phototherapy or systemic therapy, including retinoid, methotrexate, and cyclosporine.

Overall, there were higher rates of diabetes, hypertension, high cholesterol, coronary artery disease, and stroke among the men with psoriasis, findings that confirm previous studies, according to the researchers.

"These factors have been found to be associated with ED in recent studies," they report.

Hello everyone. I am 57 and I had my first sign of psoriasis when I was 22. I woke up one morning and looked in the mirror and seeing about 50 brand new red spots spread out around my stomach and the sides of my chest and on my thighs scared me, I had no idea what was wrong. My first visit to a dermatologist confirmed that I had guttate psoriasis and I was given a prescription for a topical creme or ointment and told that it would clear but it would eventually come back. Less than a year later I was taking PUVA treatments - that's where I would take one or more green pills before my appointment, then stand naked in a UVA light box wearing a special pair of dark goggles several times a week. My skin would always eventually clear with the light treatments but it would return sooner or later. Reading the warning about the pills I was taking for this treatment scared me and I quit taking them in the late 1970's. I haven't taken any light treatments or other medication for it in almost 30 years and have just learned to live with the occasional flare ups for the most part until now. My psoriasis never really itched much most of my life, but that has changed steadily over the last couple of years. The itching has become almost unbearable and I'm scratching so much It feels like I'm scraping my skin off. Some nights I dream of using a grinding wheel to scratch with. Bathing with Dove soap seems to help for a little while after I shower. My wife recommended using her Lubriderm but that and other moisturizing lotions seems to do nothing for the itching and turns the spots bright red and makes them even more tender and sensitive and irritated looking. Tonight I'm trying a heavy application of calamine lotion. So far (about 30 minutes) the itching has subsided but I'm keeping it close by when I go to bed tonight.

Had an appointment with my dermatologist today and we have decided it's time to come off of Stelara see this post: Coming off Stelara

So here is what is going to happen. I'm going onto a trial of an JAK (Janus Kinase) Inhibitor, but I can't do this until I have a worse PASI/Psoriasis score for psoriasis and psoriatic arthritis Yes I need to get more psoriasis!

After using Stelara for two years my skin was around 99% clear and I was coping with the psoriatic arthritis well, but now it's failing. so I have been given the option to continue with Stelara or go for the Trial. So I have gone for the Trial to see what happens. So if anyone has any experience of the JAK (Janus Kinase) Inhibitors I would be grateful.

At the moment I have a Psoriasis Score of 17 with plaques on the front of my lower legs, and the Psoriatic Arthritis is getting worse. So it's No Medication, No Creams, No Nothing. then an appointment with a Rheumatologist in two weeks time. Two weeks after that an appointment with the top dermatologist. If my score is high enough to commence the trial I will have more tests and start.

If my score has not gone up enough I will have to wait another month. then another and so on, till my score is high enough to start the trial. no one knows how long this will take to get my score higher, but at least I don't have to worry about what is causing my flare ups any more, and can eat, drink, and do what I like  

Ever the optimist I did ask what if my score gets better and actually goes down instead of going up! she said we will see. So I'm coming off any medication and lets see what happens.

I will keep this thread updated as I go on. but for now it's time for some Pizza and Wine.

Hi Guys,

Just thought I'd pop a quick post this morning. I saw my rheumatologist yesterday morning and after some initial visual checks he did some ultrasound scans of my painful joints... Both the consultant and the student Dr who were meeting with me were horrified at the amount of inflammation and fluid around my joints and tendons in my wrists.

So, I am finally (after 20 years of joint pain) a confirmed case of Psoriatic Arthritis!! You have no idea how much relief I felt on getting the diagnosis, I cried with joy because I have proof that the pain etc. wasn't all in my head for all these years.

He's prescribed me Methotrexate (MTX) so had to go for chest x-rays after my appointment, I am assuming to confirm that I have no TB lesions in my chest, and I should be starting the tablets in the next couple of weeks once my GP gets a letter from my consultant.

I know some of you guys are on MTX for the same condition and I wondered if you could tell me how effective you find it to be, how long it took to kick in and be effective and if the side effects wear off over time (if you experienced any)...

I had some steroid injections into my worst joints yesterday and woke up this morning completely pain free (well, except where the Dr hit a vein giving me the injection) for the first time since early August last year. I feel wonderful, I could make a cup of tea this morning without having to use 2 hands to lift the kettle.

Now I just have to do some research to see if I can continue with my career in medical microbiology given my new "immunocompromised" status. Would be gutted to have to give it up, am jobseeking atm after being made redundant earlier this month and have a number of applications in for med micro roles...

Thanks for all your help in advance.

Krissie

Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms. It primarily causes abdominal pain, diarrhea (which may be bloody if inflammation is at its worst), vomiting (can be continuous), or weight loss, but may also cause complications outside the gastrointestinal tract such as skin rashes, arthritis, inflammation of the eye, tiredness, and lack of concentration.

Psoriasis patients are at a nearly fourfold increased risk of developing Crohn’s disease, and the risk is higher in psoriatic arthritis patients.

These findings from 174,646 prospectively followed participants in the Nurses’ Health Study and the Nurses’ Health Study II are consistent with the results of genomewide association studies which have found susceptibility genes common to both psoriasis and inflammatory bowel disease, especially genes in the interleukin-23 pathway, Dr. Wenqing Li said at the annual meeting of the Society for Investigative Dermatology.

"Further understanding of the mechanisms that mediate both psoriasis and Crohn’s disease could eventually lead to elucidation of new targets for interventions that may modulate the incidence or activity of both diseases," added Dr. Li of Harvard Medical School, Boston.

Of note, the psoriasis patients were not at significantly increased risk for developing ulcerative colitis. This suggests that psoriasis may share fewer overlapping pathways with ulcerative colitis than it does with Crohn’s disease, he continued.

Women in the Nurses’ Health Study were prospectively followed from 1996 to 2008, whereas those in the NHS II were followed from 1991 to 2005. During follow-up, there were 188 incident cases of Crohn’s disease and 240 of ulcerative colitis in the study population. All diagnoses of inflammatory bowel disease were confirmed by two gastroenterologists blinded as to whether or not the affected patients also had psoriasis, Dr. Li noted.

The combined analysis of the two studies included 47,618 person-years of prospective follow-up of psoriasis patients and 2,401,883 person-years of follow-up of participants without psoriasis. The psoriasis patients had an age-adjusted 3.74-fold increased risk of developing Crohn’s disease.

Having psoriasis was still an independent risk factor for Crohn’s disease, with an associated 3.5-fold relative risk, in a multivariate analysis that was adjusted for body mass index, physical activity, smoking status, alcohol consumption, use of oral contraceptives, and postmenopausal hormone therapy as well as age.

Based upon 5,661 person-years of prospective follow-up of subjects with psoriasis and comorbid psoriatic arthritis, affected patients had a 6.8-fold increased of Crohn’s disease in a multivariate analysis.

Multivariate analysis was appropriate because patients with psoriasis had a higher BMI, tended to be older, consumed more alcohol, and were less physically active than were those without psoriasis. The psoriasis patients were also more likely to be current smokers, users of oral contraceptives, and current users of postmenopausal hormone therapy.

The risk of new-onset Crohn’s disease was significantly greater among psoriasis patients whose dermatologic disease was diagnosed when they were younger than 40 years than it was among those diagnosed later in life. The risk was also greater in those with at least a 10-year history of active psoriasis. However, as 87% of patients with psoriasis had mild skin disease based upon the involved body surface area, this study didn’t have sufficient power to determine if the risk of Crohn’s disease was greater in individuals with more severe psoriasis, according to Dr. Li.

To ensure that the increased risk of inflammatory bowel disease associated with having psoriasis wasn’t in some way affected by the use of tumor necrosis factor inhibitors to treat psoriasis, Dr. Li and coinvestigators conducted a separate analysis restricting follow-up through 2004, the year the biologic therapies were approved for psoriasis. This didn’t change the results.

Sleep Apnea is a sleep disorder characterized by abnormal pauses in breathing or instances of abnormally low breathing, during sleep. Each pause in breathing, called an apnea, can last from a few seconds to minutes, and may occur 5 to 30 times or more an hour.

Objective: In a cross-sectional study, we explored whether obstructive sleep apnea and hypopnea syndrome (OSAHS) is associated with psoriasis characteristics and metabolic parameters.

Methods: Thirty-five patients with chronic plaque psoriasis underwent a nocturnal polysomnography study and were analysed for Apnoea–Hypopnoea Index to assess OSAHS severity and Framigham score to predict the absolute risk of coronary artery disease at 10 years. The association of OSAHS with psoriasis was examined according to psoriasis characteristics (PASI and DLQI scores, disease duration and previous use of systemic treatments), metabolic parameters (Body Mass Index – BMI, waist to hip ratio – WHR, lipid profile) and other comorbidities (obesity, hypertension, arthritis and cardiovascular disease).

Results: There was no correlation between psoriasis characteristics and OSAHS. Psoriasis patients with OSAHS presented more frequent snoring and lower sleep quality compared with those without OSAHS. In univariate analyses, OSAHS was associated with increased BMI and hypertension in psoriasis patients. In multivariable logistic regression models, there was statistically significant evidence that only BMI and hypertension were associated with increased risk of OSAHS, adjusting for psoriasis characteristics, age and gender. Presence of metabolic syndrome, WHR, and smoking were not significant risk factors for OSAHS. In subgroup analyses, OSAHS correlated with duration of psoriasis (>8 years) in women (P = 0.021) and with Framigham score in men (P = 0.035).

Conclusion: OSAHS may be a comorbidity in obese psoriasis patients with hypertension. Treatment with continuous positive airway pressure and weight loss interventions should be initiated.

Source: onlinelibrary.wiley.com

Abbott scientists and independent researchers will highlight the latest investigational research findings on HUMIRA® (adalimumab) at the European League Against Rheumatism (EULAR) Congress in Berlin, Germany, from 6-9 June, 2012. The presentations include two of the longest open-label extension studies in rheumatoid arthritis (RA), featuring long-term data for disease activity and radiographic inhibition. Data will also be presented on investigational indications in axial and peripheral spondyloarthritis (SpA), moderate to severe polyarticular juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS) and health economics research.

"Data presented at this year's EULAR highlight Abbott's commitment to continue to expand our understanding of the efficacy and safety of HUMIRA and address the needs of patients and physicians across a broad spectrum of rheumatologic diseases," said John Medich, Ph.D., divisional vice president, Clinical Development, Immunology, Abbott. "Specifically, data highlighting the use of HUMIRA for long-term treatment of RA and new data in investigational indications like axial and peripheral SpA will be presented, reinforcing Abbott's ongoing investment in research in the rheumatology space."

Presentation Highlights:
Data being presented at EULAR include the comprehensive 10-year data for treatment of moderate to severe, long-standing RA in the DE019 trial and in the DE020 follow-up study. DE020 will be presented in a publication, while DE019 will be presented as a poster on 9 June.

Data will also be presented for ABILITY-I, the first, multi-national Phase 3 study evaluating the use of an anti-tumor necrosis factor (anti-TNF) medication in patients with active non-radiographic axial SpA – a debilitating condition closely related to AS that primarily presents with chronic back pain and stiffness, and can be accompanied by the presence of arthritis, and inflammation in the eye and/or gastrointestinal tract. There is currently no approved treatment for non-radiographic axial SpA. Results from 68 weeks of treatment with HUMIRA will be shown, highlighting not only the initial clinical responses in the 12-week, placebo-controlled trial, but also the responses over an additional year of treatment. These data will be presented as a poster on 7 June.

The initial results will be presented from ABILITY-2, the first Phase 3 study investigating the use of an anti-TNF medication in patients with active peripheral SpA that don't have a diagnosis of psoriatic arthritis (PsA)*. This patient population is characterized by peripheral arthritis (asymmetric, lower limb or both), enthesitis (painful inflammation where a tendon or ligament attaches to bone) or dactylitis (a painful and swollen digit), in addition to the presence of other features (family history of SpA, history of inflammation in the eye, diagnosis of other immune-mediated inflammatory diseases, sacroiliitis on MRI). There is currently no approved treatment for non-PsA peripheral SpA. Data following 12-weeks of treatment with HUMIRA will be shown as a poster on 7 June.

Additionally, clinical and patient-reported outcomes will be presented from OPTIMA, the first global prospective trial using a treat-to-target philosophy in the treatment of moderate to severe RA. Treat-to-target is focused on achieving a clearly defined treatment goal within a set duration of time and adjusting the treatment if the target is not met. This approach is aligned to EULAR and American College of Rheumatology (ACR) rheumatoid arthritis treatment recommendations.

*Results from an Analysis Evaluating the Long-term Safety of Adalimumab in Patients with Rheumatoid Arthritis, Juvenile Idiopathic Arthritis, Ankylosing Spondylitis, Psoriatic Arthritis, Psoriasis and Crohn's Disease; G. Burmester, et al
–    Abstract SAT0130; Poster; 9 June, 2012; 10:15 a.m.; Location: Poster Area.

Source: prnewswire.com

This is the start of a series of posts on Dimethylfumarates.
For long it is yet known that fumarates have a very positive effect on psoriasis and arthritic psoriasis. Still fumarates did not have their breakthrough in medicare. The causes for this will be part of this series.

In the Netherlands the use of fumarates is much more normal than in other countries, there is even a patients organization that promotes the use of a specific form and is busy starting up scientific research to prove that this form is much less toxic with a much better effect than most other medicines.

I do not write this "by my own", the texts are mainly a translation of publications of dr. L.Kunst and dr. Schweckendieck, and I will make references to existing literature on the subject.

Why do I do this?
Well, while speeding around on the different threads of this forum, I found out that there are lots of psoriasis sufferers. None of them are using fumarates, I seem to be the only one. And if I read well, I am also one of the posters that has minor problems with psoriasis, I even have arthritic psoriasis which is very "livable" and relatively under control, with very few extra problems from the medication.
I think it makes sense to share what I know. Maybe some of you will make a try with what I use, and maybe this will help them. The forum on the dutch site shows a lot of people that are very pleased with this medicine.

Below part one of a translation from the site psoriasistherapie dot nl on fumarates. As it is a translation, there may be stupid constructions in the sentences. My mastery of english is quite acceptable, but translating is quite a different job.

First some background information to build up the story.

Energy housekeeping and fumaric acid.

Fumaric aced is a body own substance. Chemically seen it is an unsaturated dicarbon acid. It is formed from cis-butanecarbonic acid (cis-barnstoneacid) under influence of succinatehydrogenasis. This biochemical conversion is a component of the so-called citric acid cycle, and takes place in the mitochondria. Mitochondria are not only the power of our cells, they play an important role in essential metabolic processes and the genetic transfer of a large number of degenerative diseases through specific mitochondrial DNA. A variety of genetic disorders can be attributed to mutations in the mitochondrial DNA, such as defects in the citric acid cycle. The citric acid cycle is a cycle in which oxidation of carbon compounds are oxidized to carbon dioxide. The carbon-containing compounds are derived from fats, sugars and amino acids. The vast majority of fuel is supplied in the form of acetyl-CoA. The citric acid cycle contains except fumaric acid, several intermediate metabolites, such as shown in the accompanying illustration.


The upper portion of pyruvic acid to acetyl-coenzyme A does not actually belong to the citric acid cycle, but it's there to follow up the glycolysis. The reactions involving NAD + conversion to NADH and GDP to GTP and FAD to FADH2 mean that energy is released and that this energy has gone into these compounds formed. This energy is required with all of the biochemical processes in the body.

More to follow in a next post.

Psoriasis patients who possess the HLA-Cw6 allele appear to be protected against the increased risk of cardiovascular and metabolic comorbidities associated with the disease.

In a study that included 199 psoriasis patients under the age of 40, those who carried the histocompatibility antigen HLA-Cw6 allele had a 66% reduction in the prevalence of comorbid hypertension and a 72% reduction in dyslipidemia, compared with HLA-Cw6-negative psoriasis patients, according to Dr. Trilokraj Tejasvi of the University of Michigan, Ann Arbor.

This is a particularly intriguing finding, he noted, because previous studies have demonstrated that HLA-Cw6-positive psoriasis patients tend to have more severe skin disease, an earlier age at disease onset, higher rates of the guttate and eruptive forms of psoriasis as well as Koebner phenomenon, and more extensive disease.

Moreover, other studies have shown that patients with more severe psoriasis tend to have higher rates of comorbid cardiovascular and metabolic disorders. For example, a large recent study that included 4,065 psoriasis patients aged 45-65 years and nearly 41,000 age- and physician practice-matched controls showed that the risk of comorbid metabolic syndrome increased from 1.2-fold in patients with mild psoriasis to twofold in those with severe psoriasis, compared with controls.

A strikingly similar twofold increased risk of the metabolic syndrome in psoriasis patients was recently reported based upon data from the National Health and Nutrition Examination Survey for 2003-2006

Since neither the NHANES psoriasis patients nor those in the U.K. study underwent genotyping, there is no way of knowing what proportion of those who were HLA-Cw6-positive had the metabolic syndrome, Dr. Tejasvi noted.

In a recent, still-to-be-published genome-wide association study, he and his colleagues found that all known psoriasis-associated single nucleotide polymorphisms explained roughly 22% of the disease’s heritability – and nearly half of were because of genes located at HLA-C.

The study included 1,134 psoriasis patients and 1,174 unaffected controls who underwent genomic DNA analysis. He and his coinvestigators examined the rates of hypertension, dyslipidemia, acute MI, and diabetes mellitus in the two groups.

One analysis was restricted to the 199 psoriasis patients and 392 controls under age 40, since the comorbid conditions under scrutiny tend to less frequently in younger people. In this under-40 analysis, the prevalence of diabetes wasn’t significantly different between psoriasis patients and controls. Neither was a history of MI.

However, 15% of the younger psoriasis patients carried the diagnosis of hypertension, compared with 6.8% of controls, and 29% of the psoriasis patients were dyslipidemic, compared with 10.5% of controls. Thus, psoriasis patients under age 40 were 2.2-fold more likely than controls to be hypertensive and 2.75-fold more likely to be dyslipidemic. Both differences were highly significant.

The prevalence of hypertension among 80 HLA-Cw6-positive psoriasis patients under age 40 was 7.5%, compared with 22% in HLA-Cw6-negative psoriasis patients under age 40. And the prevalence of dyslipidemia in the HLA-Cw6-positive group was 12.5% vs. 44% in the HLA-Cw6-negative psoriasis patients.

The under-40 psoriatic HLA-Cw6 carriers and noncarriers were essentially the same in terms of body mass index – a mean of 28 kg/m2 in both groups – and in mean age at evaluation, which was 28 years in the HLa-Cw6-positive patients and 29 years in the HLA-Cw6-negative cohort, Dr. Tejasvi reported.

Several key findings stood out in the analysis of the overall study population comprised of 1,134 psoriasis patients and 1,174 controls. One was that among control patients without psoriasis, HLA-Cw6 status was unrelated to comorbid hypertension, dyslipidemia, diabetes, or a positive history for MI. And in the full group of psoriasis patients, hypertension and dyslipidemia remained significantly less common among those who were HLA-Cw6-negative, although the association was less robust than in the below-40 subgroup. Specifically, HLA-Cw6 carriers with psoriasis were 24% less likely to be hypertensive and 25% less likely to have dyslipidemia than psoriatic HLAL-Cw6 noncarriers.

Dr. Tejasvi commented that an HLA-Cw6 protective effect against hypertension and dyslipidemia isn’t the only possible explanation for the lower rates of these two components of the metabolic syndrome found in HLA-Cw6-positive psoriasis patients. The alternate possibility is that HLA-Cw6 noncarrier status in psoriasis patients is associated with other genetic loci that increase the risk of dyslipidemia and hypertension. Sorting this out will require a prospective study with a large sample size.

Source: skinandallergynews.com

Objective: To examine the association between total physical activity, walking, and vigorous exercise and the incidence of psoriasis in women.

Design: Cohort study.

Setting: The Nurses' Health Study II, a cohort of 116 430 women aged 27 to 44 years in 1991.

Participants: The study population included 86 655 US female nurses who reported whether they had ever been diagnosed as having psoriasis and who completed detailed physical activity questionnaires in 1991, 1997, and 2001. We excluded participants with a history of psoriasis prior to 1991.

Main Outcome Measures: Risk of psoriasis by quintile of physical activity as measured by a metabolic equivalent task score.

Results: We documented 1026 incident psoriasis cases during 1 195 703 person-years of follow-up (14 years, 1991-2005). After adjusting for age, smoking, and alcohol use, increasing physical activity was inversely associated with the risk of psoriasis. The most physically active quintile of women had a lower multivariate relative risk (RR) of psoriasis (0.72 [95% CI, 0.59-0.89; P < .001 for trend]) compared with the least active quintile. Vigorous physical activity (≥6 metabolic equivalents) was associated with a reduced risk of psoriasis (multivariate RR for the highest quintile, 0.66 [95% CI, 0.54-0.81; P < .001 for trend]); this association remained significant after adjusting for body mass index (RR, 0.73 [95% CI, 0.60-0.90; P = .009 for trend]). Walking was not associated with psoriasis risk. In a subset of 550 confirmed psoriasis cases, we observed a similarly reduced risk of psoriasis associated with vigorous physical activity (multivariate RR for the highest quintile, 0.64 [95% CI, 0.48-0.86; P = .03 for trend]).

Conclusion: In this study of US women, vigorous physical activity is independently associated with a reduced risk of incident psoriasis.

Psoriasis is an immunologic disorder characterized by systemic inflammation and cutaneous plaques.1 Prospective studies have demonstrated that higher body mass index (BMI),2 weight gain, alcohol intake,3 and smoking4 are associated with an increased risk of psoriasis. However, the role of physical activity in psoriasis prevention remains undetermined. Results from cross-sectional studies have been inconsistent; an association between psoriasis and physical inactivity was observed in some studies5 - 6 but not in others.7 The Iowa Women's Health Study found that women who engaged in regular physical activity were less likely to have psoriasis than women who denied exercising regularly (age-adjusted odds ratio, 0.8 [95% CI, 0.7-0.9]).5 Another study found no difference in mean physical activity between women with and without psoriasis.7 These cross-sectional analyses did not adjust for other lifestyle factors, such as BMI, that may vary across groups of differing physical activity levels and do not permit a determination of cause and effect. No prospective studies have evaluated the association between physical activity and incident psoriasis.

Physical activity has been associated with a decreased risk of disorders characterized by systemic inflammation, including type 2 diabetes mellitus,8 colon cancer,9 coronary artery disease,10 and breast cancer.11 Walking and vigorous exercise appear to have an equal role in reducing the risk of developing coronary artery disease, type 2 diabetes, and breast cancer. A dose-response relationship has also been demonstrated, with higher amounts of physical activity associated with a lower risk of disease. The relative effects of walking and vigorous activity on psoriasis risk and the dose-response relationship between physical activity and psoriasis remain unknown. It is biologically plausible that physical activity may affect psoriasis risk through effects on systemic inflammatory mediators.

In this study, we prospectively evaluated the association between physical activity and incident psoriasis in a large cohort of women in the United States. We also assessed the association between type of physical activity (eg, walking vs vigorous exercise) and the risk of psoriasis, using detailed, repeated assessments of physical activity, and validated our findings in a subset of confirmed psoriasis cases.

Source: NO LINKS ALLOWED

BACKGROUND: With a prevalence of 0.71%, psoriasis represents one of the most frequent dermatoses in childhood.

PATIENTS AND METHODS:
Eight children with severe psoriasis who failed to respond to other therapy received a weight- adapted treatment with Enbrel (etanercept) (0.8 mg/kg body) administered subcutaneously once weekly after latent tuberculosis had been excluded. Follow-up visits were at week 4 and 12, subsequently every 12 weeks.

RESULTS: Mean age at the start of treatment was 11.8 (range 7-16), six patients were boys. Within three months, six patients reached Psoriasis Area and Severity Index (PASI) reduction of 75%. Two patients stopped use at week 12 because of ineffectiveness. Apart from local side reactions and minor infections, no adverse events were observed.

CONCLUSION: In our case series, Enbrel (etanercept) proved to be an efficient drug in juvenile psoriasis without serious adverse events. However, patient registries and further randomized, double-blinded control studies are crucial to evaluate long-term efficacy and safety of etanercept.

Source: NO LINKS ALLOWED

Objectives:  To examine the association between psoriasis and viral infections including hepatitis B, hepatitis C and human immunodeficiency viral infections in the general U.S. population.

Methods:  Population data representative of the U.S. cohort were analysed from the National Health and Nutrition Examination Survey (NHANES), 2003–2006. Hepatitis B, hepatitis C, and human immunodeficiency antibodies status were ascertained from laboratory evaluations. Univariate and multivariate analyses were performed to assess the associations between psoriasis and these viral infections.

Results:  Among 6532 participants aged 20–59 years who provided responses to their psoriasis status, 162 patients reported having psoriasis. Based on multivariate regression analyses, psoriasis was not significantly associated with positive serology for hepatitis B core [odds ratio (OR), 0.83; 95% confidence interval (CI), 0.32–2.17; P = 0.7060], hepatitis B surface [OR, 7.89; CI, 0.52–119; P = 0.1355], hepatitis C [OR, 0.24; CI, 0.03–2.01; P = 0.1915], or human immunodeficiency virus [OR, 0.73; CI, 0.09–5.93; P = 0.7646] antibodies, after adjusting for age, gender, race and smoking status.

Conclusions:  From the limited sample of the NHANES database on psoriasis and viral infections, psoriasis does not appear to be associated with an increased risk of hepatitis B, hepatitis C, or HIV infection in the U.S. population. Epidemiology of these viral infections in psoriasis needs to be continually studied and updated given their importance in management considerations.

Source: onlinelibrary.wiley.com

*Celiac (Coeliac) Disease is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy onward. Symptoms include chronic diarrhoea, failure to thrive (in children), and fatigue.

Because a number of past studies examining the connection between celiac disease and psoriasis have had contradictory findings, researchers wanted to get a better idea of the actual risk of psoriasis in patients with biopsy-verified celiac disease.

The researchers were J.F. Ludvigsson, B. Lindelöf, F. Zingone, and C. Ciacci, with the Department of Pediatrics at Sweden's Örebro University Hospital.

For their study, they used data from 28 pathology departments in Sweden to identified individuals with celiac disease diagnosed between 1969 and 2008. They found 28,958 patients with Marsh 3 villous atrophy.

They then used Cox regression to compare those celiac disease patients with 143,910 sex- and age-matched control subjects, and to assess the risk of psoriasis.

They found that celiac disease was a risk factor for future psoriasis (hazard ratio (HR) = 1.72; 95% confidence interval (CI) = 1.54-1.92. They found that, during follow-up, 401 individuals with celiac disease and 1,139 controls were diagnosed with psoriasis.

They found that the absolute risk of future psoriasis in patients with celiac disease was 135 per 100,000 person-years, with an excess risk of 57 cases per 100,000 person years.

Overall, 42% of the cases of psoriasis in patients with celiac disease could be attributed to celiac disease. Moreover, in children the team saw a strong association between celiac disease and psoriasis (HR = 2.05; 95% CI = 1.62-2.60).

Their results show that the connection between celiac disease and psoriasis seems to be far more than coincidental, as we also found a positive association between celiac disease and psoriasis before celiac diagnosis, with an odds ratio of 1.91; 95% CI = 1.58-2.31).

They conclude that individuals with celiac disease do, in fact, face an increased risk of psoriasis both before and after celiac diagnosis.

Source: celiac.com

Hey, I'm new to this website and forum but I'm not new to Psoriasis. I've been dealing with it for 24 years now. Sometimes I felt like doing that. Recently, I've had a major flare. I'm now covered more than I've ever been covered with spots and it's so painful. I'm changing my diet to see if it helps and I'm glad to see there is a forum because sometimes I feel very alone.

*Behçet's disease, sometimes called Behçet's syndrome, Morbus Behçet, or Silk Road disease, is a rare immune-mediated systemic vasculitis that often presents with mucous membrane ulceration and ocular involvements. Behçet's disease (BD) was named in 1937 after the Turkish dermatologist Hulusi Behçet, who first described the triple-symptom complex of recurrent oral aphthous ulcers, genital ulcers, and uveitis. As a systemic disease, it can also involve visceral organs such as the gastrointestinal tract.

Background: 
Behçet’s disease (BD) and psoriasis are chronic inflammatory diseases characterized by multisystemic vasculitis and epidermal hyperplasia respectively. Although it has been found that the pathogenesis of BD and psoriasis share common perspectives, reports of patients who have both diseases in concurrence are rare.

Objectives: 
To analyse and evaluate the clinical manifestations of BD patients who have psoriasis together.

Methods: 
Retrospective evaluation of the medical records of nine BD patients who were also diagnosed with psoriasis at the BD Specialty Clinic of Severance Hospital was carried out. We analysed the characteristics of patients and the clinical activity of both diseases, and also the effect of the treatment of one disease against the other.

Results: 
Of the nine BD patients who also had psoriasis, male to female ratio was 1 : 2. Two (22.2%) patients had a complete type of BD and seven (77.8%) patients had an incomplete type of BD. For the psoriatic lesions, all nine (100%) patients were diagnosed as psoriasis vulgaris. Five (55.6%) patients had BD as the preceding disease and four (44.4%) patients had psoriasis as the preceding. All five patients who formerly developed BD followed by psoriasis had an active state of BD, but the activity of psoriasis of all nine patients was minimal to average.

Conclusion: 
In this study, we evaluated the clinical manifestations of nine patients who had BD and psoriasis together. Although the exact pathogenesis remains unclear, there might be some influence by each disease to the other between BD and psoriasis.

Source: onlinelibrary.wiley.com

*Chlamydophila psittaci is a lethal intracellular bacterial species that may cause endemic avian chlamydiosis, epizootic outbreaks in mammals, and respiratory psittacosis in humans. Chlamydophila psittaci is transmitted by inhalation, contact or ingestion among birds and to mammals. Psittacosis in birds and in humans often starts with flu-like symptoms and becomes a life-threatening pneumonia.

Objective: 
Recent evidence indicates that subclinical infection by Chlamydophila psittaci occurs in a significant percentage of patients with chronic inflammatory polyarthritis, including psoriatic arthritis.

Methods: 
The presence of a subclinical C. psittaci infection was investigated in 64 patients with psoriasis, including 12 patients with psoriatic arthritis. Two hundred twenty-five healthy controls were also investigated. The presence of infection was assessed in peripheral blood mononuclear cells using several PCR protocols, targeting different regions of the bacterial genome. The DNA of other Chlamydia spp (C. pneumoniae and C. trachomatis) was also investigated.

Results: 
C. psittaci infection was observed in a significantly higher percentage of patients with psoriasis (11/64; 17.2%) compared to healthy controls (1/225, 0.4% in healthy donors; OR:46.49, 95%CI:5.87 to 368.03, p<0.0001).

No differences in age, sex, disease duration were noticed between positive and negative patients, but the majority of the positive patients were on immunomodulatory treatments.

Conclusion:
C. psittaci may be an infectious trigger possibly involved in the pathogenesis of psoriasis.

Source: onlinelibrary.wiley.com

A new purpose-built dermatology unit has opened at the Royal United Hospital to enable more patients with skin conditions to be treated.

The new unit houses clinics run both by consultants and nurses, as well as a day treatment service.

Staff treat 30 to 40 patients a day for conditions including psoriasis, skin cancer and leg ulcers.

The new facilities have replaced the Kinghorn Dermatology Unit, which was set up in an existing part of the hospital with a bequest from Sheila Kinghorn, in 1994.

Jess Ball, from Whiteway, has been treated at the hospital for six years for rheumatoid arthritis and an auto immune skin condition.

She said: "When I first came to the unit, my leg was badly ulcerated and if the staff had not intervened when they did, I would have lost my leg.

"The knowledge that they have is incredible and I feel very supported.

"There have been times when I don't know how I would have managed without their skill and care, and their wonderful sense of humour.

"The staff deserve this lovely new unit. It feels very light and spacious and welcoming, and patients and staff are sure to benefit from it."

Senior sister Jacky Strange said: "This is the first time dermatology has been in a purpose-built unit in the RUH. We had outgrown the Kinghorn unit.

"We'll continue to provide a high standard of care to our patients, but now we can do that in a light and spacious environment, that offers greater confidentiality.

"And having the extra space will allow us to expand and treat a greater number of patients."

Good evening everyone. I have always felt completely on my own since I was diagnosed with psoriasis five years ago when I was 18. Today I felt like the future was entirely hopeless and to continue on was a difficult idea to comprehend. A google search brought me to this forum and after reading posts of people with such widespread and painful psoriosis that putting on clothes is difficult, I began to feel like my story did not even compare and wondered if I even belonged. But somehow, in reading the posts I felt some kind of hope. If nothing else I felt empowered just knowing that someone else may go through their day with some of the same thoughts and experiences that I have. My outbreaks are mainly concentrated on my scalp and genital regions. While by using protopic ointment and clobex spray I am somewhat able to control the day to day discomfort of the outbreaks, I find myself unable to stop the continual feeling of helplessness. At it's worst, there are times when I feel worthless and left out from being a human. But being able to say this does give me comfort. And I must apologize for my complaining, because I know that there are many people who can't even walk out their door without their psoriosis causing great pain or being witnessed by everyone they come in contact with.