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Psoriasis Clinical Trials, Diagnosis, and Treatment
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Psoriasis

Psoriasis is a disease which affects the skin and joints. It commonly causes red scaly patches to appear on the skin. The scaly patches caused by psoriasis, called psoriatic plaques, are areas of inflammation and excessive skin production. Skin rapidly accumulates at these sites and takes a silvery-white appearance. Plaques frequently occur on the skin of the elbows and knees, but can affect any area including the scalp and genitals. Psoriasis is hypothesized to be immune-mediated and is not contagious.

The disorder is a chronic recurring condition which varies in severity from minor localised patches to complete body coverage. Fingernails and toenails are frequently affected (psoriatic nail dystrophy). Psoriasis can also cause inflammation of the joints, which is known as psoriatic arthritis. Ten to fifteen percent of people with psoriasis have psoriatic arthritis.

The cause of psoriasis is not known, but it is believed to have a genetic component. Several factors are thought to aggravate psoriasis. These include stress, excessive alcohol consumption, and smoking. Individuals with psoriasis may suffer from depression and loss of self-esteem. As such, quality of life is an important factor in evaluating the severity of the disease. There are many treatments available but because of its chronic recurrent nature psoriasis is a challenge to treat.

Current Research

For current research articles click - here

History

Psoriasis is probably one of the longest known illnesses of humans and simultaneously one of the most misunderstood. Some scholars believe psoriasis to have been included among the skin conditions called tzaraat in the Bible. In more recent times psoriasis was frequently described as a variety of leprosy. The Greeks used the term lepra (λεπρα) for scaly skin conditions. They used term psora to describe itchy skin conditions. It became known as Willan's lepra in the late 18th century when English dermatologists Robert Willan and Thomas Bateman differentiated it from other skin diseases. They assigned names to the condition based on the appearance of lesions. Willan identified two categories: leprosa graecorum and psora leprosa.

While it may have been visually, and later semantically, confused with leprosy it was not until 1841 that the condition was finally given the name psoriasis by the Viennese dermatologist Ferdinand von Hebra. The name is derived from the Greek word psora which means to itch.

It was during the 20th century that psoriasis was further differentiated into specific types.

Types of Psoriasis

The symptoms of psoriasis can manifest in a variety of forms. Variants include plaque, pustular, guttate and flexural psoriasis. This section describes each type (with ICD-10 code).

Plaque psoriasis (psoriasis vulgaris) (L40.0) is the most common form of psoriasis. It affects 80 to 90% of people with psoriasis. Plaque psoriasis typically appears as raised areas of inflamed skin covered with silvery white scaly skin. These areas are called plaques.

Flexural psoriasis (inverse psoriasis) (L40.83-4) appears as smooth inflamed patches of skin. It occurs in skin folds, particularly around the genitals (between the thigh and groin), the armpits, under an overweight stomach (pannus), and under the breasts (inframammary fold). It is aggravated by friction and sweat, and is vulnerable to fungal infections.

Guttate psoriasis (L40.4) is characterized by numerous small oval (teardrop-shaped) spots. These numerous spots of psoriasis appear over large areas of the body, such as the trunk, limbs, and scalp. Guttate psoriasis is associated with streptococcal throat infection.

Pustular psoriasis (L40.1-3, L40.82) appears as raised bumps that are filled with non-infectious pus (pustules). The skin under and surrounding pustules is red and tender. Pustular psoriasis can be localised, commonly to the hands and feet (palmoplantar pustulosis), or generalised with widespread patches occurring randomly on any part of the body.

Nail psoriasis (L40.86) produces a variety of changes in the appearance of finger and toe nails. These changes include discolouring under the nail plate, pitting of the nails, lines going across the nails, thickening of the skin under the nail, and the loosening (onycholysis) and crumbling of the nail.

Psoriatic arthritis (L40.5) involves joint and connective tissue inflammation. Psoriatic arthritis can affect any joint but is most common in the joints of the fingers and toes. This can result in a sausage-shaped swelling of the fingers and toes known as dactylitis. Psoriatic arthritis can also affect the hips, knees and spine (spondylitis). About 10-15% of people who have psoriasis also have psoriatic arthritis.

Erythrodermic psoriasis (L40.85) involves the widespread inflammation and exfoliation of the skin over most of the body surface. It may be accompanied by severe itching, swelling and pain. It is often the result of an exacerbation of unstable plaque psoriasis, particularly following the abrupt withdrawal of systemic treatment. This form of psoriasis can be fatal, as the extreme inflammation and exfoliation disrupt the body's ability to regulate temperature and for the skin to perform barrier functions.

Diagnosis

A diagnosis of psoriasis is usually based on the appearance of the skin. There are no special blood tests or diagnostic procedures for psoriasis. Sometimes a skin biopsy, or scraping, may be needed to rule out other disorders and to confirm the diagnosis. Skin from a biopsy will show clubbed Rete pegs if positive for psoriasis.

Severity

Psoriasis is usually graded as mild (affecting less than 3% of the body), moderate (affecting 3-10% of the body) or severe. Several scales exist for measuring the severity of psoriasis. The degree of severity is generally based on the following factors: the proportion of body surface area affected; disease activity (degree of plaque redness, thickness and scaling); response to previous therapies; and the impact of the disease on the person.

The Psoriasis Area Severity Index (PASI) is the most widely used measurement tool for psoriasis. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease). Nevertheless, the PASI can be too unwieldy to use outside of trials, which has led to attempts to simplify the index for clinical use.

Effect on the Quality of Life

Psoriasis has been shown to affect health-related quality of life to an extent similar to the effects of other chronic diseases such as depression, myocardial infarction, hypertension, congestive heart failure or type 2 diabetes. Depending on the severity and location of outbreaks, individuals may experience significant physical discomfort and some disability. Itching and pain can interfere with basic functions, such as self-care, walking, and sleep. Plaques on hands and feet can prevent individuals from working at certain occupations, playing some sports, and caring for family members or a home. The frequency of medical care is costly and can interfere with an employment or school schedule.

Individuals with psoriasis may also feel self-conscious about their appearance and have a poor self-image that stems from fear of public rejection and psychosexual concerns. Psychological distress can lead to significant depression and social isolation.

Epidemiology

Psoriasis affects both sexes equally and can occur at any age, although it most commonly appears for the first time between the ages of 15 and 25 years.

The prevalence of psoriasis in Western populations is estimated to be around 2-3%. A survey conducted by the National Psoriasis Foundation (a US based psoriasis education and advocacy group, which is partly funded by pharmaceutical companies) found a prevalence of 2.1% among adult Americans. The study also found that 35% of people with psoriasis could be classified as having moderate to severe psoriasis.

Around one-third of people with psoriasis report a family history of the disease, and researchers have identified genetic loci associated with the condition. Studies of monozygotic twins suggest a 70% chance of a twin developing psoriasis if the other twin has psoriasis. The concordance is around 20% for dizygotic twins. These findings suggest both a genetic predisposition and an environmental response in developing psoriasis.

Onset before age 40 usually indicates a greater genetic susceptibility and a more severe or recurrent course of psoriasis.

Cause

The cause of psoriasis is not fully understood. There are two main hypotheses about the process that occurs in the development of the disease. The first considers psoriasis as primarily a disorder of excessive growth and reproduction of skin cells. The problem is simply seen as a fault of the epidermis and its keratinocytes. An alternate viewpoint sees the disease as being an immune-mediated disorder in which the excessive reproduction of skin cells is secondary to factors produced by the immune system. It is thought that T cells (which normally help protect the body against infection) become active, migrate to the dermis and trigger the release of cytokines (tumor necrosis factor-alpha TNFα, in particular) which cause inflammation and the rapid production of skin cells. It is not known what initiates the activation of the T cells.

The immune-mediated model of psoriasis has been supported by the observation that immunosuppressant medications can clear psoriasis plaques. However, the role of the immune system is not fully understood, and it has recently been reported that an animal model of psoriasis can be triggered in mice lacking T cells. Animal models, however, reveal only a few aspects resembling human psoriasis.

Psoriasis is a fairly idiosyncratic disease. The majority of people's experience of psoriasis is one in which it may worsen or improve for no apparent reason. Studies of the factors associated with psoriasis tend to be based on small (usually hospital based) samples of individuals. These studies tend to suffer from representative issues, and an inability to tease out causal associations in the face of other (possibly unknown) intervening factors. Conflicting findings are often reported. Nevertheless, the first outbreak is sometimes reported following stress (physical and mental), skin injury, and streptococcal infection. Conditions that have been reported as accompanying a worsening of the disease include infections, stress, and changes in season and climate. Certain medicines, including lithium salt and beta blockers, have been reported to trigger or aggravate the disease. Excessive alcohol consumption, smoking and obesity may exacerbate psoriasis or make the management of the condition difficult.

Treatment

There can be substantial variation between individuals in the effectiveness of specific psoriasis treatments. Because of this, dermatologists often use a trial-and-error approach to finding the most appropriate treatment for their patient. The decision to employ a particular treatment is based on the type of psoriasis, its location, extent and severity. The patient’s age, gender, quality of life, comorbidities, and attitude toward risks associated with the treatment are also taken into consideration.

Medications with the least potential for adverse reactions are preferentially employed. If the treatment goal is not achieved then therapies with greater potential toxicity may be used. Medications with significant toxicity are reserved for severe unresponsive psoriasis. This is called the psoriasis treatment ladder. As a first step, medicated ointments or creams are applied to the skin. This is called topical treatment. If topical treatment fails to achieve the desired goal then the next step would be to expose the skin to ultraviolet (UV) radiation. This type of treatment is called phototherapy. The third step involves the use of medications which are taken internally by pill or injection. This approach is called systemic treatment.

Over time, psoriasis can become resistant to a specific therapy. Treatments may be periodically changed to prevent resistance developing (tachyphylaxis) and to reduce the chance of adverse reactions occurring. This is called treatment rotation.

Topical Treatment

Bath solutions and moisturizers help sooth affected skin and reduce the dryness which accompanies the build-up of skin on psoriatic plaques. Medicated creams and ointments applied directly to psoriatic plaques can help reduce inflammation, remove built-up scale, reduce skin turn over, and clear affected skin of plaques. Ointment and creams containing coal tar (no longer available on prescription in the UK) , dithranol (anthralin), corticosteroids, vitamin D3 analogues (for example, calcipotriol), and retinoids are routinely used. The mechanism of action of each is probably different but they all help to normalise skin cell production and reduce inflammation. Activated vitamin D and its analogues are highly effective inhibitors of skin cell proliferation.

The disadvantages of topical agents are variably that they can often irritate normal skin, can be time consuming and awkward to apply, cannot be used for long periods, can stain clothing or have a strong odour. As a result, it is sometimes difficult for people to maintain the regular application of these medications. Abrupt withdrawal of some topical agents, particularly corticosteroids, can cause an aggressive recurrence of the condition. This is known as a rebound of the condition.

Some topical agents are used in conjunction with other therapies, especially phototherapy.

Phototherapy

It has long been recognised that daily, short, non-burning exposure to sunlight helped to clear or improve psoriasis. Niels Finsen was the first physician to investigate the therapeutic effects of sunlight scientifically and to use sunlight in clinical practice. This became known as phototherapy.

Sunlight contains many different wavelengths of light. It was during the early part of the 20th century that it was recognised that for psoriasis the therapeutic property of sunlight was due to the wavelengths classified as ultraviolet (UV) light.

Ultraviolet wavelengths are subdivided into UVA (380–315 nm), UVB (315–280 nm), and UVC (< 280 nm). Ultraviolet B (UVB) (315–280 nm) is absorbed by the epidermis and has a beneficial effect on psoriasis. Narrowband UVB (311 to 312 nm), is that part of the UVB spectrum that is most helpful for psoriasis. Exposure to UVB several times per week, over several weeks can help people attain a remission from psoriasis.

Ultraviolet light treatment is frequently combined with topical (coal tar, calcipotriol) or systemic treatment (retinoids) as there is a synergy in their combination. The Ingram regime, involves UVB and the application of anthralin paste. The Goeckerman regime combines coal tar ointment with UVB.

Photochemotherapy

Psoralen and ultraviolet A phototherapy (PUVA) combines the oral or topical administration of psoralen with exposure to ultraviolet A (UVA) light. Precisely how PUVA works is not known. The mechanism of action probably involves activation of psoralen by UVA light which inhibits the abnormally rapid production of the cells in psoriatic skin. There are multiple mechanisms of action associated with PUVA, including effects on the skin immune system.

Dark glasses must be worn during PUVA treatment because there is a risk of cataracts developing from exposure to sunlight. PUVA is associated with nausea, headache, fatigue, burning, and itching. Long-term treatment is associated with squamous-cell and melanoma skin cancers.

Systemic Treatment

Psoriasis which is resistant to topical treatment and phototherapy is treated by medications that are taken internally by pill or injection. This is called systemic treatment. Patients undergoing systemic treatment are required to have regular blood and liver function tests because of the toxicity of the medication. Pregnancy must be avoided for the majority of these treatments. Most people experience a recurrence of psoriasis after systemic treatment is discontinued.

The three main traditional systemic treatments are the immunosupressant drugs methotrexate and ciclosporin, and retinoids, which are synthetic forms of vitamin A. Other additional drugs, not specifically licensed for psoriasis, have been found to be effective. These include the antimetabolite tioguanine, the cytotoxic agent hydroxyurea, sulfasalazine, the immunosupressants mycophenolate mofetil, azathioprine and oral tacrolimus. These have all been used effectively to treat psoriasis when other treatments have failed. Although not licensed in many other countries fumaric acid esters have also been used to treat severe psoriasis in Germany for over 20 years.

Biologics are manufactured proteins that interrupt the immune process involved in psoriasis. Unlike generalised immunosuppressant therapies such as methotrexate, biologics focus on specific aspects of the immune function leading to psoriasis. These drugs are relatively new, and their long-term impact on immune function is unknown. They are very expensive and only suitable for very few patients with psoriasis.

Alternative Therapy

  • Antibiotics are not indicated in routine treatment of psoriasis. However, antibiotics may be employed when an infection, such as that caused by the bacteria Streptococcus, triggers an outbreak of psoriasis, as in certain cases of guttate psoriasis.
  • Climatotherapy involves the notion that some diseases can be successfully treated by living in particular climate. Several psoriasis clinics are located throughout the world based on this idea. The Dead Sea is one of the most popular locations for this type of treatment.
  • In Turkey, doctor fish which live in the outdoor pools of spas, are encouraged to feed on the psoriatic skin of people with psoriasis. The fish only consume the affected areas of the skin. The outdoor location of the spa may also have a beneficial effect. This treatment can provide temporary relief of symptoms. A revisit to the spas every few months is often required.
  • Some people subscribe to the view that psoriasis can be effectively managed through a healthy lifestyle. This view is based on anecdote, and has not been subjected to formal scientific evaluation. Nevertheless, some people report that minimizing stress and consuming a healthy diet, combined with rest, sunshine and swimming in saltwater keep lesions to a minimum. This type of "lifestyle" treatment is suggested as a long-term management strategy, rather than an initial treatment of severe psoriasis.
  • A number of patients have reported significant improvements from sun and sea water: unfortunately, salt alone does not have any effect. Sea water contains so many minerals and different life forms (thousands of species of bacteria alone) that it will be hard to determine which of these is causing the observed effects. Interestingly, people in the tropics differentiate between "live" and "dead" sea water: "live" sea water is water that has never been covered.
  • Some psoriasis patients use herbology as a holistic approach that aims to treat the underlying causes of psoriasis.
  • A psychological symptom management programme has been reported as being a helpful adjunct to traditional therapies in the management of psoriasis.
  • It is claimed that Epsom salt may have a positive effect in reducing the effects of psoriasis.
  • There are claims that Neem oil has been in documented use in India for 6000 years. There are claims that this documentation is fraudulent.
  • It is claimed that yoga and meditative practices help psoriasis patients by 'detoxifying' the body and by the reduction of stress.
  • Sulphur has been used for many years as a safe treatment in the alleviation of Psoriasis.
  • Fasting is used by some to treat mild forms of psoriasis.


Historical Treatment

The history of psoriasis is littered with treatments of dubious effectiveness and high toxicity. These treatments received brief popularity at particular time periods or within certain geographical regions. The application of cat faeces to red lesions on the skin, for example, was one of the earliest topical treatments employed in ancient Egypt. Onions, sea salt and urine, goose oil and semen, wasp droppings in sycamore milk, and soup made from vipers have all been reported as being ancient treatments.

In the more recent past Fowler's solution, which contains a poisonous and carcinogenic arsenic compound, was used by dermatologists as a treatment for psoriasis during the 18th and 19th centuries. Grenz Rays (also called ultrasoft X-rays or Bucky rays) was a popular treatment of psoriasis during the middle of the 20th century. This type of therapy was superseded by ultraviolet therapy.

Undecylenic acid was investigated and used for psoriasis some 40 years ago.

All these treatments have fallen out of favour. One alternative treatment, fashionable in the Victorian and Edwardian eras, was Sulphur. Recently Sulphur has re-gained some credibilty as a safe alternative to steroids and coal tar.

Future Drug Development

Historically, agents used to treat psoriasis were discovered by experimentation or by accident. In contrast, current novel therapeutic agents are designed from a better understanding of the immune processes involved in psoriasis and by the specific targeting of molecular mediators. Examples can be seen in the use of biologics which target T cells and TNF inhibitors.

Future innovation should see the creation of additional drugs that refine the targeting of immune-mediators further.

Research into antisense oligonucleotides carries the potential to provide novel therapeutic strategies for treating psoriasis.

Prognosis

Psoriasis is a lifelong condition. There is currently no cure but various treatments can help to control the symptoms. Many of the most effective agents used to treat severe psoriasis carry an increased risk of significant morbidity including skin cancers, lymphoma and liver disease. However, the majority of people's experience of psoriasis is that of minor localized patches, particularly on the elbows and knees, which can be treated with topical medication. Psoriasis does get worse over time but it is not possible to predict who will go on to develop extensive psoriasis or those in whom the disease may appear to vanish. Individuals will often experience flares and remissions throughout their life. Controlling the signs and symptoms typically requires lifelong therapy.

According to one study, psoriasis is linked to 2.5-fold increased risk for nonmelanoma skin cancer in men and women, with no preponderance of any specific histologic subtype of cancer. This, however could be linked to antipsoriatic treatment.

"The Heartbreak of Psoriasis"

The phrase "the heartbreak of psoriasis" is often used both seriously and ironically to describe the emotional impact of the disease. It may include both the effect of having a chronic uncomfortable disorder and the social effects of being self conscious of one's appearance. The term can be found in various advertisements for topical and other treatments; conversely, it has been used to mock the tendency of advertisers to exaggerate (or even fabricate) aspects of a malady for financial gain. While many products today use the phrase in their advertising, it originated in a 1960s advertising campaign for Tegrin, a coal tar-based ointment.

(adapted from Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Psoriasis)





Findings From Current Research

"Ur Skin is the Thing that Everyone Sees and You Cant Change It!": Exploring the Appearance-Related Concerns of Young People with Psoriasis

Authors: Fox FE, Rumsey N, Morris M.

Centre for Appearance Research, Faculty of Applied Sciences, University of the West of England, Bristol, UK. Fiona3.fox@uwe.ac.uk

PURPOSE: The failure of research to capture the qualitative experiences of young people who have chronic skin conditions means that their psychosocial needs are poorly understood. Using a grounded theory approach, this study facilitated group discussions between adolescents with psoriasis in order to rapidly identify themes about their support needs. METHODS: Three online focus groups were hosted in a real time forum. In total, 8 young people aged 11-18 years were recruited through the websites of psoriasis support organizations. Focus groups lasted an average of 1 hour and data was analysed using grounded theory techniques. RESULTS: Appearance-related concerns are central to the experiences of young people with psoriasis. Participants constructed their individual struggle (It and Me) in physical, emotional, motivational and intellectual terms. A strong sense of Us developed as participants recognized the value of meeting peers with psoriasis. This enabled groups to blame Them for their negative social experiences. DISCUSSION: The findings are discussed in the context of literature around adolescence and appearance. It is suggested that the experience of negative social encounters in adolescence may have long-term implications for appearance anxiety specifically and self-esteem generally. The potential of peer support to improve these outcomes is considered.

Journal: Dev Neurorehabil. 2007 Apr-Jun;10(2):133-41.
Adapted from PubMed; click here to access full journal article.




Phase II Clinical Trial of Bexarotene Gel 1% in Psoriasis

Authors: Breneman D, Sheth P, Berger V, Naini V, Stevens V.

University of Cincinnati College of Medicine, Department of Dermatology, Clinical Research Division, Cincinnati, OH 45219, USA. debra.breneman@uc.edu

We report the results of a nonrandomized, open-label pilot trial investigating the safety, tolerability, and efficacy of bexarotene gel 1% in treating chronic mild to moderate plaque psoriasis. Twenty-four adults with mild to moderate stable plaque psoriasis involving 15% or less of their body surface were enrolled. Patients applied bexarotene gel 1%, using an application frequency escalation regimen, starting at once every other day and increasing to 4 times daily as tolerated and beneficial for up to 24 weeks. The primary efficacy instrument was a Physician's Global Assessment (PGA) score evaluating the overall response to treatment. This utilized individual signs of psoriasis and the percent of body surface area involvement. Safety assessments included physical examinations, recording of adverse events, and laboratory safety evaluations. Fifteen out of 24 enrolled patients (63%) achieved at least 50% improvement by PGA score at 2 or more consecutive visits, and 6 (24%) achieved clearing of 90% or more. Six patients maintained a response throughout 8 weeks of follow-up. An increased response appeared to correlate with a higher frequency of gel application. Adverse events occurred primarily at application sites and were mild or moderate in severity. Bexarotene gel 1% was active in treating mild to moderate plaque psoriasis with achievement of durable responses in some patients and was well-tolerated. A randomized, placebo-controlled study would be useful in confirming these results.

Journal: J Drugs Dermatol. 2007 May;6(5):501-6.
Adapted from PubMed; click here to access full journal article.




Measures Used in Specifying Psoriasis Lesion(s), Global Disease and Quality of Life: A Systematic Review

Authors: Garduno J, Bhosle MJ, Balkrishnan R, Feldman SR.

Department of Dermatology, Center for Dermatology Research, Wake Forest University School of Medicine, Winston-Salem, NC, USA.

Objective: To assess which measures are utilized to quantify lesions, disease severity, and quality of life in the current literature on psoriasis vulgaris. Methods: A MEDLINE search was performed with the keyword 'psoriasis' and the following limits 'All Adult: 19+ years', 'published in the last 5 years', 'English', 'Randomized Controlled Trial', and 'Humans'. The 'Methods' section of the individual articles were reviewed for inclusion criteria that described the study participants' state of psoriasis or disease generalization at baseline, methods used to classify or measure psoriasis during the study, the primary and secondary endpoints, and the quality of life measures utilized in each study. Results: A search resulted in a total of 180 articles, out of which 134 were utilized for the review. The criteria most commonly utilized were 'moderate to severe psoriasis', 'BSA >/=10%', 'mild to moderate psoriasis', and 'severe psoriasis'. PASI was the most commonly used measure to describe the extent of psoriasis. The most common QoL measure used was DLQI, being used in 54.8% of the articles that used some form of QoL measure/s. Discussion: Various measures are being utilized for the same purpose of generalizing disease/lesion severity and determining 'quality of life'.

Journal: J Dermatolog Treat. 2007;18(4):223-42.
Adapted from PubMed; click here to access full journal article.




Alefacept: Its Safety Profile, Off-Label Uses, and Potential as Part of Combination Therapies for Psoriasis

Authors: Scheinfeld N.

Department of Dermatology, St Luke's Hospital, New York, NY, USA.

Objectives: To review literature regarding alefacept, a biologic therapy for psoriasis. Methods: A PubMed search using the term alefacept was done through December of 2006 and articles reviewed. Abstracts concerning alefacept presented at the meeting of the Annual meeting of the American Academy of Dermatology in 2004, 2005 and 2006 were reviewed. Attention was paid to alefacept's safety profile, off-label uses, and potential as part of combination therapy for psoriasis. Results: Alefacept is a very safe treatment for psoriasis alone or in conjunction with other therapies. It has been used, anecdotally, with some effect in diseases besides psoriasis. Conclusions: The utility of checking CD4 counts while administering alefacept for 12 weeks is unclear. While no side effects have been linked to CD4 counts lower than 250/cc(3), due to the fact that in clinical trials alefacept was discontinued when the CD4 count was lower than 250/cc(3), the effect of administration of alefacept to patients with low CD4 counts is unknown. Alefacept appears to be the safest biologic therapy for the treatment of psoriasis, safety that has been borne out in patients who have received as many as nine courses of alefacept. Intramuscular alefacept's consistent ability to decrease the psoriasis area and severity index (PASI) scores in psoriatic patients is not as great as phototherapy, cyclosporine, methotrexate or tumor necrosis factor alpha blockers. Repeated courses of alefacept are best used in patients who have previously responded to the medication, so that patients who have found alefacept useful when grouped achieve higher and more consistent improvements of PASI scores with each successive course of alefacept. A test that would identify likely responders would greatly increase the utility of the medication. While reports assessing the combination of alefacept and narrow band ultraviolet B phototherapy have only studied small numbers of patients ( approximately 60), the combination of phototherapy and alefacept appears synergistic and extremely effective with studied patients achieving PASI 75 in more than 75% of cases and thus merits further study. Combinations of alefacept with etanercept, acitretin, and methotrexate have been used anecdotally but effectively to treat recalcitrant psoriasis. Reported effective off-label uses of alefacept include: generalized lichen planus, alopecia areata, steroid-resistant or steroid-dependent acute graft-versus-host disease, scleroderma, nail psoriasis, and palmoplantar psoriasis.

Journal: J Dermatolog Treat. 2007;18(4):197-208.
Adapted from PubMed; click here to access full journal article.




Current and Future Management of Psoriasis

Authors: Menter A, Griffiths CE.

Baylor Research Institute and Southwestern Medical School, Dallas, Texas 75246, USA.

Management of psoriasis begins with identification of the extent of cutaneous disease. However, a holistic, contractual approach to treatment is encouraged, with particular reference to psychosocial disability and quality-of-life issues. The presence of psoriasis on palms, soles, body folds, genitals, face, or nails, and concomitant joint disease, are also important when considering treatment options. An evidence-based approach is essential in delineating differences between the many available treatments. However, archaic approaches, especially combinational ones, are routinely used by some clinicians, with inadequate prospective or comparative evidence. Treatments currently available are: topical agents used predominantly for mild disease and for recalcitrant lesions in more severe disease; phototherapy for moderate disease; and systemic agents including photochemotherapy, oral agents, and newer injectable biological agents, which have revolutionised the management of severe psoriasis. Other innovative treatments are undergoing clinical studies, with the aim of maintaining safe, long-term control of the condition.

Journal: Lancet. 2007 Jul 21;370(9583):272-84.
Adapted from PubMed; click here to access full journal article.




Use of Biological Agents in Patients with Moderate to Severe Psoriasis: A Cohort-Based Perspective

Authors: Jones-Caballero M, Unaeze J, Peñas PF, Stern RS.

Department of Dermatology, Beth Israel Deaconess Medical Center, GZ 522, 330 Brookline Ave, Boston, MA 02215, USA.

OBJECTIVE: To compare characteristics of patients enrolled in a long-term multicenter cohort trial who had used biological therapies for treatment of psoriasis with those who had not used these agents. DESIGN: Retrospective analysis of users vs nonusers of biological therapies. SETTING: Database from the PUVA Follow-up Study, a multicenter, 30-year study of patients originally treated with psoralen UV-A (PUVA) for moderate to severe psoriasis. Patients A total of 521 patients who completed the last cycle of follow-up of the PUVA Follow-up Study. MAIN OUTCOME MEASURES: Demographic data, severity data (physician global assessment), type of biological therapy used, patients' opinions about their therapy, and their best treatment. RESULTS: Seventy-four of 521 patients (14%) used biological therapies: 65% etanercept (n = 48), 22% infliximab (n = 16), 11% efalizumab (n = 8), and 8% alefacept (n = 6). Users of biological therapies were younger, had more formal education, and were more likely to have had a greater extent of psoriasis at entry than the other cohort members. In 1998, those who used biological treatments were more likely than other cohort members to have been assessed as having severe psoriasis. In 2004, no significant difference was noted. Users of etanercept considered this agent to be as effective as methotrexate and more effective in clearing their skin and having fewer adverse effects than PUVA or UV-B. The proportion of patients originally enrolled in the 16 centers who had used biological agents varied greatly (0%-33%). CONCLUSION: After short durations of therapy, patients' opinions about biological agents tended to be positive.

Journal: Arch Dermatol. 2007 Jul;143(7):846-50.
Adapted from PubMed; click here to access full journal article.




Developments in Systemic Immunomodulatory Therapy for Psoriasis

Authors: Berger EM, Gottlieb AB.

Department of Dermatology, Tufts-New England Medical Center, Tufts University School of Medicine, Tufts-NEMC Box #114, 750 Washington Street, Boston, MA 02111, United States.

Psoriasis is an inflammatory skin condition that can be accompanied by joint disease. Pre-biological and biological systemic therapies are effective. Dermatologists have used systemic immunomodulators including methotrexate to treat moderate-to-severe disease for over 30 years. Pre-biological agents have toxicities and side effects that can be difficult to tolerate and require frequent monitoring. Beginning with alefacept in 2003, several biologics including cell-adhesion-molecule antagonists and cytokine antagonists such as tumor necrosis factor-blockers gained approval for psoriasis. They greatly advanced our understanding of psoriasis pathogenesis. Because they are so new, their safety is not established. Tumor necrosis factor-blockers have controversial associations with certain cancers and infections. Biologics require clinical monitoring and have specific contraindications. Scientists are exploring several new therapeutic targets.

Journal: Curr Opin Pharmacol. 2007 Jul 10
Adapted from PubMed; click here to access full journal article.






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