Psoriasis: More than Skin Deep

By Jennifer Wider, M.D.

Society for Women’s Health Research

Newswise — Psoriasis is a chronic disease of the immune system that affects the skin. As many as 7.5 million Americans suffer from psoriasis, according to the National Institutes of Health. Unlike other diseases of the immune system which affect women more often than men, psoriasis occurs about equally in men and women.

Psoriasis is not contagious and cannot be spread from person to person. There are five known forms of the disease. “The most common form, plaque psoriasis, appears as raised, red patches or lesions covered with a silvery white buildup of dead skin cells called scale,” explains Bruce F. Bebo, Jr., Ph.D., director of research and medical programs at the National Psoriasis Foundation in Portland, Ore.

For some people, psoriasis can be a nuisance, for others, it can be debilitating. The symptoms vary from person to person and can include:

* Red, itchy patches of skin that are covered with silver-colored scales.

* Dry, irritated or cracked skin that can bleed when scratched.

* Disorders of the fingernails or toenails including thickened or ridged nails. The nails can become brittle and in some cases, detach from the nail beds.

Most cases of psoriasis wax and wane and include flare-ups which last for a few weeks to months. Some people will go into remission for months to years. But in most cases, the psoriasis will reappear.

Psoriasis can also lead to psoriatic arthritis, which can cause pain and swelling in the joints. Roughly one-tenth to one-third of people with psoriasis will also have psoriatic arthritis, according to the National Psoriasis Foundation. Psoriatic arthritis can lead to joint erosion and get in the way of daily functioning.

Although it affects both genders equally, recent studies show that there may be a racial or ethnic link. “It seems that psoriasis is most common in Caucasians and slightly less common in African Americans. Worldwide, psoriasis is most common in Scandinavia and other parts of northern Europe. It appears to be far less common among Asians and is rare in Native Americans,” Bebo points out.

Research has identified some differences between the sexes in psoriasis related to smoking and alcohol consumption.

Smoking increases the risk of developing psoriasis and can make the disease more severe, especially in women, but the risk goes down if you stop smoking. Alcohol appears to affect psoriasis in men more strongly than in women. Researchers don’t know why, but alcohol consumption appears to be a risk factor for psoriasis in men but not women and it may lower treatment response in men.

The cause of psoriasis isn’t fully clear. The disease is related to a malfunction in the immune system, which results in T-cells attacking healthy skin cells. What triggers the T-cell malfunction isn’t known, but many researchers cite genetic and environmental factors as possibilities. The most noteworthy risk factor for psoriasis is family history. Roughly 30 percent of people with psoriasis have a close relative with the disease.

Diagnosing psoriasis is often done in a doctor’s office. “No special blood tests or diagnostic tools exist to diagnose psoriasis. The physician or other health care provider usually examines the affected skin and decides if it is from psoriasis. Less often, the physician examines a piece of skin (biopsy) under the microscope,” explains Bebo.

There are several therapies for psoriasis available to patients, which focus on reducing skin inflammation and plaque formation. Looking to the future, there are “a number of new treatments in the psoriasis pipeline,” Bebo said, which may help reduce the burden of this chronic and disabling disease. The types of treatments in development include biologics, monoclonal antibodies and immune system modulators.

Women with psoriasis who are pregnant, may become pregnant, or are breastfeeding should discuss carefully with their doctors their treatment options, as some treatments for psoriasis may cause birth defects. There is, however, some good news for pregnant women. Research has shown that hormonal changes during pregnancy may lead to improvements in psoriasis symptoms, providing temporary relief.

You can visit the National Psoriasis Foundation online at http://www.psoriasis.org/.

Sleep Selectively Preserves Emotional Memories

As poets, songwriters and authors have described, our memories range from misty water-colored recollections to vividly detailed images of the times of our lives.

Now, a study led by researchers at Beth Israel Deaconess Medical Center (BIDMC) and Boston College offers new insights into the specific components of emotional memories, suggesting that sleep plays a key role in determining what we remember – and what we forget.

Reported in the August 2008 issue of the journal Psychological Science, the findings show that a period of slumber helps the brain to selectively preserve and enhance those aspects of a memory that are of greatest emotional resonance, while at the same time diminishing the memory’s neutral background details.

“This tells us that sleep’s role in emotional memory preservation is more than just mechanistic,” says the study’s first author Jessica Payne, PhD, a Harvard University research fellow in the Division of Psychiatry at BIDMC. “In order to preserve what it deems most important, the brain makes a tradeoff, strengthening the memory’s emotional core and obscuring its neutral background.”

Previous studies have established the key role that sleep plays in procedural memory, demonstrating that the consolidation of procedural skills (such as typing or playing the piano) is greatly enhanced following a period of sleep.

But sleep’s importance in the development of episodic memories – in particular, those with emotional resonance– has been less clear.

“Emotional memories usually contain highly charged elements – for example, the car that sideswiped us on the ride home – along with other elements that are only tangentially related to the emotion, such as the name of the street we were traveling on or what store we’d just passed,” explains study author Elizabeth Kensinger, PhD, an Assistant Professor in the College of Arts and Sciences at Boston College. “We were interested in examining whether sleep would affect memory for all of these elements equally, or whether sleep might allow some of the event features to decay at a faster rate than others.”

The authors tested 88 college students. Study participants were shown scenes that depicted either neutral subjects on a neutral background (a car parked on a street in front of shops) or negatively arousing subjects on a neutral background (a badly crashed car parked on a similar street). The participants were then tested separately on their memories of both the central objects in the pictures and the backgrounds in the scenes. In this way, memory could be compared for the emotional aspects of a scene (the crashed car) versus the non-emotional aspects of the scene (the street on which the car had crashed.)

Subjects were divided into three groups. The first group underwent memory testing after 12 hours spent awake during the daytime; the second group was tested after 12 nighttime hours, including their normal period of nighttime sleep; and the third baseline group was tested 30 minutes after viewing the images, in either the morning or evening.

“Our results revealed that the study subjects who stayed awake all day largely forgot the entire negative scene [they had seen], with their memories of both the central objects and the backgrounds decaying at similar rates,” says Payne. But, she adds, among the individuals who were tested after a period of sleep, memory recall for the central negative objects (i.e. the smashed car) was preserved in detail.

“After an evening of sleep, the subjects remembered the emotional items [smashed car] as accurately as the subjects whose memories had been tested only 30 minutes after looking at the scenes,” explains Kensinger. “By contrast, sleep did little to preserve memory for the backgrounds [i.e. street scenes] and so memory for those elements reached a comparably low level after a night of sleep as it did after a day spent awake.”

“This is consistent with the possibility that the individual components of emotional scene memory become ‘unbound’ during sleep,” adds Payne, explaining that “unbinding” enables the sleeping brain to selectively preserve only that information which it calculates to be most salient and worthy of remembering. A real-world example of this tradeoff, she adds, is the “weapon focus effect” in which crime victims vividly remember an assailant’s weapon, but have little memory for other important aspects of the crime scene. Traumatic memories, such as the flashbacks experienced among individuals with post-traumatic stress disorder, can demonstrate similar disparities, with some aspects of an experience seemingly engraved in memory while other details are erased.

“Sleep is a smart, sophisticated process,” adds Payne. “You might say that sleep is actually working at night to decide what memories to hold on to and what to let go of.”

This study was supported, in part, by grants from the National Science Foundation and the National Institute of Mental Health. Coauthors include Elizabeth Kensinger, PhD, of Boston College, Robert Stickgold, PhD, of Beth Israel Deaconess Medical Center; and Kelley Swanberg of Harvard University.

Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School, and consistently ranks among the top four in National Institutes of Health funding among independent hospitals nationwide. BIDMC is clinically affiliated with the Joslin Diabetes Center and is a research partner of Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox. For more information, visit www.bidmc.harvard.edu.

Protein Key to Control, Growth of Blood Cells

New research sheds light on the biological events by which stem cells in the bone marrow develop into the broad variety of cells that circulate in the blood. The findings may help improve the success of bone marrow transplants and may lead to better treatments for life-threatening blood diseases.

“As we better understand the biological pathways that regulate the growth of stem cells, we may identify new approaches for treating blood disorders,” said study leader Wei Tong, Ph.D., a hematology researcher at The Children’s Hospital of Philadelphia. Her study appeared online July 10 in the Journal of Clinical Investigation.

Hematopoietic stem cells (HSCs) develop into all types of blood cells: red blood cells, platelets and immune cells. HSCs, like other stem cells, have the ability to self-renew: each can give rise to more mature, developed cells with more specific functions, as well as a new stem cell. (Everyone carries HSCs in their bone marrow, unlike embryonic stem cells, which exist only in embryos.)

In her study, conducted in mice, Tong focused on a protein called Lnk that helps control HSC expansion. When a growth factor in the blood called thrombopoietin (TPO) acts on its cell receptor, it triggers signals along a pathway that includes another protein, JAK2. JAK2, in turn, causes stem cells to increase their numbers.

Tong’s group and others previously found that Lnk is a negative regulator for HSCs, acting as a brake on stem cell expansion. In the current study, they found that mice genetically engineered to lack the Lnk protein had 10 times the normal amount of HSCs in their bone marrow. Without Lnk to directly interact with JAK2 and inhibit its activity, TPO made stem cell production go into overdrive.

However, there was an unexpected potential benefit-- the expanded population of stem cells had a higher proportion of quiescent cells, those in a resting stage in the cell cycle. Quiescent stem cells, said Tong, are more likely to succeed in a recipient when they are used in bone marrow transplantation.

Although much research remains to be done, added Tong, other researchers might build on this knowledge to manipulate HSCs for more effective bone marrow transplants for cancer patients after high-dose chemotherapy or radiotherapy. It might also improve treatments for particular blood disorders. For example, aplastic anemia, severe combined immunodeficiency disorders and hemoglobin disorders involve deficiencies of specific immune cells in the blood. Using a drug to inhibit Lnk could potentially produce larger numbers of HSCs for a successful bone marrow transplant.

Myeloproliferative disorders (MPDs), on the other hand, entail the opposite danger—a sometimes-fatal overproduction of certain bone marrow cells. Clinicians might use Tong’s research on Lnk and its associated signaling pathway to curtail stem cell production and control MPDs.

The National Cancer Institute, part of the National Institutes of Health, supported Tong’s research, with additional grant funding from the McCabe Foundation and the Institutional Development Fund at Children’s Hospital. Tong’s co-authors were Alexey Bersenev, Chao Wu, and Joanna Balcerek, all of the Division of Hematology at The Children’s Hospital of Philadelphia.

About The Children’s Hospital of Philadelphia: The Children’s Hospital of Philadelphia was founded in 1855 as the nation’s first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children’s Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking third in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 430-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu

Stress, Anxiety Can Make Allergy Attacks Even More Miserable, Last Longer

A new study here shows that even slight stress and anxiety can substantially worsen a person’s allergic reaction to some routine allergens.

Moreover, the added impact of stress and anxiety seem to linger, causing the second day of a stressed person's allergy attack to be much worse.

The finding, the latest in more than three decades of study on stress and immunity, is important since allergic reactions are the fifth-most-common chronic disease in America, and medical costs to treat them can reach $3.4 billion each year.

In a report presented today (8/14) at the annual meeting of the American Psychological Association in Boston, Ohio State University researchers described recent experiments meant to gauge how psychological stress might affect allergy sufferers.

“Allergies are not minor problems,” explained Jan Kiecolt-Glaser, a professor of psychology and psychiatry at Ohio State. “A huge number of people suffer from allergies and, while hay fever, for example, is generally not life-threatening, allergy sufferers often also have asthma which can be deadly.”

Some data suggest that 38 percent of the people who suffer from allergic rhinitis also have asthma, and that 78 percent of asthma sufferers have allergic rhinitis.

Kiecolt-Glaser and Ronald Glaser, professor of molecular virology, immunology and medical genetics at Ohio State, recruited 28 men and women. All of the volunteers had a history of hay fever and seasonal allergies

The volunteers spent two half-days in a research unit at the Ohio State Medical Center. Each time, they were given the standard skin prick test several times to determine their reactions to various allergens, and blood, saliva and serum samples were taken before, after and at several times during the research project.

All of the participants were given a battery of psychological questionnaires to determine their levels of stress, anxiety, self-confidence and feelings of control over situations.

On the day that individuals were assigned to the low-stress control condition, they were given the skin prick test and then asked to read from a magazine. Then they were asked to tape themselves reading the same material aloud.

During the day that people were assigned to the experimental condition, however, they had a much tougher time.

“We used a ‘speech stressor test’ used in a lot of psychology research,” Kiecolt-Glaser said.

“Basically the participants each appeared before a panel of several ‘evaluators’ who supposedly were behavioral experts. Participants had to give a 10-minute speech, which was videotaped, and then are asked a series of math questions they had to solve without paper or pen.”

Afterwards, they had to watch their videotaped performance.

“The whole exercise is a nice stress experiment in the laboratory,” she said.

The researchers measured the raised “wheals” that formed on the arms of the participants before and after they were stressed, as well as the next day.

“The wheals on a person who was moderately anxious because of the experiment were 75 percent larger after the experiment, compared to that same person’s response on the day when they were not stressed,” Kiecolt-Glaser said, signifying a stronger reaction.

“But people who were highly anxious had wheals that were twice as big after they were stressed compared to their response when they were not stressed. Moreover, these same people were four times more likely to have a stronger reaction to the skin test one day later after the stress,” she said.

This next-day change – labeled a “late-phase reaction” – is important because it signals an ongoing and strengthening response to the allergens, and even suggests that sufferers may react strongly to other stimuli that previously hadn’t caused them to develop an allergic reaction.

Gailen Marshall, a co-investigator on the project and professor of medicine and pediatrics at the University of Mississippi, said that late phase, or delayed, reactions are typically unresponsive to the most common forms of allergy treatment, such as antihistimines.

“Late phase reactions also occur in allergic asthma and can, in the proper settings, be potentially life-threatening.

“The results of this study should alert practitioners and patients alike to the adverse effects of stress on allergic reactions in the nose, chest, skin and other organs that may seemingly resolve within a few minutes to hours after starting, but may reappear the nest day when least expected,” he said.

Partner Ronald Glaser, director of the University’s Institute for Behavioral Medicine Research, said that they stimulated cells taken from study participants and then measured the levels of cytokines like interleukin-6 (IL-6) that the cells produced.

Lymphocytes taken from participants during the study showed increased levels of cytokines like IL-6. High levels of IL-6 are part of the allergic response to an allergen, Glaser said. The researchers also measured levels of stress hormones called catecholamines and they were elevated as well.

He suggests that the raised levels of these compounds are to blame for the residual effects seen in the late-phase reaction.

“What’s interesting about this is that it shows that being stressed can cause a person’s allergies to worsen the next day,” she explained.

“This is clinically important for patients since most of what we do to treat allergies is to take antihistimines to control the symptoms – runny nose, watery, itchy eyes, and congestion.

“Antihistimines don’t deal with those symptoms on the next day.”

People may be setting themselves up to have more persistent problems by being stressed and anxious when allergy attacks begin,” Kiecolt-Glaser said.

The researchers estimate that Americans pay $2.3 billion for allergy medications each year and $1.1 billion for doctor visits to treat allergy attacks. Those amounts don’t include approximately 3.5 million workdays lost as well.

Working along with Kiecolt-Glaser, Glaser and Marshall on the project were William Malarkey, professor of internal medicine; Stanley Lemeshow, professor and dean of public health; Kathi Heffner from Ohio University; Kyle Porter, Cathie Atkinson and Byron Laskowski, all from Ohio State.

The research was supported in part by the National Institutes of Health.

Asthma in Boys May Be Just a Phase, But For Girls It May Be There To Stay

Boys may be more apt than girls to have childhood asthma, but, when compared to girls, they are also more likely to grow out of it in adolescence and have a decreased incidence of asthma in the post-pubertal years. This indicates that there may be a buried mechanism in asthma development, according to a prospective study that analyzed airway responsiveness (AR) in more than 1,000 children with mild to moderate asthma over a period of about nine years.

“We wanted to investigate what was behind the observed sex differences in asthma rates and AR,” says lead researcher, Kelan G. Tantisira, M.D., M.P.H., of Brigham and Women’s Hospital and Harvard Medical School. “This is the first study to prospectively examine the natural history of sex differences in asthma in this manner.”

Their results appeared in the second issue for August of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

Dr. Tantisira and colleagues used data from the ongoing Childhood Asthma Management Program (CAMP) that enrolled 1041 children from 5 to 12 years of age with mild to moderate persistent asthma and performed annual spirometric testing with methacholine challenges to quantify their AR.

After an average of 8.6 years and each individual had undergone eight to nine annual methacholine challenges, the researchers were able to identify a clear pattern: when it came to the amount of methacholine it took to provoke airway constriction, the girls’ reactivity did not change markedly over the years. In contrast, boys became increasingly tolerant over time to larger and larger doses of methacholine, suggesting a possible decrease in disease severity. By the age of 16, it took more than twice as much methacholine to provoke a 20 percent constriction in the boys’ airway on average as it did with the girls.

What’s more, by age 18, only 14 percent of the girls did not demonstrate any significant degree of airways responsiveness, compared to 27 percent of boys.

“While our results were not unexpected, they do point to intriguing potential mechanisms, to explain the gender differences in asthma incidence and severity. Especially intriguing is that the differences in gender begin at the time of transition into early puberty.” said Dr. Tantisira.

This study into the natural history and sex differences in asthma marks the beginning of what many hope will be a long investigation into the subject.

“It will be of great interest to follow these children over time to see what happens with AR and severity of asthma in adulthood,” wrote Jorrit Gerritson, M.D., Ph.D., in an accompanying editorial.

This is precisely Dr. Tantisira’s next step: Dr. Tantisira and colleagues now have 12 years of data for the cohort, and is looking into investigating the characteristics of the individuals who attained clinically “normal” AR during follow-up. “Most of the original cohort has now reached adulthood,” said Dr. Tantisira. “We are now able to perform a secondary analysis with an emphasis on those who have reached clinical ‘normalcy.’”

Hope for Patients with COPD

For the first time, a drug therapy appears to reduce lung function loss in patients with moderate to severe chronic obstructive pulmonary disease (COPD), according to the results of a randomized, double-blind, placebo-controlled trial in 42 countries.

The Toward a Revolution in COPD Health (TORCH) study investigated the effects of combined salmeterol, a ß-agonist, and fluticasone propiniate, an inhaled cortical steroid, either alone or in combination, on mortality, exacerbations, health-related quality of life and rate of decline in lung function as measure by forced expiratory volume in one second (FEV1) in patients with COPD.

The results are published in the second issue for August of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

“Pharmacotherapy with salmeterol plus fluticasone propionate, or the components, reduces the rate of decline on FEV1 in patients with moderate to severe COPD, thus slowing disease progression,” wrote Bartolome R. Celli, M.D., lead author of the study and professor at Tufts University School of Medicine. “To date, smoking cessation is the only intervention that has conclusively been shown to alter the rate of decline in FEV1,” remarked Dr. Celli. This is the first demonstration of an effective pharmacothrerapy in COPD.

The TORCH study randomized more than 6,000 patients with moderate to severe COPD from 42 countries to receive either salmeterol (SAL; 50 μg), fluticasone propionate (FP; 500 μg), the two in combination (SFC; 50/500 μg), or placebo. After baseline FEV1 was recorded, patients were re-evaluated every 24 weeks to determine the rate of decline in FEV1.

“The rate of decline in FEV1 was slowest in patients on SFC and fastest in those randomized to the placebo arm,” wrote Dr. Celli. “From week 24 onward, the adjusted rate of decline in FEV1 was 39ml/year for SFC, 42 ml/year for both SAL and FP and 55 ml/year for placebo.”

Although the study was not formally powered to detect differences in rate of decline of FEV1, the results were highly significant (p<0.001.) The rate of decline in treatment groups was similar across a number of variables, including sex, age, ethnicity and body mass index. Furthermore, the slower rate of decline in FEV1 appeared to be associated with a lower risk of exacerbation.

“Although treatment did not abolish the accelerated decline in lung function [that occurs with COPD], it did ameliorate it substantially,” wrote Dr. Celli, while noting that “the mechanism responsible for the effect on rate of decline is not clear, as all treatments have potentially significant nonbronchodilator effects.” Clarifying those mechanisms is the goal of the next phase of the research, with the comparison between a long-acting bronchodilator drug and placebo with respect to FEV1 decline.

In the meantime, “the TORCH study brings some clarity to the treatment picture and provides some hopeful signs for patients with COPD,” wrote Samy Suissa, Ph.D., of McGill University, in the accompanying editorial. “This study also demonstrates that no treatment [placebo] is not an option for patients with moderate to severe COPD.”