Monday, April 30, 2012

Monday Hepatitis C News Ticker-Research and Headlines

Most management decisions were relatively simple, and most patients could be followed primarily by nurse practitioners and physician assistants The field of HCV therapeutics is moving rapidly and much remains to be learned; thus, firm predictions are inherently risky. It is likely, however, that for the foreseeable future, management decisions will require much more thought than they did in the “easy” days of interferon alfa–based regimens.

Interferon-Associated Retinopathy and Non-HCV Related Eye Conditions
This paper reports a case of pegylated interferon-associated retinopathy in a patient with chronic hepatitis C. A 32-year-old female with chronic hepatitis C undergoing pegylated interferon and ribavirin combination therapy complained of visual blurring. Features of interferon-associated retinopathy, including ocular complications such as cotton wool spots, retinal hemorrhages, macular edema, and branch retinal vein occlusion, were found in the fundus of both of her eyes

Coffee reduced HCV replication with regular coffee having a more pronounced effect. Coffee significantly reduced HCV replication at concentrations achievable by coffee consumption, while caffeine as well as caffeine degradation products interfered with HCV replication at high concentrations (about 100 µM or more).

Website 

Advances in the treatment of hepatitis C virus infection.
Thomas DL. Antivir Med. 2012 Apr;20(1):5-10.

The addition of a protease inhibitor (PI) to what has been the standard HCV therapy of peginterferon alfa and ribavirin dramatically improves sustained virologic response rates in treatment-naive patients with genotype 1 infection.

Similar results have been observed in some treatment-experienced patients in whom prior peginterferon alfa/ribavirin therapy has failed. The use of these new agents has also permitted response-guided therapy, wherein early sustained virologic response to treatment allows for a shortened treatment duration.

However, these new PIs add cost and adverse effects to HCV therapy. Boceprevir is associated with increased risk of anemia and dysgeusia, and telaprevir is associated with increased risk of anemia and skin and gastrointestinal adverse effects. Early studies indicate that the addition of PIs results in high response rates in patients with HCV/HIV coinfection. Other studies suggest that combinations of PIs and other direct-acting antivirals may ultimately permit cure when used in interferon sparing regimens....

New @ NATAP

Analysis of long-term persistence of resistance mutations within the hepatitis C virus NS3 protease after treatment with telaprevir or boceprevir





Liz Highleyman
Produced in collaboration with hivandhepatitis.com 
Adding GS-7977 to pegylated interferon and ribavirin for 12 weeks led to a sustained response rate of 90% for previously untreated chronic hepatitis C patients with difficult-to-treat genotype 1, researchers reported at the 47th International Liver ...Continue Reading...

Journals

Annals Of Hepatology
May-June, Vol. 11 Issue 3, 2012

Does the persistently normal aminotransferase levels in hepatitis C sitll have relevance?
Jorge Méndez-Navarro, Margarita Dehesa-Violante

Prevention of hepatocellular carcinoma: a concise review of contemporary issues
Vincent Wai-Sun Wong, Henry Lik-Yuen Chan

Treatment of recurrent genotype 4 hepatitis C after liver transplantation: early virological response is predictive of sustained virological response. An AISF RECOLT-C Group Study
Francesca Romana Ponziani, Alessandro Milani, Antonio Gasbarrini, Raffaella Zaccaria, Raffaella Viganò, Maria Francesca Donato, Maria Cristina Morelli, Lucia Miglioresi, Luisa Pasulo, Maria Rendina, Daniele Di Paolo, Maria Marino, Pierluigi Toniutto, Stefano Fagiuoli, Maurizio Pompili

In The News

Media Advisory - Interview Local Nurses Dedicated to the Hepatitis C Community: National Nursing
Week - May 7 to 13, 2012

TORONTO, April 30, 2012 /PRNewswire via COMTEX/ -- During National Nursing Week, Canadians will recognize and celebrate the important contributions nurses make daily to patient care in Canada. The role nurses play in the prevention and management of chronic hepatitis C, a potentially life-threatening virus, provides a powerful example of their impact as supporter, educator and counsellor.

Canadians living with chronic hepatitis C often fear the judgment of others because the virus infecting them is often associated with injection drug use. The reality is that people can contract the virus through a number of different ways including, body piercings, tattoos, blood transfusions or personal care items (razors).

Members of the Canadian Association of Hepatology Nurses (CAHN) build trusted relationships with patients by not focusing on how the hepatitis C virus was contracted, but rather on providing care and support that is beneficial, respectful and can lead to a cure.

The road to a cure is a difficult journey for patients living with chronic hepatitis C. While treatments can be very successful at getting rid of the virus, the stigma associated with the disease often requires patients to struggle through chemotherapy-like side effects in isolation.

CAHN wants to shatter the stigma for those people living with chronic hepatitis C by helping Canadians recognize that anyone, including someone they know and love, could be living with this virus. Stigma must not be a barrier to detection and treatment.

This National Nursing Week, celebrate the leadership provided by CAHN nurses in the prevention and management of chronic hepatitis C.

What: Interview opportunities with nurses and individuals living with chronic hepatitis C willing to share their stories Who: Cheryl Dale, President of the Canadian Association of Hepatology Nurses, CAHN members and individuals living with chronic hepatitis C Where: The following communities across Canada: Ontario (Toronto, Oakville, Mississauga, Guelph, Hamilton, Kitchener-Waterloo, Newmarket, Sutton, Sudbury, North Bay, and London), Quebec (Montreal), British Columbia (Vancouver, Kelowna, and Nanaimo), Alberta (Edmonton), Nova Scotia (Halifax), and Saskatchewan (Prince Albert) When: National Nursing Week (May 7-13, 2012)

SOURCE Canadian Association of Hepatology Nurses
Copyright (C) 2012 PR Newswire. All rights reserved

Hep C Bulletin: Medication Management
There are hundreds of medications that are metabolized by the liver - both prescription and over-the-counter drugs. In an ideal world, each person would have a physician who knows all about his or her medical history and monitors every pharmaceutical he or she takes. In the real world, many of us are left to fend for ourselves in this arena. Instead of turning one's well-being over to the medical system, being diagnosed with Hepatitis C should put those affected in the driver seat to control their fate:
• by making sure they know what kind of stress every drug taken places on the liver
• by instigating a dialogue with their primary healthcare provider about monitoring their liver's health when necessary

In the end, develop the patience to learn about your medications and the courage to speak up to a doctor about their effect on your liver. Being responsible for these two simple steps can help those with chronic Hepatitis C take an active role in receiving the best healthcare possible.
Continue Reading....

Gilead Sciences Looks For Hepatitis C Cure
Why the emphasis on hep c? While Gilead Sciences has branched out into treatments for cardiovascular diseases, its primary expertise in in anti-viral drugs, particularly for HIV infections, which lead to AIDS if untreated. Because of the effectiveness of its single-tablet, multi-drug combinations, Gilead dominates that market. Gilead also markets Viread for Hepatitis B. The past generation of Hepatitis C therapies have limited effectiveness, have a number of side effects, and cannot be administered orally.

Before the Pharmasset acquisition Gilead had four hepatitis drugs in phase II trials, and three in phase I, and said they would likely be made into a successful combination therapy. Pharmasset added Phase III candidate PSI-7977 (now GS7977), Phase II candidate Mericitabine, and Phase II candidate PSI-938, all for hep C. Pharmasset also brought candidates for HIV and hepatitis B treatment.

Thursday Gilead executives reviewed recent hep C data and clarified their strategy. The GS-7977 plus ribavirin hepatitis C (HCV) genotype 1 Phase 2 study showed no detectible virus after 12 weeks of treatment, but at end of treatment the majority of patients relapsed. GS-7977 plus BMS-790052 (owned by Bristol Myer BMY) showed high hepatitis C cure rates: >90% for genotype 2/3 and 100% for genotype 1.

Based on those and other results, Gilead is designing Phase III studies that could be fully enrolled by the end of May. Several paths are available to get therapies to market, but they need to talk more to regulators before the final trials are initiated. They would clearly prefer an all-Gilead single tablet regimen that cures most hep C, so working with Bristol Myer would be a fall back position. Given the number of drugs Gilead owns and could combine with 7977, it is a good, but not certain, bet that something will work.

At the same time it is a race, since other companies are also trying to break into the all-oral hepatitis market. It is a huge market. An estimated 150 million people have chronic hepatitis C, with the U.S. figure likely somewhere between 3 and 6 million (many people have undiagnosed hep c).

It is too early, I think, to put a number on the value of a hep c cure, but note that Gilead paid $11 billion for Pharmasset. They went through most of their cash and borrowed some $5.5 billion to do it. Gilead annual cash flow runs around $2 billion.

The main risk here is that a competitor (or multiple competitors) will also create an all-oral hepatitis c therapy, and might even gain FDA approval first. Even so, it is a big market and I don't think Gilead's present price reflects much of this opportunity.............
Read full article here

Stem Cells

Stem cell researchers map new knowledge about insulin production      
Monday, 30 April 2012   

Scientists from The Danish Stem Cell Center (DanStem) at the University of Copenhagen and Hagedorn Research Institute have gained new insight into the signaling paths that control the body's insulin production. This is important knowledge with respect to their final goal: the conversion of stem cells into insulin-producing beta cells that can be implanted into patients who need them. The research results have just been published in the journal PNAS.

Insulin is a hormone produced by beta cells in the pancreas. If these beta cells are defective, the body develops diabetes. Insulin is vital to life and therefore today the people who cannot produce their own in sufficient quantities, or at all, receive carefully measured doses – often via several daily injections. Scientists hope that in the not-so-distant future it will be possible to treat diabetes more effectively and prevent secondary diseases such as cardiac disease, blindness and nerve and kidney complications by offering diabetes patients implants of new, well-functioning, stem-cell-based beta cells.

"In order to get stem cells to develop into insulin-producing beta cells, it is necessary to know what signaling mechanisms normally control the creation of beta cells during fetal development. This is what our new research results can contribute," explains Professor Palle Serup from DanStem.
"When we know the signaling paths, we can copy them in test tubes and thus in time convert stem cells to beta cells," says Professor Serup.

The new research results were obtained in a cooperative effort between DanStem, the Danish Hagedorn Research Institute and international partners in Japan, Germany, Korea and the USA. The scientific paper has just been published in the well-respected international journal PNAS (Proceedings of the National Academy of Sciences of the United States of America) entitled Mind bomb 1 is required for pancreatic β-cell formation.

Better control of stem cells
The signaling mechanism that controls the first steps of the development from stem cells to beta cells has long been known.

"Our research contributes knowledge about the next step in development and the signaling involved in the communication between cells - an area that has not been extensively described. This new knowledge about the ability of the so-called Notch signaling first to inhibit and then to stimulate the creation of hormone-producing cells is crucially important to being able to control stem cells better when working with them in test tubes," explains Professor Palle Serup.

This new knowledge about the characteristics of the Notch signaling mechanism will enable scientists to design new experimental ways to cultivate stem cells so that they can be more effectively converted into insulin-producing beta cells.

David vs Goliath in stem cells: the global power of blogs
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The conflict in Ireland over stem cells is still brewing and bubbling this week as I’ve been blogging it.

It is remarkable to me that as just one person I have in a few days been able to have a substantial impact in that dialogue via this blog.

There has been a rather large push lately, especially in the past week, by the “adult stem cells only” crowd in Ireland to advance their cause via press releases and use of traditional media.
For example, the Irish Times published a piece on stem cells in Ireland that almost entirely regurgitated verbatim verbiage from the Adult Stem Cell Foundation of Ireland (ASFI). Rather than a news piece, it was really a propaganda piece.

A more balanced piece was found in the Irish Examiner, presenting arguments from both ASFI, which only advocates use of adult stem cells, and also the Irish Stem Cell Foundation, which advocates the use of all stem cells.

What does the Internet “think” of this issue?
A Google search for Adult Stem Cell Foundation of Ireland yields some remarkable results. While the Irish Times propaganda piece pops up as #1 in the search results sadly, the Irish Examiner piece is #4. Strikingly, two of my blog pieces (here and here) from this week are sandwiched in between at #2 and #3. I also posted another piece that is I believe #12 in the search results.

Thus, in just a manner of 4 days the pieces just mentioning ASFI on this blog have generated enough traffic and interest to be of major importance by Google, impact that is essentially comparable to those of two major traditional newspapers in Ireland. The Times’ circulation in 2011 was almost 400,000 and the Examiner is about 60,000 I believe.

How is it that a blog written by me can compete with these relatively gargantuan media businesses? The reality is that highly read blogs written by a single person can vie with newspapers for influence on specific topics.

Perhaps my pieces will fade in Google’s view over time, but the impact now is surprising to me. I take this power in a very sober manner and consider this a big responsibility. At the same time this tells me that even one patient advocate or stem cell researcher can have a surprisingly powerful influence on the discourse on specific issues.

Of course this power can and is used effectively by people on the other side of the stem cell battlefront. Many examples of powerful “adult stem cells only” blogs are apparent on the Internet.
No matter one’s opinion on issues such as stem cells, an indisputable reality of today is that blogs are quite powerful tools.

Healthy You

Vitamin D supplements may protect against viral infections during the winter
New research published in the Journal of Leukocyte Biology suggests that the older population could benefit from vitamin D supplementation in autumn and winter to protect against viral infections
Vitamin D may be known as the sunshine vitamin, but a new research report appearing in the Journal of Leukocyte Biology shows that it is more than that.

According to the report, insufficient levels of vitamin D are related to a deficiency in our innate immune defenses that protect us from infections, neoplasias or autoimmune diseases. Since vitamin D levels decrease during autumn and winter when days are shorter and sunlight is relatively weak, this may explain why people are more prone to viral infection during these times. It also suggests that vitamin D supplementation, especially in older populations, could strengthen people's innate immunity against viral infections.

"There are numerous studies showing the benefits of maintaining adequate Vitamin D levels. As more and more research into Vitamin D is conducted, we are learning that it is extremely important for human health. Our study is no different, and vitamin D supplements should be considered one of many tools that might help when conventional therapies are not enough," said Victor Manuel Martinez-Taboada, M.D., a researcher involved in the work from the Division of Rheumatology at the Hospital Universitario "Marque's de Valdecilla," Facultad de Medicina at the Unversidad de Cantabria, in Santander, Spain.

To make this discovery, the researchers compared the changes in the blood levels of vitamin D among three groups of healthy subjects: young (age range: 20-30), middle (age range: 31-59), and elderly (age range: 60-86). They found decreased levels of vitamin D with aging, prompting researchers to compare whether such changes kept any relationship with toll-like receptor (TLR) expression measured on lymphocytes and monocytes and function after in vitro stimulation with specific ligands for each of the nine human TLRs and measurement of effector molecules, such as proinflammatory cytokines. Specifically, they found that the TRL most affected by a vitamin D insufficiency is TLR7, which regulates the immune response against viruses. Finally, scientists studied whether there was any difference in the three age groups depending on the season of the year since it is well known that a limited sun exposure during darker winter months is related with vitamin D deficiency.

"Any school teacher will tell you that people tend to be sicker during the winter than any other time of the year," said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology. "There have been numerous studies showing several environmental factors during winter months may allow viruses to spread easier. This study shows that sunlight, or more precisely the lack of vitamin D, could have a role in the seasonally higher rates of infection. More extensive studies must be conducted for this link to be conclusive, but since vitamin D supplements are inexpensive and generally safe, this is a really exciting discovery."

###

The Journal of Leukocyte Biology publishes peer-reviewed manuscripts on original investigatins focusing on the cellular and molecular biology of leukocytes and on the origins, the developmental biology, biochemistry and functions of granulocytes, lymphocytes, mononuclear phagocytes and other cells involved in host defense and inflammation. The Journal of Leukocyte Biology is published by the Society for Leukocyte Biology

Details: Lorena Alvarez-Rodriguez, Marcos Lopez-Hoyos, Maite Garcia-Unzueta, Jose Antonio Amado, Pedro Muñoz Cacho, and Victor Manuel Martinez-Taboada. Age and low levels of circulating vitamin D are associated with impaired innate immune function. J Leukoc Biol May 2012 91:829-838; doi:10.1189/jlb.1011523 ; http://www.jleukbio.org/content/91/5/829.abstract

Anxiety, Depression Often Go Hand-in-Hand With Arthritis

Mental health screening, treatment could improve quality of life for these patients, report suggests

MONDAY, April 30 (HealthDay News) -- Depression or anxiety affect one-third of Americans with arthritis who are aged 45 or older, a new study shows.

Researchers from the U.S. Centers for Disease Control and Prevention also found that even though anxiety is nearly twice as common as depression among people with arthritis, doctors tend to focus more on depression in these patients.


The study included nearly 1,800 people with arthritis or other rheumatic conditions who took part in the CDC's Arthritis Conditions and Health Effects Survey. Among the study participants, 31 percent reported anxiety and 18 percent reported depression.

One-third of the patients reported at least one of the two conditions and 84 percent of those with depression also had anxiety. Only half of those with anxiety or depression sought mental health treatment in the previous year, according to the study, which was published in the April 30 issue of the journal Arthritis Care & Research.

"Given their high prevalence and the effective treatment options that are available, we suggest that all people with arthritis be screened for anxiety and depression," study leader Dr. Louise Murphy, of the Arthritis Program at the CDC, said in a journal news release.

"With so many arthritis patients not seeking mental health treatment, health care providers are missing an intervention opportunity that could improve the quality of life for those with arthritis," she added.
In the United States, 27 million people age 25 and older have osteoarthritis, and 1.3 million adults have rheumatoid arthritis, according to the American College of Rheumatology.

More information
The U.S. National Institute of Arthritis and Musculoskeletal and Skin Diseases offers advice on how to live with arthritis.
Copyright © 2012 HealthDay. All rights reserved.

Of Interest

Is Marijuana Medicinal?
By: DONALD I. ABRAMS, M.D. and JODIE TRAFTON, PH.D.
04/24/12 

POINT: Cannabis can relieve neuropathic pain.
As an oncologist, I treat cancer patients who have nausea, vomiting, weight loss, pain with and without opioids, insomnia, and depression. With cannabis, I can recommend that they try one medicine instead of five or six prescriptions that will interact either with one another or with their cancer chemotherapy.

Studies show that cannabis and cannabinoids are effective for peripheral neuropathic syndromes associated with HIV, multiple sclerosis, or posttraumatic or postsurgical causes. A study of diabetic neuropathy is ongoing; cannabis has not yet been studied for chemotherapy-induced neuropathy. Other data show that cannabis and cannabinoids may be synergistic with opioids in relief of chronic pain without altering pharmacokinetics.



We conducted a randomized, placebo-controlled study of cannabis for patients with HIV-related peripheral neuropathy at San Francisco General Hospital because preclinical studies and anecdotal patient reports said it was helpful. Average neuropathic pain scores in the week before being admitted to our research center were about 60 out of 100.

After a 2-day run-in period, patients were randomized to smoke cannabis or placebo three times a day for 5 days. Among 50 patients who completed the study, neuropathic pain decreased by about 34% with cannabis versus 17% with placebo. Our threshold for a positive response was at least a 30% reduction in pain; this was reported by 52% on cannabis and 24% on placebo (Neurology 2007;68:515-21).

We also used a more objective heat-capsaicin method to assess pain. An area on the forearm was heated to 40° C for half an hour and then capsaicin (the active ingredient in chili peppers) was applied. This creates an area of hypesthesia and allodynia that can be measured using a brush and a piece of foam while the patient looks in another direction.

On the heat-capsaicin tests, the area of hypesthesia or allodynia either increased or was the same after smoking placebo but decreased approximately 30% after smoking cannabis. We calculated that the number needed to treat to get a beneficial effect was 3.6, which is equivalent to that with gabapentin, the mainstay treatment for our patients with HIV-related peripheral neuropathy.

A crossover study in 28 patients with HIV-associated neuropathy at the University of California, San Diego found that pain decreased with cannabis versus placebo. The number needed to treat was 3.5. (Neuropsychopharmacology 2009;34:672-680).

Investigators at the University of California, Davis, randomized 38 patients with central and peripheral neuropathic pain to low- or high-dose cannabis or placebo. They found a linear analgesic dose response for both doses of cannabis, compared with placebo, and reported that the effect was not due to lysis of anxiety but to reduction of core nociception as well as emotional responses to pain. (J. Pain 2008;9:506-21).

Dr. Donald I. Abrams
A randomized, double-blind, four-period crossover study in Montreal looked at 23 participants with postsurgical neuropathic pain who inhaled increasing dosages of tetrahydrocannabinol (THC). Results showed that the average daily pain intensity was significantly lower and quality of sleep improved in the highest-dose THC group, compared with the placebo group (CMAJ 2010;182:e694-701).

We recently completed a study funded by the National Institute on Drug Abuse to look at effects of combined use of opioids and cannabis, in which
we also assessed effects on pain.

We saw a significant 26% reduction in pain with the addition of vaporized cannabis in the cohort as a whole. Pain reduction was greater in the morphine group (a 31% decrease) compared with the oxycodone group (a 23% decrease). We saw no adverse safety effects. Although we know quite well that the study was too small to make a definitive claim, this was a tantalizing demonstration of potential synergy between opioids and cannabinoids, (Clin. Pharmacotherapeutics 2011;90:844-51).

Every 10 years since cannabis was removed from the medical formulary in 1942, some august government body in the United States looks at cannabis in medicine. They all conclude the same thing – that it’s a valuable medicine, and should be available. That usually goes ignored, however. An Institute of Medicine report in 1999 said the accumulated data indicate a potential therapeutic value for cannabinoid drugs in the treatment of pain, control of nausea and vomiting, and appetite stimulation.

Dr. Donald I. Abrams is a professor of clinical medicine at the University of California, San Francisco. He declared having nothing to disclose except that he went to college in the 1960s. This debate took place at the annual meeting of the American Academy of Pain Medicine.

COUNTERPOINT: But chronic use is harmful.
Marijuana doesn’t meet standards to be considered a medicine.

There’s a massive lack of standardization in the product. Compounds have very different, in some cases opposing, effects. Potency varies depending on the strain and how it was prepared.

There’s also no standardization around administration. Smoking or inhaling marijuana – the most common routes speed drug uptake and the effects of cannabinoids on reward processing, which increases addictiveness.

Smoking marijuana is carcinogenic and causes lung damage. Yes, a study suggested twice-a-month use doesn’t really change your lung capacity, but that changed with daily, frequent use. The typical use pattern is about four times per day, daily, in medical patients.

Pain studies looked at acute use of cannabis for a week or so. They haven’t looked at chronic effects. We don’t know the impact of tolerance and dependence in patients with chronic pain, or the effect of constant activation of reward circuits by marijuana on new behavior patterns over time. That’s typically what you have trouble with in chronic pain patients – getting them up, getting them going, getting them back into life. Marijuana could make that more difficult.

Dr. Jodie Trafton
A meta-analysis of 18 randomized, double-blind, controlled trials of cannabis for chronic pain found a greater effect with cannabis than with placebo, but this was not huge. If a patient starts out with a pain score of 8 out of 10, it will drop to about 7.4 – a 7.5% reduction in score. We’re talking about going from severe to a little less severe pain. Patients on cannabis were much more likely to have alterations in perception, motor function, and cognitive function (Pain Med. 2009;10:1353-68).

In the crossover study of 23 patients that Dr. Abrams cites, low-dose and high-dose THC decreased pain, but there was no difference in the middle doses, compared with placebo. And look at the levels of pain scores: You’re going from an average of 6.1 to 5.4, from moderate pain to moderate pain. That’s less than 1 point on a 10-point scale, and you’re getting all of the adverse effects and behavioral changes in conjunction with that. Is that worth it?

The 28-patient crossover study he cites started with 34 patients. There were some serious cannabis-related issues, including acute psychosis and intractable cough, in the patients who didn’t complete it. One patient started using methamphetamine again. This is not a particularly low rate of problems.

We don’t have a lot of data to say what happens to patients with chronic pain who use marijuana over time. There are more data on what happens when people in the general population use marijuana chronically. The best characterized chronic effects include a motivational syndrome, poor concentration, attention and judgment, impaired social skills, introversion, deteriorating personal habits and depersonalization, mood disorders, anxiety disorders, insomnia, increased risk of schizophreniform illness and psychosis, more negative life events, and withdrawal.

Studies have found functional impairments related to chronic marijuana use. People who use marijuana over long periods of time develop at least partially persistent problems on neuropsychological tests – problems that don’t go away even if they stop using marijuana.

There’s also evidence of a relationship between cannabis and mood disorders. Cross-sectional studies show that people who use cannabis daily or near-daily are 3.4 times more likely to have major depression. Longitudinally, if you are diagnosed with cannabis dependence, you have a 6.4-fold increased chance of being diagnosed with major depression within a 12-month time period.

It appears that cannabis is inducing the mood disorders, not the mood disorders driving cannabis use. A Dutch study of 3,854 adults with no history of mood disorders found that cannabis use at baseline was associated with a doubling in risk for developing any mood disorder, a 60% increased risk for major depression, and a five-fold increased risk for bipolar disease (Addiction 2007;102:1251-60).

If cannabis use makes people tend toward mood disorders, and chronic pain patients tend toward mood disorders, how much harder are you making it by suggesting they try marijuana to get that 1-point decrease in pain?

Frequent marijuana use is associated with development of dependence. Withdrawal symptoms occur whenever drug levels start to decrease over time. Withdrawal starts within 2-4 hours, and symptoms last for weeks. Symptoms include irritability, anger or aggression, nervousness or anxiety, sleep difficulty, decreased appetite or weight loss, restlessness, depressed mood, and a variety of physical symptoms causing significant discomfort.

The main reasons that people say they want to use medical marijuana are to treat nervousness, anxiety, insomnia, and depressed mood. All of these potentially are withdrawal symptoms.

One study showed a vast majority of California patients seeking a physician’s recommendation for medical marijuana – well over 95% were already self-medicating with marijuana. We would expect that population to be dependent.

A separate study confirmed that 10 of the 15 "clinical benefits" reported by 1,746 medical marijuana users were the easing of problems that can be found on a list of withdrawal symptoms (J. Psychoactive Drugs 2011;43:128-35).

Chronic pain patients already have high comorbidity with depression, functional problems, and high rates of disability. Recommending medical marijuana increases risk in an already at-risk population.

Jodie Trafton, Ph.D., is director of the Program Evaluation and Resource Center in the Office of Mental Health Operations, Veterans Affairs Palo Alto (Calif.) Health Care System. The views expressed are those of Dr. Trafton and do not necessarily represent those of the Department of Veterans Affairs. She declared having no financial disclosures.
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Hepatitis C Virus Therapeutics: At the End of the Beginning

Topics in Antiviral Medicine

Editorial - Hepatitis C Virus Therapeutics: At the End of the Beginning

Robert T. Schooley, MD

Those of us who have been engaged in HIV therapeutics for the past 2 decades remember all too well the excitement of the 24-month period from 1994 to 1996 that witnessed the treatment paradigm shift from sequential failing regimens of nucleoside analogue reverse transcriptase inhibitors (nRTIs) to stable, “fully” suppressive combination regimens. AIDS as we knew it during the first 15 years of our awareness of the illness has shifted in the most recent 15 years from an inexorably progressive disease to one that can be arrested for a prolonged period of time.1 The speed of this paradigm shift was the result of a well-integrated research effort that included basic, translational, and clinical components that were able to take advantage of a robust pipeline of antiretroviral drugs. Many have argued that the transformation in the prognosis of HIV infection was one of the most impressive demonstrations in recent history of the value of investments in biomedical research.

Although it has received less comment, the equally rapid application of research findings to clinical practice in the United States and Europe was also unprecedented. The translation of research findings to clinical practice was even more impressive in view of the complexity of initial combination treatment regimens and the need for physicians to incorporate rapidly evolving laboratory management tools such as plasma HIV-1 RNA assays and genotypic and phenotypic resistance tests.

The impact of the research findings would never have been realized in the absence of a talented and dedicated HIV treatment community that has continued to bring advances in therapy from clinical trials to the clinic in short order. By the efficient introduction of research findings into medical practice, it is estimated that more than 2.8 million quality-adjusted life-years were saved in the United States between 1989 and 2003.

The HIV treatment community that emerged during the first phase of the epidemic included physicians from a number of different disciplines, including internal medicine, infectious diseases, oncology, dermatology, general medicine, and others.

Despite the broad spectrum of professional training experiences, the HIV treatment community was relatively cohesive, interactive, and well defined. Because of the complexity of HIV management, it quickly became apparent that the best (and most contemporary) care came from those who devoted most of their professional time to HIV care and worked in multidisciplinary teams that included specialists with HIV-specific knowledge in their own subspecialties.

The vast majority of those who stepped forward to do this were those who had been caring for patients with the illness during the “palliative era.” It was a natural step for those who had become comfortable with the disease and its patient population to follow therapeutic developments into the modern treatment era.

We have now entered an era in hepatitis C virus (HCV) therapeutics that promises to be analogous to the “wonder years” of 1994 to 1996 in HIV therapeutics. The first 2 direct- acting antivirals (DAAs) for HCV infection were approved less than a year ago, and more than 30 additional drugs are in clinical trials. When either of the 2 new HCV protease inhibitors is combined with peginterferon alfa and ribavirin,treatment success rates for previously untreated HCV genotype 1–infected patients have increased from approximately 45% to the 60% to 70% range.3,4

As with the case of HIV antiretroviral treatment, it is quite clear that combination treatment will be required for most (or all) patients with HCV infection. It is also clear that as more DAAs emerge from clinical trials and enter clinical practice, management decisions will be complex and will require substantial expertise in many of the same skill sets that characterize contemporary HIV management.

Since the introduction of interferon alfa monotherapy in the early 1990s, HCV therapeutics has been characterized by gradually improving treatment success rates but only incremental increases in the number of people seeking therapy.

Most of those treated received therapy because progression of their liver disease forced the issue. Because accurate assessment of liver disease usually required a liver biopsy, most treatment candidates ended up in the hands of hepatologists before therapy was contemplated. Treatment for HCV was usually undertaken by hepatologists and their nurses, and patients were either cured and returned to the primary care system, or experienced treatment failure and returned to the primary care system for general medical care, with intermittent returns to the hepatologist for complications of liver disease.

In the setting of a fairly steady number of new patients who entered the treatment population as treatment-initiation decisions were made on a one-by-one basis, the number of people actively treated for HCV has remained relatively stable over time (see Box).

Box. HIV and Hepatitis C Virus (HCV) Care Paradigms

Click Image To Enlarge


In contrast, HIV-infected persons are generally referred to HIV specialists and even if treatment succeeds (as is the case for many), these patients then remain in care for life. Thus, the number of people in HIV care has continued to rise steadily, and HIV treatment capacity has expanded correspondingly. As in other areas of medicine, there are geographic disparities, but the overall capacity of the HIV care system has managed so far to keep up with demand.

Current indications are that over the next 18 months to 24 months, we will witness the end of the “interferon alfa” eraof HCV management.5 As this happens, the dialogue about whether to initiate HCV therapy will shift from “Are you telling me that my liver disease is so bad that I really can’t wait any longer?” to “I’m ready for my virectomy; what are we waiting for?”. If treatment success can be achieved in 12 weeks to 24weeks with well-tolerated, all-oral regimens, and if treatment success rates rise to the 90% to 95% range (which seems quite feasible), it is quite likely that there will be a very large influx of HCV-infected persons into the treatment queue.

The roll-out of HCV awareness and screening campaigns will further stimulate treatment demand. Although treatment will be greatly simplified for the patient, it is assumed that for the near future, it will remain complicated for the practitioner. Treatment-initiation decisions will be easier, but treatment management may become more complex before it gets easier. In the peginterferon/ribavirin era, once treatment began, management mainly consisted of following HCV RNA levels for futility and managing well-defined toxicities with dose modification.

Most management decisions were relatively simple, and most patients could be followed primarily by nurse practitioners and physician assistants The field of HCV therapeutics is moving rapidly and much remains to be learned; thus, firm predictions are inherently risky. It is likely, however, that for the foreseeable future, management decisions will require much more thought than they did in the “easy” days of interferon alfa–based regimens.

Considerations in crafting combination regimens will likely include HCV genotype, treatment history, and drug-drug interactions as well as patient-centered considerations such as patient genetics, regimen complexity, toxic effect profile, and adherence challenges.

Management of therapy will be guided by plasma HCV RNA kinetics, and decisions about drug discontinuation and substitution will require detailed knowledge of adverse-effect profiles; resistance-barriers, magnitude and pathways; and future treatment options.

Therefore, at the same time that we can expect a large increase in the number of people seeking therapy, we should also expect that more complex treatment paradigms will require much more ongoing active management.

It is unlikely that the gastroenterology community alone can respond adequately to the challenges posed by dramatically increased numbers of HCV-infected patients seeking much more complex treatment regimens.

Most HCV care is currently provided by the minority within the hepatology community who are interested in viral hepatitis. It is also highly unlikely that gastroenterologists or hepatologists not currently primarily engaged in viral hepatitis therapeutics will be motivated by rapidly changing treatment paradigms to close their procedure rooms to manage a large influx of “E and M” (evaluation and management) patients. Second, as treatment decisions become less amenable to algorithm-guided management by nonphysicians, it seems likely that some of the current HCV treatment community will exit the field.  This leads us to ask from where the next generation of HCV treaters might be recruited.

Given the complexity of treatment decisions (at least over the short- to mid-term), HCV care will likely not migrate from the subset of presently engaged hepatogists to the primary care community. It will instead require the development of a new community of treaters with an interest in complex treatment decisions guided by an appreciation of disease pathogenesis. These physicians will need to be comfortable dealing with psychosocial issues, close laboratory monitoring, response-guided therapy, drug-drug interactions, and a host of other issues.

Having worked through all of these issues in the management of HIV disease, the community of HIV-treating physicians seems uniquely situated to step to the forefront and assume responsibility for managing a disease that is shifting from a liver disease to a viral disease in the coming all oral treatment era. It will, of course, be essential to maintain strong relationships with the hepatology community because expert management of liver disease will continue to be a required element of multidisciplinary HCV care.

The evolution of a care system in which hepatologists are called upon primarily to manage liver disease collaboratively could actually increase the number of hepatologists engaged in HCV care, because virtually the entire hepatology community would be comfortable managing liver disease, though only a subset will remain comfortable managing complex antiviral regimens.

 Much research remains to be done as we work through the host of promising HCV therapeutics in the pipeline, but itseems likely that the current 24-month period following the approval of the first 2 DAAs will be viewed as the end of the beginning in HCV therapeutics. It is essential that we now thoughtfully plan for the coming treatment era if we are to bring research advances to the clinic as rapidly as we did in HIV therapeutics 15 years ago.

Mortality from viral hepatitis has recently surpassed that of HIV.6 We are armed with a rapidly evolving understanding of disease pathogenesis and an exciting array of new therapeutic agents, so prospects for dramatic advances in HCV therapy have never been better. The HIV treatment community can and should play a pivotal role in bringing these advances to the clinic.

Financial Disclosure: Dr Schooley has served as a consultant to 3-V Biologicals, Gilead Sciences, Inc, Inhibitex, Inc, Johnson & Johnson Services, Inc, Laboratory Corporation of America, Merck & Co, Inc, Santaris Pharma, and Tobira Therapeutics. He has stock options for Achillion Pharmaceuticals, Inc.

References
1. Palella FJ, Jr., Delaney KM, Moorman AC, et al. Declining morbidity
and mortality among patients with advanced human immunodeficiency
virus infection. HIV Outpatient Study Investigators. N Engl J
Med. 1998;338:853-860.
2. Walensky RP, Paltiel AD, Losina E, et al. The survival benefits of
AIDS treatment in the United States. J Infect Dis. 2006;194:11-19.
3. Jacobson IM, McHutchison JG, Dusheiko G, et al. Telaprevir for previously
untreated chronic hepatitis C virus infection. N Engl J Med.
2011;364:2405-2416.
4. Poordad F, McCone J, Jr., Bacon BR, et al. Boceprevir for untreated
chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1195-
1206.
5. Lok AS, Gardiner DF, Lawitz E, et al. Preliminary study of two antiviral
agents for hepatitis C genotype 1. N Engl J Med. 2012;366:216-
224.
6. Ly KN, Xing J, Klevens RM, Jiles RB, Ward JW, Holmberg SD. The
increasing burden of mortality from viral hepatitis in the United
States between 1999 and 2007. Ann Intern Med. 2012;156:271-278.



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Successful antiviral treatment of chronic hepatitis C in patients with rare comorbidities. Two case-reports.

Ann Hepatol. 2012 May;11(3):404-8.

Successful antiviral treatment of chronic hepatitis C in patients with rare comorbidities. Two case-reports.

Guardigni V, Fabbri G, Grilli A, Contini C.

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Department of Clinical and Experimental Medicine, Section of Infectious Diseases, University of Ferrara, via Fossato di Mortara, 23, Ferrara, I-44100, Italy.

Abstract
Antiviral therapy in patients suffering from chronic hepatitis C virus (HCV) infection and rare comorbidities cannot be easily started, as it can reduce the likelihood of a good therapeutic response with an increased frequency of side effects. We report two patients presenting unusual comorbidities associated with chronic C hepatitis: one with the Ehlers-Danlos Syndrome (EDS), a rare genetic disease caused by a defect in collagen synthesis, the other one with the Charcot Marie Tooth (CMT) disease, an uncommon but severe form of demyelinating peripheral neuropathy. Both patients were successfully treated with pegylated Interferon (Peg-IFN) and ribavirin (RBV) combined therapy, with the achievement of a sustained viral response (SVR) and a low occurrence of adverse effects. Up to now there are no reports of patients suffering from chronic C hepatitis associated with these uncommon but severe comorbidities treated with antiviral therapy. In conclusion, in such clinical situations, anti-HCV therapy may be started and tailored, especially if the patient is highly motivated and if optimal predictors of response (i.e. young age, favourable genotype and low baseline viraemia) do exist.

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Sunday, April 29, 2012

Interferon-Associated Retinopathy and Non-HCV Related Eye Conditions

Korean J Ophthalmol. 2012 Apr;26(2):147-150.
Published online 2012 March 22.
http://dx.doi.org/10.3341/kjo.2012.26.2.147
PMCID: PMC3325622
Copyright © 2012 The Korean Ophthalmological Society

Pegylated Interferon-Associated Severe Retinopathy in a Patient with Chronic Hepatitis

Hee Young Kang1 and Min Chul Shin21Konyang University Kim's Eye Hospital, Seoul, Korea.
2Department of Ophthalmology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Korea. Corresponding author.Corresponding Author: Min Chul Shin, MD, PhD. Department of Ophthalmology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, #77 Sakju-ro, Chuncheon 200-704, Korea. Tel: 82-33-240-5176, Fax: 82-33-241-8063, Email: mcshin@hallym.ac.kr
Received May 19, 2008; Accepted August 4, 2010.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0 ) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract
This paper reports a case of pegylated interferon-associated retinopathy in a patient with chronic hepatitis C. A 32-year-old female with chronic hepatitis C undergoing pegylated interferon and ribavirin combination therapy complained of visual blurring. Features of interferon-associated retinopathy, including ocular complications such as cotton wool spots, retinal hemorrhages, macular edema, and branch retinal vein occlusion, were found in the fundus of both of her eyes. Pegylated interferon combination therapy was stopped, and the retinopathy of the patient was treated with intravitreal bevacizumab injections and panretinal photocoagulations. This case shows that pharmacokinetically improved pegylated interferon has ocular complications for patients with chronic hepatitis C. Accordingly, patients undergoing pegylated interferon treatment for hepatitis C need regular eye examinations for protection of their vision.

Keywords: Chronic hepatitis C, Interferon-associated retinopathy, Ocular vision, Pegyalted interferon

Interferon is a monotherapy or combination therapy antiviral drug for patients suffering from chronic hepatitis C. Certain ocular complications from interferon therapy have been reported, however, such as cotton wool spots [1-7], retinal hemorrhages [1-7], and optic neuropathy [8], among others. By pegylation of polyethylene glycol (PEG) to interferon, pharmacokinetially improved pegylated interferon has a larger molecular weight and a longer half life in the serum than non-pegylated interferon [3], which increases the efficacy of the drug for chronic hepatitis C patients. Non-pegylated interferon has a 12% to 16% clearance rate in the serum, whereas the 50% to 60% clearance rate of pegylated interferon makes it safer for long-term use by patients [3]. Even though pegyalted interferon is a more effective drug for chronic hepatitis C patients, to our knowledge there are no existing reports or studies about pegylated interferon-associated ocular complications such as interferon-associated retinopathy. To bring the issue to light, this study reports a case of pegylated interferon-associated acute and irreversible severe retinopathy in a patient with chronic hepatitis C.

Case Reports
A 32-year-old female was diagnosed with chronic hepatitis C (grade 3/4, stage 2/4, genotype 2a/c) in February of 2007. She underwent treatment with pegylated interferon-α2b 80 micrograms and ribavirin combination therapy for 5 months (from February of 2007 until July of 2007). She was also treated with subcutaneous insulin injections for a previous condition of pregnant diabetic mellitus diagnosed seven years before. She was first referred to ophthalmology in February of 2007 for a diabetic retinopathy examination. Her vision was 0.6 in both eyes, and intraocular pressure was 11 mmHg in the right eye and 12 mmHg in the left eye. Fundus examination found moderate nonproliferative diabetic retinopathy (NPDR) in the right eye and mild NPDR in the left eye. Accordingly, a follow-up visit to check her eyes was scheduled for six months later. She felt visual blurring two months later, and we referred to a past ophthalmologic exam in June of 2007. At that time, her best corrected visual acuity was 0.04 in both eyes. Previous fundoscopy revealed retinal hemorrhages, cotton wool spots, macular edema, and new vessels elsewhere (NVE) in both eyes (Fig. 1). The pegylated interferon and ribavirin combination therapy was stopped, and the patient was treated with intravitreal 0.05 mL bevacizumab (Avastin) injections. Panretinal photocoagulations were added.

Retinal hemorrhages, cotton wool spots, macular edema, and new vessels were found in both of the patient's eyes.


After completion of treatment, the patient's retinal hemorrhages, cotton wool spots, and macular edema improved (Fig. 2). The retinal non-perfusion areas (Figs. 3 and ​4) and the best corrected visual acuity of the patient did not improve. As of June, we began regular ophthalmic examination of her eyes every other week.
(A,B) After intravitreal bevacizumab injections and panretinal photocoagulations, the cotton wool spots and retinal hemorrhages regressed, but the new vessels remained.
At the late arteriovenous phase (A,B), many microaneurys and new vessels were found. At the mid-venous phase, non-perfusion was more severe in the left eye (D) than in the right eye (C).
At the late arteriovenous phase (A,B) and mid-venous phase (C,D), new vessels and non-perfused areas progressed.


Discussion
Standard interferon therapy in chronic hepatitis C patients causes various ocular complications, including branch retinal vein occlusion [2], subconjunctival hemorrhages [5], visual blurring, papilledema [8], neovascular glaucoma, and retinal detachment [9], among others. The most common among the ocular complications are retinopathy-parapapillary retinal hemorrhages at the posterior pole, and cotton wool spots [1,2,4]. These features of retinopathy occur in approximately 18% to 86% of alpha interferon-treated chronic hepatitis C patients [1]. A study by Jain et al. [4] has reported that these features of retinopathy may occur between 4 to 12 weeks after the start of interferon and ribavirin combination therapy, and will regress within 4 to 12 weeks after therapy stops. The pathogenesis of these features of retinopathy is unknown, however, the hypothesis that interferon interferes with retinal microcirculations is persuasive [7]. In this respect, interferon treatment for patients with abnormal microcirculation diseases, such as diabetic mellitus or hypertension, has a very high risk of causing interferon-associated ocular complications [6,7].

The patient in this case, due to previous diagnosis of diabetic mellitus, belonged to a high-risk group for interferon-associated ocular complications. The patient presented with retinal hemorrhages, cotton wool spots, macular edema, and retinal ischemic changes in both of her eyes. These ocular complications progress more acutely and severely than the progression of complications in a state of pre-pegylated interferon treatment, and the patient's vision decreased irreversibly.

Usually, interferon-treated patients have reversible interferon-associated retinopathy [1-7]. Cases of severe, irreversible visual impairment are very rare [10]. Chronic hepatitis C patients must undergo examination of their eyes before interferon treatment begins, and they must follow up with a second exam within three months of starting treatment. Particularly for high-risk patients with hypertension or diabetes mellitus, not only are regular follow-up examinations very important, but also stopping the interferon treatment at the right time is critical. This report shows that patients treated with pegylated interferon combined with ribavirin may have irreversible and severe ocular complications. This study proposes that chronic hepatitis C patients treated with pharmacokinetically improved pegylated interferon must also be managed with regular and exact ophthalmic examinations on an ongoing basis.
References


HCV Related Eye Condition

 
 
Dry eye - The Schirmer test
HCV infection has been associated with several eye disorders, according to this 2009 study hepatitis C patients, especially those with advanced stages of fibrosis, were more likely to exhibit severe ocular surface damage and signs of dry eye. In another 2011 study researchers concluded that the hepatitis C virus infection causes dry eye. The data also showed - "There was no linear association between time of hepatitis C infection and intensity observed in dry eye tests." *patients in the study did not undergo therapy

Dry eye
A dry eye is caused by a disturbance in the tear film overlying the ocular surface. It may be the result of deficient aqueous production (eg, Sjogren syndrome, lacrimal gland dysfunction/obstruction) or increased evaporation (eg, contact lens use, allergies, Meibomian gland dysfunction, low blink rate). Patients may report burning, pain, foreign body sensation, photophobia, and blurred vision. Diagnosis is usually made based on the history and clinical examination, but a number of more objective tests are available.

 The Schirmer test
The Schirmer test uses filter paper to wick up tears and measure the amount of production, as shown in a patient with Sjogren syndrome. Treatment is initially supportive with artificial tears and the avoidance of offending medications or exposures. For patients with refractory cases, treatment of the underlying systemic illness or surgery may be required


Non-HCV Related Eye Conditions 
 
 
 
 
Blepharitis is an inflammation of the eyelash follicles, along the edge of the eyelid. The cause is overgrowth of the bacteria that is normally found on the skin.
Eyelids have the following symptoms:

Crusty
Reddened
Swollen
Itching
Burning

Blinking causes a granular sensation (like sand or dust in the eye)
Loss of eyelashes may occur

The primary treatment is careful daily cleansing of the edges of the eyelids, to remove the skin oils that the bacteria feed on. Your health care provider might recommend using baby shampoo or special cleansers. Antibiotic ointments may also be helpful in controlling bacteria on the lids.
If seborrheic dermatitis or rosacea are causing the problem, seek treatment for those conditions.

Causes
Blepharitis is usually caused by seborrheic dermatitis or a bacterial infection, and sometimes it is a combination of both. Allergies and eyelash infestation with lice may also cause blepharitis, although these causes are less common.

This condition is characterized by excess oil production in the glands near the eyelid. Too much oil creates an environment where the normal bacteria found on the skin can overgrow. The eyelids appear red and irritated, with scales that cling to the base of the eyelashes.

Blepharitis may be connected to repeated styes and chalazia. Risk factors are seborrheic dermatitis of the face or scalp, rosacea, lice, and allergies.

Tests & diagnosis
An examination of the eyelids during an eye examination is usually enough to diagnose blepharitis.

Prognosis
The likely outcome is good with treatment. Continued attention to lid cleanliness may be required to prevent repeated problems. Continued treatment will typically make the eyes less red and more comfortable.

Prevention
Cleaning eyelids carefully will help prevent blepharitis.
If a specific skin condition is present, it should be treated.

Complications
Styes
Chalazia

The image shown is from a patient with ocular rosacea and shows eyelid telangiectasias (yellow arrow) and inspissated meibomian glands (white arrow). Treatment consists of eyelid hygiene, lubricant eye drops, systemic antibiotics for refractory cases, and the discriminate use of steroids in case of ulcers or conjunctivitis



What is a sty?
A sty (sometimes spelled stye) is a tender, painful red bump located at the base of an eyelash or under or inside the eyelid. The medical term for a sty is hordeolum (plural, hordeola).
A sty results from an acute infection of the oil glands of the eyelid (meibomian glands) that occurs after these glands have become clogged. A sty also may arise from an infected hair follicle at the base of an eyelash. The bacterium Staphylococcus aureus is responsible for 90%-95% of cases of styes. Staph aureus is frequently found on the skin. A sty can develop as a complication of blepharitis (inflammation of the eyelid).
The term external hordeolum has been used to refer to a sty that develops at the base of an eyelash involving a hair follicle of the eyelid, whereas the term internal hordeolum refers to a sty arising due to an inflamed meibomian gland under the eyelid.
A sty is sometimes confused with a chalazion (see below), which is a cyst or a specific type of scarring (due to chronic inflammation) arising in the meibomian glands of the eyelid. In contrast to a sty, a chalazion is usually painless.

What are the signs and symptoms of a sty?
The first symptoms of a sty are generally redness, tenderness, and pain in the affected area. The eye may feel irritated or "scratchy." Later symptoms can include swelling, discomfort during blinking of the eye, watering of the eye, and sensitivity to light. A common sign of a sty is a small, yellowish spot at the center of the bump that develops as pus expands in the area.

Who is most susceptible to the development of a sty?
Styes are very common. People of all ages can develop a sty, and males and females are equally affected. There is a slight increase in incidence of styes during the third to fifth decades of life. People with certain chronic conditions (diabetes mellitus, chronic blepharitis [inflammation of the eyelid], seborrhea, and chronic debilitating illnesses) are more prone to developing styes than the general population. In many susceptible people, stress seems to trigger the development of a sty. Studies have shown that those who have high levels of blood lipids are more susceptible to blockages in the oil glands, including those of the eyelid and, therefore, are more likely to develop a sty.

What is the treatment for a sty?
Application of a warm compress or warm washcloth to the affected area for 10 minutes, four to six times a day, can speed rupture of the sty and aid in the relief of symptoms. A sty should not be pressed or squeezed to facilitate drainage, since this can spread or worsen the infection. If a sty persists for several days, a doctor may lance (drain) the infection under local anesthesia in his or her office. Children who require surgical drainage of a sty may need a general anesthetic. Antibiotic ointments and/or steroid ointments sometimes are prescribed to treat a sty. Rarely, systemic (oral) antibiotics are recommended for persistent or multiple styes. Over-the-counter pain medications may be used to alleviate pain and tenderness. Contact lenses and eye makeup should never be worn during treatment for a sty.

What is the prognosis (outcome) of a sty?
A sty is harmless in the majority of cases. In most cases, a sty ruptures on its own within a few days to a week, leading to relief from symptoms. Some people will require medical or surgical treatment of a sty, as described in the following section. A sty does not cause intraocular damage (damage to the eye). Styes often recur. Complications of styes are rare (see below).

Are there any potential complications resulting from a sty?
Complications of a sty are rare. The infection may spread to other eyelash follicles, leading to multiple styes. A chalazion (a form of scarring of the glands in the eyelid that may include the formation of cysts) is the most common complication that develops from a sty. Chalazia can be large enough to deform the cornea of the eye and interfere with vision, and they may cause a cosmetic problem. Other potential complications include a generalized infection (cellulitis) of the eyelid, and improper drainage of a sty may lead to deformity or disruption of eyelash growth. Progression of a sty to a systemic infection (spreading throughout the body) is extremely rare, and only a few instances of such spread have been recorded.

Can a sty be prevented?
While it is impossible to completely prevent the development of a sty, good hygienic practices, including proper hand washing, can help prevent all forms of infection, including a sty. Other measures that can help prevent styes include never sharing cosmetics or cosmetic eye tools (such as lash curlers or eyelash combs) with others, keeping eye tools clean, discarding old or contaminated eye makeup, keeping all cosmetics clean, and not touching the eye and surrounding areas.

Sty (Stye, Hordeolum) At A Glance
A sty (sometimes spelled stye and medically referred to as a hordeolum) is a tender, painful red bump located at the base of an eyelash or under or inside the eyelid.

Application of a warm compress or warm washcloth to the affected area for 10 minutes, four to six times a day, can speed rupture of the sty and aid in the relief of symptoms.
Styes are common and are generally harmless.
A chalazion (a form of scarring of the glands in the eyelid that may include the formation of cysts) is the most common complication that develops from a sty.



Chalazion
Conservative treatment for small, asymptomatic chalazions begins with lid massage, moist heat, and topical mild steroid drops. Firm pressure on the lid may express thick secretions. Oral tetracyclines will minimize the risk of infection. Surgical incision and curettage allows for drainage and is performed for large, symptomatic chalazions (shown). Biopsy of recurrent chalazions should be performed to rule out sebaceous cell carcinoma.



 Chalazion
A chalazion is a lump of the lid that is caused by obstruction of an oil gland within the upper or lower eyelid. This lump may increase in size over days to weeks and may occasionally become red, warm, or painful.

The gland involved in the formation of a chalazion is a modified oil gland that lies within the eyelid. There are about 40 of these glands within each of the upper and lower lids. These glands secrete oil into the tears. When one of these glands becomes blocked, it can increase in size and cause a visible lump.

Although a sty is also a lump in the eyelid caused by obstruction of an oil gland, a chalazion is not a sty. A sty, or hordeolum, represents an acute infection of the gland. A chalazion is not an infection but is an inflammation of the area. Inflammation is a process in which the body reacts to a condition and produces a swelling, redness, pain, or warmth. A sty is usually more painful than a chalazion and may look infected.

Chalazions are lipogranulomas of either a meibomian gland or a Zeis gland. They develop when lipid breakdown products leak into the surrounding tissues from either bacterial enzymes or retained sebaceous secretions and incite a granulomatous inflammatory reaction. On examination, chalazions appear as single, firm, nontender nodules deep within the lid or tarsal plate (shown). They are more common on the upper vs lower lid because of the increased number and length of meibomian glands on the upper lid. Eversion of the eyelid may show a dilated meibomian gland.



Basal cell carcinomas
Basal cell carcinomas are the most common form of skin cancer overall, and also the most common epithelial tumor of the eyelid. Patients may describe a nonhealing ulcer that bleeds with only mild trauma. On examination the tumor may have the following characteristics: painless nodule, shiny and waxy, indurated, firm and immobile, pearly, rolled border, and small telangiectatic vessels.

Treatment is surgical excision, radiation therapy, chemotherapy, or photodynamic therapy depending on the tumor size, location, and histologic type. The image shown is of a biopsy-proven basal cell carcinoma of the upper lid margin. Note the loss of cilia (madarosis) in the area of the tumor.



Conjunctivitis - Pinkeye

Conjunctivitis, also known as pinkeye, is an inflammation of the conjunctiva, the thin, clear tissue that lies over the white part of the eye and lines the inside of the eyelid.

What Causes Pinkeye?
Pinkeye has a number of different causes, including:
Viruses
Bacteria (such as
gonorrhea or chlamydia)
Irritants such as shampoos, dirt, smoke, and pool chlorine

Allergies, like dust, pollen, or a special type of allergy that affects some contact lens wearers
Pinkeye caused by some bacteria and viruses can spread easily from person to person, but are not a serious health risk if diagnosed promptly. Pinkeye in newborn babies, however, should be reported to a doctor immediately.

Viral conjunctivitis is an infection of the mucous membrane of the surface of the eye. The most common virus responsible is adenovirus, but other viruses have also been identified including herpes simplex, varicella-zoster, picorna, pox, and human immunodeficiency virus. Infections are usually self-limited, but compared to bacterial conjunctivitis they last longer (2-4 weeks), show less inflammation, do not have purulent discharge, and a preauricular lymph node may be palpable. Most patients report itching, foreign body sensation, tearing, redness, and photophobia.

Treatment is largely supportive with artificial tears, cold compresses, and good hand hygiene. Antiviral therapy is reserved for cases of varicella-zoster and herpes simplex infection. Patients in whom appropriate therapy fails or corneal involvement develops should be referred to an ophthalmologist.



Bacterial conjunctivitis

Types of Conjunctivitis Bacterial conjunctivitis is a common type of pink eye, caused by bacteria that infect the eye through various sources of contamination. The bacteria can be spread through contact with an infected individual, exposure to contaminated surfaces or through other means such as sinus or ear infections.

The most common types of bacteria that cause bacterial conjunctivitis include Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae and Pseudomonas aeruginosa. Bacterial conjunctivitis usually produces a thick discharge or pus and can affect one or both eyes.
As with any bacterial infection, antibiotics are required to eliminate the bacteria. Treatment of bacterial conjunctivitis is typically accomplished with topical antibiotic eye drops and/or eye ointments. The treatment usually takes from one to two weeks, depending on the severity of the infection.

Viral conjunctivitis is another common type of pink eye that is highly contagious, because airborne viruses can be spread through sneezing and coughing. Viral conjunctivitis also can accompany common viral upper respiratory infections such as measles, the flu or the common cold.
Viral conjunctivitis usually produces a watery discharge. Typically the infection starts in one eye and quickly spreads to the other eye.

Unlike with bacterial infections, antibiotics will not work against viruses. No eye drops or ointments are effective against the common viruses that cause viral conjunctivitis. But viral conjunctivitis is self-limited, which means it will go away by itself after a short time.

Typically with viral conjunctivitis, the third through the fifth days are the worst. After that, eyes begin to improve on their own. Treatment of viral conjunctivitis usually involves supportive therapies, such as eye drops, that help reduce the symptoms: for example, vasoconstrictors to whiten the eye, decongestants to reduce the surface swelling and antihistamines to reduce
occasional itching. Treatments are usually continued for one to two weeks, depending on the severity of the infection.

Gonococcal and chlamydial conjunctivitis are bacterial forms related to infections from sexually transmitted diseases including gonorrhea and chlamydia. Newborn babies may be exposed when they pass through the birth canal of an infected mother.

Trachoma is a form of chlamydial infection that causes scarring on the eye's surface. Trachoma is the world's leading cause of preventable blindness.

Neonatal conjunctivitis found in newborn babies can cause blindness when left untreated. Up to 10 percent of all pregnant women in the United States have a sexually transmitted chlamydial infection. If these infections are untreated in mothers, the possibility that a newborn infant will develop a related eye infection ranges from 10 percent to 20 percent.*

Another type of sexually transmitted disease related to the herpes simplex
virus type 2 found in the genital area can infect eyes of infants as they are born. Herpes simplex virus type 1, a cause of cold sores on the mouth, also can cause a type of eye herpes that results in pink eye.

If you are pregnant and suspect you may have a sexually transmitted disease, you need to be checked and possibly treated for any infection before the birth of your baby.

Allergic conjunctivitis caused by eye allergies is very common. Eye allergies, like other types, can be triggered by allergens including pollen, animal dander and dust mites.

The most common symptom of allergic conjunctivitis is itchy eyes, which may be relieved with special eye drops containing antihistamines to control allergic reactions. These eye drops are available both over the counter and by prescription.

Avoiding the allergen is also important in the treatment of allergic conjunctivitis. Allergic conjunctivitis can be seasonal or perennial (year-round), depending on the allergen causing the reaction.

Giant papillary conjunctivitis (GPC) usually involves both eyes and often affects soft contact lens wearers. This condition may cause contact lens intolerance, itching, a heavy discharge, tearing and red bumps on the underside of the eyelids.

Non-infectious conjunctivitis from eye irritation causing a pink eye can result from many sources, including smoke, diesel exhaust, perfumes and certain chemicals. Some forms of conjunctivitis also result from sensitivity to certain ingested substances, including herbs such as eyebright and turmeric.**

Certain forms of pink eye, including giant papillary conjunctivitis, can be caused by the eye's immune responses, such as a reaction to wearing contact lenses or ocular prosthetics (artificial eyes).
A reaction to preservatives in eye drops or ointments also can cause toxic conjunctivitis.

Bacterial conjunctivitis is a microbial infection involving the mucous membrane on the surface of the eye. It can be differentiated from viral conjunctivitis by the purulent discharge (shown). It is typically benign and self-limiting, but significant ocular morbidity may develop. In sexually active individuals, Neisseria gonorrhoeae and Chlamydia must be considered. If clinically suspicious, culture specimens and gram stains can be used to identify the specific etiologic agent. The mainstay of treatment is empiric topical antibiotic therapy with a broad-spectrum agent, with systemic antibiotics reserved for N gonorrhoeae and Chlamydia. Frequent handwashing and avoidance of shared linens can help prevent the spread of infection.



Pterygia
A pterygium is an elevated, superficial, external ocular mass that forms over the perilimbal conjunctiva and extends onto the corneal surface. Pterygia are caused by collagen degeneration and fibrovascular proliferation. Increased exposure to ultraviolet light is a risk factor. Clinically, patients may be asymptomatic, or complain of symptoms related to the elevation of the conjunctiva such as redness, itching, blurred vision, and irritation. Patients are typically observed without intervention unless there is significant discomfort or obstruction of the visual axis.



Corneal abrasion 
If the cornea (the membrane that covers the front of the eye) is damaged, the eye becomes inflamed and often very sensitive to light. Damage may occur as a result of an injury, often you get a scratch on your eye from a foreign object or from something else like if you walk through some tall bushes and get scratched in the eye by a branch. Or, if you fall in some dirt while rollerblading or cycling and your eye gets scratched by a pebble.
Call your health care provider right away if you do get a scratch like this on the surface of the eyeball. An infection can occur from the ulceration. You will be given prescription eye drops and sometimes oral medication to prevent infection. The eye can heal very quickly, but you must seek attention quickly with this kind of injury.

With the use of blue light, the fluorescein defect of a corneal abrasion may be more pronounced and will appear yellow-green (shown). Corneal abrasions typically heal without serious complications over time with supportive care: ice compresses and nonsteroidal anti-inflammatory eye drops. Prophylactic antibiotics are commonly prescribed, especially for traumatic or surgical abrasions. Close follow-up is necessary because of the risk of developing a corneal ulcer.




Subconjunctival hemorrhage



Subconjunctival hemorrhage is a bright red patch appearing in the white of the eye. This condition is also called red eye.

Symptoms
A bright red patch appears on the white of the eye. The patch does not cause pain and there is no discharge from the eye. Vision does not change.

Treatment
No treatment is needed. You should have your blood pressure regularly checked.

Causes
A subconjunctival hemorrhage occurs when a small blood vessel breaks open and bleeds near the surface of the white of the eye (bulbar conjunctiva). It may happen without injury, and is often first noticed when you wake up and look in a mirror.
Sudden increases in pressure such as violent sneezing or coughing can cause a subconjunctival hemorrhage. The hemorrhage may also occur in persons with high blood pressure or who take blood thinners.

A subconjunctival hemorrhage is common in newborn infants. In this case, the condition is thought to be caused by the pressure changes across the infant's body during childbirth.

Tests & diagnosis
The health care provider will perform a physical exam and look at your eyes.
Blood pressure should be tested. If you have other areas of bleeding or bruising, more specific tests may be needed.

Prognosis
A subconjunctival hemorrhage usually goes away on its own in about 1 week.

Prevention
There is no known prevention.

Complications
There are usually no complications.
The image shown is of a subconjunctival hemorrhage, a condition that can be easily managed with conservative treatment on an outpatient basis.

Images courtesy of Wikimedia Commons
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