NSAIDs May Worsen Arthritis Inflammation

By Pat Anson, PNN Editor

Ibuprofen, naproxen and other non-steroidal anti-inflammatory drugs (NSAIDs) are often recommended as safer and more effective pain relievers than opioids. As evidence, anti-opioid activists often cite a 2018 study that found NSAIDs worked “significantly better” than opioids in reducing pain intensity for patients with osteoarthritis.

That study by VA researcher Erin Krebs, MD, is cited nearly a dozen times in the newly revised CDC opioid guideline, which recommends that patients avoid opioids and use topical or oral NSAIDs for osteoarthritis pain.

But according to a new long-term study, NSAIDs may actually worsen inflammation and weaken cartilage in patients with knee osteoarthritis, contributing to a painful joint condition called synovitis.

“The goal of our study was to analyze whether NSAID treatment influences the development or progression of synovitis and to investigate whether cartilage imaging biomarkers, which reflect changes in osteoarthritis, are impacted by NSAID treatment,” says lead author, Johanna Luitjens, MD, a postdoctoral scholar in the Department of Radiology and Biomedical Imaging at the University of California, San Francisco.

“NSAIDs are frequently used to treat pain, but it is still an open discussion of how NSAID use influences outcomes for osteoarthritis patients. In particular, the impact of NSAIDs on synovitis, or the inflammation of the membrane lining the joint, has never been analyzed using MRI-based structural biomarkers.”

Luitjens and her colleagues enrolled 277 people with moderate to severe osteoarthritis who used NSAIDs for at least one year, comparing them to a control group of 793 patients who were not treated with NSAIDs. All participants underwent an MRI of the knee at the start of the study and had another MRI four years later. 

The results showed no long-term benefits from NSAID use. The initial MRIs found joint inflammation and cartilage quality were worse in the participants taking NSAIDs, and their knee joints deteriorated even more after four years. 

“In this large group of participants, we were able to show that there were no protective mechanisms from NSAIDs in reducing inflammation or slowing down progression of osteoarthritis of the knee joint,” said Luitjens, who will present her findings next week at the annual meeting of the Radiological Society of North America (RSNA).

Luitjens says there are two possible reasons for the ineffectiveness of NSAIDs. One is that the anti-inflammatory effects of NSAIDs may not be sufficient to prevent synovitis. It’s also possible that patients with synovitis who use NSAIDs may be more physically active due to pain relief, which could have worsened their synovitis. 

In either case, Luitjens believes more evidence is needed to support the continued use of NSAIDs as a treatment for osteoarthritis.

“The use of NSAIDs for their anti-inflammatory function has been frequently propagated in patients with osteoarthritis in recent years and should be revisited, since a positive impact on joint inflammation could not be demonstrated,” she said.

The 2018 Krebs study did not look at how NSAIDs affected joint inflammation. It focused mainly on pain intensity, function and quality of life, and found few differences between opioids and NSAIDs, leading Krebs to conclude that opioids were “not superior” to NSAIDs. As my late colleague Roger Chriss pointed out, researchers also found no harmful effects in patients who took opioids for a year. There was no opioid misuse, addiction or overdoses — a detail rarely mentioned in news coverage of the study.

Osteoarthritis is a joint disorder that leads to thinning of cartilage and progressive joint damage. Knee osteoarthritis is quite common and affects over 250 million people worldwide. Nearly 40 percent of Americans over the age of 45 have some degree of knee osteoarthritis.

How Inflammation Can Lead to Chronic Pain

By Drs. Prakash Nagarkatti and Mitzi Nagarkatti, University of South Carolina

When your body fights off an infection, you develop a fever. If you have arthritis, your joints will hurt. If a bee stings your hand, your hand will swell up and become stiff. These are all manifestations of inflammation occurring in the body.

We are two immunologists who study how the immune system reacts during infections, vaccination and autoimmune diseases where the body starts attacking itself.

While inflammation is commonly associated with the pain of an injury or the many diseases it can cause, it is an important part of the normal immune response. The problems arise when this normally helpful function overreacts or overstays its welcome.

Generally speaking, the term inflammation refers to all activities of the immune system that occur where the body is trying to fight off potential or real infections, clear toxic molecules or recover from physical injury. There are five classic physical signs of acute inflammation: heat, pain, redness, swelling and loss of function. Low-grade inflammation might not even produce noticeable symptoms, but the underlying cellular process is the same.

Take a bee sting, for example. The immune system is like a military unit with a wide range of tools in its arsenal. After sensing the toxins, bacteria and physical damage from the sting, the immune system deploys various types of immune cells to the site of the sting. These include T cells, B cells, macrophages and neutrophils, among other cells.

The B cells produce antibodies. Those antibodies can kill any bacteria in the wound and neutralize toxins from the sting. Macrophages and neutrophils engulf bacteria and destroy them. T cells don’t produce antibodies, but kill any virus-infected cell to prevent viral spread.

Collateral Damage

Additionally, these immune cells produce hundreds of types of molecules called cytokines – otherwise known as mediators – that help fight threats and repair harm to the body. But just like in a military attack, inflammation comes with collateral damage.

The mediators that help kill bacteria also kill some healthy cells. Other similar mediating molecules cause blood vessels to leak, leading to accumulation of fluid and influx of more immune cells.

This collateral damage is the reason you develop swelling, redness and pain around a bee sting or after getting a flu shot. Once the immune system clears an infection or foreign invader – whether the toxin in a bee sting or a chemical from the environment – different parts of the inflammatory response take over and help repair the damaged tissue.

After a few days, your body will neutralize the poison from the sting, eliminate any bacteria that got inside and heal any tissue that was harmed.

Inflammation is a double-edged sword. It is critical for fighting infections and repairing damaged tissue, but when inflammation occurs for the wrong reasons or becomes chronic, the damage it causes can be harmful.

Allergies, for example, develop when the immune system mistakenly recognizes innocuous substances – like peanuts or pollen – as dangerous. The harm can be minor, like itchy skin, or dangerous if someone’s throat closes up.

Chronic inflammation damages tissues over time and can lead to many noninfectious clinical disorders, including cardiovascular diseases, neurodegenerative disorders, obesity, diabetes and some types of cancers.

The immune system can sometimes mistake one’s own organs and tissues for invaders, leading to inflammation throughout the body or in specific areas. This self-targeted inflammation is what causes the symptoms of autoimmune diseases such as lupus and arthritis.

Another cause of chronic inflammation that researchers like us are currently studying is defects in the mechanisms that curtail inflammation after the body clears an infection.

While inflammation mostly plays out at a cellular level in the body, it is far from a simple mechanism that happens in isolation. Stress, diet and nutrition, as well as genetic and environmental factors, have all been shown to regulate inflammation in some way.

There is still a lot to be learned about what leads to harmful forms of inflammation, but a healthy diet and avoiding stress can go a long way toward helping maintain the delicate balance between a strong immune response and harmful chronic inflammation.

Prakash Nagarkatti, PhD, and Mitzi Nagarkatti, PhD, are Professors of Pathology, Microbiology and Immunology at the University of South Carolina. They receive funding from the National Science Foundation and the National Institutes of Health.

This article originally appeared in The Conversation and is republished with permission.

FDA Warns Amazon and Walmart About Selling Misbranded Drugs

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration has issued another warning to consumers not to purchase or use dietary supplements marketed for pain relief under the brand names “Artri” or “Ortiga” due to potentially dangerous pharmaceutical ingredients. Use of the products has led to liver toxicity and at least one death, according to the agency.

The FDA issued its first first warning about the supplements in January and followed up with a second warning  in April. The latest warning includes Amazon, Walmart and another retailer that continued to sell the supplements, which are marketed with claims that they treat arthritis and osteoarthritis, restore cartilage, and stop joint deterioration.

In a warning letter sent to Amazon last week, the FDA said it had purchased Artri and Ortiga supplements through its website and had them delivered through the company’s delivery service.

Laboratory testing confirmed the supplements purchased through Amazon contained diclofenac, a non-steroidal anti-inflammatory drug (NSAID), and dexamethasone, a corticosteroid used to treat inflammatory conditions.

Neither drug is mentioned on product labels, which list ingredients such as glucosamine and turmeric. The FDA warned Amazon that introducing or delivering a misbranded drug is a violation of federal law.  

“Failure to adequately address this matter may result in legal action including, without limitation, seizure and/or injunction. Please submit a written response to this letter within fifteen working days from the date of receipt, explaining the specific steps you have taken to address any violations,” the FDA letter states.

Similar warning letters were sent to Walmart and Latin Foods Market, which had previously issued voluntary recalls for the supplements, but still continued to sell them.

It appears the Artri and Ortiga supplements have now been removed from the websites of all three companies. The supplements were being marketed primarily to Spanish-speaking consumers, with claims they are “highly effective in restoring cartilage” and “fights arthritis.”  

Diclofenac raises the risk of cardiovascular events, such as heart attack and stroke, as well as serious gastrointestinal bleeding and damage. When used long term or in high doses, dexamethasone and other corticosteroids can result in serious withdrawal symptoms if a consumer suddenly stops taking them. Both drugs can also interact with other medications.

The FDA encourages healthcare providers and patients to report side effects involving use of the products to its Adverse Event Reporting System. .

Newly Discovered Gut Bacteria Linked to Rheumatoid Arthritis

By Meagan Chriswell, University of Colorado Medicine

Rheumatoid arthritis affects 1 in 100 people worldwide. It causes inflamed, painful and swollen joints, often in the hands and wrists, and can lead to loss of joint function as well as chronic pain and joint deformities and damage. What causes this condition has been unknown.

In our recently published study, my colleagues and I found an important clue to a potential culprit behind this disease: the bacteria in your gut.

Rheumatoid arthritis is an autoimmune condition, meaning it develops when the body’s immune system starts to attack itself. Proteins called antibodies, which usually help fight off viruses and bacteria, begin to attack the joints instead.

The origins of the antibodies that cause rheumatoid arthritis have been an area of study for many years. Some research has shown that these antibodies can start forming at sites like the mouth, lung and intestines over 10 years before symptoms arise. But until now, it was unclear why researchers were finding these antibodies in these particular areas.

We wanted to investigate what could trigger the formation of these antibodies. Specifically, we wondered if bacteria in the microbiome, a community of microorganisms that live in the intestines, might be the ones activating the immune response that leads to rheumatoid arthritis.

Since microbes commonly live at the same sites as the antibodies driving rheumatoid arthritis, we hypothesized that these bacteria could be triggering the production of these antibodies. We reasoned that though these antibodies were meant to attack the bacteria, rheumatoid arthritis develops when they spread beyond the intestines to attack the joints.

First, we sought to identify the intestinal bacteria targeted by these antibodies. To do this, we exposed the bacteria in the feces of a subset of people at risk for developing rheumatoid arthritis to these antibodies, allowing us to isolate just the bacterial species that reacted and bound to the antibodies.

We found that one previously unknown species of bacteria was present in the intestines of around 20% of people who were either diagnosed with rheumatoid arthritis or produce the antibodies that cause the disease.

As a member of the Cherokee Nation of Oklahoma, I suggested we name this species Subdoligranulum didolesgii (“didolesgii” means arthritis or rheumatism in Cherokee) as a nod to the contributions that other Indigenous scholars have made to science as well as the fact that rheumatoid arthritis affects Indigenous people at a higher rate than other populations.

Subdoligranulum didolesgii has not been detected in the feces of healthy people before, and it is currently unknown how prevalent this bacteria is in the general population.

We also found that these bacteria can activate specialized immune cells called T cells in people with rheumatoid arthritis. T cells drive inflammatory responses in the body, and have been linked to the development of different autoimmune diseases.

These findings suggest that these gut bacteria may be activating the immune systems of people with rheumatoid arthritis. But instead of attacking the bacteria, their immune system attacks the joints.

Why This Bacteria?

It is still unknown why people with rheumatoid arthritis develop an immune response to Subdoligranulum didolesgii. But we think it may be the culprit when it comes to rheumatoid arthritis because this bacteria is found only in the intestines of people with rheumatoid arthritis, and not in the intestines of healthy people.

While many immune responses happen in the intestines, they are usually self-contained and do not spread to other areas of the body. However, we believe that a particularly strong intestinal immune response against Subdoligranulum didolesgii could allow antibodies to bypass the intestinal “firewall” and spread to the joints.

To confirm our hypothesis, we gave mice an oral dose of Subdoligranulum didolesgii and monitored their reaction. Within 14 days, the mice began to develop joint swelling and antibodies that attacked their joints.

My colleagues and I hope this research can shed light on the origins of rheumatoid arthritis. Our next goal is to discover how common these bacteria are in the general population and test whether the presence of these bacteria in the gut may lead to the development of rheumatoid arthritis in people.

It’s important to note that antibiotics are unlikely to be helpful treatment for the microbiomes of patients with rheumatoid arthritis. Although Subdoligranulum didolesgii may be triggering an autoimmune response for some people with rheumatoid arthritis, antibiotics eliminate both helpful and harmful bacteria in the gut. Additionally, removing the bacteria won’t necessarily stop the immune system from attacking the joints once it has started.

Nevertheless, we believe that these bacteria can be used as tools to develop treatments for rheumatoid arthritis and hopefully ways to prevent disease from happening in the first place.

Meagan Chriswell is a MD/PhD Candidate in Immunology at the University of Colorado Anschutz Medical Campus. She does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article.

This article originally appeared in The Conversation and is republished with permission.

Epstein-Barr Virus Linked to Autoimmune Conditions

By Dr. Forest Tennant, PNN Columnist 

The Epstein-Barr virus (EBV) is a herpes virus that normally resides after infection as an organism in the epithelial tissues of the throat and lymphocytes. Most humans carry the virus and blood tests will often show low levels of EBV antibodies.  

Recent research has determined that in some people, for unknown reasons, the virus will reactivate and/or produce antibodies that carry toxic elements to tissues in the body such as the spinal cord. EBV infected lymphocytes can then cross the blood brain barrier and enter the brain, spinal cord and spinal fluid.  

This situation is now referred to as “EBV autoimmunity” and is reported by multiple medical institutions and researchers to be a major, causative factor in multiple sclerosis, systemic lupus, rheumatoid arthritis, and about 2% of the world’s cancer cases.  

Autoimmunity and Arachnoiditis 

Adhesive Arachnoiditis (AA) has long been known to be an inflammatory disease in which cauda equina nerve roots become adhered by adhesions to the arachnoid lining of the spinal canal. We have also long suspected that autoimmunity was a factor in AA, but until now there has been no compelling reason for this belief. 

In our review of over 800 confirmed cases of AA by magnetic resonance imaging (MRI), along with medical history and symptoms, a single fact emerged. Almost all cases had multiple herniated or protruding intervertebral discs prior to the development of AA. These discs were often in both the cervical and lumbar-sacral regions of the spine.  

Epidural injections, spinal taps or surgery often appeared to accelerate the development of AA. But further research revealed that most persons with MRI-documented AA had other medical conditions known to be common in persons with autoimmune disease. These included: burning mouth or feet, small fiber neuropathies, fibromyalgia, carpal tunnel, Hashimoto’s thyroiditis, Sjogren’s (dry eyes), Raynaud’s, irritable bowel, migraine, temporal mandibular joint pain (TMJ), chronic fatigue, arthritis, Tarlov cysts, mast cell conditions, and POTS. Persons with a genetic connective tissue disease of the Ehlers-Danlos Syndrome type were also significantly affected.  

From this we concluded that AA is usually a late-stage component of a multisystem, autoimmune, inflammatory disease. 

Between our realization that AA is associated with multiple medical conditions and the discovery that EBV causes significant autoimmunity, we began EBV testing in persons with MRI-documented AA. Essentially every case showed very high (sometimes above laboratory testing ability) antibody levels. Some showed evidence of EBV reactivation. Another finding has been that some persons with AA have high levels of cytomegalovirus, other strains of herpes, and/or Lyme. 

EBV is now known to cause a multitude of autoimmune conditions. Our studies indicate that AA is a late-stage development of an autoimmune disorder at least partially caused by EBV. This discovery leaves us little option but to recommend that each person with AA determines if they have multiple autoimmune manifestations including herniated discs and, if so, seek EBV antibody testing and become knowledgeable about control measures. 

Forest Tennant, MD, DrPH, is retired from clinical practice but continues his research on the treatment of intractable pain and arachnoiditis. This column is adapted from an updated bulletin recently issued by the Arachnoiditis Research and Education Project. Readers interested in subscribing to the bulletins should click here.

The Tennant Foundation gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.  

New Treatment Offers Hope for Lupus Patients

By Dr. Eric Morand, Monash University, Australia

When real patients have unprecedented positive outcomes to a new treatment, it’s tempting to talk about it as “breakthrough” for medical science. This describes the excitement around a new report from researchers in Germany of a radical new treatment for lupus.

The patients in the study – five people with severe lupus – went into remission following pioneering CAR T-cell treatment, which uses genetically altered cells.

What is lupus, why is this such big news, and what could it mean for other patients and diseases?

Around 5 million people are affected by some form of lupus worldwide. The most common form of lupus is technically known as systemic lupus erythematosus. Though not widespread, it is more common than multiple sclerosis (MS). Both are “autoimmune” diseases where the immune system attacks its owner instead of the germs it is supposed to fight.

MS is an autoimmune disease where the immune system attacks nerve tissue. In contrast, lupus can affect any organ in the body. Treatments for lupus have been so poor for so long that even wealthy and famous people with the disease – like pop star and actor Selena Gomez – have had organ failure resulting in the need for a kidney transplant. A lot of complicating factors have made it hard to improve outcomes for people with the disease.

Firstly, the variety of tissues lupus can affect means no two patients are exactly alike. Diagnosis is hard and often delayed. This also means we researchers have to deal with a lot of complexity as we try to work out what is causing the disease. This clinical variability makes measuring improvement in response to treatment difficult, and many clinical trials have likely failed due to measurement issues.

Second, there is variation between patients in which part of the immune system goes wrong. This means different patients will need different treatments – and we still do not know with certainty how to get this right. But progress is happening fast.

Innate and Adaptive Immunity

The immune system is in two parts, innate and adaptive.

The “innate” immune system responds fast but non-specifically to viruses and other germs that hit the body with a slug of germ-killing inflammatory proteins. The “adaptive” immune system is slower but more precise. It swings into action after the innate immune system and provides long lasting defense against the invading germ.

When you are vaccinated against a disease (such as COVID), the fever and aches you might get in the first day or two is your innate immune system at work. But the long-lasting protection from antibodies is provided by a part of your adaptive immune system, a key part of which is delivered by cells called “B cells”.

In lupus, both parts of the immune system are involved, and both have been successfully used to develop medicines. Earlier this year, the Therapeutic Goods Administration approved anifrolumab, a drug which blocks “interferon”, a crucial protein made by the innate immune system.

Another drug which works on B cells of the adaptive immune system, called belimumab, was approved a few years ago. Unfortunately, neither drug is on Australia’s Pharmaceutical Benefits Scheme yet, so access is extremely limited.

However, we now know that interferon and B cells are both important, and so very strong treatments that almost completely eradicate either could be useful. That is where this potential new treatment comes in.

Already Used to Treat Cancer

Treatments to destroy B cells are used in cancers like lymphoma. The most powerful of these uses CAR-T cells, which train a type of natural cell to be an assassin of the B cell.

CAR-T medicines are highly complex to make, and extremely expensive – but they work.

T cells are collected from the blood, then re-engineered in a special laboratory.

Now, this new report shows targeting B cells using this approach could be effective in lupus too. Building on a first-ever patient treated in this way by the same group a year ago, doctors in Germany created a “homemade” CAR-T treatment and used it in five patients with severe lupus.

Remarkably, all five patients had near complete eradication of disease, allowing them to stop conventional medicines, like steroids, with potentially harmful side effects.

What This Means for Other Patients

So what does it mean for patients in Australia? Well, most centres aren’t able to make their own CAR-T treatments, so delivering this potential treatment will require a commercial approach.

However, it might be quicker to market than other treatments in development as it takes a proven approach into a new disease, rather than being new from the ground up.

One day we might even be able to extend such treatments to other autoimmune diseases, like MS, where B cell-directed treatments have been helpful, as well as in lupus.

This would need to be balanced against risk. Importantly, short term side effects of CAR-T treatment (which include brain and bone marrow problems) can be severe. For this reason, such a treatment would only be used for the most severe cases in which standard treatments have failed, like the patients in the German trial.

Long-term side effects are also unknown at this time, and of course suppressing the immune system so profoundly in the setting of a pandemic is not without major risks.

Formal trials of a commercial CAR-T medicine for lupus are in the advanced planning stages already, and Australia is likely to be front and centre of these due to our lupus expertise and trial-friendly regulatory environment. With all these advances, we can at last tell our patients, and our friends and family with lupus, that there is light at the end of what has been a very long tunnel.

Eric Morand, MD, is a clinical rheumatologist and Head of the School of Clinical Sciences at Monash Health, Monash University in Australia.  Dr. Morand consults with companies involved in lupus drug development, including Novartis and AstraZeneca. He receives funding from Australia’s National Health and Medical Research Council and Lupus Research Alliance US, and is a Director of Rare Voices Australia.

This article originally appeared in The Conversation and is republished with permission.

Older Adults Look Beyond Western Medicine for Help With Joint Pain

By Pat Anson, PNN Editor

Most older Americans use over-the-counter pain medication and exercise to manage their joint pain, according to a large new survey of adults over age 50. Marijuana, opioids and non-steroidal anti-inflammatory drugs (NSAIDs) were rated the most effective pain relievers among those who used them.

The survey of 2,277 adults aged 50 to 80 was conducted online and over the phone early this year as part of the University of Michigan’s National Poll on Healthy Aging. It found that many older adults looked beyond conventional Western medicine for help with their joint pain, but few talked to their doctors about it.

Eight out of ten people (80%) with joint pain said they were confident they could manage it on their own. The survey found that two-thirds (66%) used over-the-counter pain relievers such as NSAID’s or acetaminophen.

The vast majority (89%) also used non-pharmacologic treatments to manage their symptoms, including exercise (64%), massage (26%), physical therapy (24%), splints or braces (13%), and acupuncture or acupressure (5%).

One in four (26%) said they take supplements, such as glucosamine, chondroitin and turmeric, while 11% use cannabidiol (CBD) products and 9% use marijuana.

Only a minority use prescription-based treatments, such as non-opioid pain relievers (18%), steroid joint injections (19%), oral steroids (14%), opioids (14%) and disease-modifying anti-rheumatic drugs (4%).

NATIONAL POLL ON HEALTHY AGING

“There are sizable risks associated with many of these treatment options, especially when taken long-term or in combination with other drugs. Yet 60 percent of those taking two or more substances for their joint pain said their health care provider hadn’t talked with them about risks, or they couldn’t recall if they had,” said Beth Wallace, MD, Assistant Professor of Internal Medicine at Michigan Medicine and a staff rheumatologist at the VA Ann Arbor Healthcare System.

“This suggests a pressing need for providers to talk with their patients about how to manage their joint pain, and what interactions and long-term risks might arise if they use medications to do so.”

Both NSAIDs and oral steroids have health risks, especially for older adults. Chronic NSAID use can worsen medical conditions such as hypertension, kidney disease, gastrointestinal bleeding and cardiovascular disease. Short-term use of oral steroids is associated with similar problems, as well as increased risk of developing diabetes, cataracts, insomnia, depression, and anxiety.

The risks are even greater if NSAIDs and oral steroids are taken together. Despite this, about one in four older adults taking oral steroids for joint pain said they had not discussed the potential risks with their provider.

Joint pain is common among older adults, including those who have not been formally diagnosed with arthritis. Nearly half of those surveyed reported joint pain that limited their daily activities, but few rated their symptoms as severe and most regarded joint pain as a normal part of aging.

Those with severe joint pain were somewhat fatalistic about it, with nearly half (49%) agreeing with the statement that “there is nothing a person with arthritis or joint pain can do to make their symptoms better.” Only 10% of those with mild joint pain agreed there was nothing they could do about it.

“Older adults with fair or poor physical or mental health were much more likely to agree with the statement that there’s nothing that someone with joint pain can do to ease their symptoms, which we now know to be untrue. Health providers need to raise the topic of joint pain with their older patients, and help them make a plan for care that might work for them,” said poll director Preeti Malani, MD, a Michigan Medicine physician who specializes in geriatrics and infectious diseases.

Why I Still Take Precautions Against Covid

By Victoria Reed, PNN Columnist

We are three years into the Covid-19 pandemic, and while life has still not returned to normal, it’s understandable for people to be tired of hearing about the virus and less concerned about catching it. Scientists know more about covid and have developed tools to treat and even prevent the most serious outcomes.

But many of us who are suffering from chronic illness or chronic pain are still wearing masks, practicing social distancing and taking other precautions.

As I go out and about in my daily life, I’ve noticed that mask use is somewhat minimal. People don’t seem to be as concerned about the virus and its variants, even as cases are skyrocketing again. I’m one of the few who still wears a mask in crowded indoor places, airplanes and restaurants.

Fortunately, I have not yet been infected with covid. I attribute that to always being cautious in public (sometimes even outside) and when around family members who I know aren’t taking precautions. Being vaccinated and boosted is another layer of protection I believe has helped me.

The choice to be vaccinated is a personal one and should not be looked at as a political issue or be a source of ridicule. The same goes for mask use. Sometimes people look at me funny because I still wear a mask, but I am “allowed” to do that, just as others are equally allowed to stop wearing theirs.

I don’t judge people who choose not to wear a mask, and conversely, I shouldn’t be judged for wearing one.

Part of my caution comes from having a dysfunctional and overactive immune system, which is altered by a medication I take to control symptoms of rheumatoid arthritis (RA). This medication suppresses a certain part of the immune system that is implicated in the development of RA.  Rheumatoid arthritis primarily attacks the joints, but can also attack the heart, lungs and eyes.

Having to take this particular med (commonly called a biologic), makes me more vulnerable to contracting all types of infection, including covid. It also makes it more difficult to recover from infections and can lead to serious or even deadly complications. 

In addition, the threat of possibly ending up with long covid, when symptoms linger for months or longer, is a concern of mine, especially since fatigue is a major part of long covid syndrome. Profound and disabling fatigue is also a feature of RA and fibromyalgia, so anything I can do to prevent another illness that causes fatigue is important to me. Even mild cases of covid can cause long covid, according to researchers.

Covid can also lead to physical complications. Studies have shown that the virus can cause neurological problems, difficulty breathing, joint or muscle pain, blood clots or other vascular issues, chest pain and unpleasant digestive symptoms.

Furthermore, the virus has been associated with increased psychological problems, such as depression and anxiety. The media has reported on the unfortunate suicides of people who had been suffering from long covid and were unable to get any relief besides ending their own lives.

In the long term, it remains to be seen how covid will affect the millions of us who are already suffering from chronic pain and illness. Fortunately, there are treatments that help with the symptoms and recovery for the majority of people who become infected. There are also medications that can save the lives of those who are at high risk of severe illness.

As more time passes, I’m sure other treatments will emerge, and I’m hopeful that as a chronic pain sufferer with multiple chronic illnesses, I will be okay if I do someday end up getting sick with covid.

Victoria Reed lives in northeast Ohio. She suffers from endometriosis, fibromyalgia, degenerative disc disease and rheumatoid arthritis. 

Experimental Gel Could Replace Damaged Knee Cartilage

By Pat Anson, PNN Editor

Clinical trials on humans may begin as soon as next year on an experimental hydrogel designed to replace damaged cartilage in arthritic knees, according to researchers at Duke University, who say the gel is up to three times stronger than natural cartilage.   

Implants made of the material are currently being tested on sheep by Sparta Biomedical, a medical device company that is developing a line of synthetic cartilage.

“If everything goes according to plan, the clinical trial should start as soon as April 2023,”  Benjamin Wiley, PhD, Sparta’s chief technology officer and a Duke chemistry professor, said in a press release. “I think this will be a dramatic change in treatment for people.”

Wiley says hydrogel implants could someday be used as an alternative to total knee replacement surgery, one of the fastest growing elective procedures in the United States. About one in six adults suffer from knee osteoarthritis, a painful disorder that leads to thinning of cartilage and progressive joint damage.

Often considered the treatment of last resort, knee replacement surgery can be problematic. Studies have found that about a third of the patients who have their knees replaced continue to experience chronic pain. The artificial joints also have a limited life span and sometimes need to be replaced after a few years.   

“There's just not very good options out there,” said Wiley.

To make the hydrogel, Wiley and his team took thin sheets of cellulose fibers and infused them with a water absorbing polymer, creating a Jello-like material that is surprisingly strong. The cellulose fibers act like the collagen in natural cartilage, giving the gel strength when pulled or stretched.

Natural cartilage can withstand up to 8,500 pounds per inch of tugging and squishing before reaching a breaking point. The hydrogel can handle even more pressure and is 66% stronger than cartilage when compressed, the equivalent of parking a car on a postage stamp.

“It’s really off the charts in terms of hydrogel strength,” Wiley says.

Duke researchers first reported in 2020 that they had developed a hydrogel strong enough for knees, but using it to replace cartilage presented some design challenges. Hydrogels are difficult to attach directly to bone or cartilage to keep them from breaking loose or sliding off during intense activities.

They got around that problem by cementing and clamping the hydrogel to a titanium base, which is then anchored into a small hole where the damaged cartilage used to be. Tests showed the design stays fastened 68% more firmly than natural cartilage on bone.

In wear tests, the researchers took the hydrogel and natural cartilage and spun them against each other a million times, with a pressure similar to what the knee experiences during walking. Using high-resolution X-ray imaging, they found that the artificial cartilage held up three times better than the real thing.

DUKE UNIVERSITY IMAGE

And because the hydrogel mimics the smooth and cushiony nature of real cartilage, it protects other joint surfaces from being damaged as they slide against the implant. Other researchers have tried replacing cartilage with implants made of metal or polyethylene, but because those materials are stiffer than cartilage, they can chafe against other parts of the knee.

The research study, published in the journal Advanced Functional Materials, was funded by Sparta Biomedical and Duke University.

An experimental gel also shows promise as a treatment for low back pain caused by degenerative disc disease, according to a recent small study. Hydrafil – an injectable gel developed by ReGelTec – fills in cracks and tears in damaged discs, restoring the disc’s structural integrity. The injection procedure is minimally invasive and only takes about 30 minutes.

Early Use of Methotrexate Slows Rheumatoid Arthritis

By Pat Anson, PNN Editor

Early treatment with methotrexate can significantly reduce joint pain and inflammation in patients showing early signs of rheumatoid arthritis (RA), according to a new study by Dutch researchers.

First used as a chemotherapy treatment because it prevents cancer cells from dividing, methotrexate became a first-line therapy for RA in the 1980’s because it also acts as an immune system inhibitor. RA is a chronic autoimmune disease in which the body’s own defenses attack joint tissues, causing pain, swelling, inflammation and bone erosion. 

Treatment with methotrexate usually isn’t initiated until RA is diagnosed, but researchers at Leiden University Medical Centre (LUMC) in the Netherlands found that early treatment of patients in the "pre-rheumatic phase" helped slow progression of the disease.

"At present, methotrexate is only prescribed to the patient following a rheumatoid arthritis diagnosis," said lead author Annette van der Helm, PhD, Professor of Rheumatology at LUMC. "But that is too late. By then, the disease is already considered chronic."

Van der Helm and her colleagues enrolled 236 patients who had joint pain and inflammation that could be seen on an MRI. Although RA was suspected, it was not yet confirmed. Half the patients were treated with methotrexate and the other half with a placebo. The effects of the treatments were assessed a year later.

The study findings, published in The Lancet, show that early treatment with methotrexate did not prevent the development of RA, but the diagnosis was delayed. Patients in the methotrexate group also had less pain and morning stiffness than those treated with a placebo. Their physical function was also better and their MRI scans showed less joint inflammation.

"This is an important step towards reducing disease burden for this group of patients," says Van der Helm. "This chronic disease is extremely burdensome to patients and their families. Our study is paving the way toward arthritis prevention."

In 2019, over a million people were prescribed methotrexate in the United States, where it is approved as a treatment for RA, psoriasis and cancer. The drug is also used “off-label” for lupus, migraine, multiple sclerosis, Crohn’s Disease and other autoimmune problems.   

‘Abortion-Inducing Drug’

Ironically, the Dutch study comes at a time when some female patients in the U.S. are losing access to methotrexate because the drug can cause miscarriages and be used to end ectopic pregnancies. After last month’s Supreme Court ruling that overturned Roe vs. Wade, over half the states enacted or implemented abortion limits, including some that specifically list methotrexate as an “abortion-inducing drug.”  

Although the state laws don’t prohibit methotrexate from being used for other purposes, some doctors, pharmacies and insurers have become cautious about prescribing or dispensing the drug. The Arthritis Foundation has heard from several women who’ve had trouble getting methotrexate, including some beyond childbearing age.

“Some of the stories we’ve gotten in are of women who are over the age of 50 — they are past their reproductive years — and they’re still being asked really invasive questions and having roadblocks thrown up,” Dr. Anna Hyde of the Arthritis Foundation told NBC4 in Washington.

Up to 90% of RA patients are prescribed methotrexate at some point. It doesn’t work for everyone and can have side effects, but it’s the only affordable option for many patients, costing about $50 for a month’s supply of generic methotrexate tablets. Other treatments for RA, such as disease modifying biologic drugs, can cost as much as $3,000 a month and are not covered by insurance.  

Women Losing Access to Arthritis Drugs Due to Abortion Bans

By Pat Anson, PNN Editor

It didn’t take long for last month’s Supreme Court decision overturning Roe v. Wade to have a ripple effect on the U.S. healthcare system – including unintended consequences for women of childbearing age who have painful conditions such as lupus, rheumatoid arthritis, migraine and multiple sclerosis (MS).

Methotrexate and other drugs used to treat autoimmune and neurological conditions can also be used to induce abortions because they prevent cells from dividing. Although not commonly used for that purpose, methotrexate is officially listed in Texas as an “abortion-inducing drug” – an abortifacient -- putting practitioners at risk of running afoul of the state’s $10,000 bounty on anyone who helps a woman end a pregnancy after six weeks.

Even in states where abortion is legal, physicians, pharmacists and other healthcare providers have become cautious about prescribing or dispensing methotrexate.

“I received an email from my rheumatologist today that they are stopping all refills of methotrexate because it is considered an abortifacient,” a Virginia woman with lupus posted on Twitter just days after Roe was overturned. “If this is happening in a blue state with no trigger law, think of those in red states where abortion isn’t even legal. And those states that have trigger laws causing extreme and immediate loss of access.”

On the same day Roe was overturned, another poster on Twitter said his wife’s rheumatologist took all his female patients off medications that might cause a miscarriage

“So those patients are going to have to go off the drugs that were helping to control their condition and have worse health outcomes. People are going to die because of this,” he said.

The Lupus Foundation of America and Arthritis Foundation said they were aware of the situation and encouraged affected patients to contact them directly.

In an op/ed published in JAMA Neurology, neurologists at UC San Francisco School of Medicine warn the new abortion limits could have life-changing and life-threatening consequences for women with migraine, MS and epilepsy.

"Even if prescribed for a neurological condition, there are reports from patients across the country stating they are now unable to access methotrexate because it can also be used to induce abortion," wrote lead author Sara LaHue, MD, of the UCSF Department of Neurology. "This could increase risk of morbidity, mortality and irreversible disability accumulation for women with neurologic diseases."

Ironically, some treatments for neurological conditions also increase the likelihood of an unplanned pregnancy because they reduce the effectiveness of hormonal contraceptives. Physicians may become reluctant to prescribe those drugs to women of childbearing age.

Some neurologists may also rule out the use of monoclonal antibodies for women — not because they are used in abortions, but because they may harm a fetus.

"In many settings, women with MS are treated with less effective therapies, because these medications are perceived to be safer in pregnancy," said co-author Riley Bove, MD, of the UCSF Department of Neurology. "Often, neurologists are not familiar with how to time or optimize certain medications, or of their updated safety profile. The reversal of Roe v. Wade may reinforce decisions to stick with the less effective therapies, which may result in irreversible disability for some women with MS."

This week the Health and Human Services Department (HHS) warned retail pharmacies they are at risk of violating federal civil rights law if they deny women access to medications used in abortions. The warning specifically mentions methotrexate when its prescribed to someone with rheumatoid arthritis or some other disabling condition.

“If the pharmacy refuses to fill the individual’s prescription or does not stock methotrexate because of its alternate uses, it may be discriminating on the basis of disability,” HHS said..

Walking Reduces Pain From Knee Osteoarthritis

By Pat Anson, PNN Editor

It may seem counterintuitive, but a new study suggests that walking may be the best medicine to reduce knee pain from osteoarthritis.

Nearly 40 percent of Americans over the age of 45 have some degree of knee osteoarthritis, a progressive joint disorder caused by inflammation of soft tissue, which leads to thinning of cartilage and joint damage. Osteoarthritis (OA) of the knee is not to be taken lightly, as studies have found that it is strongly associated with early death, high blood pressure, diabetes, elevated cholesterol and cardiovascular disease, particularly for women.

Moderate exercise like walking may help prevent all of those health problems.

In a multi-year study of 1,212 people over the age of 50, researchers at Baylor College of Medicine found that participants who walked for exercise at least 10 times had 40% less risk of developing frequent knee pain than non-walkers.

“Until this finding, there has been a lack of credible treatments that provide benefit for both limiting damage and pain in osteoarthritis,” said Grace Hsiao-Wei Lo, MD, assistant professor of Immunology, Allergy and Rheumatology at Baylor and lead author of the study published in Arthritis & Rheumatology.

“These findings are particularly useful for people who have radiographic evidence of osteoarthritis but don’t have pain every day in their knees,” Lo explained in a press release. “This study supports the possibility that walking for exercise can help to prevent the onset of daily knee pain.  It might also slow down the worsening of damage inside the joint from osteoarthritis.”  

Lo says walking for exercise has other health benefits, such as improved cardiovascular health and decreased risk of obesity, diabetes and even some cancers. Walking is also a free activity with minimal side effects.

“People diagnosed with knee osteoarthritis should walk for exercise, particularly if they do not have daily knee pain,” says Lo, who is chief of rheumatology at the Michael E. DeBakey VA Medical Center in Houston. "If you already have daily knee pain, there still might be a benefit, especially if you have the kind of arthritis where your knees are bow-legged.”

FTC Sues Footwear Company Over Pain Relief Claims

By Pat Anson, PNN Editor

The U.S. Federal Trade Commission has filed a lawsuit against a California footwear company, alleging it makes false claims that its shoes can relieve knee, back and foot pain. It’s the latest salvo in a long-running legal battle between the FTC and the Gravity Defyer Medical Technology Corporation.

According to the FTC complaint, Gravity Defyer and its owner, Alexander Elnekaveh, violated a 2001 order barring him from using deceptive advertising that makes unsupported scientific claims. The FTC says the company’s ads target people aged 55 and older, telling them its “pain defying footwear” made with “hybrid VersoShock technology” can relieve suffering from arthritis, joint pain, plantar fasciitis and heel spurs.

“Ignoring a prior Commission order, Gravity Defyer and its owner used false pain-relief claims to target older Americans and undercut honest competitors,” Samuel Levine, Director of the FTC’s Bureau of Consumer Protection, said in a statement. “Health-based claims require science-based proof, and faking it by misusing studies and customer reviews breaks the law.”

The 2001 FTC order stems from another company operated by Elnekave, which sold a magnetic fuel-line device that allegedly could reduce gasoline consumption by as much as 27 percent. The FTC says those claims were false and misleading.

Gravity Defyer sells an expensive line of athletic shoes, casual shoes, dress shoes, hiking shoes, boots and sandals for men and women.

They range in price from $140 for a pair of sandals to $235 for work boots.

The company sells the shoes on its website, Amazon and at retailers around the country, including The Walking Company, Hammacher Schlemmer, and Shoe City. It advertises its products on Arthritis Today and WebMD, as well as numerous other publications and websites.

Asked to comment on the FTC complaint, the company sent a statement to PNN claiming that its First Amendment right to free speech was being violated.

GRAVITY DEFYER AD

“Gravity Defyer apprised the FTC of the obvious logical flaws in its stance – and that its stance violates Gravity Defyer’s First Amendment right to disseminate, and consumers’ right to receive, truthful, non-misleading scientific information. The FTC was unrelenting in its strange position,” the company said.

In April, Gravity Defyer filed a lawsuit of its own against the FTC. Much of it hinges on a small 2017 study that the company has long used to justify its pain-relieving claims. The study, recently published the Journal of the American Podiatric Association, found that Gravity Defyer’s “shock-absorbing sole” reduces knee pain an average of 85 percent, significantly better than traditional soles.

The FTC says the study has “substantial flaws” because of its small size (52 participants) and duration (5 weeks), and because it relied on participants’ self-reported pain levels.

“It was also only designed to measure knee pain. Thus, the study was not sufficient to determine the effects of wearing Gravity Defyer’s footwear on knee, back, ankle or foot pain, or pain associated with the specific conditions claimed,” the FTC said.

The Commission, which voted 4-0 to file the complaint, is seeking an order permanently barring Gravity Defyer and Elnekaveh from making misleading or deceptive pain-relief claims, as well as civil penalties.

My Botched Anesthesia During Surgery

By Victoria Reed, PNN Columnist

Have you ever had elective surgery that didn’t go as planned, but instead caused more pain? Did it make you think twice about having surgery again?

Having a chronic illness means that some surgeries are necessary to improve quality of life. People suffering from rheumatoid arthritis (RA) often end up having surgeries, as joint pain and deformity are common complications. Surgeries can include joint replacement or removal of rheumatoid nodules -- subcutaneous lumps or masses that can attach to underlying tissue.

Nodules are associated with more severe forms of RA and usually occur near elbow joints or joints of the hands and feet. About 20% of RA patients suffer from these nodules, which usually aren’t painful, but can cause complications.

I am one of the 20% of RA patients who has developed these nodules. Years ago, I had one growing on the underside of my right big toe. It grew so large that it was causing pain, and I was having trouble walking on that foot. I was compensating for the discomfort by using just the outside of my foot, so I consulted with a podiatrist to talk about having the nodule removed.

The doctor advised me that it could be surgically removed, but also that it could possibly grow back over time. Considering that it was affecting my ability to walk comfortably, I decided to go ahead with the surgery.

For some reason, the doctor did not want to use general anesthesia during the surgery and opted for local injections of an anesthetic to numb the toe.  This did not go well for me. As the surgical assistant injected the medication, he must have hit a nerve because it caused some of the most excruciating pain of my life! It was more painful than childbirth. As I screamed in pain, he injected the toe THREE more times, each one being equally painful.

Needless to say, that was a very traumatic experience, but the toe was indeed numb enough to cut into. After the nodule was removed, which was described in the pathology report as a “wad of gum” type of mass, I was sent home to recover, hopeful that the toe would be as good as new.

It wasn’t.

As the anesthetic wore off, I realized that I had no feeling in the toe. I called the office and inquired as to why I still had no feeling in it and was told to give it time. They assured me that the sensation would eventually return. A week passed, then another week, and still there was no feeling in parts of the toe. Other parts had a new and strangely painful tingling sensation. I called the office again and was told to allow more time for full sensation to return.

Nine years have passed and there has been no improvement. I suffer from sharp, stabbing nerve pain in that toe, which is still completely numb in certain spots. Unfortunately, the nodule has grown back as well. I’m not sure if the injections caused the nerve damage or if the actual removal of the nodule did, but had I received general anesthesia, I would not have had to suffer through those excruciatingly painful injections.

Because of that horrible experience, I am now very reluctant to consider elective surgery again.

We, as chronic pain sufferers, must always advocate for ourselves. Or have someone advocate for us, if we are unable. We should question the decisions made by our medical providers if they don’t seem right or if we are unsure or nervous about a procedure. While there are many competent doctors and surgeons, unfortunately, there are some that are not and who don’t always have our best interest in mind.

I never could have predicted the horrible outcome of that surgery. But the lesson I’ve learned is to ask as many questions as possible prior to any procedure and to thoroughly research any physician who is going to cut into my body. One good question to ask is, “How many of these surgeries have you performed?” Newer surgeons can be perfectly capable, but the more experienced a surgeon is, the better the outcome will likely be for you.

RA can present many challenges, mainly severe pain, but it can also affect a patient’s mobility and morbidity. I will need to decide if I want to have another surgery to remove the recurrent toe nodule or decide if it is something I can learn to live with. Either way, I have learned some valuable lessons.

Victoria Reed lives in Cleveland, Ohio. She suffers from endometriosis, fibromyalgia, degenerative disc disease and rheumatoid arthritis. 

Lipofilling Improved Pain and Function in Patients with Finger Osteoarthritis

By Pat Anson, PNN Editor

People who suffer from painful arthritic fingers have few treatment options to choose from. They can wrap their hand in a splint, take anti-inflammatory drugs or get steroid injections into their finger joints – all of which provide only temporary relief. More invasive surgical treatments include joint fusions or reconstruction, which can impair hand motion and take weeks to recover from.

German researchers have found that a less invasive treatment commonly used in plastic surgery – injecting fat tissue from one part of the body into another -- can provide lasting improvements in pain and function for patients with finger osteoarthritis. The technique – called lipofilling – resulted in “highly significant clear improvement" with no complications in a small pilot study of 15 patients.     

"We believe that for our patients the reduction of pain represents the most striking and important result, which also has the most pronounced and highly significant effect," said co-author Max Meyer-Marcotty, MD, Clinic for Plastic, Reconstructive, and Aesthetic Surgery/Hand Surgery in Lüdenscheid, Germany.

"Even over a long-term follow-up, the transfer of fatty tissue to arthritic fingers joints appears to provide a safe and minimally invasive alternative to conventional surgery for patients with osteoarthritis.”

In the lipofilling procedure, Meyer-Marcotty and his colleagues used liposuction to take a small sample of each patient's fatty tissue from their upper thigh or hip area. The autologous fat was then injected into their arthritic finger joints. Patients wore a splint around the treated fingers and took pain relievers for a week. There were no infections or other complications reported.

The researchers followed outcomes in 25 finger joints for an average of 44 months after treatment, and found that pain scores fell from a median of 6 (on a 10-point scale) before treatment to just 0.5 points at follow-up. Grip strength of the treated fingers approximately doubled, while fist closure and hand function performing everyday tasks also improved.

“Even after a follow-up examination period of 44 months, the transfer of fatty tissue to arthritic finger joints has shown itself to be a minimally invasive, safe, and promising alternative to conventional surgical techniques aimed at alleviating arthritic complaints, and one that among other things entails a highly significant improvement in postsurgical pain levels,” researchers reported in the journal Plastic and Reconstructive Surgery. “Further long-term follow-up studies of even larger patient cohorts would be needed to further corroborate these initial positive findings.”

In recent years, lipofilling procedures have been increasingly used in plastic and reconstructive surgery, as well as stem cell therapy.

When injected into patients, mesenchymal stromal cells (MSCs) in fat tissue can regenerate damaged or diseased tissue, including cartilage in arthritic joints. A small 2019 study found that MSCs collected from a patient’s bone marrow can significantly reduce pain from knee osteoarthritis for up to a year.

Osteoarthritis is a progressive joint disorder caused by the inflammation of soft tissue, which leads to thinning of cartilage and joint damage in the knees, hips, fingers and spine.

"The chance to preserve the joint with a minimally invasive procedure is of particular interest in the early, albeit painful, phases of finger osteoarthritis," said Meyer-Marcotty. "Since the lipofilling procedure is nondestructive, conventional joint surgery can still be performed later, if needed."