What COVID-19 Teaches Us About Rare Diseases

By Roger Chriss, PNN Columnist

Sunday, February 28th is Rare Disease Day -- a day created to recognize and increase awareness of rare diseases that affect millions of people worldwide. This year that includes the effects of Covid-19 on the rare disease community.

The National Organization of Rare Disorders reports that there are over 7,000 rare diseases. A disease is considered rare in the U.S. if it affects fewer than 200,000 people; while in Europe a disease is classified as rare if it affects fewer than 1 in 2,000 people. Although each disease is rare, there are so many conditions that roughly 1 in 17 people are affected by a rare disease.

Rare Disease Day 2021 is occurring amid a pandemic. Covid-19 has increased awareness of medical problems like anosmia, a loss of sense of smell. In it congenital form, anosmia affects only 1 in 10,000 people, but now it is seen in millions infected with the coronavirus. For most, the loss of smell is temporary, but for some Covid patients it persists long after the initial infection.

“One might think that it is not important to be able to smell nature, trees, forests,” Evan Cesa told AP News. “But when you lose the sense of smell, you realize how truly lucky we are to be able to smell these things.”

Long Haul Covid

In a recent study, University of Washington researchers monitored 300 recovering Covid patients in the Seattle area and found that 30% reported worse health and quality of life in the wake of the illness. Some were unable to perform simple chores, lift heavy objects or walk for more than a short distance.

Chronic Covid syndrome (CSS), also known as long-haul Covid, seems to occur in about 10% of infected people. In addition to loss of smell, long haulers often have disabling fatigue, headache, shortness of breath, weakness and brain fog – symptoms that are strikingly similar to chronic fatigue syndrome (CFS/ME).

Research on how to manage long-haul Covid is looking at treatments already used for rare disorders. A clinical trial of low-dose naltrexone (LDN) is underway. LDN is sometimes used to treat refractory chronic pain conditions, and is being explored for lupus and obsessive-compulsive disorder.

The pandemic has created new challenges for the rare disease community. Accessing medical care amid a pandemic has been tricky, in particular for people whose immune function is compromised. And the handful of deaths associated with Covid vaccines has raised questions for people with severe thrombocytopenia (ITP), a rare platelet disorder.

Covid-19 is revealing what living with a rare disease is like. Some people with long-haul Covid are reluctant to disclose their condition, much as people with rare disorders often struggle with when and how to share information about their diagnoses.  

People with long haul Covid are struggling to gain recognition for their disability. As NPR reports, long haulers have asked the federal government for disability coverage, rights and protections -- but it's unclear if they qualify under the Americans with Disability Act.

While Covid-19 has increased awareness of rare diseases, it’s also slowing rare disease research and complicating care. This year, many Rare Disease Day events are being held online due to the pandemic.

Hopefully, Rare Disease Day in 2022 will take place in a post-Covid world.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research.

Who Develops Intractable Pain Syndrome?

By Forest Tennant, PNN Columnist

It is clear that a small percentage of chronic pain patients can develop Intractable Pain Syndrome (IPS), which is constant, incurable pain that has cardiovascular and endocrine complications. But which unfortunate chronic pain patients will succumb to this fate?

To this end, we have been surveying persons with IPS to understand who they are and how they developed the syndrome. Without knowledge as to “who” and “how” IPS occurs, it will be impossible to either prevent the condition, identify it in early stages or stop its progression.

In a survey of persons with IPS, we found that many were older and primarily female. Out of 28 patients surveyed, 20 were female and 8 were male, and their ages ranged from 34 to 77 years. The average age was 56 years.

In addition, these individuals had been ill and experienced chronic pain for many years. Only two of the 28 patients surveyed reported pain of less than five years duration. The majority could actually recall the day, month and year that their chronic pain shifted to IPS. 

Almost all reported three major manifestations:

• 100% Physical function declined

• 86% Needed medication to sleep

• 82% Mental functions declined

Key laboratory tests were frequently abnormal:

• 71% Hormone abnormality

• 53% High inflammatory markers 

• 32% High glucose levels 

The 28 patients surveyed were asked what medical conditions caused their IPS. Surprisingly, the majority said they had multiple diagnoses, which are listed below by condition:

• 20 Adhesive Arachnoiditis

• 9 Ehlers-Danlos Syndrome

• 7 Cervical Neck Neuropathy

• 5 Osteoarthritis

• 2 Reflex Sympathetic Dystrophy (CRPS)

• 2 Interstitial Cystitis

• 2 Traumatic Brain Injury

• 1 Rheumatoid Arthritis

• 1 Stroke

These findings show that IPS can develop from a relatively small number of painful conditions, with Adhesive Arachnoiditis and Ehlers-Danlos Syndrome the most common ones reported. Persons with IPS almost all report severe insomnia and declines in their physical and mental abilities. And laboratory tests validate the abnormal physiological impact of their non-stop constant pain.

In a separate clinical analysis of 40 persons with IPS, we found that over 60% had symptomatic characteristics in common, from constant pain and difficulty sleeping to sugar cravings and cold hands and feet. For a list of over two dozen IPS symptoms, click here.

Our mission forward as the IPS Research and Education Project is to bring recognition and treatment of IPS to every community across the globe. This presents a great challenge for us; to instruct and inform all concerned parties in acknowledging that IPS is a serious syndrome, and that it is exceedingly different from what is commonly known as chronic pain.

Forest Tennant is retired from clinical practice but continues his research on intractable pain and arachnoiditis. This column is adapted from newsletters recently issued by the IPS Research and Education Project of the Tennant Foundation. Readers interested in subscribing to the newsletter can sign up by clicking here.

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

Abuse of Rx Opioid Painkillers Unchanged During Pandemic

By Pat Anson, PNN Editor

An alarming spike in U.S. overdose deaths during the COVID-19 pandemic does not appear to be fueled by increased abuse of opioid painkillers, according to a new nationwide analysis of urine drug tests.

The Drug Enforcement Administration approved an exemption last year allowing patients to connect with doctors via telehealth – without a physical examination -- to get prescriptions for opioids and other controlled substances. While the relaxed rules made it easier for patients to get pain medication during the pandemic, they have not resulted in more diversion or abuse of oxycodone and hydrocodone, according to the Millennium Health Signals Report. Urine positivity rates for the two opioids remained flat during 2020.

“Despite the hardships faced during the pandemic, it is encouraging to see that positivity rates for non-prescribed use of hydrocodone and oxycodone have not changed,” said Michael Parr, MD, an addiction treatment specialist and consultant to Millennium.

“Patients requiring opioids for the treatment of pain have faced difficulty obtaining medications, as well as stigma, before the pandemic. Perhaps this data will reassure clinicians who have taken additional steps to safely prescribe these medications during the pandemic.”

There was an uptick in positivity rates for non-prescribed tramadol, a weaker opioid, particularly in Ohio, Tennessee and Kentucky. Millennium said there were more cases of people with substance use disorders using tramadol as their “drug of preference.”

Millennium researchers also found that positivity rates for non-prescribed gabapentin (Neurontin) showed little change in 2020 – but they remain at levels nearly three times higher than positivity rates for oxycodone, hydrocodone and tramadol. The abuse of non-prescribed gabapentin did rise significantly in Ohio and Virginia.

POSITIVITY RATES FOR NON-PRESCRIBED PAIN MEDICATIONS

SOURCE: MILLENNIUM HEALTH

The abuse of gabapentin has been going on for years, but with little public attention. Gabapentin is a non-opioid nerve medication increasingly prescribed for pain, despite the fact many patients say it doesn’t help and has too many side effects. Drug abusers, however, have found that gabapentin can heighten the effect of heroin and other street drugs.

While positivity rates for non-prescribed pain medication were mostly unchanged during the pandemic, they soared for illicit fentanyl and methamphetamine, increasing 78% and 29%, respectively.

After initially increasing in the early stages of the COVID-19 crisis, Millennium found that positivity rates for cocaine and heroin soon returned to pre-pandemic levels.

Another encouraging sign is that positivity rates for carfentanil, a deadly fentanyl analogue, have flatlined to nearly zero. It is unclear why carfentanil abuse has fallen so sharply, but Millennium said it may be because the pandemic has disrupted manufacturing and supply routes from China.     

Home-Based Virtual Reality Reduces Chronic Low Back Pain

By Pat Anson, PNN Editor

A new clinical study has found that home-based virtual reality (VR) therapy can significantly reduce pain levels in people suffering from chronic lower back pain. Patients who watched VR programs also reported better mood, reduced stress and that pain interfered less with their sleep.

The study, published in the Journal of Medical Internet Research, is the first controlled trial to compare home-based VR therapy to a “sham” or placebo treatment for chronic pain. The research was funded by AppliedVR, a Los Angeles-based company that is developing therapeutic VR content to help treat pain and other conditions.

Eighty-nine people used the company’s EaseVRx headset daily for eight weeks, immersing themselves in relaxing and meditative VR programs designed to make their pain seem less important, similar to cognitive behavioral therapy. A control group received the sham treatment, watching routine nature scenes with the headset. All participants had chronic low back pain for at least six months.   

By the end of the study, 87 percent of people in the VR group reported less pain intensity, with nearly two-thirds experiencing at least a 30% reduction in pain compared to the control group. There were also significant improvements in sleep, mood and stress in the VR group.

Importantly, the improvements in pain and other symptoms were cumulative over time – meaning the relief was long-lasting and not just when people were watching VR programs.

“If you look at the results graph, you’re able to see the trajectory of pain and pain intensity very reliably declining over the course of the eight weeks. It’s a really strong time trend. It’s not just a random effect,” explained Beth Darnall, PhD, AppliedVR’s chief science advisor.

You can see the graph below. Over the course of 56 days, average pain intensity fell by 43% in patients using the EaseVRx headset, compared to 23% in the control or sham group.

JOURNAL OF MEDICAL INTERNET RESEARCH

Most of the research to date on VR therapy has focused on treating acute pain in hospitalized patients. AppliedVR is trying to demonstrate that virtual reality can also be used to treat chronic pain at home. A small study released last summer showed that home-based VR therapy reduced pain in people with fibromyalgia and chronic low back pain.

Darnall was hesitant to say if there were any pain conditions that VR therapy might not useful for.

“At the end of the day, pain is pain,” said Darnall, who is a pain psychologist at Stanford University. “This basic approach, in which we’re equipping people with self-regulatory skills, is going to be beneficial and broadly applicable for every pain condition.

“We have multiple studies in progress that are testing this device on different populations. It’s really going to be an exciting year, because there’s going to be an explosion of research that’s really going to inform our understanding of how this may help people across different disease conditions.”   

AppliedVR’s headset received breakthrough device designation from the Food and Drug Administration last year. The company hopes to get clearance from the FDA later this year to begin selling the devices. Due to a recent decision by Medicare to start covering breakthrough medical devices, the company is hopeful that private insurers will also start paying for VR therapy. 

Study Finds Regular Exercise Reduces Migraine Triggers

By Pat Anson, PNN Editor

Two-and-a-half hours of moderate to vigorous exercise a week can significantly reduce migraine triggers like stress, depression and poor sleep, according to a new survey that found more than two-thirds of migraine sufferers do not get enough exercise.

“Migraine is a disabling condition that affects millions of people in the United States, and yet regular exercise may be an effective way to reduce the frequency and intensity of some migraines,” says lead author Mason Dyess, DO, a Senior Fellow at the University of Washington School of Medicine.

“Exercise releases natural pain killers called endorphins, helps people sleep better and reduces stress. But if people with migraine are not exercising, they may not be reaping these benefits.”

The survey involved 4,647 people diagnosed with migraine. About three-fourths of participants had chronic migraine, meaning 15 or more migraines a month. The others had episodic migraine, or up to 14 a month.

Participants completed a questionnaire about their migraines, sleep, depression, stress, anxiety and the amount of exercise they get each week.

Researchers then divided them into five groups based on their level of exercise: those who did not exercise; people who exercised up to 30 minutes per week; those who exercised 31 to 90 minutes; people who exercised 91 to 150 minutes; and participants who exercised more than 150 minutes per week.

Types of exercise that qualified as moderate to vigorous included jogging, very brisk walking, playing a sport, heavy cleaning and bicycling.

Researchers found that only 1,270 participants – about 27 percent -- reported the highest level of exercise. Those who got less than 150 minutes of exercise had increased rates of depression, anxiety and sleep problems:

• Depression was reported by nearly half of people who got no exercise, compared to 25% of those that exercised the most.

• Anxiety was reported by 39% of people in the no exercise group, compared to 28% of people in the high exercise group.

• Sleep problems were reported by 77% of people in the no exercise group, compared to 61% in the high exercise group.

Researchers also found an association between exercise and increased frequency of migraines. Among people in the no exercise group, nearly half had 25 or more headache days per month. That compares to only 28% of people in the high exercise group.

“There are new therapeutics available for migraine, but they are very expensive. People with migraine should consider incorporating more exercise into their daily life because it may be a safe and low-cost way to manage and minimize some of the other problems that often accompany migraine,” said Dyess.

Two-and-a-half hours a week of moderate to vigorous exercise, or 150 minutes, is the minimum amount recommended by the World Health Organization.

The study findings, which will be presented at the annual meeting of the American Academy of Neurology in April, have not yet been peer-reviewed or published. One weakness of the study was that participants self-reported their exercise minutes, rather than having their activity monitored with a device. It also only shows an association between exercise and migraines, and does not prove cause and effect. 

Stem Cells Restore Function in Patients Paralyzed by Spinal Cord Injuries

By Pat Anson, PNN Editor

Intravenous injection of mesenchymal stem cells (MSCs) in patients paralyzed by spinal cord injuries led to significant improvement in their motor functions, according to a team of researchers at Yale University and Sapporo Medical University in Japan.

The study findings, published in the Journal of Clinical Neurology and Neurosurgery, focused on 13 patients who suffered spinal cord injuries (SCIs) after falls or trauma. Some lost the ability to use their arms and legs, while others suffered coordination and sensory loss, or experienced bowel and bladder dysfunction.

For more than half of the patients, substantial improvements in motor function were observed within weeks of being injected with autologous MSCs derived from their own bone marrow. Although this was a small observational Phase 2 study, researchers are excited by the findings.

"The idea that we may be able to restore function after injury to the brain and spinal cord using the patient's own stem cells has intrigued us for years," said senior author Stephen Waxman, MD, a professor of neurology, neuroscience and pharmacology at Yale. "Now we have a hint, in humans, that it may be possible."

One of the patients profiled was a 34-year-old man who was left partially paralyzed and bedridden after a fall. He received an intravenous injection of MSCs 47 days after his injury. Two weeks after the infusion, voluntary movement was restored to his lower extremities and he was walking with the support of a walker.

In another case, a 47-year-old man left bedridden after a diving accident showed rapid improvement after a stem cell infusion. He was able to drive a wheelchair the next day, walk and climb stairs after two weeks, and eat independently after eight weeks.

Other patients paralyzed after similar injuries were able to breath again without assistance, regain control of their bowel functions, and perform independent living tasks such as dressing and grooming.

“Although this initial case study was unblinded and uncontrolled, the SCI patients appeared to demonstrate a tendency of relatively rapid improvement of neurological function that was often apparent within a few days following infusion of MSCs,” researchers said.

“We would emphasize that this case series describes an early study on a small number of patients. In addition to being unblinded and uncontrolled, this study has a number of limitations. We cannot rule out observer bias nor a contribution of surgical intervention to recovery in cases where this intervention occurred, or spontaneous recovery.”

Other case studies have also shown that stem cells can restore motor and sensory function in patients paralyzed by spinal cord injuries.

The Mayo Clinic reported in 2019 that a California man paralyzed from the neck down in a surfing accident was able to walk again after being injected with his own stem cells. Researchers emphasized the man was a “super-responder” and that other paralyzed patients injected with stem cells don’t have such a dramatic recovery.

According to the National Spinal Cord Injury Statistical Center, over 17,000 Americans suffer spinal cord injuries each year. Chronic pain is a serious problem that can result from SCI, affecting about two-thirds of patients, with one out of three reporting their pain as severe.

Opioid Promotion Cited in FDA Warning Was Stopped in 2019

By Pat Anson, PNN Editor

A California pharmaceutical company that received a warning letter from the Food and Drug Administration over its promotion of a controversial opioid painkiller stopped using the marketing material over a year ago.

The FDA sent the warning letter to AcelRx Pharmaceuticals last week. The agency told the company to stop making “false and misleading claims” about Dsuvia, a potent opioid tablet used to relieve acute pain in hospital settings.

The “Tongue and Done” banner ads and tabletop displays emphasized how easy Dsuvia is to administer by using a plastic applicator that releases a single tablet directly into a patient’s mouth. The FDA said the promotions were misleading and dangerous.

“AcelRx has disseminated promotional communications that undermine key prescribing conditions required for the safe use of this opioid product. Dsuvia was approved with special restrictions requiring that it only be prescribed in a certified medically supervised setting by health care practitioners trained to properly administer it,” the FDA said in a statement.

“This promotion dangerously undercuts FDA-required conditions on the proper administration of the drug, which requires particular diligence to minimize the risk of serious or even fatal adverse events.”

The letter warns AcelRx to either stop using the marketing material or cease distributing Dsuvia. It gave the company 15 days to respond or face “further regulatory action.”    

ACELRX PROMOTION

But in a filing with the Securities and Exchange Commission, AcelRx said it could “easily address” the FDA’s concerns because it stopped using the “Tongue and Done” promotions in late 2019.

“The Company intends to respond to the FDA within the timeframe requested in the Letter and seek guidance and clarification from the FDA on the concerns raised in the Letter,” the SEC filing states. “The Company cannot give any assurances, however, that the FDA will be satisfied with its response to the Letter or that such response will resolve the issues identified in the Letter.”

Few Adverse Events Involve Dsuvia

The FDA approved the use of Dsuvia in 2018 over the objections of anti-opioid activists who said it was a “dangerously unnecessary opioid medication" that would be diverted, abused and lead to more overdoses. There is little evidence any of that has occurred.

Dsuvia contains sufentanil, an opioid 10 times stronger than fentanyl. It was developed to fulfill an unmet need in military and civilian hospitals, where patients need quick relief from acute trauma pain and can’t wait for opioids to be administered intravenously. Each Dsuvia tablet comes in a single dose applicator. The tablets quickly dissolve under the tongue and are not available for home use.

Those safety measures appear to be working. The FDA’s Adverse Events Reporting System lists only six cases involving Dsuvia in 2019 and 2020. There were no deaths and none of the cases were considered serious.

AcelRx recently published the results of a clinical study that showed surgery patients treated with Dsuvia used significantly fewer opioids than those treated with traditional IV opioids. They were also discharged sooner.

The FDA’s belated warning letter to AcelRx about its Dsuvia marketing comes as the agency faces renewed scrutiny for its regulation of opioids.

Acting FDA Commissioner Dr. Janet Woodcock is reportedly under consideration by President Biden for a formal nomination to the job, which has drawn the ire of some anti-opioid activists. A letter sent to the Acting Secretary of Health and Human Services accuses Woodcock of “dereliction of duty” for failing to address the opioid crisis by halting the approval of new opioids. Woodcock has been Director of the FDA’s Center for Drug Evaluation and Research for over 25 years.

Would Drug Legalization Reduce Overdoses?

By Roger Chriss, PNN Columnist

As the overdose crisis worsens, public health data and biostatistics become more important. Debates about opioid prescribing and drug legalization often center on two key concepts: incidence and prevalence as applied to drug use, substance use disorder (SUD) and overdoses.

Brandeis University researcher Andrew Kolodny, MD, recently argued against drug legalization on Twitter.

“Some critics of reducing Rx opioids don't believe that repeated use of highly addictive drugs cause addiction and/or they believe all drugs, including heroin & cocaine should be available over the counter. They don't believe that easy access can increase prevalence of SUD,” said Kolodny, who founded Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid activist group.

Conversely, Columbia University professor Carl Hart, the author of “Drug Use for Grown-Ups,” believes legalizing recreational drugs would help reduce overdoses by making the drug supply safer.

“A large proportion of these deaths are caused by adulterated substances purchased on the illicit market. A regulated market, with uniform quality standards, would virtually put an end to contaminated drug consumption and greatly reduce fatal accidental drug overdoses,” Hart told Columbia Magazine.

Both claims hinge on a proper understanding of incidence and prevalence. In epidemiology, incidence is the rate of new-onset diagnosis of a medical condition. It is measured over a given period of time -- typically a year -- though sometimes the time period is shortened to a week for an urgent problem, such as a viral pathogen like the coronavirus.

By contrast, prevalence measures the total number of people in a population who have a specific medical condition. For prevalence, the duration of the condition is important. For an infectious disease, it may be brief. But for cancer, SUD and many other chronic conditions, it may last a lifetime.

For instance, the incidence of opioid use disorder (OUD) among people who are on long-term opioid therapy is 8-12%, according to the National Institutes of Health. But unlike claims frequently made by PROP, only a small fraction of patients who abuse prescription opioids start using heroin, less than 4% over a five-year period. So, making a clear distinction between OUD involving prescription opioids versus heroin becomes important.

The prevalence of OUD is a cumulative total of all people with OUD over time. This is because OUD and other substance use disorder diagnoses are lifetime diagnoses that remain on a person’s medical records forever. When we count people with OUD, we are counting everyone ever diagnosed with the condition, though in practice sometimes the OUD diagnosis is dropped due to administrative error, poor record-keeping or deliberate obfuscation.

This means that OUD prevalence can go up over time even when the incidence of OUD is going down. In fact, that is what is happening at present.

A recent report from the Substance Abuse and Mental Health Services Association showed modest declines for both prescription opioid misuse and heroin use. This came at a time when U.S. drug deaths were rising, fueled primarily by overdoses involving illicit fentanyl.

These counterintuitive trends make for intense debate about the success or failure of the 2016 CDC opioid guideline and state laws restricting prescription opioid use. A recent study from Indiana University concluded that limits on legal opioid prescribing may have actually driven more people to illicit drugs.

"Our work reveals the unintended and negative consequences of policies designed to reduce the supply of opioids in the population for overdose. We believe that policy goals should be shifted from easy solutions such as dose reduction to more difficult fundamental ones, focusing on improving social conditions that create demand for opioids and other illicit drugs," said co-author Brea Perry, PhD, a professor of sociology at Indiana University.

Even if drug legalization were to reduce drug risks, an increase in the number of drug users could lead to more harms. For instance, if an illicit drug harms 10% of users and there are 1 million users, that results in 100,000 people harmed. If that drug is then legalized and made safer, harming only 1% of users, that seems like an improvement. But if the number of users rises to 15 million, then 150,000 people would be harmed.

Since we don’t know how these numbers would change under a legalized drug regime, any claims about changes in incidence or prevalence are speculative at best.

What is counted and how it is expressed are very important in debates about the role of prescription opioids or drugs in general in SUD and overdose deaths. A failure to be specific about methodology or using data that is not well-founded can result in specious or even deceptive claims. And counterintuitive results are possible, as we are seeing at present in the ever-evolving overdose crisis.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research.

Latina and Asian Women at Significantly Higher Risk from Lupus

By Pat Anson, PNN Editor

Asians and Latinos diagnosed with systemic lupus erythematosus (SLE) are significantly more likely to die from the disease than other racial groups, according to a new analysis by the Centers for Disease Control and Prevention. The CDC set up half dozen state registries over a decade ago to help track the illness.

SLE is the most common form of lupus, a condition in which the body's immune system attacks its own healthy tissues, especially joints and skin, causing flare-ups of pain and fatigue that keep nearly half of adult patients from working.

In an effort to better understand why the disease disproportionately affects women and people of color, CDC researchers analyzed a database of over 800 SLE patients in San Francisco from 2007 to 2017. About 90 percent of them were female. Mortality rates were highest in racial and ethnic minorities who died during the study period,

“Asian females with SLE were four times more likely to die than were Asian females without SLE in the general San Francisco County population, and Hispanic/Latina females with SLE were six times more likely to die than were persons in the corresponding general populations,” researchers reported. “Higher mortality within these populations might be the result of more severe outcomes and manifestations of SLE, as previously demonstrated, or possibly less access to care.”

The mean age at death for people with SLE was 62 years. On average, Black persons died 6.8 years earlier than White people with SLE, while people of Hispanic/Latino ethnicity died 9.5 years earlier.

A recent study published in the journal Arthritis and Rheumatology estimated that over 200,000 Americans suffer from SLE, a number that comes statistically close to officially reclassifying the illness as a rare disease. The Rare Diseases Act of 2002 classifies conditions as rare when they affect 200,000 or fewer Americans. Until now, SLE disease estimates were larger but unverified.

“Our study potentially redefines systemic lupus erythematosus as a rare disease in the United States and lays the groundwork for where we need to focus our efforts to reduce the burden of this disease on Americans,” said lead investigator and rheumatologist Peter Izmirly, MD, an associate professor in the Department of Medicine at NYU Langone Health.

Rare-disease classification could, according to Izmirly, significantly improve efforts to study and treat SLE by reducing the number of participants needed for clinical trials.

Current treatments for lupus include steroids or other anti-inflammatory and immunosuppressing medications, including newer biologic drugs made from living cells.

A Flawed Person's Drug Problem Isn't a Moral Failing

By Dr. Lynn Webster, PNN Columnist

Rush Limbaugh was as controversial as he was politically influential. In fact, Nicole Hemmer, a research scholar at Columbia University, called Limbaugh "the man who created Donald Trump" and opined that Limbaugh created the political foundation that catapulted Trump to power.

In 2020, President Trump returned the favor by awarding Limbaugh the Medal of Freedom, our highest civilian honor, for his "decades of tireless devotion to our country."

But the Independent points out that Limbaugh also left behind a legacy of "divisiveness, cruelty, racism, homophobia, bigotry, and sexism." And Rolling Stone said the radio host "trafficked in bigotry and cruelty."

RUSH LIMBAUGH

It's hard to argue with either of those statements. To me, Limbaugh was a deeply flawed human being who caused harm. But some statements about him go too far.

When Limbaugh died this week after a lengthy battle with lung cancer, Mark Frauenfelder, editor of The Magnet, tweeted: "Rush Limbaugh, the sex tourist and drug addict whose four marriages, mockery of people after their deaths, and overt racism and misogyny made him a beloved icon of American conservatism, is dead at 70." 

That statement is troubling. Overt racism and misogyny are character flaws. Drug addiction, however, is not. It's unfortunate to see Limbaugh's detractors point to his well-documented problems with painkillers as moral failings. This supports my firm belief that our culture holds deeply negative views of people with addiction.  

History of Back Pain and Drug Use 

Limbaugh began abusing prescription painkillers after his spinal surgery in the 1990s. He was eventually arrested on drug charges — specifically, charges of fraud to conceal information to obtain prescriptions, also known as "doctor shopping." In exchange for having the charges dropped, Limbaugh agreed to undergo drug treatment and pay $30,000 in court costs. He posted $3,000 bail and was released.

I wrote about Limbaugh's prescription drug problem in my book, "Avoiding Opioid Abuse While Managing Pain." What we knew about Limbaugh's problem, as I said at the time, was that he abused large quantities of prescription opioids for several years; kept his abuse secret from family, friends and colleagues; entered a rehabilitation program twice, but relapsed each time; remained successful without a visible reduction in functioning while he used drugs; and was suspected of buying drugs illegally. 

What we didn't know, and perhaps now can never ascertain, is whether Limbaugh had an addiction or an undiagnosed psychiatric disorder (although some may argue his professional conduct was evidence of a disturbed personality). We also can't know whether his main motivation for using drugs was to control physical pain, to mask emotional pain or stress, to seek a "high," or some combination of those reasons.  

The answers to these questions — about his history of drug abuse, mental health and motivation — would have told us whether his opioid use disorder (OUD) was treatable with better pain control or, tragically, was an incurable disease.  

Limbaugh exemplifies the type of patient most physicians face when treating serious pain conditions. Sometimes, opioids fail to provide adequate relief for them. And, increasingly, patients cannot access the opioids they need due to misguided polices and regulations.   

How Society Views Addiction 

Some people may agree with Limbaugh's political and social views, and others may not. But conflating his drug abuse and associated illegal activities with the opinions he expressed about social issues harms people who suffer from the disease of addiction. It also makes it more difficult for people with severe pain to receive the care they deserve, whether their abuse is caused by addiction or, as is often the case, a symptom of undertreated pain. 

Many of those with addiction may not have the power or influence to bail themselves out of prison or pay tens of thousands of dollars in court costs. They may remain in prison for years and suffer the loss of their careers, reputations, homes and even their families.  

Generally, our society views people with addiction as flawed, weak and hopeless. We distance ourselves from those who have the disease, and we allow the criminal justice system to have jurisdiction over them, making it difficult or even impossible for them to receive treatment.  

We may never know why Rush Limbaugh made the choices he did. But, just as we would never think of berating him for falling victim to lung cancer, we also shouldn't chastise him for misusing painkillers. We may have a right to judge Limbaugh's behavior, but we cannot, in decency, judge his disease. 

Lynn R. Webster, MD, is a vice president of scientific affairs for PRA Health Sciences and consults with the pharmaceutical industry. He is author of the award-winning book The Painful Truth, and co-producer of the documentary It Hurts Until You Die. Opinions expressed here are those of the author alone and do not reflect the views or policy of PRA Health Sciences. You can find Lynn on Twitter: @LynnRWebsterMD.

Cannabis Reduces Blood Pressure in Older Adults

By Pat Anson, PNN Editor

Medical cannabis is being used to treat dozens of health conditions, from chronic pain, muscle spasms and nausea to hepatitis, HIV and glaucoma.  Now we’re learning that cannabis may also be a useful treatment for high blood pressure.

A small study conducted by researchers at Ben-Gurion University of the Negev (BGU) in Israel found that cannabis significantly reduces systolic and diastolic blood pressure in older adults with hypertension. The study, recently published in the European Journal of Internal Medicine, is believed to be the first to document the cardiovascular benefits of cannabis.

“Older adults are the fastest growing group of medical cannabis users, yet evidence on cardiovascular safety for this population is scarce,” said lead author Dr. Ran Abuhasira of BGU and Soroka University’s Cannabis Clinical Research Institute. "This study is part of our ongoing effort to provide clinical research on the actual physiological effects of cannabis over time."

Twenty-six patients aged 60 and older either smoked cannabis or ingested it through oils, while their blood pressure, heart rate, and body measurements were monitored.  After three months of cannabis therapy, their mean 24-hour systolic and diastolic blood pressures were reduced by 5.0 mmHg and 4.5 mmHg, respectively. Blood pressure was lowest three hours after ingesting cannabis and at night.

Researchers believe that pain relief, the primary reason most patients use medical cannabis, may have contributed to lowered blood pressure.

Previous studies by BGU researchers found that cannabis significantly reduced pain in older adults living with cancer, Parkinson's disease, post-traumatic stress disorder, ulcerative colitis, Crohn's disease, multiple sclerosis and other chronic conditions. Most patients also said their quality of life improved.

A growing number of seniors are discovering the medical benefits of cannabis. A recent survey of patients at a geriatric clinic in Southern California found that over half were using cannabis on a daily or weekly basis, usually to treat pain, difficulty sleeping, anxiety and depression. Although medical marijuana has been legal in California since 1996, nearly two-thirds of those surveyed said they used cannabis for the first time as older adults.

AMA Scolded for Seeking Changes in CDC Opioid Guideline

By Pat Anson, PNN Editor

Eight months after the American Medical Association told the CDC that its controversial opioid guideline has “harmed many patients” and needs to be revised, an anti-opioid activist group has accused the AMA of employing false moral arguments to justify using opioid medication to relieve human suffering.

The letter from Physicians for Responsible Opioid Prescribing (PROP) to AMA President Susan Bailey, MD, takes issue with the AMA’s position that the U.S. “no longer has a prescription opioid epidemic” and instead faces an overdose crisis fueled by illicit fentanyl and other street drugs.

“These statements send a strong message that opioid prescribing for pain is no longer problematic, and that the CDC’s recommended guardrails are no longer needed. Nothing could be further from the truth,” says the PROP letter, which was signed by the organization’s board of directors.

“There is compelling evidence that many of those currently struggling with opioid dependence and addiction were introduced to opioids through use of medically prescribed opioids used to treat chronic pain. Medically prescribed opioids remain a common gateway to illicit opioid use and are themselves frequent causes of opioid addiction and overdose, even if illicit opioids currently cause the greater number of deaths.”

The CDC’s 2016 guideline was only intended for primary care physicians treating chronic pain, but its voluntary recommendations on opioid prescribing have been widely adopted as policy by federal agencies, states, insurers, pharmacies and doctors of all specialties. The guideline has not only failed to reduce drug deaths – which now stand at record highs – but federal health experts admit that widespread misuse of the guideline has caused “serious harm” to patients, including forced tapering, withdrawal, uncontrolled pain and suicide.    

PROP’s letter to the AMA goes even further than the CDC recommendations, suggesting that opioid medications should only be used for short-term acute pain and end-of-life care.  

“All moral, ethical, regulatory, legal and political arguments that opioids are needed so that people do not suffer needlessly should apply specifically to short-term pain management where there is proven benefit, and not to long term pain management where evidence of benefit is largely anecdotal, and there is compelling evidence of harm,” PROP said.

“Why then is the AMA applying the moral argument to the false premise that people will suffer needlessly if they do not have unrestricted access to opioids? By all means apply moral arguments and principles to make sure opioids are available for the right indications, but it makes no sense at all to suggest that removing guidance on opioid dose and duration is needed so that people with chronic pain do not suffer.”

AMA: ‘Misguided Focus’ on Opioids Harms Patients

To be clear, opioid addiction is rare in patients and the AMA never said that people should have “unrestricted access to opioids.” The AMA called for balanced and individualized care based on patient need, not one-size-fits-all guidelines that dictate dosages or the type of treatment everyone should get.    

In a February 19th letter to PROP, AMA President Dr. Susan Bailey said the group mischaracterized the AMA’s position on opioid treatment.

“When policies or organizations focus only on the restriction of a legitimate pharmacologic option to help patients with pain, they miss the chance to address the complexity of policies needed to truly help patients with pain. That misguided focus also has led to harmful stigmatization and other stressors,” Bailey said.

“That is why the AMA provided comprehensive recommendations on the 2016 CDC Guideline and why we continue to advocate for policies that support comprehensive, multidisciplinary, multimodal pain care, including opioid therapy when appropriate.”

“Patients with chronic pain and patients with substance use disorder both need access to multimodal treatments for their medical care,” said Dr. Chad Kollas, a palliative care specialist who is an AMA delegate and Secretary of American Academy of Hospice and Palliative Medicine (AAHPM).

“AMA and AAHPM have recognized the importance of pursuing balanced opioid policy, policy that protects access to opioid analgesics for patients with medically legitimate needs for those medications, while also protecting the public safety and reducing potential harms of prescribed medications.”

Kollas said PROP’s belated response to the AMA’s position may be an attempt to deflect attention away from a recent report that found deaths due to illicit fentanyl soaring, while overdoses involving prescription opioids remained flat.  The research adds to a growing body of evidence suggesting the CDC opioid guideline was ineffective and misdirected.

Although opioid prescribing is at 20-year lows, PROP founder Dr. Andrew Kolodny has said prescriptions “still have a very long way to go” and should be reduced even further. Kolodny recently advised the World Health Organization in the development of a new guideline for treating chronic pain in children, which recommends that opioids only be given to children who are dying or in palliative care.

Slow Progress on Guideline Update

Faced with growing criticism of its own guideline, the CDC announced in 2019 that it was working on an update or possible expansion of its recommendations. Progress has been slow since then.  An advisory group appointed by the agency last summer has had only two preliminary meetings and will not review suggested changes to the guideline until next month, according to an update given Tuesday to the CDC’s Board of Scientific Counselors (BSC).

Draft guidelines are not expected to be available for public comment until the end of this year, meaning any revisions will likely not be finalized until 2022. Patient advocates told the BSC they were disappointed by the lack of progress.

“I would like to urge the members of this panel to please take seriously the issue of timely revision of the CDC guidelines for chronic pain. We have a catastrophe welling out across the country in a wholly marginalized and invisible group. On top of that, we are losing working physicians at a steady rate,” said Terri Lewis, PhD, a patient advocate and rehabilitation specialist. “Everybody is in the gun sights of policy that is not working for anybody. I beg you to please make this an urgent priority.”

Finding Love Again While Living With Chronic Pain

By Crystal Lindell, PNN Columnist 

When you have chronic pain, love stories can be triggering.  

For a while, I had to Facebook mute everyone on my friend’s list who posted about their relationships. I hated them so much for being happy. And I hated myself for hating them. 

My last boyfriend and I started dating before I had debilitating chronic pain. As my health declined, so did our relationship.  

I knew it was the beginning of the end when he finally said the unsayable out loud to me on the phone.  

“Look. I just don’t want to have to take care of you for the rest of your life.” 

The words struck me like a punch in the eyes. I honestly hadn’t seen it coming. Worst still, we dated for three more months because I didn’t have the strength to leave him.  

Those words left sprawling scars. And in 2017, when I started to suspect that I might have Ehlers-Danlos Syndrome — a painful genetic condition that has no cure — I burned them into my brain like a prophecy. 

The idea of never getting better was now knotted up with the idea that no man would ever love me. Somehow, I convinced myself that I deserved such a fate.  

I mean, I can’t expect a guy to take care of me for THE REST OF HIS LIFE. It’s rude. It’s cruel. Men deserve more from their lives than my doctors’ appointments, ER trips and medical debt. My ex was right.  

I resigned myself to a lifetime of horrible Tinder dates and one-night stands. After all, what right did I have to expect anything more than that?  

Ok, yes, this is the part where I’m going to tell you I met the love of my life. I know. Gross. 

If you want to stop reading now because you hate love, I completely understand. But I want to tell you something real quick before you go — it is possible to find love when you have chronic pain.  

I found him. He found me.  

We found each other.  

We met at a local political meeting. I went up to a local candidate to ask about opioid access for pain patients, he overheard me and asked for my number.  

Hydrocodone literally brought us together.

Yes, we both have chronic pain. I think that’s the secret. 

People will tell you that two sick people shouldn’t date, but in my experience, it makes for a much better match than one sick person and one healthy person.  

There’s a uniquely humbling empathy you develop when your body falls apart. It’s the kind of empathy that only comes when you lose your childhood sense of invulnerability.  

The truth of it is, like most stories involving real people, our fairy tale wasn’t a straight line.  

While he asked for my number in August of 2017, we went on one date and then mostly lost track of each other. Other than some social media comments and a couple run-ins at local political events, I didn’t really hear from him again until March 2018. 

That’s when he sent me a Facebook message. “Hey, are you going to that debate at the library tonight?” 

He sent it on March 15, 2018. I read it right after I got home from the doctor. The same day that I was officially diagnosed with Ehlers-Danlos Syndrome.  

I went to the debate. He did too. 

The next day he sent me a text, “Apologies if this is a bit direct, but you’d been saying that you felt run-down and sick last time I saw you. But you looked freaking great yesterday.” 

A couple days later he took me to a movie. It was well past midnight as we left the theater, so he suggested a little gyro stand known for its authentic food and 2 a.m. closing time. 

As we sat in the car, getting Tzatziki sauce all over our faces, I told him the story of my ex. How he had hated my health issues. How he had told me he didn’t want to have to take care of me for the rest of my life. How much those words screwed with my head. 

About a week later he came over with a Blu-ray copy of “Thor: Ragnarok,” ended up spending the night and we never looked back. Other than work trips we haven’t spent a night apart since.  

Almost three years later, we now share heated blankets, coordinate doctor appointments and deal with weather-induced pain flares together on the couch. 

He proposed recently. On Christmas morning. he put a ruby ring under the tree and then made sure I opened it last.  

As I unwrapped the large box meant to disguise the ring’s shape, he leaned over to give me a kiss, completely oblivious to my unwashed hair and lack of makeup. 

Then, he went silent.  

“Um, are you proposing?” I asked when I saw the ring.  

“Yes,” he said.  

“So, like, you’re cool with spending the rest of your life with me?” I asked.  

“Well, I was going to do that either way,” he said.  

A proposal. At home. In my pajamas. With nobody else around.  

Only a fellow chronic pain patient could understand the magic in that.  

“I do have one more question,” he said.  

“What?” 

“Are you sure you’re never going to get better? Because I don’t want to have to take care of you for the rest of your life,” he said.  

Then he burst out laughing, so proud of his joke.  

Well look at that. Those words have been reclaimed. Our love took them back.  

They don’t control me anymore. Now, they belong to me and my fiancé. 

Crystal Lindell is a journalist who lives in Illinois. After five years of unexplained rib pain, Crystal was finally diagnosed with hypermobile Ehlers-Danlos syndrome.

Mexicans ‘Dying in Pain’ Because Rx Opioids Limited in U.S.

By Pat Anson, PNN Editor

Efforts to limit opioid prescribing in the United States are driving some Americans across the border to Mexico to purchase opioid medication, according to a new study that found shortages of painkillers in some of Mexico’s poorest regions.  

Mexico, along with many other third-world countries, have relatively low rates of opioid prescribing. Faced with international criticism that pain was going untreated, the Mexican government launched an initiative in 2015 to improve access to opioids for terminally ill patients in palliative care.

Doctors were allowed to write more prescriptions and there was expanded insurance coverage of opioids, which led to a steady increase in opioid dispensing in Mexico over the next few years – a period when opioid prescribing in the U.S. was falling sharply.

A team of researchers at UCLA, with funding from the U.S. National Institutes of Health, looked at prescription drug data in Mexico from 2015 to 2019. They found a steady increase in opioid dispensing nationwide, but the growth was concentrated in wealthier Mexican states and major metropolitan areas, particular those along the U.S. border. The research findings, published in The Lancet Public Health, suggest that some of the opioids intended for Mexican citizens wound up in American medicine cabinets.

"People in the poorest areas of Mexico are dying in pain," said lead author David Goodman-Meza, MD, an assistant professor of medicine at the David Geffen School of Medicine at UCLA. "A lot of work needs to be done to increase access to opioids for those who have a medical need for them in Mexico.”

Goodman-Meza and his colleagues found the highest opioid prescribing rates in Baja California, Mexico City, Nuevo Leon, Sonora and Jalisco. Fentanyl was the most frequently dispensed opioid medication, followed by methadone, morphine, tapentadol, oxycodone and hydromorphone.

Baja California, Nuevo Leon and Sonora all border the United States, and have a “heavy concentration of pharmacies” just a few miles away from San Diego, El Paso and other U.S. cities. The researchers noted that many of these pharmacies had an increase in opioid dispensing during the study period.

Although they did not examine cross-border purchase data, researchers believe “medical tourism” by Americans probably contributed to more opioid prescriptions being filled in Mexico.

"As the U.S. has tried to curb the epidemic related to prescription opioids by instituting structural mechanisms such as closing 'pill mills' and instituting prescription drug monitoring programs (PDMPs), individuals may be getting around them by going to Mexico to get opioids," Goodman-Meza said. "Continued surveillance at border crossings is necessary to avoid unmonitored entry of opioids into the U.S."

Unintended Consequences of PDMPs

Another unintended consequence of U.S. policy to limit opioid prescribing is that it may be forcing some patients to turn to illicit drugs.

A new study published in JAMA looked at state efforts to combat the opioid epidemic by using PDMPs to track opioid prescriptions. A team of Indiana University researchers found that while opioid misuse and “doctor shopping” by patients declined, drug deaths continued to increase, fueled largely by overdoses linked to illicit fentanyl, heroin and cocaine.    

“Heightened demand for diverted and illicit drugs might arise from limiting the supply of prescription opioids under certain conditions. These unintended consequences may occur if the fundamental causes of demand for opioids are not addressed and if the ability to reverse overdose is expanded without increasing treatment of opioid overdose,” researchers found.

“We believe that policy goals should be shifted from easy solutions (eg, dose reduction) to more difficult fundamental ones, focusing on improving social conditions that create demand for opioids and other illicit drugs.”

A 2019 study of PDMPs was more explicit, finding there was a “consistent, positive, and significant association” between them and heroin overdoses. A study conducted the previous year also found an increase in heroin deaths associated with PDMPs, along with a decline in overdoses linked to prescription opioids.  

CDC Focused on Rx Opioids While Fentanyl Deaths Soared 1,040%

By Pat Anson, PNN Editor

A new report from the Centers for Disease Control and Prevention documents an alarming increase in overdose deaths and how the agency’s 2016 prescription opioid guideline failed to stop the drug crisis from growing worse.

The study looked at fatal overdoses from 2013 to 2019, a period when U.S. drug deaths rose by over 56 percent, culminating with 70,630 Americans dying from overdoses in 2019.  

Deaths involving prescription opioids remained relatively flat during that period, while overdoses involving other substances rose, led by an astounding 1,040% increase in deaths linked to illicit fentanyl and other synthetic, mostly black market opioids. Overdoses involving heroin, cocaine and stimulants such as methamphetamine also rose.

DRUGS INVOLVED IN U.S. OVERDOSE DEATHS (2013-2019)

“Sharp increases in synthetic opioid- and psychostimulant-involved overdose deaths in 2019 are consistent with recent trends indicating a worsening and expanding drug overdose epidemic. Synthetic opioids, particularly illicitly manufactured fentanyl and fentanyl analogs, are highly potent, increasingly available across the United States, and found in the supplies of other drugs,” researchers reported in the CDC’s Morbidity and Mortality Weekly Report.

“Similarly, psychostimulant-involved deaths are likely rising because of increases in potency, availability, and reduced cost of methamphetamine in recent years. The increase in synthetic-opioid involved deaths in the West and in psychostimulant-involved deaths in the Northeast signal broadened geographic use of these substances.”

The new CDC study adds to a growing body of evidence suggesting that the agency’s controversial opioid guideline has been ineffective and misdirected. While the guideline helped reduce the already shrinking supply of opioid medication – prescription opioid use is now at 20-year lows – drug deaths linked to illicit fentanyl and other substances kept rising. Overdoses hit a record high last spring.

"This represents a worsening of the drug overdose epidemic in the United States and is the largest number of drug overdoses for a 12-month period ever recorded," the CDC said in a recent health advisory.

‘I Don’t Really Want to Die’

Many pain patients – including those who have used opioids safely and responsibly for years – now have difficulty obtaining opioid analgesics and live with untreated or poorly treated pain. A recent study found that nearly half of primary care clinics in the U.S. are unwilling to accept new patients on opioids, because they had either stopped prescribing them or feared scrutiny by law enforcement and regulators if they did.

“Why am I treated like a criminal for needing opioids? For 26 years opioids are the only treatment that allows me to have a life,” a pain patient recently told PNN. 

“My doctor stopped prescribing my pain medication without my consent, leading to rapid tapering and abrupt discontinuation. No medication and haven't heard from her since. She won't return my calls,” another patient said.  

“I'm at a very desperate point in my life,” said a patient with Complex Regional Pain Syndrome (CRPS). “The meds don't address my needs and I'm at my end. If something doesn't give right away, I will be gone! I don't really want to die but I feel that it is the only option left.” 

Some anti-opioid activists have turned a blind eye to pleas from patients and want opioid prescriptions reduced even further.

“Opioid scrips have been trending in a more cautious direction, (though we still have a very long way to go) while opioid OD deaths have soared. Some see this as a policy failure. They may not realize the main goal of more cautious Rx opioid use is to reduce incidence of OUD,” Dr. Andrew Kolodny, founder of Physicians for Responsible Opioid Prescribing (PROP), wrote in a recent Tweet.

But when asked by another poster if there have been declines in OUD — opioid use disorder — because fewer opioids are being prescribed, Kolodny said he didn’t know.

“OUD incidence isn't tracked. We're 25 years into an epidemic of OUD but still have lousy surveillance. So no hard data but if fewer people are exposed to a highly addictive drug, it's a safe bet that fewer people will become addicted,” Kolodny replied.

The CDC is currently working on an update and possible expansion of its opioid guideline – with the goal of releasing a revised guideline late this year. The agency’s Board of Scientific Counselors is holding a public hearing this Tuesday, February 16th to get an update from an “Opioid Workgroup” that is considering changes to the guideline. People interested in listening to the meeting online can register clicking here.