Latest news with #arthritis
Medscape
2 days ago
- Business
- Medscape
Chronotherapy in RA Treatment: Tantalizing but Under-Studied
Morning stiffness is common for people with arthritis and that got researchers to thinking that if they could time drug therapy to match the body's rhythms when pain receptors are most active, they could relieve that morning stiffness and potentially target flares. That concept, known as chronotherapy or chronomedicine, aims to synchronize drug delivery to the body's circadian rhythms. A few small clinical trials and observational studies have evaluated this concept, but most recently researchers in Japan completed a multicenter, nonrandomized, controlled study that found that almost twice as many patients who took baricitinib at night had a measurable improvement in symptoms than patients who took the Janus kinase (JAK) inhibitor in the morning. Amanda Sammut, MD 'Chronotherapy refers to the strategic timing of medication, therapies, or other medical interventions to align with the body's natural circadian rhythms,' Amanda Sammut, MD, chief of rheumatology at Harlem Hospital Center in New York City, told Medscape Medical News. 'The goal of chronotherapy is to optimize therapeutic efficacy and minimize adverse events.' Progress Slows After Nobel Prize In 2017, Jeffrey Hall, Michael Rosbash, and Michael Young won the Nobel Prize in Medicine for their work isolating a gene that controls the normal daily biological rhythms. However, as researchers in Italy who have studied chronotherapy in inflammatory joint diseases have noted, transition of that knowledge to clinical practice has proceeded slowly. 'Growing knowledge of chronobiology applied to inflammatory joint diseases could stimulate the development of new drug strategies to treat patients in accordance with biological rhythms and minimize side effects,' the Italian researchers wrote. 'It should be evidence-based,' John Hogenesch, PhD, a neuroscientist at Cincinnati Children's Hospital, Cincinnati, who has researched circadian rhythms, told Medscape Medical News. 'Yet there are only about 140 studies in 50 years looking at drug timing.' Sammut noted that chronotherapy is not yet incorporated into major rheumatoid arthritis (RA) treatment guidelines. 'The temporal administration of anti-inflammatory agents to coincide with this cytokine surge presents a theoretically sound strategy to improve disease activity,' she said. Akira Hashiramoto, MD, PhD The most recent research in Japan, led by Akira Hashiramoto, MD, PhD, at Kobe University, Kobe, Japan, assigned 122 patients with RA to four open-label treatment groups: Either baricitinib 2 mg or 4 mg in the morning or evening. The primary endpoint was the percentage of patients with at least 20% improvement in the American College of Rheumatology response criteria (ACR20) at 12 weeks. Some of the secondary endpoints included ACR20, ACR50, and ACR70 response rates at other timepoints as well as changes in the Clinical Disease Activity Index (CDAI) at the same timepoints out to 1 year. Hashiramoto told Medscape Medical News that the changes in swollen joint count (SJC) significantly improved in the evening vs the morning dosing group throughout the 52-week study period, and that changes in tender joint count, patient global assessment, and physician global assessment mostly occurred before 3 months. 'Therefore, we believe that the most important mechanism for achieving sustained CDAI remission at weeks 12, 24, and 52 is that chronotherapy maximized the effect of baricitinib by week 12 after initiation, when all components of CDAI have responded well,' he said. 'The results demonstrate the crucial importance of the treat-to-target strategy.' Earlier studies demonstrated the potential of chronotherapy. Researchers in Berlin, led by Frank Buttgereit, MD, at Charité-Universitätsmedizin Berlin, Berlin, Germany, reported in 2008 that modified-release prednisone reduced the duration of morning stiffness in RA. In 2013, Buttgereit's group reported that low-dose prednisone chronotherapy when added to existing disease-modifying antirheumatic drugs produced significantly higher response rates than placebo for ACR20 — 48% vs 29% ( P < .001), and more than double the rate for a 50% improvement (22% vs 10%, P < .006). A 2011 study in Japan found that methotrexate chronotherapy can improve RA symptoms compared with traditional dosing methods, but Sammut cautioned that the results may not be entirely related to chronotherapy. The study switched patients from the standard methotrexate dose three times daily to once daily at bedtime, but with the same weekly dosing. 'So even though the results showed improved disease activity scores and functional capacity, it may not be related to the actual chronotherapy portion alone,' Sammut said. Role of the Circadian Clock The body's circadian clock is central to chronotherapy. A few studies have explored the role of the body's internal clock in RA pathophysiology, including one by Buttgereit's group in Berlin. Buttgereit's group reported in 2015 that circadian disruption altered circulating leukocyte rhythms in patients with RA. Specifically, they found the rhythms of effector CD8 + and CD4+ T cells, and interleukin (IL)–6R+ CD8+ T cells were abolished in patients with RA; and that IL-8R+ monocytes, CD20+ CD27+ memory B cells, and CD20+ human leukocyte antigen –DR+ activated B cells, which were not rhythmic in healthy individuals, had rhythmic circulation in the peripheral blood of patients with RA. Researchers at Nova Southeastern University in Davie, Florida, conducted a literature review in 2023 in which they identified four common clock genes that were dysregulated in patients with RA: Circadian locomotor output cycles kaput; brain and muscle ARNT like-1 ; period ; and cryptochrome. Research has also been conducted on the diurnal variation of symptoms of polymyalgia rheumatica. In a 2016 observational study, Danish researchers reported that plasma concentrations of IL-6, IL-8, tumor necrosis factor–α, IL-1β, and IL-4 varied with time in both patients treated with prednisolone and untreated patients, peaking between 4:00 AM and 8:00 AM. With the exception of IL-1β, concentrations of these cytokines and of IL-10 were higher throughout the 24-hour observation period in treated patients, as were melatonin and cortisol levels, the latter peaking around 2:00 AM and 8:00 AM, respectively. Farshid Guilak, PhD In his laboratory at Shriners Hospitals for Children — St. Louis — Farshid Guilak, PhD, has been researching circadian rhythms and timed-release therapy to minimize arthritic flares and prevent disease progression in people with RA or juvenile idiopathic arthritis. 'It turns out that not only does our brain have this region that cycles but virtually every other tissue in the body is on a 24-hour clock,' Guilak told Medscape Medical News. 'Unlike the master clock, they're called the peripheral clocks.' These peripheral clocks in the joints dictate the ebb and flow of pain within them, he said. 'The exact reason is not completely known, but my belief is that our tissues also have periods of activity and rest,' Guilak said. 'During the night we elevate a lot of the proteins and genes that are related to repair and regeneration, things that are related to cleaning out the cells, such as the process of autophagy. It's very important in the brain and memory that if you don't have these sleep periods, you don't actually allow your tissues to reset and repair themselves.' Inflammatory mediators peak between 3:00 AM and 5:00 AM, he said. 'This is one reason why many people with arthritis wake up with morning stiffness,' he said. 'The clock regulates about 50% of drug transporters, targets, and metabolizing enzymes,' Hogenesch said. 'About half of all small-molecule drugs have a short (less than 12-hour) half-life. This means as many as 25% of all drugs may be influenced by when they are taken.' Guilak's group reported that people who work night shift had a 25% higher risk for knee osteoarthritis and a 30% higher risk of having knee replacement than nonshift workers. 'Disruption of sleep is a major risk factor for arthritis,' he said. 'Doing shift work or getting < 6 hours of sleep a night significantly increases the risk of osteoarthritis.' Challenges in Adapting Chronotherapy in RA Chronotherapy faces several barriers before it gains wider acceptance as a treatment approach in RA. One involves identifying specific circadian patterns in individual patients. 'The gold standard is the dim-light melatonin onset assay, which is only done in a tiny subset of patients in a tiny subset of academic medical centers,' Hogenesch said. More practical methods, he said, are using surveys, such as the Munich ChronoType Questionnaire, or actigraphy, which uses wearables, such as a Fitbit or Oura ring. 'So [it will be] surveys and wearables for the near future,' he said. The complexity of medical regimens for patients with RA poses another barrier to wider acceptance, Summat said. 'The medication regimen for patients with RA, and for many other chronic diseases, usually includes multiple medications,' she said. 'When you include timings of medications, it may make it more complicated and more difficult to adhere to the regimen.' But other patients may be amenable to having a medication schedule, Sammut said. 'Timing of medications is something that we should think about in our patients already,' she said. 'For instance, if a patient is on a proton pump inhibitor, we would recommend taking it on an empty stomach half an hour before eating or drinking anything.' She suggested that physicians and pharmacists should collaborate on developing medication plans for patients. Individual patients' sleep schedules are another factor to consider with chronotherapy, Sammut added. Chronotherapy With Other Drugs The JAK inhibitors tofacitinib and upadacitinib could potentially be used for chronotherapy in RA, Hashiramoto said. 'The half-life, time after administration of the drug to reach maximum plasma concentration, or drug withdrawal of tofacitinib and upadacitinib are different from that of baricitinib, so the efficacy of bedtime dosing must be demonstrated in clinical trials,' he said. 'However, in our limited experience, tofacitinib tends to respond well in patients who start with only a single evening dose, with similar results to baricitinib 2 mg in the evening,' he said. 'For upadacitinib, once daily in the evening is as effective as baricitinib.' Based on his group's research, Hashiramoto said that chronotherapy does not increase adverse events with either tofacitinib or upadacitinib. 'We hope that follow-up studies of chronotherapy will be conducted in Europe and the United States, not only for baricitinib, but also for other JAK inhibitors,' he said. Emerging Research: Unlocking Gene Circuits Guilak's research group has been investigating 'chronogenetics,' circadian-based gene circuits that can be programmed into stem cells and that, once implanted in the body, match the patient's circadian clock to deliver anti-inflammatory drugs daily at a specific time. The stem cells are administered in a drug-eluting implant — 'like a spaghetti string rod full of cells injected under the skin,' he said — that is inserted into the joint. It's designed to release drugs once a day. Guilak reported that these gene circuits produced effective amounts of IL-1 receptor antagonist in mice. More recently, Guilak's group reported on an implant that responds to both circadian and inflammatory signals to release therapeutic levels of IL-1 receptor antagonist not only at a specific time but also in response to activation of pain receptors. His group recently received a grant from the Advanced Research Project Agency for Health to develop the implant. 'Our goal is to get this into patients in the next 3-5 years,' he said. Hashiramoto reported receiving honoraria from AbbVie and honoraria and grants from Eli Lilly Japan. Guilak is an employee and shareholder of Cytex Therapeutics and has applied for patents on concepts on chronogenetics. Sammut and Hogenesch reported no relevant financial relationships.
Medical News Today
4 days ago
- General
- Medical News Today
Cosentyx UnoReady and Sensoready pens: What to know about each
Cosentyx UnoReady (secukinumab) and Sensoready (secukinumab) are brand-name injections. They're both prescribed for plaque psoriasis, hidradenitis suppurativa, and certain types of arthritis. Certain factors may determine the injection pen that's right for you. This article explains the main similarities and differences between Cosentyx UnoReady and Sensoready. If you're considering taking one of these drugs, discussing this information with your doctor can help you decide if one of these treatments may be right for you. Cosentyx UnoReady and Sensoready have been approved by the Food and Drug Administration (FDA) to treat the following conditions in adults: Cosentyx UnoReady and Sensoready have been approved by the Food and Drug Administration (FDA) to treat the following conditions in children: The Cosentyx UnoReady pen and Sensoready pen are approved to treat the same conditions, but the pen you're prescribed may depend on your dosage. They also share some features, including: both pens come with a concealed needle, meaning you won't need to purchase needles or attach them to the pen. both pens will sound with a 'click' when the injection starts and when the injection is nearly finished, so you know that you receive the full dose. neither pen requires pressing a button to 'activate' the injection. both pens may be injected in the same body areas: your lower stomach, the front of your thighs, or your upper outer arms (if someone else is giving your injection). But there are differences between them that can determine whether one or the other is a better fit for you. Cosentyx is also available in prefilled syringes. If you'd like to learn about how Cosentyx UnoReady and Sensoready pens compare versus the prefilled syringe, ask your doctor or pharmacist. The Cosentyx UnoReady pen and Sensoready pen are approved to treat the same conditions, but the pen you're prescribed may depend on your dosage. The Cosentyx UnoReady pen delivers a 300-mg dose, while the Cosentyx Sensoready pen delivers a 150-mg dose. Two Sensoready pens may be used to deliver a 300-mg dose. Below are instructions for how to use the Cosentyx UnoReady pen. Your doctor or pharmacist will train you to use the pen to give yourself Cosentyx injections. Let them know if you have questions or concerns about how to use the UnoReady pen. Remove the Cosentyx UnoReady pen from the refrigerator 30 to 45 minutes before your dose. Doing so allows the pen to reach room temperature, making the injection more comfortable. Check the viewing window and ensure that the liquid is clear, and the color is colorless or slightly yellow. Air bubbles may also be visible, which is normal. Wash your hands, then clean the injection site with an alcohol wipe and allow it to dry. You may inject Cosentyx UnoReady doses into your lower stomach, the front of your thighs, or your upper outer arms (if someone else is giving your injection). Do not inject into skin that is bruised, hard, tender, scaly, or red or discolored. You also should not inject into an area of skin affected by psoriasis, or area with scars or stretch marks. Do not shake the UnoReady pen. shake the UnoReady pen. Remove and dispose of the cap. Position the UnoReady pen at a 90-degree angle against the injection site, with the viewing window facing you. Press the pen firmly against the skin and hold. You should hear the first 'click' sound, which indicates the injection has started. Keep holding the pen against your skin. Watch the viewing window on the UnoReady pen; you should see a moving green indicator, which shows the injection progress. You'll hear a second 'click' sound, which indicates the injection is nearly finished. After you hear the second 'click', hold the pen in place for another 5 seconds. Once the green indicator fills the viewing window and has stopped moving, you can remove the UnoReady pen from your skin and dispose of it in a sharps container. When you're first prescribed the Cosentyx Sensoready pen, your doctor or pharmacist will show you how to give yourself injections. Cosentyx Sensoready pen instructions are included below, but reach out to your doctor or pharmacist if you have questions or concerns about how to use Cosentyx Sensoready pens. Remove the Cosentyx Sensoready pen from the refrigerator 15 to 30 minutes before your dose. This allows the pen to reach room temperature, which helps make the injection more comfortable. Look at the Sensoready pen viewing window and ensure the liquid is clear with a colorless or slightly yellow appearance. Air bubbles may also appear, which is normal. If your prescribed dose is 150 mg, you'll give one injection. If your prescribed dose is 300 mg, you'll need to use two Cosentyx Sensoready pens to give two injections. You should choose a different injection site for each injection if your dose requires two injections. Wash your hands, then clean the injection site with an alcohol wipe and allow it to dry. You may inject Cosentyx Sensoready doses into the front of your thighs, your lower stomach, or your upper outer arms (if someone else is giving your injection). Avoid giving an injection into skin that is tender, bruised, red or discolored, hard, or scaly. Do not inject into an area of skin affected by psoriasis, or area with stretch marks or scars. Do not shake the Sensoready pen. shake the Sensoready pen. Remove and throw away the cap. Hold the Sensoready pen at a 90-degree angle against the injection site. Press and hold the Sensoready pen firmly against the skin at the injection site. You should hear the first 'click' sound, which signals the injection has started. Continue holding the Sensoready pen firmly against your skin. Watch the progress of the injection using the 360-degree viewing window on the Sensoready pen. You should see a green moving indicator. When the pen sounds a second 'click', the injection is nearly complete. Continue holding the Sensoready pen against your skin until the green moving indicator fills the viewing window and stops moving. Once the green indicator stops moving, the injection is complete. You may now dispose of the Sensoready pen into a sharps container. If your dose is 300 mg, repeat these steps with a new Sensoready pen at a different injection site. If you're prescribed Cosentyx UnoReady or Sensoready, you may wonder how effective either drug is for treating your condition. Prescribing information: Here's a brief look at how effective Cosentyx UnoReady and Sensoready were found to be in clinical trials. Clinical trials found Cosentyx UnoReady and Sensoeady effective at treating: For details about how these drugs performed in clinical trials, see the prescribing information for Cosentyx UnoReady and Sensoready. Keep in mind that trial results may not apply to your individual health situation. Treatment guidelines: Another way to see whether a drug is considered effective is to look at treatment guidelines. When an organization includes certain drugs in treatment guidelines, this means that research has shown the drug to be safe and effective. Cosentyx UnoReady and Sensoready both contain the same active ingredient (what makes a drug work), secukinumab. Below is information on treatment guidelines that recommend secukinumab as a treatment for approved uses of Cosentyx UnoReady and Sensoready: Cosentyx UnoReady and Sensoready may not be right for you if you have certain medical conditions or other factors that affect your health. The two drugs share some of the same precautions, but they also have different ones. Some of these precautions are mentioned below. If any of the following medical conditions or other health factors are relevant to you, talk with your doctor before using Cosentyx UnoReady or Sensoready. The Cosentyx UnoReady and Sensoready pens are approved to treat the same conditions, but differences between the two can determine which is a better fit for you. A few key differences include: The UnoReady pen cap isn't made with latex, making it a better option if you have a latex allergy. The UnoReady pen can only deliver a 300-mg dose. The Sensoready pen, on the other hand, delivers a 150-mg dose. Two Sensoready pens may be used to give a 300-mg dose. This makes the Sensoready pen more versatile in its dosing options. The UnoReady pen is rectangular in shape, while the Sensoready pen is triangular. You may find one pen more comfortable to hold and use than the other based on your preferences. To learn more about how the Cosentyx UnoReady and Sensoready pens compare, talk with your doctor or pharmacist. They can help decide if either pen is a better option for you. Disclaimer: Medical News Today has made every effort to make certain that all information is factually correct, comprehensive, and up to date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or another healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses. Psoriasis Psoriatic Arthritis Pharmacy / Pharmacist Drugs Arthritis
Daily Mail
24-05-2025
- Health
- Daily Mail
Beauty expert reveals how to treat common foot conditions before summer: from fungal nails to verrucas
When was the last time you really thought about the state of your feet? Truth is we should all monitor them closely, not least because signs of illnesses such as diabetes, heart disease and arthritis can show up there first. 'As we age, we develop increasing problems with our feet due to wear and tear of the joints, loss of the fatty pads that cushion our soles and a reduction in skin elasticity,' says Molly Chilvers, podiatrist and brand ambassador for footcare treatment cream Footmender.
Daily Mail
22-05-2025
- Health
- Daily Mail
Doctors issue warning over mystery rise of young, fit women with crippling medieval condition
Looking at these women — with their slim waists and active lifestyles — you'd never guess they're battling a disease once reserved for overweight, wine-guzzling aristocrats. But gout, the crippling condition historically dubbed the 'disease of kings', is making a shocking comeback — and this time, it's hitting a very different crowd. Since 1990, rates have increased by more than 63% globally, linked to rising obesity rates and more availability of rich foods. Around 8.3million Americans have gout. But while overweight, beer-drinking men in their fifties are still most at risk, a new high risk group has emerged. A growing number of young, seemingly healthy women have spoken out about how they have been left crippled by the ailment, with searing pain and swollen joints. Gout is a form of inflammatory arthritis caused by a buildup of uric acid in the body. This excess forms razor-sharp crystals that lodge in the joints, triggering sudden, intense pain — often in the big toe. The body releases uric acid when it breaks down certain foods like rich red and organ meat, seafood, alcohol and sugary drinks. Los Angeles based actress Avery Norris also is not a typically candidate for gout, with a slim physique and active lifestyle. She got the condition when she was 22 years old Your browser does not support iframes. So what's behind the mysterious surge in young women getting a disease that once plagued the palace? Dr Heather Viola, an internist at Mount Sinai in New York, says the rise is 'multifactorial', blaming modern diet and lifestyle shifts. 'More people than ever consume high amounts of sugary drinks like soda and juice sweetened with high-fructose corn syrup,' she tells 'These sugars increase uric acid production, a key player in gout.' Add to that the Western diet's love for red meat, seafood, and processed food, and you have a perfect storm. Dr Viola says that hormonal changes also put women at greater risk of gout. During menopause estrogen levels decline. 'This hormone plays a protective role by enhancing excretion of uric acid through the kidneys, so with less of it to play with, there's more chances of gout occurring,' she explains. One study found that women who have never given birth or been pregnant have double the odds of reaching the menopause before the age of 40, compared to those who have been pregnant. With more and more women in the US saying no to motherhood, there could be a link between more women experiencing early menopause and a growth in those contracting gout. Rising rates of obesity among young adults also interfere with how the body handles uric acid. Samantha Pearlman, a realtor from Atlanta, says she was blindsided when she was diagnosed with gout at 40. Mary Fran Emerson from Atlanta is another young woman battling gout and she joked that she asked her husband to chop her foot off because the pain was so intense Samantha Pearlman, a realtor from Atlanta, says she was shocked when she was diagnosed with the condition at 40 It started with shooting pain in her left toe one night. There was no injury, no bite, nothing obvious — but the pain was intense. At urgent care, she was told it was gout. In a TikTok video, she admitted: 'I guess I feel ignorant because I didn't even think about gout... no sign of injury, nothing with the toenail, no signs of a bite... It's one sided, not the other.' She was given a steroid shot and prescription meds — but also a new reality to face. 'I feel kind of silly,' she says. 'I didn't even know gout was a thing anymore. 'I feel like the little bit I learned about gout when I was younger was that it was like an old-time disease... from like 75 to 100 years ago. 'I'm not the typical patient… it's usually middle-aged men with a horrible diet, who drink a lot of beer and are overweight and that's clearly not me.' 'I'm not even overweight anymore. I recently lost 75 pounds and I eat fairly healthy. So I don't even know how I got gout to be honest with you.' Los Angeles-based actress Avery Norris was just 22 when she was diagnosed — also far from the stereotypical patient. She lives a healthy lifestyle and maintains a slim figure. But she also has type 2 diabetes, which studies show increases gout risk due to insulin resistance and higher uric acid levels. When a flare hits, she says she's down for one to two weeks and often unable to walk. To manage the condition, she takes medication and avoids red meat. Meanwhile, Mary Fran Emerson from Atlanta says her gout pain was so unbearable at one point she joked about asking her husband to chop her foot off. She doesn't drink heavily, eats well, and still couldn't believe her diagnosis. Dr Heather Viola, who is based out of Mount Sinai in New York, told that the spike among young women is 'multifactorial'. She says sugary soda is one factor to blame, along with the rise of processed foods While the big toe is still the most common target, Dr Viola says gout can strike ankles, knees, fingers, wrists, and elbows, and sometimes multiple joints at once. 'It may become chronic, leading to long-term joint damage if untreated… the pain and inflammation can be intense and debilitating.' Attacks usually peak within 12 to 24 hours, and can leave patients barely able to walk. Anti-inflammatory drug can be prescribed to help lessen the symptoms, while steroid injections offer rapid pain relief. To reduce risk, experts advise cutting back on sugary drinks and processed foods — and keeping a healthy weight. Because these days, gout doesn't care what you look like — and even the fittest bodies aren't immune to the 'disease of kings.'
Medscape
22-05-2025
- Health
- Medscape
Episode 1: Joint Pain in Paradise: A Closer Look at Arthritis and HS
This transcript has been edited for clarity. For more episodes, download the Medscape app or subscribe to the podcast on Apple Podcasts, Spotify, or your preferred podcast provider. Ginette A. Okoye, MD: Hello. I'm Dr Ginette Okoye. Welcome to the Medscape InDiscussion podcast series on hidradenitis suppurativa (HS). Today we'll be discussing the diagnosis and treatment of arthritis in HS with our guest, Dr Rebecca Manno. Dr Manno is a board-certified rheumatologist specializing in autoimmune and inflammatory conditions such as rheumatoid arthritis (RA), lupus, vasculitis, and scleroderma. She practices at Comprehensive Orthopaedic Global in the US Virgin Islands and is an adjunct assistant professor of medicine at Johns Hopkins University. Thank you for joining us today, and welcome to the Medscape InDiscussion podcast. Rebecca Manno, MD, MHS: Hi. Thank you so much for having me. This is such a pleasure. Okoye: Well, I am particularly excited to have you because, as you know, patients with HS often report joint symptoms and arthritis and arthropathy. I would love to get the definitions of those from you; they're known comorbidities of HS, and they contribute to the quality-of-life impact. But the joint symptoms haven't been well characterized, and they're often described by people like me, dermatologists. I don't think we quite have the expertise that you have in describing the joints, examining the joints, and knowing which imaging tests to record. I'm thrilled to have this conversation so you can help us all get better at this. Why don't you tell us a little bit about how you came to develop an expertise in HS. Manno: This story starts with a little bit of background on my personal career journey. I did my medical training, including rheumatology fellowship, at big academic centers in Baltimore, Maryland. And I joined the faculty in the Division of Rheumatology at Johns Hopkins in 2011. Throughout all of this, as with many of us who trained at big academic centers, you have access to every specialist and subspecialist in medicine that you can imagine. This makes it easy to stay in your rheumatology lane or whatever your specialty is. It made it easy to stay in my RA, lupus, vasculitis, gout lane, because for anything that expanded beyond your specialty, there's somebody right down the hallway who can help. Five years ago, I made a big career and life change and moved to the Virgin Islands, where I am currently the only full-time rheumatologist. I went from a big academic center with a huge medical infrastructure and an infinite number of providers and specialists to the opposite of the spectrum. The Virgin Islands is an amazing, close, tight-knit community, but we do have limited resources, especially when it comes to healthcare. Specifically, in our Virgin Islands territory, we have very, very limited dermatology access in general. Most of the HS is cared for either by primary care doctors or surgeons. So really, the way that I started having a referral pathway for HS patients was from my surgical colleagues. I had a conversation with one of our outstanding surgeons. He said, 'Rebecca, I just don't want to operate on this person again. I know that there are these medications out there, and we probably can do better for him. Would you see this patient and see if you can help?' And I said, absolutely. This opened the door to conversations and collaborations in our medical community here between rheumatology, surgery, and the primary care doctors and dermatology when we have some help there as well, about how to best take care of these patients. Okoye: Wow. That's, that's an amazing example of this kind of cross-specialty care for patients. After this episode, you may have several dermatologists interested in coming to the Virgin Islands to help you. Manno: Absolutely. Okoye: When you've been seeing patients with HS who have joint symptoms, what are the most common symptoms you've encountered, and which joints are more commonly affected? Manno: When I see patients with HS and arthritis in my clinic, there are two pathways or two scenarios. The first pathway is a patient who may be referred to me specifically for HS. Let's talk about that scenario first. When that patient is referred to me for HS I'm looking at their skin, but I'm a rheumatologist, so I'm going to start talking to them about their joints, whether they like it or not. I'm going to ask them about joint pain, swelling, stiffness, and striking inflammatory symptoms. And it is certainly a large proportion of these patients who do have joint symptoms; it can be a spectrum. The next step then is evaluating that, so if there is obvious synovitis or swelling on exam. I'll go down the path of evaluating them for a defined rheumatic disease. Do they have undiagnosed RA? Do they have undiagnosed axial spondyloarthritis? And sometimes I find those things, and then sometimes I don't. Yet on my exam of this patient who was sent to me for something that doesn't have to do with their joints, there is synovitis on exam. In those patients, it tends to be in the small joints of the hands. So the proximal interphalangeal (PIP) joints, sometimes the metacarpophalangeal (MCP) joints, enthesitis, and tendonitis, especially in the elbows and knees. Large joint arthritis is less common, but I've certainly seen it in the knees and ankles as well. In general, if these patients do not have a defined rheumatic disease that I can attribute their inflammatory arthritis to, and it's associated with the HS, it tends not to be a destructive arthritis. I have seen some exceptions to that rule. The second scenario would be a patient referred to me for joint pain — a typical rheumatology consult. We get these all the time, patients with joint pain. And then I uncover an HS diagnosis. These are patients in whom, truthfully and regrettably, I probably would have missed the HS diagnosis 5 years ago in Baltimore because HS is not a comorbidity in rheumatology we typically ask about. In our history or in our review of systems, when we're working up an inflammatory arthritis or joint pain, we're good at asking about psoriasis, skin manifestations of lupus or dermatomyositis, ulcers for pyoderma, and erythema nodosum for sarcoidosis. But we don't ask about HS. And I realized that when I started asking about it — and we'll be looking for it on our physical exam as well — but I recognize that if I didn't ask about it, a lot of patients may not tell me about it. They are embarrassed. They think that it's not relevant to what we're talking about. If I don't ask about it, and then I find it on physical exam, I say, why didn't you tell me about this? And they're like, oh, well, that's nothing. You see how patients may not bring that to the forefront, and that could be whatever subspecialist they're seeing, either because they're ashamed, they're embarrassed, or they don't think that you can help with it. They're worried that you're going to be judging them for something. That was eye-opening to me as well. Okoye: What I heard there is rheumatologists should be asking more about HS symptoms, and certainly dermatologists should be asking more about joint symptoms. Now that I have a captive rheumatologist, I have so many questions, one of which is, what are the typical symptoms you'll find in enthesitis or tendonitis? Manno: With enthesitis and tendonitis, it tends to be pain with active resistance. For example, let's talk about epicondylitis, which is an enthesitis or a tendonitis. It's really common, and it doesn't have to be indicative of a systemic inflammatory disease. Typically, that's your tennis elbow or your golfer's elbow — anything where you apply resistance to the insertion point of the tendon. For example, lifting your coffee cup or a gallon jug of water, when you're applying resistance to that tendon at the insertion point, it is going to elicit pain. It's a good way to try to differentiate that pain from arthritis. Arthritis will be painful, even with a passive range of motion. Okoye: For a dermatologist who hasn't had your training, how would you describe a quick joint exam? Manno: I think there are a couple of ways. First would be asking the questions. Even before laying hands on the patient, the doctor should ask questions about their joint symptoms. I think this is a space that is wide open for investigation. Similar to 'how now' with psoriasis and psoriatic arthritis, there are several simple screening instruments to use if patients are experiencing inflammatory joint symptoms, which should then prompt the referral to rheumatology. I think the same could be said for something similar for HS in the future. Start even just with a simple question: 'Do you have joint pain?' Because patients will sometimes say no, they're all right. Then you're done. When they say yes, the question is which joints and how long does it last? And is there swelling associated with it? The question of which joints, that's going to help to direct your physical exam, especially as a dermatologist, because I don't expect you to do the head-to-toe joint exam. How long? If they say, oh, I had a pain in my knee for 5 minutes last week, that's okay. It's better. We're done. But if the answer is, I have had this pain in my hands and in the morning, I can no longer hold my coffee cup because my hands are so stiff now, the focus of the exam is going to be on the hands and the small joints. Then you can ask, is there swelling associated with it? The patient may say, no, there's no swelling, or they'll say yes, there absolutely is. That also helps you to really pay close attention to those joints where if there has been swelling. Especially if they say that there's been swelling in a large joint, such as the knee, you can ask: Has it been large enough to where someone has drained fluid out of your knee? Something like that. We'll get a better sense of how long this has been going on and how severe. Then, when moving to the physical exam, admittedly, some of the more subtle synovitis, especially in the small joints of the hands and the wrists that I have seen in HS, can be more subtle. But I have absolutely seen the more robust, synovial hypertrophy — thickening of the joints and the small joints of the hands and in the feet with these patients. Certainly, looking at the joints that are the most affected is important. Does it look swollen? Are you seeing normal landmarks palpating it? Do you feel any fluid? Is it tender when you push on the joint itself, or is it not tender when you push on the joint and it's tender when you push somewhere else, like on a tendon insertion point? A quick and easy exam that we often teach medical students and our fellows to quickly look for synovitis in the MCPs or in the metatarsophalangeal joints (MTPs) is what's called an MCP squeeze or an MTP squeeze, where you just squeeze across two through four of the MCPs or one through five on the MTPs. If you do that and patients don't have synovitis or pain, it should elicit nothing. But if there is synovitis there, then patients will say, that's painful. So that's a good screening test instead of going joint by joint in the small joints of the hands, where it can be tricky, or in the feet. Okoye: Super high yield. I agree with you that there's room in HS for this type of screening tool. I hope you might be willing to work with a dermatologist to create that. Manno: Yes. Okoye: Let's move on to treatment. What are your go-to treatment options for patients with both HS and arthritis? Manno: Nonsteroidal anti-inflammatory drugs (NSAIDs) absolutely have a role to help acutely with the pain and the inflammation of arthritis. Many of the patients that I see are younger, so we aren't dealing with as many of the other comorbidities that may negate the use of NSAIDs, but of course we have to use them carefully given other medications they're using or if there's renal insufficiency and so on. I like NSAIDs quite a bit. I like topical NSAIDs, especially for the hands or for the knees. They can be very effective. They are not going to be as effective for other joints, such as the shoulders, for example. And then systemic NSAIDs if that's appropriate for the patient. I do find that the biologics, if we are using them to treat their HS, also treat the arthritis, which certainly can be effective. And if there is a clearly defined inflammatory arthritis, methotrexate can be helpful as well. I have not seen improvement in the joint symptoms or, if there is an inflammatory arthritis associated with the HS, with antibiotic regimens alone. Okoye: That makes sense. Let's go back to the NSAIDs. Are you referring to NSAIDs over the counter, such as ibuprofen, or are you referring to prescription NSAIDs? Manno: It depends on the specific patient scenario. I will often use the COX2 inhibitors for two reasons. One, there is slightly better gastric protection. Some patients tolerate them a bit better, and they have a longer duration of action. Ibuprofen only lasts about 4-6 hours. Patients are taking it multiple times throughout the day or are not taking it. Whereas naproxen and many of the COX2 inhibitors are once-a-day or twice-a-day drugs, which are easier for patients to take. Okoye: You mentioned methotrexate. Do you combine methotrexate and biologics in some patients? Manno: Absolutely. Certainly, if they have a defined inflammatory arthritis that is independent of the HS, then methotrexate in combination, especially with the tumor necrosis factor (TNF) alpha inhibitors, may give us additional benefit, especially for peripheral arthritis. This has not been studied in terms of if it's just HS-associated, but methotrexate in general can give a nice benefit for inflammatory arthritis of the small joints. Of course, we have to be careful, depending on our patient population, if we have young women who are considering pregnancy, and so on. We have to ask all of those right questions. But methotrexate in combination especially with the TNF-alpha inhibitor can be a nice combo for inflammatory arthritis. Okoye: That's interesting, because we use low-dose methotrexate around a range of 10 mg/wk for people whom we believe have anti-adalimumab antibodies or anti-infliximab antibodies. What's the range of the doses you're using for arthritis? Manno: For inflammatory arthritis, we will usually use doses between 15 and 25 mg/wk. Okoye: Okay, so a little bit higher. That's great. Dermatologists are quite comfortable with methotrexate, so that's certainly something we can add. You mentioned topical NSAIDs. I'm not as familiar with that group of drugs. Can you tell us a bit more about those and which ones you prefer? Manno: Diclofenac gel, which used to be prescription only, is now available over the counter, although some insurance companies will still pay for it if you write it as a prescription. It can be kind of expensive if purchased over the counter. It got its FDA approval for osteoarthritis of the hands and the knees because of the absorption; the joints are so close to the skin, which helps with easy absorption. I find it can be highly effective. I'll tell patients to apply it two to three times a day as needed. It is a little bit easier when you're in a warm climate, and so your knees may be exposed more, and you're not wearing long pants all of the time. It can be a great additional tool. And then it doesn't cause the gastrointestinal (GI) upset that we can see with NSAIDs. Okoye: Back to the bigger picture question here: Do you think the joint disease in HS is HS of the joints, or do you think patients with HS are more likely to have other inflammatory types of arthritis? Manno: I think this is a fantastic question, and I think this is the question that we should really have some good research agendas moving forward on. I think both are true. The data that do exist, especially in the dermatology literature, show us that patients with HS have an increased risk of also having another autoimmune disease. We know that's true in autoimmune diseases in general. If you've got one, you're allowed to have as many as you darn well please. So, those data are very clear that there is an increase in prevalence of RA and axial spondylarthritis in patients with HS. I think there's no doubt that you can have more than one, but it should be very clearly defined. If we're going to call it 'RA and HS,' it should be very, very clearly defined. This is where serologies and even classification criteria can be very helpful. Now, I know classification criteria are not diagnostic criteria, but they give us some boundaries when we're thinking about how to consider the different organ manifestations of an inflammatory process. Do I think that our HS patients are at higher risk for having these inflammatory processes? The data that we already have say yes, but there's a second scenario as well: the HS patients that don't have serologies, have an inflammatory arthritis, and have robust systemic inflammation. Now, on the one hand, you could call these patients 'seronegative RA,' and they would meet criteria for seronegative RA. Technically, yes, these patients don't have antibodies. They have hypogammaglobulinemia; they have a sedimentation rate and a C-reactive that's through the roof. They have anemia of chronic inflammation. You could call these patients 'seronegative RA,' but when you treat the HS, the arthritis improves. And now it gets complicated, because many of the treatments we're using for the HS also treat inflammatory arthritis. I'm going to share a case with you. I fully recognize this is a case of 'N of 1.' This is quite an extreme case, but I've seen several other instances that are in this similar neighborhood. I had a young man with terrible HS: stage 3, multiple sites, multiple locations. He responded partially to TNF-alpha inhibitors and steroids. We struggled to have consistent medical therapy for him for a lot of reasons, mostly access to medications and care. Ultimately, we sent him off-island to the United States, and he had multiple surgical procedures by a very skilled plastic surgeon; he was in the hospital for about a month and had multiple excisions and skin grafts. He did extremely well. Let me tell you, when I first met this young man, he clearly had advanced HS, but he also had a raging inflammatory arthritis. He had synovitis of the small joints of his hands and his wrists, where he was developing contractures at his PIP joints. He had developed some deformity of his fifth PIP on both hands. He had joint pain to the extent that he wasn't able to work. It wasn't just the skin; it was the joint symptoms too. When we sent him off-island, he had extensive surgical interventions. When he came back a couple of months later, I saw him. His arthritis was gone. His inflammatory markers were normal. His labs looked great. He was not on medical therapy. And he continues to do well today. Now, I'm not saying that this surgical intervention is the way to go about it, but if this was all seronegative RA from the beginning, it should not have improved with this type of intervention. That is an extreme example, and perhaps it is an outlier, but I think that it is telling us something about the robust inflammatory process of HS that goes beyond just the skin. Okoye: It tells us about this idea that we're starting to develop now, which is that HS tissue itself drives the inflammation. So, by debulking so-called HS, you decrease systemic inflammation, and that is telling with your patient. Wow, there's lots of work to be done in this area. Do you do serologies in these patients? Which ones? Manno: I will check serologies to look for a concurrent rheumatic disease because if they have the inflammatory arthritis and they're anti-cyclic citrullinated peptide (CCP) high titer positive, I'm going to call that RA with HS. I am going to check the antinuclear antibodies (ANA), and I will probably check double-stranded DNA if there are some joint symptoms associated with it as well. I want to know those things too, especially if I'm thinking about a biologic, and which ones to choose safely. And then I'll check serologies based on any other specific signs or symptoms. If they're having any GI issues, I will work them up for inflammatory bowel disease. and I will check anti-saccharomyces antibodies. I will check anti-neutrophil cytoplasmic antibody (ANCA), specifically perinuclear ANCA, which can be seen in inflammatory bowel disease as well. And of course, I'll have a GI workup for them too. But in general, unless I'm going down a path that they have an additional rheumatic disease, their serologies are going to be negative. But they will have hypogammaglobulinemia with immunoglobulin G levels that can be 2500 or 3000; they're polyclonal on serum protein electrophoresis. But it is just another example of how inflammatory they are. Okoye: What do you think is the role of exercise or physical therapy for the joint symptoms in HS? Manno: I think there is an important role for it. We know so much about the role of exercise in many of our rheumatic diseases that involve the musculoskeletal system, such as RA, dermatomyositis, and axial spondyloarthritis. We consider exercise to be just as important a part of the prescription as the disease-modifying antirheumatic drug or their biologic agent, and the data strongly support that. And it starts with some education for the patients who think, Am I going to make this worse? Especially when they're dealing with a musculoskeletal problem like arthritis, and I would say even with HS patients, because they're worried about moving too much. From an arthritis standpoint, I can say definitively, no, you are not going to make it worse. Now, I'm not going to recommend that they go join a CrossFit gym and do really high-impact exercise that is high velocity. Things that are not high impact can still be extremely beneficial. It just means that they should be slow, controlled movements. Absolutely, exercise is key. The goal of exercise is to increase strength and muscle mass, which will help with overall body composition. Weight management is important, but it's body composition. We want our patients not to be undermuscled, which is what they are. We want them to gain muscle. I think something important, with our HS patients, is giving them an exercise prescription. I'll start with something very simple: find out what they like to do. They'll say, well, I like to go walking. Great. I want you to walk for 15 minutes once a week, and at the end of your walk, you're going to do 10 air squats, or you're going to do 10 step-ups. Okoye: Very specific. Manno: Very specific, and you're going to do that for a month, and then you're going to increase it to twice a week. Simple and specific, so it's achievable. The other thing that I will do is refer our patients to a physical therapist for a home-based resistance exercise program, which can be supervised for some time by the therapist and then can be translated into something at home. Okoye: Wow, Dr Manno, I have to go back and listen to this podcast to finish taking my notes for my patients. This has been enlightening, and I don't think that this resource exists anywhere else yet, so I really appreciate all you do for patients with HS. And I thank you for coming on the podcast. Manno: I thank you for inviting rheumatology to the conversation about HS. We are definitely, as a community, happy to be here and be a part of this. Thank you for all that you're doing as well. Okoye: Today, we talked to Dr Manno about the diagnosis and treatment of arthritis in HS. Thank you for joining us. Please take a moment to download the Medscape app to listen and subscribe to this podcast series on hidradenitis suppurativa. This is Dr Ginnette Okoye, for the Medscape InDiscussion podcast. Association between Hidradenitis Suppurativa and Inflammatory Arthritis: A Systematic Review and Meta-Analysis Comorbidities and Quality of Life in Hidradenitis Suppurativa Prevalence of Musculoskeletal Symptoms in Patients With Hidradenitis Suppurativa and Associated Factors: Cross-Sectional Study Diagnostic Delay in Hidradenitis Suppurativa: Still an Unsolved Problem Improving Hidradenitis Suppurativa Management: Consensus Statements From Physicians and Patients' Perspectives Management of Lateral Epicondylitis: A Narrative Literature Review 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee Efficacy and Safety of Topical NSAIDs in the Management of Osteoarthritis: Evidence From Real-Life Setting Trials and Surveys Methotrexate and Its Mechanisms of Action in Inflammatory Arthritis Hidradenitis Suppurativa and Rheumatoid Arthritis: Evaluating the Bidirectional Association
