Lead With Lupus (8.2.2024) Save

Doctor. 08/02/2024, and this is the RheumNow podcast. Hi, I'm Doctor. Cush with RheumNow. We're going to start with lupus.

But first, in 1984, I moved to Dallas, Texas from New York. And the one thing about living in Dallas is they love their football and they love their cowboys. I got there in the summertime at the beginning of training camp and football season and every sports report, every news report always began with the Cowboys. There was a famous, sports reporter, who just moved to Dallas at the time. His name was Dale Hansen.

He had an over thirty year career, at Channel eight and he was, great at his job. But it didn't matter if it was football season in the fall or if it was hockey season in the winter or the beginning of baseball season in April, he always started his sportscast talking about the cowboys. And I just didn't get it until I heard him on an interview once who he said always always you lead with the cowboys because then you've got them for the rest of the segment. Maybe that's a lesson for how we should teach or how I'll do my podcast. So let's start with lupus.

Lancet Rheumatology did an interesting study about the protective effects of LLDAS, the low disease activity state for lupus. This is a prospective multinational cohort study done from 2013 to 2020. Almost three thousand five hundred lupus patients followed for nearly three years and they found that the LLDAS, metric for doing well was achieved at least once in seventy three percent of people. But sustained LLDAS is really what you need. That's an LLDAS that's for three months or more.

Those people, much less, had significantly less damage overall. They had greater chance of remission. They had a greater chance of not flaring. The benefits of these were about 40% more for each of those parameters if you did in fact achieve LLDAS and kept it, at that level for three months or more. This sort of speaks to how do you know your lupus patients are doing well?

You don't usually measure anything other than things that truly aren't predictive, like proteinuria and complement levels. There are in a few people, but not on the whole. We need a better daily practice measure of how lupus patients are doing. Maybe we'll come across that soon. General Rheumatology reported the results of the TRUST study, and this is a study of the use of tacrolimus.

What do you think? What do you say? I say tacrolimus. We'll call it TAC. In thirteen fifty five lupus nephritis patients, they've had who were on tacrolimus for, the majority of them for more than ten years.

Using tacrolimus in their population was associated with significantly less use of steroids. When they started out they were taking an average of sixteen milligrams per day and at the end of, the follow-up period, which was, one year later, the average dose was seven milligrams. They also, showed that it was well tolerated and that, you know, but they did have serious adverse events, serious adverse events, usually hospitalizable things, serious things, things that change morbidity, if not mortality, almost ten percent with tacrolimus. So while calcineurin inhibitors are important in the management of lupus and an alternative in lupus nephritis, think we're using less of that and using more of the newer agents, which probably are safer and probably have better long term results. A US database of pediatric, hospital admissions identified eight thousand five hundred kids with lupus in at least one hospitalization.

They found that, infection was an, infrequent cause of hospitalization thirteen percent of the eight thousand five hundred kids with bacterial pneumonia being the most common. But the important part is while, infections are an important number but a low number of hospitalizations for lupus in kids, it is the major cause of in hospital mortality. So they found that forty percent of their childhood lupus cases actually had, not forty percent, I'm sorry, it was zero point four percent. So it's a very low number actually died, but it was five times that amount that died from infection. Again, the thing is that it's not that common, but when it happens, it does carry substantial morbidity mortality risk.

The highest mortality was seen with the often unrecognized infections, pneumocystis and occult fungal infections. This is what you need to keep in mind in your patients who are immunosuppressed, especially with lupus, when they get hospitalized. I think this applies to adults, the only difference being that kids probably have more severe lupus than do adults in my opinion. I think the data backs that up. Current opinion in rheumatology does a nice overview review of calcinosis cutis, which they remind us is seen in forty percent of patients with systemic sclerosis, and it's problematic.

It has a lot of morbidity associated with it. People who get calcinosis are more likely to have a longer disease duration, evidence of vascular dysfunction and osteoporosis for some reason, I'm not sure why. The diagnosis certainly by radiography but we don't really have any good medical treatment. So everybody's got their little cha cha cha dance they do with medical therapy for, calcinosis and I don't really have my own, but they'd say what many experts have said to me, it is surgical debridement of calcinosis that probably works the best. Being a partner with a good, plastic surgeon is probably how you can best manage those patients, whether it's systemic sclerosis or dermatomyositis or other autoimmune disease.

That's probably how you, need to manage that. Remember NXP-two antibody positive dermatomyositis high rates of calcinosis. The journal Muscle and Nerve, which you don't read, that I scanned, compared, one hundred patients with psoriatic disease, both psoriasis and psoriatic arthritis, to 100 controls and found that psoriatic patients have a 20 fold higher, prevalence of neuropathy. I was surprised by this, but then again when you read the fine print you find that when they controlled for comorbidities that frequently affect psoriatic disease, that the significance of neuropathy in psoriatic disease goes away. Meaning that neuropathy, which is common in psoriatic disease, is, riding the coattails of the comorbidities that they often get diabetes, obesity, you know, go down the list of the many things that they get.

An osteoporosis journal had an interesting report co authored by one of our good, teachers, Mike McClung. This comes from JBMR, the Journal of Bone and Mineral Research. This basically said that treatment of osteoporosis actually benefits both males and females. It's really been shown most for women, right, and seldom for men, and that was the purpose of the report. They compared 100 psoriatic to 100 controls, they, no, I'm sorry, different numbers, four thousand three hundred women and seven ninety two men who had, DEXA defined hip osteoporosis.

They showed that about thirty percent of both the men and women had hip fractures. They also showed that treatment with alendronate in this larger cohort significantly lowered the hip fracture rates in both men and women by almost seventy five-eighty percent. So that was kind of the report here that men benefit from even bisphosphonate therapy as far as having a protective effect on hip outcomes. I thought that was worth teaching on this week. The journal Nutrients had an article that you would love because you're a rheumatologist and all rheumatologists love all things vitamin D.

Yeah, I'm not one of you, but I put it up because just to give you some yayas and feel goods. This comes from Maurizio Cucillo in Italy and his co workers. They did a literature review of many articles looking at the beneficial effects of vitamin D, and found that number one, it's common amongst rheumatic patients. Guess what? It's common amongst everybody.

And they showed that low levels of vitamin D were linked to a number of different problems, across the board, and that included, loss of muscle strength, musculoskeletal pain, joint pain, sarcopenia, and falls. All those were significant and all those reports were found in patients with myositis, PMR, SLE, RA, scleroderma, etc. Again, you love vitamin D data. Show me the vitamin D data where giving back vitamin D makes all those problems falling, sarcopenia, musculoskeletal pain, loss of muscle strength get better and go away. I don't see many of those.

I'm not arguing with you about the benefits of vitamin D on bone health and immune function, but I do think that you like vitamin D data more than I, and I put that up there just for you so that you would be happy today. I'll avoid all my snarky comments. The BMJ had, and and, what was the other article? Cartilage and osteoarthritis had two articles about, NSAIDs. And I thought this is important.

We're using less NSAIDs these day. The BMJ reported The, United Kingdom experience in their analysis of hazardous NSAID use. They define hazardous as giving NSAIDs to someone over age 65, especially without gastro protection, people taking anticoagulants and those with heart failure, chronic kidney disease or prior history of peptic ulcer or GI bleed. They in their analysis, this is I believe a nice analysis showed that it cost The UK, over £31,000,000 over the last ten years. And so I think that this is important, and a reminder as to maybe where we absolutely positively shouldn't be using nonsteroidals.

Tahina Nioji had an interesting article in osteoarthritis and cartilage about, patients who are receiving nonsteroidals inappropriately despite the contraindication to use. So in her cohort analysis of over thirty five thousand patients with newly diagnosed osteoarthritis, they found that three thousand two hundred had, a contraindication to use. And I think eight thousand five hundred had a precaution against the use of an oral nonsteroidal. Nonetheless, twenty seven percent were on oral nonsteroidals and twenty one percent of those were taking them inappropriately despite the contraindication or precautions. This is a little bit worrisome.

Why have rules if no one's gonna follow them? So again, what they did find in those people that were getting the NSAIDs despite the warnings, they were also getting a higher amount of narcotics and they were also using way less physical therapy. Again, rules are meant to be followed. If you're not following them, you're a rule breaker and it's gonna go on your permanent record. You're gonna get in trouble.

Not by me because I think all rheumatologists are perfect. I have talked in the past a lot about polypharmacy. I think it's the big bad player in chronic disease management and we are guilty as our primary care doctors and everyone. You know, if you're on, I used to play softball and baseball. When you're in softball leagues, there was a 10 run rule.

If the other team got ahead by 10 runs, the game's over. I think there should be a 10 run rule for drugs. If your patient's on 10 drugs or more, the game's over, you need to worry big time about polypharmacy. This report in JAMA showed that in the last twenty years, polypharmacy has doubled. So using several large databases, and they define polypharmacy as being on five drugs or more, which I think is a very mild and lenient definition.

But in 2020, twenty four percent of, I believe this is elderly, guilty of polypharmacy or their doctors are guilty of polypharmacy. But in 2020, twenty years later, it's almost doubled to forty percent or so. That's why we see it. I like this RA study about who's going to get better with RA. It's called the first study.

It's a study of fourteen hundred, RA patients, who are newly treated. And they found that, about half of them achieve a HAC DI of less than point five. That's doing very well. They found that about a quarter or a third of them, achieved a VAS of less than four. So what they found was that, who were the patients that achieved both of those and did so within the first six months of therapy?

They found that those people were more likely to be seropositive and actually to be treated with JAK inhibitors. They found the ones who are not likely to do that were going to be older, have previously failed two or more either biologic or targeted synthetics, have high baseline HACs, or be on chronic steroids. It turns out in their analysis comorbidities were not predictors of poor outcomes early on in RA. I find that interesting. The CHECK study is a study of femoral acetabular impingement syndrome.

I don't know about you, but I've been plagued by this a few times with patients. These patients tend to be younger. They have hip pain. It's often worse with activity. It can be diagnosed radiographically and by physical maneuvers.

This is an article from the British Journal of Sports Medicine, prospective cohort studies of, I think the number was like one hundred and fifty patients undergoing well, they were in their clinics. And basically they showed that patients who had this femoroacetabular impingement syndrome had a subsequent higher risk of developing, Hippo A within ten years, and that's like six point eight five fold higher. And they had a forty eight fold higher risk of having end stage radiographic HIP OA. The point being that femoroacetabular impingement syndrome, when you're diagnosing it in the 40s and 50s, is someone who's got high risk of future, need for hip surgery. And it probably has to do with the morphology of the hip joint, whether it's the acetabular or femoral portion, that's abnormal, that causes the impingement, that causes symptom, and maybe it's that abnormal anatomy that's the forerunner to what will ultimately become degenerative arthritis of the hip.

I thought this was interesting. We had two big reports this week on calcium pyrophosphate disease. I don't think we discussed this often enough. One was from arthritis and rheumatology, and it really gave you some of the features of the disease. This was in about six eighteen patients in a cohort study used to define the recently published criteria for calcium pyrophosphate deposition disease.

But in that cohort, they showed that, fifty six percent female, mean age 74 years, and how did they present clinically, and then it could have more than one presentation. Almost all of them at some point in this cohort had acute CPP, arthritis, and they don't go into how it was diagnosed. Half of them had recurrent acute arthritis, and that those patients were more likely to have longer disease duration, hence the recurrence. I think that those patients, this recurrent inflammatory arthritis are also the ones we might call chronic CPPD. There's also, about twenty five percent who had persistent inflammatory arthritis.

I think these are the ones we would call, the RA like arthritis manifestations. And a minority, seven percent, had the Crowned Den syndrome. The second report was seen in Rheumatology, where it was just a good review of calcium pyrophosphate disease, and it's really a nice full read, you know, five page read. I gave you in my review article of this, I think, like 10 or 12 bullets, the ones I wrote down that I thought I would repeat here to instill you to maybe go and read this is that CPPD is often mistaken for other diseases, including gout, RA, PMR or OA. Again, why patients with, CPPD, share a, coexistence with osteoarthritis is unclear, although they may have that because they may share similar risk factors.

But again, the association is not entirely understood, nor is the association between CPPD and the many different metabolic conditions that go along with it hyperparathyroidism, hemochromatosis, hypomagnesemia, and hypophosphatasia. Again, a lot of CPPD patients will have those and you need to probably search for those. It is in many ways, follows the same path as does gout. It's got a high association with many comorbidities just like gout. It's largely mediated through the initiation of the NLRP3 inflammasome.

We know that urate crystals will excite the inflammasome, and obviously it must be the same for calcium pyrophosphate crystals. Lastly, I'd say that your diagnosis is going to be by synovial fluid, also supported by radiography, but they made an important point in case for the use of ultrasonography, which is more and more being used obviously to diagnose both gout and pseudo gout. They do go over the therapy and say that prednisone has the highest, benefit to risk ratio of all the drugs. They sort of tacitly allow you to use colchicine, although I personally wouldn't, and they even go into why there is some evidence for biologic therapy, IL-six therapies and DMARDs like hydroxychloroquine, but I don't know other than having chronic inflammatory RA like disease that I'd be using those therapies. I don't think there are any studies proving those points.

There are studies proving the efficacy of both prednisone and colchicine. The last big report this week, on the podcast is the report from Annals of Internal Medicine about the use of methotrexate in knee osteoarthritis. This was a two zero seven and the patients were those with radiographic knee osteoarthritis with a pain score of greater than four out of ten. And they were randomized to either placebo or weekly methotrexate with a six week escalation from ten to twenty five milligrams per week. And they stayed on their background analgesics, and they did an assessment at six months and twelve months.

The primary endpoint at six months was actually better achieved with and statistically so by those who are taking methotrexate. So who were these patients? Two thirds were women, average age 61 years, half of them had pretty advanced knee OA, Kelgren Lawrence grades of three and four. And what they found was that, not all patients had completed the study, only eighty six percent. Their final analysis was sixty six versus sixty eight patients and the change in pain scores, when methotrexate went from 6.4 down to 5.1.

These are mean scores. Placebo didn't really change 6.8 to 6.2. So that was significant at 0.03, also significant for other WOMAC, subscores like function and stiffness. And there were really no increased rates of adverse events, and there were a few equally split between placebo and methotrexate. So we reported, again from UR and from ACR about methotrexate being used in hand OA.

Am I using methotrexate in OA of the knee or hand? No, because I think these studies are small. I think that they have flaws in them. I think that, there are equally a similar number of studies and patients treated with this where it didn't work. And I'm biased because in the late 1980s, want to say, maybe 1990, I did a two year study of this.

I think I treated almost 20 patients with either placebo or weekly methotrexate fifteen a week. They were not inflammatory, OAs. They were garden variety, degenerative, no effusion, normal sed rate, normal CRP. And ultimately, I thought there was a benefit because I had a few patients say, oh, wow, I'm doing great. But when you unblind the study, there was no difference.

So I think that this is interesting. It might be the only positive data we have out there about a demode, meaning a DMAR that might work in a way. Demodes are supposed to structurally change and improve the disease and that's another reason why we don't have that. But this is encouraging and I think someone, with a lot of money should do this trial because who's going do this trial? Mean, Warner Lambert who developed methotrexate is no longer in business and a generic company is not going to do this.

But let's tune in maybe we'll see the answer to this in years to come. That's it for this week on the podcast. Hope you're doing well. We look forward to seeing you soon. Watch out for RheumNow Live.

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