Fibromyalgia at the EULAR 2020 Meeting Online

I have selected a few studies, which were presented at the 2EULAR 2020 Meeting, which has been online because of Covid-19.

The first study has been by B. Kundakci and colleagues [1]: „THU0461 THE COMPARATIVE EFFICACY OF NON-PHARMACOLOGICAL INTERVENTIONS FOR FIBROMYALGIA: A SYSTEMATIC REVIEW WITH BAYESIAN NETWORK META-ANALYSIS“.The authors looked at 78 studies (n = 5,639 participants). Multidisciplinary treatment was the best for improving pain, sleep and depression, balneotherapy and exercise were the most effective treatments for FIQ and fatigue. Allow me to intervene, as one doesn't treat the Fibromyalgia Impact Questionnair, but nevertheless one can see improvement in the score of this questionnaire. 47 exercise trials (n = 3,271 participants) were also analysed. Strengthening showed the greatest benefits for FIQ, pain and depression, whereas aerobic exercise was the best for fatigue and sleep. As the effect size tvaries between interventions and outcomes, the authors conclude, that „the results of this study may be used to guide the selection of the most effective non-pharmacological interventions according to the predominant symptom in individual patients.“ Though the approach with comparing effect sizes is a good idea, I doubt that this will happen in real life.

My next selection is the study by L. López-Núñez and colleagues [2]: „THU0462 CHARACTERIZATION OF PATIENTS WITH FIBROMYALGIA AFFECTS WITH OR WITHOUT JOINT HYPERLAXITY SYNDROME“. If you have read more on my blog you know about my long lasting interests in hyperlaxity or the benign hypermobility syndrome. In their conclusion the authors point out: „Our work revealed that FM patients with JHS are different from FM without JHS, by manifesting differences in certain clinical, anthropometric, and bone metabolism features.“ The Body Mass Index and Muscle Mass were less in the FM-JHS group. The FM-JHS group also had less bone mineral density (BMD) at total hip DXA, which might be due to the lesser weight. So the study gives interesting data, but implications on treatment are not emminent.

The next study is by S. A. A. Tabra and colleagues [3]: „THU0471 VITAMIN D SUPPLEMENTATION; IS IT EFFECTIVE IN FIBROMYALGIA PATIENTS?“ 100 adult patients of primary FMS (according to the 2010 ACR criteria for FMS) associated with vitamin D insufficiency (21-29 ng/mL) took part in this interventional double-blinded study. 21-29 ng/ml is just below normal and after six months the vitamin D group had a level of just above the lower limit (36.8 +/- 3.9 ng/ml). May this be as it is, there have been differences in the results between the vitamin D group and the placebo group. Gth authors concluded, that „Vitamin D supplement is effective as an adjuvant therapy in improving functional status, quality of life and psychological status in fibromyalgia patients with vitamin D insufficiency.“ Please repeat the study with a higher level of vitamin D as a goal.

A. Negm and J. Alsaleh presented [4]: „THU0484 FIBROMYALGIA AND MULTIPLE SWITCHING OF BIOLOGICS IN SPONDYLOARTHRITIS“. The authors looked at 305 patients; but there were only 43 patients with coexisting fibromyalgia. They concluded: „FM coexistence with SpA might impact clinical evaluation of disease activity and possibly negatively affect self-measurement of treatment response. In our study, SPA patients exposed to more biologics if they have coexisting FM; Moreover, they are more frequent switchers among biologics including TNFi and IL17i.“ The study shows that our tools to make treatment decisions in spondyloarthopathies are too inaccurate if it comes to concomitant fibromyalgia.

A. Gomez-Centeno and colleagues presented the folloeing study [5]: „AB0952 COENZYME Q10, TRYPTOPHAN AND MAGNESIUM: A NUTRITIONAL SUPPLEMENT IN THE TREATMENT OF FIBROMYALGIA SYMPTOMS“. I don't know if I should already start to whince. The authors studied 23 patients, whereof 3 dropped out. They found an improvement, but: „no statistically significant differences were found among the studied variables.“ If the statistics do not support your hypothesis, it is premature to draw conclusions. Conduct a study of a larger number of patients and do so for at least half a year. My educated guess is that you won't find statically significant differences.

A. Keskin and colleagues asked [6]: „AB0954 IS CONNECTIVE TISSUE MASSAGE EFFECTIVE IN INDIVIDUALS WITH FIBROMYALGIA?“ They concluded: „According to our results, connective tissue massage has been shown to be effective in reducing the number of painful areas in addition to the positive effects of clinical pilates exercises in individuals with FM. In order to increase the effectiveness of treatment in individuals with FM, we recommend the use of connective tissue massage as an additional treatment method.“ The authors compared an interventional group of N=15 to a control group of N=17. And they found no statistically significant differences in the Fibromyalgia Impact Questionnare (FIQ), the Health Assessment Questionnare (HAQ), the Beck Anxiety Inventory (BAI), the Short Form-36 (SF-36) and the Cognitive Exercise Therapy Approach (BETY) Scale; there has been a difference in the Pain Location Inventory (p=0.023). This is cherry picking and not science. The authors should have formulated a hypothesis and an endpoint.

A. Moshrif and colleagues presented a study on vertical nail ridging [7]: „AB0956 VERTICAL NAIL RIDGING IN PATIENTS WITH FIBROMYALGIA: FREQUENCY, PROPOSED GRADING AND CORRELATION WITH OTHER DISEASE FEATURES.“ The authors concluded: „vertical nail ridging is a frequent finding and can be considered helpful for diagnosis of patients with FM.“ The authors found 98.6% vertical nail ridging in the fibromyalgia group, and they found vertical nail ridging in 76.2% of the control group. If vertical nail ridging is related to stressful conditions, why not look there in the first place? Of what use is a test, if the control group shows the same sign in a high proportion of patients? Maybe the next study shows a correlation between number of freckles in red haired fibromyalgia patients and the development of the FIQ score in the next six months. And please look for a study on vertical nail ridging on PubMed; there is none. The reference in the study [8] is a talk, which has been held in 2007, concerning vertical nail ridging it says: „Another stress-related nail habit that Dr. Mayoral discussed is people who rub their fingers over their thumb nail, which can create a ridge across the nail. This rubbing causes a distortion of the nail plate, and when the nail grows, a raised ridge forms in the middle of the nail.“ I guess looking for vertical nail ridging won't make it into the ACR Fibromyalgia Criteria.

M. Giovale and colleagues presented the following study [9]: „LOW-ENERGY PULSED ELECTROMAGNETIC FIELD THERAPY REDUCES PAIN IN FIBROMYALGIA: A RANDOMIZED SINGLE-BLIND CONTROLLED PILOT STUDY.“ 21 women with fibromyalgia were evaluated in TWO groups, one receiving active treatment under single-blinded condition. Makes me whince again. „In all endpoints, we observed a general reduction at T4 and T8 compared to T0 also for FIQ, VAS pain, SS, SF-36, regardless of the treatment arm and the decrease was higher in the active treatment arm compared to the placebo group, albeit not reaching statistical significance.“ I haven't found the definition of an endpoint. The authors concluded: „The results of our pilot study show that PEMF is more effective than placebo in reducing widespread pain in fibromyalgia while confirming that a placebo effect is clear in this complex disease.“ No, that is what the sponsor of the study likes to hear. The study showed no statistically significant difference between the two groups.

Hoping for better studies in future meetings concernig fibromyalgia.

References:

[1] Kundakci B, Kaur J, Shim SR, et al: THU0461 THE COMPARATIVE EFFICACY OF NON-PHARMACOLOGICAL INTERVENTIONS FOR FIBROMYALGIA: A SYSTEMATIC REVIEW WITH BAYESIAN NETWORK META-ANALYSIS. Annals of the Rheumatic Diseases 2020;79:463-464. http://dx.doi.org/10.1136/annrheumdis-2020-eular.803

[2] López-Núñez L, Blanch J, Ciria Recasens M, et al: THU0462 CHARACTERIZATION OF PATIENTS WITH FIBROMYALGIA AFFECTS WITH OR WITHOUT JOINT HYPERLAXITY SYNDROME. Annals of the Rheumatic Diseases 2020;79:464. http://dx.doi.org/10.1136/annrheumdis-2020-eular.4115

[3] Tabra SAA, Abu-Zaid MH, Hablas S: THU0471 VITAMIN D SUPPLEMENTATION; IS IT EFFECTIVE IN FIBROMYALGIA PATIENTS? Annals of the Rheumatic Diseases 2020;79:468-469. http://dx.doi.org/10.1136/annrheumdis-2020-eular.487

[4] Negm A, Alsaleh J: THU0484 FIBROMYALGIA AND MULTIPLE SWITCHING OF BIOLOGICS IN SPONDYLOARTHRITIS. Annals of the Rheumatic Diseases 2020;79:475-476. http://dx.doi.org/10.1136/annrheumdis-2020-eular.6224

[5] Gomez-Centeno A, Ramentol M, Gonzalez MJ, et al: AB0952 COENZYME Q10, TRYPTOPHAN AND MAGNESIUM: A NUTRITIONAL SUPPLEMENT IN THE TREATMENT OF FIBROMYALGIA SYMPTOMS. Annals of the Rheumatic Diseases 2020;79:1769-1770. http://dx.doi.org/10.1136/annrheumdis-2020-eular.5531

[6] Keskin A, Basakci Calik B, Gur Kabul E, et al: AB0954 IS CONNECTIVE TISSUE MASSAGE EFFECTIVE IN INDIVIDUALS WITH FIBROMYALGIA? Annals of the Rheumatic Diseases 2020;79:1770-1771. http://dx.doi.org/10.1136/annrheumdis-2020-eular.6316

[7] Moshrif A, Abdelkareem M, Moneer M, et al: AB0956 VERTICAL NAIL RIDGING IN PATIENTS WITH FIBROMYALGIA: FREQUENCY, PROPOSED GRADING AND CORRELATION WITH OTHER DISEASE FEATURES. Annals of the Rheumatic Diseases 2020;79:1771. http://dx.doi.org/10.1136/annrheumdis-2020-eular.5317

[8] American Academy of Dermatology. (2007, November 12). Feeling Stressed? How Your Skin, Hair And Nails Can Show It. Science Daily. Retrieved December 30, 2019 from www.sciencedaily.com/releases/2007/11/071109194053.htm

[9] Giovale M, Novelli L, Rampoldi S, et al: AB0958 LOW-ENERGY PULSED ELECTROMAGNETIC FIELD THERAPY REDUCES PAIN IN FIBROMYALGIA: A RANDOMIZED SINGLE-BLIND CONTROLLED PILOT STUDY. Annals of the Rheumatic Diseases 2020;79:1772. http://dx.doi.org/10.1136/annrheumdis-2020-eular.6409

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Effect of Tai Chi versus Aerobic Exercise for Fibromyalgia

Recently there has been a study on tai chi versus aerobic exercise for fibromyalgia. Tai chi or maybe better tai ji quan (太极拳), has a long history in China. Tai ji quan combines physical exercises and meditation. One can find balance between tension and relaxation. So it’s interesting to have a study in a syndrome, where patients have lost the ability to relax.

Ch. Wang and colleagues published this study: “Effect of tai chi versus aerobic exercise for fibromyalgia: comparative effectiveness randomized controlled trial” [1]. The authors concluded: “Tai chi mind-body treatment results in similar or greater improvement in symptoms than aerobic exercise, the current most commonly prescribed non-drug treatment, for a variety of outcomes for patients with fibromyalgia. Longer duration of tai chi showed greater improvement. This mind-body approach may be considered a therapeutic option in the multidisciplinary management of fibromyalgia.”

There is a little shortcoming, however: “Participants attended the tai chi training sessions more often than participants attended aerobic exercise.”

All in all, we should encourage fibromyalgia patients to include tai chi into their exercise plan.

Links:

[1] BMJ 2018;360:k851 doi: https://doi.org/10.1136/bmj.k851

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Fibromyalgia and Stem Cells

In 2010 a patient told me about stem cells in the treatment of fibromyalgia [1]. What are stell cells? I’ll introduce some of these cells to you. Stem cells are undifferentiated cells, which differentiate into other cells like liver or other organ cells or hematopoietic cells. You have fetal or adult stem cells. Bone marrow transplants use stem cells from the bone marrow of the patient (autologous) or from a donor (allogenic). Allogenic grafts bear the risk of graft-versus-host disease (GVHD), a serious condition, which might lead to death. The more matching the donor’s proteins are, the less risky the transplant will be. Transplanting a xenograft means using cells from another species. The FDA issued a warning about stem cells [2]: “FDA has not approved any stem cell-based products for use, other than cord blood-derived hematopoietic progenitor cells (blood forming stem cells) for certain indications including certain blood cancers and some inherited metabolic and immune system disorders.”

Today someone tried to put an ad for a stem cell therapy on my blog: ”Fibomyalgia is called a invisible syndrome. Because it is so difficult to diagnose this disease by lab test. 2%-4% of the people are affected by this syndrome and most of them are women. Fibromyalgia treatment [a link to a commercial page]“. Concerning these stem cells what we have is the Frischzellentherapie [live-cell therapy] by Niehans. The cells are derived out of sheep fetus for instance, a xenograft (graft of a different species) – that would make it a FDA non-approved therapy. The last article on Frischzellentherapie has been by de Ridder and colleagues in 1987 [3]: “[2 cases of death following cell therapy].” The authors told us: “In one instance, a 75-year-old woman died 30 days after an intramuscular injection of quick-frozen fresh cells from the effects of an immune-complex vasculitis; in the other, a 60-year-old woman died 14 days after "original fresh-cell treatment after Prof. Niehans" from perivenous leucoencephalitis.”

The page is well done showing two models, who pose as medical doctors; I looked up the photographs on Google Images. These models are always equipped with stethoscopes. Maybe they want to listen to the sound of the stem cells or expect tender points to squeak with pain. Interestingly they were also used on a homepage for a dentist in Bulgaria – for what would he have use for a stethoscope?

And they offer two links for research papers. The first link brings you to an article in German about the history of the Frischzellentherapie. Niehans himself had written, however [4]: „Neben «Organschädigungen» und «Altersgebrechen» könne mit ihr etwa die damals mit dem Begriff «Mongolismus» bezeichnete heutige «Trisomie  21» ebenso geheilt werden wie auch die «Fehlentwicklung» Homosexualität.“ [Translation: "In addition to "organ damage" and "old age", the "trisomy 21", which was then referred to as the "Mongolism", could be cured as well as the" misdevelopment" homosexuality.”]

The Frischzellentherapie [live-cell therapy] has been popular in Germany during the 50ies and 60ies. Wikipedia has an article in German [5], which tells us on risks: “[Like any foreign tissue, fetal cattle or sheep cells can cause severe allergic reactions to an allergic shock with cardiac arrest. There is no scientific evidence of the efficacy of the therapy. Therefore, evidence-based medicine basically rejects cell therapy.]” And: [“Medical practitioners refer to the preparations used as a risk material, in which there is the risk that diseases of an animal are transmitted to humans, for example BSE, rabies or Q-fever. The World Health Organization (WHO) issued a warning. Other risks arise from the possible occurrence of autoimmune diseases.”]

In 2015 there has been an article on unauthorized living cell therapies in Switzerland [6], as there is no such authorization. Penal proceedings against clinics using these therapies have been initiated then.

Have a look at scientific articles! Oh, sorry there are none. Here are a few searches on stem cells and fibromyalgia:

("Adult Stem Cells"[Mesh]) AND "Fibromyalgia"[Mesh] No documents match your search terms

("Fibromyalgia"[Mesh]) AND "Mesenchymal Stromal Cells"[Mesh] No documents match your search terms

("Fibromyalgia"[Mesh]) AND "Tissue Therapy, Historical"[Mesh] No documents match your search terms

“Cellular (cell) therapy can be defined as the use of natural cells to treat a disease. It starts with the selection of organs cells from a fetal animal specially bred for this purpose”, boasts the homepage of this doubtable stem cell therapy. And: “Due to the fact that this fetal cells DO NOT contain antigens, they are not recognized as foreign by the human body.” How could this be as the cells are from a another species (animal)? So the second link to an article is worthless as it looks at human mesenchymal stem cells [7].

Monthly injections will cost 512.91 US$ and capsules to be taken orally 431.91 US$. Lots of certificates: “Not tested on Animals” – wow, you kill animals, but are proud that you didn’t test it on animals – wait a second, don’t tell me you did unapproved human testing. More likely you didn’t test it at all.

I cannot recommend this “therapy”. You better stay away from it.

Links and References: 

[1] http://rheumatologe.blogspot.de/2010/02/fibromyalgie-and-stem-cells.html

[2] https://www.fda.gov/newsevents/publichealthfocus/ucm286218.htm and https://www.fda.gov/aboutfda/transparency/basics/ucm194655.htm

[3] https://www.ncbi.nlm.nih.gov/pubmed/2954809

[4] Niehans P. 20 Jahre Zellulartherapie. Berlin, München, Wien: Urban & Schwarzenberg 1952,  (= Beihefte zur Medizinischen Klinik, 47), https://stem-cells-therapy.com/papers/v5jpnbdbzido.pdf?x19010

[5] https://de.wikipedia.org/wiki/Frischzellentherapie

[6] https://www.swissmedic.ch/aktuell/00673/02700/index.html?lang=de

[7] http://www.sciencedirect.com/science/article/pii/S0002937803009967  

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Disparities between Objective Measures and Self-report in Fibromyalgia at the 2017 EULAR Annual Meeting in Madrid

There has been a session with four speakers named “Closing the gap between objective measures and self-report in fibromyalgia” at the 2017 EULAR Annual Meeting in Madrid.

M. Henriksen talked on [1]: “DIVERGENCES BETWEEN OBJECTIVE AND SELF-REPORTED PHYSICAL FUNCTION IN FIBROMYALGIA”. “In fibromyalgia (FM), intolerance to physical activity, with increased pain and experience of early muscle fatigue, is a predominant feature.” “Much like central sensitization of pain, it has been suggested that impaired sensory-motor interaction is present in FM, which may be a cause for observed discrepancies between perceived and objective signs of muscle fatigue.” Dr. Henriksen outlined a controlled experiment, in which objective measures were compared to perceived fatigue in fibromyalgia (FM) patients and healthy volunteers after a muscle exhaustion test. FM patients showed central nervous system processes of muscular fatigue “without any evidence of peripheral muscle fatigue”. “The study supports a hypothesis about abnormal sensory-motor interaction among FM patients that can explain the discrepancies between perceived and observed physical disability in FM.”

B. Walitt presented [2]: “COGNITIVE FOG: SUBJECTIVE AND OBJECTIVE

UNDERSTANDINGS OF THE SYMPTOM OF DYSCOGNITION”. Conclusions: “… the experience of cognitive fog is not well captured by current testing paradigms. Subjective complaint is a poor predictor of objective cognitive performance. The neuronal mechanisms responsible for the experience of cognitive fog may be separate from those required to perform cognitive tasks.” Fibro fog is another name for this condition. Sometimes in therapy one can see it that patients unable to read two pages of a book are happy again to read, once the fibro fog is gone.

F. Estevez-Lopez talked on [3]: “ASSOCIATIONS OF PAIN-RELATED COGNITIONS WITH THE DISCORDANCE BETWEEN SUBJECTIVE AND OBJECTIVE PHYSICAL FUNCTION IN FIBROMYALGIA: THE AL-ANDALUS PROJECT”. In the Al-Andalus Project 405 female FM patients and 193 age matched controls were studied with “the Pain Catastrophizing Scale, Chronic Pain Self-efficacy Scale, and physical functioning subscales of the Revised Fibromyalgia Impact Questionnaire (FIQR) and Short Form-36 (SF-36) health survey”. Conclusions: “Although both are markedly impaired, subjective physical function is more impaired than objective physical function in fibromyalgia. Catastrophizing is associated with this discordance.” Allow me to match this with own observations. FM patients were always surprised looking at the Borg scale (rating of perceived exertion) before and after physical training.

L. Piggott looked from the patient’s perspective [4]: “THE DRUGS DON’T WORK”. She talked about “her own search for answers and cure to Fibromyalgia in an attempt to salvage her life and independence, prior to accepting that this is a long-term condition which will require self-management and perseverance.” Mrs. Piggott made the observation that “drugs don’t work”. I can understand the frustration of any FM patient, when drugs don’t work. I’ve written quite often on fibromyalgia and that I don’t think drugs would be the solution [5]. Often drugs create new problems. Analgesics have a place in acute pain (nociceptive pain), but aren’t of much use in chronic pain (non-nociceptive / central pain). F. Wolfe has shown how little effective modern antidepressants are [6]: “Physicians and patients should be realistic about the potential benefits of antidepressants in FMS. A small number of patients experience a substantial symptom relief with no or minor adverse effects. However, a remarkable number of patients dropout of therapy because of intolerable adverse effects or experience only a small relief of symptoms, which does not outweigh the adverse effects.”

There are disparities between objective measures and self-report in fibromyalgia, but in recognizing these, we can gain a new perspective, which enables us as health care professionals to help our patients instead of adding harm.

Links and References:

[1] DOI: 10.1136/annrheumdis-2017-eular.7148

[2] DOI: 10.1136/annrheumdis-2017-eular.7215

[3] DOI: 10.1136/annrheumdis-2017-eular.7185

[4] DOI: 10.1136/annrheumdis-2017-eular.7191

[5] http://rheumatologe.blogspot.de/search?q=Fibromyalgia

[6] https://www.ncbi.nlm.nih.gov/pubmed/22452526

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