In Useful Gout Myths and Lies I introduced Horizon’s Gout Lies campaign. Where I presented an overview with a view to explaining more. As I discovered details about the campaign.
Now I have lots of information. So I’ll present it in several parts. Including links back to my websites where I’ve presented or discussed these facts before.
Today, I’ll start with Horizon’s Press Release announcing the campaign – “Horizon Therapeutics plc Launches New Data-Driven Campaign to Reset the Dialogue on Gout”
The Science of Gout Lies
The emphasis on this campaign being “Data-Driven” lies in two paragraphs. That include references to 9 studies. Normally, I’d include the references as footnotes. But here I have two reasons not to…
- These references are the heart of the campaign. So deserve more prominence.
- I shall explain the references in separate articles. Grouped by the posters I introduced in the previous article.
The Science of Gout Lies Introduction
Approximately 9.2 million people in the United States live with gout, a chronic, progressive, inflammatory form of arthritis1 that is caused by excess uric acid in the body and can require aggressive disease management. Gout may become uncontrolled in a portion of the population; uncontrolled gout is characterized by abnormally high levels of uric acid and persistent symptoms despite the use of conventional therapies2. Due to misperceptions of gout’s systemic impact and severity, it has largely been under-recognized and undertreated3. However, over the last decade, breakthrough research into the pathophysiology of gout has redefined how the disease should be addressed to support patient care.
- ① 9.2 Million American Gout Sufferers
- Chen‐Xu, Michael, Chio Yokose, Sharan K. Rai, Michael H. Pillinger, and Hyon K. Choi. “Contemporary prevalence of gout and hyperuricemia in the United States and decadal trends: the national health and nutrition examination survey, 2007–2016.” Arthritis & Rheumatology 71, no. 6 (2019): 991-999.
The prevalence of gout was 3.9% (9.2 million) among US adults in 2015-2016 (5.2% [5.9 million] among men and 2.7% [3.3 million] among women)
- ② Uncontrolled Gout
- Treatments for Chronic Gout. The Arthritis Foundation. Accessed April 26, 2019. Archived: https://web.archive.org/web/20180112050748/http://www.arthritis.org/about-arthritis/types/gout/articles/chronic-gout.php
Allopurinol: For patients who overproduce uric acid; have kidney failure, kidney stones or tophi; use aspirin; or who don’t respond to probenecid.
Febuxostat: For patients with mild to moderate kidney or liver disease. Has an effectiveness and side effects similar to allopurinol.
Probenecid: For patients who cannot tolerate allopurinol. NOT for elderly patients; those with kidney failure or kidney stones; those who take aspirin (it blocks the effect of probenecid); those who overproduce uric acid.
Lesinurad: For patients whose gout is not controlled by an optimally-dosed xanthine oxidase inhibitor alone. Patients with compromised kidney function (CrCl <45 mL/min) should not take it. Pegloticase: For patients for whom standard medications have failed to lower uric acid levels.
- ③ Untreated Gout
- Doherty, Michael, Tim L. Jansen, George Nuki, Eliseo Pascual, Fernando Perez-Ruiz, Leonardo Punzi, Alexander K. So, and Thomas Bardin. “Gout: why is this curable disease so seldom cured?.” Annals of the rheumatic diseases 71, no. 11 (2012): 1765-1770. Why does your gout doctor seldom cure gout?
the authors describe how gout is a widespread disease that is well understood medically. But they note that only a minority of gout patients get effective treatment. So the report continues to investigate possible reasons for poor gout treatment.
The Science of Gout Lies Data
Gout Lies illustrates the ways that the presentation of gout can be deceptive, such as how damage can continue after the end of a flare4,5,6,7,8 or the misconception that tophi – urate deposits that look like lumps under the skin – are a cosmetic issue and not a clinical concern6,8-9. Provocative vintage-style posters help demonstrate how gout is much more complex than its apparent presentation, and damage to the bones, joints and tissue can occur even in the absence of pain and other symptoms.4-8
- ④ Gout Is Not Intermittent
- Perez-Ruiz, Fernando, and Ana Maria Herrero-Beites. “Evaluation and treatment of gout as a chronic disease.” Advances in therapy 29, no. 11 (2012): 935-946.
One of the limitations for successful treatment of gout is to consider it as an intermittent disease rather than a chronic inflammatory disease which, if improperly treated, leads to chronic clinical manifestations. In addition, gout is linked to increased cardiovascular morbidity and mortality.
- ⑤ Tophi Can Grow Without Flares
- Puig, J. G., E. De Miguel, M. C. Castillo, A. López Rocha, M. A. Martínez, and R. J. Torres. “Asymptomatic hyperuricemia: impact of ultrasonography.” Nucleosides, Nucleotides, and Nucleic Acids 27, no. 6-7 (2008): 592-595.
Urate deposits (tophi) in tendons, synovium, and other soft tissues were detected in 12 patients (34%). Increased vascularity (inflammation) was evident in 8 of these patients (23%). Tophi were more frequently found in knees than in ankles and were especially prevalent in the distal patellar tendon. The presence of tophi was unrelated to the known duration of hyperuricemia
- ⑥ Gout Pain Is Complicated
- Schett, Georg, Christine Schauer, Markus Hoffmann, and Martin Herrmann. “Why does the gout attack stop? A roadmap for the immune pathogenesis of gout.” RMD open 1, no. Suppl 1 (2015): e000046.
two essential molecular phases can be distinguished in gout: the first one is the precipitation of MSU crystals and their ingestion by mononuclear phagocytes leading to inflammasome activation. This molecular process, which depends on the production of IL-1 and is characterised by the massive recruitment of neutrophils, explains the clinical symptoms of an acute gout attack. The second phase is the formation of tophi resembling aggNETs, which depends on high densities of neutrophils, and their death by NETosis, which allows densely packing MSU crystals, neutralising and degrading the involved proinflammatory cytokines and resolving inflammation
- ⑦ Gout Is Very Complicated
- Rada, Balázs. “Neutrophil extracellular traps and microcrystals.” Journal of immunology research 2017 (2017).
A recent work by Pieterse et al. emphasized the critical role of phagocytes engulfing small urate microaggregates (SMA) in hyperuricemic blood. These SMAs form first before they grow into long, needle-shaped MSU crystals that are known to trigger NET release. Phagocytes take up SMAs and prevent the formation of MSU crystals and NETs in the circulation.
- ⑧ Tophi and Bone Erosion
- McQueen, Fiona M., Anthony Doyle, Quentin Reeves, Angela Gao, Amy Tsai, Greg D. Gamble, Barbara Curteis, Megan Williams, and Nicola Dalbeth. “Bone erosions in patients with chronic gouty arthropathy are associated with tophi but not bone oedema or synovitis: new insights from a 3 T MRI study.” Rheumatology 53, no. 1 (2014): 95-103.
Erosions were strongly associated with tophi but not bone oedema or synovitis. MRI bone oedema was relatively uncommon and low grade. These findings highlight the unique nature of the osteopathology of gout.
- ⑨ How Tophi Erode Bones
- Dalbeth, Nicola, Barnaby Clark, Kate Gregory, Greg Gamble, Timothy Sheehan, Anthony Doyle, and Fiona M. McQueen. “Mechanisms of bone erosion in gout: a quantitative analysis using plain radiography and computed tomography.” Annals of the rheumatic diseases 68, no. 8 (2009): 1290-1295.
we have demonstrated a close relationship between bone erosion and the presence and size of intraosseous tophus. Direct visualisation of these tophi within sites of erosion strongly implicates these lesions as causative in the pathogenesis of bone erosion in gout.
Your Dialogue on Gout Lies
Apologies for the highly technical content here. Once I summarize the reports. I’ll return here to reword this gout science in layman’s terms.