Gout with the dusty enemy: immune cells, ready for another bout?

Gout is caused by deposits of crystals of a substance called uric acid (also known as urate) in the joints, which leads to inflammation. Periods of time when gout symptoms appear are called flares. Flares can be unpredictable and debilitating, developing over a few hours and causing severe pain in the joints. A popular link between high meat consumption and uric acid has been accepted for centuries. However, not all people with a high level of uric acid go on to develop the disease. Additional factors, such as genetics, comorbidities, lifestyle or occupation impact who develops gout. Inorganic dust is made up of mineral based dust such as asbestos, silica and coal. Some occupations involve high exposure to these substances; such as cleaners, maintenance staff, plumbers, electricians, car fitters, welders, and machinery mechanics. This occupational exposure has already been linked to an increased occurrence of other inflammatory rheumatic diseases such as rheumatoid arthritis. But a new study presented this week at the Annual European Congress of Rheumatology (EULAR 2019), demonstrates that occupational exposure to inorganic dust is a previously unknown risk factor for gout and also confirm known risk factors, such as alcoholism and obesity.

The study included 6,120 cases who were diagnosed with gout between 2006 and 2012 (with no additional gout diagnoses during the previous six years) from the population-based healthcare database of the Western Swedish Health Care Region. Data on occupation was collected from official registries and a job exposure matrix for inorganic dust previously developed was used to assign exposure status. Each case was matched with up to five controls in the census register by Statistics Sweden based on age, sex, and place of residence who were also employed during the predictor period. Data on predefined comorbidities known to be potential risk factors for gout (psoriasis, renal disease, alcohol abuse, obesity and diuretic treatment) were collected and analyzed as possible cofounders to occupational exposure to inorganic dust. Analyses were conducted on the whole population and stratified by gender. Initial analysis demonstrated a significant association between gout and occupational exposure to inorganic dust in all patients. The association was further analyzed using multivariate analysis to adjust for risk factors found to be related to both gout and exposure to inorganic dust within the study. Once this was done, the relationship was attenuated in all patients but remained significant in women.

The study included data on known risk factors as possible cofounders to occupational exposure to inorganic dust and multivariate analysis showed that gout was very strongly associated with obesity and alcoholism. Results show that gout is more than twice as likely in alcoholic patients, and more than three times as likely in obese patients. A direct link between dusts and gout has not been presented by Authors, but hints could come from a scientific paper published in 2016, by scientists which analyzed the role of a genetic variant of Toll-like receptor TLR4. Beside molecules, this surface protein also recognizes crystal structures, not only made with uric acid, but also silica and calcium aggregates. Upon activation, TLR4 triggers a sterile cellular inflammatory response driven by a cellular protein complex called inflammosome. This mimics like a pathogen (e.g. bacteria) is invading the body and alerts immune system to react as a consequence. Immune cells will not realize this for some time, but will continue to amplify the inflammatory response deeming that some organism is still hidden. Facing big crystals, immune cells like macrophages will not be able to swallow them up and destroy, but they will just continue to enhance inflammation and, of course, local pain.

Valgerdur Sigurdardottir, MD, University of Gothenburg, Sahlgrenska Academy, Department of Rheumatology and Inflammation Research, Sweden, commented: “Gout is a disabling disease that is very common across Europe. Identification of risk factors is very important as it allows us to recognize those susceptible to developing the disease and implement early prevention and management strategies. This is the first time occupational exposure to inorganic dust has been shown to be associated with the development of gout. Further study is needed to understand the dangers of exposure to inorganic dust in relation to gout and other inflammatory rheumatic diseases”.

  • Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry

Scientific references

Sigurdardottir V et al. Ann Rheum Dis. 2018; 77(3):399-404.

Dehlin M, Drivelegka P et al. Arthritis Res Ther. 2016; 18:164.

Rasheed H et al. PLoS One. 2016 Jan 25; 11(1):e0147939.

Informazioni su Dott. Gianfrancesco Cormaci 1569 Articoli
- Laurea in Medicina e Chirurgia nel 1998 (MD Degree in 1998) - Specialista in Biochimica Clinica nel 2002 (Clinical Biochemistry specialty in 2002) - Dottorato in Neurobiologia nel 2006 (Neurobiology PhD in 2006) - Ha soggiornato negli Stati Uniti, Baltimora (MD) come ricercatore alle dipendenze del National Institute on Drug Abuse (NIDA/NIH) e poi alla Johns Hopkins University, dal 2004 al 2008. - Dal 2009 si occupa di Medicina personalizzata. - Detentore di un brevetto sulla preparazione di prodotti gluten-free a partire da regolare farina di frumento immunologicamente neutralizzata (owner of a patent concerning the production of bakery gluten-free products, starting from regular wheat flour). - Autore di un libro riguardante la salute e l'alimentazione, con approfondimenti su come questa condizioni tutti i sistemi corporei. - Autore di articoli su informazione medica, salute e benessere sui siti web salutesicilia.com e medicomunicare.it

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