How RA Bubbled Up in the Risk-Factor Cauldron of 19th Century Paris


With some historical analysis, a British rheumatologist unearths a persuasive explanation for the emergence of rheumatoid arthritis when and where it did, in fact, arise.

It has been suggested that seropositive rheumatoid arthritis (RA) is a relatively contemporary disease in the Western World. Examinations of skeletal remains in Europe have revealed no evidence of erosive RA prior to 1800.1

The first acknowledged description of RA is a dissertation presented in Paris in 1800 by Augustin Jacob Landré-Beauvais.2 His thesis was relatively unrecognized until 1853, when Jean-Martin Charcot published his own doctoral thesis on 'goutte asthenique primitive.’ Charcot observed that this new condition accounted for 5% of all admissions to long-term residential care at the Salpêtrière hospital Paris.

Illustrations by Charcot’s co-worker Jean Cruveilhier leave no doubt that what was being described at this time was seropositive RA.3

Why did this disease emerge in Paris at the turn of the 19th century and become so highly prevalent with such speed? Reviewing what we now know about the environmental risk factors that trigger seropositive RA – cigarette smoking, bronchietasis, and periodontitis – the unusual living conditions and habits of 19th century Parisians may provide an explanation.

  • Cigarette smoking

Smoking is associated principally with seropositive rather than [[{"type":"media","view_mode":"media_crop","fid":"25753","attributes":{"alt":"","class":"media-image media-image-right","height":"176","id":"media_crop_2740135630814","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"2411","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"float: right;","title":" ","typeof":"foaf:Image","width":"179"}}]]seronegative RA.4 It  is the key environmental risk factor for RA and is estimated to be responsible for 35% of ACPA-positive case. In individuals carrying two copies of the HLA-DRB1 SE, 55% of ACPA-positive RA is attributable to smoking.5

Smoking emerged in France, and by the 19th century was fashionable in Paris.

Le Musée Du Fumeur Paris chronicles the history of smoking, demonstrating that 19th century Paris was the forerunner of the prevalence of smoking in Europe.6

  • Bronchiectasis

Bronchiectasis is a significant risk factor for seropositive RA, with a 10-fold increased prevalence in RA patients as opposed to osteoarthritic controls. Bronchiectasis precedes the development of RA in the majority of patients.7 Significantly elevated levels of anti-citrullinated α-enolase peptide-1 antibody levels (9% of cases) have been observed in bronchiectasis patients.8 With the advent of HRCT of the lung, studies reported a prevalence of bronchiectasis in 25% of seropositive RA cases in never-smokers.9

Before 1800, only 3% of the world's population lived in cities. A large body of research has identified links between urbanization and an increased risk of exposure to infectious diseases.10 Most cases of bronchiectasis are caused by infections such as tuberculosis bacterial pneumonia, measles, and Bordetella pertussis.11

It is no surprise, therefore, that bronchiectasis was first described in 1819, by Laennec, in Paris.12 In 1800, Paris (Ville de Paris) was by far the most densely populated city in Europe, having 41,086 residents per square mile. London was a distant second (8137 inhabitants per square mile). Until 1795, metropolitan France was the most populous European country and the third most populous country in the world, behind only China and India.13

  • Infection with Porphyromonas gingivalis and chronic periodontitis

The Gram-negative anaerobic bacterium Porphyromonas gingivalis is generally accepted as an etiological agent for chronic periodontitis.14 Studies indicate that P. gingivalis is commonly transmitted by contact with an infected family member or partner: The relative risk of a child being colonised if two parents are colonised, compared to neither parent, is 5.8 (48% vs 8%).15 In 75% of couples with one partner known to have chronic periodontitis, the DNA patterns of isolates from husband and wife were indistinguishable.16

Interestingly, Louis Pasteur hypothesized a bacterial cause for periodontitis in 19th century Paris, although it had been described in 1728 by the “father of modern dentistry,” Pierre Fauchard (1678-1761).17,18  Periodontitis existed in Paris before1800;  however, the most overcrowded living conditions in Europe are likely to have greatly increased the risk of infection with P. gingivalis and this organism  becoming increasingly associated  with periodontal disease in 19th century Paris.

ACPA titres in RA patients have been demonstrated to correlate with the presence of periodontitis.  ACPA-positive RA patients were more likely to have moderate to severe periodontitis (56%) than patients who were anti-CCP negative (22%) (p = 0.01). This finding was independent of the smoking history.19

However, it is now accepted that it is not periodontitis per se that is a risk for seropositive RA, but P. gingivalis infection as a mechanistic link between periodontitis and seroppositive RA via expression of the P. gingivalis peptidylarginine deiminase (PPAD).20 Smokers with periodontitis demonstrate six-fold lower anti-P. gingivalis antibodies than non-smoking periodontitis patients. This and other data suggest that periodontitis is associated with seropositive RA in non-smokers.21 Quirke et al  demonstrated antibodies to PPAD in 25% of RA sera compared with 5% of the controls.22


French rural depopulation resulted in Paris having the most overcrowded living conditions in Europe. Infection with P. gingivalis and organisms known to trigger bronchiectasis are likely to have greatly increased, resulting in the emergence of seropositive RA in Parisian non-smokers in the early 19th century.

The emergence of smoking at about the same time will have also contributed significantly.



1) Research Notes: Tennessee Origins Of Rheumatoid Arthritis. Bruce M. Rothschild Number 5 - April 1991.

2) Landre-Beauvais AJ. The first description of rheumatoid arthritis. Unabridged text of the doctoral dissertation presented in 1800.  Joint Bone Spine (2001) 68:130-143.

3) Maladies des vieillards. Goutte et rhumatisme. In: Oeuvres completes de JM Charcot, Tome VII. Paris: Lecrosnier et Babe, 1890. Translated into English by W.S. Tuke. Clinical lectures on senile and chronic diseases by J.M. Charcot. London: The New Sydenham Society, 1881.

4) Heliövaara M, Aho K, Aromaa A, et al  Smoking and risk of rheumatoid arthritis. J Rheumatol. (1993) 20:1830-1835.

5) Källberg H, Ding B, Padyukov L et al.Smoking is a major preventable risk factor for rheumatoid arthritis: estimations of risks after various exposures to cigarette smoke.  Ann Rheum Dis. (2011) 70:508-511.


7)  Walker WC. Pulmonary infections and rheumatoid arthritis.Q J Med (1967) 36:239–251.

8) Quirke AM, Perry E, Kelly C et alPatients with bronchiectasis, with or without rheumatoid arthritis, have an elevated anti-citrullinated peptide antibodies (ACPA) response.Ann Rheum Dis. (2014) 73 Suppl 1:A71-2. doi: 10.1136/annrheumdis-2013-205124.163.

9) Hassan WU, Keaney NP, Holland CD, Kelly CA.   High resolution computed tomography of the lung in lifelong non-smoking patients with rheumatoid arthritis. Ann Rheum Dis. (1995) 54:308-310.

10) Alirol E, Getaz L, Stoll B, Chappuis F, Loutan L.  Urbanisation and infectious diseases in a globalised world. Lancet Infect Dis. (2011) 11:131-141.

11)  McShane PJ, Naureckas ET, Gregory T, Strek ME.  Non–Cystic Fibrosis Bronchiectasis. American Journal of Respiratory and Critical Care Medicine (2013) 188:647-656.

12)  Roguin A. Rene Theophile Hyacinthe Laënnec (1781-1826): The Man Behind the Stethoscope.  Clinical Medicine & Research. (2006) 4:230-235.


14)  Bodet C, Chandad F, Grenier D.  Pathogenic potential of Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia, the red bacterial complex associated with periodontitis   Pathologie Biologie. (2007) 55:154–162. (Article in French.)

15)  Tuite-McDonnell M, Griffen AL, Moeschberger ML, et al.Concordance of Porphyromonas gingivalis colonization in families.J Clin Microbiol. (1997) 35:455-461.

16)  van Steenbergen TJ, Petit MD, Scholte MH et al. Transmission of Porphyromonas gingivalis between spouses. J. Clin Periodontol. (1993) 20:340-345.

17)  Feinstein S (2008). Louis Pasteur: The Father of Microbiology. Enslow Publishers, Inc. pp. 1–128. ISBN 978-1-59845-078-1

18)  Pierre Fauchard (1678-1761).  Le Chirurgien dentiste, ou Traité des dents. (1728)

19)  Dissick A, Redman RS, Jones M et al.  Association of periodontitis with rheumatoid arthritis: a pilot study.  J Periodontol. (2010) 81:223-230.

20) Maresz KJ, Hellvard A, Sroka A, et al.Porphyromonas gingivalis Facilitates the Development and Progression of Destructive Arthritis through Its Unique Bacterial Peptidylarginine Deiminase (PAD).PLoS Pathog. (2013) Sept. 9(9). doi:10.1371/journal.ppat.1003627

21)  Lappin DF, Apatzidou D, Quirke AM et al.  Influence of periodontal disease, Porphyromonas gingivalis and cigarette smoking on systemic anti-citrullinated peptide antibody titres.Clin Periodontol. (2013) 40:907-915.

22)  Quirke AM, Lugli EB, Wegner N et al. Heightened immune response to autocitrullinated Porphyromonas gingivalis peptidylarginine deiminase: a potential mechanism for breaching immunologic tolerance in rheumatoid arthritis.Ann Rheum Dis (2014)  73:263-269.


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