A nationwide study of the epidemiology of relapsing polychondritis

Abstract

Objective: Relapsing polychondritis (RP) is a rare autoimmune inflammatory disease that attacks mainly cartilaginous structures or causes serious damage in proteoglycan-rich structures (the eyes, heart, blood vessels, inner ear). This study shows results regarding the epidemiology, progression, and associations of this highly variable disease by collecting all cases from a 124-million-person-year Central European nationwide cohort.

Methods: We used the Hungarian Health Care Database to identify all persons with possible RP infection. We followed patients who had International Classification of Diseases 10th edition code M94.1 at least once in their inpatient or outpatient records between January 1, 2002 and December 31, 2013 in Hungary. We classified these patients into disease severity groups by their drug consumption patterns between January 1, 2010 and December 31, 2013. We analyzed the regional distribution of RP incidences as well. Overall maps of comorbidity are presented with network layouts.

Results: We identified 256 patients with RP among cumulatively 11.5 million registered inhabitants. We classified these patients into four severity classes as "extremely mild" (n=144), "mild" (n=22), "moderate" (n=41), and "severe" (n=4). Two additional groups were defined for patients without available drug data as "suspected only" (n=23) and "confirmed but unknown treatment" (n=22). The age and sex distributions of patients were similar to worldwide statistics. Indeed, the overall survival was good (95% confidence interval for 5 years was 83.6%-92.9% and for 10 years was 75.0%-88.3% which corresponds to the overall survival of the general population in Hungary), and the associations with other autoimmune disorders were high (56%) in Hungary. Almost any disease can occur with RP; however, the symptoms of chromosomal abnormalities are only incidental. Spondylosis can be a sign of the activation of RP, while Sjögren syndrome is the most frequent autoimmune association. Regional distribution of incidences suggests arsenic drinking water and sunlight exposure as possible triggering factors.

Conclusion: The good survival rate of RP in Hungary is probably associated with the early diagnosis of the disease.

Keywords: autoimmune comorbidity; cohort of Hungary; environmental factors; incidence rate; network representation; severity prevalence.

Figure 1

Network layout of most important lifetime comorbidities observed in Hungarian RP population. Notes: Each point (node of the graph) represents a disease group indicated by labels. Points are connected with edges if diseases were diagnosed in the same patient between 2002 and 2013, regardless of time coincidence. The thickness of the edges indicates the number of affected patients, and transparency is higher for higher P-values. Only the most intensive, significant connections are represented. Note that RP is connected to each disease (this condition is part of the definition of the network), but these edges are very transparent. Size of the nodes is proportional to the number of patients affected in the disease group. Shape of the node indicates the type of the disease group: circle for three-character ICD10 code, triangle for ICD10 section or merged consecutive sections, and squares for ICD10 chapters. Chapter groups labeled by “Others from” count cases with disease groups not represented separately, for example, “Others from M00–M99” does not include M94.1. This visual representation of comorbidities provides a map-like overview of possible long-term consequences or preliminary indicators of RP. Abbreviations: RP, relapsing polychondritis; ICD10, International Classification of Diseases 10th edition.

Figure 2

Same-day-comorbidity network of the Hungarian RP population. Notes: The network and the layout definition is the same as for the lifetime comorbidity network, except that edges connect diseases if they occurred in the same person on the same day. Abbreviation: RP, relapsing polychondritis.

Figure 3

Number of newly diagnosed patients for each year during the examined period. Abbreviation: RP, relapsing polychondritis.

Figure 4

Age structure diagram of patients diagnosed with ICD10 M94.1. Notes: Both sexes are affected equally. RP appears most likely in the population aged 40–60 years. The inset shows the standardized age structure. Abbreviations: RP, relapsing polychondritis; ICD10, International Classification of Diseases 10th edition.

Figure 5

Distribution of number of patients according to drug consumption. Abbreviation: NSAID, nonsteroid anti-inflammatory drug.

Figure 6

Box plot for number of days of hospitalization versus disease progression levels. Notes: The progression level was identified from drug consumption patterns. Number of days increases as the disease progresses to more severe levels.

Figure 7

Regional distribution of incidence ratios. Note: The high difference between the two neighboring southern regions (Southern Great Plain and Southern Transdanubia) hints for possible environmental triggering effects. Abbreviation: RP, relapsing polychondritis.

Figure 8

Residence of patients with RP. Notes: (A) the prevalence region is located by the place of residence of the patient. (B) shows the sunlight exposure and (C) the arsenic content of drinking water. B is reproduced with permission from the Hungarian Meteorological Service (HMS). Hungary sunlight, sunshine duration and cloud cover conditions. Available from: http://met.hu/eghajlat/magyarorszag_eghajlata/altalanos_eghajlati_jellemzes/sugarzas/. C is reproduced with permission from National Public Health Service. [Drinking Water Quality, 2012] Ivóvíz minőség, 2012. Available from: https://www.antsz.hu/data/cms52115/Ivovizminoseg_2012_honlapra_20140404.pdf. Abbreviation: RP, relapsing polychondritis.