Prevalence of Inflammatory Rheumatic Diseases in a Rheumatologic outpatient clinic : analysis of 12626 cases

Inflammatory rheumatic diseases are a heterogeneous class of often chronic autoimmune disorders. They are among the most common chronic diseases. They cause major health problems in the general population. This study assessed the distribution of inflammatory systemic rheumatic diseases in a rheumatologic outpatient clinic. The medical records of patients diagnosed with any type of inflammatory rheumatic disease between January 1, 2006 and December 31, 2016 in a non-hospital-based rheumatologic outpatient practice in Mashhad, Iran were retrospectively studied. Diagnoses were made using the agreed-upon classification criteria. Data regarding each patient‘s diagnosis, age at onset of disease, and gender was extracted from their files. The total number of patients was 12,626. The most common diseases were rheumatoid arthritis (47.30%), spondyloarthropathies (17.23%), systemic lupus erythematosus (8.10%), gout (7.84%), and vasculitis (6.84%). Patients were aged from 1 to 93 years, with a mean age of 41.17±39.70 years. Most patients were in the third, fourth, and fifth decade of life. Sixty-four percent of all patients were female. The overall sex ratio (women to men) was 1.8:1. The proportion of women was 95% in Takayasu's arteritis, 92% in systemic lupus erythematosus, 87% in Sjögren‘s syndrome, 78% in rheumatoid arthritis, and 24% in ankylosing spondylitis. The age at onset of inflammatory rheumatic diseases in Mashhad, Iran is lower than that in some other regions. The frequency of Behcet's disease, systemic lupus erythematosus, and systemic sclerosis was greater in this study than in most other studies, but gout, polymyalgia rheumatica, and psoriatic arthritis were less frequent in the current study.


Introduction __________________________
Rheumatic disorders are among the most prevalent chronic diseases of the musculoskeletal system and connective tissue, and they can affect a wide range of age groups. Encompassing a large number of arthritis and autoimmune diseases, they can affect the bones, joints, and other components of the musculoskeletal system, causing morbidity or disability with resultant healthcare utilization [1]. Rheumatic disorders are mainly responsible for an inability to work and early retirement, a fact which highlights their enormous social and economic impact [2]. The economic burden of rheumatic diseases is often more substantial than other chronic conditions, including cardiovascular diseases and cancer [3]. Unfortunately, despite the growing disease burden associated with rheumatic diseases, inadequate attention has been paid to them and to arthritis in the scientific literature [4].
There are more than 150 classified rheumatic disease conditions with specific pathogenesis, clinical picture, treatment, and prognosis. For successful treatment, identifying each condition and its variations is essential [1]. Rheumatic diseases can be divided into two major groups: inflammatory rheumatic diseases (IRDs) and non-inflammatory rheumatic diseases. As the most common rheumatic diseases, non-inflammatory rheumatic diseases are highly age-dependent and usually have a better prognosis [5]. About 5% of the population, however, suffer from a chronic inflammatory rheumatic disease [6]. Statistics show that, in America, a higher number of disabilities are caused by inflammatory rheumatic diseases with arthritis than by heart disease, cancer, or diabetes [7].
As a heterogeneous group of often chronic immunemediated disorders, inflammatory rheumatic diseases cause inflammatory reactions in various body tissues. The primary target is the musculoskeletal system; these disorders cause joint pain (arthralgia) and restricted mobility, leading to irreversible damage and disability. Some internal organs, including the heart and kidneys, can also be affected [8,9]. There are over 30 autoimmune rheumatic diseases; some of the most common ones are rheumatoid arthritis, lupus, scleroderma, juvenile idiopathic arthritis, Sjögren's syndrome, spondyloarthropathies, polymyalgia rheumatica, and systemic vasculitis [10].
The epidemiological and demographic features of vasculitis [11], giant cell arteritis [12], Takayasu's arteritis [13], and sarcoidosis [14] in northeastern Iran have previously been reported. This study aimed to analyze the inflammatory rheumatic disease profile of patients visiting an outpatient rheumatology practice in Mashhad, Iran and compare the prevalence and distribution of different inflammatory rheumatic diseases.

Materials and Methods _________________
The medical records of patients diagnosed with any type of inflammatory rheumatic disease between January 1, 2006 and December 31, 2016 in a non-hospital-based rheumatologic outpatient practice in Mashhad, Iran were retrospectively studied.
The following conditions were defined as noninflammatory conditions and were excluded from this study: osteoarthritis, osteoporosis, noninflammatory back pain, soft tissue rheumatism, complex regional pain syndrome, fibromyalgia, malignancy and hypertrophic osteoarthropathy. Patients with infectious arthritis were also excluded.
The agreed classification criteria were used to make the diagnosis (Table 1). Data regarding diagnosis, age at disease onset, and gender was extracted from the patients' files.

Statistical analysis
SPSS software (Statistical Package for the Social Sciences) 20 was used for data entry and analysis. Continuous data was shown as mean and standard deviation (mean±SD), and categorical variables were shown as percentages.
Patients' ages ranged from 1 to 93 years, with a mean of 41.17± 39.70 years. Most patients were in the third, fourth, or fifth decade of life. Figure 1 shows the distribution of age at disease onset in the studied patients.
Sixty four percent of all patients were female. The overall sex ratio (women to men) was 1.8:1. The proportion of women was 95% in Takayasu's arteritis, 92% in SLE, 87% in Sjögren's syndrome, 78% in RA, and 24% in AS. The most common age of onset for AS, reactive arthritis (ReA), Takayasu's arteritis, Still's disease, Behcet's disease, and SLE was in the twenties, whereas the most common age of onset for Granulomatosis with polyangiitis (GPA), sarcoidosis, psoriatic arthritis (PsA), APS, inflammatory bowel disease (IBD), palindromic rheumatism, and systemic sclerosis was in the thirties. The most common age of onset for RA was in the forties. The total number of patients with JIA was 359 (2.8%).

Discussion ____________________________
The exact etiology and pathogenesis of inflammatory rheumatic diseases remain unclear today. However, among a host of factors, a variable combination of individual genetic predisposition, environmental factors, and dysregulated immune responses have been singled out as the underlying causes of these autoimmune diseases [15]. The role of genetic predisposition, in particular the influence of distinct HLA haplotypes, has been highlighted in most of these diseases. Moreover, environmental factors including nutrition, infection, and exposure to sunlight have been pinpointed as being responsible for the development of the disease [16].
A number of reports on the epidemiology and prevalence of rheumatic diseases seen in rheumatology practices have been published [17][18][19][20]. The inflammatory rheumatic patients in this study were compared with other populations in Germany [17], the Netherlands [18], Belgium [19], and Nigeria [20] ( Table  3).     In Nigeria [20], a study was performed to examine the prevalence and distribution of rheumatic diseases in a tertiary hospital outpatient practice. The study consisted of a small number of patients restricted to a tertiary institution in southwestern Nigeria, which, however, cannot represent the true prevalence of each rheumatologic disorder in the general community of the studied region.

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Overall, inflammatory rheumatic diseases are more common in females than in males [21,22]. In the current study, the proportion of women was lower compared to the study carried out in Germany (64% versus 71%).
Inflammatory rheumatic diseases can occur at any age [23] (age range in the current study was 1-93 years). In this study, the mean age at disease onset was 41 years, which was lower than in the study carried out in Germany (51 years). The reason for this difference may lie in the fact that the population of Iran is younger than the population of Germany.
About half of the patients with inflammatory rheumatic diseases have RA. The frequency of RA in this study (47.5%) was slightly lower than that in the German study (50.6), but it was higher than its level in studies performed in Belgium (45.8%) and the Netherlands (45.2%).
The percentage of SLE (the second most common disease) was higher in the present study (8.1%) than in the three other above-mentioned studies.
This difference can also be explained by the lower age of the Iranian population, since SLE is a disease of young adults.
The frequency of spondyloarthropathies was slightly lower in this study than in studies in Germany and the Netherlands. The most common subtype of spondyloarthropathies in this study was undifferentiated spondyloarthropathy, whereas the prevalence of ankylosing spondylitis in this study corresponded to its level reported in a study performed in Germany, i.e. less frequent than in the other two studies. The prevalence of arthritis in patients with psoriasis is 9.1% in Iran [24]. The frequency of PsA in the current study was less than three other studies.
Systemic sclerosis was seen more frequently in this study (2.36%) than in three other studies.
The prevalence of Behcet's disease (BD) in Iran was 68 per 100,000 inhabitants, which is the second highest prevalence after Turkey (80-370 per 100,000) worldwide [25]. The frequency of Behcet's disease among patients in the present study was 4.18%. The three other studies did not report any patients with Behcet's disease due to the rarity of BD in these countries. Behcet's disease is classified as a vasculitis [26]. It is possible that, in the aforementioned studies, BD was considered a vasculitis, and, therefore, its rate was not reported separately.
PMR was much less frequent in Iran (0.4%) in comparison with other studies (Germany, 3.8%; the Netherlands and Belgium, 5.6%). PMR is a disease of the elderly. Thus, its current low prevalence can be associated with the younger population of Iran.
The prevalence of gout in Iranian population is 0.13% [25]. The frequency of gout in the present study matched its rate in the study carried out in Germany; however, it was higher than the other two studies.
Juvenile idiopathic arthritis (JIA) is the most common chronic pediatric rheumatologic disease. Only 359 cases of juvenile idiopathic arthritis were recorded here. The small number of such cases can be explained by the fact that the database is maintained in adult rheumatology units. During the last decade, the number of pediatric rheumatologists has increased in Iran; at present, most pediatric patients with rheumatologic problems are visited by pediatric rheumatologists.
Some patients who fulfill the criteria for a diagnosis of an autoimmune disease have overlapping features of a second autoimmune illness. In 30%-52% of patients with SLE, RA, or Sjögren's syndrome, the second autoimmune disease, rheumatic or nonrheumatic, will occur [27]. Sjogren's syndrome and APS can develop in many other IRDs. If SS or APS develops in patients with other IRDs, the diseases are called secondary Sjogren's syndrome or secondary APS. In this study, the association of these 2 disorders with any other IRDs as overlap syndromes was not taken into account. About 0.6% of patients in the current study had overlap syndromes. The most common overlap syndromes (2 IRDs) were RA-SLE (rhupus) and RA-SSc.
The database used in this study had several limitations: it only included patients visited by rheumatologists; it did not give information on the situation of patients who never reached the specialized sector. There is no information on how the diseases are diagnosed and treated at the level of the general population.

Conflicts of interest
The authors declare no conflicts of interest.