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

Document Type: Original Article

Authors

1 Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Faculty of Medicine, Islamic Azad University, Mashhad Branch, Iran

Abstract

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 rheumatologicoutpatient 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.

Keywords

Main Subjects


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-dependentand 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 immune-mediated 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 disorders were defined as inflammatory rheumatic diseases: rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), spondyloarthropathies, Sjogren’s syndrome (SS), dermatomyositis/ polymyositis, relapsing polychondritis, sarcoidosis, vasculitides, adult onset Still's disease, juvenile idiopathic arthritis (JIA), antiphospholipid antibody syndrome (APS), crystal-induced arthritis, familial Mediterranean fever (FMF), acute rheumatic fever, polymyalgia rheumatica (PMR), SAPHO (Synovitis–acne–pustulosis–hyperostosis–osteitis), RS3PE (remitting seronegative symmetrical synovitis with pitting edema), mixed connective tissue disease (MCTD), and palindromic rheumatism.

The following conditions were defined as noninflammatory conditions and were excluded from this study: osteoarthritis, osteoporosis, non-inflammatory 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.

Results_______________________________

The total number of patients with inflammatory rheumatic disease was 12,626. Table 2 presents the distribution of patients separately grouped based on their diagnoses. The most common diseases were RA (47.30%), spondyloarthropathies (including ankylosing spondylitis, psoriatic arthritis, reactive arthritis and enteropathic arthritis) (17.23%), SLE (8.10%), gout (7.84%), and vasculitis (6.83%).

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 [17-20]. 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).

Table 1. The used classification criteria for inflammatory rheumatic diseases

Disease

Classification criteria

Acute rheumatic fever

2004 World Health Organization Criteria for the Diagnosis of Rheumatic Fever and Rheumatic Heart Disease

Adult onset Still's disease

Yamaguchi criteria

Antiphospholipid antibody syndrome

Revised Sapporo Classification Criteria for Anti-phospholipid Syndrome

Ankylosing Spondylitis

Modified New York, 1984

Behcet's disease

Revised International Criteria for Behçet’s Disease

Cryoglobulinemic vasculitis

Preliminary classification criteria for the cryoglobulinaemic vasculitis

CPPD

McCarty and colleagues

Dermatomyostis/ Polymyositis

Bohan and Peter Criteria for Polymyositis and Dermatomyositis

Eosinophilic granulomatosis with polyangiitis

ACR 1990 criteria for Churg-Strauss syndrome

Familial Mediterranean Fever

Tel Hashomer Medical Center

Giant cell arteritis

American College of Rheumatology Classification Criteria for Giant Cell Arteritis

Gout

ACR/EULAR

Granulomatosis with polyangiitis

ACR criteria

Hypocomplementemic urticarial vasculitis

1982 Schwartz et al.

Inclusion body Myositis

The proposed European Neuromuscular Centre (ENMC) 2011

IgA Vasculitis

American College of Rheumatology 1990 Criteria for the Classification of Henoch-Schönlein Purpura

Juvenile Idiopathic Arthritis

IL AR Classification Criteria for Juvenile Idiopathic Arthritis

Microscopic polyangiitis

ACR 1990

Mixed Connective Tissue Disease

Alarcón-Segovia Criteria

Palindromic rheumatism

Pasero and Barbieri

Polyarteritis nodosa

American College of Rheumatology Criteria for Classification of Polyarteritis Nodosa

Polymyalgia Rheumatica

ACR/EULAR 2012 provisional classification criteria for Polymyalgia rheumatica

Polychondritis

Modified (Damiani) criteria

Psoriatic Arthritis

CASPAR Classification Criteria for Psoriatic Arthritis

Reactive arthritis

French Society of Rheumatology (FSR)

Rheumatoid arthritis

ACR/EULAR 2010

RS3PE

Olive criteria

SAPHO

Benhamou criteria

Sarcoidosis

Visser’s Criteria for Sarcoidosis in Patients with Arthritis and Bihilar Lymphadenopathy

Sjogren's syndrome

Revised International Classification Criteria for Sjogren’s Syndrome

Systemic lupus erythematosus

SLICC criteria for the classification of systemic lupus erythematosus

Systemic sclerosis

American College of Rheumatology/European League against Rheumatism Classification Criteria for the Classification of Systemic Sclerosis

Takayasu' arteritis

American College of Rheumatology Classification Criteria for Takayasu’s Arteritis

Undifferentiated seronegative spondyloarthropathy

ESSG criteria

Vasculitis

Revised International, Chapel Hill Consensus Conference Nomenclature of Vasculitides

CPPD: Calcium-Pyrophosphate-Deposition; ACR: American College of Rheumatology; EULAR: European League Against Rheumatism; ILAR: International League Against Rheumatism; CASPAR: Classification of Psoriatic Arthritis; RS3PE: Remitting seronegative symmetrical synovitis with pitting edema; SAPHO: Synovitis–Acne–Pustulosis–Hyperostosis–Osteitis; SLICC: Systemic Lupus International Collaborating Clinics; ESSG: European Spondyloarthropathy Study Group 

Fig. 1. Age distribution of the patients

 

Table 2. Distribution of patients and their diagnoses, female % and ages

Disaese

Frequency no. (%)

Female (%)

Age (years)

Minimum

Maximum

Mean

RA

5973 (47.30)

78.5

16

90

46.69

SLE

1023 (8.10)

92.0

3

74

31.74

SPA

Total

 

2176 (17.23)

42.0

3

76

33.44

AS

 

665 (5.26)

24.2

9

75

34.12

ReA

 

113 (0.89)

32.7

8

71

28.45

PsA

 

373 (2.95)

59.0

3

76

38.47

Enterpathic

 

104 (0.82)

57.7

17

74

37.06

USPA

 

921 (7.29)

1.37

5

72

31.12

Inflammatory  myopathies

Total

 

167 (1.32)

60.2

3

74

36.29

DM

 

67 (0.53)

48.1

3

68

38.43

PM

 

99 (o.78)

78.1

8

70

34.75

IBM

 

1 (0.00007)

100

74

74

74.00

SSc

299 (2.36)

79.9

4

85

40.25

SS

111 (0.87)

87.4

16

75

46.44

PMR

52 (0.41)

51.9

40

84

66.42

Vasculitidies

Total

 

864 (6.84)

51.5

5

86

34.54

LVV

Total

 

95 (0.75)

72.9

17

83

45.49

TAK

 

50 (0.38)

95.7

17

48

28.33

GCA

 

45 (0.35)

46.2

44

83

64.19

MVV

Total

 

23 (0.18)

53.4

11

82

41.00

PAN

 

23 (0.18)

50.0

11

82

41.00

KD

 

0 (0)

-

-

-

-

SVV

Total

 

138 (1.09)

48.5

5

66

34.23

AAV

Total

83 (0.65)

51.5

11

66

35.90

GPA

49 (0.38)

50.0

11

61

33.00

EGPA

23 (0.18)

33.3

23

66

51.07

MPA

11 (0.08)

75.1

19

35

27.00

ICV

Total

55 (0.43)

48.3

5

54

21.40

AGBM

0 (0)

-

-

-

-

CV

3 (0.0002)

75.1

35

43

39.00

IGAV

52 (0.41)

37.5

5

54

20.50

HUV

0 (0)

-

-

-

-

VVV

Total

 

529 (4.18)

47.3

11

78

33.40

BD

 

529 (4.18)

47.1

11

78

33.40

CS

 

0 (0)

-

-

-

-

SOV

Total

 

79 (0.62)

45.4

5

86

34.5

CLA

 

71 (0.56)

45.0

11

86

38.00

CA

 

0 (0)

-

-

-

-

PCNSV

 

0 (0)

-

-

-

-

IA

 

0 (0)

-

-

-

-

OTHERs

 

8 (0.0006)

50.0

18

30

24.00

Sarcoidosis

 

 

307 (2.4)

65.8

15

81

40.57

Crystal induced arthritis

Total

 

994 (7.78)

14.9

8

93

52.59

Gout

 

991 (7.84)

14.9

8

93

52.52

CPPD

 

3 (0.0002)

33.3

70

86

78.00

Relapsing polychodritis

3 (0.0002)

33.3

22

55

43.00

Juvenile idiopathic arthritis

359 (2.84)

49.3

1

16

10.60

Familial Mediterranean fever

8 (0.0006)

50.0

7

37

18.25

Antiphospholipid antibody syndrome

22 (0.17)

72.7

16

80

33.77

Acute rheumatic fever

76 (0.6)

46.1

4

40

16.88

Still's disease

95 (0.8)

58.9

17

80

30.42

Mixed connective tissue disease

2(0.0001)

100

28

52

40.00

Palindromic rheumatism

17 (0.13)

76.5

25

71

41.65

RS3PE

1 (0.00007)

100

23

23

23.00

SAPHO

1 (0.00007)

0

16

16

16.00

Overlaps

Total

76 (0.28)

86.8

16

70

36.86

RA+SLE

32 (0.25)

96.8

16

60

35.75

RA+SSc

18 (0.14)

94.4

16

59

37.11

RA+DM

3 (0.0002)

100

43

61

54.67

RA+PM

1 (0.00007)

100

30

63

44.00

RA+PBS

1 (0.00007)

100

45

45

45.00

SLE+SSc

3 (0.0002)

100

27

42

34.50

SLE+PM

1 (0.00007)

100

24

24

24.00

SLE+IBD

1 (0.00007)

100

23

23

23.00

SLE+Taka

1 (0.00007)

100

20

20

20.00

PSA+Gout

2 (0.0001)

50.0

52

54

53.00

IBD+DM

1 (0.00007)

100

64

64

64:00

IBD+Takayasu

1 (0.00007)

100

20

20

20.00

DM+PSA

1 (0.00007)

0

29

29

29.00

DM+SSc

4 (0.0003)

50

28

70

49.50

PM+SSc

4 (0.0003)

0

30

65

44.00

Total

12626 (100)

64.20

1

93

41.17

RA: Rheumatoid Arthritis; SLE: Systemic Lupus Erythamtosus; SPA: spondyloarthropathies; AS: Ankylosing Spondylitis; ReA: Reactive Arthritis, PsA: Psoriatic Arthritis; USPA: undifferentiated spondyloarthropathies; DM: dermatomyositis; PM: polymyositis; IBM: Inclusion Body Myositis; SS: Sjogren's Syndrome; SSc: Systemic Sclerosis; PMR: polymyalgia rheumatica; LVV: Large Vessel Vasculitis; TAK: Takayasu arteritis; GCA: Giant Cell Arteritis; MVV: medium vessel vasculitis; PAN: polyarteritis nodosa; KD: Kawasaki Disease; SVV: Small Vessel Vasculitis; AAV: antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis; MPA: microscopic polyangiitis; GPA: granulomatosis with polyangiitis (Wegener’s); EGPA: eosinophilic granulomatosis with polyangiitis (Churg-Strauss); ICV: Immune Complex Vasculitis; SVV: small vessel vasculitis; AGBM: anti-glomerular basement membrane disease; CV: Cryoglobulinemic Vasculitis; IGAV: IgA vasculitis (Henoch-Schonlein); HUV: Hypocomplementemic Urticarial Vasculitis; VVV: Variable Vessel Vasculitis; BD: Behcet’s Disease; CS: Cogan’s Syndrome; SOV: Single-Organ Vasculitis; CLA: Cutaneous Leukocytoclastic Angiitis; CA: Cutaneous Arteritis; PCNSV: Primary Central Nervous System Vasculitis; IA; Isolated Aortitis; CPPD: calcium-pyrophosphate-deposition; RS3PE: Remitting seronegative symmetrical synovitis with pitting edema; SAPHO: Synovitis–Acne–Pustulosis–Hyperostosis–Osteitis

Table 3. Comparative data of patients with inflammatory rheumatic diseases

Variable

Germany 17

N= 25653

Netherland 18

N=33076

Iran

N= 12626

Belgium 19

N=1566

Nigeria 20

N=82

Female %

71.00

-

64.20

-

-

Mean age at onset (years)

51.50

-

41.17

-

-

Rheumatoid arthritis%

50.6

45.2

47.30

45.8

25.6

Systemic lupus erythamtosus %

4.72

1.7

8.10

1.9

12.1

Systemic sclerosis %

1.2

0.6

2.36

-

7.3

Spondyloarthropathies (total) %

22.61

20.8

17.23

-

4.8

Ankylosing spondylitis %

5.79

8.6

5.26

10.2

-

Reactive arthritis %

0.2

2.5

0.89

2.6

2.4

Psoriatic arthritis %

8.26

6.1

2.95

8.2

2.4

Sjogren's syndrome %

1.7

2.2

0.87

1.5

7.3

Vasculitides %

2.1

1.3

6.83

-

-

Behcet’s disease %

-

-

4.18

-

-

Juvenile idiopathic arthritis %

-

1.3

2.82

-

-

Dermatomyositis/ polymyositis %

-

-

1.32

-

1.2

Gout %

8.5

1.3

7.78

3.5

39.0

Polymyalgia rheumatica %

3.8

5,6

0.41

5.6

2.4

Overlap syndromes %

 

 

0.6

 

 

 


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.

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.

Acknowledgments

The authors are grateful to the patients for their cooperation.

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