Rheumatoid Arthritis

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WHO-ICD-10 version:2010

Diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism

Certain disorders involving the immune mechanism

OMIM Number

180300

Mode of Inheritance

Unproved inheritance

Gene Map Locus

1p13, 1p36.13, 1q22, 1q31-q32,2q32.2-q32.3,5q31, 5q13,6p21.3, 6q23,16p13,17q13.2,21q22.3

Description

Rheumatoid arthritis (RA) is a chronic inflammatory, autoimmune disease. RA is a systemic disease that can also affect extra-articular tissues throughout the body including the skin, blood vessels, heart, lungs, and muscles. The most prominent feature in RA is synovitis affecting synovial joints which can lead to impair the range of the joints movement (deformity). There are other features which are common in RA like vasculitis, osteoporosis and lymphoma. The cause of rheumatoid arthritis is unknown. There is no known cure for rheumatoid arthritis. The aims of treatment include relief of pain, reduction of inflammation, functional improvement, control of disease activity, and prevention of deformities.

RA affects approximately 0.5%-1% of the global adult population. Women are affected three times more often than men and the age of onset is usually during the fourth and fifth decades of life.

Several genes have been associated with RA. However, the association of HLA-DR4 alleles and AR has been confirmed in most ethnic groups, although the subtype varies. Genetic variations in the NFKBIL1, PTPN8, SLC22A4, RUNX1, MHC2TA, STAT4, PTPN22, TRAF1, and C5 genes have been associated with susceptibility to RA.

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
180300.G.1Arab Rheumatoid arthritisNG_002432.1:g.31279G>C, NM_001114974.2:c.1259+2577G>ASaxena et al. 2017 511 cases compared t...
180300.G.2.1United Arab Emirates Rheumatoid arthritisNM_002116.8:c.231G>CAl-Dhmanie. 2019 38 patients

Other Reports

Jordan

See table above, Qatar > Saxena et al. 2017

Kuwait

Sattar et al. (1988) described a patient with IDDM who 2-years after diagnosis, went on to develop rheumatoid arthritis, followed by ankylosing spondylitis. HLA typing revealed the presence of HLA A2, A9, B8, B27, DR3, and DR4 antigens. Sattar et al. (1988) suspected that the patient was simultaneously genetically susceptible to all of these diseases.

Grub et al. (1988) studied a group of 18 Kuwaiti, 23 Japanese, and 41 Swedish rheumatoid arthritis patients for the prevalence of anti-Ig reactive with Glm (a) Ig. Grub et al. (1988) detected an inverse relationship among the frequency distribution of allotype Glm (a) and anti-allotype demonstrating that the stimulus for the anti-allotype was not the patients' own allotype.

Bahr et al. (1989) performed HLA-DR and tuberculin tests on 46 Arab rheumatoid arthritis patients, 111 tuberculosis patients, and a control group of 79 subjects. Rheumatoid arthritis cohort constituted of 32 females and 14 males aged 18 to 57 years, with disease severity of mild in 23, moderate in 19, and severe in 4 patients, the majority of patients underwent treatment with gold in 15 subjects, penicillamine in 17 patients, or chlorambucil in 9 persons. Tuberculosis cohort comprised 92 males and 19 females aged 17 to 55 years, of those 48 were Arabs and 63 were of Indian or Pakistani origin. The control group involved 42 males and 37 females aged 20 to 60 years, of those 48 were of Arab origin and 31 were Indians or Pakistanis. All groups underwent examination through employing skin test reagents with new tuberculins including tuberculin, leprosin A, scrofulin, and vaccine with a reaction of 2mm and above considered positive. The study results confirmed the hypothesis of mycobacteria, or autoantigens cross reactive with mycobacteria involvement in the etiology of rheumatoid arthritis. Furthermore, the study illustrated that subjects with rheumatoid arthritis having various HLA-DR haplotypes presented diverse regulations and specificity of responsiveness to mycobacterial antigens. [Bahr GM, Sattar MA, Stanford JL, Shaaban MA, Al Shimali B, Siddiqui Z, Gabriel M, Al Saffar M, Shahin A, Chugh TD, et al. HLA-DR and tuberculin tests in rheumatoid arthritis and tuberculosis. Ann Rheum Dis. 1989; 48(1):63-8.]

Sattar et al. (1990) determined the prevalence of HLA A, B, C and DR antigens through typing 85 Arab rheumatoid patients with classical or definite rheumatoid arthritis with sex- and age-matched control group. Subjects were sorted into two categories depending on the rheumatoid factor as: seropositive (n=64, F:M ratio was 2.6:1, mean age 40.5 years) or seronegative (n=21, F:M ratio was 3.2:1, mean age 38.2 years). Throughout comparison among case and control groups, a significant increase was found in the prevalence of HLA-A10, B8, B21, and DR3, while a decrease was observed in the patients group in HLA-DR5. No correlation was observed among HLA-DR4 and rheumatoid arthritis within Arab patients residing in Kuwait. In the same year, Sattar (1990) described three young adult patients with seronegative polysynovitis affecting the peripheral joints. All three patients displayed pitting edema of both dorsums of hands and feet. They all followed a benign course, with a complete resolution within 15 months of onset.

Al-Awadhi et al. (1999a) studied 48 Arabs (43 women, 5 men) with rheumatoid arthritis to see if they had an increased prevalence of hypothyroidism. The patients were compared to a group of 90 control subjects of similar demographic features. Seven patients were found to have elevated TSH levels; none in the control group. Of these seven, six had sub-clinical hypothyroidism. Three of these seven had anti-thyroglobulin antibodies, while all seven had anti-thyroid microsomal antibodies, suggesting that the cause of hypothyroidism in these patients with RA was autoimmune. Thyroid scan was performed on five of the patients with elevated TSH, and all five were found to show diffuse goiter. Simultaneously, Al-Awadhi et al. (1999b) investigated the role of bone resorption markers in the etiology of osteopenia in rheumatoid arthritis. They used ELISA and radio-immunoassays to estimate serum concentrations of IL-6, osteocalcin, type I collagen carboxyterminal telopeptide (ICTP), intact parathyroid hormone (PTH), and spot urine concentrations of type I collagen (NTx), and deoxypryridinoline (Dpd) in 25 patients with active and 25 with suppressed form of the disease, as well as 25 healthy control subjects. All individuals studied were females. Patients with active disease had significantly higher levels of serum IL-6, ICTP, and urine NTx, compared to patients with suppressed form as well as controls. Similarly, patients with the active form had significantly lower concentrations of serum osteocalcin and intact PTH compared to the patients with suppressed form and controls. No significant correlation could be detected between bone resorption markers and serum IL-6 and intact PTH in patients with the disease.

Alsaeid et al. (2003) studied the prevalence of certain HLA DR alleles in 64 children with Juvenile RA. Children with oligoarticular JRA showed a higher prevalence of DR3 alleles, compared to 64 ethnically matched controls. Patients with positive antinuclear antibodies as well as those with chronic anterior uveitis also had a higher prevalence of DR3 alleles. The allele DRB*0307 was found in a significant proportion of children with either oligoarticular or polyarticular JRA. The DRB*0308 allele was, however, detected only in children with the oligoarticular form. Both these alleles were absent in the control group, indicating the possibility that they might confer a genetic susceptibility to JRA.

Uppal et al. (2007) studied the association between RA and ACE gene polymorphism in 60 RA patients. They found a significant over-representation of the DD genotype and the D allele in this group. Logistic regression analysis indicated that the DD genotype conferred a relative risk for development of RA of a multitude of 3. Later, Uppal et al. (2008) carried out a study at the faculty of Medicine at Kuwait University to examine whether peripheral blood levels of inflammatory cytokines vary in rheumatoid arthritis (RA) patients according to different disease variables. This aim of the study was to assist in identifying peripheral blood cytokine markers associated with various disease markers. The study consisted of 42 seropositive RA patients who were distinguished through the age at onset, sex, disease duration, severity, activity, and ACR functional class. Subjects and controls underwent assessment of the production levels in mitogen-stimulated PBMCs of five pro-inflammatory cytokines (IFNgamma, TNFalpha, TNFbeta, IL-8, and IL-18) and three anti-inflammatory cytokines (IL-4, IL-10, IL-13). The assessment revealed that higher levels of IL-4 were associated with females, higher levels of IL-10 were correlated with the involvement of < or =2 DMARDs, higher levels of IL-18 were linked with non-erosive disease and younger age at onset, higher TNFbeta levels were allied with older current age of patients, and higher IL-8 levels were coupled with established or late disease.

Dhanusi et al. (2012) investigated the association of a 192 bp CA repeat polymorphism in the IGF-I gene with Rheumatoid Arthritis. This study utilized 52 healthy controls and 68 RA patients, 97% of whom were found to carry the wild-type allele. All controls carried the wild-type allele. Of the small proportion of samples that carried the variant, all were Arab and had RA. Significantly more male patients (14%) carried the variant when compared to female patients (2%). In addition, RA patients had significantly lower levels of plasma IGF-I.

Alfadhli and Nizam (2014) studied 22 Kuwaiti patients with RA and compared the spliced variants in the CTLA4 gene in these patients with those in 22 healthy controls. Patients with RA showed a reduced frequency of the mCTLA4-672, sCTLA4-562 and N-CTLA4-292 variants. Alfadhli and Nizam (2013) concluded that the expression pattern of the CTLA4 gene could also be playing a role in autoimmunity.

Lebanon

See table above, Qatar > Saxena et al. 2017

Oman

Pountain (1991) studied 1925 Omani adults aged 16 and over in a house-to-house survey in representative areas of Oman. Pountain (1991) estimated the prevalence of RA to be 8.4 per thousand adults. Pountain (1991) further concluded that cases of RA were less often seropositive than in European populations which may account for the lower prevalence of erosive disease.

Saudi Arabia

Al-Swailem et al (2006) examined the frequency of HLA-DRB1 alleles amongst Saudi patients with Rheumatoid Arthritis.  The study included 70 patients (13 males, 57 females) and 70 healthy volunteers.  The prevalence of RA in females was significantly higher than in males.  In addition, the age of onset in females was also lower than in males.  HLA typing using PCR-SSOP showed an increased frequency of the DRB1 *04 allele compared to the controls.  On the other hand, DRB1 *06 showed a negative association with RA.

See table above, Qatar > Saxena et al. 2017

United Arab Emirates

See table above, Qatar > Saxena et al. 2017

Namas et al. (2019) undertook a 3-year retrospective study of Emirati patients diagnosed with RA. There were a total of 414 patients, giving a prevalence rate of 2.72% for the Emirati population. The most common extra-auricular manifestation was xerophthalmia, and the most frequent co-morbidities were dyslipidemia, hypertension, diabetes, and GERD. 

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