Clinical Profile and Comorbidities Associated with Rheumatoid Arthritis Patients in Sudair, Saudi Arabia.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic, debilitating condition that has a significant effect on the lives of patients, their families, and society at large. AIMS: The aim is to determine the clinical profile and any comorbidities associated with RA patients in the Sudair region of Saudi Arabia. SUBJECTS AND METHODS: Sixty patients were included in this cross-sectional observational study, both newly or already diagnosed with RA, fulfilling the 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria for RA. They were followed up in the rheumatology clinic in King Khalid Majmaah Hospital in the Majmaah province from January 2017 to December 2020.
RESULTS: The subjects' mean age was 47.87 ± 11.55 years, 52 female and 8 male (female-to-male ratio 6.5:1). About 23.3% of patients with RA had positive family history. The main comorbidities and associated diseases were hypertension (18.3%) and hypothyroidism (15%). The most frequently involved joints were the wrist, metacarpophalangeal, proximal interphalangeal, elbow, and knee joints. Subjects were positive in 66.7% for rheumatoid factor and 78.3% for anti-cyclic citrullinated peptide. Both markers were positive in 60% of the patients.
CONCLUSION: Approximately one-quarter of the studied group had a family history of RA. Hypertension followed by hypothyroidism was the most common comorbidities reported in our study. Copyright:

INTRODUCTION

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that occurs more frequently in women than in men. The prevalence rate ranged from 0.5% to 1% of the population, and there was a regional disparity.[1] RA etiology remains unknown. It primarily attacks the synovial membranes of the joints and causes chronic inflammation. On its progression, the joints are damaged and destroyed, the tendons and ligaments debilitated,[2] causing progressive disability, early death, and social and economic burdens. RA diagnosis requires accurate medical history and physical examination, along with selected laboratory testing.[3]

The clinical presentation of the disease initially affects small joints, progressing to larger joints. Symmetrical involvement manifests locally as pain, tenderness, swelling, and warmth of the joints, accompanied by morning stiffness for >30 min, and the general symptoms are fatigue, fever, and weight loss. The extra-articular features of RA occur later after the onset, as the disease involves other organs, such as skin, visual, cardiopulmonary, renal, gastrointestinal, and nervous systems.

Early and aggressive treatment after the first 12–16 weeks of symptoms, with either disease-modifying antirheumatic drugs,[4] or biology therapy such as antitumor necrosis factor-α,[56] reduces the rate of disease progression.

Various studies are conducted in different Saudi Arabia regions and based on our literature search, no previous study has evaluated the characteristics of RA patients in Sudair region. Therefore, our research aimed to study the patients with RA from the Majmaah province who attended the rheumatology clinic in King Khalid Majmaah Hospital (KKMH) and determine the clinical profile and comorbidities associated with RA.

SUBJECTS AND METHODS

This is a cross-sectional observational study involving Saudi patients with RA. They were newly or previously diagnosed with RA and were followed up in the rheumatology clinic in KKMH from January 2017 to December 2020. Sixty patients diagnosed with RA, according to the 2010American College of Rheumatology/European League Against Rheumatism Diagnostic Criteria,[7] were included in the study. The research was approved by the central institutional review board of the Ministry of Health, SA.

The patients' demographic characteristics, main comorbidities, associated diseases, and clinical conditions were evaluated based on their medical records. If at least one first-degree parent had been diagnosed with RA, the family history was considered positive. Blood tests, including a rheumatoid factor (RF), and anti-cyclic citrullinated peptide (anti-CCP) levels were performed routinely at admission to the clinic.

The disease activity was evaluated during the study using the disease activity score DAS28 (specifically erythrocyte sedimentation rate [ESR]) as follows: Remission, DAS28 ≤2.6; low disease activity, 2.6 < DAS28 ≤3.2; moderate disease activity, 3.2 < DAS28 ≤5.1; and high disease activity, DAS28 >5.1.

All characteristic features of patients with RA seen at KKMH were statistically analyzed using IBM SPSS version 26. Categorical data were expressed as frequencies and percentages, whereas age was defined as mean ± standard deviation. Pearson's Chi-square and Fisher's exact tests were applied to observe associations between various study parameters. A P < 0.05 was considered statistically significant.

Ethical considerations

This research was approved by the ethical review committee of the Ministry of Health KSA vides reference on 2019-0083E.

RESULTS

Data were collected from 60 individuals (52 women, 86.7%; 8 men, 13.3%). The mean age of the patients was 47.87 ± 11.55 years. The female-to-male ratio was 6.5:1. The duration of establishing the diagnosis for most of the patients was <5 years, 36 individuals (60%), followed by 5–10 years, 13 individuals (21.7%), and >10 years, 11 individuals (18.3%). Out of the total, 23.3% had a family history of RA. The DAS28 score for 37 patients (61.7%) was between 3.2 and 5.1, and 23 patients (38.3%) had a score >5.1. The clinical characteristics of the individuals with RA are presented in Table 1.

Table 1

Clinical characteristics of rheumatoid arthritis population (n=60)

Parameter	n (%)
Mean age (years)	47.87±11.55
Sex
Female	52 (86.7)
Male	8 (13.3)
Female:Male ratio	6.5:1
Duration of diagnosis (years)
>5	36 (60.0)
Between 5 and 10	13 (21.7)
>10	11 (18.3)
Family history of RA
No	46 (76.7)
Yes	14 (23.3)
DAS-28 (%)
Remission ≤2.6	0 (0.0)
Low 2.6 and ≤3.2	0 (0.0)
Moderate 3.2 and ≤5.1	37 (61.7)
High >5.1	23 (38.3)

RA: Rheumatoid arthritis, DAS: Disease activity score

In this study, we investigated the main comorbidities and associated diseases. We found that the most common were hypertension 11 (18.3%), followed by hypothyroidism 9 (15%), diabetes mellitus 8 (13.3%), dyslipidemia 4 (6.7%), bronchial asthma 3 (5%), and coronary artery disease 1 (1.7%), respectively. The results are presented in Table 2.

Table 2

Details of the main comorbidities and associated disease (n=60)

Parameter	n (%)
Hypertension	4
No	49 (81.7)
Yes	11 (18.3)
Hypothyroidism
No	51 (85.0)
Yes	9 (15.0)
Diabetes mellitus
No	52 (86.7)
Yes	8 (13.3)
Dyslipidemia
No	56 (93.3)
Yes	4 (6.7)
Bronchial asthma
No	55 (95)
Yes	3 (5)
Coronary artery disease
No	59 (98.3)
Yes	1 (1.7)

Table 2 presents the site of joints' clinical involvement. The upper limb joints were affected more than the lower limbs; distal interphalangeal joints were involved in 5 (8.3%) of the patients, proximal interphalangeal (PIP) joints 47 (78.3%), metacarpophalangeal (MCP) joints 49 (81.7%), wrists 51 (85.0%), elbows 25 (41.7%), shoulders 15 (25.0%), knees 22 (36.7%), ankles 7 (11.7%), and feet 14 (23.3%) patients, respectively. Collectively 18 (30%) deformities were observed in the patients whose hand deformities were present in 8 (13.3%) patients. Swan-neck was noted in 6 (10%) patients, boutonniere, z-shaped thumb, and ulnar deviation in 4 (6.7%) patients [Table 2]. The percentage of elevated ESR and C-reactive protein (CRP) among the studied groups was 50 (83.3%) and 31 (51.7%), respectively. RF was positive in two-quarters of the patients, and 47 (78.3%) had positive anti-CCP [Figure 1].

Figure 1

Laboratory findings in patients with rheumatoid arthritis

Table 3 depicts the association of deformities RF and Anti-CCP. About 3 (7.5%) and 2 (5%) of patients with deformities in hands and swan neck deformity have positive RF. Whereas patients having Boutenniere deformity, Z-shaped thumb deformity and ulnar deviation had negative RF and negative anti-CCP, which was statistically significant. With regards to anti-CCP, 50% of the patients with hand deformities and swan neck deformity, respectively, had positive anti-CCP (P < 0.05).

Table 3

Joint involvement and deformities in patients with rheumatoid arthritis (n=60)

	n (%)
Joints involvement in patients
DIP joints
No	55 (91.7)
Yes	5 (8.3)
PIP joints
No	13 (21.7)
Yes	47 (78.3)
MCP joints
No	11 (18.3)
Yes	49 (81.7)
Wrists
No	9 (15.0)
Yes	51 (85.0)
Elbows
No	35 (58.3)
Yes	25 (41.7)
Shoulders
No	45 (75.0)
Yes	15 (25.0)
Knees
No	38 (63.3)
Yes	22 (36.7)
Ankles
No	53 (88.3)
Yes	7 (11.7)
Feet
No	46 (76.7)
Yes	14 (23.3)
Deformities in patients with rheumatoid arthritis
Presence of hands’ deformities
No	52 (86.7)
Yes	8 (13.3)
Swan-neck
No	54 (90.0)
Yes	6 (10.0)
Boutonniere
No	56 (93.3)
Yes	4 (6.7)
Z-shaped thumb
No	56 (93.3)
Yes	4 (6.7)
Ulnar deviation
No	56 (93.3)
Yes	4 (6.7)

DIP: Distal interphalangeal, PIP: Proximal interphalangeal, MCP: Metacarpophalangeal

Anti-CCP and RF were found to have a significant relationship (P = 0.006). In 15% of the patients, RF and anti-CCP were negative, according to our finding, whereas both markers were positive in 60% of the patients. The association between RF and anti-CCP was also observed to be significant in female patients (P = 0.022); both markers were positive in 59.6% of the female patients. However, no significant association was observed between RF and anti-CCP in male patients (P = 0.107) [Table 4].

Table 4

Association between rheumatoid factor, anti-cyclic citrullinated peptide, and sex

Associations RF	Anti-CCP		χ2, P
	Negative, n (%)	Positive, n (%)
Overall (n=60)
Negative	9 (15.0)	11 (18.3)	9.62, 0.006*
Positive	4 (6.70)	36 (60.0)
Females (n=52)
Negative	7 (13.5)	11 (21.2)	6.84, 0.022*
Positive	3 (5.80)	31 (59.6)
Male (n=8)
Negative	2 (25.0)	0 (0.0)	4.44, 0.107*
Positive	1 (12.5)	5 (62.5)

*A P<0.05 was considered statistically significant. RF: Rheumatoid factor, Anti-CCP: Anti-cyclic citrullinated peptide

DISCUSSION

In the current study, the mean age of the patients was 47.87 ± 11.55 years. Females were more commonly affected than males in a ratio of 6.5:1, and the rate was slightly higher than in other studies.[89] The <5 years (60%) duration of diagnosis was higher than that observed in the Al-Ghamdi study.[10]

An implication of a genetic component among RA patients has been reported in studies.[1112] However, there is little epidemiological data available in Saudi Arabia about the family history of RA. In our study, about 23.3% of the patients reported at least one first-degree relative affected by RA.

Approximately 60% of RA patients had moderate disease activity; these findings were similar to those of another study conducted by Attar.[13] The comorbidities and associated diseases such as hypertension 11 (18.3%) and diabetes mellitus 8 (13.3%) were more than the reported in the Al-Ghamdi study,[10] and less than the Al-Bishri study.[9] Our results reported that around 9 patients with RA (15.0%) had hypothyroidism, which contrasted the rates of 4% and 8.5% reported in Mosli's[14] and Al-Bishri's patients,[9] respectively. Other comorbidities and associated diseases (dyslipidemia, bronchial asthma, and coronary artery disease) were the least common, occurring in 6.7%, 5%, and 1.7% of the patients, respectively.

The upper limb joints were affected more than the lower limbs; hence, the most commonly involved joints were the wrist, MCP, PIP, elbow, and knee. The overall pattern of joint involvement observed is comparable to that reported in the Alballa study.[8] Other joints were involved less frequently.

The presence of hand deformities presented an impact on daily life function and added useful prognostic information as an early sign of a more severe stage of the disease.[15] In our study, 8 (13.3%) patients with RA had hand deformities. Swan-neck deformities were observed in 6 patients (10.0%), while Boutonniere, Z-shaped thumb, and ulnar deviation deformities of the fingers were observed in four patients (6.7%).

ESR was raised in 83.3% of the cases, which is consistent with the reported in Alballa's patient,[8] and CRP was increased by 51.7%, which is inconsistent with the reported 76% in Attar's patients.[16] As a sign of chronic disease, anemia is observed in RA, where it usually correlates with the disease activity, particularly to the degree of articular inflammation.[17] Anemia was observed in 30.0% of our patients, and these findings were less than the reported data by Al-Ghamdi and Attar.[10]

The percentage of patients with a positive RF (66.7%) was comparable to that found in Attar's study (65%).[16] However, a substantially higher number of patients were observed to have positive RF in research conducted by Omair (93.2%),[18] Alballa (79.5%),[8] and Al-Bishri et al. (76.1%),[9] however; a smaller number was presented in the Attar's study (54%).[13] In scientific reviews, anti-CCP is regarded as having high specificity (98%) for RA and being detected in the early stages of the disease before the appearance of the typical clinical features. Therefore, it is widely used as a routine laboratory test for RA diagnosis in clinical practice.[19] In the present study, anti-CCP was detected in 47 (78.3%) patients, and these findings were inconsistent with investigations conducted by Omair (98.3%)[18] or Attar (57.2%).[16]

There was an apparent relationship between the presence or absence of RF and anti-CCP; both were negative in 9 (15.0%) patients and both positive in 36 (60.0%) patients. Moreover, both markers were positive in 59.6% of the female patients among the studied groups and comparable with those of another study.[18]

Since our research included patients who attended only in the Majmaah province, the findings might not represent the entire population with RA correctly. Planning to develop a national database such as a Saudi arthritis registry is an essential step in monitoring the RA cases in the country and could elucidate several different aspects related to the disease.

CONCLUSION

Approximately one-quarter of the studied group had a family history of RA. Hypertension was the most common comorbidity reported in our study, and hypothyroidism was more prevalent among the studied group as compared to other RA populations. Larger sample size studies are needed in the future to confirm our findings.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.