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Immunological InvestigationsA Journal of Molecular and Cellular Immunology

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Rheumatoid arthritis: A single-center Egyptianexperience

B. R Sakr, M. M Elfishawi, M. H ElArousy, A. K Hatw, A. N AbdulKarim, A. BTammam, A. N Kotp, M. E Hamed, I. E Genedy, E. D. El Desouky & Z. O Nawito

To cite this article: B. R Sakr, M. M Elfishawi, M. H ElArousy, A. K Hatw, A. N AbdulKarim,A. B Tammam, A. N Kotp, M. E Hamed, I. E Genedy, E. D. El Desouky & Z. O Nawito (2018)Rheumatoid arthritis: A single-center Egyptian experience, Immunological Investigations, 47:3,293-302, DOI: 10.1080/08820139.2018.1425700

To link to this article: https://doi.org/10.1080/08820139.2018.1425700

Published online: 16 Jan 2018.

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Rheumatoid arthritis: A single-center Egyptian experienceB. R Sakra, M. M Elfishawia, M. H ElArousyc, A. K Hatwc, A. N AbdulKarimc, A. B Tammamc,A. N Kotpc, M. E Hamedc, I. E Genedyc, E. D. El Desoukyb, and Z. O Nawitoa

aRheumatology and Rehabilitation Department, Kasr Al-Ainy Hospital, Cairo University, Cairo, Egypt;bEpidemiology and Biostatistics Department, National Cancer Institute, Cairo University, Cairo, Egypt;cMedical students, faculty of medicine, Cairo University, Cairo, Egypt

ABSTRACTObjective: Demonstration of rheumatoid arthritis (RA) characteristicsin a large cohort of Egyptian patients.Methods: Retrospective analysis of data of 3219 RA patients attend-ing the Rheumatology outpatient clinic, Kasr Alainy Hospital, CairoUniversity; from January 1995 till December 2015.Results: Mean age at disease onset was 36.1 ±13.4 years; 2774 (84%)were females and mean disease duration was 12.9 ±7.9 years.Regarding number of joint affected at disease onset; polyarticularpattern was found in 77.1%, pattern of joint involvement; combinedsmall and large joints involvement was in 83.2%, subcutaneousnodules in 14.2%, interstitial lung disease in 0.3%, secondarySjogren’s syndrome in 10.5%, hand bony erosions at diagnosis in20.6%. Rheumatoid factor was positive in 52%.

There was annual increase in the newly diagnosed cases(P = 0.017) reflecting increase in patients’ awareness and improve-ment of medical service, also annual increase in: mean age of onset(P < 0.001) reflecting changes in health measures, also in cases withmonoarticular or oligoarticular patterns at disease onset (P = 0.02,0.01 respectively) reflecting earlier diagnosis of patients and inpatients with small joint involvement (P = 0.001) with a significantdecline in: polyarticular pattern (P = 0.001), combined small and largejoint affection (P < 0.001), and number of cases with hand bonyerosions (P = 0.01) denoting earlier diagnosis, tight disease control.Conclusion: We found a female predominance, younger age at dis-ease onset, lower frequency of extra articular manifestations, morefrequent polyarticular pattern at disease onset and less erosive dis-ease, denoting changing referral patterns, earlier diagnosis, improveddisease control in Egyptian RA patients over 2 decades.

Abbreviations: SNs: Subcutaneous nodules; 2ry SS: 2ry Sjogren’ssyndrome; ILD: Interstitial lung disease; ACPA: Anti-cyclic citrullinatedpeptide antibodies; DMARDs: Disease modifying anti-rheumaticdrugs.

KEYWORDSEgypt; epidemiology;rheumatoid arthritis

Introduction

Rheumatoid arthritis (RA) is a common autoimmune systemic inflammatory diseasewith an overall prevalence of 0.5%-1% (Aletaha et al., 2010). The interaction of

CONTACT B. R Sakr [email protected] Rheumatology and Rehabilitation Dept, Kasr Al-Ainy hospital,Kasr Al-Aini St, Cairo, EgyptThis article has been republished with minor changes. These changes do not impact the academic content of the article.

Supplemental data for this article can be accessed here.

IMMUNOLOGICAL INVESTIGATIONS2018, VOL. 47, NO. 3, 293–302https://doi.org/10.1080/08820139.2018.1425700

© 2018 Taylor & Francis

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genetic and environmental factors results in a cascade of immune reactions (Aletahaet al., 2010). A number of extra-articular manifestations and comorbidities arepresent in RA patients, which result in increased mortality (Gibofsky, 2014). RA isseen more often in females with an overall female to male ratio of 2:3 (Doran et al.,2002).

Many risk factors are associated with an increased risk of RA, ranging from infectionsand vaccinations to hormonal risk factors, such as breastfeeding and number of pregnan-cies, as well as lifestyle-related factors, such as diet, smoking, and obesity. In addition,studies have suggested an association between RA and periodontitis (Gerlag et al., 2016).

Previous studies suggested that RA patients of different ethnic origins may exhibitdifferent manifestations and outcomes, which enables the development of different tar-geted treatment modalities (Almeida Mdo et al., 2014). In our country, there are fewreports about disease manifestations and characteristics of RA especially among largeEgyptian cohort along a long term period of follow up; the present study was designed todescribe the demographic, clinical characteristics of patients with RA attending a tertiaryEgyptian medical institute over a period of 20 years.

Material and methods

Study design

This was a retrospective, observational, single center, Egyptian study.

Data source

The data source for the current study was the registration follow-up files of a cohort of3219 RA patients aged ≥18 years who fulfilled the 1987 ACR revised criteria for diagnosisof RA (Arnett et al., 1988), attending the outpatient clinic of Rheumatology Department inKasr Alainy Hospital, Cairo University from 1995 to 2015. This tertiary medical centerreceives around 20,000 case/year with different rheumatic diseases (14,000 case/year asnew cases and 6000 case/year as follow-up patients). The protocol was reviewed andapproved by the Research Ethics Committee (REC) (ethics approval umber N-27–2017).We did not rely on the new 2010 ACR/EULAR criteria because the studied RA Egyptianpatients were diagnosed from 1995 and we wanted to compare them with RA cases fromprevious studies which also relied on the older criteria.

Data collection

Demographic characteristics included: {age at disease onset and age at initial visit which isthe age of diagnosis, sex, residence, marital status, consanguinity, family history ofautoimmune disease, and whether smoker or not}.

– Clinical data included: {disease duration, number of joints affected; in the form ofpolyarticular, oligoarticular, or monoarticular at disease onset, types of joint involve-ment at disease onset as small, large joints, or combined small and large joints}

294 B. R. SAKR ET AL.

– Presence of extra-articular manifestations (e.g., subcutaneous nodules (SNs), 2rySjogren’s syndrome (2ry SS), skin vasculitis and interstitial lung disease (ILD) werealso documented)

– Serological tests as rheumatoid factor (qualitative rheumatoid factor) and anti-cycliccitrullinated peptide antibodies (ACPA) were included.

– Plain radiographs of hands and wrists were assessed for the presence or absence ofbony erosions.

– History of drug intake was also reported {disease modifying anti-rheumatic drugs(DMARDs); methotrexate, leflunomide, antimalarial drugs, and gold therapy andglucocorticoids.

– History of comorbidities, e.g., hypertension, diabetes.

Procedures to improve case finding

In order to minimize selection bias, patients who missed regular monthly follow up formore than 5 years were excluded from the study.

Statistical methods

Data management and statistical analysis were performed using Statistical Package forSocial Sciences (SPSS) version 21. Numerical data were summarized using means andstandard deviations. Categorical data were summarized as frequency and percentages.Time trend analysis was done using linear regression model. All P values are two-sided; Pvalue ≤ 0.05 were considered significant.

Results

Demographic characteristics

A total of 3219 RA patients were identified in a 20 years’ interval (1995–2015). Their meanage at disease onset ranged from 18 to 61 with a mean of 36.1 ± 13.4 years. Diseaseduration ranged from 0.5 to 53 years with mean of 12.9 ± 7.9 years. Around 24.9% ofpatients with subcutaneous nodules were smokers while only 16.4% were nonsmokers(P = 0.001), moreover 34.5% of patients having hand erosions at diagnosis were smokersvs 30.5% nonsmokers (P = 0.225), also RF was positive in 66.9% of smokers and negativein 64% (P = 0.369). Demographic data of our patients are shown in Table 1, while Table 2describes their disease characteristics.

Drug intake by the studied RA population

Methotrexate was received by 2668 (82.8%) patients, hydroxyl chloroquine by 1641(51%),leflunomide by 606 (18.8%), Gold therapy by 55(1.7%), and glucocorticoids by1452 (45%)patients. None of the patients were using biological therapy.

IMMUNOLOGICAL INVESTIGATIONS 295

Variations in RA characteristics during the past 20 years

There was a significant statistical annual increase by 0.13% in the newly diagnosed cases(P = 0.017) throughout the studied period (Figure 1), while there was a significant annualdecrement by 0.4% in female % (P = 0.02). Also, we found a significant annual increase inthe mean age of disease onset by 0.2 year (P < 0.001) (Figure 2).

Concerning the number of joint affection at RA onset in our patients; there was astatistically significant annual increase in monoarticular and oligoarticular presenta-tions at disease onsetby 0.1% and 0.9% (P = 0.02, 0.01 respectively). On the contrary,polyarticular pattern showed significant annual decline by 1.2% (P = 0.001)(Figure 3).

Regarding types of joints affected at disease onset, there was an annual decrement incombined small and large joint affection by 0.9% (P < 0.001), while small joint affectionshowed a steady annual increment by 0.6% (P = 0.001) (Figure 4).

Table 1. Demographic data of the studied RA population.Demographic data Frequency (N (%))

Age at initial visit, diagnosis (years) 20–75 (40.5 ± 12.6)Range [Mean± SD]Sex (Females) 2774 (84%)ResidencyGreat Cairo 2179 (67.8%)Delta, Lower Egypt 146 (4.5%)Upper Egypt 241 (7.5%)Missing 653(20.2%)Consanguinity 163(5%)Smokers 303(9.4%)Marital statusSingle 346 (10.7%)Married 2624 (81.6%)Divorced 43 (1.3%)Missing 84 (2.6%)Widow 122 (3.8%)Co-morbiditiesHypertension 91 (2.8%)Diabetes 266 (8.2%)Positive family history of autoimmune diseases 243 (7.5%)

Figure 1. Variations in newly diagnosed RA patients.


Figure 3. Variations in pattern of joint involvement.

Figure 2. Variations in sex distribution of RA patients.

Figure 4. Variations in type of joint involvement.


Presence of 2ry Sjogren’s syndrome increased annually by 0.5% (P = 0.03), whilesubcutaneous nodules decreased annually by 0.4% (P = 0.068).

Annual decline in the number of cases with bony hand erosions at diagnosis by 0.5%was detected (P = 0.01). Females were more prone to have erosions (33% versus 29% inmales); although this was not statistically significant (P = 0.39). Also, RF positive caseswere significantly higher in the erosive group (34% versus 28% seronegative) (P = 0.019).

Discussion

To the best of our knowledge, this is the first and largest retrospective study describingdemographic and disease characteristics of RA among a large cohort of Egyptian patientsover a long period of time (20 years).

Our results showed a higher incidence of RA in women (5.2:1), this was comparable tothat reported in Western population (4–5:1) (Kvien et al., 2006) and in Algeria (5.9:1)(Slimani et al., 2014) but was lower than reported in the Brazilian population (8:1)(Almeida Mdo et al., 2014).

Females represented 84% of the sample size matching with that observed in theCOMORA (COMOrbidities in Rheumatoid Arthritis) study (81.7%) conducted on 4586RA patients from 17 different countries (Dougados et al., 2014), also in agreement with astudy conducted by Alian et al, 2017 on 1142 RA Egyptian patients (Monocentric study)where females represented (79.6%) of cases (Alian et al., 2017).

The mean age of our RA patients at disease onset was 36.1 ±13.4 years and at initialvisit where it was diagnosed was 40.5 ±12.6 years which was comparable to that men-tioned by Imanaka et al (Imanaka et al., 1997) where it was (37.5 ±14.1 and 42.6 ±14.3,respectively). While it was lower than that reported in other populations, e.g., Omani RApatients (44.5 ±14.5 ys) (Al-Temimi, 2010), Algerian (50.1 ±14.5 ys) (Slimani et al., 2014),Brazilian (47.5 ±11.03 ys) (Almeida Mdo et al., 2014), and that reported in the COMORAstudy (56 ±13 ys) (Dougados et al., 2014).

The mean age of our RA patients at disease onset was 36.1 ±13.4 years and at initialvisit where it was diagnosed was 40.5 ±12.6 years, showing that there was time delaybetween age of onset and diagnosis which may be attributed to the fact that patientssought medical advice from primary care physicians or other specialists such as orthope-dic surgeons, rather than consulting a rheumatologist from the outset. A lack of awarenessof the need to see a rheumatologist from the patient and the primary care physician maytherefore limit early diagnosis of RA. This was also the case in the United Arab ofEmirates (Zafar et al., 2012), this could be overcomed by increasing patients’ awarenessand by anticipation of awareness programs and public campaigns.

Only 9.4% of our patients were smokers which were lower than that reported in theCOMORA study (13.2%) (Dougados et al., 2014); this can be explained by the communitytraditions in revulsion of cigarette smoking among females who represented the vastmajority of our patients. 24.9% of patients with subcutaneous nodules were smokerswhile only 16.4% were nonsmokers (P = 0.001), this is in agreement with a study onUSA RA patients where Saag KG et al (Saag et al., 1997) reported that Pack cigarettesmoking was associated with subcutaneous nodules (P = 0.051), also this was in line withNyhäll-Wåhlin et al (Nyhäll-Wåhlin et al., 2006) who stated that in Sweden RA patientssmoking was associated with rheumatoid nodules (P < 0.001), moreover 34.5% of patients


having hand erosions at diagnosis were smokers vs 30.5% nonsmokers (P = 0.225), this isin line with Yin et al (Yin et al., 2017) who stated that there was no association betweensmoking status with the presence of radiographic erosions (P = 0.66).

Regarding comorbidities, 8.2% of patients were diabetics and 2.8% had hypertensionwhich appear to be lower than frequencies observed in the general Egyptian population(15.5% for diabetes, 26.3% for hypertension) (Ashour et al., 1995; Hegazi et al., 2015), alsothis is lower than frequencies reported by Alian et al, 2017 (Alian et al., 2017) where 32.2%of the Egyptian RA patients recruited in that study were hypertensive and 20.1% werediabetic, again our frequency was lower than that reported by Al-Bishri et al, 2013 (Al-Bishri et al., 2013) in a study conducted on 340 RA patients where 31% of patients werediabetic and 36% had hypertension, this may be explained by the high percentage ofcorticosteroids intake among the patients of the latter 2 studies (87.1% and 80.8%,respectively), while it was only 45% in our patients, we could not discuss these comorbid-ities in relation to cardiovascular complications of RA despite its importance in EgyptianRA patients (Elshereef et al., 2015) due to shortage of data in the registry files regardingthis point which is one of the limitations we faced. In addition, the association betweenRA and periodontitis could not be assessed due to lack of documented data regarding thisaspect in the registry files.

The main reported extra-articular manifestations in our RA patients were SNs (14.2%)and 2ry SS (10.5%), which is lower than other populations, e.g., in the Brazilian population{SNs (19.4%) and 2ry SS (46.9%)} (Almeida Mdo et al., 2014), in Turkish patients (18.1%for SNs) (Calguneri et al., 2006), in the United Arab of Emirates (2ry SS 28%) (Badshaet al., 2008) and in Omani patients (2ry SS 24.4%). ILD was reported in 0.8% of our RApatients, which was lower than that reported in Saudi Arabian RA patients (2.7%) (Al-Bishri et al., 2013) and Omani RA patients (3%) (Al-Temimi, 2010); this may be attributedto our previous relying on the less accurate conventional radiography for diagnosis of ILDdue to high expenses of high resolution CT chest.

Compared to other countries, Egyptian patients seem to have less erosive disease(20.6%) at disease diagnosis vs. 68.1% in Algeria (Slimani et al., 2014), 62.2% in Brazil(Almeida Mdo et al., 2014), 55.2% in the United Arab Emirates (Badsha et al., 2008), and42% in Kuwaiti patients (Al-Salem and Al-Awadhi, 2004) denoting earlier diagnosis andthe effect of anticipation of support groups, awareness programs, and public campaignssimilar to efforts anticipated in the United Arab of Emirates (Zafar et al., 2012).

Around 52% of patients were positive for RF which was close to the Brazilianpopulation (49.2%) (Almeida Mdo et al., 2014; Da Mota et al, 2010), while it wasless than Kuwaiti, Omani, Saudi Arabian, and Sweden patients, where it was 60%, 76%,and 73%, respectively (Al-Bishri et al., 2013; Al-Salem and Al-Awadhi, 2004; Al-Temimi, 2010; Hallert et al., 2014).

Methotrexate was the most commonly used DMARD; where it was received by 82.8%RA patients while it was in the Saudi Arabian (74.4%) (Al-Bishri et al., 2013), Algerianpatients (72.2%) (Slimani et al., 2014), and in the COMORA study (88.6%) (Dougadoset al., 2014). None of our patients were on biologic therapy that could be attributed to thefinancial problems in our country; making treatment with conventional DMARDs com-pulsory although the rate of biologic use in clinical practice is rising to treat moderate tosevere RA that has not responded to conventional DMARDs .


In the present study, time trend analysis revealed a significant annual increase by 0.13%in the newly diagnosed RA cases (P = 0.017) which may reflect increase in patients’medical awareness and improvement of medical service in our country during the last20 years.

We detected a significant annual decrement by 0.4% in female RA patients (P = 0.02)which was less than that recorded in a study done on 446 RA patients from OlmstedCounty, Minnesota where there was a modest increase in women from 1995 to 2007 by2.5% (P = 0.02) (Myasoedova et al., 2010).

Our study revealed a significant annual increase in the mean age of disease onset by0.2 year (P < 0.001). Concordantly, in a study conducted on 566 Japanese patients from1960 to 1990; the age of onset increased significantly from 37.5 to 46.9 years. This increasemay reflect changes in health measures (e.g., increase in life span and change in socio-economic status) (Imanaka et al., 1997).

Polyarticular pattern of joint affection at disease onset was the most commonly detected(80.3%) among our RA patients who were in concordance with that reported in literature(Hecht et al., 2015), but it showed significant decline annually. While there was a statisticallysignificant annual increase in both monoarticular and oligoarticular presentations which maybe explained by the earlier diagnosis of arthritis patients in the last decade.

An interesting finding in our data was the steady annual decline in number of cases withbony hand erosions at diagnosis by 0.5% (P = 0.01) denoting earlier diagnosis and more tightdisease control and anticipation of support groups, awareness programs, and public cam-paigns similar to efforts anticipated in the United Arab of Emirates (Zafar et al., 2012).

In our study, there was no statistical difference between males and females regardingthe presence of hand erosions [33% of the studied RA females (n = 2774) had erosions,while 29% of males had erosions (P = 0.39)], which was statistically comparable withresults of the quantitative standard monitoring of patients with RA (QUEST-RA) programwhich was established to include 6004 RA patients from 70 sites in 25 countries wherewomen had erosions more often than men (P = 0.36) (Sokka et al., 2009). Also, number ofRF positive cases was significantly higher in the erosive group which was in agreementwith previous studies (Hecht et al., 2015; Van Steenbergen et al., 2014).

Our study has several limitations: first, this is a retrospective study where shortage of someimportant data documented in the registry files was a major obstacle in our research, second;patients were included using the 1987 ACR criteria for RA diagnosis instead of the new 2010ACR/EULAR criteria, this is because we studied patients diagnosed from 1995 and we wantedto compare RA Egyptian patients with RA cases from previous studies which also relied on theolder criteria. The third limitation was that ACPA test was done for only 269 (8.3%) patientsdue to financial causes. Also although cardiovascular disease is an important comorbidity(Elshereef et al., 2015) we could not document its percentage or correlate it with othercomorbidities as DM, hypertension due to lack of data in the registry files regarding thispoint. Furthermore, the association between RA and periodontitis could not be assessed dueto lack of documented data regarding this aspect in the registry files.

The changing referral patterns and change in awareness of the public and primary carephysicians/providers about RA (Zafar et al., 2012) is one of the most important factorsthat influenced our research.


Conclusion

The present study describes RA characteristics in a tertiary referral hospital, carried on alarge cohort of Egyptian patients over a long period of time (2 decades). We found afemale predominance, younger age at disease onset, lower frequency of extra-articularmanifestations, more frequent polyarticular pattern at disease onset and less erosivedisease.

This 20 year follow-up cohort has demonstrated that during a period of changingreferral patterns and earlier disease recognition, earlier diagnosis, improved disease con-trol, and fewer signs of disease progression (i.e., erosions) are found in Egyptian RApatients. Some conclusions about the cultural and ethnic comparisons would be importantas well.

Ethical approval

This article does not contain any studies with human participants or animals performed by any ofthe authors.

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AbstractIntroductionMaterial and methodsStudy designData sourceData collectionProcedures to improve case findingStatistical methods

ResultsDemographic characteristicsDrug intake by the studied RA populationVariations in RA characteristics during the past 20€years

DiscussionConclusionEthical approvalReferences

rheumatoid arthritis: a single-center egyptian experience...rheumatoid arthritis introduction...

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