Epidemiology of Adult Rheumatoid Arthritis.

Definition :

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease of undetermined aetiology involving primarily the synovial membranes and articular structures of multiple joints. The disease is often progressive and results in pain, stiffness, and swelling of joints. In late stages deformity and ankylosis develop.

Incidence and Prevalence:

Worldwide prevalence is approx 1%. Its incidence and prevalence is more in developed countries and less in developing countries except India. There is now some evidence that prevalence and severity of this disease is decreasing.

Morbidity and Mortality

It is now not considered as a benign disease .Patients of rheumatoid arthritis experience lower life expectancy than general healthy population. Risk of infections ,cardiovascular disease and other co-morbid conditions like depression is also high. Approx 50% patients stop working after 10 years of diagnosis of disease.

Risk Factors:

Female gender, old age ,positive family history, heavy smoking and ethnicity (Pima Indians) are established risk factors for onset of this disease.

Protective Factors.

Pregnancy, Oral contraceptive pills ,Fish ,Olive oil and vegetarian diet are considered as protective factors but evidence is not so strong and more research is needed to be done in these areas.

Detection and Conclusion.

Public awareness regarding the diagnosis of this disease as early as possible is needed. Because early diagnosis and early start of aggressive treatment by disease modifying agents is important in slowing the progression of rheumatoid arthritis.

References

Epidemiology of Adult Rheumatoid Arthritis.

Introduction

Rheumatoid arthritis is a chronic systematic inflammatory disorder of unknown cause. It affects the peripheral joints in a systemic manner. Within 10 years of onset it causes great disability. Arthritis is the dominant clinical manifestation, involving many joints, especially those of the hands and feet. The course is variable, but often chronic and progressive, leading to deformity and disability. In most cases of RA, the patient has remissions and exacerbations of the symptoms.

This means that there are periods of time when the patient "feels good" and times when the patient "feels worse". There will likely be times that a patient with RA "feels cured". It is important to understand that there are very few patients that have complete remission of the disease and it is essential that the RA patient does not stop the treatment program

Methods and definitions

The method of searching the topic was through internet by medical databases like Pubmed, medical magazines in science direct.com and http://scholar.google.com (a new feature of google search engine for searching only academic papers. It's in beta version)

Keywords used for searching were Epidemiology of adult rheumatoid arthritis, Mortality and morbidity of rheumatoid arthritis, Nutrition and rheumatoid arthritis, Pregnancy and rheumatoid arthritis, Rheumatoid arthritis in developing countries.

Definitions.

Rheumatoid factor.

The test for rheumatoid factor (RF) is used to help diagnose rheumatoid arthritis (RA

Environmental factors

The term ‘environment’ is frequently used to describe all those susceptibility factors leading to disease that are not explicable on the basis of an identifiable genetic marker.

1987 Criteria for the Classification of Acute Arthritis of Rheumatoid Arthritis

In 1958 American college of Rheumatology [1]presents the diagnostic criteria for rheumatoid arthritis . Then in 1987 it presents another diagnostic criteria. the reason being "improved clinical knowledge and other forms of arthritis misdiagnosed as RA are now separately classified"[2]

Criterion	Definition
1. Morning stiffness	Morning stiffness in and around the joints, lasting at least 1 hour before maximal improvement
2. Arthritis of 3 or more joint areas	At least 3 joint areas simultaneously have had soft tissue swelling or fluid (not bony overgrowth alone) observed by a physician. The 14 possible areas are right or left PIP, MCP, wrist, elbow, knee, ankle, and MTP joints
3. Arthritis of hand joints	At least 1 area swollen (as defined above) in a wrist, MCP, or PIP joint
4. Symmetric arthritis	Simultaneous involvement of the same joint areas (as defined in 2) on both sides fo the body (bilateral involvement of PIPs, MCPs, or MTPs is acceptable without absolute symmetry)
5. Rheumatoid nodules	Subcutaneous nodules, over bony prominences, or extensor surfaces, or in juxtaarticular regions, observed by a physician
6. Serum rheumatoid factor	Demonstration of abnormal amounts of serum rheumatoid factor by any method for which the result has been positive in <5% of normal control subjects
7. Radiographic changes	Radiographic changes typical of rheumatoid arthritis on poster anterior hand and wrist radiographs, which must include erosions or unequivocal bony decalcification localized in or most marked adjacent to the involved joints (osteoarthritis changes alone do not qualify)

· · * For classification purposes, a patient shall be said to have rheumatoid arthritis if he/she has satisfied at least 4 or these 7 criteria. Criteria 1 through 4 must have been present for at least 6 weeks. Patients with 2 clinical diagnoses are not excluded. Designation as classic, definite, or probable rheumatoid arthritis is not to be made.

· Table no 1 .[2]

International Classification of Diseases-10 (ICD-10) OF ADULT RHEUMATOID ARTHRITIS.[3]

Adult rheumatoid arthritis attracts the coding in ICD-10 from M05-M06

M05.3

Rheumatoid arthritis with involvement of other organs and systems

M05.9

Seropositive rheumatoid arthritis, unspecified

M06

Other rheumatoid arthritis

M06.0

Seronegative rheumatoid arthritis

M06.4

Inflammatory Polyarthropathy

M06.9

Rheumatoid arthritis, unspecified

Routine data and descriptive studies .

Prevalence is Approx 1% worldwide. However the prevalence is not same across the world. Women are affected 2-3 times more than men. Prevalence increases with age and sex differences diminish with increase in age. It affects all races but it is more common in certain races like Pima Indians[4] (prevalence 5.3-6.0) and in the Chippewa Indians (6.8%)[5].

It is rare in rural parts of China, Hong Kong [6] ,Indonesia, Japan .One study fails to find even a single case of Rheumatoid arthritis in Nigeria.[7] Prevalence in Northern Europe and North America is 0.5 -1.1%.[9][10][11][12][13]Southern Europe=0.3-0.7%.[14][15]There is higher incidence if we go from south to north Europe. Prevalence in developing countries is 0.1 -0.5% [16][17]. But in India ,the prevalence of rheumatoid arthritis is .75% ,is similar to the developed countries.

Reason might be north Indian population is genetically closer to the Caucasians than to other ethnic groups.[18]

Prevalence and incidence rates of RA worldwide (cases per

100 inhabitants)

Population		Prevalence rates	Incidence rates
North America	• USA (general population)	0.9–1.1	0.02–0.07
	• USA (native-Americans)	5.3–6.0	0.09–0.89
North Europe	• England	0.8–1.10	0.02–0.04
	• Finland	0.8	0.03–0.04
	• Sweden	0.5–0.9
	• Norway	0.4–0.5	0.02–0.03
	• Netherlands	0.9	0.05
	• Denmark	0.9
	• Ireland	0.5
South Europe	• Spain	0.5
	• France	0.6	0.01
	• Italy	0.3
	• Greece	0.3–0.7	0.02
	• Yugoslavia	0.2
South America	• Argentina	0.2
	• Brazil	0.5
	• Colombia	0.1
Asia	• Japan	0.3	0.04–0.09
	• China	0.2–0.3
	• Taiwan		0.3
	• Indonesia	0.2–0.3
	• Philippines	0.2
	• Pakistan	0.1
Middle East	• Egypt	0.2
	• Israel	0.3
	• Oman	0.4
	• Turkey	0.5
	• Africa	0–0.3

TABLE NO 2 TAKEN FROM [19]

Incidence and prevalence of rheumatoid arthritis is decreasing in developed world .[12][13] But especially in women not in men and proposed causes are

Use of oral contraceptives by females after 1960s .[20]

There is decrease in severity of disease .[21][22]

Change in classification criteria of rheumatoid arthritis .[23]

Birth cohort effect.

Norfolk study.[13]

The first study in uk for prevalence of rheumatoid arthritis was done in 1958 by Lawrence JS.[24]Since then the classification criteria had changed and to see whether there is any decrease in prevalence of disease Norfolk study was conducted in primary setting . By stratified randomization according to seven age and gender bands,7050 patients were mailed and then positive responders for disease were examined by rheumatologist. The overall response rate was 82%. Sixty-six cases of RA were identified. Extrapolated to the population of the UK, the overall minimum prevalence of RA is 1.16% in women and 0.44% in men. If we look at fig.2 which compares the data from both studies, it is clear that prevalence in women is decreasing in all age groups except in 75+group.but the prevalence in men had increased.

Figure 1 and 2 taken from [44]

MORTALITY AND MORBIDITY

It is now considered as a malignant disease and with increase mortality and morbidity and poor prognosis. Life expectancy decreases by 3-10 years according to severity and age of onset of disease. It is debilitating disease and limit the patient daily activities. It is also associated with serious co morbid conditions like infections ( common cause of death in developing countries) cardiovascular disease[25], respiratory disease [26]etc.

Drugs taken for this disease are associated with serious side effects. Depression is more common in rheumatoid arthritis patients due to pain ,economic burden ,lose of work which ultimately leads to suicide.

Suicide and RA

A prospective study[27] with 13-yr follow-up ,data taken from national hospital discharge registers of all suicides (1296 males, 289 females) committed during the years 1988–2000 in Finland.

Results show 52.6% women with rheumatoid arthritis committed suicide as against 17.3% women with non RA. 90% of RA women were suffering from depressive disorders before suicide. RA males were less depressive but committed suicide after short period of disease.

Disability and RA.[28]

Cohort study done to determine the impact of rheumatoid arthritis on employment status in the early years of diagnosis. Two cohorts of patient were chosen with similar employment status and cohort 1 with 162 patients and disease onset between 1989 and1992 and cohort 2 with 134 patients and disease onset between 1994 and 1997. The rates for work disability for the RA cases 1, 2, 5 and 10 yr after symptom onset were 14, 26, 33 and 39% respectively. For cohort 2, the rates for work disability 1 and 2 yr from onset were 23 and 33% respectively. This shows the aggressive nature of this disease.

ECONOMIC BURDEN OF DISEASE .

Rheumatoid arthritis posses great economic burden on patients due to expensive drugs ,multiple hospitalisation, rehabilitation costs and absence from work. A systemic review by Cooper NJ. of University of East Anglia, Norwich , UK estimates average cost of UK£3575-£3638 per patient per year.

Risk factors

It is multi factorial disease with interaction of both genetic and environmental factors. Exact cause is still unknown.

Gender.

It is 2-3 times more common in women.

Age

Incidence of this disease increases with age but it can occur at any age.

Genetic factors

Persons with positive family history of disease are more prone to develop this disease. It Contributes about 60 % in aetiology of RA.[29].It shows that environmental factors also contribute in aetiology of disease.

Socio-economic factors.

Some evidence in U.K. that poor prognosis in socially deprived people.[13]

Infectious agents.

Some infectious agents are implicated but evidence is poor .The probable agents are Parvovirus, rubella virus, Epstein-Barr virus, borrelia burgdorferi etc.[19]

Lifestyle.

Smoking is now established risk factor. It also aggravate the disease course.A study in Sweden concludes that smoking causes RF positive RA in both sexes.[30]

Hormonal factors

As this disease is more common in women so it seems that some hormonal factors might be involved. Many studies have been done to know the relationship between oral contraceptive pills and pregnancy with rheumatoid arthritis . Spector TD did the case control study(1990)[31] and suggest that oral contraceptives and parity is protective against rheumatoid arthritis. But in the same year he did metaanalysis on protective effect of OCP on RA[32] and he select 6 case control and 3 longitudinal. studies and concluded that OCP might not have any protective effect but may change the course of disease.

Prospective cohort study[33] of 140 women were followed from last trimester of pregnancy and 6 months postpartum. This study concluded that there was little effect of pregnancy on rheumatoid arthritis outcome plus great variability of disease. Researcher criticise the previous studies and make argument that many previous studies were retrospective (recall bias) without any validated methods and sample size was small.

This study was followed by another study in Netherlands[34] and came up with same conclusions but they followed cohorts for 12 years and ascertain that multiple pregnancies and ocp use before symptoms was associated with good outcome (less radiographic joint damage and a better functionallevel).

Dietary factors.

Some dietary factors also been implicated as risk factors but the evidence is not strong .Some dietary factors are also investigated for its beneficial role in alleviating the symptoms of rheumatoid arthritis but according to NICE guidelines [35]if we put patient on diet for long time the patient will develop some nutritional deficiencies.

Fish oil ,olive oil are beneficial for patients. [36][37][38]

Fasting and vegetarian diet also improves the pain score. [39]

Tea ,coffee and caffeine consumption .[40]

A cohort study was done in Birmingham, USA, started in 1986 in older women 31,336 women from age range of 55-69 years were selected without rheumatoid arthritis . By 1997 156 cases of rheumatoid arthritis were diagnosed. Results show the relative risk of 2.58, 95% CI 1.63-4.06 for women who consume >4 cups of decaffeinated coffee while for women with daily consumption of >3 cups of tea show RR of 0.39, 95% CI 0.16-0.97) compared with women who were never drinker of tea.

Ethnicity

More common in native Americans. But now there is evidence that incidence and prevalence is decreasing in this group as well.[41]

Detection and prevention.

Early diagnosis of disease is key in slowing the progression of rheumatoid arthritis. The diagnosis of disease is purely on clinical grounds. The only screening test or rheumatoid arthritis is detection of rheumatoid factor in blood. But it is non specific and can also be present in normal patients especially in older patients.

High risk patients especially with strong family history should be screened for RF and should be warned of smoking , becoming obese and taking balanced diet.

As we don’t know the exact cause of rheumatoid arthritis so unfortunately it cannot be prevented . efforts should be directed at early diagnosis of disease and then early start of aggressive treatment by disease modifying drugs .

Conclusion.

Rheumatoid arthritis is a destructive disease with no known cause and no cure and great variability in its expression and prevalence . Drugs are given to slow the progression of disease . Risk factors include positive family history , heavy smoking with long duration and ethnicity.

Recommendations.

Efforts should be directed at improving the quality of life of patients .
Decrease the waiting time for patients with rheumatoid arthritis.
More rheumatologist should be trained and recruited in developing countries. (In Kenya of 16 million population there is only one rheumatologist)
Drugs at cheaper rates should be supplied to developing countries.
Educate the people about early symptoms of disease and instructions regarding smoking cessation, weight reduction, exercise and balanced diet.

Future Research questions.

To know the exact cause of disease.
To know the exact relationship between diet and rheumatoid arthritis.

More studies need to be done in developing countries to know the exact incidence and prevalence .

References.

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4.Del Puente A, Knowler WC, Pettitt DJ, Bennett PH .High incidence and prevalence of rheumatoid arthritis in Pima Indians.
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