IN RHEUMATOID ARTHRITIS By
Dr. ATMA S. RAJ
Dissertation Submitted to The Tamil Nadu Dr. M.G.R. Medical University, Tamil Nadu in partial fulfillment of the requirements for
the degree of
DOCTOR OF MEDICINE
In Specialty of
GENERAL MEDICINE (BRANCH – I) COIMBATORE MEDICAL COLLEGE
COIMBATORE
APRIL 2015
t able of c ontents
No. Sl. Particulars Page Nos.
1. Certificate i
2. Declaration ii
3. Ethics Committee Certificate iii
4. Digital receipt issued by Turnitin iv 5. Plagiarism certificate issued by Turnitin v
6. Acknowledgments vi – viii
7. List of Abbreviations ix
8. List of Tables x
9. List of Figures xi
10. List of Graphs xii
11. Introduction 1 – 3
12. Aims and objectives 4
13. Review of literature 5 – 56
14. Methodology 57 – 62
15. Observation and results 63 – 84
16. Discussion 85 – 95
17. Conclusion 96 – 97
18. Summary 98 – 100
19. Bibliography xiii – xiv
20. Proforma xv – xvii
21. Consent Form xviii – xxi
22. Key to Master Chart xxii
23. Master Charts xxiii – xxvi
c ertificate
This is to certify that the dissertation “STUDY ON CARDIAC MANIFESTATIONS IN RHEUMATOID ARTHRITIS” is a bona fide research work done by Dr. ATMA S. RAJ, Post Graduate in M.D General Medicine under my direct guidance and supervision to my satisfaction, in partial fulfillment of the requirements for the degree of M.D General Medicine.
Date: Dr. M. RAVEENDRAN M.D.
Professor and Unit Chief, M-4
Date: Dr. KUMAR NATARAJAN M.D.
Professor and Head of Department Department of General Medicine
Date: Dr. REVWATHY M.D. D.G.O. D.N.B.
Dean Coimbatore Medical College
d eclaration
I hereby declare that this dissertation entitled “
STUDY ON CARDIAC MANIFESTATIONS IN RHEUMATOID ARTHRITIS”
is a bona fide and genuine research work carried out by me under the guidance ofDr. M. Raveendran M.D.
, Professor, Department of Medicine, Coimbatore Medical College, Coimbatore.Place: Coimbatore
Dr. ATMA S. RAJ
Date :
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a cknowledgements
This thesis would not have become a reality, but for the incessant and unconditional support and guidance of God Almighty, the extent of which can never be measured, nor be forgotten.
I would like to express my sincere thanks to The Dean,
Prof.
Rewvathy M.D D.G.O D.N.B
for her able guidance and encouragement, which was a constant source of inspiration.It is the presence of a few that one feels a clean sense of pureness and reverence, perhaps possibly only in front of those who have lived an exemplary life, in a principled way for a whole lifetime. And it is with this feeling that I must state that, it has been a privilege to work under my teacher and guide
Prof. M. Raveendran
M.D
., Department of General Medicine. His vast knowledge in the subject, his quest for perfection and uncompromising attitude towards quality, be it in my theses, in patient care or presentations, have been a great inspiration to me, and will surely leave a mark in my life. It is with a deep sense of respect and gratitude that I thank him for his ever helping nature and able guidance.It is my privilege and honour to extend my respect, regards and gratitude to
Prof. Dr. Kumar Natarajan M.D
., Head of the Department of General Medicine, Coimbatore Medical College, Coimbatore for all the encouragement and guidance and for the great teacher he is.I wish to extend my sincere gratitude to
Prof. S. Usha M.D., Dr. V. Usha Padmini M.D. and Dr. P. Balamurugan M.D
., Assistant Professors, Department of General Medicine for their ever affectionate and whole hearted help, every time I approached them.I would like to extend my sincere gratitude to
Prof. Dr A.
Mahesh M.D. DM, Department of Rheumatology
andDr.
Chakkaravarthy M.D DNB Cardiology
under whom I have worked during my theses, for their guidance and help.I am grateful to the director, administrator and all the officials of Coimbatore Medical College for their help and permission to carry out this study availing all the required facilities in this institution.
I am grateful to all my seniors and colleagues whose critics and praises gave me the push to complete my thesis.
I am extremely grateful to all the patients without whose cooperation this study would have been rendered incomplete.
I am quite aware that thanking the members of the family is quite unnecessary. However, the support given by them in making this thesis a reality can never be undermined, which has vehemently persuaded me to acknowledge my parents Adv. U. T. Rajan and Adv. P.P. Susheela as well as my in laws, Justice P.S. Gopinathan and Dr. P.R. Geetha MD, who very fondly cares and loves me as their own daughter. My sister, Mrs. Rukma S. Raj, my brother in law, Mr. Ramu Ramesh Chandra Bhanu and my sister in law, Ms.
Gayathri P.G. IRS, have also given me full support and encouragement throughout the progress of this thesis. Last but not the least, my husband, Adv. P.G. Jayashankar LL.M., BCL (Oxon.), who has been a source of constant encouragement, love, support and care and without whose aid this thesis would not have ever materialized, also requires a special mention, to whom I am inextricably indebted.
l ist of a bbreviations
1. ACR : American College of Rheumatology 2. CCP : Cyclic Citrullinated Peptide
3. DIP : Distal Interphalangeal Joint
4. DMARD : Disease Modifying Anti Rheumatic Drug
5. ESR : Erythrocyte Sedimentation Rate 6. HCQS : Hydroxychloroquine
7. JVP : Jugular Venous Pulse 8. LV : Left Ventricle
9. MTX : Methotrexate
10. MVP : Mitral Valve Prolapse
11. PIP : Proximal Interphalangeal Joint 12. RA : Rheumatoid Arthritis
13. RF : Rheumatoid Factor 14. SD : Standard Deviation 15. SJC : Swollen Joint Count 16. TJC : Tender Joint Count 17. TR : Tricuspid Regurgitation 18. MTP : Metatarsophalangeal joint
l ist of t ables
# Name of the Table Page No.
1 Pathological, echocardiography and clinical prevalence of
rheumatoid heart disease 34
2 Modified ACR criteria 1987 42
3 Classification Criteria for Rheumatoid arthritis 44
4 Steinbrocker’s functional classification 59
5 Mean age of patients and controls 64
6 Age and sex distribution in Rheumatoid Arthritis patients 64 7 Duration of disease and cardiac abnormalities in RA
patients 68
8 Correlation of subcutaneous nodules with cardiac
abnormalities 70
9 Rheumatoid factor and cardiac abnormalities 74 10 Baseline characteristics of RA patients and control subjects 75
11 ECG in RA patients Vs controls 76
12 Profile of patients with cardiac abnormalities 77 13 Comparison of variables between patients without cardiac
abnormalities with patients having cardiac abnormalities 78 14 Echocardiographic and Doppler variables in patients and
controls 81
l ist of f igures
# Particulars of Figures Page No.
1 Model for the etiology of Rheumatoid arthritis 11 2 Pathogenesis of rheumatoid arthritis 14
3 Rheumatoid arthritis -etiology 15
4 Pathogenesis of Joint involvement in Rheumatoid arthritis
18 5 Symmetrical joint involvement in Rheumatoid
arthritis
19
6 Rheumatoid arthritis usually affects joints 20
7 Ulnar and radial deviation 21
8 Swan neck deformity 22
9 Bountonniere deformity 22
10 Piano- key movement 23
11 Flat feet 24
12 Stages of Rheumatoid arthritis 25
13 Extra- articular manifestations of Rheumatoid arthritis 26
14 Rheumatoid nodule 28
15 Scleritis in a patient with Rheumatoid arthritis 31 16 Cervical spine involvement in Rheumatoid arthritis 32
l ist of g raphs
# Particulars of Graphs Page No.
1. Prevalence of RA in various population geographically 7 2. Incidence of RA decreases over 40- year period in
Minnesota study
9 3. Prevalence of selected autoimmune diseases 12
4. Age distribution with sex 65
5 Association of age with cardiac abnormalities in RA patients
66 6 Distribution of cardiac abnormalities with sex of the
patients
67 7 Association of duration of disease with cardiac
abnormalities
69 8 Positive correlation with subcutaneous nodules 71 9 Association of tender joint count with cardiac
abnormalities in RA patients
72 10 Association of swollen joint count with cardiac
abnormalities in RA patients
74 11 Association of rheumatoid factor with cardiac
abnormalities
74 12 Cardiac abnormalities by echocardiography 80 13 LVID diastole in patients & controls 81
14 LVID systole in patients and controls 82
15 EF in patients Vs controls 82
16. Diastolic dysfunction as suggested by E/A reversal 83 17 Diastolic dysfunction suggested by S/D ratio 84
i ntroduction
Rheumatoid arthritis is a chronic inflammatory disease of unknown etiology affecting approximately 1% of the adult population worldwide.1 Its primary target is the synovium where it results in uncontrolled proliferation of the synovial tissue. This results in excessive fluid production which leads to the erosion of the surrounding bone, ultimately damaging the tendons and ligaments.
Even though rheumatoid arthritis is principally a disease of joints, several extra – articular manifestations are also noted involving cardiac, pulmonary, haematological, ocular and neurological systems.
Rheumatoid arthritis has a prevalence between 0.7% to 1.5%. As per the studies by Malaviya et al, the prevalence of rheumatoid arthritis in Indian rural population is 0.75%.2 However, the recent studies show an increase of the prevalence rate at 1%.3
Jean Martin Charcot made a significant contribution towards the identification of cardiac lesions in patients with rheumatoid arthritis.4 He identified that out of a group of 9 patients who were clinically suspected to have rheumatoid arthritis, 4 patients had post-mortem findings of carditis. Thus he gave the initial description of cardiac involvement in
rheumatoid arthritis in 1881 by commenting that “cardiac lesions occurred pretty frequently in nodular rheumatism”.
Ever since a lots of research work were done on the same in many Western and European countries which came forth with many cardiac lesions in patients with rheumatoid arthritis including pericardial effusion, constrictive pericarditis, mitral stenosis, mitral regurgitation aortic regurgitation, aortic root dialatation, left ventricular systolic and diastolic dysfunction and pulmonary arterial hypertension.
Prakash et al (1973) did the first echocardiography in patients with rheumatoid arthritis from which they inferred that of the 16 RA patients evaluated with echocardiography 7 had pericardial involvement.5
According to the study of Wislowska and Kowalik, patients with nodular rheumatoid arthritis had more common cardiac involvement when compared to non-nodular RA.6
Jaunatey et al came out with the conclusion that the occurrence of LV dysfunction and pulmonary hypertension was more common in patients suffering from rheumatoid arthritis.7
When 39 patients of RA were compared with 40 control subjects, Maione et al found that 26% of patients with rheumatoid arthritis had left ventricular dysfunction.8
Rheumatoid arthritis patients having pericardial disease remains frequently asymptomatic during life. But autopsy of these patients revealed pericardial disease as a common finding. In 35 patients known to have rheumatoid arthritis were studied, Corrao et al found pericardial effusion to be the most common cardiac manifestation in these patients.9
When compared to western patients with rheumatoid arthritis, the Indian patients with RA are found to have a milder disease as well as lesser systemic manifestations, which was supported by Kaushal et al (1988).10
When the occurrence of subcutaneous nodules in RA patients from the white race were in the range of 20-30%, Malaviya et al (1993) reported that only 8.5% of north Indian patients with RA were having subcutaneous nodules.
a ims and o bjectives
AIM
To document the incidence of cardiac involvement in patients suffering from Rheumatoid Arthritis (RA)
OBJECTIVES
Ø To observe the cardiac manifestations in patients with RA by echocardiograph, collect the data, and to analyse the same.
Ø To investigate the correlation between RA and cardiac diseases.
Ø To find out the relation, if any, between cardiac lesions with the degree, severity and duration of RA.
r eview of l iterature
HISTORICAL ASPECTS
Soranus, an Ephesian, who lived in the 2nd century AD, wrote a treatise describing a poly-arthritis with morning stiffness in which the “joints become twisted with the toes and fingers either turned sideways or bent over backwards, or resting immovable upon their neighbours”.11 Charaka had indicated about chronic disease with joint swellings and subcutaneous nodules two thousand years ago.
However, such descriptions could also possibly point out to what might have been tophaceous gout. There is a description about a polyarticular disease characterized by remissions and exacerbations, which has been particularly explained as “the joints of his fingers have been as it were inverted and bulging out with the knots showing on their inner rather than the outer aspects of the fingers” in the translation from Latin by Short, of Sydenhams (1676) which perhaps is the first description of swan neck deformity.
Augustine Jacob Landre- Beauvais, a French medical student, in 1800, gave a detailed case report of rheumatoid arthritis, describing an acute onset of poly-arthritis in a 35 year old female, which gradually ceased leaving behind deformity of the wrists and hands.
Garrod coined the term rheumatoid arthritis in 1859.11 However the term rheumatoid arthritis came into use in 1941, prior to that it was known by many different terms such as proliferative arthritis, atrophic arthritis etc.12
The relationship between joint inflammation and heart disease was first suggested by Bouillaud in 1863.13 In 1881 Jean Martin Charcot described endocarditis and pericarditis in ‘chronic rheumatism’ differentiating cardiac disease in rheumatic fever from that in other forms of rheumatism (Rheumatoid heat disease).3
Echocardiographic assessment was first done to evaluate cardiac manifestations in RA by Prakash et al in 1973.4 The diagnosis of Rheumatoid arthritis is made on the basis of the modified ACR criteria.
PREVALENCE OF RHEUMATOID ARTHRITIS
Graph 1: Prevalence of RA in various population geographically
The incidence and severity of Rheumatoid arthritis is variable worldwide. Overall the prevalence ranges from 0.1-5.3%. The highest prevalence is seen in the Pima Indians, USA. The Native American Yakima, Pima and Chippewa tribes of North America showed prevalence rates of about nearly 7% studies from Africa and Asia has showed lower prevalence rates in the range of 0.2-0.4%. Its
incidence and prevalence of varies according to the geographic location both globally and also between the ethnic groups within the same country.
As in the case of many autoimmune diseases, the incidence of rheumatoid arthritis is more common among females with a female to male ratio of 2-3:1. Many theories have been proposed among which the role of oestrogen in enhancing the immune response holds stronger since oestrogen can stimulate the production of tumour necrosis alpha (TNF– α ). It is one of the most important cytokines implicated in the pathophysiology of rheumatoid arthritis.
In India the prevalence of rheumatoid arthritis2 in rural population of 0.7% according to Malaviya et al (1993). In the recent decades, the overall incidence of RA has been decreasing which can be attributed to the advanced treatment options in rheumatoid arthritis mainly after the introduction of methotrexate and early detection and initiation of treatment for the same.
Graph 2:
ETIOLOGY
Association of RA with many pathologic agents like viruses including retroviruses and Mycoplasma have been talked about but a clear cut etiologic could not be established. A specific pathogen resulting in RA is unlikely. In a genetically susceptible individual, molecules produced by the pathogens will result in repeated
inflammatory damage via induction of cytokines which ultimately result in breakdown of tolerance which further leads to autoimmunity.
Environmental factors add on to these events.
Possible Infectious Causes of Rheumatoid Arthritis
1. Mycoplasma
2. Parvovirus B19 direct synovial infection 3. Retroviruses
4. Enteric bacteria -
5. Mycobacterium molecular mimicry(QKRAA) 6. EBV (Ebstein –Barr virus)
7. Bacterial cell walls - Macrophage activation
FIGURE: 1 – Model for the Etiology of RA
There are many evidences supporting the role of genetic predisposition for the development of rheumatoid arthritis. The major risk for the development of rheumatoid arthritis is conferred to the presence of alleles located within the major histocompatibility complex (MHC) especially within the HLA- DRB1 gene which encodes the MHC II-beta chain molecule. The major role of HLA- DRB1 gene in this disease is due to the presence of the shared epitope in these alleles which is associated with the production of anti-CCP antibodies, which by itself go in for worse disease outcomes. Among the various alleles
held responsible, HLA –DRB1 allele *0401 is known to have a high risk for the disease whereas HLA-DRB1 *0101,*0404,*1001 and *0901 confers a moderate risk. In 50 -70 % of Northern Europeans, the major risk alleles belong to the *0401 or *0404 group whereas in Asians namely Japanese, Koreans and Chinese, the major susceptibility is to those with *0405 and *0901 alleles.
Graph 3:
The susceptibility to the development of rheumatoid arthritis have also been linked due to several non- MHC alleles, most of these associations being described in patients with anti–CCP antibody
positive disease. The presence of these alleles also is accounted for their association with other autoimmune diseases like Type -1 diabetes mellitus, systemic lupus erythematosis and multiple sclerosis in these patients.
AUTOIMMUNITY
Even many years before the onset of clinical arthritis, patients can have the evidence of autoimmunity in their body. RF’s and anticitrullinated protein antibodies, are the most common autoantibodies which can result in the development of rheumatoid arthritis. Autoantibodies recognized by RA are:
Ø joint antigens - type II collagen
Ø systemic antigens - glucose phosphate isomerase.
The autoantibodies can cause local activation of complement resulting in synovial inflammation .
PATHOGENESIS
The CD4+ cells are the most important orchestrators of cell mediated immune responses, and are responsible for the release and activation of a cascade of cytokines that are responsible for the disease whether it is at the local site of destruction at the joint synovial
membrane or the diffuse attack at the organ systems, responsible for the many extra- articular manifestations.
In genetic studies, rheumatoid arthritis is strongly associated with major histocompatibilty complex class II antigens HLA- DRB1*0404 and DRB1*0401.
Figure: 2 – Pathogenesis of RA
Th2 - type 2 helper T cell
Th0 is precursor of type 1 and type 2 helper T cells
In a genetically predisposed individual, the presence of environmental factors such as smoking and infectious agents like streptococcal infection and viral infections like Ebstien- Barr virus (EBV) and Parvovirus B19 and Mycoplasma trigger the development of RA by subsequent synovial T cell activation .
Figure:3 Rheumatoid Arthritis – Etiology
Antigen presenting cells (APCs) interact with the T cell receptor and class II major histocompatibility complex (MHC) peptide antigen resulting in CD4+ T cell activation. Synovial CD4+ T cells differentiate into Th1 and Th 17 cells. CD4+ Th cells in
turn activate the B cells to differentiate into plasma cells destined to produce the auto antibodies comprising the rheumatoid factors (RFs) and the anti- cyclic citrullinated peptide (CCP) antibodies inside the joints. This in turn activate the complement pathway and amplify the inflammation.
T - effector cells activate the synovial macrophages (M) and fibroblasts (SF) to secrete pro inflammatory mediators , the most important of which is tumour necrosis factor alpha (TNF-alpha).
This upregulates adhesion molecules on endothelial cell resulting in leukocyte influx into the joint.
The production of other inflammatory mediators like interleukin-1(IL-1), IL-6 and granulocye macrophage colony stimulating factor (GM-CSF) are also stimulated.
The integrity of any bone is determined by the balance between bone formation and bone destruction, of which the main role is played by TNF – alpha. A soluble mediator , Wnt , promotes osteoblastogenesis and bone formation. TNF- alpha upregulates the expression of DKK-1. The elevated levels of DKK-1 results in internalization of the Wnt receptors on the osteoblast precursors in turn leading to the inhibition of bone formation.
Osteoclastogenesis is the erosion of bone which also is influenced by many signalling molecules, especially TNF- alpha.
Receptor activator of nuclear factor k B ligand (RANKL) is expressed by stromal cells, synovial fibroblasts and T cells. RANKL will bind to its receptor RANK on the osteoclast precursors and in turn forms the activated osteoclasts resulting in bone resorption. The activity of RANKL is regulated by osteoprotegerin, a decoy receptor of RANKL that blocks osteoclast formation.
Thus the balance between bone formation and bone resorption is deranged in RA. The inflammatory mediators mainly TNF- alpha signals the increased bone resorption and decreased bone formation and finally bone remodelling at sites of inflammation.
Figure 4: Pathogenesis of Joint involvement in Rheumatoid arthritis
CLINICAL FEATURES
The start of the disease is usually insidious but can be episodic or acute. Between the age of 25 and 55 years, the incidence of rheumatoid arthritis increases, then until the age of 75 it plateaus and there after the incidence decreases. The symptoms of RA are mainly due to inflammation of the joints, tendons and bursae which manifests as early
morning joint stiffness lasting for more than one hour and which decreases with physical activity, typically involving the small joints of the hands and feet. Initially the joint involvement may be symmetrical monoarticular, oligoarticular (≤ 4joints) or polyarticular (>5joints).
Figure 5: Symmetrical joint involvement in Rheumatoid arthritis
When some patients presents with inflammatory arthritis but with very few features of joint involvement and other characteristics of RA, are classified undifferentiated inflammatory arthritis . These are the
patients who later get diagnosed as RA with high number of swollen and tender joints . They will be positive later for rheumatoid factor and anti - CCP antibodies and with higher physical disability.
Early disease is characterized by pain and other cardinal signs of inflammation. Damage and deformity usually does not occur early in the course of the disease. The most frequently involved joints are the wrists, metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints.
Figure 6
The involvement of distal interphalangeal (DIP) joints can occur in rheumatoid arthritis but mostly it may be due to the coexistence of osteoarthritis.
Many a number of irreversible deformities do occur in rheumatoid arthritis as a result of progressive destruction of the joints and soft tissue. These include
Ø Ulnar deviation – due to subluxation of MCP joints with subluxation of proximal phalanx to the volar side of the hand.
Figure 7
Ø Swan neck deformity- hyperextension of the PIP joint with flexion of the DIP joint.
Figure 8: Swan neck deformity
Ø Bountonniere deformity – flexion of the PIP joint with hyperextension of the DIP joint.
Figure 9: Bountonniere deformity
Ø Z-line deformity - subluxation of the first MCP joint with hyperextension of the first interphalangeal joint.
Ø Piano- key movement of ulnar styloid – subluxation of the distal ulna due to inflammation around the ulnar styloid and tenosynovitis of the extensor carpi ulnaris.
Figure 10
Ø Flat feet – inflammation around the ankle and mid tarsal region
Figure 11: Flat Feet
Another important joint involved in RA is the atlantoaxial joint of the cervical spine. Its potential to cause compressive myelopathy and neurologic dysfunction, though rare, makes it clinically significant.
When compared to other spondyloarthritides, the involvement of thoracic and lumbar spine is very unusual in rheumatoid arthritis.
Figure 12: Stages of Rheumatoid arthritis
EXTRA – ARTICULAR MANIFESTATIONS
Extra – articular manifestation of rheumatoid arthritis can occur during the course of rheumatoid arthritis or even before the appearance of arthritis. Since rheumatoid arthritis is a systemic disease, the constituitional symptoms like low grade fever, fatigue and weight loss are very common, and especially it tends to occur more commonly in patients with positive rheumatoid factor. The most commonly observed extra – articular manifestations include anemia, pulmonary nodules, subcutaneous nodules and secondary Sjogren’s syndrome. Some of the
manifestations like Felty’s syndrome and vasculitis are almost becoming of decreased incidence now.
Figure 13: Extra – articular manifestations of Rheumatoid arthritis
RHEUMATOID NODULES
These are subcutaneous nodules which are non-tender and firm with a characteristic histologic picture. The typical sites of occurrence of these nodules are on the extensor surfaces and other pressure points like forearms. They are almost exclusively found in those patients who are seropositive for rheumatoid factor. If a patient presents with rheumatoid nodules but absent rheumatoid factor, then a careful assessment should be done to rule out other possibilities like chronic tophaceous gout. Rarely they can also present in the sclera and also in the viscera like in the lungs and the heart.
The mature rheumatoid nodule has a central area of necrosis which is surrounded by a corona of palisading fibroblasts. This is further surrounded by a collagenous capsule with perivascular collections of chronic inflammatory cells.
In patients with definite or classic rheumatoid arthritis, almost 15 to 20% of patients will have rheumatoid nodules. But sometimes patients may present with multiple rheumatoid nodules over the hands without any obvious arthritis, and such a condition is called rheumatoid nodulosis. Many a clinicians have observed that some patients who are on methotrexate , the cornerstone drug in the treatment of rheumatoid
arthritis, may develop new nodules or enlargement of the existing nodules. Though the exact pathophysiology behind this mechanism is not known, stopping methotrexate in these patients may lead to regression of these nodules. The histologic picture of these nodules suggest their development due to the triggering by small vessel vascultits.
Figure 14: Rheumatoid nodule
PULMONARY DISEASE
Pleural disease is usually small and asymptomatic. This is more common in men. They usually have low pH with low glucose and many a times it misleads the treating physicians by giving a picture
simulating that of empyema. It can also manifest as nodules in the lung, again making it difficult to differentiate it from cancer, which necessitates an excisional biopsy. Diffuse interstitial fibrosis result in dyspnoea which can later on lead to the development of honeycomb pattern in the chest radiograph.
When compared to yester years, the incidence of pulmonary hypertension shows a rising trend which though usually asymptomatic, can be picked up by non invasive echocardiographic examinations. Up
to 30% of patients with rheumatoid arthritis are found to have mild pulmonary hypertension as shown by echocardiograms.
VASCULITIS
One of the most dreaded complication of rheumatoid arthritis is systemic rheumatoid vasculitis, which has become increasingly uncommon in the recent years. This decline is due to the marked improvement in the treatment of rheumatoid arthritis including methotrexate and other biological agents.
Clinical vasculitis usually presents as follows
Ø Distal arteritis (including from splinter hemorrhage, nail fold infarcts, and gangrene )
Ø Palpable purpura
Ø Peripheral neuropathy (mononeuritis multiplex)
Ø Arteritis of viscera, including heart, lungs, bowel, kidney, liver, spleen, pancreas, lymph nodes, and testis
Ø Cutaneous ulceration (including pyoderma gangrenosum)
OCULAR
Keratoconjunctivitis sicca (dry eyes) from secondary Sjögren syndrome is the most common ophthalmologic manifestation of RA.
Other manifestations of rheumatoid arthritis in eye are scleritis and epislcleritis and it occurs in less than 1% of patients with rheumatoid arthritis.
Figure 15: Scleritis in a patient with rheumatoid arthritis
NEUROLOGICAL
Neurological manifestations of rheumatoid arthritis include mainly peripheral nerve entrapment syndrome including carpal tunnel syndrome and tarsal tunnel syndrome. Other conditions include subluxation of C1-C2 producing myelopathy and mononeuritis multiplex produced by vasculitis.
Figure 16: Cervical spine involvement in Rheumatoid arthritis
HAEMATOLOGICAL
The most common haematological abnormality in rheumatoid arthritis is normocytic normochromic anaemia. This is seen usually in anaemia of chronic disease. This anaemia correlates with ESR and the disease activity , thus a very high ESR and severe anaemia is related to high disease activity. One of the characteristics of this anaemia is that three- fourth of such anaemia will respond well to treatment of rheumatoid arthritis and one fourth will respond to iron therapy.
Also associated with rheumatoid arthritis is thrombocytosis with it having a very significant relationship with disease severity. Only exception is the presence of Felty’s syndrome which is a triad of rheumatoid arthritis, splenomegaly and neutropenia. It is mainly seen in patients with very severe rheumatoid arthritis which is accompanied by fever with hepatomegaly, thrombocytopenia and lymphadenopathy.
Some patients with rheumatoid arthritis have large granular lymphocytes with nearly complete absence of neutrophils which is known as “large granulocyte lymphocyte syndrome”, which is thought to be a form of T-cell leukemia.
CARDIOVASCULAR DISEASE
Patients with rheumatoid arthritis can develop various cardiac manifestations including pericarditis, myocarditis, endocardial inflammation, atherosclerosis, conduction defects, coronary arteritis, granulomatous aortitis or valvular disease. One of the most common cause of premature death in patients with rheumatoid arthritis is the cardiac involvement especially cardiac failure and myocardial infarction.
Pathogenesis and clinical presentation of cardiac involvement in patients with rheumatoid arthritis in comparison to echocardiographic assessment has been shown in the table.
Table 1
Pathological, echocardiography and clinical prevalence of rheumatoid heart disease13
PERICARDIAL DISEASE
The most common cardiac complication of Rheumatoid arthritis is pericarditis. It is found in 30-50% of autopsy cases29-31 and in up to 30% by echocardiography.
Autopsy(%) Echocardio graphy(%)
Clinical(%)
Pericarditis 11-50 20-40 1-4
Myocarditis
Focal,non specific Diffuse, necrotizing Granulomatous
30 Rare Rare
4-30 - -
Rare - -
3-5 - -
Amyloid infiltration Rare - - Conduction system
disease
unknown - rare Valvular disease 6-50 30-40 rare Coronary artery disease 15-20 - rare
Histopathology shows chronic inflammation and fibrosis. The pericardial fluid is usually a clear exudate with high protein and lactate dehydrogenase, low glucose and containing mainly neutrophils.
The commonest symptom is dull central or sharp pleuritic chest pain, dyspnoea, peripheral oedema and hepatic or gastrointestinal congestion may occur in constrictive disease. In tamponade , symptoms and shock can rapidly develop and require emergency intervention.
Pericardial rub occurs in 30-40% of clinical cases. Other signs (tachycardia, ectopic, diminished heart sounds) are non-specific. Pulsus paradoxus and Kussmaul’s sign may occur. In constriction, a pericardial knock may be heard due to early cessation of ventricular filling. Constriction associates with high jugular venous pulse and a prominent y descent of early ventricular filling.
Harle et al reported a case of constrictive pericarditis in a 39 years old female with seropositive rheumatoid arthritis of 17 years duration who succumbed to progressive constrictive pericarditis. Their report emphasized the importance of early diagnosis of constrictive pericarditis in any patient presenting with features of congestive heart failure and also the importance of early pericardiectomy over sole medical therapy.32
MYOCARDITIS
Myocarditis is found in upto 30% of autopsy cases. It can be diffuse or focal, non- specific or pathognomonic nodular rheumatoid myocarditis. The compact anatomy and relationship of the atrioventricular node to the aortic root and interventricular septum make it vulnerable to damage from inflammation of adjacent structures and can lead to conduction abnormalities. Amyloid deposition in RA is associated with restrictive cardiomyopathy.
ARTERITIS
It is present in upto 20% of autopsy cases, affecting mainly medium sized and small intra myocardial arteries. This may lead to patchy myocardial necrosis due to micro infarction or ischemia.33, 34
Corraro et al studies 35 patients of RA and found that 61.1% of patients had pericardial effusion. Mitral valve thickening was seen in 22.9%, aortic root dilatation in 34.3%, isolated mitral regurgitation, mitral valve prolapse and isolated aortic regurgitation in 5.7% each.
None of their patients had any cardiac symptoms or signs.17
Maione et al studies 39 patients of RA and compared them with 40 control subjects. Their study revealed ventricular diastolic dysfunction in 26% of RA patients. This was the only statistically
significant abnormality between the two groups. Pericardial disease constituted only 3 (7.7%) patients and pericardial adhesion in 1 patient.7
Wisloska, Sypula and Kowalik studied 35 patients with RA having subcutaneous nodules and compared them with 35 patients without nodules and 35 control subjects. Their study revealed a significantly higher incidence of cardiac involvement (71.9%) in RA patients with subcutaneous nodules as compared with 42.9% in non- nodular RA and 22.9% in the control group.5
Jaunatey et al studies 47 patients of RA and compared them with 47 control subjects. Their study showed a significant left ventricular diastolic dysfunction and pulmonary hypertension in patients with RA as compared to control subjects. There was no significant difference between the groups in pericardial involvement, valvular regurgitation and aortic root diameter.6
146 RA patients were evaluated by Dawson et al which showed significant cardiac disease ie reduced left ventricular dysfunction in 9%, moderate mitral regurgitation in 4%, aortic stenosis in 4%, pericardial disease in 1%. In 21% of patients in whom pulmonary function test where done, they were found to have pulmonary hypertension without associated lung disease.18
There was a higher incidence of ischemic heart disease in patients with RA as supported by Rincon et al study. According to the study, the incidence of cardiovascular events were higher in rheumatoid arthritis patients, which could not be explained by cardiac risk factors.
A number of studies were evaluated by Kita and Erb 19 which led to the conclusion that the cause of ischemic heart disease in RA is multifactorial. The cardiac events in RA were strongly influenced, either directly or indirectly by the treatment modalities in RA. In the treatment of RA the role of NSAIDS were so important, which were later known to increase hypertension risk in these individuals and which lead eventually to congestive cardiac failure.
Another important risk factor was the use of methotrexate in RA and its relationship with hyperhomocysteinemia. Hyperhomo- cysteinemia by itself was an individual risk factor in RA for the occurrence of cardiac involvement.
This was evaluated by Landewe et al20 in patients. A cohort study enrolling 623 (six twenty three) patients were followed up for a period of 12 years. The patients in whom methotrexate was used as the treatment modality had higher incidence of cardiovascular events (crude
risk ratio - 4.1). The study emphasised the role of homocysteine in RA which was elevated in methotrexate receiving patients.
C OURSE OF THE D ISEASE
According to the recent epidemiological studies, it has been showed that the incidence of rheumatoid arthritis is declining. This can be attributed not to the change in the pattern of the disease over years, but to the earlier and effective treatment modalities in the current era, especially the disease modifying anti- rheumatic drugs (DMARDs).
In a case of well established rheumatoid arthritis, the median life expectancy is less when compared to the control population. Although the traditional factors associated with excess mortality in rheumatoid arthritis patients were infection, renal failure and respiratory failure, now it has been studied that the major killers in rheumatoid arthritis are congestive cardiac failure, ischemic heart disease and peripheral atherosclerosis. In a 25 year prospective follow up study done in 208 patients with rheumatoid arthritis, the data was that the median life expectancy was reduced by 7 years in men and 3 years in women. What is the reason for this increasing cardiovascular complications in patients with rheumatoid arthritis? The reasonable explanation given is that in rheumatoid arthritis, a large amount of inflammatory cytokines
are produced like tumour necrosis alpha and platelet derived growth factor, which will activate the endothelial and subendothelial myofibroblasts, all of which contribute to accelerated atherosclerosis.
Thus the factors contributing to atherosclerosis in patients with rheumatoid arthritis are
Ø Inflammatory cytokines
Ø Prothrombotic factors (e.g., increased platelets, fibrinogen, and thromboxane
Ø Medications (e.g., steroids
Factors associated with poorer prognosis in rheumatoid arthritis
Ø Positive rheumatoid factor in serum
Ø Positive anticitrullinated protein in serum Ø Rheumatoid nodules
Ø Depression
Ø Elevated Health Assessment Questionnnaire level of disability Ø Persistent ESR elevation (serving as a surrogate for disease
control)
Ø Presence of shared epitope(QKRAA)on class II major histocompatibilty genes.
ACR criteria for clinical remission of RA
15A minimum of 5 of the following criterion should be present for at least two consecutive months
Ø Morning stiffness not to exceed 15 minutes Ø No fatigue
Ø No joint pain
Ø No joint tenderness or pain on movements
Ø No soft tissue swelling in joints or tendon sheath
Ø ESR less than 30 mm / hour (females) and <20mm / hour (males)
Patterns of progression
16§ Monocyclic pattern
ü A single cycle with remission for at least one year ü Seen in 20% of patients.
§ Polycyclic pattern
ü Intermittent or continuing subtypes.
ü Seen in 70% of patients
§ Progressive patterns
ü Seen in 10% of patients,
ü Progressively increasing joint involvement.
DIAGNOSIS
MODIFIED ACR CRITERIA-198714
This is 92% sensitive and 89.3% specific. At least 4 criteria’s must be present of the following in a given patient and criteria 1-4 should be present for a period of 6 weeks to make a diagnosis of RA.
In order to improve early diagnosis of RA patients so as to benefit them from the early introduction of disease-modifying therapy, the 1987 ACR classification was revised in 2010 by the collaborative effort between American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). This new Classification Criteria introduced a positive test for serum anti-cyclic citrullinated peptide (anti-CCP) antibodies, which has greater specificity for the diagnosis of rheumatoid arthritis than rheumatoid factor. With a diagnostic specificity of 95%, it has become a valuable biomarker of diagnostic as well as prognostic significance.
This newer criteria is a “classification criteria” as opposed to a
“diagnostic criteria” and does not consider the presence of rheumatoid nodules or joint damage since the occurrence of these findings are very rare in early RA.
Table 3
Classification Criteria for Rheumatoid Arthritis
Thus this classification criteria has a score from 0-10 and a score
≥6 fulfill the definitive diagnosis of Rheumatoid arthritis.
LAB FINDINGS AND IMAGINGS
Majority of the patients with RA have anemia of chronic disease, thrombocytosis and raised acute phase reactants especially ESR and CRP. The degree of anemia is proportional to the activity of the disease and the normalization of the hemoglobin can be seen once the therapy for controlling the disease has been started. Once the inflammation has been controlled the platelet count may also return to normal. The elevated ESR and CRP is proportional to the disease activity. The persistent elevation of these parameters shows a poor prognosis both in terms of joint destruction and mortality. The total blood count may be normal, elevated or severely depressed (as in case of Felty’s syndrome).
The most characteristic laboratory abnormality in RA is the presence of rheumatoid factor. It is an autoantibody directed against the constant (Fc) region of IgG. At the time of presentation with the disease, about 50% of cases are positive for rheumatoid factor. The rest of the 20–35% of cases shows positivity in the first 6 months after diagnosis of RA. Even though the presence of rheumatoid factor is not unique to RA, its presence in rheumatoid arthritis is implicated with more severe articular disease. Almost all patients with the extra- articular features are seropositive for rheumatoid factor. Lately it is
found that autoantibodies most specific for RA are directed against citrullinated proteins, anticyclic citrullinated peptide (anti-CCP) antibodies, which are present are present in 60–70% of patients with RA at diagnosis. Anti -CCP are 90–98% specific for RA and they are often present in the serum years before RA is diagnosed (similar to rheumatoid factor), and have a strong correlation with erosive disease.
RA is also associated with multiple other autoantibodies, especially antinuclear antibodies (30% of patients) and antineutrophilic cytoplasmic antibodies (ANCA , especially in the perinuclear type (seen in 30% of patients).
Differential of a positive rheumatoid factor
Ø Rheumatic diseases Ø Infections
Bacterial: Endocarditis, osteomyelitis
Viral: Hepatitis C, parvovirus, influenza, EBV Ø RA, SLE, Sjogren syndrome
Ø Chronic inflammatory conditions
Ø Liver disease, inflammatory bowel disease Ø Aging
DIFFERENTIAL DIAGNOSIS
Many a diseases can mimic Rheumatoid arthritis, especially in the early course of disease.
Ø Acute viral syndromes
Ø Hepatitis B & C, EBV, Parvovirus, Rubella Ø Systemic lupus erythematosis
Ø Psoriatic arthritis Ø Reactive arthritis Ø Hypothyroidism Ø Paraneoplastic
Ø Chronic tophaceous gout Ø Osteoarthritis
Acute viral syndromes can produce a polyarthritis that mimics RA. But this is usually self-limited, usually resolving over 2–4 weeks.
Osteoarthritis with severe deformities of the hands from bony proliferation of the DIP and PIP joints (Heberden and Bouchard nodes)
may confuse some inexperienced clinicians; the keys here are DIP joint involvement and the bony, instead of soft tissue, joint abnormalities.
TREATMENT
For patients with a symmetric polyarthritis in three or more joint areas involving the hands, feet, or both for at least 6 weeks, and a presumptive diagnosis of RA, aggressive treatment is warranted.
Patients generally are apprehensive and concerned about developing a chronic, debilitating disease. Anxiety, depression, loss of self-esteem, inability to work, and an inability to develop new coping behaviours may evolve. This “learned helplessness” must be combated by education, reassurance, counselling, and the confident attitude of the physician. Most important is the initiation of a program to down regulate the activity of the synovitis with the goal of inducing a remission, or at least marked improvement, in the disease. Disease- modifying therapy is indicated at this point as are some adjunctive therapies. Early intervention may offer the greatest likelihood of preventing disability, and there may be a window of opportunity to have a significant impact on the trajectory of the disease over a lifetime.
The treatment of rheumatoid arthritis begins with the diagnosis, estimation of the patients prognosis and the chalking out of a therapeutic
plan. The first and foremost thing is the starting aggressive treatment with disease- modifying anti rheumatic drugs (DMARDS). When the diagnosis of rheumatoid arthritis has been made and if the patient is having very little features of inflammatory arthritis due to other causes like infection, malignancy or metabolic diseases, we should initiate the patient with DMARD therapy as soon as possible, because this is the only effective way of preventing or controlling the joint damage and for preventing loss of function and for reducing the pain.
The fundamental treatment plan for inflammatory arthritis are DMARDs and all other therapeutic approaches for rheumatoid arthritis are just adjuncts to this.
Keys to optimize outcome of rheumatoid arthritis:
Ø Early diagnosis
Ø DMARD therapy as early as possible Ø Strive for remissions in all patients
Ø Recognize and treat co-morbid conditions
Ø Cooperation and communication between primary care physician and rheumatologist
The aim of treatment is achieving remission and further maintenance of remission by continuing therapy. Early DMARD therapy is associated with better long-term outcomes.
IMPORTANT ADJUNCTS Ø Education
Ø Pain Control
Ø Rest, Exercise and activities of Daily Living Ø Role of the Rheumatologist in Management Ø Complementary Therapy and Diet
ASSESSING RESPONSE TO THERAPY
Assessing the effectiveness of a therapeutic approach is crucial to the appropriate management of an individual patient. In most clinical practices, this assessment is done by physician gestalt or global assessment after a careful history, examination, laboratory studies, and radiographs. In most situations, this approach leads to quality care.
However, when intensive monitoring is applied with a goal of tighter control, better outcomes can be achieved.
ESTIMATING PROGNOSIS
The challenge for the physician is to form an appreciation for the severity of a patient's disease and formulate a treatment plan accordingly. A patient who has low-grade attacks of synovitis that are separated in time from each other would be much less likely to advance to joint deformity than a patient who has continuous, highly active synovitis.
Factors suggesting a poor prognosis:
1. Generally severe or aggressive baseline disease 2. poor function
3. presence of rheumatoid factor and anti-CCP antibodies 4. elevation of acute-phase markers
Presence of erosions and narrowing of joint space on imaging studies early in the disease also are predictive of more destructive disease.
FUTURE DIRECTION
The growing body of data lends credence to the belief that early diagnosis and initiation of therapy in RA is appropriate and necessary to maximize the short-term and long-term benefits to the patient. It may
afford a window of opportunity for substantive disease modification, which may lead to long-term protective benefits. In addition to the growing emphasis on early intervention, the rheumatology community is continually striving to improve overall response rates among current patients and to expand intervention into untreated populations.
There also is a strong desire to develop therapies that work in 90% to 100% of patients, not the 60% seen today. The long-term goal of treatment intervention should be to achieve remission. Although a unique opportunity for intervention may exist early in the course of disease, it is believed that DMARDs should be introduced at all stages of disease for long-term disease modification. What also has become fundamentally clear is that even in later stages of disease, the use of DMARDs can reduce symptoms and signs, improve function, and slow structural progression.
The remarkable efficacy and safety of biologic agents has been reassuring. Monitoring for adverse events and for unforeseen occurrences must continue, however. Differences between agents also warrant considerable research. It may be that different populations and disease states would be better suited to one or another agent as monotherapy or particularly in combination with other agents. In the
future, we may see improvements in combination approaches including combination biologic agents. To date, combination biologic approaches have led to increased risks of infection, however. With the right targets or the appropriate modulations of dosages, we may be able to overcome this increased risk.
The future may see additional agents being used as adjuncts. An example would be the use of statin agents. 3-Hydroxy-3-methylglutaryl- coenzyme A (HMG-CoA) reductase inhibitors (statins) have significant benefits toward lowering cholesterol and reducing risks of cardiovascular events. The fact that patients with RA are at increased risk of cardiovascular mortality itself might be reason to consider statin use. Statins may influence other inflammatory factors, however, effecting the symptoms and signs of disease. In one study, 116 patients with RA were randomly assigned to receive placebo or 40 mg of atorvastatin in addition to their existing DMARD regimen. After 6 months, significant improvements were seen in disease activity scores and reductions in C-reactive protein and erythrocyte sedimentation rates, suggesting modest anti-inflammatory effects.
In the years ahead, it will be increasingly important for rheumatologists and primary care physicians treating patients with RA
to expect rigorous confirmation of efficacy and safety by double-blind, placebo-controlled studies of all new products and long-term registries to ensure the safety of these agents in the long run. Physicians must be armed with data because their patients will be armed with testimonies from the Internet and convincing ads from television, newspapers, and magazines for many diverse therapies. Another issue will be finding suitable patients to enrol in studies of the most promising medications that are ready to move into advanced phase trials. Rheumatologists must take a leading role in ensuring their patients have the chance to participate in studies of the most promising drugs and devices.
m ethodology
The study is undertaken on the patients approaching the out- patient (OP) department as well as the IP department of the Coimbatore Medical College Hospital, Coimbatore during the period of study (ie September 2013 to August 2014). A total of fifty (50) subjects who had, approached the Rheumatology Department in the Hospital, and having satisfied the modified ACR (2010) criteria were selected for the study.
These patients were compared with another fifty (50) control group, who had come to the OP department for non-specific complaints. The control group was selected on a random basis.
SELECTION CRITERIA (a) Inclusion criteria
Ø Adult patients (both sex) between the age group of 18 to 60 Ø Patients satisfying modified ACR criteria (2010) for RA
(b) Exclusion criteria
Ø Pregnant women
Ø Minors (below the age of consent)
Ø Persons suffering from congenital heart diseases Ø Persons suffering from ischemic heart diseases Ø Persons suffering from valvular heart diseases Ø Persons suffering from hypertension
Ø Persons suffering from diabetes mellitus
Ø Persons not capable of giving consent (psychiatric patients ) Ø Persons unwilling to undergo the study (who refused to consent)
All patients were evaluated with : ü Detailed history
Age, sex, duration of RA, presence and duration of morning stiffness, chest symptoms, list of painful joints, presence of other systemic disease, and history of extra- articular manifestations of RA were documented. Treatment history was also taken. Functional status of the patients was recorded on the Stienbrocker’s scale.
ü Examination
A systemic examination of all joints were done for features of activity, tender joint count and swollen joint count estimation was done.
ü Tender joint count and swollen joint count
A simplified 28 joint articular index was described by Fuch’s et al was used to assess disease activity. Twenty – eight joints included 10 proximal interphalangeal joints of fingers, 10 metacarpophalangeal joints, and the wrist, elbow, shoulder and the knee joints bilaterally.21
Cardiovascular examination was done in detail. Abdominal, respiratory and neurological examination was done. Extra- articular manifestations were carefully looked for and documented.
Table 4
ü Investigations
The following investigations were done with special emphasis:
Erythrocyte sedimentation rate (ESR)
Was obtained by Westergren method. Venous blood was anti- coagulated with tri sodium citrate dihydrate in the ratio of 4:1 and
thoroughly mixed by gentle, repeated inversion and used to fill a Westergren - Katz tube to the zero mark. The tube was then replaced in a vertical position in a rack, which is not exposed to direct sunlight, draught or vibration and incubated at room temperature for 60 minutes.
After this time, the distance (in mm) form the bottom of the surface meniscus to the top of sedimenting red cells read and reported as the ESR result. Tests were performed within 2 hours of taking the blood sample.
Rheumatoid factor (IgG)
A quantitative assay was performed using a latex fixation Lab kit.
C-reactive protein
Quantitative assay was performed using latex agglutination kit Routine investigations
Hemoglobin estimation, Blood urea, serum creatinine and blood sugar estimation was done
Echocardiography
With the patient in supine and left lateral position using a Hewlett Packard Sonos 2500 scanning machine, M-mode, two dimensional and Doppler echocardiography was performed. Cardiac position, cardiac
chambers, atrial and ventricular septae, valves, pericardium, great vessels, ejection fraction, peak velocities across valves and grading of regurgitations if any, were documented.
Doppler echocardiography was employed to obtain left ventricular filling profile from trans mitral flow. To record trans mitral flow the ultrasonic beam was aligned as much as possible to the blood flow direction and the highest clear signal was considered.
The following variables were evaluated as indices of left ventricular filling: Peak early (E) and late (A) trans mitral filling velocities and their ratio (E/A), slope of the descending limb of the E wave (slope EF) and deceleration time (DT) defined as the time interval required for the E velocity to decline from its peak to the base line.
To obtain pulmonary venous flow the sample was placed at the orifice of the left anterior pulmonary vein. The variables measured included peak pulmonary venous flow velocity during ventricular systole (S), peak pulmonary venous flow during ventricular diastole (D) and S/D ratio were estimated. Left ventricular mass was calculated using the Penn convention.23
Elecrocardiography
A 12 lead electrocardiogram was performed on all subjects of the study.
Radiographic assessment
Routine PA view chest X-rays were taken for all patients and controls.
STATISTICAL METHODS
Descriptive statistics that is, mean with standard deviation and frequency distributions were performed for continuous and categorical variables, respectively. To see significant differences between the groups for continuous variables, students “t” test (unpaired two tailed) was performed and to see the difference between the means in skewed distribution, Mann Whitney U test was used. For comparing categorical variables, Chi square and Fisher’s exact test were used, p ≤ 0.05 has been considered as statistically significant.
o bservation and r esults
The study is undertaken on the patients approaching the outpatient (OP) department as well as the IP department of the Coimbatore Medical College Hospital, Coimbatore during the period of study (ie September 2013 to August 2014). A total of fifty (50) subjects who had, approached the Rheumatology Department in the Hospital, and having satisfied the modified ACR (2010) criteria were selected for the study.
These patients were compared with another fifty (50) and control group, who had come to the OP department for non-specific complaints. The control group was selected on a random basis.
AGE AND SEX DISTRIBUTION
The study included 50 patients with rheumatoid arthritis and 50 control subjects. Out of the 50 patients, 31 were females and 19 were males. The age and sex distribution of patients with rheumatoid arthritis is shown in table 6 and that of control subjects in table 7.
Table 5: Mean age of Patients and Controls Total Males Females Mean age
(years)
Patients 50 31 19 42.70
Controls 50 23 27 41.64
In the study group the maximum incidence of rheumatoid arthritis was between 24 to 50 years (93%) age group. The youngest patient was 24 years and the oldest patient was 62 years. The mean age group of the patients with RA was 42.7 years with a standard deviation of 9.98 years.
The disease was found to be more common in females with a male to female ratio of 1:1.6 (3:5). Cardiac abnormalities among these patients were seen maximum in 41-50 years age group.
Table 6: Age and Sex Distribution in Rheumatoid Arthritis Patients Age groups
(years)
No. of cases (%)
Females (%)
Males (%) 20-30 6 (12) 3 (50) 3 (50) 31-40 15 (30) 8 (53.3) 7 (46.7) 41-50 19 (38) 11 (57.9) 8 (42.1) 51-60 8 (16) 7 (87.5) 1 (12.5) 61-70 2 (4) 2 (100) 0 (0)
TOTAL 50 31 19
Graph 4: Age distribution with sex in RA patients
0% 20% 40% 60% 80% 100%
20-30 31-40 41-50 51-60 61-70
Percentage
Ag e in ye ars
Females Males
In the present study, till the age of 50 years, both males and females are almost equally affected with rheumatoid arthritis and after the age of 50 years, a female preponderance is seen.
