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Product Details
| ISBN-13: | 9781463431310 |
|---|---|
| Publisher: | AuthorHouse |
| Publication date: | 09/19/2011 |
| Sold by: | Barnes & Noble |
| Format: | eBook |
| File size: | 5 MB |
Read an Excerpt
A Handbook Of Rheumatic Fever
By Alok Ranjan
AuthorHouse
Copyright © 2011 Dr. Alok RanjanAll right reserved.
ISBN: 978-1-4634-3133-4
Chapter One
Rheumatic Fever (RF)
Introduction
Definition:
Rheumatic fever is expressed as autoimmune inflammatory reaction to collagen fibrils and to the ground substance of connective tissue leading to multisystem involvement and is presumed to be due to antigen mimicry of group A, ß-hemolytic streptococcal pharyngeal infection (GABHS).
RF is the most common cause of acquired heart disease in children and young adults worldwide.
Historical Aspects
Rogers (1910): Noted the extreme rarity if not complete absence of RF in India. He observed "Tropical countries differ in a remarkable way from the temperate in almost complete absence of RF". Although RF used to be considered a disease of temperate climates, it is now more common in tropical countries, particularly in developing countries
Drury: First ever etiological classification of circulatory diseases in India
Kutumbiah (1935): First Indian doctor to report that rheumatism in childhood was very common in India.
Incidence and Prevalence
Incidence
Peak Incidence: 5-15 yrs (School going children)
< 5 yrs.: It is not uncommon to see Acute Rheumatic fever (ARF) in children less than 5 years also. In Indian series up to 40% episodes have been documented in less than 5 years of age. The youngest age of child reported with ARF is 3 yrs.
National (India) average
6/1000 (Padmawati et al)
In her series, Delhi recorded the highest incidence of 11/1000 children.
ICMR (Indian Council of Medical Research):
This study conducted on school children showed higher incidence in urban school children (3.7 – 8 per 1000) as compared to rural school children (3.5 per 1000)
Prevalence:
Prevalence in Indian population is higher than developed countries
US: 0.6 per 1000
Different studies in India have shown following figures: Prevalence
Total population Berry (1972): 1.62/1000 Dhawan/Grover: 0.9/1000
School Children Agarwal: 0.31 % Padmawati: 0.15 % Rao: 0.10 % Devichand: 3.96 %
Reasons for higher and persistently high prevalence in India:
1. Overpopulation 2. Poverty 3. Illiteracy 4. Over crowding 5. Lack of access to medical care 6. Poor compliance (Drop out rate from secondary prophylaxis was 30 %)
Pathogenesis
Actual pathogenesis of acute rheumatic fever (ARF) remains hypothetical. There is strong but indirect evidence that Group A Streptococci (GABHS) causes initial and recurrent attacks of RF.
The GABHS infection like any other bacterial infection leads to immune reaction from body. The antibody or cell mediated inflammatory response against GABHS cross reacts with human tissues and leads to development of RF.
The major factors that are related to risk of RF are the magnitude of the immune response to the antecedent streptococcal pharyngitis and persistence of organism in throat during convalescence.
Epidemiology of GABHS infection in relation to RF:
GABHS can cause pharyngitis (rheumatogenic strains), acute glomerulo-nephritis (nephritogenic strains) or pyoderma (skin strains). The precise factors accounting for rheumatogenicity or nephritogenicity are not known. RF and acute glomerulonephritis (AGN) can occur in same patient and rarely can occur simultaneously also. Although some nephritogenic and skin strains may cause pharyngitis but they do not cause RF. AGN can result from certain rheumatogenic and skin strains.
GABHS pharyngitis attacks spread rapidly due to droplet transmission.
*RF follows tonsillopharangeal infection but not infection at other sites
Characteristics of Etiological agent:
Group A streptococci (ß - hemolyticus)
Streptococci are rapidly killed by penicillin during mitosis (log phase of growth). Also once phagocytosed by white blood cells, streptococci are highly susceptible to the antibacterial action of oxygen radicals and other antibacterial substances within phagosomes. Therefore, streptococcal infection is primarily extracellular, and its virulence depends on its resistance to phagocytosis followed by invasiveness and toxin production. Resistance to phagocytosis is due to presence of capsule and surface M proteins. The hyaluronate capsule resists phagocytosis and internalization of the organism by epithelial cells. It also disrupts connections of epithelial cells and promotes invasion into deeper tissues. The capsule is non antigenic.
Resistance to phagocytosis is further enhanced by several anti-complementary effects of M protein, and by its precipitation of fibrinogen on the bacterial surface. Thus, these 2 factors play an important role in virulence of streptococci. Surface M protein is highly antigenic and induction of type specific anti M antibodies is immunoprotective. However, the multiplicity of M types are responsible for the repetitive nature of GABHS infections and thus for recurrent bouts of RF. Over the period of time, the virulent GABHS strains tend to lose these virulence factors (M protein and capsule). Although, transmission of these attenuated strains lead to high rates of GABHS pharyngitis but the overall incidence of RF decreases. Benign, persistent throat carriage may result from epithelial cell internalization of less encapsulated strains. They may grow more slowly and be less readily eradicated by penicillin.
Characteristics of Rheumatogenic strains of GABHS:
M types 1, 3, 5, 6, 14, 18, 19, 27 and 29 Distinct structural characteristics of M proteins Long terminal antigenic domain Epitopes that are shared with human heart tissue Heavily encapsulated, forms mucoid colonies Resist phagocytosis Do not produce opacity factor
Toxins produced by streptococci:
Streptolysin S Cell-surface bound hemolysin One of the most toxic proteins known (weight by weight) Causes rapid destruction of cell membranes Very cardiotoxic.
Streptolysin O Oxygen labile hemolysin Potent cardiac toxin.
Streptokinase Liquefies fibrin
Desoxyribonuclease Liquefies nucleic proteins
Hyaluronidase Promotes rapid spread of the organisms through tissues (e.g., cellulites and lymphangitis).
Many of these secreted toxins have the properties of superantigens. They nonspecifically and powerfully stimulate the host's immune response.
Host Factors:
Only humans develop ARF Genetic predisposition: Familial Tendency: 2 % (India, Padmawati) Genetic predisposition is due to Presence of specific B cell alloantigen High incidence of class II HLA antigen • HLA DR 4,21,3,7 DRW 53, DW 10 HLA A 19
Association of HLA antigens has also been demonstrated in Indian studies
Jhinghan et al: Increased frequency of HLA –A33/ D3. Decreased incidence of HLA D 2 Basir Wani (IHJ 1992): Increased frequency of HLA DR4 and HLA A 19. Significant decrease in B5, B13
Few characteristics point to presence of other unknown host factors causing RF
Rare before 5 yrs of age. Rare in identical twins (about 20 %) than in twins with other immunological disease such as atopic allergy and hyperthyroidism. No clear association with class I HLA antigen Definite association with a non HLA B cell antigen
The inflammatory reaction:
RF develops due to autoimmune reaction against GABHS.
– Cross-reactivity is due to 'antigen-mimicry' (Molecular mimicry)
– The damage to heart is due to cell-mediated immunity mediated by T lymphocytes and macrophages.
– Type 2 Hypersensitivity reaction
Components of GABHS and cross-reactivity with human tissues
Pathogen Component Cross-reactivity
Capsule Hyaluronic acid Joints
Cell wall M Protein/M associated protein Myocardium
Group carbohydrate N-acetyl glucosamine rhamnose Valvular tissue
Cell membrane Protein/lipid/Carbohydrate Myocardial sarcolemma Subthalamic and Caudate nucleus
Pathology
The disease process in RF is diffuse although the organs mainly involved are heart, joints, brain and cutaneous and subcutaneous tissues. A generalized small vessel vasculitis occurs but unlike other vasculitis the thrombotic lesions are not seen. In acute phase of RF, exudative and proliferative inflammatory reactions to connective or collagen tissue occur.
The basic structural change in collagen is fibrinoid degeneration. There is perivascular infiltrate of large cells with polymorphous nuclei and basophilic cytoplasm arranged in rosette around an avascular centre of fibrinoid (Aschoff nodule or body, the hallmark of RF). Aschoff bodies are present in any area of myocardium but not in other affected organs. They are most often seen in the intraventricular septum, wall of left ventricle or left atrial appendage. Aschoff nodule in proliferative phase is pathognomonic of rheumatic carditis. Aschoff bodies are observed in only 30 – 40 % of cases of RF. Its presence is not suggestive of recent or active carditis
Aschoff nodule
Pathognomonic histological lesion seen in RF. Not seen in first 3-4 weeks of ARF. Mature Aschoff's nodule is 1 mm to 1 cm in size. It consists of a perivascular infiltrate of Aschoff's cells and Anitschkow cells arranged in a rosette around an avascular center of fibrinoid. Other cells that can be found in Aschoff body are polymorphonuclear cells and lymphocytes. Aschoff cell or multinucleate giant cell has 1-5 nuclei and basophilic cytoplasm Anitschkow cell (cardiac histiocyte or monocyte) is a uninucleate cell with eosinophilic cytoplasm. This cell is normally present in heart but due to active inflammation of ARF, an increase in cytoplasm leads to 'owl-eyed' appearance of the cell.
Gross pathology seen in RF:
• Acute Rheumatic Fever: Acute Inflammatory Phase
– Heart – Pancarditis
– Joints - Migratory polyarthritis Immune complex mediated manifestation
– Skin – Erythema Marginatum
– CNS – Sydenham Chorea
* In Subacute nodule, Erythema marginatum and Chorea: The underlying pathological feature is vasculitis
The acute phase resolves without any permanent damage to any organs except heart (Rarely, Jaccoud's arthritis may develop)
• Chronic Rheumatic Fever
Only organ to be affected is heart (Exception Jaccoud's arthritis). Characterised by deforming fibrotic valvular disease.
Progression of valvular stenosis or damage may not entirely be related to recurrent RF infections. Initial alteration in the structure of valve due to valvulitis, changes the blood flow pattern across the valve causing undue hemodynamic trauma to valve. This hemodynamic trauma leads to more fibrosis, thickening and calcification. The rate of progression of fibrosis is higher in patients with more severe initial insult to valve.
Valve fibrosis and scarring are not specific to RHD can occur after valvulitis (inflammation of all valve layers) due to any cause e.g., RF, brucellar, rickettsial or viral infection. However other infections are very rare in comparison to RF.
The interval between ARF and development of chronic heart disease in usually 10 – 20 years but this phase is considerably shorter in developing nations.
The interval between ARF and development of tight MS could be as short as 1 yr (Paul ATS)
Valvulitis due to any cause leads to affection and disruption of all valve layers. The pathological feature is presence of inflammatory cells and vascularisation in all layers. These features are not seen in myxomatous degeneration of valves or other non inflammatory pathologies affecting valves.
Clinical Features of RF
• Commonest age group: 5-15 years
• Starts as fever with a history of antecedent sore throat (about 2-3 weeks before onset of fever)
Major Clinical Manifestations: Five
• Polyarthritis
• Carditis
• Sydenham Chorea
• Subcutaneous nodules
• Erythema marginatum
Joint Manifestations:
Joint symptoms due to ARF are either due to arthritis (major manifestation) or arthralgia (minor manifestation).
1. Polyarthritis:
Most common (70 %) but least specific Incidence of polyarthritis as seen in Indian series Roy et al 32 % Dhawan/Grover et al 75 % Agarwal et al 68 % Sanyal et al 67 %
Definition:
Polyarthritis is defined as involvement of 2 or more joints. Monoarthritis although unusual, can occur due to RF.
In Indian series:
Sanyal et al: Polyarthritis – 87 %; Monoarthritis – 13 % Agarwal et al: Polyarthritis – 93 %; Monoarthritis – 7 %
Pattern of involvement
Sudden onset with joint pain reaching its peak in 12-24 hours
Larger joints
Typically involves 5 or more joints
Legs first and then spreads to arms.
The incidence of different joints is as follows:
• Stollerman: – Knee 75 % – Ankle 50 % – Wrist, elbow, hip, small joints of legs 12-15 % – Shoulder and smaller joints of hands 7-8 %
• Sanyal – Knee 86 % – Ankle 65 % – Wrist 28 % – Hip 15 % – Elbow 11 % – Shoulder 8 % – Uncommon: Spine, metatarsal, temporomandibular, metacorpo-phalangeal and sternoclavicular
Characteristics of polyarthritis due to RF: It is almost always asymmetric, migratory Pain lasts for approximately 1 week in one joint; by the time the joint pain in a particular joint has subsided then the arthritis has migrated to another joint involves larger joints.
Typical clinical features of arthritis are present: The joints are swollen, warm, red and tender (minimal redness). Patients complain of severe pain and limitation of movements.
'Pain at rest' is the characteristic feature
Pain is often disproportionate to objective signs (modest swelling and minimal redness)
Duration of polyarthritis
Usually resolves within a week (can last for 3-4 weeks) and shows dramatic response to salicylates (within 48 hours). If there is no response to salicylates within 48 hours the diagnosis of RF should be questioned. Rarely some patients do not respond brilliantly to salicylates, requiring supplemental corticosteroids. The arthritis due to RF always resolves with no permanent damage to joints except in rare case of Jaccoud's arthritis.
Jaccoud's arthritis
The characteristic deformities of chronic post rheumatic fever arthritis are found in the hand (rarely in feet) and consist of flexion of the metacarpophalangeal joints associated with ulnar deviation of the fingers, most marked in the fourth and fifth digits. The deformities are apparently due to periarticular, fascial, or tendinous fibrosis rather than to synovitis.
This deformity can also affect the feet. Just as the deformity is more marked in the medial digits when the hand is involved, the deformity is most severe in the great toe and the second toe if a foot is affected.
Jaccoud's arthritis is also seen as sequelae to SLE.
(Continues...)
Excerpted from A Handbook Of Rheumatic Fever by Alok Ranjan Copyright © 2011 by Dr. Alok Ranjan. Excerpted by permission of AuthorHouse. All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
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Table of Contents
Contents
Rheumatic Fever (RF)....................1Incidence and Prevalence....................2
Pathogenesis....................4
Pathology....................8
Clinical Features of RF....................10
Laboratory Investigations....................22
Diagnosis of RF....................28
Treatment....................32
Treatment of ARF....................35
Recurrences Vs Rebounds of RF....................39
Secondary Prevention of RF....................42
Future....................46
Recommended Reading....................47
Abbreviations....................48