Page 455 - Textbook of Pathology, 6th Edition

2. Subsequent attacks of streptococcal infection are generally target tissues in RHD i.e. cardiac muscle, valves, joints, skin, 439
associated with exacerbations of RF. neurons etc. Further evidences in support are as under:
3. A higher incidence of RF has been observed after 1. Cell wall polysaccharide of group A streptococcus forms
outbreaks and epidemics of streptococcal infection of throat antibodies which are reactive against cardiac valves. This is
in children from schools or in young men from training supported by observation of persistently elevated
camps. corresponding autoantibodies in patients who have cardiac
4. Administration of antibiotics leads to lowering of the valvular involvement than those without cardiac valve
incidence as well as severity of RF and its recurrences. involvement.
5. Cardiac lesions similar to those seen in RHD have been 2. Hyaluronate capsule of group A streptococcus is identical
produced in experimental animals by induction of repeated to human hyaluronate present in joint tissues and thus these
infection with β-haemolytic streptococci of group A. tissues are the target of attack.
6. Patients with RF have elevated titres of antibodies to the 3. Membrane antigens of group A streptococcus react with
antigens of β-haemolytic streptococci of group A such as anti- sarcolemma of smooth and cardiac muscle, dermal fibroblasts
streptolysin O (ASO) and S, anti-streptokinase, anti- and neurons of caudate nucleus.
streptohyaluronidase and anti-DNAase B.
7. Socioeconomic factors like poverty, poor nutrition, density MORPHOLOGIC FEATURES
of population, overcrowding in quarters for sleeping etc are RF is generally regarded as an autoimmune focal
associated with spread of infection, lack of proper medical inflammatory disorder of the connective tissues
attention, and hence higher incidence of RF. throughout the body. The cardiac lesions of RF in the form
8. The geographic distribution of the disease, as already of pancarditis, particularly the valvular lesions, are its
pointed out, shows higher frequency and severity of the major manifestations. However, supportive connective
disease in the developing countries of the world where the tissues at other sites like the synovial membrane,
living conditions are substandard and medical facilities are periarticular tissue, skin and subcutaneous tissue, arterial
insufficient. Populations in these regions develop recurrent wall, lungs, pleura and the CNS are all affected
throat infections which remain untreated and have higher (extracardiac lesions).
incidence of RF. CHAPTER 16
9. The role of climate in the development of RF has been A. Cardiac Lesions
reported by some workers. The incidence of the disease is The cardiac manifestations of RF are in the form of focal
higher in subtropical and tropical regions with cold, damp inflammatory involvement of the interstitial tissue of all
climate near the rivers and waterways which favour the the three layers of the heart, the so-called pancarditis. The
spread of infection. pathognomonic feature of pancarditis in RF is the presence
10. There is evidence to support the role of heredity. of distinctive Aschoff nodules or Aschoff bodies.
Susceptibility to develop RF in families, occurrence in The Heart
identical twins and in individuals with HLA class II alleles THE ASCHOFF NODULES OR BODIES. The Aschoff
supports the inherited characteristic of the disease. nodules or the Aschoff bodies are spheroidal or fusiform
Despite all these evidences, only a small proportion of distinct tiny structures, 1-2 mm in size, occurring in the
patients with streptococcal pharyngeal infection develop interstitium of the heart in RF and may be visible to naked
RF—the attack rate is less than 3%. There is a suggestion eye. They are especially found in the vicinity of small
that a concomitant virus enhances the effect of streptococci in blood vessels in the myocardium and endocardium and
individuals who develop RF. occasionally in the pericardium and the adventitia of the
proximal part of the aorta. Lesions similar to the Aschoff
B. IMMUNOLOGIC EVIDENCE. It has been observed that nodules may be found in the extracardiac tissues.
though throat of patients during acute RF contain Evolution of fully-developed Aschoff bodies involves 3
streptococci, the clinical symptoms of RF appear after a delay stages all of which may be found in the same heart at
of 2-3 weeks and the organisms cannot be grown from the different stages of development. These are as follows:
lesions in the target tissues. This has led to the concept that
lesions have immune pathogenesis. 1. Early (exudative or degenerative) stage. The earliest
A susceptible host, on being encountered with group A sign of injury in the heart in RF is apparent by about 4th
streptococcus infection, mounts an autoimmune reaction by week of illness. Initially, there is oedema of the connective
formation of autoantibodies against bacteria. These tissue and increase in acid mucopolysaccharide in the
autoantibodies cause damage to human tissues due to cross- ground substance. This results in separation of the
reactivity between epitopes in the components of bacteria collagen fibres by accumulating ground substance.
and the host. Streptococcal epitopes present on the bacterial Eventually, the collagen fibres are fragmented and
cell wall, cell membrane and the streptococcal M protein, disintegrated and the affected focus takes the appearance
are immunologically identical to human molecules on and staining characteristics of fibrin. This change is
myosin, keratin, actin, laminin, vimentin and N-acetylgluco- referred to as fibrinoid degeneration.
samine. This molecular mimicry and crossreactivity between 2. Intermediate (proliferative or granulomatous) stage.
streptococcal M protein in particular and the human It is this stage of the Aschoff body which is pathognomonic
molecules forms the basis of autoimmune damage to human of rheumatic conditions (Fig. 16.24). This stage is apparent