Lecture 15: Septic arthritis and Rheumatic Fever

Question 1

If we see…

Clinical Presentations

• Child with fever
• Hot, swollen knee joint(s)

What are the possible causes?

Answer 1

Differential Diagnosis

• Septic arthritis
• Rheumatic fever
  
  • Other reactive arthritis
  • Trauma (fracture, muscular injury)

Question 2

What are the 3 Gram positive cocci?

Answer 2

Gram-Positive Cocci

Streptococci (in chains or diplococci)

• Alpha haemolytic Strep. pneumoniae
• Beta haemolytic group A strep. (Strep. pyogenes)

Staphylococci (in clumps or clusters)

• Coagulase positive Staph. aureus

Question 3

Describe the features of Strep Pyogenes

Answer 3

Streptococcus pyogenes is a species of Gram-positive bacteria.

• It is present with beta haemolytic (complete breakdown of red cells in blood agar around colonies leaving it transparent) cocci in chains.
• It is predominant species harboring Lancefield group A antigen, so often called group A streptococcus (GAS).

Question 4

Describe the micoanatomical features of Group A Streptococcus (strep pyogenes)

Answer 4

>100 types of group A strep. recognised based on distinct surface M proteins (emm gene)

• M protein helpful in _resisting phagocytosi_s and is important virulence factor
  
  • Differing M types associated with different clinicial syndromes e.g. impetigo
  • Different M types from pharyngitis
• Important active extracellular products ‘toxins’ and antigens. Streptolysin is a streptococcal hemolytic exotoxin. Types include streptolysin O (SLO), which is oxygen-labile (NADase); and streptolysin S (SLS), which is oxygen-stable.
• Peptidoglycan cell wall is site of action of penicillin.
• Fimbriae protruding thru capsule (hyaluronic acid) is important for adherence to epithelial cells; Associate with M proteins.

Question 5

What are the overall consequences of Group A streptococcal disease? (strep pyogenes)

Answer 5

Acute pyogenic/suppurative infections

(and later) Nonsuppurative inflammatory (e.g. acute rhematic fever and rheumatic heart disease)

Question 6

Describe the features of Sptic arthritis

Answer 6

Septic arthritis is an example of a suppurative complication of group A strep.

Presence of infection from bacteria in bone and marrow and/or joint space.

• General systemic symptoms include fever and malaise (unwellness)
• Swelling, erythema and tenderness around the affected joint.
• Clinically, joint held in position that maximises intracapsular volume (flexed knee, flexed abducted, ext-rotated hip).

Arthritis is limitation of movement, hot joint and pain or tender to palpate. Arthralgia is pain.

Question 7

Septic arthritis occurs most frequently in childhood (age <10 years). Why are children susceptible to bone and joint infections?

Answer 7

Because they have growth plates (not fused)- f_high Blood supply._

Question 8

What ar ethe causes of Septic Arthritis?

Answer 8

Causes

Common bacterial causes are Staphylococcus aureus and Streptococcus pyogenes

• Staphylococcus aureus is the commonest pathogen causing bone and joint infection.
• Streptococcus pyogenes is the second most common pathogen of septic arthritis (i.e. group A streptococcal septic arthritis, Streptococcus pyogenes arthritis, suppurative arthritis, pyogenic arthritis).

Question 9

Describe the treatment of Septic Arthritis

Answer 9

Treatment

• Drainage and washout of the septic joint is often needed for both diagnosis (culture of joint fluid) and treatment
• Intravenous antibiotics are needed initially and total course of antibiotics likely to be long (>2-3 weeks)

Question 10

Describe the features of Rhematic Fever

(how does it develop)

Answer 10

Acute Rheumatic Fever (ARF)

Acute rheumatic fever is auto-immune response following throat infection (pharyngitis) with Streptococcus pyogenes.

• They may not remember the sore throat- didn’t cause pain
• The bug may be gone by the time they come in with rheumatic fever

Throat infection with group A strep., then latent period of several weeks before symptoms of ARF begin

• Generalised inflammation attacking certain parts of the body (heart, joints, skin and/or brain)
• Can cause l_asting damage to mitral and/or aortic valves, t_hus rheumatic heart disease (RHD)
  
  • RHD is the most common form of childhood heart disease in the world (developing countries and New Zealand)

Note that rheumatic fever is a differential diagnosis (esp. for New Zealand) from septic arthritis.

Question 11

Acute rheumatic fever is ___________ response following ___________with __________________(bacteria)

Answer 11

Acute rheumatic fever is auto-immune response following throat infection (pharyngitis) with Streptococcus pyogenes.

Question 12

Describe the critera for Rheumatic Fever diagnosis

Answer 12

Diagnostic Criteria

Diagnosis needs 2 major criteria, or 1 major and 2 minor criteria.

Major Criteria

• Carditis (inflammation of heart valves)
• Polyarthritis (>1 joint with arthritis)
• Sydenhams chorea (movement disorder)
• Erythema marginatum (rash) (rare)
• Subcutaneous nodules (very rare)

Minor Criteria

• Fever
• Polyarthralgia
• History of rheumatic fever
• Raised acute phase reactants (C-reactive protein (CRP),
• erythrocyte sedimentation rates (ESR))
• Prolonged PR interval on ECG

Acute rheumatic fever diagnosis based on clustering of evidence plus evidence of a preceding streptococcal infection

1. Rising or elevated streptococcal antibody titires; OR
2. Positive group A streptococcus throat culture

Question 13

What do you see in an EEG in a patient with rheumatic heart disease

Answer 13

Prolongation of PR interval (conduction defect)

Question 14

_________ is commonest presenting symptom of acute rheumatic fever, up to 75% of first attacks

Answer 14

Arthritis is commonest presenting symptom of acute rheumatic fever, up to 75% of first attacks

Question 15

What are 2 clinical signs of rheumatic heart disease?

Answer 15

1) Prolongation of PR interval in EEG
2) Murmer during oscultation (due to the valves not closing properly)

Question 16

Describe Arthritis in Rheumatic fever

What is unique about arthritis in rheumatic fever? (e.g. compared to septic arthritis)

Answer 16

Arthritis In Rheumatic Fever

Arthritis is commonest presenting symptom of acute rheumatic fever, up to 75% of first attacks

• Typically, arthritis of ARF is extremely painful, u_nable to weight bear_
• Large joints are usually affected, esp. knees and ankles

UNIQUE: Polyarthritis is usually asymmetrical and migratory (one joint becoming inflamed as another subsides)

• e.g. yesterday the left ankle was sore, now it’s the knee etc.
• pain moves and you tend to have more than 1 joint involved.

Question 17

What is the name of the movement disorder associated with Rheumatic fever?

Answer 17

Sydenhams Chorea In Rheumatic Fever

Question 18

Describe Sydenhams Chorea

Answer 18

Sydenhams Chorea In Rheumatic Fever

Sydenham chorea is caused by group A streptococcus. Group A streptococcus bacteria can react with basal ganglia to cause this disorder.

Sydenham chorea is a major sign of ARF.

Sydenham chorea mainly involves jerky, uncontrollable and purposeless movements of the hands, arms, shoulder, face, legs, and trunk. These movements look like twitches, and disappear during sleep.

Question 19

What is the unoccmon characteristic skin rash found in people with rheumatic fever?

Answer 19

Erythema Marginatum

Question 20

Describe Erythema Marginatum

Answer 20

Erythema Marginatum In Rheumatic Fever

Characteristic skin rash, but uncommon <10% of first attacks of ARF

• Found on trunk upper arms and legs, but not face. Can be difficult to see in dark-skinned.
• Spread outwards in a circular shape, edge become raised, red, and centre clears.

It can persist intermittently for weeks to months, no other symptoms and often not noticed by patient.

Subcutaneous nodules are extremely uncommon

Question 21

Describe the mechanism of rheumatic fever

Answer 21

Mechanism of Rheumatic Fever

Rheumatic fever (e.g. carditis and chorea) occur from autoimmune mechanisms related to molecular mimicry

• Normal host response to group A streptococcus produce antibodies to bacterial antigens
• Production of cross-reactive antibodies gives immune recognition and response against pathogen, but produce antibodies which recognise both host and microbial antigens.
  
  • Human cardiac myosin and streptococcal M protein are likely important antigens in the pathogenesis of rheumatic heart disease. Antibodies cross react with collagen or cardiac valvular endothelia antigens, then T cells infiltrate leading to inflammation (arthritis) or long-term damage (carditis then RHD)
  • Auto antibody-mediated neuronal cell signalling in c_erebrospinal fluid_ may be part of pathogenesis in chorea

Recurrent rheumatic fever attacks due to repeated strep infections lead to increased scar formation in the valve.

• After initial attack of ARF and carditis, the valve scars and then is neovascularized (new vessels) which perpetuates disease
• Preventing recurrences crucially important

Question 22

___________and streptococcal_______________ are likely important antigens in the pathogenesis of rheumatic heart disease

Answer 22

Human cardiac myosin and _streptococcal M protein a_re likely important antigens in the pathogenesis of rheumatic heart disease

Question 23

How do you test for rheumatic fever?

Answer 23

Tests of Rheumatic Fever

Streptococcal antibody titres are very important part of confirming diagnosis

• Most acute rheumatic fever cases _do not have culture positive throat (_often no history of sore throat either). Even when Grp A strep cultured, could be represent carriage, does not confirm recent infection.
• Tests used are plasma anti-streptolysin O (ASO) and anti-deoxyribonuclease B (anti-DNase B) titres
  
  • ASO titre level is highest about 3-6 weeks after infection (about when children present with ARF
  • Can takes 2 months to decline, and 6 months to back to normal

Tests of Rheumatic Fever: Lab Results

Interpretive Ranges of ASO

• <240 Recent streptococcus pyogenes infection unlikely (normal)
• 240-480 Equivocal
• >480 Recent streptococcus pyogenes infection likely

Interpretive Ranges of Anti-DNase B

• <200 Recent streptococcus pyogenes infection unlikely (normal)
• 200-680 Equivocal
• >680 Recent streptococcus pyogenes infection likely

Interpretation of streptococcal antibody titres is age dependent. Lower levels are seen in very young and patients >15yrs.

2-4 folds increase or decrease in titres performed 14-21 days apart is indicative of recent infection.

Question 24

Describe the treatment and recurrence preention of Rheumatic fever

Answer 24

Treatment

• No active treatment
• Bed ridden for 2 weeks

Recurrences Prevention

Penicillin

_Preventing recurrences i_s crucially important using penicillin (until they’re 21)

• Streptococcus pyogenes remains exquisitely susceptible to this antibiotic
• (Compare with >90% Staphylococcus aureus produces beta-lactamase or penicillinase, that makes it resistant to penicillin. need to use flucloxacillin)

Question 25

Describe the mechanism of penicillin

Answer 25

Mechanism of Penicillin

Peptidoglycan is main component of bacterial cell wall

• Transpeptidase is part of family of enzymes bound to cell membrane called penicillin binding proteins.
• Transpeptidase reforms peptide cross links

Penicillin resembles NAM and _binds the transpeptidas_e (inhibits it). It is used to treat S. pyogenes

Either oral or parenteral forms is used, which is based on peak levels and duration of activity in serum, absorption and compliance

Question 26

What are the different types of formations of penicillin?

Answer 26

Formulations of Penicillin

Formulations of penicillin is based on side chain. All penicillins are excreted by both GFR and tubular secretion.

1) Aqueous (water soluble) penicillin G (intravenous) has very high peak rapidly (15-30min), but excreted rapidly within 2-4hr.

• It is used for treating acute severe infections in places like meningitis, blood stream, pneumonia, septic arthritis.

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2) Benzathine penicillin G (intramuscular injection) is low concentration of serum penicillin G (only 1-2% of peak that aqueous gives), but detectable amounts in serum >3 weeks.

• Pain at injection site is problem. Lignocaine and buzzy toy have better pain reduction than lignocaine alone, (only ≤13 years)

3) Phenoxymethylpenicillin ‘penicillin V’ (oral) is absorbed well from GI tract (~40% of same dose given as aqueous penicillin G, so are good for mild to mod infections (acute pharyngitis)).