This is the most common cause of sore throat by a wide margin.

Aetiology: > 200 viral subtypes can cause pharyngitis ^[3]:

• Rhinovirus (30–50%) — the classic common cold virus
• Coronavirus (10–15%) — including seasonal coronaviruses
• Influenza (5–15%)
• RSV (5%), parainfluenza (5%), adenovirus, enterovirus ^[3]

Pathophysiology:

1. Virus enters via droplet/contact → inoculates nasopharyngeal/oropharyngeal epithelium
2. Viral replication in epithelial cells → direct cytopathic effect (cell damage and death)
3. Innate immune response → release of inflammatory mediators (bradykinin, prostaglandins, IL-1, IL-6, TNF-α) → vasodilation, oedema, pain receptor stimulation
4. Pain receptors (nociceptors) in pharyngeal mucosa are sensitised → sore throat
5. The inflammation also triggers increased mucus production (rhinorrhoea) and stimulates sneezing reflexes

Why does it resolve? Because the adaptive immune response (T cells, antibodies) clears the virus within 7–10 days in immunocompetent individuals. The mucosal inflammation subsides as the viral load drops.

Key clinical point: Generally 24–72h incubation, > 90% resolve in 10 days (but can reach 14 days in a minority) ^[3].

Aetiology: Epstein-Barr virus (EBV), a herpesvirus (HHV-4). Transmitted via saliva ("kissing disease").

Pathophysiology:

1. EBV infects oropharyngeal epithelium → then infects B lymphocytes via CD21 receptor
2. Infected B cells proliferate → massive reactive T cell response (these are the "atypical lymphocytes" seen on blood film)
3. Lymphoid tissue hypertrophy (tonsils, lymph nodes, spleen) → exudative tonsillitis, generalised lymphadenopathy, splenomegaly
4. Immune complex formation → can trigger transient hepatitis, rash (especially if amoxicillin given — occurs in ~90% of EBV patients given aminopenicillins, likely due to altered immune response causing hypersensitivity)

Why is it important? ^[1]

• Epstein-Barr mononucleosis is a common "pitfall (often missed)" — because it can mimic severe bacterial tonsillitis with exudates and fever
• Tonsillitis with a covering membrane may be caused by Epstein-Barr mononucleosis ^[1] — the greyish-white membrane over tonsils can be mistaken for diphtheria or bacterial tonsillitis
• In HK, EBV is also the primary aetiological agent for NPC ^[4] — a long-term consequence of EBV latency in epithelial cells

Aetiology: Group A β-haemolytic Streptococcus (GAS, Streptococcus pyogenes). Accounts for 5–15% of adult and 15–30% of paediatric pharyngitis ^[3].

Pathophysiology:

1. GAS adheres to pharyngeal epithelium via M protein and lipoteichoic acid
2. Produces virulence factors:
   • Streptolysin O and S → lyse host cells, responsible for β-haemolysis
   • Streptococcal pyrogenic exotoxins (SPE) → superantigens → massive T cell activation → scarlet fever rash
   • Hyaluronidase, streptokinase → facilitate tissue invasion
3. Intense PMN infiltration → purulent exudates on tonsils
4. Regional lymph node reaction → tender anterior cervical lymphadenopathy (jugulodigastric nodes)

Why does GAS matter clinically?

• Not because the pharyngitis itself is dangerous (it's usually self-limiting)
• But because of non-suppurative complications driven by molecular mimicry:
  • Acute rheumatic fever (ARF) ^[7]: antibodies against GAS M protein cross-react with cardiac myosin, joint synovium, and brain tissue → pancarditis, migratory polyarthritis, Sydenham's chorea
  • Post-streptococcal glomerulonephritis (PSGN): immune complex deposition in glomeruli
• And suppurative complications: peritonsillar abscess (quinsy), retropharyngeal abscess, suppurative cervical lymphadenitis

Pathophysiology:

1. Chronic inflammation of paranasal sinus mucosa → persistent mucopurulent secretions
2. Secretions drain posteriorly along the posterior pharyngeal wall (postnasal drip/PND)
3. This irritates the pharyngeal mucosa → chronic sore throat, throat-clearing, cough
4. Patients often describe a "tickle" or "something dripping" at the back of the throat, worse on lying down

Why is this a probability diagnosis? Because chronic rhinosinusitis is very common (5–12% prevalence) and postnasal drip is one of the top three causes of chronic cough. Patients often present with "sore throat" when the real problem is in the sinuses.

Aetiology: Candida albicans (most common), a commensal yeast of the oral cavity.

Pathophysiology:

1. Normally kept in check by competing oral flora, salivary defences, and mucosal immunity
2. Disruption of any of these → Candida overgrowth:
   • Steroid inhalers ^[1] → local immunosuppression + mucosal thinning
   • Diabetes ^[1] → hyperglycaemia favours fungal growth + glycosylation impairs neutrophil function
   • Antibiotics → kill competing bacteria → Candida flourishes
   • HIV/AIDS → CD4 T cell depletion → loss of mucosal immune surveillance
   • Dentures, poor oral hygiene, xerostomia
3. Candida adheres to mucosa → forms pseudohyphae → superficial invasion → white, curd-like plaques that can be scraped off revealing erythematous, sometimes bleeding base

Clinical pearl: Common in infants ^[1] (immature immune system) and in debilitated/immunosuppressed adults.

This is a classic "masquerade." The sore throat isn't really a sore throat — it's referred cardiac pain.

Pathophysiology of referred pain:

• Myocardial ischaemia activates cardiac nociceptors → afferents travel via cardiac sympathetic nerves → synapse in upper thoracic (T1–T4) spinal cord segments
• These segments also receive somatic afferents from the chest wall, arm, jaw, and throat
• The brain misinterprets the visceral cardiac pain as coming from somatic structures → "throat tightness," jaw pain, arm pain

When to suspect: Exertional "throat tightness" in a patient with cardiovascular risk factors (hypertension, diabetes, hyperlipidaemia, smoking, family history of IHD). The pain is not actually in the pharynx — it's deep and constricting.

Key aetiologies in HK:

• HPV-related oropharyngeal SCC (HPV 16/18): HPV-associated H&N cancer occurs primarily in the oropharynx including tonsils and the base of tongue ^[4]. Younger male patients, higher number of sexual partners. Better prognosis than HPV-negative cancers.
• Tobacco/alcohol-driven SCC: Synergism between smoking and alcohol in development of HNSCC is well established ^[4]. Typically in older males.
• NPC (EBV-driven): Endemic in Southern China including Hong Kong ^[4]. Frequently originates from pharyngeal recess known as fossa of Rosenmüller ^[4]. May present as sore throat, epistaxis, nasal obstruction, or (commonly) a painless neck mass.

Pathophysiology of HPV-driven carcinogenesis:

• HPV infects basal epithelial cells of tonsillar crypts
• Viral oncoproteins E6 and E7 inactivate tumour suppressors p53 and Rb ^[4] → uncontrolled cell proliferation
• Distinct from tobacco-driven cancers: HPV-positive tumours are typically p16-positive, non-keratinising, and more radiosensitive

Diagnostic tip: The triad — hoarseness, pain on swallowing and referred ear pain → pharyngeal cancer ^[1]

Pathophysiology:

• Agranulocytosis (absolute neutrophil count < 0.5 × 10⁹/L) → loss of the primary defence against bacteria in mucosal surfaces → pharyngeal mucosa becomes vulnerable to bacterial and fungal invasion → severe necrotising pharyngitis/ulceration
• Drug-induced agranulocytosis is the most common cause — think carbimazole (antithyroid drug), clozapine, methotrexate, chemotherapy, sulphonamides
• Acute leukaemia → bone marrow failure → pancytopenia → neutropenic sore throat + anaemic pallor + bleeding gums

Clinical clue: Sore throat that is disproportionately severe with mucosal ulceration/necrosis in a patient on high-risk medications, or with unexplained pallor, fatigue, bleeding, and fever.

(a) Acute Epiglottitis ^[1][3]

"Admit if any suspicion of epiglottitis — and do not examine the throat" ^[1]

• Aetiology: Haemophilus influenzae type b (Hib) classically in children; in adults, Streptococcus, Staphylococcus, and other organisms
• Pathophysiology: Bacterial infection of the epiglottis and supraglottic structures → rapid swelling of the epiglottis → airway obstruction. The epiglottis can swell to several times its normal size within hours.
• Why not examine the throat? Because manipulating the pharynx (e.g., with a tongue depressor) can trigger laryngospasm or complete airway obstruction in an already compromised airway. This is a life-threatening emergency.
• Clinical features: Rapid onset sore throat, high fever, muffled "hot potato" voice, drooling (because swallowing is too painful), stridor, tripod positioning (sitting up, leaning forward, neck extended)

(b) Peritonsillar Abscess (Quinsy) ^[1]

• Pathophysiology: Bacterial tonsillitis → infection spreads beyond the tonsillar capsule into the peritonsillar space (between the tonsil and the superior constrictor muscle) → abscess formation
• Clinical features: Severe unilateral sore throat, trismus (difficulty opening mouth — because the abscess irritates the medial pterygoid muscle), "hot potato" voice, uvular deviation to the contralateral side, drooling

(c) Pharyngeal/Retropharyngeal Abscess ^[1]

• Pathophysiology: Infection of the retropharyngeal lymph nodes (which drain the nasopharynx, sinuses, and middle ear) → suppuration → abscess in the retropharyngeal space
• More common in children < 5 years (retropharyngeal lymph nodes atrophy by age 6)
• In adults, often secondary to penetrating pharyngeal trauma (e.g., FB, instrumentation)
• Danger: Can extend into the mediastinum (the retropharyngeal space communicates with the posterior mediastinum) → mediastinitis → sepsis → death

(d) Diphtheria ^[1]

• Very rare ^[1] due to vaccination, but must be considered in unvaccinated individuals
• Aetiology: Corynebacterium diphtheriae, produces diphtheria exotoxin
• Pathophysiology: Toxin inhibits protein synthesis (ADP-ribosylation of EF-2) → epithelial necrosis → formation of a tough, grey-white pseudomembrane over the pharynx that can obstruct the airway
• Toxin also causes distant damage: myocarditis, peripheral neuropathy
• S/S: airway pseudomembrane formation, fever, sore throat, extensive cervical LN ('bull's neck appearance') and rarely peripheral neuritis and myocarditis ^[3]

(e) HIV/AIDS ^[1]

• Acute HIV seroconversion illness (2–4 weeks after exposure) presents as a mononucleosis-like syndrome: sore throat, fever, lymphadenopathy, maculopapular rash, oral ulcers
• Chronic HIV → opportunistic infections (Candida, HSV, CMV), Kaposi sarcoma, lymphoma of Waldeyer's ring
• Always consider HIV in a young patient with severe/recurrent pharyngitis, oral candidiasis, or unexplained lymphadenopathy

Extremely common in Hong Kong given the dietary culture (steamed fish with many small bones). A fish bone lodges most commonly in the palatine tonsil, base of tongue, or vallecula. Patient reports a sharp pain on one side of the throat, worse with swallowing, often pointing to the exact spot. Lateral soft tissue neck X-ray may show radio-opaque FB but sensitivity is limited. Flexible nasendoscopy or OGD may be needed.

• Gonococcal pharyngitis ^[1]: Neisseria gonorrhoeae infection of the pharynx from orogenital contact. Often asymptomatic or mildly symptomatic → easily missed. Diagnose by pharyngeal swab for NAAT.
• Herpes simplex (type II) ^[1]: Can cause pharyngitis with painful vesicles/ulcers, especially in sexually active young adults. HSV-1 more commonly affects oropharynx; HSV-2 classically genital but can cause pharyngitis via orogenital contact.
• Syphilis ^[1]: Primary chancre can occur on the tonsil or pharynx (painless ulcer). Secondary syphilis can cause mucous patches (painless, greyish-white erosions on oral mucosa) and pharyngitis. Think of this in MSM populations.

• Laryngopharyngeal reflux (LPR) ^[5]: Reflux of gastric content all the way to the larynx and pharynx
• Pathophysiology: Pepsin and acid damage the pharyngeal and laryngeal mucosa, which lacks the protective mechanisms of the oesophagus (no peristaltic clearance, thinner epithelium, less bicarbonate secretion)
• Key feature: May occur without classic heartburn if the refluxate bypasses the oesophageal mucosa rapidly → patient presents primarily with ENT symptoms: chronic sore throat, throat clearing, globus, hoarseness, chronic cough ^[5]
• This is why patients with GERD may present initially to RESP, CARD or ENT ^[5]

• Spasm of the cricopharyngeus muscle (upper oesophageal sphincter) → globus sensation ("lump in throat")
• Often functional/stress-related but can be associated with GERD
• Not truly a "sore" throat but patients describe discomfort

• Recurrent painful oral ulcers (canker sores) — can involve the pharynx
• Pathophysiology incompletely understood; likely T cell-mediated immune response triggered by local trauma, stress, hormonal changes, food sensitivities (e.g., sodium lauryl sulphate in toothpaste)
• Important to distinguish from Behçet disease ^{[1] [8]}: oral ulcer (almost all) — deep, multiple painful ulcers with well-defined borders and necrotic base ^[8]. Behçet also has genital ulcers, uveitis, and skin lesions.

• Subacute (de Quervain's) thyroiditis ^[9]: Pain in the thyroid region that may radiate to the angle of the jaw and ears ^[9] → can be mistaken for sore throat
• Pathophysiology: Post-viral granulomatous inflammation of the thyroid (Coxsackie, mumps, adenovirus) → follicular destruction → release of stored T4 → thyrotoxic phase, then hypothyroid phase, then recovery ^[9]
• Clue: Tender thyroid gland, elevated ESR (often > 50), fluctuating thyroid function tests, preceding viral illness

• Mucocutaneous lymph node syndrome — a medium-vessel vasculitis in children < 5 years
• Features include: high fever > 5 days, bilateral conjunctivitis, oral mucosal changes (strawberry tongue, cracked lips, pharyngeal erythema), cervical lymphadenopathy, polymorphous rash, extremity changes
• Pharyngitis/sore throat is part of the mucosal involvement
• Critical complication: Coronary artery aneurysms → must treat early with IVIG + aspirin

What it does: Detects the Group A carbohydrate antigen on the surface of S. pyogenes directly from a throat swab specimen, using immunochromatographic technology (similar principle to a COVID rapid antigen test).

Why it's useful: Results available in 5–10 minutes at the point of care → allows same-visit decision-making about antibiotics.

Performance ^[3]:

A negative RADT should be backed up by culture ^[3] — especially in children and adolescents where the consequences of missed GAS (rheumatic fever) are greatest. In adults, some guidelines accept a negative RADT as sufficient to withhold antibiotics because the risk of ARF is much lower.

Limitation: Cannot distinguish between illness and carrier states ^[3]. Approximately 5–20% of school-age children are asymptomatic GAS carriers. A positive RADT in a child with clear viral symptoms (cough, rhinorrhoea) may represent carriage, not active infection.

What it does: Detects heterophile antibodies (non-specific IgM produced by polyclonally activated B cells during EBV infection) that agglutinate horse or bovine erythrocytes.

Performance:

• Sensitivity: ~85% in adolescents/adults, but only ~25–50% in children < 4 years (their immune systems produce fewer heterophile antibodies)
• Specificity: ~95–100% (false positives rare; can occur in HIV, lymphoma, SLE)
• Timing: May be negative in the first week of illness → repeat at 1–2 weeks if initially negative but clinical suspicion remains high

Interpretation:

• Positive Monospot + compatible clinical features (fever, pharyngitis, posterior cervical lymphadenopathy, fatigue) = EBV infectious mononucleosis
• Negative Monospot ≠ exclusion, especially early in illness or in young children → send EBV-specific serology

This is arguably the most important single blood test for sore throat because it screens for several serious diagnoses simultaneously.

Why check it? To unmask diabetes mellitus as the underlying cause of recurrent oropharyngeal candidiasis. Hyperglycaemia promotes Candida growth (sugar is a carbon source for yeast) and impairs neutrophil chemotaxis and phagocytosis through glycosylation of immune proteins.

• Fasting glucose ≥ 7.0 mmol/L or random glucose ≥ 11.1 mmol/L (with symptoms) → diabetes
• HbA1c ≥ 48 mmol/mol (6.5%) → diabetes

When Monospot is negative but EBV is still suspected (children < 4y, early illness, immunocompromised), send specific EBV antibodies:

Interpretation logic:

• VCA IgM positive + EBNA IgG negative = acute primary EBV infection (EBNA antibodies take 6–12 weeks to develop, so their absence confirms this is not reactivation or past infection)
• VCA IgG positive + EBNA IgG positive + VCA IgM negative = past infection / immune

For NPC screening in HK: EBV VCA IgA and plasma EBV DNA are used as serological markers. Elevated EBV DNA has been incorporated into NPC screening programmes in Southern China ^[4].

• Non-specific but help gauge severity and monitor progress
• Markedly elevated ESR (often > 50 mm/hr) in subacute (de Quervain's) thyroiditis ^[9] — this is a key distinguishing feature
• Elevated CRP in bacterial infections, abscess formation
• Serial CRP useful for monitoring response to treatment in deep neck space infections

Purpose: Confirm preceding GAS infection — relevant mainly when investigating post-streptococcal complications (rheumatic fever, PSGN), NOT for acute diagnosis of pharyngitis (serology takes > 2 weeks to rise).

• Serology is not helpful as it takes > 2 weeks ^[3] for diagnosing acute pharyngitis
• ASO titre rises 1–3 weeks after GAS infection, peaks at 3–5 weeks
• Anti-DNase B is more sensitive for skin infections and persists longer
• A rising titre (paired sera 2 weeks apart) is more meaningful than a single elevated value

When thyroiditis is suspected (anterior neck tenderness radiating to jaw/ears, elevated ESR):

• Thyrotoxic phase (early): ↓ TSH, ↑ free T4 (stored hormone leaking from damaged follicles)
• Hypothyroid phase (later): ↑ TSH, ↓ free T4 (follicular cells depleted)
• Radioactive iodine uptake will be low in all phases (distinguishes from Graves' disease where uptake is high)

Consider in any patient with:

• Unexplained recurrent pharyngitis / oral candidiasis in a young adult
• Mononucleosis-like syndrome with negative Monospot
• Risk factors (MSM, IVDU, unprotected sexual contact, high-prevalence region)
• 4th-generation HIV Ag/Ab combo assay (detects p24 antigen + HIV-1/2 antibodies) — window period ~2 weeks

The single most important microbiological investigation for acute sore throat. There are three modalities:

Technique matters: Swab must be taken from the tonsillar surface and posterior pharyngeal wall — not just the buccal mucosa or tongue. Inadequate sampling is the most common reason for false-negative results.

For diphtheria: Throat swab and PCR for toxins ^[3]. Culture is on tellurite agar or Löffler's medium.

For gonococcal pharyngitis: Throat swab for NAAT (nucleic acid amplification test) — routine culture is insufficient as N. gonorrhoeae is fastidious.

When peritonsillar or deep neck abscess is drained (needle aspiration or incision & drainage), the pus should be sent for:

• Gram stain and aerobic + anaerobic culture
• Most commonly polymicrobial: GAS + oral anaerobes (Fusobacterium, Prevotella, Peptostreptococcus)

Indications: Suspected epiglottitis (if patient is stable enough), suspected retropharyngeal abscess, foreign body.

Important caveat: A lateral neck X-ray is a screening tool. If epiglottitis is strongly suspected clinically, do NOT delay management for imaging — go straight to securing the airway in a controlled environment (theatre/ICU).

The investigation of choice for deep neck space infections and neck masses.

• Imaging modality of choice for cancer of the oral cavity and oropharynx ^[4]
• Provides optimal visualization of soft-tissue infiltration of the tumour ^[4]
• Detection of cervical lymph node metastasis ^[4]
• Superior to CT for delineating tumour margins, perineural spread, and base of skull invasion (especially for NPC)
• Less useful in acute infection (CT is faster and more readily available in the emergency setting)

• Useful for evaluating cervical lymphadenopathy and guiding FNAC
• USG has limited use in oropharyngeal cancer but is a useful adjunct for FNAC to ensure accurate aspiration of a deeply seated lymph node swelling ^[4]
• Useful for evaluating thyroid in suspected thyroiditis (heterogeneous, hypoechoic gland with ↓ vascularity in de Quervain's)

Relevant when:

• Pulmonary TB suspected (chronic sore throat + hoarseness + constitutional symptoms → CXR for apical infiltrates/cavitation)
• Lemierre syndrome (septic pulmonary emboli → multiple cavitating nodules)
• NPC staging (lung metastases)
• Suspected foreign body aspiration

The cornerstone investigation for any chronic or suspicious sore throat, and for visualising the supraglottic and glottic structures that cannot be seen on simple oral examination.

Procedure: Thin flexible fibreoptic scope passed through the nose → nasopharynx → pharynx → larynx. Performed awake with topical anaesthesia (lignocaine spray).

What it visualises:

• Nasopharynx: Fossa of Rosenmüller (NPC origin site), adenoids, Eustachian tube orifices
• Oropharynx/Hypopharynx: Base of tongue, valleculae, piriform fossae, posterior pharyngeal wall
• Larynx: Epiglottis, vocal cords (mobility, masses, oedema), subglottic region
• LPR signs: Posterior laryngeal oedema, interarytenoid pachydermia ("cobblestoning"), vocal cord erythema

Indications:

• Persistent sore throat > 3 weeks (rule out malignancy)
• The triad: hoarseness, pain on swallowing and referred ear pain ^[1]
• Suspected epiglottitis (ONLY in controlled setting with anaesthetic backup)
• Hoarseness lasting > 3 weeks
• Unilateral symptoms, neck mass, suspected NPC

Purpose: Exclude the presence of synchronous lesion ^[4] — patients with one head and neck SCC have a 10–15% risk of having a second primary tumour elsewhere in the upper aerodigestive tract ("field cancerization").

• Performed under general anaesthesia
• Allows examination under anaesthesia (EUA) of the full upper aerodigestive tract
• Staging examination is recommended at the initial evaluation of all patients with primary cancers of the upper aerodigestive tract ^[4]
• Enables incisional biopsy of suspicious lesions for histopathological diagnosis

The definitive investigation for any suspected malignancy.

Important principle: In a patient with a neck mass suspected to be metastatic from an H&N primary, you should identify and biopsy the primary tumour first (via panendoscopy). Open excisional biopsy of the neck mass should be avoided until the primary is found, because it can compromise subsequent surgical management (seeding the wound, altering tissue planes).

Once a patient has had an episode of ARF, they need long-term secondary prophylaxis to prevent recurrent GAS pharyngitis (which triggers further ARF attacks → progressive valvular damage) ^[7]:

• Acute [ARF]: single dose IM benzylpenicillin ^[7]
• Chronic: prolonged penicillin Tx till 21y ^[7]

Duration of secondary prophylaxis:

• ARF without carditis: 5 years or until age 21 (whichever is longer)
• ARF with carditis but no residual valve disease: 10 years or until age 21
• ARF with residual valve disease: 10 years or until age 40 (some guidelines say lifelong)

Pathophysiology: GAS infection breaches the tonsillar capsule → spreads into the potential space between the capsule and the superior constrictor muscle (the peritonsillar space) → pus accumulates → abscess forms. The abscess compresses adjacent structures: the medial pterygoid muscle (→ trismus), the soft palate (→ uvular deviation), and the pharyngeal airway (→ "hot potato" voice, potential airway obstruction).

Frequency: Most common suppurative complication of tonsillitis. Typically occurs in adolescents and young adults.

Consequences if untreated: Can extend into the parapharyngeal space → carotid sheath involvement → internal jugular vein thrombosis → or extend inferiorly to mediastinum → mediastinitis → sepsis → death.

Pathophysiology: Infection from the pharynx drains to the retropharyngeal lymph nodes (which sit between the pharyngeal constrictor muscles and the prevertebral fascia) → nodes suppurate → retropharyngeal abscess. This space communicates directly with the posterior mediastinum (no fascial barrier below the level of the T4 vertebra) → potential for catastrophic mediastinitis.

Key population: Children < 5 years (retropharyngeal nodes are prominent in this age group and atrophy by age 6). In adults, usually occurs after penetrating pharyngeal trauma or instrumentation.

Pathophysiology: GAS spreads from the tonsils via lymphatics to the draining cervical lymph nodes (primarily jugulodigastric/level II) → bacterial replication within the node overwhelms local immune defences → node becomes filled with pus. Presents as a tender, fluctuant neck mass with overlying erythema and fever.

Classically associated with Fusobacterium necrophorum ^[3] — an anaerobic gram-negative rod that normally colonises the pharynx.

Pathophysiology: Pharyngeal/peritonsillar infection → bacteria invade the lateral pharyngeal space → reach the internal jugular vein (IJV) → infect the vein wall (phlebitis) → thrombus forms within the IJV (septic thrombosis) → fragments of infected thrombus break off → septic emboli travel to the lungs (→ cavitating pneumonia, lung abscesses), joints (→ septic arthritis), liver (→ hepatic abscesses), brain (→ meningitis, brain abscess).

Classically a/w Lemierre syndrome (septic thrombophlebitis of IJV) with risk of carotid blowout and other devastating consequences ^[3].

"The forgotten disease" — was common in the pre-antibiotic era, became rare, and is now re-emerging.

• Otitis media (bacterial spread to middle ear via Eustachian tube)
• Sinusitis (bacterial spread to paranasal sinuses)
• Mastoiditis (extension from middle ear to mastoid air cells)
• Meningitis (rare — haematogenous spread or direct extension from retropharyngeal abscess)
• Necrotising fasciitis (rare but devastating — GAS invades deep fascial planes of the neck)

This is the most important non-suppurative complication and the primary reason we treat GAS pharyngitis with antibiotics.

Pathophysiology: molecular mimicry ^[7]

• Delayed immune response to infection with certain strains of GAS ^[7]
• Cross-reactiveness targeting cardiac proteins (anti-M) ^[7]
• Result: inflammation in endocardium, myocardium and pericardium ^[7]

Step-by-step mechanism:

1. GAS M protein is structurally similar to human cardiac myosin, laminin, tropomyosin, and keratin
2. During the pharyngeal infection, the immune system generates antibodies against GAS M protein
3. These anti-M antibodies cross-react with cardiac proteins → bind to cardiac tissue → activate complement → recruit inflammatory cells → pancarditis
4. T cells sensitised to streptococcal antigens also cross-react with cardiac valve tissue → ongoing inflammation

Clinical S/S: preceded by strep throat 2–3 weeks before ^[7]:

• Pancarditis ^[7]: Characteristically, rheumatic heart disease is the only disease that affects all three layers of the heart ^[7] — endocarditis (valvulitis → murmurs), myocarditis (heart failure), pericarditis (effusion, friction rub). Murmurs: transient MR/AR murmur, MDM at apex (Carey-Coombs murmur) ^[7]
• Arthritis (75%): asymmetrical, predominantly large joints ^[7] — migratory polyarthritis (the arthritis "migrates" because immune complexes deposit sequentially in different joints)
• Sydenham's chorea ^[7]: T cell-mediated damage to basal ganglia (caudate and putamen) → involuntary choreiform movements
• Erythema marginatum ( < 5%) ^[7]: immune complex deposition in dermal vessels
• Subcutaneous nodules (5–7%) ^[7]: granulomatous reaction over bony prominences

Occurs in ≥1/2 of all ARF patients, but typically takes 10–30 years to become manifest ^[7].

Pathogenesis: repeated ARF attacks → progressive fibrosis → fusion/distortion of cusps ^[7].

Why does it progress? Each episode of ARF causes a round of inflammatory damage to the valves. During healing, the damaged valve tissue is replaced by fibrosis. Repeated episodes → cumulative fibrosis → thickening, calcification, and fusion of valve leaflets and chordae tendinae. The mitral valve is most commonly affected because it endures the highest mechanical stress (left-sided pressures).

Affects: Site — MV alone, AV+MV, AV alone, TV (rare). Pathology — MS > MR+MS > MR ^[7].

Important cause of chronic VHD but ↓ incidence (∵ good Abx management of GAS pharyngitis) ^[7].

Pathophysiology: Immune complexes (streptococcal antigen–antibody complexes) deposit in the glomerular basement membrane → activate complement (C3 consumption → low C3) → inflammatory cascade → proliferative glomerulonephritis.

Timing: 1–3 weeks after pharyngeal GAS infection (or 3–6 weeks after skin GAS infection).

Clinical findings: acute nephritis — haematuria, variable proteinuria, renal impairment ^[15].

Diagnosis: clinical findings of acute nephritis + documentation of recent GAS infection by culture or serology ^[15].

Key distinguishing feature from IgA nephropathy: PSGN occurs 1–3 weeks after pharyngitis (latent period for immune complex formation), whereas IgA nephropathy is classically synpharyngitic (usually within 5 days of URTI) ^[15] — the haematuria occurs simultaneously with the URTI, not after a delay.

Prognosis: majority have excellent outcome especially children ^[15]. However, some patients develop glomerulosclerosis → HTN, recurrent proteinuria and renal insufficiency 10–40 years after initial illness ^[15].

Important note: Unlike ARF, antibiotics do NOT reliably prevent PSGN. The immune complex formation may already be underway by the time pharyngitis is recognised. ARF prophylaxis is generally useful ≤9 days of onset (but less clear for other complications) ^[3].

A milder form of post-streptococcal joint inflammation that does not fulfil Jones criteria for ARF. Non-migratory, involves large or small joints, onset 1–2 weeks post-infection. Important because some cases may progress to carditis — these patients should be monitored and some guidelines recommend secondary prophylaxis.

Strictly speaking, scarlet fever is a toxin-mediated complication of GAS pharyngitis, not a true immune-mediated post-infectious complication.

Pathophysiology: Certain strains of GAS produce streptococcal pyrogenic exotoxins (SPE A, B, C) → these act as superantigens → non-specific activation of up to 20% of all T cells (vs. < 0.01% with conventional antigens) → massive cytokine release → diffuse erythematous rash with sandpaper texture, Pastia's lines (accentuated rash in skin folds), strawberry tongue, and circumoral pallor.

A controversial entity: acute onset OCD or tic disorder temporally related to GAS infection, hypothesised to be caused by anti-neuronal antibodies cross-reacting with basal ganglia (similar mechanism to Sydenham's chorea but with psychiatric rather than motor manifestations).