What are the differential diagnoses for a patient with a unilateral painful tonsil stone and white spots on the same tonsil, without systemic symptoms, following a resolved upper respiratory infection (URI)?

Differential Diagnoses for Unilateral Painful Tonsil Stone with White Spots

The most likely diagnosis is a tonsillolith (tonsil stone) causing localized inflammation and irritation, but you must actively exclude bacterial tonsillitis (particularly Group A Streptococcus), peritonsillar abscess, and less commonly, unilateral necrotizing tonsillitis or tonsillar malignancy.

Primary Differential Diagnoses

1. Tonsillolith with Secondary Inflammation (Most Likely)

• Tonsilloliths are calcified accumulations of cellular debris and microorganisms in tonsillar crypts that commonly cause localized pain and visible white material 1, 2
• The unilateral presentation with white spots visible on examination is consistent with a lodged tonsil stone, which can range from barely visible to several centimeters 1, 3
• Pain occurs when tonsilloliths become large enough to cause pressure or when they trigger secondary inflammation in the surrounding tonsillar tissue 1, 3
• The recent URI may have increased tonsillar debris accumulation, predisposing to stone formation 3
• Absence of systemic symptoms (fever, malaise) makes this more likely than acute bacterial infection 2

2. Group A Streptococcal (GAS) Pharyngitis

• Even without systemic symptoms, GAS pharyngitis must be excluded because it can present with unilateral tonsillar exudates and requires antibiotic treatment to prevent complications 4
• White spots could represent streptococcal exudates rather than a tonsillolith 4
• Clinical diagnosis alone is unreliable—you must perform either a rapid antigen detection test (RADT) or throat culture to confirm or exclude GAS 4
• The absence of fever does not rule out GAS, as not all patients report fever 4
• Key distinguishing features favoring GAS include: tonsillopharyngeal erythema, tender anterior cervical lymphadenopathy, absence of cough/rhinorrhea/hoarseness 4

3. Chronic GAS Carrier with Intercurrent Viral Infection

• Approximately 10% of healthy children (and some adults) are chronic GAS carriers with positive throat cultures but no active infection 4, 5
• The recent URI (viral) may have caused pharyngeal irritation in a chronic carrier, making differentiation from acute GAS pharyngitis difficult 4
• Carriers typically have persistence of the same GAS strain over time and do not require treatment unless specific circumstances exist 4

4. Peritonsillar Abscess (Early Stage)

• Unilateral tonsillar pathology with pain should raise concern for peritonsillar abscess, especially if there is asymmetric tonsillar enlargement or uvular deviation 4
• Early abscess may present without obvious fluctuance or systemic symptoms initially 4
• Look for: trismus, muffled "hot potato" voice, drooling, or inability to swallow secretions 4

5. Tonsillolith with Actinomycotic Infection

• Actinomyces species can colonize tonsilloliths and cause chronic, indolent infection with recurrent symptoms 3
• This presents similarly to simple tonsilloliths but may have more persistent or recurrent pain 3
• Consider if patient has history of recurrent tonsillar infections 3

6. Unilateral Necrotizing Tonsillitis (Rare but Serious)

• Plaut-Vincent angina (fusospirochetosis) or Prevotella species can cause unilateral necrotizing tonsillitis with white necrotic material 6
• More common in immunocompromised patients or those with poor oral hygiene 6
• Key red flags: necrotic-appearing tissue, foul odor, progressive symptoms, or failure to improve 6

7. Tonsillar Malignancy (Must Not Miss)

• Unilateral tonsillar pathology, especially in adults >40 years with tobacco/alcohol use, requires exclusion of squamous cell carcinoma 4
• Malignancy typically presents with persistent unilateral tonsillar enlargement, ulceration, or firm mass 4
• Any unilateral tonsillar abnormality that persists beyond 2-3 weeks warrants ENT referral for biopsy 4

Algorithmic Diagnostic Approach

Step 1: Assess for Bacterial Infection

• Perform RADT or throat culture immediately to exclude GAS pharyngitis 4
• If positive: treat with penicillin regardless of symptom severity to prevent complications 4
• If negative in adult: no further testing needed unless high clinical suspicion 4

Step 2: Physical Examination Findings

• Examine for peritonsillar abscess signs: asymmetric tonsillar enlargement, uvular deviation, trismus, fluctuance 4
• Assess the white material: if it can be expressed from crypts or appears as discrete calcified material, favors tonsillolith 1, 2
• If material appears as confluent exudate coating the tonsil, favors infectious etiology 4
• Check for cervical lymphadenopathy: tender anterior nodes suggest acute infection; firm, fixed nodes suggest malignancy 4

Step 3: Risk Stratification for Serious Pathology

• Age >40 years + tobacco/alcohol use + persistent unilateral findings = ENT referral to exclude malignancy 4
• Immunocompromised state, diabetes, or recent radiotherapy = higher risk for necrotizing infection 4, 6
• Progressive symptoms, necrotic appearance, or foul odor = urgent ENT evaluation 6

Step 4: Management Based on Diagnosis

• If tonsillolith confirmed and GAS excluded: expectant management, manual removal if accessible, consider tonsillectomy only if recurrent and symptomatic 2
• If GAS positive: penicillin V 500mg PO BID-QID × 10 days (or benzathine penicillin G 1.2 million units IM × 1) 4
• If peritonsillar abscess suspected: urgent ENT consultation for needle aspiration or incision and drainage 4

Critical Pitfalls to Avoid

• Failing to perform microbiological testing (RADT or culture) and relying on clinical diagnosis alone for pharyngitis 4
• Assuming absence of fever excludes bacterial infection—GAS pharyngitis can occur without fever 4
• Missing early peritonsillar abscess by not examining for asymmetry, uvular deviation, or trismus 4
• Dismissing persistent unilateral tonsillar pathology in adults without considering malignancy 4
• Treating chronic GAS carriers with repeated antibiotic courses when they have intercurrent viral infections 4
• Not recognizing that tonsilloliths can coexist with bacterial infection—the white material could be both stone and exudate 1, 3, 2

When to Refer to ENT

• Any unilateral tonsillar abnormality persisting >2-3 weeks 4
• Suspected peritonsillar abscess or inability to exclude it clinically 4
• Recurrent tonsilloliths causing significant symptoms 2
• Necrotic-appearing tissue or progressive symptoms despite appropriate treatment 6
• Patient meets Paradise criteria for recurrent tonsillitis (≥7 episodes in 1 year, ≥5/year for 2 years, or ≥3/year for 3 years) 5, 2