Infectious Oral Lesions: Viral, Fungal, and Other Infections

Core Review

Candidiasis (Oral Candidiasis, Candidosis, Thrush)

Oral candidiasis is the most common oral fungal infection. The causative organism is typically Candida albicans (~80-90% of cases), though non-albicans species (C. glabrata, C. tropicalis, C. krusei, C. parapsilosis) are increasingly recognized, especially in immunocompromised patients. Candida is a commensal organism in up to 40-60% of healthy individuals — infection represents overgrowth, not acquisition.

Predisposing factors (the "Candida checklist"):

• Antibiotics (broad-spectrum, especially long courses) — eliminate competing bacterial flora
• Corticosteroids (inhaled or systemic) — immunosuppression
• Xerostomia (drug-induced, radiation-induced, Sjögren's syndrome) — loss of salivary antimicrobial functions
• Immunosuppression (HIV/AIDS, chemotherapy, transplant, diabetes mellitus — especially poorly controlled)
• Dentures (especially full maxillary dentures worn continuously — occlusion, maceration)
• Smoking (epithelial changes and local immunosuppression)
• Nutritional deficiencies (iron, folate, vitamin B12)
• Infancy and old age

Four major clinical forms:

1. Pseudomembranous Candidiasis (Thrush)

Classical presentation: White, curd-like ("cottage cheese") plaques that can be WIPED OFF with gauze, leaving an erythematous, often bleeding base. The pseudomembrane is composed of desquamated epithelial cells, fibrin, inflammatory cells, and fungal hyphae.

Location: Any oral mucosal surface. Buccal mucosa, palate, tongue, and oropharynx are common.

Symptoms: Often asymptomatic. May cause mild burning or altered taste. Infants may be fussy with feeding.

Distinguishing feature: Can be wiped off (unlike leukoplakia, lichen planus, or hyperplastic candidiasis). This is a KEY diagnostic test.

Variants:

• Acute pseudomembranous: Associated with antibiotic use, corticosteroids
• Chronic pseudomembranous: Associated with immunosuppression (HIV — may be the presenting sign)

2. Erythematous (Atrophic) Candidiasis

Presentation: Red, atrophic patches. No white pseudomembrane. Smooth, depapillated appearance on the tongue. May be painful or burning.

Common subtypes:

• Acute erythematous (antibiotic sore mouth): Generalized erythema, often painful. Follows broad-spectrum antibiotics. The tongue may be depapillated and tender.
• Chronic erythematous (denture stomatitis / chronic atrophic candidiasis): Erythematous mucosa precisely matching the denture-bearing area (palate). Almost exclusively associated with full maxillary dentures worn continuously (24 hours/day). The denture creates a protected, moist, acidic environment. Often ASYMPTOMATIC. Grade I: petechiae/pinpoint erythema; Grade II: diffuse erythema (most common); Grade III: papillary hyperplasia (irreversible tissue change requiring surgical removal).
• Median rhomboid glossitis: Well-demarcated, rhomboid erythematous area on midline posterior dorsum of the tongue, anterior to circumvallate papillae. Often now considered a form of chronic erythematous candidiasis.
• Angular cheilitis (perlèche): Erythematous fissuring/scaling at the corners of the mouth. Frequently mixed fungal (Candida) and bacterial (Staphylococcus aureus, β-hemolytic streptococci). Associated with loss of vertical dimension of occlusion (redundant skin folds at commissures creating moist environment), nutritional deficiencies (B vitamins, iron), and xerostomia.

3. Chronic Hyperplastic Candidiasis (Candidal Leukoplakia)

Presentation: White plaque that CANNOT be wiped off (must be distinguished from pseudomembranous). May be speckled (red and white). Firm on palpation.

Location: Most common on the anterior buccal mucosa (commissural area). Also lateral tongue.

Clinical significance: This is the form of candidiasis most associated with epithelial dysplasia and malignant transformation. It is considered a potentially malignant disorder. While Candida may not directly cause the dysplasia, chronic infection in the setting of risk factors (smoking, alcohol) may promote malignant change.

Diagnosis: Biopsy is indicated. Histology shows candidal hyphae penetrating the epithelium, with hyperkeratosis, epithelial hyperplasia, and varying degrees of dysplasia.

Treatment: Antifungal therapy PLUS elimination of risk factors (smoking cessation). Resolution of the white plaque after antifungal therapy confirms the candidal component. Persistent leukoplakia after antifungal treatment requires biopsy to rule out dysplasia/carcinoma.

4. Angular Cheilitis (Perlèche)

As described above — erythematous fissures at the labial commissures. Mixed fungal-bacterial etiology. Associated with:

• Loss of vertical dimension (edentulous patients, worn dentures)
• Nutritional deficiencies (riboflavin/B2, folate, iron)
• Xerostomia
• Lip-licking habit (especially in children)

Candidiasis: Diagnosis and Management

Diagnosis: Clinical appearance + history of predisposing factors. Smear with KOH (potassium hydroxide) preparation shows pseudohyphae and budding yeast. Culture on Sabouraud agar. Biopsy for chronic hyperplastic form.

Non-pharmacologic management: Remove or modify predisposing factors: improve denture hygiene (soak overnight, remove at night), manage xerostomia, improve glycemic control in diabetics, address nutritional deficiencies.

Pharmacologic management (general principles): Topical antifungals are first-line for uncomplicated cases. Nystatin oral suspension (not absorbed — topical effect only). Clotrimazole troches. For denture stomatitis, treat the denture (soak in nystatin or dilute sodium hypochlorite) AND the tissue. For immunocompromised/refractory cases, systemic antifungals (fluconazole). Angular cheilitis: combination antifungal-antibacterial cream.

NBDHE note: Always verify specific antifungal medications and doses against current prescribing information and institutional guidelines.

Herpes Simplex Virus (HSV) Infections

Herpes simplex virus exists as two serotypes: HSV-1 (predominantly oral) and HSV-2 (predominantly genital), though either can infect either site. The virus establishes latency in sensory ganglia (trigeminal ganglion for oral HSV) and reactivates with triggers (stress, sunlight, fever, trauma, immunosuppression, menstruation). Once infected, the patient carries the virus for life.

Primary Herpetic Gingivostomatitis

Classic presentation: First-time HSV infection, usually in children and young adults. Prodrome of fever, malaise, lymphadenopathy, followed by eruption of multiple, small vesicular lesions on keratinized and non-keratinized oral mucosa. Vesicles rapidly rupture → multiple, shallow, painful, punctuate ulcers with erythematous halos throughout the mouth (gingiva, tongue, buccal mucosa, palate, lips). The gingiva is intensely erythematous, swollen, and bleeds easily ("gingivo"stomatitis). Perioral vesicles/crusts may be present.

Key features for NBDHE:

• DIFFUSE gingival involvement (distinguishes from recurrent intraoral herpes which spares the gingiva)
• MULTIPLE coalescing ulcers throughout the mouth (not just one area)
• Acute, febrile illness with lymphadenopathy
• Lesions heal without scarring in 7-14 days
• Most common in ages 1-5 years, but can occur at any age

Distinguish from:

• Recurrent aphthous stomatitis: NO vesicles, NO fever, NO diffuse gingivitis, ulcers on NON-keratinized mucosa only, occurs in older patients, recurring pattern
• Erythema multiforme: Target (iris) skin lesions, hemorrhagic crusting of lips, NO diffuse gingivitis, drug or infection trigger
• Herpangina: More posterior (soft palate, tonsillar pillars), NO gingival involvement, caused by Coxsackie virus (enterovirus)

Recurrent Herpes Labialis (Cold Sore, Fever Blister)

Classic presentation: Prodrome of tingling/burning at the site 6-24 hours before eruption. Then vesicles appear at the VERMILION BORDER of the lip (mucocutaneous junction), coalesce, crust over, and heal in 7-10 days without scarring.

Location: Vermilion border of the lips (especially near the commissure). Less commonly: perioral skin, nasal mucosa.

Triggers: Stress, sunlight, fever, illness, trauma (dental procedures — advise pre-treatment with antivirals for patients with frequent/severe recurrences), menstruation, immunosuppression.

Clinical note: Dental appointments can trigger outbreaks in susceptible patients. Prophylactic antivirals (e.g., starting 1-2 days before and continuing through the procedure) may be considered for patients with frequent recurrence.

Recurrent Intraoral Herpes

Classic presentation: In immunocompetent patients, recurrent intraoral HSV almost exclusively involves the KERATINIZED mucosa — the hard palate and attached gingiva. Presents as a small cluster of vesicles that rupture to form small, shallow, punctuate ulcers with erythematous halos. Heals in 7-10 days.

Key distinguishing point: Recurrent intraoral herpes = KERATINIZED mucosa (hard palate, attached gingiva). Aphthous ulcers = NON-KERATINIZED mucosa (buccal, labial, floor of mouth, soft palate, ventral tongue). This distinction is heavily tested.

In immunocompromised patients (HIV, transplant, chemotherapy), recurrent HSV can be more extensive and involve non-keratinized sites, resembling primary herpetic gingivostomatitis.

Distinguish from:

• Aphthous ulcers: Larger, deeper, single or few, non-keratinized mucosa, NO vesicles, recurrent pattern
• Herpes zoster: Unilateral, dermatomal distribution, more painful, older patients

Herpetic Whitlow

HSV infection of the finger — occupational hazard for dental professionals who treat patients with active HSV lesions without gloves. Presents as painful vesicles on the finger. Prevented by universal precautions (gloves!).

Human Papillomavirus (HPV) Lesions

HPV is a DNA virus with >200 genotypes. Some are associated with benign lesions, others with malignancy.

Squamous Papilloma

Clinical appearance: Exophytic, papillary ("cauliflower-like"), pedunculated (stalked) or sessile mass. Usually solitary. White to pink.

Location: Any oral mucosal surface. Palate, tongue, and lips are common.

Etiology: HPV types 6 and 11 (low-risk types).

Clinical significance: BENIGN. Treatment: surgical excision. Recurrence is uncommon.

Verruca Vulgaris (Common Wart)

Clinical appearance: White, exophytic, papillary, sessile mass with a rough, "warty" surface. Usually solitary. Fingers of children are the most common site; autoinoculation to the oral cavity can occur.

Location: Oral — lips, gingiva, anterior tongue.

Etiology: HPV types 2 and 4 (cutaneous HPV types).

Clinical significance: BENIGN. May spontaneously regress. Surgical excision if treatment desired.

Condyloma Acuminatum (Venereal Wart)

Clinical appearance: Larger, broader, cauliflower-like mass. Often multiple, may be clustered. Pink.

Location: Oral — predominantly sexually transmitted (orogenital contact). Labial mucosa, soft palate, lingual frenum.

Etiology: HPV types 6 and 11 (low-risk, but same types as genital warts).

Clinical significance: BENIGN but sexually transmitted. Surgical excision. Screen for other STIs.

Multifocal Epithelial Hyperplasia (Heck's Disease)

Clinical appearance: Multiple, small, flat-topped, dome-shaped papules (cobblestone appearance). Color similar to surrounding mucosa. Extensive involvement (multiple sites).

Location: Buccal, labial, and lingual mucosa.

Epidemiology: Primarily in children and young adults. Higher prevalence in certain populations (Inuit, Native American).

Etiology: HPV types 13 and 32.

Clinical significance: BENIGN, often spontaneously regresses in adolescence. No treatment required.

HPV and Oral Cancer — Key Points

High-risk HPV types (especially HPV-16, also 18, 31, 33, 35) are strongly associated with oropharyngeal squamous cell carcinoma (OPSCC), particularly of the base of tongue and tonsillar region. HPV-associated OPSCC has a better prognosis than tobacco/alcohol-associated OPSCC and is increasing in incidence, particularly in younger, non-smoking men. The oral cavity proper may also be affected, but the association is strongest with the oropharynx. HPV vaccination (Gardasil 9 — covers HPV types 6, 11, 16, 18, 31, 33, 45, 52, 58) is recommended by the CDC for routine vaccination at age 11-12 (can start at age 9) and catch-up through age 26 (and can be considered through age 45).

Varicella-Zoster Virus (VZV)

Varicella (Chickenpox) — Primary VZV Infection

Oral manifestations: Small vesicles/ulcers on the oral mucosa (especially palate and buccal mucosa) concurrent with the skin rash. Lesions are self-limited and heal without scarring.

Herpes Zoster (Shingles) — VZV Reactivation

After primary varicella infection, VZV establishes latency in dorsal root ganglia and cranial nerve ganglia (including the trigeminal ganglion). Reactivation leads to herpes zoster.

Classic presentation: Pain, burning, or paresthesia in a DERMATOMAL distribution (trigeminal nerve divisions) preceding the rash by 1-4 days. Then unilateral, clustered vesicles on an erythematous base in the affected dermatome.

Oral involvement: When VZV reactivates in the trigeminal ganglion:

• V20ter area: Skin of the lower eyelid, upper lip, and side of nose. Oral vesicles/ulcers on the maxillary gingiva and hard palate. Nasociliary nerve involvement (Hutchinson's sign — lesion on the tip of the nose) indicates risk of ocular involvement (corneal ulceration, uveitis) → urgent ophthalmology referral.
• V30rea: Skin of chin, lower lip. Oral vesicles/ulcers on the mandibular gingiva, anterior tongue, and floor of mouth.

Key features distinguishing herpes zoster from recurrent HSV:

• Zoster: UNILATERAL, dermatomal distribution, severe pain, older patients (>50 years)
• HSV: Bilateral, crosses midline, less pain, younger patients (usually)

Complications: Postherpetic neuralgia (PHN) — persistent severe pain in the affected dermatome lasting months to years after the rash heals. More common in patients >60. Prevention: early antiviral therapy. Vaccination: Shingrix (recombinant zoster vaccine) is recommended by CDC for adults ≥50 years (two doses), and for immunocompromised adults ≥19 years.

Herpangina

Etiology: Coxsackie A virus (most commonly A16, also A2, A4, A5, A6, A10) — an enterovirus.

Clinical presentation: Acute onset of fever, sore throat, dysphagia, and malaise. Small vesicles (1-2 mm) on the SOFT PALATE, tonsillar pillars, uvula, and posterior pharynx. Vesicles rupture → small, painful ulcers with red halos (1-2 mm). The anterior mouth (gingiva, buccal mucosa) is typically SPARED.

Key distinguishing feature: Posterior oral cavity/soft palate involvement; SPARES the gingiva. This distinguishes from primary herpetic gingivostomatitis (diffuse gingivitis + anterior involvement).

Epidemiology: Most common in children (ages 3-10). Summer/fall seasonal pattern.

Treatment: Self-limited — resolves in 3-7 days. Supportive care (hydration, analgesics).

Hand, Foot, and Mouth Disease (HFMD)

Etiology: Coxsackie A16 (most common), enterovirus 71, and other coxsackieviruses.

Clinical presentation: Fever, malaise, followed by oral vesicles/ulcers AND cutaneous vesicles on the hands (palms) and feet (soles). Oral lesions similar to herpangina (posterior palate, tonsillar pillars, tongue, buccal mucosa). The triad of oral + hand + foot involvement is pathognomonic.

Epidemiology: Most common in young children (outbreaks in daycare/schools). Spring/fall seasonal pattern.

Severe form: Enterovirus 71 can cause severe neurological complications (aseptic meningitis, encephalitis). More prevalent in Asia-Pacific region.

Clinical Application

The dental hygienist must recognize infectious oral lesions to: (1) determine if the patient is contagious (HSV, VZV, herpangina — infection control implications); (2) identify underlying immunosuppression (candidiasis may be the presenting sign of undiagnosed HIV, diabetes); (3) distinguish infectious from non-infectious lesions (HSV vs. aphthous; candidiasis vs. leukoplakia) to guide appropriate management; (4) provide patient education about transmission, recurrence, and trigger management.

Common Traps

• Confusing HSV and aphthous ulcers — HSV = keratinized mucosa, vesicles, possible fever; aphthous = non-keratinized, NO vesicles, recurrent
• Thinking all candidiasis looks like thrush — erythematous form is common and easily missed
• Forgetting that chronic hyperplastic candidiasis is a potentially malignant disorder
• Confusing herpes zoster with recurrent HSV — zoster is UNILATERAL (does not cross midline) and dermatomal
• Thinking herpangina = HSV — herpangina is posterior (soft palate, tonsillar pillars) and spares the gingiva; caused by Coxsackie virus