Bacterial, Viral and Fungal Diseases

Dr. Sook-Bin Woo

Brigham and Women’s Hospital

Associate Professor or Oral Medicine and Diagnostic Sciences

Harvard School of Dental Medicine

Types of infections Bacterial Fungal Viral Mycobacterial Spirochetal Rickettsial Retroviral Prion

Bacterial infections

Caries – what bacteria? Periodontal disease – what bacteria? Soft tissue infections - may be extension

of periodontal infection or may be non-periodontal

Actinomycosis

Several types– Cervico-facial– Pulmonary– Ileo-cecal– Pelvic – CNS– Periapical (less known, but probably the most common in

the orofacial region)

Board-like very firm swelling with drainage; often an infected tooth in area

Actinomycosis

Histology– On draining the area, typical “sulfur granules”

- yellowish granules within pus– On histologic examination, large clumps of

filamentous, gram -positive BACTERIA, not fungi (in spite of -mycosis), with radiating periphery and surrounded by neutrophils

Treatment of Actinomycosis

Periapical– Curettage and 2-3 weeks of antibiotics

Cervico-facial– Long-term penicillin x 6 months or more

Soft tissue bacterial infections

Usually associated with poor neutrophil function– reduced numbers of neutrophils (quantitative)– poor functioning of neutrophils (qualitative)

such as is seen in diabetes mellitus– immunocompromised in general, poor

lymphocyte function

Soft tissue bacterial infections

Clinical appearance– Abscess formation with pain, swelling,

drainage Management

– Identify underlying problem - systemic or local– Incision and drainage (I and D)– Culture and sensitivity (different tubes)– Antibiotics may be necessary

Management of Staph infections

Penicillin? Amoxicillin with clavulonate Methicillin-resistant staph (MRSA)

Fungal infections

Superficial fungal infections– Most common is candidiasis (candidosis)

Deep fungal infections– Histoplasmosis - Ohio-Mississippi valley– Zygomycosis (Phyllum Zygomycota, class Mucorales,

Rhizopus)– Aspergillosis– Cryptococcosis – farms

Candida

Non-septate hyphae originating from conidia

Most common one is C. albicans Others include C. tropicalis, glabrata,

kruseii, C. dubliniensis– may be resistant to the usual anti-fungal

therapy

Candidiasis - Acute and Chronic

Acute - rapid onset

Pseudomembranous (“thrush”)

Yellow-white plaques and papules that wipe off with some difficulty leaving a red, raw surface; do not always wipe away

Atrophic (angular cheilitis)

Corners of mouth are cracked, fissured, weepy; may not see any white papules

This man presented with this lesion on the tongue that is asymptomatic.

Why is this not thrush?

Candidiasis Chronic - usually long-standingAtrophic (denture sore mouth)Usually bright red, sore area under and outlining a

denture baseHyperplasticChronic muco-cutaneous candidiasis associated

with skin candidiasis and usually endocrinopathyLook like leukoplakia, and does not wipe off easilyAssociated with hairy leukoplakia

Median rhomboid glossitis Candidal infection in the midline of the tongue

just anterior to the circumvallate papillae Candida is clearly identified on biopsy in the

form of penetrating hyphae Used to think it was developmental but never

saw this in younger patients If treat with anti-fungals, lesion now

asymptomatic but often still present.

Diagnosis Clinical appearance KOH (potassium hydroxide preparation) using

a scrape Culture (not the best way - what % of

population are carriers?); a good procedure for speciation if the patient is not responding to routine anti-fungal therapy

Biopsy to identify hyphae (using PAS with diastase stain) - rather drastic

Special stains for fungi

Per-iodic acid Schiff stain with diastase digestion (PAS with D)

Methenamine silver stain

Treatment

Classes of drugs Polyenes - nystatin and amphotericin Imidazoles Triazoles - fluconazole New agents

Prescriptions

Nystatin suspension 1:100,000 iu/ml

Dispense ______ ml (300-500)

Swish and spit out/swallow 5 ml q6h x 10 days

Clotrimazole 10 mg troches

Dispense _________ troches

Take one troche q6h x 10 days

Prescriptions

Fluconazole 100 mg tablets– Dispense ____ tablets; take one tablet x ____

day(Vaginal yeast infxs treated with 1 dose) Amphotericin

– May be given as a swish and spit out preparation– Usually given iv for systemic infection; toxic– Begin with 1 mg, then up to 0.5 mg/kg

Topical therapy for angular cheilitis Mycolog cream

– Mixture of mycostatin (nystatin) and Kenalog (triamcinolone); antifungal and anti-inflammatory

– Dispense 15 g tube. – Apply to affected site TID; or apply to denture

base TID

Vytone– Iodoquinol and hydrocortisone

Treatment of denture (fomite)

Plastic prosthesis such as full denture– 1:10 Chlorox:water - make up in gallon

containers– Soak overnight

Metal prosthesis– 5 ml of nystatin in water or 15 ml of

chlorhexidine in water– Oralsafe: Sodium benzoate – safe for both

Deep fungal infections

Usually presents as a single necrotic ulcer that is persistent

In the case of zygomycosis, usually in diabetics and presents as a persistent sinus infection

Cryptococcosis - often as meningitis in HIV infected individuals

Diagnosis

Because they are deep infections, tissue should be obtained for microscopy and for culture since microscopy alone has limited ability to identify these organisms

Necrosis often occurs because the fungi occlude blood vessels leading to infarction

Management of herpes labialis Prophylaxis

– Sunscreen to prevent injury to the tissues and reactivation of virus

Treatment: always at the first prodrome (tingling)– Topical therapy

» 5% acyclovir cream» 1% penciclovir cream» 10% docosanol cream» 2000 mg valacyclovir BID x 1 day

HSV/immunocompromised Immunocompromised patients

– Occur anywhere - attached and non-attached mucosa – May look like aphthous ulcers (canker sores)

Treatment– Acyclovir 400 mg 3-5 x /day x 10 days (low

bioavailability)– Valacyclovir 500 mg 2-3 x /day x 10 days– Famciclovir 500 mg bid x 10 days

Management of recurrent intraoral HSV

Acyclovir 200-400 mg 3-5 times a day x 7-10 days

Valacyclovir is 3-5 times more bioavailable than acyclovir

Valacyclovir 500-1000 mg 2-3 times a day x 7-10 days

Pain control

Topical anesthetics2% viscous lidocaine– Dispense _(300)_ ml– Swish and spit out 5 ml tid (if necessary,

before meals)

Mix this 1:1:1 with Kaopectate (or Maalox) and Benadryl

Benadryl alone as swish and spit out

Treatment

Hydration, topical pain control (2% viscous lidocaine applied topically); systemic pain control

Treat with anti-viral– Acyclovir (valacyclovir has 3-5X bioavailability

of acyclovir)– Famciclovir (penciclovir)

Erythema multiforme

Erythema multiforme (EM) is hypersensitivity to HSV usually, or even Mycoplasma pneumoniae

Stevens-Johnson syndrome (SJS) or Toxic Epidermal Necrolysis Syndrome (TENS) are variations of the same necrolytic hypersensitivity reaction usually to drugs

Erythema multiforme• Erythema multiforme

• HSV-associated in > 70% of cases; hypersensitivity reaction to HSV and not the active HSV lesion

• HSV usually 7 days prior, and may be asymptomatic• Culture will be negative• Smaller number associated with Mycoplasma

pneumoniae; 2 x antibody titer• Skin lesions occur on face and extremities• Oral mucosa almost always involved• Can be just recurrent oral EM

Varicella-zoster infection

Primary infection: chickenpox (varicella)

Secondary infection: herpes zoster

- Strikingly dermatomal and unilateral

- Usually lumbar

- Location depends on which nerve is involved such as V1, V2 or V3

Treatment

Hydration, pain control Anti-virals as above

Post-herpetic neuralgia

May be debilitating esp in older adults Neuralgia – shooting, paroxysmal pain,

burning, allodynia May last for many years Treat zoster aggressively within 48 hours Vaccine (usually for those > 60yrs)

Hairy Leukoplakia

EBV infection– most often associated with (?) tending to infect

lymphocytes– In HL, it infects the epithelial cells leading to a white

lesion.– First described in HIV infected persons, but seen in

any immunocompromised patient; rare cases in healthy persons

Hairy leukoplakia

ClinicalWhite slightly “hairy” plaque usually on lateral

tongue, but may be on dorsum or on buccal mucosa; painless; diagnosis via biopsy

HistologyBallooned cells with dense viral inclusions and

chromatin condensations against the nuclear membrane

Concomitant candidal infection in >50% of cases

Management

Reduce immunosuppression Treat candidiasis No specific therapy If HIV/AIDS related, HAART will usually

resolve lesions

CMV infection

Usually in immunocompromised patients (infection of GI and retina too)

Clinical– Presenting as a single or multiple large painful

ulcers present for weeks or months– Diagnosis via biopsy

Histology– Large virally-infected cells with large eosinophilic

nucleoli

Treatment

If localized, excision

Radiation (especially to gingiva and palate)

Intra-lesional injection of vinblastine

Human papillomavirus (HPV)

Causes many papillary/warty growths such as plain skin wart (verruca vulgaris), genital warts, oral warts

In patients who are immunocompromised, they may have many such warts

Types > 100 sub-types HPV-6 and -11 usually benign HPV-16 and -18 usually seen with

premalignant and malignant lesions (same for cervix); 31, 33 and 35 also high risk

Association with squamous cell carcinoma of oropharynx and tonsils

Gardasil works against 6,11, 16 and 18

Clinical If white/keratotic with distinct finger-like

projections - verruca vulgaris If soft, with more pink appearance -

papilloma If large, condyloma If flat papules or nodules, thick Heck

disease (HPV 13 and 32); endemic in many low socio-economic communities

Heck disease

HPV -13, -32, 55 Common in Central and South America

where it is clustered in families; resolves as children grow older

Common in Saudi Arabia and Africa

Identification of virus

Replication in nucleus Viral DNA is integrated into human

genome In situ hybridization techniques

Treatment

Excision if single Use of chemical agents - imiquomod,

podophyllin resin (tough in mouth, why?) Will tend to recur especially if skin warts

are present

Coxsackie virus and Enterovirus infection

Hoof-and-mouth disease in livestock In humans

– hand-foot-mouth disease– Herpangina– lymphonodular pharyngitis

Coxsackie virus and Enterovirus infection

Clinical Usually in children. usually epidemic in spring and

fall Caused by Coxsackie A or B, or enterovirus 71. Painful ulcers usually in the oropharynx area, the

posterior palate, soft palate for herpangina May or may not see lesion on skin of hands and

feet in HFM disease No skin involvement in herpangina

Coxsackie virus infection

Treatment– Supportive care only– Self-remitting

Other viral diseases

Variola - measles - Koplik spots Mumps (viral parotitis)

Treatment: Supportive care

Mycobacterial infections

Three of importance

- tuberculosis (Mycobacterium tuberculosis)

- leprosy (Mycobacterium leprae)

- infection by Mycobacterium avian intracellulare (usually in patients with AIDS)

Tuberculosis

Primary infection is in lung (air-borne)

May get secondary infection in mouth from inoculation by sputum onto an ulcerated area

Usually presents as a nodule or an ulcer

Importance: emergence of multi-drug resistant TB is a problem especially poor countries and prisons (overcrowding, poor diagnosis, poor follow-up, poor compliance)

Tuberculosis

Histology

Caseating granulomas that contain acid-fast bacilli

(Remember that true granulomas are collections of epithelioid histiocytes)

Treatment

Drugs such as isoniazid, rifampin, ribavarine for months

Compliance and follow-up are essential for disease control

Granuloma - terminology “-oma” of granulation tissue

– Not true granuloma, but a mass of granulation tissue eg. ??

True granuloma: collection of epithelioid histiocytes; often associated with multinucleated giant cells and lymphocytes

– Classic granulomatous disease include infections (TB, foreign body reaction, sarcoidosis, Crohn disease, orofacial granulomatosis)

Leprosy

Mycobacterium leprae attacks the nerve fibers; subsequent injury does not elicit pain and leads to more injury and tissue destruction until auto-amputation occurs

Leprosy

Histology

Non-caseating granulomas that contain acid-fast bacilli

Treatment

Dapsone

MAI infection

Unlike TB and leprosy, this mycobacterium rarely causes granuloma formation

Usually seen in HIV infection

Histology

Identification of acid-fast bacilli

Treatment

Spirochetal infections

Borrelia vincentis - ANUG (acute necrotizing ulcerative gingivitis), now called necrotizing periodontal disease

Syphilis - treponemal pallidum Lyme disease - Borrelia burgdorferi

Treatment of spirochetal infxs

ANUG– Penicillin– Metronidazole– Debridement after acute stage

Syphilis– Penicillin