Opath1 - Block 2 - Fungal Infections

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List of fungal infections

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- Candidiasis - most common oral fungal infection
- Histoplasmosis
- Coccidiodomycosis
- Cryptococcosis
- Zygomycosis
- Aspergillosis

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Candida albicans

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- yeast-like fungal organism
- Dimorphism: yeast form and hyphae form
- Yeast form - circular shape. Does not invade tissue.
- Hyphae form - long shaped. Invades tissue. Pathogenic!

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Common causes of candidiasis

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- broad-spectrum antibiotics
- immunosuppression
- idiopathic

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Clinical patterns of candidiasis

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- pseudomembranous
- erythematous
- chronic hyperplastic
- mucocutaneous

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Pseudomembranous candidiasis (thrush)

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- Clinical: removable creamy-white patches
- Patients are usually immunocompromised (i.e. babies)
- Sx: very mild, may have burning sensation and foul taste

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Erythamatous candidiasis

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- Much more common, most patients are not immunocompromised
- The mucosa is thinned and red

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4 common clinical presentations of erythamatous candidiasis

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- denture stomatitis
- acute atrophic candidiasis
- median rhomboid glossitis
- angular cheilitis

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Denture stomatitis

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- Clinical: varying degrees of erythema localized to denture-wearing area on maxilla
- rarely symptomatic
- denture stomatitis can also be caused by allergy to denture material and unusual pressure on the mucosa
- Presence of candida - candida is always present on the denture. Fungal hyphae may or may not penetrate epithelium. Pt wears denture continuously.

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Acute atrophic candidiasis

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- often after broad spectrum of antibiotics, or suffer from xerostomia
- diffuse loss of filiform papillae of the dorsal tongue
- burning tongue sensation

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Median rhomboid glossitis (central papillary atrophy)

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- A well-demarcated erythromatous zone affects the midline posterior dorsal tongue, due to loss of filiform papillae
- Smooth or nodular
- Usually asymptomatic
- Kissing lesion: palatal lesion caused by contacting dorsal tongue

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Angular cheilitis

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- fissuring and scaling of the corners of the mouth. Candidiasis is one cause.
- Candida infection can be seen in conditions that allow saliva to pool at the corners of the mouth, i.e. loss of vertical dimension, and drooling.
- Exfoliative cheilitis: Cheilocandidiasis, caused by licking
- need to correct the underlying cause

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Chronic hyperplastic candidasis

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- White plaque that is not removable, background may be red and inflamed
- Usually asymptomatic
-
- Biopsy is necessary: clinically resemble premalignant lesions
- Histology: candidal hyphae penetrating the hyperparakeratotic layer of the epithelium

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Mucocutaneous candidiasis

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- Immunological disorders - pts develop immunological disorders as a baby, and candidal infections affect all mucosal surfaces (mouth, skin, nails, etc)
- Endocrine-candidiasis syndrome, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy -- patients develop autoantibodies against their endocrine glands. Develop endocrine abnormalities later in life.

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Histoplasmosis, Coccidiodomycosis, and Cryptococcus (general)

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- Inhalation of spores and develop primary lesions in the lungs
- Lung: from asymptomatic to cough, chest pain & hemoptysis
- Oral lesions: Usually preceded by pulmonary lesion. Implantation of infected sputum in oral mucosa.
- Hematogenous spread: inflammation erodes into pulmonary blood vessels and can spread.

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Histoplasmosis, Coccidiodomycosis & Cryptococcosis: Oral Lesions

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- Clinical features: chronic non-healing ulcer(s), may penetrate bone
- Biopsy is needed. Serology and cultures are also helpful.
- Histopathology: granulomatous inflammation. Special stains are used to demonstrate the fungus
- Tx: antifungal agents

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Causes for nonhealing ulcers

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- deep fungal infections
- oral squamous cell carcinoma
- traumatic ulceration
- oral TB
- primary syphillis

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Histoplasmosis

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- Inhalation of spores of Histoplasma capsulatum
- The most common systemic fungal infection in US
- The most common deep fungal infection in HIV+ patients
- Endemic areas in US: Mississippi and Ohio River Valleys

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Coccidiodomycosis

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- Inhalation of spores of Coccidiodes immitis
- Endemic areas: central valley of California “valley fever”

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Cryptococcosis

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- Inhalation of spores of Cryptococcus neoformans
- Present in the droppings of pigeons
- Normally causes no problem in immunocompetent people
- A significant cause of death for HIV+ patients before HAART therapy

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Zygomycosis

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- Caused by fungal organisms of the phylum Zygomycota
- Also called “mucormycosis”, “phycomycosis”
- Angiotropic: invade vessel wall, result in ischemia, infarction and necrosis
- Histology: extensive tissue necrosis and the characteristic fungal hyphae

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Zygomycosis is an opportunistic infection infecting what people?

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- uncontrolled diabetics that develop ketoacidosis
- immunocompromised pts

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Zygomycosis - rhinocerebral form

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- Primarily affects the nose, maxillary sinus and midface, with frequent extension to the brain
- Nasal obstruction, epistaxis, facial pain, visual disturbances and headache
- Oral cavity: starts with intraoral swelling of the maxillary alveolar process and the palate. Without treatment, it proceeds to develop palatal necrosis and perforation

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Zygomycosis - Dx, Tx, and prognosis

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- Dx: cannot differentiate from malignancy and requires biopsy/culture
- Tx: surgical debridement, systemic antifungal tx, and management of the underlying predisposing condition
- Prognosis: Poor. There is 60% death rate for rhinocerebral zygomycosis.

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4 types of aspergillosis

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- Mycetoma (aspergilloma)
- Allergic fungal sinusitis
- Local invasive aspergillosis
- Disseminated aspergillosis

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Mycetoma (aspergilloma)

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- Normal patients
- A mass of fungal hyphae
- No tissue invasion
- Tx: Surgical debridement

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Allergic fungal sinusitis

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- Ectopic patients
- Allergic mucin, eosinophils and scattered fungal hyphae
- Tx: Surgical debridement and corticosteroid

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Local invasive aspergillosis

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- Tissue invasion
- May spread to adjacent anatomic structure (CNS)
- Prognosis and Tx depends on patients’ immune status

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Disseminated aspergillosis

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- Immunocompromised & DM pts
- Widespread infection
- Tx: Surgical debridement and systemic antifungal agent, management of the underlying predisposing condition
- Prognosis poor

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Early phase of HIV: Acute phase of HIV infection

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- self-limiting illness within weeks (immunocompenent)
- high levels of virus production, viremia, and reduction of CD4+ T cells
- Seroconversion: Production of Anti-HIV antibodies, useful for screening.
- CD4+ T cells return to near normal numbers.

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Middle phase: Clinical latent period

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- A stage of relative containment of the virus
- Continue HIV replication
- Continue CD4+ cell loss
- Asymptomatic, some may be persistent lymphadenopathy and minor opportunistic infections

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Final phase: crisis phase

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- Break down of host defenses system
- Profound loss of CD4+ cells, full blown AIDS

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HIV transmission

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- Body fluids such as semen and blood are usually the source of infection
- Saliva of HIV patients contains virus but transmission of HIV via saliva is rare

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Oral and Maxillofacial Lesions Strongly Associated with HIV Infection

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- Candidiasis
- Oral Hairy Lerukoplakia
- Kaposi’s Sarcoma
- Non-Hodgkin’s lymphoma
- Periodontal Disease

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Candidiasis in HIV patients

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- Oral candidiasis is the most common intraoral manifestation of HIV infection
- Most common: Candida albicans
- An indication of patients’ immune status: CD4 count low
- HAART significantly reduces the frequency

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Oral Hairy Leukoplakia

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- The most common EBV-related lesion in HIV+ patients
- Clinical: Faint or thickened white vertical streaks that do not rub off. Lateral tongue most common.
- Histopathology: Hyperkeratosis and layer of “ballooning cells” in the upper spinous layer. Histo is suggestive, but not specific.
- Detect EBV by immunohistochemistry or by in situ hybridization
- Tx: not needed

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HIV-Associated Kaposi’s Sarcoma

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- The most common malignancy in HIV patients
- A malignant vascular tumor caused by HHV8/KSHV
- Manifest as multiple lesions of the skin. oral mucosa & viscera
- Oral cavity: palate, tongue & gingiva. Starts as flat purple macular lesions and later develops into nodules. Invades bone.
- Biopsy necessary
- HAART has significantly reduced KS prevalence

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HIV-associated Non-Hodgkin’s Lymphoma

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- The 2nd most common malignancy in HIV patients
- Caused by EBV (and maybe KSHV)
- Majority are high grade B-cell lymphoma.. very malignant!
- Usually occur in extranodal locations. CNS is most common.

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HIV-associated periodontal disease

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- 3 atypical patterns: 1) Linear gingival erythema, 2) Necrotizing ulcerative gingivitis/stomatitis, 3) Necrotizing ulcerative periodontitis
- Not response to conventional perio tx.
- Rapid progression

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Linear gingival erythema

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- Linear band of erythema involving the free gingival margin
- Don’t confuse with marginal gingivitis

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Necrotizing ulcerative gingivitis/stomatitis

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- Ulceration/necrosis of one or more interdental papillae without loss of periodontal attachment

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Necrotizing ulcerative periodontitis

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- Gingival ulceration/necrosis associated with rapid progression loss of periodontal attachment
- Multiple isolated defects often are seen in contrast with the diffuse pattern associated with typical chronic periodontitis

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Other Oral and Maxillofacial Lesions Associated with HIV Infection

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Diffuse Infiltrative Lymphocytosis Syndrome
Human Papillomavirus
Aphthous Ulcerations
Molluscum Contagiosum
Oral Squamous Cell Carcinoma
Mycobacteria
Histoplasmosis
HSV and EBV

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Diffuse Infiltrative Lymphocytosis Syndrome

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- CD8 lymphocytosis and lymphadenopathy
- HIV-ASSOCIATED SALIVARY GLAND DISEASE - Salivary gland enlargement, particularly parotid gland, caused by CD8 lymphocytic infiltrate. High risk to develop B-cell lymphoma. Patients need to be monitored.

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Human Papillomavirus Infection in HIV Patients

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- Verruca vulgaris (common wart) and oral squamous papilloma
- Multiple exophytic and papillary nodules
- HAART treated patients show increased prevalence of HPV-related lesion
- Surface looks like cauliflower

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Aphthous Ulcerations in HIV patients

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- HIV patients have increased frequency to develop all forms of aphthous ulcer (minor, major and herpetiform)
- In contrast to normal patients, most HIV patients develop major or herpetiform variants

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How do you differentiate a herpetiform apthous ulceration from a herpetic ulcer?

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- herpetic ulcer starts out a a vesicle. herpetiform apthous ulcer does not.
- herpetiform apthous ulcer only occurs on mucosa that is NOT bound to bone. herpetic ulcers happen only on mucosa bound to bone.

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Molluscum Contagiosum in HIV Patients

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- caused by poxvirus
- oral lesions are rare
- small dome shaped papules with central depression
- HIV patients: hundreds of lesions, sometimes large. little tendency to resolve itself.

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Oral Squamous Cell Carcinoma in HIV Patients

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The tumor has the same risk factor in HIV patients as in normal population, but tends to occur at a younger age

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gag codes for...

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nucleocapsid proteins

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pol codes for...

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reverse transcriptase, protease, etc.

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env codes for...

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viral coat proteins

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HAART

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reverse transcriptase inhibitor
protease inhibitor
integrase inhibitor
CCR5 inhibitor (coreceptor for HIV-1)

- The treatment does not kill cells infected by the virus, but can drive HIV to undetectable levels in many patients.
- prolong survival time