Humphrey Shao MD,MHS

OverviewWHO Staging criteria

Opportunistic infectionsFor each disease:

Epidemiology Clinical Manifestations Diagnosis

WHO Clinical Staging of HIV Disease inAdults and AdolescentsCLINICAL STAGE 1

AsymptomaticPersistent generalized lymphadenopathy

WHO Clinical Staging of HIV Disease inAdults and AdolescentsCLINICAL STAGE 2

Moderate unexplained weight loss(<10% of presumed or measured body weight)aRecurrent respiratory tract infections: sinusitis,

tonsillitis, otitis media and pharyngitis)Herpes zosterAngular cheilitisRecurrent oral ulcerationPapular pruritic eruptionsSeborrhoeic dermatitisFungal nail infections

Varicella Zoster Virus Disease: Epidemiology

Reactivation of VZV that had been latent in dorsal root ganglia since original infection with VZV (chickenpox)

Herpes zoster occurs in 3-5% of adults in the United States; more prevalent in immunocompromised and elderly

Varicella Zoster Virus Disease: Epidemiology

Incidence 15-25 times greater in HIV-infected than in general population

Can occur at any CD4 countAdvanced immunosuppression may

change manifestations but does not substantially change incidence

Varicella Zoster Virus Disease: Clinical Manifestations

Herpes zoster (shingles): prodrome of pain in affected dermatome, then characteristic skin lesions in same dermatomeExtensive skin involvement or visceral

involvement are rareProgressive outer retinal necrosis may be

seen, usually with CD4 count <50 cells/µL Rapid progression and vision loss

Acute retinal necrosis due to peripheral necrotizing retinitis may occur at any CD4 count (more often at higher CD4)

Varicella Zoster Virus Disease: Clinical Manifestations

Chickenpox: primary VZV infection, uncommon in adults and adolescentsRespiratory prodrome, then vesiculopapular

lesions (face and trunk > extremities)In advanced immunosuppression, may persist

for weeks

Reports of transverse myelitis, encephalitis, vasculitic stroke

Varicella Zoster Virus Disease: Diagnosis

Clinical diagnosis based on appearance of lesions

Viral culture or antigen detection from swabs from fresh lesion or tissue biopsy

HERPES ZOSTER (VALICELLA ZOSTER INFECTIONS

BACTERIAL SKIN INFECTION (PRURITIC PAPURIC ERUPTIONS)

BACTERIAL SKIN INFECTION (PRURITIC ECZEMATOUS ERUPTIONS)

Seborrheic Dermatitis

SEBORRHEIC DERMATITIS

Seborrheic Dermatitis

WHO Clinical Staging of HIV Disease inAdults and AdolescentsCLINICAL STAGE III

Unexplained severe weight loss (>10% of presumed or measured body weight)

Unexplained chronic diarrhea for longer than one month

Unexplained persistent fever (above 37.6°C intermittent or constant, for longer than

one month)Persistent oral candidiasisOral hairy leukoplakia

CLINICAL STAGE 3 cont;Pulmonary tuberculosis (current)Severe bacterial infections (such as

pneumonia, empyema, pyomyositis, bone or joint infection, meningitis or bacteraemia)

Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis

Unexplained anaemia (<8 g/dl), neutropaenia (<0.5 × 109 per litre) or chronic

Thrombocytopaenia (<50 × 109 per litre)

Mucocutaneous Candidiasis: Epidemiology

Oropharyngeal and esophageal candidiasis are commonMost common in patients with CD4 count <200 cells/µLPrevalence lower in patients on ART

Vulvovaginal candidiasis Occurs in non-HIV-infected women; does not indicate

immunosuppressionIn advanced immunosuppression, may be more severe or

recur more frequentlyUsually caused by Candida albicans; other species

(especially C glabrata) seen in advanced immunosuppression, refractory cases

Mucocutaneous Candidiasis: Clinical ManifestationsOropharyngeal (thrush):

Pseudomembranous: painless, creamy white plaques on buccal or oropharyngeal mucosa or tongue; can be scraped off easily

Erythematous: patches on anterior or posterior upper palate or tongue

Angular cheilosisEsophageal: retrosternal burning pain or

discomfort, odynophagia, fever; on endoscopy, whitish plaques with or without mucosal ulceration

Vulvovaginal: creamy discharge, mucosal burning and itching

Mucocutaneous Candidiasis: Diagnosis

Oropharyngeal:Usually clinical diagnosisKOH preparation, culture

Esophageal:Clinical, with trial of therapyEndoscopy with histopathology and culture

Vulvovaginal:Clinical diagnosis, KOH preparation

WHO Clinical Staging of HIV Disease inAdults and Adolescents

CLINICAL STAGE IVHIV wasting syndromePneumocystis pneumoniaRecurrent severe bacterial pneumoniaChronic herpes simplex infection

(orolabial, genital or anorectalof more than one month’s duration or visceral

at any site)Oesophageal candidiasis (or candidiasis of

trachea, bronchi or lungs)Extrapulmonary tuberculosis

CLINICAL STAGE IV cont;

Kaposi’s sarcomaCytomegalovirus infection (retinitis or infection of

other organs)Central nervous system toxoplasmosisHIV encephalopathyExtrapulmonary cryptococcosis including meningitisDisseminated non-tuberculous mycobacterial infectionProgressive multifocal leukoencephalopathyChronic cryptosporidiosis (with diarrhoed)Chronic isosporiasisDisseminated mycosis (coccidiomycosis or

histoplasmosis)

CLINICAL STAGE IV cont;

Recurrent non-typhoidal Salmonella bacteraemia

Lymphoma (cerebral or B-cell non-Hodgkin) or other solid HIV-associated tumours

Invasive cervical carcinomaAtypical disseminated leishmaniasisSymptomatic HIV-associated nephropathy

or symptomatic HIV-associatedcardiomyopathy

Pneumocystis jiroveci Pneumonia: EpidemiologyCaused by P jiroveci (formerly P carinii)Ubiquitous in the environmentInitial infection usually occurs in early

childhoodPCP may result from reactivation or new

exposureIn immunosuppressed patients, possible

airborne spread

PCP: EpidemiologyRisk factors:CD4 count <200 cells/µLCD4% <15% Prior PCPOral thrushRecurrent bacterial pneumoniaUnintentional weight lossHigh HIV RNA

PCP: Clinical Manifestations

Progressive exertional dyspnea, fever, nonproductive cough, chest discomfort

Subacute onset, worsens over days-weeks (fulminant pneumonia is uncommon)

Chest exam may be normal, or diffuse dry rales, tachypnea, tachycardia (especially with exertion)

Extrapulmonary disease seen rarely; occurs in any organ, associated with aerosolized pentamidine prophylaxis

PCP: Diagnosis

Clinical presentation, blood tests, radiographs suggestive but not diagnosticOrganism cannot be culturedDefinitive diagnosis should be sought

Hypoxemia: characteristic, may be mild or severe (PO2 <70 mm/Hg or A-a gradient >35 mm/Hg)

LDH >500 mg/dL is common but nonspecific

PCP: Diagnosis

CXR: various presentationsMay be normal in early diseaseTypical: diffuse bilateral, symmetrical

interstitial infiltratesMay see atypical presentations, including

nodules, asymmetric disease, blebs, cysts, pneumothorax

Cavitation or pleural effusion is uncommon(unless caused by a second concurrent process)

Chest CT, thin-sectionPatchy ground-glass attenuationMay be normal

PCP: Diagnosis

Definitive diagnosis requires demonstrating organism:Induced sputum (sensitivity <50% to >90%)

Spontaneously expectorated sputum: low sensitivityBronchoscopy with bronchoalveolar lavage

(sensitivity 90-99%)Transbronchial biopsy (sensitivity 95-100%)Open lung biopsy (sensitivity 95-100%)

HPV (MUCOSAL VIRAL WARTS)

HPV II GENITALIA

COMMON SITES FOR KAPOSIS SARCOMA

COMMON SITES FOR KAPOSIS SARCOMA

EXTENSIVE CUTENOUS KAPOSIS SARCOMA

EXTENSIVE CUTENOUS KAPOSIS SARCOMA

Cryptococcosis: Epidemiology

Caused by Cryptococcus neoformans Most cases seen in patients with CD4

count<50 cells/µL

5-8% prevalence in HIV-infected patients in developed countries before widespread use of effective ART

Incidence much lower with use of ART

Cryptococcosis: Clinical Manifestations

Subacute meningitis or meningoencephalitis(most common presentation) Fever, malaise, headacheNeck stiffness, photophobia, or other classic

meningeal signs and symptoms in 25-35% of casesLethargy, altered mental status, personality

changes (rarely)

Acute illness with nuchal rigidity, seizures, focal neurologic signs observed in developing countries

Cryptococcosis: Clinical Manifestations

Disseminated disease is common: often pulmonary infection with or without meningeal involvementCough, dyspnea, abnormal chest X ray

Skin lesionsPapules, nodules, ulcers, infiltrated plaques

seen in disseminated disease

Cryptococcosis: Diagnosis

Detection of cryptococcal antigen (CrAg) in CSF, serum, bronchoalveolar lavage fluid (can have false-negative results)

India ink stain (lower sensitivity)Blood culture (positive in 75% of those with

cryptococcal meningitis)Patients with positive serum CrAg should

have CSF evaluation to exclude CNS disease

CSF findingsMildly elevated protein, normal or slightly low

glucose, few lymphocytes, many organismsElevated opening pressure