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HIV/AIDS. Humphrey Shao MD,MHS. Overview. WHO Staging criteria Opportunistic infections For each disease: Epidemiology Clinical Manifestations Diagnosis. WHO Clinical Staging of HIV Disease in Adults and Adolescents. CLINICAL STAGE 1 Asymptomatic Persistent generalized lymphadenopathy.
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HIV/AIDS Humphrey Shao MD,MHS
Overview • WHO Staging criteria • Opportunistic infections For each disease: • Epidemiology • Clinical Manifestations • Diagnosis
WHO Clinical Staging of HIV Disease inAdults and Adolescents • CLINICAL STAGE 1 • Asymptomatic • Persistent generalized lymphadenopathy
WHO Clinical Staging of HIV Disease inAdults and Adolescents • CLINICAL STAGE 2 • Moderate unexplained weight loss • (<10% of presumed or measured body weight)a • Recurrent respiratory tract infections: sinusitis, tonsillitis, otitis media and pharyngitis) • Herpes zoster • Angular cheilitis • Recurrent oral ulceration • Papularpruritic eruptions • Seborrhoeic dermatitis • Fungal 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 count • Advanced 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 dermatome • Extensive skin involvement or visceral involvement are rare • Progressive 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 adolescents • Respiratory 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
WHO Clinical Staging of HIV Disease inAdults and Adolescents • CLINICAL 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 candidiasis • Oral 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 common • Most common in patients with CD4 count <200 cells/µL • Prevalence lower in patients on ART • Vulvovaginal candidiasis • Occurs in non-HIV-infected women; does not indicate immunosuppression • In advanced immunosuppression, may be more severe or recur more frequently • Usually caused by Candida albicans; other species (especially C glabrata) seen in advanced immunosuppression, refractory cases
Mucocutaneous Candidiasis:Clinical Manifestations • Oropharyngeal (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 cheilosis • Esophageal: 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 diagnosis • KOH preparation, culture • Esophageal: • Clinical, with trial of therapy • Endoscopy with histopathology and culture • Vulvovaginal: • Clinical diagnosis, KOH preparation
WHO Clinical Staging of HIV Disease inAdults and Adolescents • CLINICAL STAGE IV • HIV wasting syndrome • Pneumocystis pneumonia • Recurrent severe bacterial pneumonia • Chronic herpes simplex infection (orolabial, genital or anorectal • of 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 sarcoma • Cytomegalovirus infection (retinitis or infection of other organs) • Central nervous system toxoplasmosis • HIV encephalopathy • Extrapulmonarycryptococcosis including meningitis • Disseminated non-tuberculousmycobacterial infection • Progressive multifocal leukoencephalopathy • Chronic cryptosporidiosis (with diarrhoed) • Chronic isosporiasis • Disseminated 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 carcinoma • Atypical disseminated leishmaniasis • Symptomatic HIV-associated nephropathy or symptomatic HIV-associated • cardiomyopathy
Pneumocystisjiroveci Pneumonia: Epidemiology • Caused by P jiroveci (formerly P carinii) • Ubiquitous in the environment • Initial infection usually occurs in early childhood • PCP may result from reactivation or new exposure • In immunosuppressed patients, possible airborne spread
PCP: Epidemiology Risk factors: • CD4 count <200 cells/µL • CD4% <15% • Prior PCP • Oral thrush • Recurrent bacterial pneumonia • Unintentional weight loss • High 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 diagnostic • Organism cannot be cultured • Definitive 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 presentations • May be normal in early disease • Typical: diffuse bilateral, symmetrical interstitial infiltrates • May 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-section • Patchy ground-glass attenuation • May be normal
PCP:Diagnosis • Definitive diagnosis requires demonstrating organism: • Induced sputum (sensitivity <50% to >90%) • Spontaneously expectorated sputum: low sensitivity • Bronchoscopy with bronchoalveolar lavage (sensitivity 90-99%) • Transbronchial biopsy (sensitivity 95-100%) • Open lung biopsy (sensitivity 95-100%)
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, headache • Neck stiffness, photophobia, or other classic meningeal signs and symptoms in 25-35% of cases • Lethargy, 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 involvement • Cough, dyspnea, abnormal chest X ray • Skin lesions • Papules, 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 findings • Mildly elevated protein, normal or slightly low glucose, few lymphocytes, many organisms • Elevated opening pressure