HIV-associated Pulmonary Disease. Classic and Challenging Cases from the HIV/AIDS Clinic and Beyond QUESTION: HIV-associated Pulmonary Diseases

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1 Classic and Challenging Cases from the HIV/AIDS Clinic and Beyond Laurence Huang, MD Professor of Medicine University of California San Francisco Chief, HIV/AIDS Chest Clinic Zuckerberg San Francisco General Hospital HIV, Infectious Diseases, and Global Medicine Division, Division of Pulmonary and Critical Care Medicine HIV-associated Pulmonary Disease The spectrum of pulmonary diseases in HIV-infected persons is broad: HIV-associated Opportunistic infections Neoplasms Miscellaneous conditions Antiretroviral therapy (ART)-associated Non HIV-associated HIV-associated Pulmonary Diseases Opportunistic Infections Non-infectious Neoplasms Bacteria Pulmonary Kaposi sarcoma Mycobacteria Pulmonary Non-Hodgkin Lymphoma Pneumocystis Lung cancer Fungi Viruses Miscellaneous Conditions Parasites Lymphocytic interstitial pneumonitis Nonspecific interstitial pneumonitis COPD Pulmonary arterial hypertension Pulmonary fibrosis I spend the majority of my clinical time A. Inpatient care B. Critical care C. Outpatient care D. None of the above Crothers, Morris and Huang. Chapter 90. Textbook of Respiratory Medicine Laurence Huang, MD Copyright 2012

2 Outline Case-based approach = Interactive (ARS) Outpatient focus Cases from my HIV/AIDS Chest Clinic and beyond Classic and challenging cases old and new Wide range of backgrounds and experience Clinical and management pearls Professional society, National guidelines CD4 < 100 cells/µl Case 1 Several months of increasing dyspnea Exercise tolerance currently < 1 block Denies fever; no change in chronic cough Lungs hyperresonant, quiet breath sounds (bilateral) All Slides are in Syllabus Case 1 A. Bacterial pneumonia B. Pneumocystis pneumonia (PCP) C. COPD/emphysema D. Pulmonary Kaposi sarcoma (KS)

3 COPD-Key Points 1. HIV-infected individuals are subject to the entire spectrum of pulmonary disease. The presence of HIV infection cannot exclude the possibility that the patient presents with a non-hiv-associated pulmonary disease. 2. HIV-infected individuals are at increased risk for COPD (independent of cigarette smoking) and perhaps COPD exacerbations, may develop COPD at an earlier age, and may have an accelerated decline in their FEV1. Drummond, MB, Kunisaki, KM and Huang, L. Obstructive lung diseases in HIV: A clinical review and identification of key future research needs. Semin Respir Crit Care Med 2016;37: COPD-Key Points 3. No HIV-specific guidelines. Diagnosis (pulmonary function tests, PFTs) and treatment identical to non- HIV-infected individuals. COPD Diagnosis and Management: COPD Exacerbations: Eur Respir J 2017; 49: B. An isolated decrease in DLco = most frequent finding in HIV-infected individuals. If moderate-to-severe COPD and persistent symptoms and/or frequent exacerbations: 4. Triple therapy (inhaled glucocorticoid, LABA, LAMA) associated with decreased exacerbations but increased risk for pneumonia. Case 2 Case 2 CD4 = 400 cells/µl 5 days of fever, chills, chest pain, cough productive of purulent sputum, and dyspnea Lungs Egophony, increased tactile fremitus, and bronchovesicular breath sounds (right)

4 A. Bacterial pneumonia B. Pneumocystis pneumonia (PCP) C. COPD/emphysema D. Pulmonary Kaposi sarcoma (KS) Bacterial Pneumonia-Key Points 1. Most frequent HIV-associated opportunistic pneumonia 2. Rates are 25-fold higher than among non-hiv-infected Rates increase as CD4 cell count decreases Rates of pneumococcal bacteremia are fold higher than age-matched controls 3. Specific causative agent identified in 40-75% Streptococcus pneumoniae (40%) Haemophilus influenzae (10-15%) Staphylococcus aureus (5%) Beware community MRSA! Pseudomonas aeruginosa (5%) Feikin. Lancet Infect Dis 2004;4: Bacterial Pneumonia-Key Points 4. USPHS Treatment Guidelines (reviewed July 2017) 5. Treatment and outcome (HIV+ vs. HIV-) No differences in the time to clinical stability, the length of hospitalization, or mortality Christensen. Clin Infect Dis 2005;41: Preventive strategies Combination antiretroviral therapy Pneumococcal vaccine (CD4>200 cells/µl) Trimethoprim-sulfamethoxazole (CD<200 cells/µl) Risk factor modification Cigarettes, injection and smoked illicit drugs Case 3 CD4 > 300 cells/µl (HIV RNA undetectable) Several months of increasing dyspnea Exercise tolerance currently < 1 block Denies fever; no change in chronic cough Lungs hyper-resonant, quiet breath sounds (bilateral)

5 Case 3 A. Bacterial pneumonia B. Pneumocystis pneumonia (PCP) C. COPD/emphysema D. Pulmonary Kaposi sarcoma (KS) Pulmonary Nodules-Key Points Pulmonary Nodules-Key Points 1. Fleischner Society, Radiological Society of North America, Updated No HIV-specific guidelines. 3. Pulmonary nodules are a frequent chest CT finding in HIV-infected individuals 25% of 158 HIV-infected individuals Triplette. AIDS 2017;31: Differential diagnosis of pulmonary nodules in HIV is BROAD * Increase in size mandates diagnostic w/u (e.g., biopsy, surgical removal

6 Case 4 Case 4 CD4 = 100 cells/µl 3 weeks of fever, cough (non-productive), and dyspnea Lungs Bilateral inspiratory crackles Heart Tachycardic, no gallops or murmurs A. Bacterial pneumonia B. Pneumocystis pneumonia (PCP) C. COPD/emphysema D. Pulmonary Kaposi sarcoma (KS) PCP-Key Points 1. PCP classically presents with 2-4 weeks of gradually progressive symptoms Often HIV identifying (and AIDS-defining) diagnosis 2. CXR with bilateral reticular or granular opacities 3. Chest HRCT useful to rule out PCP absence of ground-glass opacities Chest High Resolution CT (HRCT) scan of HIV-infected individual with PCP

7 PCP-Key Points Case 5 4. Bronchoscopy with bronchoalveolar lavage (BAL) remains the gold standard diagnostic procedure Sensitivity = 89% to >98% (Broaddus 1985, Golden, 1986, Huang 1995) 5. USPHS Treatment Guidelines (updated July 2017) Trimethoprim-sulfamethoxazole is the first-line treatment (and prophylaxis) regimen TMP-SMX drug resistance? Emerg Infect Dis CD4 = 50 cells/µl 3 weeks of fever, cough, and dyspnea HEENT mild oral candidiasis, no KS lesions Lungs coarse breath sounds Other no hepatosplenomegaly, no cutaneous KS lesions Case 5 A. Bacterial pneumonia B. Pneumocystis pneumonia (PCP) C. COPD/emphysema D. Pulmonary Kaposi sarcoma (KS)

8 Kaposi s Sarcoma-Key Points 1. Pulmonary KS can present in the absence of mucocutaneous disease The absence of mucocutaneous KS cannot rule out (significant) pulmonary KS. 2. Nevertheless, most patients with pulmonary KS will have mucocutaneous disease 3. KS seen almost exclusively in MSM Kaposi s Sarcoma-Key Points 4. Patients with pulmonary KS may have concurrent opportunistic infection (>25%) 5. Key: MSM and characteristic CXR 6. Diagnosis: BAL to r/o OI Pulmonary KS in trachea seen on bronchoscopy Case 6A CD4 = 400 cells/µl 3 weeks of fever, night sweats, cough, and dyspnea Gradual weight loss Case 6A Close-up Lungs coarse breath sounds (right)

9 A. Tuberculosis (TB) B. Cryptococcal Pneumonia C. Endemic Fungal Pneumonia D. Lung Cancer Case 6B CD4 = 100 cells/µl 3 weeks of fever, night sweats, cough, and dyspnea Gradual weight loss HEENT cervical lymphadenopathy Lungs coarse breath sounds (right) Other hepatomegaly Case 6B A. Tuberculosis (TB) B. Cryptococcal Pneumonia Has anyone seen my key? C. Endemic Fungal Pneumonia D. Lung Cancer

10 Tuberculosis-Key Points 1. Many of the HIV-associated pulmonary diseases have important extrapulmonary manifestations Tuberculosis-Key Points 3. The characteristic radiographic presentation of TB depends on the CD4 cell count 2. At CD4 cell count <200, TB often presents with extrapulmonary disease Lymph nodes (cervical, supraclavicular, axillary) Liver Bone marrow, Genitourinary and Central Nervous System High CD4 count = upper lung zone disease, often with cavitation Low CD4 count = diffuse disease (including miliary), mid+lower lung zone disease, cavitation less common, hilar and mediastinal adenopathy Normal chest radiographs (~10%) Aderaye. Infection 2004;32: Tuberculosis-Key Points 4. Diagnosis begins with expectorated sputum x 3 sent for AFB smear and mycobacterial culture Negative sputum smears are common, particularly among those with advanced immunocompromise and with noncavitary disease Yield of sputum mycobacterial culture is similar to HIV- and is not affected by degree of immunocompromise Sputum sent for nucleic acid amplification testing becoming front line diagnostic test Pleural fluid (with biopsies) should be sent if +pleural effusion Extrapulmonary biopsies/samples Tuberculosis-Key Points 5. USPHS Treatment Guidelines (updated September 2017) Same as for HIV- Initial 4-drug regimen: INH, rifampin, ethambutol and pyrazinamide (+Vitamin B6) x ~2 months (while awaiting cultures and sensitivities) If pan-sensitive, stop ethambutol and pyrazinamide and continue INH and rifampin for a total of 6 months (~4 additional months)

11 Case 7 Case 7 CD4 < 50 cells/µl (HIV RNA ~2K copies/ml) Cough (occasional phlegm) Lungs clear to auscultation Case 7 A. Tuberculosis (TB) B. Cryptococcal Pneumonia C. Endemic Fungal Pneumonia D. Lung Cancer

12 Lung Cancer-Key Points 1. Clinical presentation and diagnosis compared to non- HIV-infected patients HIV-infected significantly younger (median age 50 vs. 68 years) Adenocarcinoma and squamous carcinoma predominate Stage IIIB/IV disease (77%) Outcomes probably comparable Case 8 CD4 = 285 cells/µl on HAART (nadir < 100 cells/µl) 2-3 months gradually progressive dyspnea, slight cough No fever Unremarkable Case 8 A. Tuberculosis (TB) B. Cryptococcal Pneumonia C. Endemic Fungal Pneumonia D. Lung Cancer

13 Hypersensitivity Pneumonitis-Key Points ART-associated Pulmonary Disease 1. Patient only developed symptoms after experiencing a rise in CD4 cell count due to HAART In hypersensitivity pneumonitis, the underlying mechanism of disease is host-mediated lung damage in response to inhaled antigen Initial CXR Follow-up CXR 2. Increase in reports of sarcoidosis or sarcoidosis-like disease Sarcoidosis IRIS and OI presentation PM Case 9 Case 9 CD4 > 300 cells/µl (HIV RNA undetectable) Severe shortness of breath, audible wheezing Lungs clear to auscultation but diminished breath sounds CXR after therapeutic intervention

14 A. Tuberculosis (TB) B. Cryptococcal Pneumonia C. Endemic Fungal Pneumonia D. Lung Cancer Life-Threatening Tracheal Stenosis! Immune Reconstitution-Key Points 1. Immune Reconstitution Syndrome Describes paradoxical worsening of opportunistic infection with concurrent treatment of HIV and OI days to months 2. Pulmonary diseases TB, pulmonary MAC, PCP, Cryptococcus Presents with worsening, recurrent (occasionally new) symptoms and CXR findings Hirsch. Clin Infect Dis 2004;38: Lawn. Lancet Infect Dis 2005;5: Immune Reconstitution-Key Points 3. Diagnosis of EXCLUSION Non-adherence Drug resistance Concurrent or superimposed process 4. Related to immune response to residual organism and/or antigen Hirsch. Clin Infect Dis 2004;38: Lawn. Lancet Infect Dis 2005;5: CD4 = 100 cells/µl Case 10 2 weeks of fever, cough (non-productive), and dyspnea More recently, cough productive of purulent sputum Lungs bilateral inspiratory crackles and focal findings (egophony, decreased breath sounds)

15 Case 10 A. Tuberculosis (TB) B. Cryptococcal Pneumonia C. Endemic Fungal Pneumonia D. Lung Cancer PCP and Bacterial Pneumonia- Key Points PCP and Cryptococcus 1. HIV-infected patients may present with more than one concurrent disease PCP diagnosed in 14 of 111 bacterial pneumonia cases (12.6%) Afessa. Chest Bacterial infection complicates PCP in ~10% 2. Beware: Concurrent diseases that present with identical clinical and radiographic features PCP and Cryptococcal pneumonia most often present with bilateral reticular or granular opacities

16 SUMMARY HIV-associated Pulmonary Disease The spectrum of pulmonary diseases in HIV-infected persons is broad: HIV-associated Opportunistic infections (BP, TB, PCP) Neoplasms (KS, NHL, lung cancer) Miscellaneous conditions (COPD, LIP, NSIP, PAH) ART-associated (HP, sarcoidosis, TB-IRIS, PCP) Non HIV-associated (Pulmonary nodules? Tracheal stenosis) SUMMARY HIV-associated Pulmonary Disease Classic presentations of HIV-associated pulmonary diseases Presentations vary and overlap Patients may present with more than one concurrent pulmonary disease (PCP and BP) New era of ART-related pulmonary conditions THANKS!