45 yo man with AIDS, LE edema, and pulmonary nodules

1. 45 yo man with AIDS, LE edema, and pulmonary nodules Anh Innes, M.D. March 4, 2003

3. History 45 yo man with AIDS, CD4+ of 8, admitted for left LE edema and groin pain. Pt s/p local trauma to leg 3 days PTA + tactile fevers and chills; denied cough, SOB, hemoptysis

4. History,cont. PMH HIV dx 1992 Crypto meningitis PCP Oral thrush Bacillary angiomatosis x 2 Hepatitis C with cirrhosis Meds: none Social: IVDA x 25 years (speed) Occ ETOH, + tobacco (10 pack-years) Prior homosexual contacts Homeless

5. Physical Exam AFVSS 98% RA HEENT: no oral thrush Lungs: CTA Abd: slightly distended with fluid wave Ext: L groin-- edema, erythema, fluctuant mass LLE > RLE No rashes

6. Data 9.1 5.1 163 Na 128, K 4.2 Alk 435, AST 55, ALT 52 LN dissection: MRSA abscess and bacteremia Warthin-Starry stain + = BA HHV-8 + = KS Other tests and diagnostic measures?Other tests and diagnostic measures?

7. Bronchoscopy revealed slightly raised, erythematous, hypervascular lesions of the airway consistent with KS Findings R>L�which would not have been expected by CT scan Does this confirm diagnosis of KS? What about BA? How to treat? Doxycycline x 2 months, HAART for KS BA: vascular proliferative manifestations of bartonella infection Think BA in a non-homosexual patient with Kaposi�s Reported in HIV, post-heart and renal transplant and chemotherapy, a few immunocompetent patients BA esp when CD4 <100; one study with 42 patients with BA�average CD4 count = 21 Skin�well circumscribed, polypoid, obviously vascuar erythematous lesions with or without crusting often surrounded by erythematous collar; tender, friable, bleed easily; nodules angiomatous or violaceous, but if subcutaneous they may not affect skin color Severe anemia�usually out of proportion to to overall condition KS generally less well-circumscribed, less friable, lack erythematous collar, usually not painful Peliosis hepatis�venous lakes inside hepatic tissue; unusual before HIV, Weight loss, fever, abdominal pain, hepatomegaly, spleomegaly, increase alk phosphataseBronchoscopy revealed slightly raised, erythematous, hypervascular lesions of the airway consistent with KS Findings R>L�which would not have been expected by CT scan Does this confirm diagnosis of KS? What about BA? How to treat? Doxycycline x 2 months, HAART for KS BA: vascular proliferative manifestations of bartonella infection Think BA in a non-homosexual patient with Kaposi�s Reported in HIV, post-heart and renal transplant and chemotherapy, a few immunocompetent patients BA esp when CD4 <100; one study with 42 patients with BA�average CD4 count = 21 Skin�well circumscribed, polypoid, obviously vascuar erythematous lesions with or without crusting often surrounded by erythematous collar; tender, friable, bleed easily; nodules angiomatous or violaceous, but if subcutaneous they may not affect skin color Severe anemia�usually out of proportion to to overall condition KS generally less well-circumscribed, less friable, lack erythematous collar, usually not painful Peliosis hepatis�venous lakes inside hepatic tissue; unusual before HIV, Weight loss, fever, abdominal pain, hepatomegaly, spleomegaly, increase alk phosphatase

8. BA vs KS BA, cont. or slightly elevated bili, transaminitis Pulmonary�polypoid endobronchial lesions, parenchymal mass (hypervascular) with pleural effusion and parietal involvement; interstitial pneuonia Radiographic appearance often with intense contrast enhancement�nodes and parenchymal mass�due to ectatic vascular spaces seen in the resected mass Common imaging: lung nodules, mediastinal adenopathy, peripheral adenoatphy, pleural effusions, ascites, abdominal adenopathy, soft tisue mases, low attenuation lesions in the liver and/or spleen�dramatic enhancement with contrast injection; Lung noduels�no spiculation, primarily associated with vascular structures, some septal thickening, many nodules peripheral Lymph node�mediastinal adenopathy, hilar adenopathy, abdominal and mesenteric�dramatic contrast enhancement Pleural effusions can be large Rapid improvement with antibiotics; recurrence does occur; Path�PMN infiltration (compared with KS�lymphocytic); granular extracytoplasmic material consists of bacilli which stain with warthin-Starry silver stain�most important diagnostic feature Organism difficult to cultureBA, cont. or slightly elevated bili, transaminitis Pulmonary�polypoid endobronchial lesions, parenchymal mass (hypervascular) with pleural effusion and parietal involvement; interstitial pneuonia Radiographic appearance often with intense contrast enhancement�nodes and parenchymal mass�due to ectatic vascular spaces seen in the resected mass Common imaging: lung nodules, mediastinal adenopathy, peripheral adenoatphy, pleural effusions, ascites, abdominal adenopathy, soft tisue mases, low attenuation lesions in the liver and/or spleen�dramatic enhancement with contrast injection; Lung noduels�no spiculation, primarily associated with vascular structures, some septal thickening, many nodules peripheral Lymph node�mediastinal adenopathy, hilar adenopathy, abdominal and mesenteric�dramatic contrast enhancement Pleural effusions can be large Rapid improvement with antibiotics; recurrence does occur; Path�PMN infiltration (compared with KS�lymphocytic); granular extracytoplasmic material consists of bacilli which stain with warthin-Starry silver stain�most important diagnostic feature Organism difficult to culture

9. Kaposi�s sarcoma Most common tumor in HIV + Classic, African, organ-transplant, HIV Associated with HHV-8 Virus demonstrated in HIV+ homosexuals, HIV- homosexuals, classic KS HIV and HHV-8 interact Clinical features: 30-50% pulmonary 60% pleural effusion Palliative treatment Indications for chemotherapy >25 skin lesions Cutaneous KS unresponsive to therapy Symptomatic visceral Extensive edema

10. �Regression of AIDS-Related Pulmonary Kaposi�s Sarcoma after HAART� First report of pulmonary KS regression after HAART 44 yo man with HIV, pulmonary infiltrates, progressive dyspnea and hemoptysis Bronch with bx diagnostic of KS HAART initiated 2 months later: symptoms resolved, CXR improved Protease inhibitors have direct antiviral effect on HHV-8?

11. �Antiretroviral Therapy with Protease Inhibitors in HIV Type-1 and HHV-8-Coinfected Patients� 6 pts coinfected with HHV-8 and HIV 4 of 6 with KS Measured PBMC HHV-8 DNA Plasma HIV-1 RNA CD4+ T cell counts KS lesions regressed in 3 of 4 Other tx used 3 pts with rising CD4+ and concurrent falling HHV-8 DNA Direct effect of PI on HHV-8 not proven; temporal correlation shown B/c recent case reports indicated clearance of peripheral blood mononuclear cells� HHV8 DNA followng HAART, including PI Measured time course of PBMC HHV8 DNA levels, plasma HIV1 RNA leoad, and CD4 T cell counts in 6 coinfected subjects 4 of 6 with KS Fluctuation of HHV8 viral load over time appeared to be independent of treatment (both before and after) But�fluctuation of HHV8 viral load did mirror changes in CD4 lymphocyte counts�increasing counts with decreased viral load�suggesting indirect effectB/c recent case reports indicated clearance of peripheral blood mononuclear cells� HHV8 DNA followng HAART, including PI Measured time course of PBMC HHV8 DNA levels, plasma HIV1 RNA leoad, and CD4 T cell counts in 6 coinfected subjects 4 of 6 with KS Fluctuation of HHV8 viral load over time appeared to be independent of treatment (both before and after) But�fluctuation of HHV8 viral load did mirror changes in CD4 lymphocyte counts�increasing counts with decreased viral load�suggesting indirect effect

12. �Impact of New Antiretroviral Combination Therapies in HIV-infected Patients in Switzerland� Prospective multicenter study of 3785 men and 1391 women with HIV 1764 homosexual men Pts followed 1988-1996 Reduction in progression to AIDS and mortality during HAART (from 95-96) One of the largest cohorts of HIV infected individuals worldwide No stringent inclusion and exclusion critera Likely to be representative of HIV infected patients in general practice First study�1997�evaluated disease progression and survival�shown to have improvements in both with antiretroviral combination therapyOne of the largest cohorts of HIV infected individuals worldwide No stringent inclusion and exclusion critera Likely to be representative of HIV infected patients in general practice First study�1997�evaluated disease progression and survival�shown to have improvements in both with antiretroviral combination therapy

13. �Risk of HIV-Related Kaposi�s Sarcoma and Non-Hodgkin�s Lymphoma with Potent Antiretroviral Therapy� This study: in addition to showing rate of progression to new AIDS defining events after HAART, now looking at all OI and malignancies Hazard ratio of 0.08 with CI 0.03-0.22�decreased risk of developing KS after HAART as compared to without HAART No significant trend for NHLThis study: in addition to showing rate of progression to new AIDS defining events after HAART, now looking at all OI and malignancies Hazard ratio of 0.08 with CI 0.03-0.22�decreased risk of developing KS after HAART as compared to without HAART No significant trend for NHL

14. Kaposi�s Sarcoma Pathogenesis of HHV-8 and possible interaction with HIV currently being studied Bacillary angiomatosis should be in differential, especially for �unusual� KS cases HAART improves immune status ? regression of KS Symptomatic pulmonary involvement: consider treatment with chemotherapy

15. References Aboulafia DM. Mayo Clin Proc 1998;73:439-443. De Milito A, Catucci M, Venturi G, et al. J Med Virol. 1999;57:140-44. Egger M, Hirschel B, Francioli P, et al. BMJ 1997;315:1194-99. Holkova B, Takeshita K, Cheng DM, et al. J Clin Oncol 2001;19:3848-51. Ledergerber B, Telenti A, Egger M. BMJ 1999;319:23-24. Tam HK, Zhang Z, Jacobson LP, et al. Int J Cancer 2002;98:916-22. Up to Date 11.1