MedPeds Morning Report

Tiffany Milner, MD August 12, 2011

HPI

Princess Marina Hospital - Gaborone, Botswana 5 year old male who presents to the A&E with facial puffiness, tachypnea, and bilateral lower extremity edema. Mom has noted the edema for a few weeks, and it has been getting worse. He is less active than usual, seems tired, and is not interested in eating. He has not had any recent fevers or night sweats. He coughs occasionally, but this is no different from usual. No recent viral infections, no GI complaints, no bleeding or bruising.

Further HPI
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PMH: - Pulmonary TB, currently on continuation phase - Frequent AOM and URIs Medications: - Isoniazid - Rifampin Allergies: none Family Hx: no heart, liver, or kidney disease Social Hx: Lives with mother, grandmother, and 2 sisters in Moshupa, 61km from Gaborone.

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Physical Exam
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Vitals: T 37, HR 115, BP 80/40, RR 35, SpO2 87% Wt 17.5kg (15%), Ht 103 cm (2.4%) HEENT: facial puffiness, numerous dental caries, scarred TMs bilaterally Neck: Bilateral anterior cervical LAD, +JVD CV: tachycardic, hyperdynamic precordium, PMI displaced inferiorly and laterally Resp: tachypneic, occasional cough, crackles bilaterally Abd: hepatomegaly at 4 cm below RCM, splenomegaly at 3 cm below LCM, soft, nontender, nondistended, no ascites Ext: 2+ pitting edema in bilateral lower extremities up to the thigh

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What are you thinking?

Heart failure
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What is the most common cause of heart failure in children?

Congenital malformations
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What about a 77 year old man?

Ischemic heart disease

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What is the most likely cause of new onset HF in a 7 year old boy in Botswana, who is currently being treated for TB?

Etiologies of Heart Failure

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Structural defects: VSD, PDA, AVSD, AR, MR, tricuspid atresia, inflow obstruction, outflow obstruction Cardiomyopathy: dilated, hypertrophic, restrictive Myocarditis: viral (adenovirus, coxsackie B, influenza, HIV), Chagas, Mycoplasma, etc HTN systemic or pulmonary HTN Hypermetabolic states anemia, sepsis, hyperthyroidism Fluid overload liver failure, renal failure, iatrogenic Vitamin deficiencies/Toxins Coronary artery disease, dysrhythmias, autoimmune disease

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HIV-Associated Cardiovascular diseases

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Dilated Cardiomyopathy Lymphocytic Interstitial Myocarditis Pericardial Effusion Infective Endocarditis Malignancy (myocardial Kaposi sarcoma and B-cell immunoblastic lymphoma) Vasculitis Accelerated Atherosclerosis

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Testing
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CXR

Testing
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HIV test positive CBC microcytic anemia, leukopenia BUN/Cr, AST, ALT within normal limits Abdominal ultrasound hepatomegaly, splenomegaly, para-aortic lymphadenopathy Echocardiogram RV dilatation with increased RA and PA pressure, significantly decreased LV function

In the hospital
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Started on diuretic therapy (lasix and spironolactone) and afterload reduction (ACE-inhibitor) Continued on anti-TB therapy Started on cotrimoxazole Once clinically stable, he was discharged to home, with follow up at the BotswanaBaylor Childrens Center of Clinical Excellence

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Botswana-Baylor Childrens Center for Clinical Excellence

HPI - In Clinic
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5 year old HIV positive male who just completed 6 months of anti-TB therapy, recently admitted to the hospital and newly diagnosed with HIV-associated cardiomyopathy who presents with his mother for hospital follow up and initiation of HAART. Mom attended adherence classes this morning Current medications: - just finished INH and rifampin - cotrimoxazole daily - lasix 20mg BID - spironolactone 5mg twice daily - captopril 6.25mg TID CD4 count not back yet

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Physical Exam in clinic

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Ht 103 cm (2%), Wt 16.9kg (10%) T 37, HR 103, BP 100/70, RR 28, SpO2 N/A General: small, thin, edematous, no acute distress HEENT: facial puffiness, extensive dental caries, nares clear Neck: supple, bilateral submandibular and cervical LAD CV: hyperactive precordium with displacement of PMI Resp: occasional cough, few adventitious sounds throughout, no wheezing Abd: hepatomegaly at 3cm below RCM, splenomegaly at 2cm below LCM Ext: 1+ bilateral lower extremity edema

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What AIDS-defining illnesses does he have?

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Tuberculosis (just finished treatment) - WHO clinical stage 3 Moderate malnutrition (wasting syndrome) - WHO clinical stage 3 HIV-associated cardiomyopathy - WHO clinical stage 4

AIDS defining illnesses

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Bacterial pneumonia, recurrent Candidiasis of the bronchi, trachea, or lungs Candidiasis, esophageal Cervical carcinoma, invasive, confirmed by biopsy Coccidioidomycosis, disseminated or extrapulmonary Cryptococcosis, extrapulmonary Cryptosporidiosis, chronic intestinal Cytomegalovirus disease Encephalopathy, HIV-related Herpes simplex: chronic ulcers or bronchitis, pneumonitis, or esophagitis Histoplasmosis, disseminated or extrapulmonary Isosporiasis, chronic intestinal

Impression and Plan

5 year old boy with AIDS, WHO Clinical Stage 4 due to HIV associated cardiomyopathy, who has moderate malnutrition and clinical evidence of heart failure. Initiate HAART discuss side effects and IRIS - Abacavir (NRTI) - Lamivudine (NRTI) - Efavirenz (NNRTI) Continue cotrimoxazole Continue lasix, spironolactone, captopril Referral to nutrition for education and supplements Check weight and renal function in 2 weeks at follow up

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6 months later
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Repeat echocardiogram EF 64%, normal intracardiac anatomy with good LV function, but moderate biventricular dilatation CXR persistent cardiomegaly CD4 140/7% Viral load undetectable Off captopril, and now beginning to wean diuretics

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2 years on HAART
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7 year old male, WHO Clinical Stage 4, Treatment Stage 1, clinically well. Wt 20.2kg (7.7%), Ht 116cm (5.5%) Physical exam: dental caries, lungs clear, PMI at 5th intercostal space, lateral to midclavicular line, liver 2cm below RCM, spleen not palpable CD4 917/30%, viral load < 400, Hgb 11.5 Medications: Abacavir (ABC) Lamivudine (3TC) Efavirenz (EFV)

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A few learning points

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What do you worry about with abacavir (NRTI)?

Hypersensitivity (check HLA-B*5701)

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What do you worry about with efavirenz (NNRTI)?

Nightmares, psychiatric problems, difficulty with school

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Why not use zidovudine (NRTI) as first line in this patient?

It is associated with cardiomyopathy

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Cardiac Disease in HIV

Fro m t h e Pe d ia t ric Pu lm o n a ry a n d Ca rd ia c Co m p lic a t io n s o f Ve rt ic a lly Tra n s m it t e d HIV In fe c t io n St u d y Gro u p n 25% of deaths > 10 years old were due to cardiac

disease

51% of children with HIV-related deaths had chronic cardiac disease prior to death 28% of children had serious cardiac events after AIDS diagnosis 35% of patients who died during the study had cardiac dysfunction Risk factors: Encephalopathy, wasting, low CD4, prior history of serious cardiac event No statistical difference in congenital cardiovascular malformations Left ventricular dysfunction is a frequent manifestation

Cardiac disease as a cause of death increases with increasing age

Lin e a r a g e t re n d s fo r t h e u n d e rlyin g c a u s e o f d e a t h in 9 3 HIV-re la t e d d e a t h s

HIV Epidemiology 2009

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33.3 million people were living with HIV 2.5 million children were living with HIV 2.3 million of those children live in sub-Saharan Africa 53% of women living with HIV in low- and middle-income countries received ARV to prevent vertical transmission of the virus 7000 new HIV infections each day - 1000 children < 15 years old - 2460 15-24 years old The number of children receiving ART has increased from 75,000 in 2005 to 360,000 in 2009 The fastest growing population of HIV-positive patients are ages 15-24

Global prevalence of HIV 2009

What is the next challenge for our 7 year old patient?

Disclosure of diagnosis Adolescence and difficulties with adherence Lack of family support Depression, low self-esteem Sexual activity, substance abuse Denial and misinformation about HIV

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Disclosure

Optimizing adherence
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Establish trust with patient and family Problem solve with patient and family ie: financial troubles, school troubles, medication side effects, food insecurity, etc Peer Support Groups ie: Teen Club Reminders pill boxes, watches, cell phones Frequent, regular follow up Simplify medication regimen when possible

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What happens when he turns 18?

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In Botswana, he would just walk down a different hall in the same clinic In Salt Lake, he would go over to University Hospital and be seen by our adult ID doctors Report from Dr. Pavia: - almost 30 children with HIV in SLC - 1/3 are adolescents - 2 recently transitioned over to clinic 1A - some go off to college - some are lost to follow up

Is he at higher risk for cardiac disease?

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Accelerated atherosclerosis has been observed in young HIV-infected adults and children without traditional risk factors Cardiotoxicity is associated with zidovudine use (NRTI) Protease inhibitors are known to have side effects of lipodystrophy, atherosclerosis, dyslipidemia, and insulin resistance

Transitions of Care Known Barriers

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Delay in establishing care with an adult provider Lack of insurance coverage Limited knowledge and experience with pediatric-onset chronic conditions Limited communication between pediatric and adult providers Pediatrics family-centered approach vs the more independent adult approach Reluctance to leave familiar and trusted providers

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Suggestions for improvement

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Begin transitions early and in a developmentally appropriate way Communication between pediatric and adult providers Transition clinics giving teenagers the opportunity to practice independent disease management Extra training for adult providers on the adult sequelae of pediatric-onset chronic conditions

References
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http://cardiophile.org/2009/08/pulmonary-edema-seen-on-chest-x-ray-supine-view.html Barbaro, et al. Incidence of Dilated Cardiomyopathy and detection of HIV in myocardial cells of HIV-positive patients NEJM 2002;347(2):140. Keesler, Marcie, Cardiac Manifestations of HIV Infection in Infants and Children Annals of the New York Academy of Sciences, 946: 169-178. Madriago, Erin, Heart Failure in Infants and Children Pediatrics in Review 2010;31;4. Melvin, Cheitlin, Cardiac involvement in HIV-infected patients Uptodate 2010. Reiss, John, Health Care Transition: Youth, Family, and Provider Perspectives Pediatrics 2005;115;112. Simpkins, Evelyn, Thinking about HIV infection Pediatrics in Review 2009;30;337 Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. August 16, 2010; pp 1-219. UNAIDS Report on the Global AIDS Epidemic 2010. www.cdc.gov/hiv www.aidsinfo.nih.gov

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When to start HAART

Definitive: All children < 12 months of age

Recommended: > 12 months, and CDC Clinical Category B or C disease > 12 months and < 5 years, and CD4 < 25% > 5 years and CD4 < 350 > 12 months with viral load > 100,000

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Consider Asymptomatic or mild symptoms

What drugs to start

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Triple therapy, from at least 2 different classes Usually 2 NRTIs + PI (zidovudine, lamivudine, lopinavir/ritonavir) Or 2 NRTIs + NNRTI (zidovudine, lamivudine, nevirapine)