Morning Report 11.1.10 g p

Morning g Report p 11.1.10
Lindsay Petty

The Case
22 yo F with h/o HIV, feels like it is hard to
breathe.

Except
You aren’t in Chicago.
You are in . . .

Lesotho
www.worldatlas.com

Most of the Country

Baylor Clinical Center of Excellence

The Medical Record
Bukanas!

Mokhotlong
The Loneliest Place on Earth

Queen Elizabeth II Hospital
(Not allowed to take pictures)

Back to the Case . . .
22 yo HIV+ F feels like it is hard to breathe.
What would you like to know?

HPI
• 1.5 months increasing SOB and DOE
• C Can only l walk lk a f few steps t without ith t SOB
• 20 lb weight loss
• Subjective fevers
• Night sweats
• Malaise
• Weakness
• Orthopnea
• PND
• Was seen in clinic 3 yrs ago, dx’ed with HIV, didn’t f/u.

Past Medical History
• Past Med Hx:
– HIV, CD4 unknown at present
• Past Surgical Hx:
– None
• Medications:
– None
• Allergies:
– NKDA
• Fam Hx:
– Mother passed away. Father unknown. Maternal grandparents are
healthy healthy.
• Social Hx:
– Multiple male partners.

What is your differential at this point?

Cardiac:
-CHF
DDx: DOE of Gradual Onset
-High output heart failure
-Pericardial Effusion
-Valvular dysfunction
-Cardiomyopathy y p y ( (Dilated or Restrictive) )
-Myocarditis (viral vs. nonviral
-Eisenmenger’s Syndrome
ID:
-TB
-PCP
-Myocarditis
Myocarditis
-Pericarditis: TB, Coxsackie, EBV, etc
-Sepsis
-MAI
-Fungal pneumonia
-Endocarditis: Bacterial or Fungal
Respiratory:
-Pulmonary Infection
-COPD
-Asthma
-Pleural effusion
-Lung g tumor
-Pulmonary HTN
-ILD
-LIP
GI:
-Ascites Ascites
-Liver disease
Neuro:
-Neuromuscular dz
Other:
-Pregnancy
-Carbon monoxide poisoning
-Obesity
-Altitude
Endo:
-Hypothyroidism
Heme/Onc:
-Anemia
-Malignancy: lung, lymphoma
causing tracheal compression,
cardiac tumor
-Thromboembolism
Renal:
-Nephrotic syndrome
-ESRD 2/2 HIV nephropathy

Cardiac:
-CHF
DDx: DOE of Gradual Onset
-High output heart failure
-Pericardial Effusion
-Valvular dysfunction
-Cardiomyopathy y p y ( (Dilated or Restrictive) )
-Myocarditis (viral vs. nonviral)
-Eisenmenger’s Syndrome
ID:
-TB
-PCP
-Myocarditis
Myocarditis
-Pericarditis: TB, Coxsackie, EBV, etc
-Sepsis
-MAI
-Fungal pneumonia
-Endocarditis: Bacterial or Fungal
Respiratory:
-Pulmonary Infection
-COPD
-Asthma
-Pleural effusion
-Lung g tumor
-Pulmonary HTN
-ILD
-LIP
GI:
-Ascites Ascites
-Liver disease
Neuro:
-Neuromuscular dz
Other:
-Pregnancy
-Carbon monoxide poisoning
-Obesity
-Altitude
Endo:
-Hypothyroidism
Heme/Onc:
-Anemia
-Malignancy: lung, lymphoma
causing tracheal compression,
cardiac tumor
-Thromboembolism
Renal:
-Nephrotic syndrome
-ESRD 2/2 HIV nephropathy

Physical Exam
• Vitals: T 38.0 P 105 BP 105/65 RR 24 SpO2 96% RA
• General: NAD, cachetic, speaking in sentences
• HEENT: PERRL, EOMI, anicteric sclera, MMM, no cervical
LAD
• Cardiac: regular rhythm, distant heart sounds, no S3 or
S4, , no murmurs, , no rubs, , JVD ~8cm, , neg g hepatojugular
p j g
reflex, 2+ pulses, < 2 sec capp refill, no LE edema
• Resp: Bibasilar inspiratory crackles
• Abd: soft, NT, ND, normoactive BS, no HSM
• Neuro: CN II-XII grossly intact, 2+ reflexes

What labs and test would you need?
What labs would you like?

Initial Labs and Tests
• In Lesotho . . . • At UofC . . .

Initial Labs and Tests
• In Lesotho . . . • At UofC . . .
– CBC
– LFTs
– Bcx x 2
– UA
– Ucx
– Fungal bcx
– AFB bcx
– BNP
– Ddimer
– Cardiac Enzymes
– B-HCG
– Histo ag
Blasto ab
– Blasto ab
– Strep pneumo ag
– Legionella ag
– RVP
– ABG
– TSH
– AFB x 3
– PPD/Quantiferon Gold
– Lymphocyte subsets
– Viral load
– HIV genotype
– CXR
– EKG
– TTE
– Chest CT- PE protocol vs. High Res ILD protocol
– ?Bronch? With PCP

Initial Labs and Tests
• In Lesotho . . .
– Hemoglobin
–CBC
– LFTs
– CD4 count
– AFB x 3
–CXR
• At UofC . . .
– CBC
– LFTs
– Bcx x 2
– UA
– Ucx
– Fungal bcx
– AFB bcx
– BNP
– Ddimer
– Cardiac Enzymes
– B-HCG
– Histo ag
– Blasto ab
– Strep pneumo ag
– Legionella ag
– RVP
– ABG
– TSH
– AFB x 3
– PPD/Quantiferon Gold
– Lymphocyte subsets
– Viral load
– HIV genotype
– CXR
– EKG
– TTE
– Chest CT- PE protocol vs. High Res ILD protocol
– ?Bronch? With PCP

Results
11.0 6.0 2.9
3.0 198
33.4
CD4 Pending
0.4
25 22
AFBs being brought to the hospital
90
Going to the hospital for her CXR . . .

Subsequent Labs and Tests
• In Lesotho . . . • At UofC . . .

Subsequent Labs and Tests
• In Lesotho . . .
– TTE
• At UofC . . .
– TTE

Echo showed . . .
• Pericardial effusion
•Fibrin b strands st a ds in pericardial pe ca d al space
What do you want to do?

Idiopathic:
DDx: Pericardial Disease
-Often presumed to have viral or
autoimmune etiology, but no
cause found.
Cardiac:
-Early Early infarction pericarditis
-Late postcardiac injury syndrome
-Myocarditis
-Dissecting Aortic Aneurysm
Infections:
Heme/Onc:
-Radiation
-Neoplasms
-Metastatic- lung or breast CA,
Hodgkins’s, leukemia, melanoma
-Primaryy
- Rhado, teratoma, fibroma,
Lipoma, leiomyoma, angioma
-Paraneoplastic
Autoimmune:
-Rheumatic disease
- Lupus, RA, Vasculitis, scleroderma,
MCTD
-Other
- Wegener’s, Wegener s, polyarteritis nodosa,
sarcoidosis, IBD, Whipple’s,
Giant cell arteritis, Rheumatic
Fever
-Viral: Coxsackievirus, echovirus, adeno, EBV, CMV, Flu, Varicella, Rubella, HIV, HepB, Mumps,
Parvovirus B19
-Bacterial: Staph, Strep, pneumococcus, Haemophilus, Neiserria, Chlamydia, Legionella, TB,
Salmonella, Lyme
-Mycoplasma
-Fungal: Histo Histo, Aspergillosis Aspergillosis, Blasto Blasto, coccidio coccidio, actinomycosis, actinomycosis nocardia, nocardia candida
-Parasitic: Echinococcus, amebiasis, toxoplasmosis
-Infective Endocarditis w ring abscess
Up To Date
Trauma:
-Blunt
-Penetrating
-Iatrogenic

Pericardiocentesis
Can be both diagnostic and therapeutic
therapeutic.
Wh What tests would ld you send?
d?

Pericardial Fluid . . .
• AFB smears sent--> sent > negative
• Oh Other tests you can send: d
– AFB culture (more often positive but rarely
sent i in resource-limited li i d settings) i )
– Cell count/diff: bloody, high protein,
elevated l t d lleukocyte k t (l (lymphocyte h t or
monocyte)
– Adenosine Deaminase levels
–PCR

Adenosine Deaminase
• ADA: enzyme marker of cell-mediated immune
response activity to M tuberculosis, includes T-cell and
Macrophages
• Elevated levels both sensitive and specific for TB
• In pericardial fluid, fluid small study with 20 cases:
• Mean level 92, range 35-135 (nml 0-18)
• Sensitivity 100% and Specificity 83.3%, p40
• Sensitivity and Specificity, 88% and 83%
Arroyo M, Soberman JE. Adenosine deaminase in the diagnosis of tuberulous pericardial effusion. Am J Med Sci. 2008 Mar;335(3):227-9.
Tuon FF, et al. ADA and tuberculous pericarditis—a systematic review with meta-analysis. Acta Trop. 2006 Aug; 99(1):67-74.
Marthur PC, et al. Diagnostic Value of ADA Activity in Tubercular Serositis. Indian J Tuberc 2006;53:92-95.

Tuberculous Pericarditis
• Most common pericardial disease in Sub-
Saharan Africa
• Present as:
– Pericardial effusion
– Constrictive pericarditis
– Cardiac tamponade
• Pericardial disease
– In developed world, < 5% d/t TB
– SSub-Saharan b S h Af Africa, i 50 50-70% 70% d/t TB
– TB accounts for 96-100% of cases in HIV+

HIV and TB Co-infection
• TB increases viral replication in HIV
• Lesotho: 4th highest incidence of TB
in the world: 602 cases/100,000 cases/100 000 in
2005
• 88% of f TB TB-infected i f d adults d l HIV HIV+ i in
Lesotho
Coovadia, HM, et al. Childhood human immunodeficiency virus and TB co-infections: reconciling conflicting data. Int J Tuberc Lung Dis 2 (1998), 844-851.
Gray D, et al. Low Rates of Hepatotoxicity in HIV-infected Children on Anti-retroviral Therapy With and Without Isoniazid Prophylaxis.
Journal of Tropical Pediatrics. Epub Aug 26.
Clinical Practice Guidelines for Pediatric HIV Care: Lesotho COE. July 2009 (2.2)

Medical Management
How would you treat?

TB Treatment in Lesotho
Intensive Phase: 2 months
Continuation Phase: 4 months
Clinical Practice Guidelines for Pediatric HIV Care: Lesotho COE. July 2009 (2.2)

Steroids?
• Systematic review of randomized control trials
• Four trials with 469 participants.
• Three (N=411) tested adjuvant steroids in
participants with suspected TB pericarditis in
the pre-HIV era.
• Fewer participants died in intervention group,
but not statistically significant.
– RR 0.50, 050 95% CI 019128 0.19-1.28; p=0.15 015
• But, not done in setting of HIV. Need larger
placebo controlled trials trials.
Ntsekhe M et al. Adjuvant corticosteroids for tuberculous pericarditis promising, but not proven.
Q J Med. 2003;96: 593-599.

What about HAART?
• If already on ARV . . . Continue it, but
think about drug interactions.
• CD4 < 200: Start ARV 22-8 8 weeks after
initiation of ATT
• CD4 200 200-350: 350 CConsider id ARV
• CD4 > 350: Defer ARV

CXR Findings
•Enlarged g cardiac silhouette
• Cardiac shadow globular with
distinct margins
• Cardiothoracic ratio exceeding 0.55
• Active pulmonary TB in 30% patients
Reuter H et al. Role of chest radiography in diagnosing patients with tuberculosis pericarditis. Cardiovasc JS Afr. 2005 Mar-Apr; 16(2): 108-11.

• Pericardial
• Pleural
•Meningitis
• Lymph node
• Intra-abdominal
• Skeletal
Extrapulmonary TB
Clinical Practice Guidelines for Pediatric HIV Care: Lesotho COE. July 2009 (2.2)
Cruz AT, Starke Jr. Clinical manifestations of tuberculosis in children. Paediatric Respiratory Reviews 2007; 8: 107-117.
Marais, BJ et al. A refined symptom-based approach to diagnose tuberculosis in children. Pediatrics. 2006; 118(5): e1350-9.

• Who matters?
– Household contacts
TB Contacts
– Smear +
– Timing: within a year
– C Contacts with i h prolonged l d f fever, cough, h or weight i h lloss
• Get sputum smears on them if possible (early
morning, fasting)
Clinical Practice Guidelines for Pediatric HIV Care: Lesotho COE. July 2009 (2.2)

Case Follow-up
• Started on 4-drug ATT
• Given Gve a couse course o of steods steroids
• Plan to start on ARV soon
• And the CXR a couple weeks later . . .

MKSAP
A 32-year-old man is evaluated for a fever 4 weeks after receiving a
new diagnosis g of pulmonary p y tuberculosis and late-stage g HIV
infection (CD4 cell count of 10/µL and an HIV RNA viral load of
700,000 copies/mL). A four-drug antituberculosis regimen
consisting of isoniazid, rifabutin, pyrazinamide, and ethambutol
and an antiretroviral regimen g consisting g of tenofovir, ,
emtricitabine, and lopinavir/ ritonavir are initiated.
On physical examination, temperature is 38.3 °C (101.0 °F); the
remaining vital signs are normal. normal There is an enlarged enlarged, fluctuant fluctuant,
and tender right cervical lymph node that was not present 4 weeks
ago. The skin, mucosal, and cardiopulmonary examinations are
normal, and there is no evidence of hepatosplenomegaly.
A repeat CD4 cell count at today’s visit is 130/µL, and the HIV RNA
viral load is 2000 copies/mL. A chest radiograph is normal.

MKSAP
Which of the following g is the most likely y
diagnosis?
A. Hodgkin lymphoma
B B. Immune Imm ne reconstitution reconstit tion inflammatory
inflammator
syndrome
C. Kaposi sarcoma
D. Non-Hodgkin lymphoma

MKSAP
Which of the following g is the most likely y
diagnosis?
A. Hodgkin lymphoma
B B. Immune Imm ne reconstitution reconstit tion inflammator
inflammatory
syndrome
C. Kaposi sarcoma
D. Non-Hodgkin lymphoma

Key Points
• Immune reconstitution inflammatory syndrome presents as a paradoxical
deterioration in the clinical status of a patient with HIV infection after
iinitiation iti ti of f highly hi hl active ti antiretroviral ti t i l th therapy. MMost t cases of f IRIS ddevelop l
within a few weeks to a few months of commencement of HAART.
• IRIS can present in two different situations:
– an exacerbation of a partially or successfully treated opportunistic
infection
– a previously undiagnosed or subclinical infection.
• The signs and symptoms of tuberculous IRIS may include high fevers, new
or worsening lymphadenopathy, worsening of pulmonary symptoms, and a
new or increasing pleural effusion. Principles of management include
consideration of temporary HAART cessation in patients in whom
potentially ll life-threatening l f h f forms of f IRIS S develop, d l such h as in those h with h
severe neurologic disease. Most patients with IRIS are managed with
antimicrobial therapy to reduce the antigen load of the triggering
pathogen, short-term therapy with NSAIDs or corticosteroids to decrease
inflammation inflammation, and HAART continuation
continuation.

Key Points
• Lymphoma does not typically present with the sudden appearance
of tender, , fluctuant lymphadenopathy. y p p y Furthermore, , the temporal p
association of fever and lymphadenopathy with HAART initiation in
a patient with known tuberculosis is most consistent with IRIS.
• Kaposi sarcoma can affect any organ in the body, body including the
lymph nodes. However, Kaposi sarcoma typically affects the lower
extremities, face, oral mucosa, genitalia, gastrointestinal tract,
and lungs.
• The optimal time for initiation of antiretroviral therapy during
tuberculosis treatment is currently unknown. Current guidelines
suggest gg waiting g 4 to 8 weeks before initiating g HAART. Patients
already receiving HAART when antituberculosis treatment is
started require a careful assessment to evaluate for potential
drug-drug interactions.

Thanks!

Malnutrition: TTL