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Grand Rounds

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Title: PowerPoint Presentation - Internal Medicine Grand Rounds Author: bb Last modified by: Nazario Macalintal Created Date: 2/12/2007 10:17:57 AM – PowerPoint PPT presentation

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Title: Grand Rounds


1
Grand Rounds
  • Presentor Mabel Aloc, M.D.
  • March 01, 2007
  • Ledesma Hall

2
Objectives
  • To present a case of HIV / AIDS with multiple
    opportunistic infections
  • To discuss the diagnosis and management of some
    of the major complications of HIV / AIDS

3
General Data
  • R.D.
  • 24 years old
  • Female
  • Married
  • Ukrainian
  • Lawyer

4
Chief Complaint
  • word-finding difficulty

5
History of Present Illness
  • 2 weeks PTA ? word-finding difficulty /
  • headache
  • 4 days PTA ? upward rolling of eyeballs
    and stiffening of extremities. Consult was
    sought. Oxcarbazepine was prescribed.
    Cranial MRI was done. There was no
    associated fever, nausea, vomiting, dizziness.

6
Cranial MRI
7
Review of Systems
  • weight loss
  • anorexia
  • (-) rash
  • (-) heat or cold intolerance
  • (-) polyuria
  • (-) polydipsia
  • (-) dyspnea
  • (-) cough
  • (-) chest pain
  • (-) palpitations
  • (-) orthopnea
  • (-) tendency to bleed or bruise easily
  • (-) dysphagia
  • (-) constipation
  • (-) diarrhea
  • (-) dysuria
  • (-) nocturia

8
Past Medical History
  • June 2006 ? admitted due to dyspnea
  • dx Pneumocystis carinii pneumonia
  • ? HIV positive
  • CD4 count 2.3
  • CD4/CD8 ratio 0.02
  • treated with TMP/SMX

9
Family History
  • (-) Asthma
  • (-) Diabetes Mellitus
  • (-) Hypertension
  • (-) Cancer
  • (-) HIV / AIDS

10
Personal / Social History
  • monogamous
  • denies drug abuse
  • divorced first husband due to alleged battery /
    physical assault ?
  • No history of blood transfusions

11
Physical Examination
  • General 24-year-old caucasian female, drowsy, not
    in cardiorespiratory distress, with difficulty in
    self-expression, makes eye contact
  • BP 90/60mmHg HR 88bpm RR 18cpm
  • T 36.9?C
  • Weight 45kg Height 5 7 BMI 15.5
  • Skin dry skin, no lesions or tenderness
    nailbeds pink without clubbing brisk capillary
    refill, tattoo on lateral aspect of left ankle

12
  • HEENT
  • scalp without lesions or tenderness
  • conjunctivae pink without discharge
  • pupils react equally to light and accommodation
  • extraocular movements intact
  • red reflex present
  • discs cream colored with well-defined border
    bilaterally
  • A-V ratio 23
  • cornea, lens, and vitreous clear
  • retina pink, no hemorrhages or exudates
  • macula yellow
  • visual acuity 20/25
  • no ear / nose discharge
  • buccal mucosa pink and moist

13
  • Neck trachea midline, freely movable, thyroid not
    palpable lymph nodes nonpalpable
  • Chest and Lungs symmetric chest expansion,
    tactile fremitus symmetric, resonant percussion
    throughout, no crackles, no wheezes

14
  • Heart Apex beat and PMI at 5th intercostal space,
    LMCL S1 heard best at apex, S2 heard best at
    base, no murmurs regular rhythm
  • Blood Vessels no neck vein engorgement no bruits
  • Abdomen full, soft, nontender liver, spleen, and
    kidney not palpable

15
  • Lymphatic no palpable lymph nodes in neck,
    supraclavicular, axillary, epitrochlear, or
    inguinal areas
  • Musculoskeletal muscles appear symmetric with
    appropriate and equal strength bilaterally, full
    range of active and passive motion

16
Neurologic Exam
  • Mental Status Exam
  • conscious, coherent, good attention
  • impaired verbal fluency
  • Intact word comprehension
  • impaired repetition
  • Impaired naming
  • Impaired reading comprehension
  • Impaired writing

17
Cranial Nerve Examination
  • I - intact sense of smell
  • II - no visual field cuts, no papilledema
  • II, III - pupils isocoric at 3mm EBRTL
  • III, IV, VI - full EOM
  • V - intact facial sensation, strong muscles of
    mastication
  • VII - Right central facial palsy
  • VIII - Webers test is midline, Rinnes test
    AC gt BC, AU
  • IX, X - gag reflex, uvula at midline
  • XI - able to shrug shoulders and turn head
    against resistance
  • XII - tongue at midline, no atrophy noted

18
  • Motor Examination individual muscle groups are
    graded 5/5 on all extremities
  • Sensory Examination intact to pain, temperature,
    light touch, vibration and position sense, (-)
    Rombergs test
  • Deep Tendon Reflex 2 on all extremities

19
  • Cerebellar Tests able to do finger to nose test,
    able to do rapid alternating pronation /
    supination of the hands, no nystagmus
  • Meningeal Tests supple neck, (-) Kernigs sign,
    (-) Brudzinski sign
  • Pathologic Reflexes (-) Babinski sign, (-) Grasp
    reflex
  • Gait Exam able to walk on heels, toes, and tandem
    walk well

20
Salient Features
  • 24y/o female causasian
  • Expressive aphasia, headache
  • MRI T/C cerebral infection
  • Hx Pneumocystis carinii pneumonia, HIV positive
  • BMI 15.5
  • Impaired verbal fluency, repetition, naming,
    reading comprehension, and writing
  • Right central facial palsy

21
Initial Impression
  • Acquired Immune Deficiency Syndrome
  • CNS Infection, r/o Parasitic Disease with Abscess
    Formation

22
Course in the Wards
  • On admission ? mannitol, citicholine,
    oxcarbazepine started
  • ? Infectious Disease referral started
    Pyrimethamine- Sulfadoxine (Fansidar)
    and Clindamycin, and Folinic acid

23
  • 2nd H.D. ? Referral to Gastroenterology service
    due to elevated liver transaminases
  • ? Fansidar and Clindamycin shifted to
    Trimethoprim/Sulfamethoxazole
  • ? UTZ no hepatobiliary abnormalities
  • ? Anti HCV reactive
  • ? HCV RNA gt 850,000 iu/mm
  • ? started nutritional and liver support

24
  • 7th H.D. ? Referral to Ophthalmology service
    due to blurring of vision. Fluorescein
    angiography was done and CMV retinitis
    was diagnosed.
  • CMV antigenemia 13- 15wbc/smear
  • ? Valganciclovir started

25
Fluorescein Angiography
26
Fluorescein Angiography
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  • 8th H.D. ? increasing aphasia
  • ? TMP/SMX shifted to Fansidar and
    Azithromycin
  • ? Toxoplasma IgG negative

29
Stereotactic Brain Biopsy
30
  • Final Histopathologic Report
  • Inflammatory process with necrosis. No
    definite Toxoplasma cyst identified. No
    malignant cells.

31
  • Acid fast, silver, and PAS stains were negative.
  • Aerobic culture of brain tissue was negative and
    mycobacterial culture remained negative by the
    first week of incubation.
  • Repeat Toxoplasma IgG was negative.

32
  • 9th H.D. ? developed oral thrush
  • ? Nystatin started
  • Antiretroviral therapy and tests for CD4 count
    and HIV viral load were deferred until the acute
    opportunistic infections stabilized. The patient
    was discharged on the 14th H.D. alert,
    headache-free, without seizure recurrence but
    with persistent expressive aphasia.

33
1/22 1/23 1/27 1/29 1/31 2/1
WBC 2.3x109/L 2.8x109/L 2.4x109/L 3.41x109/L
Segmenters 36 55 72 75
Lymphocytes 49 30 22 13
Monocytes 14 12 4 7
Hb / Hct 13.2/ 41.2 12.8/ 40.7 11.4 / 36 11.8 / 35.8
Platelet count 138,000 141,000 105,000 123,000
SGPT (IU/L) 124 139 117
SGOT(IU/L) 214 268 199
GGTP(IU/L) 835
Ammonia 170UG/DL
34
Final Diagnosis
  • Acquired Immune Deficiency Syndrome
  • CNS lesion, probable Toxoplasma Encephalitis
  • CMV Retinitis
  • Hepatitis C
  • Oral Candidiasis
  • Pneumocystis carinii Pneumonia, Resolved

35
Acquired Immune Deficiency Syndrome
36
History
  • First recognized in mid-1981 ? clusters of
    Pneumocystis carinii pneumonia and Kaposis
    sarcoma reported in young, previously healthy
    homosexual men in New York City, Los Angeles, and
    San Francisco
  • Subsequent documentation of cases among persons
    with hemophilia, blood transfusion recipients,
    and heterosexual injecting drug users and their
    sex partners

37
  • 1983 ? cytopathic retrovirus isolated
  • 1985 ? serologic tests to detect evidence of
    infection with HIV had been developed and licensed

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43
Natural History of HIV Infection
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45
Antiretroviral Therapy
46
Indications for Initiating ART for Chronic HIV
Patients
47
Testing for Plasma HIV RNA Levels and CD4 T Cell
Count to Guide Decisions Regarding Therapy
ART-naïve On ART
HIV RNA At the time of diagnosis and every 3-4months thereafter Immediately before and at 2-8weeks after initiation of tx, then every 3-4months
CD4 T Cell At the time of diagnosis and every 3-6months thereafter
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52
Recommended Anti Retroviral Agents for Initial
Treatment of Established HIV
53
ART for Patients with Acute Opportunistic
Infection
  • The potential benefit of ART must be weighed
    against other factors
  • 1. For ART-naïve patients, the initiation of
    ART may produce an enhanced inflammatory response
    that could be detrimental in the short term.
  • 2. Poor adherence or less than optimal
    absorption may diminish effectiveness of ART and
    enhance the likelihood of emergence of
    drug-resistant HIV-strains

54
  • 3. Changing drug regimens could alter
    pharmacokinetics and result in suboptimal or,
    alternatively, toxic serum drug concentrations,
    which could enhance the likelihood of development
    of HIV resistance to antiretroviral agents

55
  • TOXOPLASMA ENCEPHALITIS

56
  • at the beginning of the AIDS epidemic,
    Toxoplasma encephalitis was the most common
    cerebral mass lesion in patients with AIDS
  • caused by a reactivation of latent infection by
    Toxoplasma gondii as a result of progressive loss
    of cellular immunity

57
Life Cycle of Toxoplasma gondii
58
Clinical Presentation
  • 90 - CD4 T-lymphocyte counts lt200/uL
  • 75 - CD4 T-lymphocyte counts lt100/uL
  • Headache, confusion, fever, lethargy, seizures,
    focal signs (hemiparesis, cranial nerve palsies,
    ataxia, sensory deficits)
  • Subacute, ranging from a few days to a month

59
Laboratory Investigations
  • serum anti-Toxoplasma IgG antibodies can be
    detected, whereas IgM antibodies are rarely found
  • CSF mild elevation of protein, moderate
    mononucleated pleocytosis (lt60 cells/mm3), slight
    decrease in glucose
  • CSF analysis more useful to rule out other
    infectious process than to confirm the diagnosis
    of TE

60
Imaging Studies
  • multiple lesions in 2/3 of cases, and 90 of
    them display ring enhancement after
    administration of contrast material
  • MRI more sensitive than CT to detect multiple
    lesions
  • Localized at the corticomedullary junction in the
    white matter, or the basal ganglia and are
    surrounded by edema and induce mass effect on
    surrounding structures

61
Brain Biopsy
  • necrotic abscesses with blood vessel with blood
    vessel thrombosis and necrosis
  • cysts containing bradyzoites, the dormant form
    of T. gondii, coexist with numerous active
    tachyzoites

62
Management of HIV-infected Patient with CNS Lesion
63
Treatment
  • pyrimethaminesulfadiazine (Fansidar)
    synergistic and sequential block on folic acid
    metabolism
  • Pyrimethamine 200mg D1, then 75mg OD
  • sulfadiazine 6g/day in 6 divided doses
  • Folinic acid 10-50mg/day

64
  • Alternative to () sulfonamide allergy
  • 1. clindamycin 600mg IV or 450mg,
  • 2. Azithromycin 1200 to 1500mg p.o. OD,
  • 3. Atovaquone 750mg p.o. QID
  • side effects cytopenia, rashes, diarrhea,
    elevated liver enzymes

65
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Corticosteroids in TE
  • to diminish cerebral edema
  • has not been shown to be either beneficial or
    harmful in TE
  • because high doses of steroids reduce the size
    of CNS lymphoma lesions, they should be
    administered only in cases with impending
    cerebral herniation during the initial medical
    treatment of presumed TE

67
  • Neurologic improvement clinically apparent in
    gt50 by D3 of therapy and in most cases by D7
  • failure to improve or worsening of symptoms
    should prompt repeat imaging studies by D10 to 14

68
Secondary Prophylaxis
  • maintenance therapy to prevent relapse which is
    likely to occur after a delay of 6-8 weeks of
    interruption of treatment
  • pyrimethamine 25-75mg/day folinic acid 10mg OD
    sulfadiazine 2-4g/day in 4 divided doses OR
    clindamycin 300mg QID or 450mg TID
  • CD4 T-cell counts above 200/uL for more than 3
    months discontinue prophylaxis

69
CMV Retinitis
70
CMV Retinitis
  • risk determined by CD4 cell count and CMV DNA
    level in the peripheral blood
  • CD4 cell counts lt200/mm3 annual risk 4-12
  • Aviremic patients lt1 risk per year even at low
    CD4 cell counts

71
CMV Retinitis Symptoms
  • painless, progressive visual loss, blurring, and
    floaters
  • usually unilateral, but may progress to the
    contralateral retina
  • retinal detachments (sudden loss of vision,
    like a curtain falling) erosion of retinal
    border at the site of a necrotic lesion allows
    the retina to be lifted off underlying tissues

72
CMV Retinitis Fundoscopy
  • Fundoscopy coalescing white exudates in a
    vascular pattern with surrounding hemorrhage and
    edema
  • lesions are peripheral initially, involve the
    fovea later, and result in visual loss
  • Retinal detachment as a late complication

73
CMV Retinitis Treatment
  • For immediate sight-threatening lesions
    Ganciclovir (GCV) intraocular implant
    valganciclovir 900mg PO qd
  • For peripheral lesions Valganciclovir 900mg PO
    bid x 14-21 days, then 900mg PO qd

74
CMV Retinitis Chronic Maintenance Therapy
  • Ganciclovir 5-6mg/kg BW/day IV 5-7 days weekly
    or 1000mg PO tid or
  • Foscarnet 90-120mg/kg BW IV qd or
  • For retinitis, ganciclovir sustained-release
    implant every 6-9 months plus ganciclovir
    1.0-1.5g PO tid

75
CMV Retinitis Duration of Chronic Maintenance
Therapy
  • Implant - replace every 6-8 months until immune
    recovery on ART
  • Systemic therapy continue for life or until
    immune recovery on ART

76
Hepatitis C
77
HCV / HIV Co-infection
  • increased rate of progression to cirrhosis
    (three-fold higher) especially in older people,
    and those with lower CD4 T lymphocyte count and
    with history of alcoholism
  • HCV infection might accelerate progression of
    HIV
  • increased frequency of antiretroviral-associated
    hepatotoxicity

78
HCV Diagnosis
  • Initial testing for detection of antibody to HCV
    ? test for HCV RNA with a qualitative assay with
    a lower limit of detection of 50 iu/ml ? more
    sensitive anti HCV testing with RIBA if negative
    HCV RNA
  • Screen for HCC using AFP and hepatic UTZ
  • ALT levels to assess activity of liver disease

79
  • Liver biopsy is recommended for all HIV-1
    infected persons with chronic HCV co-infection
    who are candidates for antiviral therapy

80
HCV Treatment
81
Treatment of HCV / HIV Co-infection
  • Ribavirin should not be given with didanosine
    because of the potential of drug-drug
    interactions leading to pancreatitis and lactic
    acidosis
  • Some NRTIs and all NNRTIs and PIs are
    potentially hepatotoxic
  • Zidovudine combined with ribavirin is associated
    with higher rates of anemia

82
  • Growth factors to manage interferon-associated
    neutropenia and ribavirin-associated anemia may
    be required

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Thank You
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CN VII Central Lesion Peripheral Lesion
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Standard Indications for HCV Therapy
  • detectable plasma HCV RNA
  • liver biopsy showing bridging or portal fibrosis

89
HCV Clinical Manifestations
  • low grade fever
  • mild RUQ pain
  • Nausea
  • Vomiting
  • anorexia
  • Dark urine
  • Jaundice
  • Fatigue
  • Spider angiomata
  • Splenomegaly
  • Caput medusa
  • Ascites
  • Jaundice
  • Pruritus
  • Encephalopathy

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  • CD4 lymphocyte count and plasma viral load
    best prognostic markers for subsequent disease
    course in an HIV-infected individual
  • CD4 lymphocyte count sensitive predictor of
    the development of symptomatic HIV infection and
    AIDS in the near term

92
  • HIV-1 RNA predictor of disease course over a
    more extended period of time and is strongly
    associated with the rate of subsequent CD4 cell
    count decline
  • higher baseline viral load more rapid decline
    in CD4 count, faster clinical progression, and
    decreased survival

93
  • viral load measures replicative rate of
    infection and its destructive potential for the
    cellular immune system
  • CD4 count gauges the extent of immune
    compromise and the present risk of opportunistic
    disease

94
  • AIDS develops in lt5 of HIV-infected adults
    within 2 years of infection
  • without therapy, AIDS develops in 20-25 within
    6 years of infection, and in 50 within 10 years
  • long-term nonprogressors 5-8 of HIV-infected
    individuals remain clinically asymptomatic with
    normal CD4 T lymphocyte count for gt8 years after
    infection

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T1-Weighted Image after Gadolinium Injection
97
T2-Weighted Image
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