Transcript PowerPoint Presentation - Internal Medicine Grand Rounds

Grand Rounds
Presentor: Mabel Aloc, M.D.
March 01, 2007
Ledesma Hall
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
General Data
R.D.
24 years old
Female
Married
Ukrainian
Lawyer
Chief Complaint
word-finding difficulty
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.
Cranial MRI
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
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
Family History
(-) Asthma
(-) Diabetes Mellitus
(-) Hypertension
(-) Cancer
(-) HIV / AIDS
Personal / Social History
monogamous
► denies drug abuse
► divorced first husband due to alleged
battery / physical assault ?
► No history of blood transfusions
►
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
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 2:3
► 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
►
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
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
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
Neurologic Exam
Mental Status Exam
► conscious, coherent,
good attention
► impaired verbal
fluency
► Intact word
comprehension
► impaired repetition
► Impaired
naming
► Impaired reading
comprehension
► Impaired writing
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 - Weber’s test is
midline, Rinne’s test – AC
> 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
Motor Examination
individual muscle
groups are graded 5/5 on all extremities
Sensory Examination
intact to pain,
temperature, light touch, vibration and
position sense, (-) Romberg’s test
Deep Tendon Reflex
+2 on all extremities
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, (-) Kernig’s
sign, (-) Brudzinski sign
Pathologic Reflexes
(-) Babinski sign, (-)
Grasp reflex
Gait Exam
able to walk on heels, toes, and
tandem walk well
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
Initial Impression
Acquired Immune Deficiency
Syndrome
CNS Infection, r/o Parasitic Disease
with Abscess Formation
Course in the Wards
On admission 

mannitol, citicholine,
oxcarbazepine started
Infectious Disease
referral: started
PyrimethamineSulfadoxine (Fansidar)
and Clindamycin, and
Folinic acid
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 > 850,000 iu/mm

started nutritional and
liver support
7th H.D.


Referral to Ophthalmology
service due to blurring of
vision. Fluorescein
angiography was done and
CMV retinitis was diagnosed.
CMV antigenemia 1315wbc/smear
Valganciclovir started
Fluorescein
Angiography
Fluorescein Angiography
8th H.D.



increasing aphasia
TMP/SMX shifted to Fansidar
and Azithromycin
Toxoplasma IgG: negative
Stereotactic Brain Biopsy
► Final
Histopathologic Report:
Inflammatory process with necrosis. No
definite Toxoplasma cyst identified. No
malignant cells.
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.
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.
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
Final Diagnosis
Acquired Immune Deficiency Syndrome
CNS lesion, probable Toxoplasma
Encephalitis
CMV Retinitis
Hepatitis C
Oral Candidiasis
Pneumocystis carinii Pneumonia, Resolved
Acquired Immune
Deficiency Syndrome
History
► First
recognized in mid-1981  clusters of
Pneumocystis carinii pneumonia and
Kaposi’s 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
► 1983
 cytopathic retrovirus isolated
► 1985  serologic tests to detect evidence of
infection with HIV had been developed and
licensed
Natural History of HIV Infection
Antiretroviral Therapy
Indications for Initiating ART for
Chronic HIV Patients
Testing for Plasma HIV RNA Levels and
CD4+ T Cell Count to Guide Decisions
Regarding Therapy
HIV RNA
CD4+ T Cell
ART-naïve
At the time of
diagnosis and
every 3-4months
thereafter
At the time of
diagnosis and
every 3-6months
thereafter
On ART
Immediately
before and at 28weeks after
initiation of tx,
then every 34months
Recommended Anti Retroviral Agents
for Initial Treatment of Established HIV
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
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
TOXOPLASMA ENCEPHALITIS
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
►
Life Cycle of Toxoplasma gondii
Clinical Presentation
90% - CD4+ T-lymphocyte counts <200/uL
► 75% - CD4+ T-lymphocyte counts <100/uL
► Headache, confusion, fever, lethargy,
seizures, focal signs (hemiparesis, cranial
nerve palsies, ataxia, sensory deficits)
► Subacute, ranging from a few days to a
month
►
Laboratory Investigations
serum anti-Toxoplasma IgG antibodies can
be detected, whereas IgM antibodies are
rarely found
► CSF – mild elevation of protein, moderate
mononucleated pleocytosis (<60
cells/mm3), slight decrease in glucose
► CSF analysis more useful to rule out other
infectious process than to confirm the
diagnosis of TE
►
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
►
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
►
Management of HIV-infected Patient
with CNS Lesion
Treatment
pyrimethamine+sulfadiazine (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
►
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
►
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
►
Neurologic improvement clinically
apparent in >50% 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
►
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
►
CMV Retinitis
CMV Retinitis
risk determined by CD4+ cell count and
CMV DNA level in the peripheral blood
► CD4+ cell counts <200/mm3 – annual risk 412%
► Aviremic patients <1% risk per year even at
low CD4+ cell counts
►
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
►
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
►
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
►
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
►
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
►
Hepatitis C
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 antiretroviralassociated hepatotoxicity
►
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
► Liver
biopsy is recommended for all HIV-1
infected persons with chronic HCV coinfection who are candidates for antiviral
therapy
HCV Treatment
Treatment of HCV / HIV Coinfection
Ribavirin should not be given with
didanosine because of the potential of drugdrug 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
►
►
Growth factors to manage interferonassociated neutropenia and ribavirinassociated anemia may be required
Thank You
CN VII
Central Lesion
Peripheral Lesion
Standard Indications for HCV
Therapy
detectable plasma HCV RNA
► liver biopsy showing bridging or portal
fibrosis
►
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
CD4 lymphocyte count and plasma viral
load – best prognostic markers for
subsequent disease course in an HIVinfected individual
► CD4+ lymphocyte count – sensitive
predictor of the development of
symptomatic HIV infection and AIDS in the
near term
►
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
►
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
►
AIDS develops in <5% 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 HIVinfected individuals remain clinically
asymptomatic with normal CD4 T
lymphocyte count for >8 years after
infection
►
T1-Weighted Image after
Gadolinium Injection
T2-Weighted Image