A 28YearOld Woman With Jaundice and Fever Chapter 22

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A 28-Year-Old Woman With Jaundice and Fever
Chapter 22
Eugene G. Martin, Ph.D. Associate Professor of
Pathology Laboratory Medicine

• Based upon LABORATORY MEDICINE CASEBOOK. An
  introduction to clinical reasoning
• Jana Raskova, MD Professor of Pathology
  Laboratory MedicineStephen Shea, MD
  Professor of Pathology Laboratory
  MedicineFrederick Skvara, MD Associate
  Professor of Pathology Laboratory MedicineNagy
  Mikhail, MD Assistant Professor of Pathology
  Laboratory MedicineUMDNJ-Robert Wood Johnson
  Medical SchoolPiscataway, NJ

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History and Presentation

• 28 y.o ? known to be HIV for 6 years
• Admitted to hospital because of jaundice and a
  fever of 102o F
• Contracted HIV from an old boyfriend who
  subsequently died. Husband refused to be tested
• Previously treated with anti-retroviral drugs
  poorly tolerated
• Developed Progressive Wasting Syndrome and
  anemia. Previous fever treated with antibiotics.
• Current problems Progressive Liver Failure with
  ? liver enzymes and jaundice occuring during the
  past five days accompanied by fever.
• Physical Exam
• Cachectic ?, oriented
• Temp. 101.8 oF
• BP 100/40
• HR 88 bpm and regular
• Skin and sclerae were icteric. No
  lymphadenopathy. Chest clear.
• Ascites. Liver and spleen markedly enlarged.
  Lower extremities were edematous

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What is Progressive Wasting Syndrome? Is
HIV-related anemia related to CD4 or viral load?
Progressive Wasting Syndrome
HIV Anemia

• Clinical syndrome in which an individual has lost
  more than 10 of his or her body weight in the
  absence of active infections or any other
  identifiable cause of weight loss.
• One of the most common symptoms of HIV infection
• Associated with malnutrition, which may
  contribute to increased immune suppression
• http//www.aidsmap.com/treatments/ixdata/english/C
  EFC89BA-7146-4966-8F39-701651DD559D.htm

• Anemia is associated with HIV disease
  progression, independent of CD4 count and viral
  load. Most common in patients with CD4
• Common causes of HIV-related anemia
• Infections e.g. B19 parovirus
• cancers of the bone marrow
• drugs which suppress the bone marrow as a
  side-effect of therapy
• AZT, foscarnet, ganciclovir, co-trimoxazole (at
  the high doses used to treat PCP anaemia is
  rare at the doses used for PCP prophylaxis) and
  dapsone
• Bleeding most common reason in HIV-negative m

4
Is HIV anemia related to CD4 count?

• Anemia is associated with HIV disease
  progression, independent of CD4 count and viral
  load. Most common in patients with CD4
• Common causes of HIV-related anemia
• Infections e.g. B19 parovirus
• cancers of the bone marrow
• drugs which suppress the bone marrow as a
  side-effect of therapy
• AZT, foscarnet, ganciclovir, co-trimoxazole (at
  the high doses used to treat PCP anaemia is
  rare at the doses used for PCP prophylaxis) and
  dapsone
• Bleeding most common reason in HIV-negative
  patients

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HEMATOLOGY
6
CHEMISTRY
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Why was Alk. Phosphatase Increased?

• Alk. Phosphatase
• Sources
• Liver hepatocytes and biliary tract mucosal
  cells
• Bone
• Intest. Mucosa
• Placenta
• Normal adolesc. 3-5x adult values (bone growth)
• Greater sensitive to biliary tract obstruction
  whether intra or extrahepatic. Does increase with
  liver cell acute injury

• Hepatic ALP Elevation
• Extrahepatic bil. Tract obstruct.
• Intrahepatic bil. Tract obstruct.
• Liver cell acute injury
• Liver passive congestion
• Drug-induced liver cell dysfunction
• Space occupying lesions
• Primary biliary cirrhosis
• Sepsis
• Dont forget bone or placental origin

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Why do you think AST is increased so modestly
(1.3 x Upper Range Normal (URN)

AST

Sources

Liver

Heart

Sk. Musc.

RBCs

Diseases with mild moderate abnormality
(

Acute hepatitis resolving phase

Chronic hepatitis

Active cirrhosis

Liver passive congestion

Drug induced liver dysfunction

Metastic liver tumor

Bile duct obstruction

CMV, inf. Mono

• In extrahepatic obstruction there usually is no
  elevation unless secondary parenchymal acute
  injury occurs
• AST/ALT ratio is elevated (1) in active
  alcoholic cirrhosis, liver congestion and
  metastatic tumor to the liver
• Etiologies for AST Elevation)
• Heart MI, Pericarditis
• Sk. Mus. Inflammation, MD, recent surgery, DTs
• Kidney Acute injury or damage, Renal infarct
• Other Intest. Infarct., Cholecystitis, shock,
  acute panreatitis, hypoparathyroidism

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GGTP

• GGTP has equal to or greater sensitivity than ALP
  in obstructive liver disease and greater
  sensitivity in hepatocellular injury (16x URN)
• Etiologies for GGT Elevation
• Liver, space-occupying lesion (M-H)
• Alcoholic active liver disease M)
• Common bile duct obstruction (M)
• Intrahepatic cholestatis (M-H)
• CMV infection, Mono infection (S/M)
• Tylenol overdose (S/M)
• Severe liver congestion (S)
• Reyes syndrome (S)
• S small, Mmedium, Hhigh

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Questions

• Discuss the status of the patients liver
• Hyperbilirubinemia Impaired hepatic excretion
  of conjugated bilirubin. This is not of hemolytic
  origin ? unconjugated bilirubin
• Hypoalbuminemia and ? protein impaired hepatic
  synthesis and malnutrition
• ? Calcium as a consequence of ? albumin
• 50 of total Ca is ionized, the remainder
  protein bound.
• A ? in serum albumin will ? ? total serum Ca
• Only hepatitis marker HBsAb. Consistent with
• Immunization
• Long ago exposure and recovery with loss of HBcAb
• No active infection (No HBeAg). No Carrier state
  (No HBsAg HBcAb)
• Transaminases (AST, ALT) are only modestly
  elevated
• Ascites and splenomegaly common in patients
  with portal hypertension
• What is the significance of the depressed amylase
  level?
• Amylase is typically elevated in pancreatitis, in
  biliary tract disease (cholecystitis, tumor,
  spasm of sphincter of Oddi). In this instance it
  is low
• Pancreatitis can occur in association with HIV
  therapy (DDI) or more commonly in alcoholic
  patients
• Because in requires good renal function to clear,
  serum amylase is sometimes elevated in renal
  failure.
• Pancreatic enzymes are important in the digestion
  of carbohydrates. In a patient losing weight it
  may be helpful to rule/out a digestive disorder

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What are the 3 stages of HIV infection?

• Acute
• 3-6 weeks after initial infection
• Non-specific symptoms resolves spontaenously
• Fever
• Rash
• Myalgia
• Middle
• Clinical latency patient asymptomatic, mild
  constitutional symptoms, lymphadenopathy
• Crisis
• Immune system breakdown
• Fever
• Loss of Weight
• Diarrhea
• Opportunistic infections and secondary neoplasms

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Urinalysis
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Miscellaneous Tests
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T Lymphocyte Subsets
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CHEMISTRY
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HEMATOLOGY
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Clinical Course

• Treatment
• Treated empirically for CMV and mycobacterium
  intracellulaire
• Diuretics and salt-poor albumin for ascites
• Liver function continued to deteriorate
• Patient developed electrolyte imbalance that
  reqd. correction
• Cytopenia worsened reqd transfusion of several
  units of packed red blood cells
• Blood and urine culture negative
• One week later oral and esophageal lesions
• Grim prognosis discussed. Patient died at home 2
  days later.
• Antemortem stool culture positive for acid fast
  organisms

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Autopsy results
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Liver Biopsy HE x120
Poorly defined granuloma composed of
epitheliodcells
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Liver Biopsy Acid Fast x120
Numerous filamentousacid-fast organismsconsisten
t with Mycobacteriumavium intracellulare.
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Impact of HIV on acquisition, activation and
outcome of TB?

• Acquisition 113 x higher risk of being infected
  than a person with no risk factors
• Mechanism HIV infects helper-T-cells leading to
  a decrease in cell-mediated immunity. Absence of
  immunity ?development or activation of the
  disease
• 37 of HIV-infected individuals develop TB within
  5 months of exposure as compared to 5 of
  patients with normal immune system
• Assessment PPD in HIV ONLY 30-50 of TB
  infected HIV patients will respond with an
  induration 10mm. THUS induration 5mm is
  considered

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HIV Positive Patient. What do you do?

• Ordinarily INH daily for 12 months
• Some recommend INH for life since eventual
  failure of the immune system will allow infection
  to progress to active disease
• If drug-resistant strain start on two drug
  regimen INH and EMB or INH and cipro for
  preventive therapy
• If an HIV-infected patient develops
  drug-resistant TB the chances of dying from the
  disease are between 72-89, even with aggressive
  therapy!!
• AIDS patients progress to MDR-TB immediately
  after infection and die within 4-19 weeks

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Esophagus

• HE x 31
• Esophagus covered by adherent grey-white membrane
• Note numerous fungal organisms as bluish wavy
  band across bottom of iimage
• Inflammatory cells, necrotic debris and
  collections of bacteria near lumen at top
• Gomori silver stain x100
• Fungi, numerous yeast and pseudohyphal forms are
  present consistent with Candida species

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Lymph node HE x12

• Atrophic lymph node
• Marked depletion of lymphocytes in both mantal
  and germinal centers
• Germinal centers are small and show signs of
  hyalinization

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Organization of spleen

• Marginal zone - assortment of mononuclear cells
• Principal function of the marginal zone is
  antigen trapping.
• SECONDARY LYMPHOID ORGANS, Art Anderson's
  Immunology Lecture Notes

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Spleen

• Patient
• Lymphoid depletion of the spleen severe
• White pullp is nearly devoid of lymphocytes
• Normal
• White pulp containing numerous lymphocytes
• Clearly delineated from the surrounding red pulp

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Case Summary

• Final Diagnosis
• AIDS
• Liver Failure
• Mycobacterium Avium intracellulare infection
• Esophageal Candidiasis

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References

• Prog. Wasting Syndrome -http//www.aidsmap.com/tre
  atments/ixdata/english/CEFC89BA-7146-4966-8F39-701
  651DD559D.htm
• HIV anemia - http//www.aidsmap.com/treatments/ixd
  ata/english/4B95EF8B-A38A-4FFB-BD5B-4D87339162B4.h
  tm
• Splleen
• SECONDARY LYMPHOID ORGANS, Art Anderson's
  Immunology Lecture Notes

• Websites containing information on HIV