Morning Report 11609

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Morning Report 1/16/09

• Anne Peery, MD

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Objectives

• Review CMV disease
• Define fever of unknown origin
• Review the differential diagnosis and initial
  evaluation for FUO

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Cytomegalovirus Disease

• Most CMV infections are asymptomatic, with the
  virus remaining latent.
• Serious disease occurs primarily in
  immunocompromised persons, especially those with
  AIDS and transplant recipients

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Cytomegalovirus Disease

• There are three recognizable clinical syndromes
• Disease in immunocompetent hosts
• Disease in immunocompromised hosts
• Perinatal disease and CMV inclusion disease

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CMV in Immunocompetent Hosts

• Acute Acquired CMV infection AKA CMV
  Mononucleosis
• Characterized by fever, malaise, myalgias and
  athralgia, splenomegaly, aytpical lymphocytes,
  relative lymphocytosis and abnormal LFTs
• Pharyngitis is rare
• Mean duration of symptoms 7-8 weeks
• Transmission occurs by sexual contacts, breast
  milk, respiratory droplets or transfusion
• Ddx includes EBV, acute HIV, Toxo, HHV-6,
  rubella, acute hepatitis, drug hypersensitivity
• Complications include mucosal gastrointestinal
  damage, Guillan-Barre, pericarditis and
  myocarditis

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CMV in Immunocompromised Hosts

• Tissue and bone marrow transplant patients are
  mainly at risk in the first 100 days after
  allograft transplantation and in particular when
  graft-versus-host disease or CMV seropositivity
  is present
• HIV-infected patients may show numerous
  manifestations and these occur most prominently
  when the CD4 count in lt100 or when the HIV viral
  load is gt10,000 copies/mcL.
• CMV is itself immunosuppresive and promotes other
  infections such as PCP and Aspergillus PNA. It
  may contribute to transplanted organ dysfunction,
  in particular, hepatitis, which can mimic organ
  rejection.
• CMV syndrome is renal transplant patient is a
  mononucleosis-like syndrome among new transplant
  recipients.

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CMV in Immunocompromised Hosts

• CMV Retinitis
• Occurs in AIDS pt with CD4 lt50 cells/mcL
• Ophthalmogic documentation of neovascular,
  proliferative lesions required for diagnosis
• Immune restoration with ART is associated with
  CMV vitreitis and CMV associated cystoid macular
  edema
• Gastrointestinal and Hepatobiliary CMV
• Serious GI CMV disease occurs in AIDS (CD4lt100)
  and after organ transplant, cancer chemotherapy
  or corticosteroids.
• Esophagitis presents with odyanophagia
• Small bowel disease may minic IBD or may present
  with ulceration or perforation.
• Colonic CMV disease causes diarrhea,
  hematochezia, abdominal pain, fever and weight
  loss

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CMV in Immunocompromised Hosts

• Pulmonary CMV
• CMV pneumonitis characterized by cough, dyspnea,
  little sputum and CXR demonstrating interstitial
  PNA. Occurs in transplant recipients with
  mortality rate 60-80 and less commonly in HIV
  patients
• Neurologic CMV
• Syndromes associated with CMV include
  polyradiculopathy, transverse myelitis,
  ventriculoencephalitis, and focal encephalitis

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Perinatal CMV

• Congential CMV infection is the most common
  congenital infection in developed countries,
  affecting 1 of all neonates
• About 10 of infected newborns to mothers with
  primary CMV will be symptomatic with CMV
  inclusion disease.
• It is characterized by jaundice, HSM,
  thrombocytopenia, purpura, microcephaly, mental
  retardation and motor disability. Hearing loss
  develops in gt then 50 of infants who are
  symptomatic at birth.

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Fever of Unknown Origin

• FUO refers to a prolonged febrile illness without
  an established etiology despite INTENSIVE
  evaluation and diagnostic testing.
• Temperature gt 38.3 measured on several occasions
• 3wk duration
• Negative blood cultures
• No apparent explanation
• 3 outpt visits or 3 hospital days

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FUO Classifications

• Classic FUO
• FUO associated with HIV
• Neutropenic/Immuno-Deficient FUO
• Nosocomial FUO

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Classic FUO Differential Diagnosis

• Infectious
• Neoplasm
• Noninfectious inflammatory disease
• Misc

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• FUO is more often caused by an atypical
  presentation of a common entity than by a rare
  disorder

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CLASSIC FUO

• Infection
• Mycobacterium tuberculosis
• Presentations of TB which escape early detection,
  are either extrapulmonary, miliary or occur in
  lungs of pts with preexisting pulmonary disease
  or immunodeficiency
• Abscesses
• Liver
• 50 present w/ RUQ tenderness, jaundice and HSM
  an equal number present ONLY w/ fever
• Spleen
• Uncommon but if untreated high mortality only
  50 presents with left sided pain and
  splenomegaly
• Perinephric
• Sterile pyuria may suggest a perinephric abscess
• Bacterial endocarditis

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CLASSIC FUO

• Malignancies
• Lymphoma
• Need excisional biopsy of abnormal LN to make
  diagnosis FNA suboptimal as tissue architecture
  is lost
• Renal Cell Carcinoma
• Classic triad flank pain, gross hematuria and
  palpable abdominal mass present in 10 cases
• Microscopic hematuria seen in gt50 cases

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CLASSIC FUO

• Inflammatory disease
• Temporal arteritis/giant cell arteritis
• HA, fever, anemia, elevated ESR
• Abrupt loss of vision, scalp tenderness
• Thyroiditis
• Stills disease (Adult-onset juvenile rheumatoid
  arthritis)
• Clinical diagnosis of exclusion suggested by
  fever, arthritis or arthralgia and rash on the
  trunk
• Fevers may antedate manifestations of arthritis
  by a year
• Additional symptoms include sore throat,
  lymphadenopathy, splenomegaly and pleurisy

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CLASSIC FUO

• Drug Fever
• Drug fevers typically occur 7 to 10 days after
  initiation and resolve w/in 48hrs of d/c
• Classically described as low-grade, sustained
  fevers, observation studies suggest that drug
  fevers, are more often spiking, reflecting
  exaggerated normal diurnal variation
• Most common meds PCNs, anti TB meds, phenytoin

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Temporal Patter of the Fever

• Persistently elevated body temperature w/ minimal
  variation (lt1?F) can be seen w/ lobar PNA or
  rickettsial infections
• Intermittent or hectic fever, an exaggeration of
  normal circadian rhythms, can be seen w/
  endocarditis, abscesses, malignancies and drug
  fever
• Pel-Ebstein fevers, episodic fevers lasting 3 to
  10 days w/ intervening afebrile periods of
  similar duration, classically associated w/
  Hodgkins and other types of lymphoma

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Temporal Patter of the Fever

• Tertian fevers, fever paroxysms on cycles of days
  1 and 3, typically seen with Plasmodium vivax
• Quartan fevers, paroxysms occuring on cycles of
  days 1 and 4, are seen with Plasmodium malaria
• Double-quotidian fevers are associated with
  Stills disease and less commonly, right-sided
  gonococcal endocarditis

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Treatment of FUO

• Do not empirically treat a stable patient with
  antibiotics
• Empiric use of antibiotics may contribute to
  difficulty in identifying the cause FUO.
• For example, fever of miliary TB may be
  suppressed by aminoglycosides or
  fluoroquinolones.
• Empiric use of corticosteroids should be avoided
  unless there is reasonable suspicion of temporal
  arteritis

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References

• Approach to FUO Cecil Medicine
• CMV Mandell, Bennett and Dolin
• Up to DateCMV
• Currents CMV
• FUO The Oslers Medicine Handbook