ID Clinical Case Conference

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ID Clinical Case Conference

• Munshi Moyenuddin, M.D., Ph.D.
• Section of Infectious Diseases
• 29 April 2002

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Case 1

• 39 y/o white male, who had been HIV positive for
  6 years, CD4 nadir was 60, developed AIDS in the
  year of diagnosis, also with previous history of
  shingles x 2, presented with three months history
  of cough, SOB, fever (never measured), and night
  sweat. The cough had been productive in the
  morning. He used over the counter cough medicine
  without much help. At the time of presentation
  his CD4 was 350 (300 for 1.5 year) and VL was
  weight-loss, hemoptysis, or travel in last
  3-years.

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Case 1

• PMHx Depression, anxiety, h/o valium overdose.
• PSHx h/o MVA 23 years ago with cracked C1, C2
  leading to chronic headache and no neurologic
  symptom.
  
• Soc Hx works as a house remodeller homosexual
  tobacco abuse-initially 3ppd-then 1ppd for a
  total of 22 years has four healthy dogs 1st
  male partner died of AIDS 6-years ago now lives
  with a male who has chronic cough.
• Meds TZV, EFV

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Case 1

• Immunization and antibodies received pneumonia
  and hep-B vaccines 5-years ago, PPD skin test was
  neg a year ago, toxoplasma IgG CMV, RPR,
  anti-HCV, and anti-HBc were neg.
• T-99.3, P-90, R-22, BP-140/85
• CV/Abd-unremarkable, Lung-scattered (B) basilar
  exp rhonchi, No JVD, Ext-no edema.
  
• WBC-15.2, Hg-14.1, Plt-267, Cr-0.8, Gl-93
• A CXR was done.

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Case 1

• CXR approximately 9-mm rounded density in the
  base of the right lung may represent pulmonary
  nodule.
  
• Sptum Cx- normal oral flora.
• CT scan of chest was done.

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Case 1

• CT Chest- innumerable 1-2 mm non-calcified
  nodules are present in a centrilobular pattern
  throughout the lungs. A subcentimeter
  non-calcified pulmonary nodule is present in the
  right upper lobe. No pleural effusions,
  atelectasis, or pneumothorax was noted.
• A bronchoscopy was done- no obstruction was
  found.
  
• BAL, bronchial wash, bronchial brush, and
  endobronchial biopsy specimens were neg for
  bacteria, fungi, AFB.
  
• Patient underwent rt thoracoscopy with lung
  biopsy from upper and middle lobe.
  Intra-surgically the lung appeared abnormal with
  small nodules.

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Case 1

• Lung biopsy- multifocal hemorrhagic interstitial
  pneumonitis with alveolar histiocytic infiltrate.
  No pathogens were identified in acid fast and gms
  stains. No viral inclusions were observed. No
  bacteria were identified in gram stain.
  Examination of giemsa and PAS stains showed
  images suggestive of toxoplasma trophozoites in
  alveolar macrophages. Pulmonary toxoplasmosis may
  elicit an interstitial pneumonitis pattern or a
  histiocytic pneumonitis pattern, both of which
  were present in the biopsy.

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Pulmonary Toxoplasmosis (PT)

• Incidence of PT is unknown. It has been more
  commonly reported in France than in the US. In a
  review of 64 French HIV cases, 39 pts (61) had
  isolated PT (CID 1996231249). HIV-related PT
  was first described in 1984, only 1 of 441 pts
  had PT (N Eng J Med 1984 310 1682). The overall
  prevalence of extracerebral T. gondii infection
  in HIV-pts has been estimated to be 1.5 to 2
  with the prevalence of pulmonary toxoplasmosis at
  0.5 (Medicine 199473306).

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Pulmonary Toxoplasmosis

• Reactivation of latent disease has been found to
  be the most common cause of PT in the
  immunocompromised host. AIDS pts with CD4 are predisposed to develop T. gondii infection.
  The most common cause of severe PT from primary
  infection is transplantation of a seropositive
  lung in a recipient. Other sources of infection
  are contact with cat feces, ingestion of
  undercooked meat, or wbc transfusions (Semin Resp
  Infect 1991651 19971298).

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Pulmonary Toxoplasmosis

• Diagnosis Most common symptoms and signs
  described in PT are cough, dyspnea and fever (CID
  199214 863). Serum lactate dehydrogenase has
  been reported to be extremely high in PT but
  lacks sensitivity or specificity and can not be
  used solely for diagnosis. In the proper clinical
  setting, positive serology, histology showing
  inflammation and organisms, or identification of
  the organism in BAL fluid is necessary to confirm
  the diagnosis.

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Pulmonary Toxoplasmosis

• Diagnosis Positive serology results may suggest
  recent or past exposure, the test alone is not
  useful in establishing the diagnosis. If
  pulmonary involvement with toxoplasma is
  suggested by the clinical syndrome, detection of
  serum IgM to T. gondii or demonstration of a
  fourfold increase in IgG serum antibody titer
  supports the diagnosis of acute infection (Semin
  Res Inf 19971298).

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Pulmonary Toxoplasmosis

• Diagnosis Radiographic evidence of pulmonary
  involvement is essential for diagnosis of PT
  however, chest radiograph showed lack of
  sensitivity and specificity and chest CT does not
  have superior diagnostic modality. Radiographic
  pattern described in the literature include
  mainly bilateral diffuse pneumonia miliary,
  multiple nodules and interstitial and lobar
  infiltrates. Isolated cases of pleural effusion
  and pneumothorax have also been described (Chest
  19911001184 Semin Res Inf 19971298).

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Pulmonary Toxoplasmosis

• Diagnosis Bronchoscopy with bronchoalveolar
  lavage and biopsy have significant utility in
  diagnosis of PT. Thoracoscopic or open lung
  biopsy remains the gold standard for diagnosis
  (Diag Cytopath 19939650 South Med J
  199487659 CID 199214863).

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Pulmonary Toxoplasmosis

• Diagnosis Pathological description of PT
  includes necrotizing pneumonia with nodules,
  diffuse alveolar damage, and interstitial
  pneumonitis. T. gondii may be found in the
  alveolar space as well as in the alveolar
  epithelial or capillary endothelial cells. Direct
  observation using Giemsa or eosin-methylene blue
  stains of lavage fluid or biopsy specimens may
  show crescent-shaped tachyzoites (JCM
  1989271661 JCM 1991292626).

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Pulmonary Toxoplasmosis

• Diagnosis Hematoxylin and eosin stain or silver
  stain may show cyst forms. Periodic acid-schiff
  stain may show intracystic amylopectin. Studies
  demonstrated superior ability of
  immunohistochemical stain using an
  avidin-biotinylated peroxidase complex in
  identifying the tachyzoites of T. gondii in
  autopsy sp. Organisms that appear to be T. gondii
  tachyzoites should be distinguished from other
  organisms of similar appearances such as
  cytomegalovirus, Leishmania, Trypanosoma,
  Pneumocystis, and Histoplasma.

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Pulmonary Toxoplasmosis

• Diagnosis Study also suggested to confirm all
  morphologic diagnosis of T. gondii with
  immunohistochemical peroxidase stain (Hum Pathol
  1994 25 652). Other study demonstrated
  diagnosis of T. gondii in BAL and lung biopsy
  specimen using indirect immuno-fluorescence assay
  with the monoclonal antibody anti-P30 to a
  membrane antigen of T. gondii (JCM 1989271661).

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Pulmonary Toxoplasmosis

• Diagnosis Polymerase chain reaction done on BAL
  fluid showed to be highly sensitive for diagnosis
  of PT (JID 1993 168 1585 JCM 1995 33 1662).
  PCR detection of T. gondii in a sputum sp has
  recently been described however, sensitivity
  remains to be evaluated (AIDS 200014910).
• The diagnosis of PT can easily be overlooked as
  no definitive clinical or radiological clues are
  specific. The biological proof of diagnosis is
  difficult, it is usually achieved by the
  microcopic visualization of tachyzoite in BAL, a
  technique of poor sensitivity.

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Pulmonary Toxoplasmosis

• Treatment for PT are based on those devised for
  encephalitis. Therapy should include
  pyrimethamine 50 to 100 mg by mouth daily with
  folic acid 10 mg by mouth daily and sulfadiazine
  1.0 to 1.5 g by mouth every 6 hours, a
  combination that is synergistic against T. gondii
  infection (Med Lett 1995 37 87). Commonly used
  alternative regimen is pyrimethamine and
  clindamycin 450 to 600 mg by mouth four times
  daily. Other combinations with limited data to
  support efficacy include pyrimethamine with
  clarithromycin or azithromycin,

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Pulmonary Toxoplasmosis

• Treatment (other combinations) pyrimethamine
  alone, pyrimethamine with atovaquone, or
  pyrimethamine with dapsone (Ann Intern Med 1995
  123 230). Chr. suppressive therapy is required
  because of high relapse rate after successful
  treatment of acute infection. Study showed
  superior efficacy of pyrimethamine 50 mg daily
  with sulfadiazine 2 g daily in preventing
  relapses (Ann Intern Med 1995123175).

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Pulmonary Toxoplasmosis

• Prophylaxis Three regimens have been
  recommended cotrimoxazole, pyrimethamine plus
  dapsone, and pyrimethamine plus sulfadoxine
  (fansidar).