Diapositiva 1

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Case Presentation2007 CIS Summer School on PID
Patricia Roessler, MD MSc University of Chile
Clinical Hospital
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• Sex male
• DOB 23/06/05, Valdivia
• Born full term, no complications
• Family History
• No siblings
• No consanguinity
• Both parents are healthy
• Bacillus Calmette Guérin vaccine (BCG) at 2 days
  of age

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• 6 w Progressive left axillar adenopathy with
  suppuration
• 5 m
• Diffuse lymphadenopathy cervicals,
  suboccipitals, inguinals
• Biopsy granulomatous lymphadenitis with necrosis
  and a great amount of fast acid bacilli

observation
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Most probable diagnosis ?

• Disseminated BCG infection

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• 7 m Anti mycobacterial treatment
  rifampin,pyrazinamide,isoniazide, ciprofloxacin
• 14m no clinical response despite 7 months of
  anti mycobacterial treatment
• Fever, diffuse lymphadenopathy, and
  hepatosplenomegaly
• Sent to Luis Calvo Mackenna Hospital (Santiago)

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What would you have done ?
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• Mycobacterial culture myc var Bovis
• Mycobacterial drug susceptibility study
• Meanwhile treatment was changed
  rifampin,azithromycin,ethambutol, amikacin,
  clofazimine
• Images BCG dissemination (splenomegaly, splenic
  hilium and retroperitoneal big adenopathies)

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(No Transcript)
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Immunologic study

• SCID was discarted
• Defect of the IL-12/23-IFN-? axis suspected.
• Samples sent to France (Laboratoire de Génétique
  Humaine des Maladies Infectieuse, Faculté de
  Medicine Necker-Enfants-malades, Université Paris
  Rene-Descartes) for immunologic and molecular
  studies.

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IL12RB1 deficiency
Flow for IL-12Rb1 on the surface of activated T
cell PHA blasts
Genetic analysis of IL-12Rb1
Mutations in IL-12Rb1
169delA/T62G
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Genetic ethiologies of Mendelian susceptibility
to mycobacterial infections
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• IFN-? 22 ?g/m2/day, 3 times per week.
• 1 month later
• adenopathies growing
• cultures still positive
• rifampicin resistance (stopped)
• 3 months later IFN-? 90 ?g/m2/day, 3 times per
  week.
• chylothorax
• deep venous thrombosis
• abdominal distention

Excessive inflammatory Response ?
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• IFN-? suspension
• Corticosteroids
• New anti mycobact treatment (based on
  mycobacterial susceptibility, USA) levofloxacine,
  rifampin, ethambutol, clofazime, izoniacide,
  streptomicine
• Low levels of isoniacid, ethambutol and
  clofazimine (malabsortion?)

due to excessive inflammation
Drug doses adjusted
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• 2 months later
• Cryptosporidium parvum diarrhea
• Suppuration from cervical and inguinal
  adenopathies smear ( for AFB)
• RSV, Klebsiella pneumoniae sepsis, ADRS
• BAL AFB
• Death

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• Thanks to Dra Alejandra King, Hospital Luis
  Calvo Mackenna and to Dr Steve Holland