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Episode #4 – a Case of Gut Discomfort

4 Cover Art

Summary

Dr. Gabriella Lamb walks us through a case of pediatric abdominal pain which leads to not one, but two new diagnoses!

Credits

Host: Sara Dong

Guest: Gabriella Lamb

Writing/Producing/Editing/Cover Art/Infographics: Sara Dong

Our Guest

Gabriella Lamb, MD, MPH

Dr. Lamb completed undergrad at Boston University, and then moved to Texas – where she attended medical school at Baylor College of Medicine, pediatric residency at University of Texas Southwestern in Dallas, and then pediatric ID fellowship at Texas Children’s Hospital.  While in fellowship, she obtained her MPH at the University of Texas Houston.  Dr. Lamb then relocated to Boston to work at Boston Children’s Hospital in August 2019.  At Boston Children’s, she is a clinician educator and the director of quality improvement for the division of infectious diseases.

Culture

Gabby told us about how she loved attending the ballet pre-pandemic, and she takes time to find ways to watch performances online instead!

Consult Notes

Consult Q

5 yo boy with fever and belly pain. Please help with antibiotics and work-up

One-liner

5 year old previously healthy boy found to have MSSA liver abscess and new diagnosis of chronic granulomatous disease

Key Points

Jump to:

Hepatic abscess in children:
 

CGD

Let’s talk about microbiology of hepatic abscesses first!  What pathogens do you need to consider?

  • Pyogenic liver abscesses in children are often polymicrobial.  Infections can be caused by aerobic, facultative, or anaerobic bacteria:
      • Enteric gram negative organisms (E.coli, Klebsiella, Enterobacter, Salmonella) or Pseudomonas
      • S.aureus, Strep spp., E.faecalis
  • Amebic abscesses (E.histolytica) can occur and may be difficult to distinguish from a pyogenic infection.  Organisms reach the liver through the portal venous system and usually cause a single, large abscess.  This possibility should be considered particularly in those who have lived in or traveled to endemic area (e.g., Africa, India, Mexico, and other parts of Central and South America)
  • Liver abscesses can be due to:
      • Direct extension from local infection (such as cholecystitis or cholangitis)
      • Hematogenous spread through hepatic artery or through portal vein from sources within abdominal cavity (e.g. appendicitis). Historically, appendicitis was a common cause of pyogenic liver abscesses, but this cause has decreased significantly with antibiotics and early surgical intervention
      • Traumatic injury, particularly in patients managed operatively and in those with concurrent injury to a hollow viscus
  • Other pathogens that might cause liver lesions, but likely appear differently on imaging compared to pyogenic liver abscess:
      • Cat scratch disease (Bartonella) is associated with multiple microabscesses of the liver and spleen.  This can be seen in otherwise healthy children or in immunocompromised children
      • M.tuberculosis: uncommon, often as multiple small abscesses as in miliary TB
      • Burkholderia pseudomallei (melioidosis)
      • Echinococcus spp: hepatic hydatid cysts
      • Candida spp can cause hepatosplenic candidiasis, often with microabscesses
      • Endemic fungal infections
  •  

How will a child with a liver abscess present?  Look for:

  • Fever
  • Abdominal pain (diffuse or localized to RUQ); Tender hepatomegaly
    • Might have referred pain to shoulder or a cough
  • Nausea
  • Vomiting
  • Anorexia
  • Jaundice is less common but can occur when abscess compresses biliary tract or parasitic infections (e.g., ascariasis) obstruct a bile duct lumen
  • Elevated WBC count or LFTs
  • Elevated inflammatory markers

Important additional history questions:

  • Travel history (if traveled to or lived in any endemic areas of parasitic infection)
  • Recent trauma, infection, or surgery
  • Kitten/cat or other animal exposure

How to manage hepatic abscess?

Antibiotic therapy alone has been successful.  Start with broad-spectrum antibiotics with activity against the most common organisms associated with the type of abscess identified.  

    • May need to consider antifungal therapy in immunocompromised patients
    • Multiple microabscesses are also treated successfully with antibiotics alone, especially in cases of cat scratch disease

Decisions regarding drainage are based on clinical presentation, condition of patient, need for micro confirmation. Optimal treatment strategies for liver abscess in children are not totally clear given rarity of presentation and are mostly inferred from adult cases.  Here is a summary of what is noted in Long’s Principles and Practice of Pediatric ID text:

      • Abscesses smaller than 4cm in diameter can be successfully treated by aspiration, with antibiotic therapy continued until patient’s clinical status improves and CT shows resolution of abscess
      • If abscess >4 cm or recurrence after aspiration, continuous drainage using CT or US-guided percutaneous catheter is indicated in addition to antibiotic therapy
      • Surgical drainage recommended with liver abscess that does not resolve with percutaneous drainage, those with rupture into peritoneal cavity, in patients with CHD who have persistent or recurrent liver abscesses

Here are a few papers related to liver abscess.  Also check out recommended chapters at the end of the Consult Notes for textbook options.

Now let’s change gears to talk more about chronic granulomatous disease (CGD).  Some of the basics:

How do you diagnose CGD?

What are the major clinical manifestations of CGD?

  • Patients will have recurrent or severe infections by bacteria or fungi
    • Bacterial infections are often symptomatic with fever or elevated inflammatory markers (but only mild leukocytosis).  
    • Fungal infections may only have a few symptoms and only noted while screening for infection or at an advanced stages
  • Most common sites of serious infection in CGD (more frequent to less frequent):
    • Pneumonia
    • Abscesses (skin, tissue, or visceral)
    • Suppurative adenitis
    • Osteomyelitis
    • Bacteremia/fungemia
    • Superficial skin infections (cellulitis/impetigo)
  • Children may also demonstrate growth failure / failure to thrive

Patients with CGD may have chronic respiratory disease (bronchiectasis, obliterative bronchiolitis, chronic fibrosis), and we also discussed the clinical entity of “mulch pneumonitis” on the show.  What is mulch pneumonitis?

  • A severe acute respiratory failure after high level exposure to aerosolized fungi.  This acute fulminant invasive fungal pneumonia in absence of iatrogenic or exogenous immunosuppression is a medical emergency highly associated with CGD
  • The patient inhales large burden of fungal spores and hyphae → develop syndrome of acute dyspnea, hypoxia, fever, and evidence of pulmonary infiltrates → symptoms can progress to fulminant respiratory failure and death within 1 to 10 days after inhalation
  • Possible exposures: cleaning gutters with dead leaves, heavy mulching, wood chipping, lawn mowing — really anything with significant amounts of exposure to mulch, trees, hay, moss, dirt, or other organic matter
  • Patients have been most successfully managed if treated with both glucocorticoids and antifungals. 
  • The correct diagnosis is important for therapy at time of presentation but also for genetic counseling and subsequent prophylaxis afterwards.

Read more here: Siddiqui S, Anderson VL, Hilligoss DM, et al. Fulminant mulch pneumonitis: an emergency presentation of chronic granulomatous disease. Clin Infect Dis. 2007;45(6):673-681. doi:10.1086/520985

We also discussed on the show that CGD patients are prone to granulomas of any hollow viscus, but how this can be especially problematic in the GI tract.

Liver abscesses are estimated to occur in about ⅓ of patients with CGD.  We discussed how liver abscesses may have distinct characteristics in the setting of CGD. 

Do liver abscesses in the setting of CGD require different management?

  • Classically, these abscesses are thought to almost always require surgery due to dense, caseous nature with difficult to drain fluid.  While surgical resection for liver abscess refractory to medical treatment is effective with low mortality, surgical morbidity may affect 56% of cases.  This has led some to favor debridement and percutaneous drainage when possible
  • An emerging approach is treatment of CGD-associated liver abscesses with high dose steroids added to the targeted IV antibiotics.  This is an attempt to modify the underlying inflammatory response.
  • Straughan DM, McLoughlin KC, Mullinax JE, et al. The Changing Paradigm of Management of Liver Abscesses in Chronic Granulomatous Disease. Clin Infect Dis. 2018;66(9):1427-1434. doi:10.1093/cid/cix1012
    • This paper compares the biochemical and clinical outcomes of CGD patients with liver abscesses treated with open surgery (OS), percutaneous drainage (IR), or steroid management (CM)
      • Of the 268 CGD patients managed at NIH from 1980-2014, 88 patients had liver involvement (26 with records to examine the questions)
      • Found improved LFTs, fewer subsequent hepatic interventions, and prolonged intervention free interval in steroid management cases compared to procedural intervention 
      • This paper suggested that invasive therapy may not be optimal for all CGD liver abscesses, and steroids may reduce systemic inflammation, immune infiltration, and capillary leak (improving liver function).

What are the important organisms of concern in patients with CGD?

Classically we learn that “catalase-positive microorganisms” cause the most issues, but this can encompass most bacterial and all fungal pathogens.  Plus, catalase is not necessary or sufficient alone for pathogenicity in CGD.  

Here is a list of the must-know organisms in the setting of CGD (North America):

  • Staph aureus
  • Serratia marcescens
  • Burkholderia cepacia
  • Nocardia
  • Aspergillus spp

Outside of North America, Salmonella and BCG are frequent infections and should suggest the diagnosis.  Consider mycobacterial infection in endemic settings!

Others that should ring alarm bells: Chromobacterium violaceum, Francisella philomiragia, Burkholderia gladioli, Granulibacter bethesdensis, Paecilomyces spp, Exophiala dermatidis

A few notes/pearls about this list:

What should be used for prophylaxis in CGD?

Although there is limiting data examining the approach, lifelong antimicrobial prophylaxis for CGD patients is considered standard of care.  Typically patients will receive trimethoprim-sulfamethoxazole (TMP-SMX) and itraconazole

What other treatment is available for CGD?

Other miscellaneous mentions and notes:

Episode Art & Infographics

Goal

Listeners will be able to discuss pyogenic liver abscess in the setting of chronic granulomatous disease.

Learning Objectives

After listening to this episode, listeners will be able to: 

  • List the common etiologies of pyogenic liver abscess
  • Compare typical pyogenic liver abscess to liver abscess in setting of chronic granulomatous disease
  • Describe pathophysiology of chronic granulomatous disease
  • List the top 5 pathogens to consider with CGD-associated infections 

Disclosures

Our guest (Gabriella Lamb) as well as the Febrile podcast and hosts report no relevant financial disclosures.

Citation

Lamb, G.., Dong, S.  “#4: a Case of Gut Discomfort”. Febrile: A Cultured Podcast.  https://player.captivate.fm/episode/86521705-0300-43f5-8010-3a4cf00797d3

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