0
Correspondence |

ResponseResponse FREE TO VIEW

Robert A. Raschke, MD
Author and Funding Information

From the Department of Medicine, Section of Critical Care, Banner Good Samaritan Medical Center.

Correspondence to: Robert A. Raschke, MD, Department of Medicine, Section of Critical Care, Banner Good Samaritan Medical Center, 1111 E McDowell Rd, Phoenix, AZ 85006; e-mail: robert.raschke@bannerhealth.com


Financial/nonfinancial disclosures: The author has reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2012 American College of Chest Physicians


Chest. 2012;141(3):836. doi:10.1378/chest.11-3005
Text Size: A A A
Published online

To the Editor:

I share the enthusiasm of Drs Besset, Schnell, and Azoulay and appreciate their observations in relation to our article on hemophagocytic lymphohistiocytosis (HLH) in CHEST.1 In clinical practice, I have put much effort into recognizing and treating HLH aggressively, as they have. Despite this, I have struggled intellectually with two of the ideas that they express: that HLH and sepsis must be differentiated, and that treatment of infection-related HLH in adults requires treatment with etoposide.

There is no pathologic gold standard for the diagnosis of HLH. It is not uncommon to detect histiocytic hemophagocytosis in patients with sepsis2 in the absence of HLH. The lack of a gold standard makes studies regarding the operating characteristics of other diagnostic tests for HLH very difficult. In their letter, Dr Besset and colleagues mention the sensitivity of diagnostic tests for HLH, but it is the specificity of these tests that would allow a physician to distinguish HLH from sepsis. As discussed in the study1, we found that the specificity of HLH-2004 diagnostic criteria in distinguishing HLH from sepsis is either poor or unknown. Many HLH diagnostic criteria are also positive in the majority of patients with sepsis. So although I wish infection-related HLH could always be distinguished from sepsis, it is not the case given the current state of our knowledge. It is possible that infection-triggered HLH may not actually be a distinct disease at all, but rather an abnormal expression of sepsis on the extreme end of the proinflammatory spectrum.3 Regardless, from a practical standpoint, the intensivist at the bedside will have to make a decision whether to start aggressive immunosuppressive therapy, and we offered a suggestion for how to do this in our review.1

We gave etoposide to several patients, but it should be noted that there are no prospective, randomized, controlled trial data to support the use of etoposide in adults, only retrospective data limited to patients with Epstein-Barr virus-related HLH.4 Etoposide is a potentially highly toxic chemotherapeutic agent that is generally contraindicated in patients with renal failure, hyperbilirubinemia, and hypoalbumenemia,5 which are all conditions that adult patients with HLH and/or septic shock syndrome are likely to suffer. Etoposide has been apparently safely given to adults who are critically ill with HLH,6 but no strong guidance was found in the literature regarding how to appropriately determine doses for these patients. Therefore, I remain cautious about making a recommendation that etoposide is required. Given the weakness of experimental evidence, physicians should weigh the risks and benefits in light of the clinical condition of the individual patient.

I believe that HLH remains underdiagnosed in many adult critical care units. Better recognition of the syndrome and its clinical and pathophysiologic relationship with septic shock should help improve the diagnosis and management of HLH, despite current shortfalls in our understanding.

Raschke RA, Garcia-Orr R. Hemophagocytic lymphohistiocytosis: a potentially underrecognized association with systemic inflammatory response syndrome, severe sepsis, and septic shock in adults. Chest. 2011;1404:933-938. [PubMed] [CrossRef]
 
Stéphan F, Thiolière B, Verdy E, Tulliez M. Role of hemophagocytic histiocytosis in the etiology of thrombocytopenia in patients with sepsis syndrome or septic shock. Clin Infect Dis. 1997;255:1159-1164. [PubMed]
 
Castillo L, Carcillo J. Secondary hemophagocytic lymphohistiocytosis and severe sepsis/systemic inflammatory response syndrome/multiorgan dysfunction syndrome/macrophage activation syndrome share common intermediate phenotypes on a spectrum of inflammation. Pediatr Crit Care Med. 2009;103:387-392. [PubMed]
 
Imashuku S, Kuriyama K, Sakai R, et al. Treatment of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) in young adults: a report from the HLH study center. Med Pediatr Oncol. 2003;412:103-109. [PubMed]
 
Takimoto CH.DeVita VT, Hellman S, Rosenberg SA. Topoisomerase interactive agents. Cancer: Principles and Practice of Oncology. 2005; Philadelphia, PA Lippincott Williams and Williams:382-384
 
Buyse S, Teixeira L, Galicier L, et al. Critical care management of patients with hemophagocytic lymphohistiocytosis. Intensive Care Med. 2010;3610:1695-1702. [PubMed]
 

Figures

Tables

References

Raschke RA, Garcia-Orr R. Hemophagocytic lymphohistiocytosis: a potentially underrecognized association with systemic inflammatory response syndrome, severe sepsis, and septic shock in adults. Chest. 2011;1404:933-938. [PubMed] [CrossRef]
 
Stéphan F, Thiolière B, Verdy E, Tulliez M. Role of hemophagocytic histiocytosis in the etiology of thrombocytopenia in patients with sepsis syndrome or septic shock. Clin Infect Dis. 1997;255:1159-1164. [PubMed]
 
Castillo L, Carcillo J. Secondary hemophagocytic lymphohistiocytosis and severe sepsis/systemic inflammatory response syndrome/multiorgan dysfunction syndrome/macrophage activation syndrome share common intermediate phenotypes on a spectrum of inflammation. Pediatr Crit Care Med. 2009;103:387-392. [PubMed]
 
Imashuku S, Kuriyama K, Sakai R, et al. Treatment of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) in young adults: a report from the HLH study center. Med Pediatr Oncol. 2003;412:103-109. [PubMed]
 
Takimoto CH.DeVita VT, Hellman S, Rosenberg SA. Topoisomerase interactive agents. Cancer: Principles and Practice of Oncology. 2005; Philadelphia, PA Lippincott Williams and Williams:382-384
 
Buyse S, Teixeira L, Galicier L, et al. Critical care management of patients with hemophagocytic lymphohistiocytosis. Intensive Care Med. 2010;3610:1695-1702. [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543