CASCIO, Antonio

Correnti P

IARIA, CHIARA

International Journal of Infectious Diseases

English

Cascio, Antonio

Correnti, Patrizia

Iaria, Chiara

Elsevier - Publisher Connector 

Scrub typhus, acute respiratory distress, and hemophagocytic lymphohistiocytosis 

International Journal of Infectious Diseases 17 (2013) e662Letter to the Editor
Contents lists available at SciVerse ScienceDirect
International Journal of Infectious Diseases
jou r nal h o mep ag e: w ww .e lsev ier . co m / loc ate / i j idScrub typhus, acute respiratory distress, and
hemophagocytic lymphohistiocytosis
We found the paper by Goswami et al., concerning a severe case
of scrub typhus (disease caused by Orientia tsutsugamushi)
complicated by acute respiratory distress syndrome (ARDS) and
acute liver failure, very interesting.1 Perhaps, however, the
possible diagnosis of secondary hemophagocytic lymphohistiocy-
tosis (HLH) should also have been considered in that setting.
HLH is a potentially fatal hyperinﬂammatory syndrome
characterized by histiocyte proliferation and hemophagocytosis.
HLH may be inherited (primary, familial, generally occurring in
infants) or secondary to infection, malignancy, or rheumatologic
disease and occurring at any age. Secondary HLH is diagnosed
using the following clinical criteria developed by the HLH Study
Group of the Histiocyte Society; having ﬁve out of eight of the
following: (1) fever, (2) splenomegaly, (3) cytopenia (affecting 2
cell lineages), (4) hypertriglyceridemia and/or hypoﬁbrinogen-
emia, (5) hemophagocytosis in the bone marrow, spleen, or lymph
nodes, (6) low or absent natural killer cell cytotoxicity, (7)
hyperferritinemia, (8) elevated soluble CD25.2
In PubMed there are at least 12 papers describing cases of HLH
in patients with scrub typhus (search strategy: (haemophagocytic,
or haemophagocytosis, or hemophagocytosis, or hemophagocytic,
or erythrophagocytosis, or macrophage activation syndrome) AND
(scrub typhus OR tsutsugamushi OR orientia)), and ARDS was
described in at least four of them,3–6 and in one case was fatal.6
In PubMed there are at least 30 papers describing patients with
scrub typhus and ARDS (search strategy: (ARDS OR acute
respiratory distress syndrome OR acute respiratory failure) AND
(scrub typhus OR tsutsugamushi OR orientia)), and many of them
were also complicated by liver failure, multiorgan failure, and
disseminated intravascular coagulation (DIC); anemia and throm-
bocytopenia were very often reported. Strangely enough, only in a
few papers was a diagnosis of HLH considered in that setting.3,5,7
HLH is a life-threatening clinical syndrome. Liver involvement
is more frequent in pediatric cases, but may be present in adults
with variable levels of transaminases up to signs of acute liver
failure and coagulopathy. Respiratory distress is frequently present
and respiratory insufﬁciency represents a negative prognostic sign
and may need assisted ventilation. HLH can be triggered by
rickettsial diseases,8–10 and it should remembered that the
identiﬁcation of hemophagocytosis in bone marrow aspirate
represents only one of 5/8 criteria needed for the diagnosis of
HLH and that a bone marrow aspirate lacking hemophagocytosis
does not rule out the diagnosis of HLH.2
HLH should be suspected in every patient with rickettsial
diseases, especially in the presence of respiratory distress or
multiorgan dysfunction. An appropriate therapy could save the
patient.
Conﬂict of interest: All authors: no conﬂicts.1201-9712/$36.00 – see front matter  2013 International Society for Infectious Disea
http://dx.doi.org/10.1016/j.ijid.2013.03.006References
1. Goswami D, Hing A, Das A, Lyngdoh M. Scrub typhus complicated by acute
respiratory distress syndrome and acute liver failure: a case report from
Northeast India. Int J Infect Dis 2013 Feb 8 [Epub ahead of print].
2. Gupta S, Weitzman S. Primary and secondary hemophagocytic lymphohistio-
cytosis: clinical features, pathogenesis and therapy. Expert Rev Clin Immunol
2010;6:137–54.
3. Kwon HJ, Yoo IH, Lee JW, Chung NG, Cho B, Kim HK, et al. Life-threatening scrub
typhus with hemophagocytosis and acute respiratory distress syndrome in an
infant. J Trop Pediatr 2013;59:67–9.
4. Jayakrishnan MP, Veny J, Feroze M. Rickettsial infection with hemophagocy-
tosis. Trop Doct 2011;41:111–2.
5. Kobayashi T, Takizawa H, Hiroshima K, Uruma T, Enokihara H, Okuyama A. [A
case of new type scrub typhus (tsutsugamushi disease) presenting with acute
respiratory failure and hemophagocytic syndrome]. Nihon Kyobu Shikkan Gak-
kai Zasshi 1992;30:447–52.
6. Iwasaki H, Hashimoto K, Takada N, Nakayama T, Ueda T, Nakamura T. Fulminant
Rickettsia tsutsugamushi infection associated with haemophagocytic syndrome.
Lancet 1994;343:1236.
7. Yang SH, Ho YH, Chu CH, Chu SY. Childhood scrub typhus in eastern Taiwan:
ten-year experience from a medical center. Acta Paediatr Taiwan 2007;48:332–
6.
8. Cascio A, Giordano S, Dones P, Venezia S, Iaria C, Ziino O. Haemophagocytic
syndrome and rickettsial diseases. J Med Microbiol 2011;60:537–42.
9. Mansueto P, Vitale G, Cascio A, Seidita A, Pepe I, Carroccio A, et al. New insight
into immunity and immunopathology of rickettsial diseases. Clin Dev Immunol
2012;2012:967852.
10. Cascio A, Pernice LM, Barberi G, Delﬁno D, Biondo C, Beninati C, et al. Secondary
hemophagocytic lymphohistiocytosis in zoonoses. A systematic review. Eur Rev
Med Pharmacol Sci 2012;16:1324–37.
Antonio Cascioa,b,c,*
Patrizia Correntic,d
Chiara Iariac,e
aProgramma di Infettivologia Speciale, Medicina Tropicale e delle
Migrazioni e Parassitologia, Policlinico ‘‘G. Martino’’, Via Consolare
Valeria n. 1, 98125 Messina, Italy
bTropical and Parasitological Diseases Unit, Department of Human
Pathology, University of Messina, Messina, Italy
cAILMI (Associazione Italiana per la Lotta contro le Malattie Infettive;
Italian Association for the Control of Infectious Diseases), University of
Messina, Messina, Italy
dUnita` Operativa Complessa di Malattie Infettive – ARNAS ‘‘Civico, Di
Cristina, Benfratelli’’, Palermo, Italy
eInfectious Diseases Unit, Azienda Ospedaliera Piemonte-Papardo,
Messina, Italy
*Corresponding author. Tel.: +39 090 2213680;
ax: +39 090 692610
E-mail address: acascio@unime.it (A. Cascio)
Corresponding Editor: Eskild Petersen, Aarhus, Denmark
Received 26 February 2013
Revised 3 March 2013
Accepted 4 March 2013ses. Published by Elsevier Ltd. All rights reserved.


Archivio istituzionale della ricerca - Università di Palermo

This article appeared in a journal published by Elsevier. The attachedcopy is furnished to the author for internal non-commercial researchand education use, including for instruction at the authors institutionand sharing with colleagues.Other uses, including reproduction and distribution, or selling orlicensing copies, or posting to personal, institutional or third partywebsites are prohibited.In most cases authors are permitted to post their version of thearticle (e.g. in Word or Tex form) to their personal website orinstitutional repository. Authors requiring further informationregarding Elsevier’s archiving and manuscript policies areencouraged to visit:http://www.elsevier.com/authorsrightsAuthor's personal copyLetter to the EditorScrub typhus, acute respiratory distress, andhemophagocytic lymphohistiocytosisWe found the paper by Goswami et al., concerning a severe caseof scrub typhus (disease caused by Orientia tsutsugamushi)complicated by acute respiratory distress syndrome (ARDS) andacute liver failure, very interesting.1 Perhaps, however, thepossible diagnosis of secondary hemophagocytic lymphohistiocy-tosis (HLH) should also have been considered in that setting.HLH is a potentially fatal hyperinflammatory syndromecharacterized by histiocyte proliferation and hemophagocytosis.HLH may be inherited (primary, familial, generally occurring ininfants) or secondary to infection, malignancy, or rheumatologicdisease and occurring at any age. Secondary HLH is diagnosedusing the following clinical criteria developed by the HLH StudyGroup of the Histiocyte Society; having five out of eight of thefollowing: (1) fever, (2) splenomegaly, (3) cytopenia (affecting 2cell lineages), (4) hypertriglyceridemia and/or hypofibrinogen-emia, (5) hemophagocytosis in the bone marrow, spleen, or lymphnodes, (6) low or absent natural killer cell cytotoxicity, (7)hyperferritinemia, (8) elevated soluble CD25.2In PubMed there are at least 12 papers describing cases of HLHin patients with scrub typhus (search strategy: (haemophagocytic,or haemophagocytosis, or hemophagocytosis, or hemophagocytic,or erythrophagocytosis, or macrophage activation syndrome) AND(scrub typhus OR tsutsugamushi OR orientia)), and ARDS wasdescribed in at least four of them,3–6 and in one case was fatal.6In PubMed there are at least 30 papers describing patients withscrub typhus and ARDS (search strategy: (ARDS OR acuterespiratory distress syndrome OR acute respiratory failure) AND(scrub typhus OR tsutsugamushi OR orientia)), and many of themwere also complicated by liver failure, multiorgan failure, anddisseminated intravascular coagulation (DIC); anemia and throm-bocytopenia were very often reported. Strangely enough, only in afew papers was a diagnosis of HLH considered in that setting.3,5,7HLH is a life-threatening clinical syndrome. Liver involvementis more frequent in pediatric cases, but may be present in adultswith variable levels of transaminases up to signs of acute liverfailure and coagulopathy. Respiratory distress is frequently presentand respiratory insufficiency represents a negative prognostic signand may need assisted ventilation. HLH can be triggered byrickettsial diseases,8–10 and it should remembered that theidentification of hemophagocytosis in bone marrow aspiraterepresents only one of 5/8 criteria needed for the diagnosis ofHLH and that a bone marrow aspirate lacking hemophagocytosisdoes not rule out the diagnosis of HLH.2HLH should be suspected in every patient with rickettsialdiseases, especially in the presence of respiratory distress ormultiorgan dysfunction. An appropriate therapy could save thepatient.Conflict of interest: All authors: no conflicts.References1. Goswami D, Hing A, Das A, Lyngdoh M. Scrub typhus complicated by acuterespiratory distress syndrome and acute liver failure: a case report fromNortheast India. Int J Infect Dis 2013 Feb 8 [Epub ahead of print].2. Gupta S, Weitzman S. Primary and secondary hemophagocytic lymphohistio-cytosis: clinical features, pathogenesis and therapy. Expert Rev Clin Immunol2010;6:137–54.3. Kwon HJ, Yoo IH, Lee JW, Chung NG, Cho B, Kim HK, et al. Life-threatening scrubtyphus with hemophagocytosis and acute respiratory distress syndrome in aninfant. J Trop Pediatr 2013;59:67–9.4. Jayakrishnan MP, Veny J, Feroze M. Rickettsial infection with hemophagocy-tosis. Trop Doct 2011;41:111–2.5. Kobayashi T, Takizawa H, Hiroshima K, Uruma T, Enokihara H, Okuyama A. [Acase of new type scrub typhus (tsutsugamushi disease) presenting with acuterespiratory failure and hemophagocytic syndrome]. Nihon Kyobu Shikkan Gak-kai Zasshi 1992;30:447–52.6. Iwasaki H, Hashimoto K, Takada N, Nakayama T, Ueda T, Nakamura T. FulminantRickettsia tsutsugamushi infection associated with haemophagocytic syndrome.Lancet 1994;343:1236.7. Yang SH, Ho YH, Chu CH, Chu SY. Childhood scrub typhus in eastern Taiwan:ten-year experience from a medical center. Acta Paediatr Taiwan 2007;48:332–6.8. Cascio A, Giordano S, Dones P, Venezia S, Iaria C, Ziino O. Haemophagocyticsyndrome and rickettsial diseases. J Med Microbiol 2011;60:537–42.9. Mansueto P, Vitale G, Cascio A, Seidita A, Pepe I, Carroccio A, et al. New insightinto immunity and immunopathology of rickettsial diseases. Clin Dev Immunol2012;2012:967852.10. Cascio A, Pernice LM, Barberi G, Delfino D, Biondo C, Beninati C, et al. Secondaryhemophagocytic lymphohistiocytosis in zoonoses. A systematic review. Eur RevMed Pharmacol Sci 2012;16:1324–37.Antonio Cascioa,b,c,*Patrizia Correntic,dChiara Iariac,eaProgramma di Infettivologia Speciale, Medicina Tropicale e delleMigrazioni e Parassitologia, Policlinico ‘‘G. Martino’’, Via ConsolareValeria n. 1, 98125 Messina, ItalybTropical and Parasitological Diseases Unit, Department of HumanPathology, University of Messina, Messina, ItalycAILMI (Associazione Italiana per la Lotta contro le Malattie Infettive;Italian Association for the Control of Infectious Diseases), University ofMessina, Messina, ItalydUnita` Operativa Complessa di Malattie Infettive – ARNAS ‘‘Civico, DiCristina, Benfratelli’’, Palermo, ItalyeInfectious Diseases Unit, Azienda Ospedaliera Piemonte-Papardo,Messina, Italy*Corresponding author. Tel.: +39 090 2213680;ax: +39 090 692610E-mail address: acascio@unime.it (A. Cascio)Corresponding Editor: Eskild Petersen, Aarhus, DenmarkReceived 26 February 2013Revised 3 March 2013Accepted 4 March 2013International Journal of Infectious Diseases 17 (2013) e662Contents lists available at SciVerse ScienceDirectInternational Journal of Infectious Diseasesjou r nal h o mep ag e: w ww .e lsev ier . co m / loc ate / i j id1201-9712/$36.00 – see front matter  2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.http://dx.doi.org/10.1016/j.ijid.2013.03.006

Scrub typhus, acute respiratory distress, and hemophagocytic lymphohistiocytosis

https://iris.unipa.it/bitstream/10447/379292/1/Scrub%20typhus%2c%20acute%20respiratory%20distress%20and%20hemophagocytic%20lymphohistiocytosis.pdf

Scrub typhus, acute respiratory distress, and hemophagocytic lymphohistiocytosis

Abstract

Similar works

Full text

Available Versions

Elsevier - Publisher Connector

Elsevier - Publisher Connector

Archivio istituzionale della ricerca - Università di Palermo