My opinion

By Dr. Dina Khalaf , Dr. Bassem Toema , Dr. Shaker Al-sadadi , Dr. Fathi Al-jehani , Dr. Mohamed Sammak
Corresponding Author Dr. Dina Khalaf
Department of Hematology and Oncology, Saad Specialist Hospital, - Saudi Arabia
Submitting Author Dr. Bassem Toema
Other Authors Dr. Bassem Toema
Department Of Clinical Pharmacology, University Of Oxford, - United Kingdom

Dr. Shaker Al-sadadi
Department of Hematology and Oncology, Saad Specialist Hospital, - Saudi Arabia

Dr. Fathi Al-jehani
Department of Hematology and Oncology, Saad Specialist Hospital, - Saudi Arabia

Dr. Mohamed Sammak
Department of Hematology and Oncology, Saad Specialist Hospital, - Saudi Arabia


Salmonella Typhi, Hemophagocytic Lymphohistiocytosis, Pancyotpenia, Typhoid Fever, Sepsis, Bacterial Immunogenicity

Khalaf D, Toema B, Al-sadadi S, Al-jehani F, Sammak M. Salmonella Typhi Associated Hemophagocytic Lymphohistiocytosis in a Previously Healthy 23 Years Old Woman. WebmedCentral INFECTIOUS DISEASES 2011;2(3):WMC001751
doi: 10.9754/journal.wmc.2011.001751
Submitted on: 12 Mar 2011 06:22:03 AM GMT
Published on: 12 Mar 2011 01:49:40 PM GMT

My opinion

A previously healthy 23 years old female was admitted with fever. All the clinical and laboratory findings of the patient are summarized in Table 1. Blood culture revealed Salmonella typhi. Bone marrow aspirate showed hemophagocytosis (figures 1 and 2). The patient received fluoroquinolone, intravenous pentaglobulins for 4 days and intravenous dexamethasone for 8 days. There was marked clinical and biochemical improvement (graphs 1, 2 and 3).

Suggestive evidence linking Hemophagocytic Lymphohistiocytosis (HLH) to Typhoid fever include:

1. Differentiating HLH from similar blood diseases

According to the Histiocyte Society guidelines, five out of eight criteria should be fulfilled for establishing diagnosis of HLH. The history of persistent high grade fever, physical examination and CT scans that revealed hepatosplenomegaly, pancytopenia, associated transaminitis, hypofibrinogenemia and elevated Lactate dehydrogenase and ferritin levels supported the evidence for HLH besides the histopathological confirmation of hemophagocytosis by bone marrow examination. Peripheral smear didn’t show fragmentation or schistocytes excluding thrombotic thrombocytopenic purpura. [1]

2. Exploring other possible causes of HLH

Complete viral screen for Cytomegalovirus, Epstein Barr virus, Hepatitis B and C Viruses, and Human Immunodeficiency Viruses 1 and 2 was negative. Antinuclear antibody, Double stranded DNA antibody, Rheumatoid Factor and Anti Neutrophil Cytoplasmic Antibody were negative ruling out the macrophage activation syndrome.

3. Positive temporal relationship and biological plausibility

Hemophagocytosis is non-specific frequent pathologic finding in the active proliferative stage of typhoid fever which coincides with the second week of infection. [2]

4. Recognized association with Gram negative aerobic bacilli

Brucella is a genus of Gram negative, non motile, non spore-forming bacilli. In a pivotal case-control study, 16 patients (5.8%) out of 276 pediatric cases of brucellosis seen over a 7-year period were found to have pancytopenia. Fourteen out of these 16 patients (87.5%) had positive blood and / or bone marrow cultures for Brucella melitensis. Also hemophagocytosis was observed in 14 out of these 16 patients (87.5%). [3]

Typhoid fever is rarely associated with HLH. In one study the bone marrow of four cases (out of fifteen cases of culture proven typhoid fever) was examined and showed infection associated Hemophagocytic syndrome. In another study, the bone marrow examinations of five patients with Typhoid fever associated with pancytopenia revealed histiocytic hyperplasia with marked phagocytosis of platelets, leukocytes and red blood cells in those affected individuals. [4][5]

5. Identification of Salmonella typhi with blood culture.

In conclusion, in areas where typhoid fever prevalence is high, hemophagocytic findings should be considered Salmonella typhi associated HLH until proven otherwise.



1.Janka Gritta. Familial and acquired hemophagocytic lymphohistiocytosis.  Eur J Pediatr 2007; 166:95–109.

2.B. Frisch, S.M. Lewis, R. Burkhardt, R. Barti. Biopsy Pathology of Bone and Bone Marrow - Biopsy Pathology Series Chapman and Hall Medical. 1985; 58-69.

3.Al-Eissa YA, Assuhaimi SA, Al-Fawaz IM, Higgy KE, Al-Nasser MN, Al-Mobaireek KF. Pancytopenia in children with brucellosis: clinical manifestations and bone marrow findings. Acta Haematol. 1993; 89:132-136.

4.Shin BM, Paik IK, Cho HI. Bone marrow pathology of culture proven typhoid fever. J Korean Med Sci. 1994; 9:57-63.

5.Udden MM, Bañez E, Sears DA. Bone marrow histiocytic hyperplasia and hemophagocytosis with pancytopenia in typhoid fever. Am J Med Sci. 1986; 291:396-400.

Source(s) of Funding

“On behalf of all the contributors, I declare that there is no support in financial or other manner”.

Competing Interests

“On behalf of all the contributors, I declare that we have no conflict of interests‟.


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