Hemophagocytic lymphohistiocytosis (HLH) and rhabdomyolysis are rare complications of typhoid fever from Salmonella enterica serovar Typhi. Herein, we describe the clinical features in a 21-year-old female from India who presented to the intensive care unit with fever, severe pancytopenia, and rhabdomyolysis

Despotovic, Vladimir

Esmaeeli, Amir

Non, Lemuel R

Patel, Rupa

American Journal of Tropical Medicine and Hygiene

English

PubMed

Lemuel R. Non

Rupa Patel

Vladimir Despotovic

Amir Esmaeeli

Crossref

Typhoid Fever Complicated by Hemophagocytic Lymphohistiocytosis and Rhabdomyolysis

Digital Commons@Becker

Washington University School of MedicineDigital Commons@BeckerOpen Access Publications2015Case report: Typhoid fever complicated byhemophagocytic lymphohistiocytosis andrhabdomyolysisLemuel R. NonWashington University School of Medicine in St. LouisRupa PatelWashington University School of Medicine in St. LouisAmir EsmaeeliWashington University School of Medicine in St. LouisVladimir DespotovicWashington University School of Medicine in St. LouisFollow this and additional works at: https://digitalcommons.wustl.edu/open_access_pubsThis Open Access Publication is brought to you for free and open access by Digital Commons@Becker. It has been accepted for inclusion in OpenAccess Publications by an authorized administrator of Digital Commons@Becker. For more information, please contact engeszer@wustl.edu.Recommended CitationNon, Lemuel R.; Patel, Rupa; Esmaeeli, Amir; and Despotovic, Vladimir, ,"Case report: Typhoid fever complicated byhemophagocytic lymphohistiocytosis and rhabdomyolysis." American Journal of Tropical Medicine and Hygiene.93,5. 1068-1069.(2015).https://digitalcommons.wustl.edu/open_access_pubs/4808Am. J. Trop. Med. Hyg., 93(5), 2015, pp. 1068–1069doi:10.4269/ajtmh.15-0385Copyright © 2015 by The American Society of Tropical Medicine and HygieneCase Report: Typhoid Fever Complicated by HemophagocyticLymphohistiocytosis and RhabdomyolysisLemuel R. Non,* Rupa Patel, Amir Esmaeeli, and Vladimir DespotovicDivision of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri; Department of Medicine,Washington University School of Medicine, St. Louis, Missouri; Division of Pulmonary and Critical Care,Washington University School of Medicine, St. Louis, MissouriAbstract. Hemophagocytic lymphohistiocytosis (HLH) and rhabdomyolysis are rare complications of typhoid feverfrom Salmonella enterica serovar Typhi. Herein, we describe the clinical features in a 21-year-old female from Indiawho presented to the intensive care unit with fever, severe pancytopenia, and rhabdomyolysis.INTRODUCTIONTyphoid fever (TF) remains to be an important etiology offever in developing countries, with an estimated 13.5 millionepisodes in 2010.1 The course of TF can range from an uncom-plicated febrile illness to life-threatening sepsis with multiorganinvolvement. We report a previously healthy Indian femalewith severe TF complicated by sepsis with multiple organdysfunction syndrome, rhabdomyolysis, and hemophagocyticlymphohistiocytosis (HLH).CASE REPORTA previously healthy 21-year-old Indian woman from south-ern India presented to our hospital with fever and confusionthat began 2 days after her arrival from India. She alsocomplained of fatigue, myalgia, and non-bloody, watery diar-rhea, occurring three to five times a day. She denies eatinguncooked food and food prepared outside her home, or anycontact with animals. No other family member or immediatecontacts in India or in the United States developed similarsymptoms. Her journey began from Vijayawada to Chennai,India, and her airline transit occurred through London,United Kingdom.On admission, her vital signs were: temperature 39.5°C,blood pressure 88/44 mmHg, heart rate 158 beats/minute, respi-ratory rate 39 breaths/minute, and oxygen saturation of 95%on room air. Physical examination was remarkable for drymucous membranes, mild muscle tenderness, splenomegaly,tea-colored urine, and disorientation. Otherwise, she had noedema, lymphadenopathy, abdominal tenderness, or skin rash.Laboratory investigations were significant for pancytopeniawith white cell count 0.9 × 109/L (absolute neutrophil count500/mm3), hemoglobin 11.6 g/dL (nadir of 7.9), and plateletcount 6 × 109/L, acute kidney injury with an elevated serumcreatinine of 1.37 mg/dL (peak of 1.64), hypokalemia (nadir of2.6 mmol/L), serum bicarbonate of 12 mmol/L, rhabdomyolysiswith creatine phosphokinase (CPK) of 83,550 U/L, and urinaly-sis showing 3+ blood. She was human immunodeficiency virusnegative, and workup for other infectious etiologies were nega-tive, including Ehrlichia PCR; dengue IgM; Leptospira serologyand urine culture; hepatitis A, B, C, and E panel; and malariarapid antigen and smear. She was started empirically on intra-venous vancomycin, cefepime, and doxycycline. Two sets ofblood culture and stool culture grew Salmonella enterica serovarTyphi (Salmonella typhi), and her antibiotics were eventuallyde-escalated to intravenous ceftriaxone. Disk diffusion methodfor susceptibility performed by the Center for Disease Controldisclosed the S. typhi to be susceptible to ampicillin, ceftriaxone,cefazolin, chloramphenicol, and trimethoprim–sulfamethoxazole,but had intermediate resistance to ciprofloxacin.With regard to her pancytopenia, patient had a negativeworkup for hemolysis, however, she fulfilled the diagnosticcriteria for HLH: presence of fever, splenomegaly, ferritin levelof 838 ng/mL, and a soluble interleukin-2 receptor (IL-2R)level of 2,939 U/mL (reference range 45–1,105 U/mL). Her pan-cytopenia eventually improved with antibiotics as is expectedfor infection-associated HLH (IAH). Her renal function alsoimproved with hydration and antibiotics. She was discharged ontrimethoprim–sulfamethoxazole 160mg/800mg two tablets twicedaily to complete a total of 2 weeks.DISCUSSIONTF by S. typhi can result in severe disease with complicationsin 10–15% of patients, including gastrointestinal bleeding,intestinal perforation, hepatitis, pancreatitis, typhoid encepha-lopathy, disseminated intravascular coagulation, hemolytic ure-mic syndrome, endocarditis, pneumonia, and rarely, reactiveHLH and rhabdomyolysis such as in our patient.2,3 Host factorsassociated with severe disease have been reported in youngerindividuals (birth through 1 year of age), the immunosup-pressed, females, and those infected with resistant S. typhi.3,4Specific genetic polymorphisms in major histocompatibilitycomplex class II and III genes have also been found in individ-uals with severe TF.5,6IAH has been most commonly associated with viral infec-tions, especially Epstein–Barr virus (EBV), but has also beenreported with pyogenic infections.7,8 IAH as a complicationof typhoid is rarely reported. The incidence is unknown inthe United States, but in a case series of 30 patients in India,two of IAH cases were in patients with TF.8 The pathophysi-ology of IAH is poorly understood, but it is suggested to bedue to hypersecretion of cytokines by persistently activatedlymphocytes and histiocytes. HLH is diagnosed using clinicaland molecular criteria. Five of eight clinical findings requiredare fever; splenomegaly; cytopenia; hypertriglyceridemia and/orhypofibrinogenemia; demonstration of hemophagocytosis inbone marrow, spleen, or lymph nodes; decreased natural killercell function; elevated ferritin level; and an elevated solubleCD25 or IL-2Rα chain ≥ 2,400 IU/mL.7 Sixty to seventy*Address correspondence to Lemuel R. Non, Division of InfectiousDiseases, Washington University School of Medicine, 660 S EuclidAvenue, Box 8051, St. Louis, MO 63110. E-mail: lnon@dom.wustl.edu1068percent of patients with IAH respond to supportive care andtreatment of the underlying infection, but severe cases, espe-cially those associated with EBV, have required chemotherapy.7The second unusual feature about this case is the degree ofrhabdomyolysis seen in the setting of enteric fever. Rhabdo-myolysis has been reported in bacterial sepsis, and in a retro-spective study in 103 patients from India, 33% were noted tobe in patients with gram-negative sepsis. However, S. typhiwas not isolated in their cohort, and the mean serum CPK of7,114 IU/L was much lower than in our patient.9 In a reviewof literature from 1996, Salmonella spp. was found to be thefourth most commonly cited cause of bacteria-induced rhab-domyolysis, with 67% of the cases leading to acute kidneyinjury.10 There have been 22 case reports of Salmonella infec-tion in the United States causing rhabdomyolysis, but onlytwo of these were due to S. typhi, with the majority beingcaused by non-typhoidal strains.11,12 It should be noted that inall the cases, rhabdomyolysis was noted when patients werebacteremic. Mechanisms proposed include sepsis causing tis-sue hypoxia, direct muscle invasion by bacteria, and alteredmetabolic activity of involved muscles.13 Despite its rarity, TFshould be included in the differential diagnosis of myositis orrhabdomyolysis in foreigners or returning travelers and shouldbe managed with treatment of an appropriate antibiotic andadequate hydration to prevent complications.CONCLUSIONTF should be suspected in returned travelers or foreignersfrom endemic countries presenting with severe febrile illnesscomplicated by pancytopenia and myalgia, which could beIAH and rhabdomyolysis, respectively. Recognition is impor-tant for prompt diagnosis and treatment with an appropriateantibiotic to prevent complications and increased mortality.Received May 24, 2015. Accepted for publication July 25, 2015.Published online August 31, 2015.Authors’ addresses: Lemuel R. Non and Rupa Patel, Division ofInfectious Diseases, Washington University School of Medicine, St.Louis, MO, E-mails: lnon@dom.wustl.edu and rrpatel@dom.wustl.edu. Amir Esmaeeli, Department of Medicine, Washington Univer-sity School of Medicine, St. Louis, MO, E-mail: esmaeelia@wusm.wustl.edu. Vladimir Despotovic, Division of Pulmonary and CriticalCare, Washington University School of Medicine, St. Louis, MO,E-mail: vdespoto@dom.wustl.edu.REFERENCES1. Buckle GC, Walker CLF, Black RE, 2012. Typhoid fever andparatyphoid fever: systematic review to estimate global mor-bidity and mortality for 2010. J Glob Health 2: 10401.2. Bhan M, Bahl R, Bhatnagar S, 2005. Typhoid and paratyphoidfever. Lancet 366: 749–762.3. Parry CM, Thompson C, Vinh H, Chinh NT, Phuong le T, HoVA, Hien TT, Wain J, Farrar JJ, Baker S, 2014. Risk factorsfor the development of severe typhoid fever in Vietnam.BMC Infect Dis 14: 73.4. Khan M, Coovadia YM, Connolly C, Sturm AW, 1999. Influenceof sex on clinical features, laboratory findings, and complica-tions of typhoid fever. Am J Trop Med Hyg 61: 41–46.5. Dunstan SJ, Stephens HA, Blackwell JM, Duc CM, Lanh MN,Dudbridge F, Phuong CX, Luxemburger C, Wain J, Ho VA,Hien TT, Farrar J, Dougan G, 2001. Genes of the class II andclass III major histocompatibility complex are associated withtyphoid fever in Vietnam. J Infect Dis 183: 261–268.6. Ali S, Vollaard AM, Kremer D, de Visser AW, Martina CA,Widjaja S, Surjadi C, Slagboom E, van de Vosse E, van DisselJT, 2007. Polymorphisms in proinflammatory genes and sus-ceptibility to typhoid fever and paratyphoid fever. J InterferonCytokine Res 27: 271–279.7. Rouphael NG, Talati NJ, Vaughan C, Cunningham K, MoreiraR, Gould C, 2007. Infections associated with haemophagocyticsyndrome. Lancet 7: 814–822.8. Singh ZN, Rakheja D, Yadav TP, Shome DK, 2005. Infection-associated haemophagocytosis: the tropical spectrum. Clin LabHaematol 27: 312–315.9. Kumar Aa, Bhaskar E, Shantha GPS, Swaminathan P, AbrahamG, 2009. Rhabdomyolysis in community acquired bacterialsepsis—a retrospective cohort study. PLoS One 4: 1–5.10. Singh U, Scheid WM, 1996. Infectious etiologies of rhabdomyoly-sis : three case reports and review. Clin Infect Dis 22: 642–649.11. Rheingold OJ, Greenwald R, Hayes PJ, Tedesco FJ, 1977.Myoglobinuria and renal failure associated with typhoid fever.JAMA 238: 341.12. Barnes P, Goldstein DA, Overturf GD, 1986. Rhabdomyolysisand pancytopenia in a young man. West J Med 144: 586–590.13. Fisk DT, Bradley SF, 2004. Rhabdomyolysis induced bySalmonella enterica serovar Typhi bacteraemia. Clin MicrobiolInfect 10: 595–597.1069TYPHOID FEVER, PANCYTOPENIA, AND RHABDOMYOLYSIS

Case report: Typhoid fever complicated by hemophagocytic lymphohistiocytosis and rhabdomyolysis

Case report: Typhoid fever complicated by hemophagocytic lymphohistiocytosis and rhabdomyolysis

Abstract

Similar works

Full text

Available Versions

Crossref

Digital Commons@Becker