Burza S , Croft SL , Boelaert M , 2018. Leishmaniasis. Lancet 117: 951–970.
Molyneux DH , Savioli L , Engels D , 2017. Neglected tropical diseases: progress towards addressing the chronic pandemic. Lancet 389: 312–325.
Wang J-Y , Cui G , Chen H-T , Zhou X-N , Gao C-H , Yang Y-T , 2012. Current epidemiological profile and features of visceral leishmaniasis in People’s Republic of China. Parasit Vectors 5: 31.
Sumegi J , Barnes MG , Nestheide SV , Molleran-Lee S , Villanueva J , Zhang K , Risma KA , Grom AA , Filipovich AH , 2011. Gene expression profiling of peripheral blood mononuclear cells from children with active hemophagocytic lymphohistiocytosis. Blood 117: e151–e160.
Milner JD et al., 2010. Sustained IL-4 exposure leads to a novel pathway for hemophagocytosis, inflammation, and tissue macrophage accumulation. Blood 116: 2476–2483.
Chiossone L et al., 2012. Protection from inflammatory organ damage in a murine model of hemophagocytic lymphohistiocytosis using treatment with IL-18 binding protein. Front Immunol 3: 239.
Filipovich AH , 2008. Hemophagocytic lymphohistiocytosis and other hemophagocytic disorders. Immunol Allergy Clin North Am 28: 293–313, viii.
Koubaa M , Maaloul I , Marrakchi C , Mdhaffar M , Lahiani D , Hammami B , Makni F , Ayedi A , Ben Jemaa M , 2012. Hemophagocytic syndrome associated with visceral leishmaniasis in an immunocompetent adult-case report and review of the literature. Ann Hematol 91: 1143–1145.
Garrido D , Fuseau M , Garrido S , Celi S , 2020. Hemophagocytic lymphohistiocytosis associated with visceral leishmaniasis. Review of cases reported. Rev Cubana Med Trop 72: e524.
Rajagopala S , Dutta U , Chandra KSP , Bhatia P , Varma N , Kochhar R , 2008. Visceral leishmaniasis associated hemophagocytic lymphohistiocytosis—case report and systematic review. J Infect 56: 381–388.
Aronson N et al., 2016. Diagnosis and treatment of leishmaniasis: clinical practice guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Clin Infect Dis 63: E202–E264.
Henter JI et al., 2007. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 48: 124–131.
Dujardin A , de La Blanchardiere A , Dina J , Stefic K , Ravel C , Bonhomme J , Verdon R , Fournier AL , 2021. Case report: leishmania and HIV co-diagnosis: how to understand medical history? Front Immunol 12: 6.
Cruz GS , de Jesus AR , Almeida RP , Porto MA , 2021. Case report: visceral leishmaniasis and hemophagocytic lymphohistiocytosis: three clinical cases, three different patterns. Am J Trop Med Hyg 105: 138–141.
Kooli I , Marrakchi W , Toumi A , Aouam A , Baba H , Chakroun M , 2021. Unusual occurrence of hemophagocytic lymphohistiocytosis in HIV-positive person with visceral leishmaniasis. HIV AIDS Rev 20: 311–313.
Badiola J , Munoz-Medina L , Callejas JL , Delgado-Garcia A , Jurado M , Hernandez-Quero J , 2021. Hemophagocytic lymphohistiocytosis associated with Leishmania: a hidden passenger in endemic areas. Enferm Infecc Microbiol Clin 39: 188–191.
Diamantidis MD , Palioura A , Ioannou M , Tsangalas E , Karakousis K , 2020. Hemophagocytic lymphohistiocytosis as a manifestation of underlying visceral leishmaniasis. Cureus 12: 5.
Alkhaldy HY , Badri R , Bakheet OSE , 2020. Visceral leishmaniasis with hemophagocytic lymphohistiocytosis (HLH). IDCases 21: 3.
Kumari S , Dhawan P , Panda PK , Bairwa M , Pai VS , 2020. Rising visceral leishmaniasis in Holy Himalayas (Uttarakhand, India)—a cross-sectional hospital-based study. J Family Med Prim Care 9: 1362–1369.
Vanhinsbergh L , Mason A , Godfrey A , 2019. Visceral leishmaniasis presenting as haemophagocytic lymphohistiocytosis. BMJ Case Rep 12: 3.
Theodosiou AA , Hiew HJ , Petridou C , 2019. An acute presentation of haemophagocytic lymphohistiocytosis due to visceral leishmaniasis in a British adult returning traveller. Acute Med 18: 184–188.
Machelart I , Lapoirie J , Viallard JF , Mirabel M , Lazaro E , Greib C , Riviere E , 2019. Visceral leishmaniasis with hemophagocytic lymphohistiocytosis in an immunocompetent adult. Med Mal Infect 49: 548–550.
Singh PK , Sharma V , 2019. Ototoxicity, a rare but reversible adverse effect of a commonly used antimicrobial agent. BMJ Case Rep 12: 3.
George JT , Sadiq M , Sigamani E , Mathuram AJ , 2019. Visceral leishmaniasis with haemophagocytic lymphohistiocytosis. BMJ Case Rep 12: 3.
Mahendiran T , Doolub G , Nisbet A , 2018. Fever in a returning traveller: visceral leishmaniasis triggering haemophagocytic lymphohistiocytosis. BMJ Case Rep 2018: bcr2018224775.
Panda PK , Mohta S , Sharma SK , Ray A , Arava S , Vyas S , 2016. A case of pseudorheumatism with submasseteric abscess and HLH in a patient with visceral leishmaniasis: a diagnostic dilemma. J Vector Borne Dis 53: 387–390.
Raina RK , Raina S , Sharma M , 2017. Visceral leishmaniasis-associated hemophagocytosis: a tale of two unexpected diagnoses from a nonendemic region. Trop Parasitol 7: 56–58.
Rios-Fernandez R , Callejas-Rubio JL , Garcia-Rodriguez S , Sancho J , Zubiaur M , Ortego-Centeno N , 2016. Tocilizumab as an adjuvant therapy for hemophagocytic lymphohistiocytosis associated with visceral leishmaniasis. Am J Ther 23: E1193–E1196.
Raina S , Raina RK , Sharma R , Rana BS , Bodh A , Sharma M , 2016. Expansion of visceral leishmaniasis to northwest sub-Himalayan region of India: a case series. J Vector Borne Dis 53: 188–191.
Ranjan P , Kumar V , Ganguly S , Sukumar M , Sharma S , Singh N , Vikram NK , Pati HP , Sood R , 2016. Hemophagocytic lymphohistiocytosis associated with visceral leishmaniasis: varied presentation. Indian J Hematol Blood Transfus 32: S351–S354.
Comont T , Martin-Blondel G , Laurent C , Berry A , Marchou B , 2015. Severe haemophagocytic lymphohistiocytosis triggered by a visceral leishmaniasis in a patient with a Rosai-Dorfman disease. Ann Hematol 94: 701–702.
Pawar S , Ragesh R , Nischal N , Sharma S , Panda PK , Sharma SK , 2015. Unique triad of pregnancy, kala azar and hemophagocytic lymphohistiocytic syndrome from a non-endemic region. J Assoc Physicians India 63: 65–68.
Merelli M , Quartuccio L , Bassetti M , Pecori D , Gandolfo S , Avellini C , De Vita S , 2015. Efficacy of intravenous cyclosporine in a case of cytophagic histiocytic panniculitis complicated by haemophagocytic syndrome after visceral leishmania infection. Clin Exp Rheumatol 33: 906–909.
Watkins ER , Shamasunder S , Cascino T , White KL , Katrak S , Bern C , Schwartz BS , 2014. Visceral leishmaniasis-associated hemophagocytic lymphohistiocytosis in a traveler returning from a pilgrimage to the Camino de Santiago. J Travel Med 21: 429–432.
Moltó A , Mateo L , Lloveras N , Olivé A , Minguez S , 2010. Visceral leishmaniasis and macrophagic activation syndrome in a patient with rheumatoid arthritis under treatment with adalimumab. Joint Bone Spine 77: 271–273.
Martin A , Marques L , Soler-Palacin P , Caragol I , Hernandez M , Figueras C , Espanol T , 2009. Visceral leishmaniasis associated hemophagocytic syndrome in patients with chronic granulomatous disease. Pediatr Infect Dis J 28: 753–754.
Patel KK , Patel AK , Sarda P , Shah BA , Ranjan R , 2009. Immune reconstitution visceral leishmaniasis presented as hemophagocytic syndrome in a patient with AIDS from a nonendemic area: a case report. J Int Assoc Physicians AIDS Care (Chic) 8: 217–220.
Kilani B , Ammari L , Kanoun F , Ben Chaabane T , Abdellatif S , Chaker E , 2006. Hemophagocytic syndrome associated with visceral leishmaniasis. Int J Infect Dis 10: 85–86.
Fiteni I , Perez-Lungmus G , Grasa J , Motis C , 2004. The hemophagocytic syndrome in an immunocompromised patient: a diagnostic challenge. Can J Infect Dis 15: 101–103.
Kontopoulou T , Tsaousis G , Vaidakis E , Fanourgiakis P , Michalakeas E , Trigoni E , Samarkos M , 2002. Hemophagocytic syndrome in association with visceral leishmaniasis. Am J Med 113: 439–440.
Bhutani V , Dutta U , Das R , Singh K , 2002. Hemophagocytic syndrome as the presenting manifestation of visceral leishmaniasis. J Assoc Physicians India 50: 838–839.
Cortés P , Cardeñosa N , Muñoz C , Durán I , Leta R , Roca-Cusachs A , Gállego M , 1997. Hemophagocytic syndrome associated with visceral leishmaniasis in an immunocompetent patient. Clin Microbiol Newsl 19: 14–16.
Bessis D , Sotto A , Taib J , Ciurana AJ , 1993. Photo quiz. Visceral leishmaniasis with hemophagocytic syndrome. Clin Infect Dis 17: 611, 829.
Rodriguezcuartero A , Salasgalan A , Perezgalvez MN , Perezblanco FJ , 1991. Hemophagocytic visceral kala azar. Infection 19: 184.
Matzner Y , Behar A , Beeri E , Gunders AE , Hershko C , 1979. Systemic leishmaniasis mimicking malignant histiocytosis. Cancer 43: 398–402.
Jordan MB , Allen CE , Weitzman S , Filipovich AH , McClain KL , 2011. How I treat hemophagocytic lymphohistiocytosis. Blood 118: 4041–4052.
Ramos-Casals M , Brito-Zeron P , Lopez-Guillermo A , Khamashta MA , Bosch X , 2014. Adult haemophagocytic syndrome. Lancet 383: 1503–1516.
Scalzone M , Ruggiero A , Mastrangelo S , Trombatore G , Ridola V , Maurizi P , Riccardi R , 2016. Hemophagocytic lymphohistiocytosis and visceral leishmaniasis in children: case report and systematic review of literature. J Infect Dev Ctries 10: 103–108.
Bode SFN et al., 2014. Hemophagocytic lymphohistiocytosis in imported pediatric visceral leishmaniasis in a nonendemic area. J Pediatr 165: 147–153.
Henter JI et al., 2007. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 48: 124–131.
Bain BJ , 2001. Bone marrow aspiration. J Clin Pathol 54: 657–663.
da Silva MR , Stewart JM , Costa CH , 2005. Sensitivity of bone marrow aspirates in the diagnosis of visceral leishmaniasis. Am J Trop Med Hyg 72: 811–814.
Salam MA , Khan MGM , Bhaskar KRH , Afrad MH , Huda MM , Mondal D , 2012. Peripheral blood buffy coat smear: a promising tool for diagnosis of visceral leishmaniasis. J Clin Microbiol 50: 837–840.
Bern C et al., 2006. Liposomal amphotericin B for the treatment of visceral leishmaniasis. Clin Infect Dis 43: 917–924.
|Past two years||Past Year||Past 30 Days|
|Full Text Views||164||164||17|
Hemophagocytic lymphohistiocytosis (HLH) is a rare and fatal complication of visceral leishmaniasis (VL). To provide a basis for early and correct diagnosis and to improve prognosis in the future, we describe a case series of VL-associated HLH in adults in our center in the past decade after review of all reported cases of adult VL-associated HLH in English through May 2022. In our case series, a total of 111 patients were diagnosed with VL. Among these patients, only six cases were diagnosed with VL-associated HLH. All patients tested positive for serology. Leishmania was detected for the first time by bone marrow aspiration (BMA) in three of the six patients and in the other three patients after three or four BMAs. It took more than 1 month from onset to diagnosis of VL for all the six cases, and the longest time was 6 months. Five of the six patients recovered after receiving sodium stibogluconate. VL-associated HLH is rare but potentially life-threatening in adults and predisposes to early delays in diagnosis. However, diagnostic techniques are not complicated or difficult, so it is more important to consider that it is not recognized by physicians. Although guidelines recommend liposomal amphotericin B as the most effective therapy, our experience suggests that sodium stibogluconate can be an alternative option when liposomal amphotericin B is unavailable or unaffordable.
Financial support: The study was supported by a grant from the Key Research and Development Project, Science and Technology Project of Sichuan Province, China (No. 2019YFS0202 to F. H.).
Disclosure: The views in this article are those of the authors and not of their institutions.
Authors’ addresses: Yao Qin, Xiaoju Lv, and Fang He, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China, E-mails: firstname.lastname@example.org, email@example.com, and firstname.lastname@example.org. Yao Qin and Ting Liu, Department of Hematology, West China Hospital, Sichuan University, Chengdu, China, E-mails: email@example.com and firstname.lastname@example.org. Qin Zheng and Mei Kang, Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China, E-mails: email@example.com and Kangmei@sina.com. Qian Wu and Linmao Zheng, Department of Pathology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China, E-mails: firstname.lastname@example.org and email@example.com.