Secondary Hemophagocytic Lymphohistiocytosis Induced by Malaria Infection in a Child with Langerhans Cell Histiocytosis

Abstract

Since the first description of infection-associated hemophagocytosis (IAHS), the list of precipitating infectious agents causing hemophagocytic syndrome has grown. A lymphohistiocytic proliferation with hemophagocytosis may develop as a result of macrophage activation, viral or bacterial infection, parasitic infestations, or malignancy. The authors report on a 3-year-old boy with Langerhans cell histiocytosis (LCH), who developed IAHS during malaria infection. Hemophagocytic syndromes may complicate the course of LCH and cause diagnostics problems. Malaria is one of many infections that can precipitate secondary hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis: review of etiologies and management

“…After the first bacteria-associated HLH cases were identified, a connection to protozoan, parasitic, and fungal infections was not far behind. Numerous reports of parasite-associated HLH have also been reported, with leishmaniasis 83,128-140 and malaria 141,142 discussion of zoonoses associated with HLH is presented in Cascio et al 83 The most common protozoans associated with HLH are presented in Table 4. Fungal organisms may cause HLH, either as a primary cause or in association with immunosuppression, as in HIV infection.…”

A multicenter study of patients with multisystem Langerhans cell histiocytosis who develop secondary hemophagocytic lymphohistiocytosis

“…17,18 Although to the best of our knowledge the underlying etiology of malignancy-associated HLH remains poorly understood, it is proposed that malignant as well as infiltrating immune cells promote inflammation by secreting cytokines, such as interferon γ, which is capable of driving the activation of macrophages and T cells. [3][4][5][6][7][8][9][10] In what to our knowledge is the largest study to date, 30 patients were included but the study focused primarily on pathology with little information provided regarding confirmatory testing for HLH, treatment, and outcome. 22,23 Collectively, these cytokines amplify a local as well as systemic cytokine cascade, supporting the belief that LCH itself may be capable of inducing an HLH-like hyperinflammation.…”

“…LCH can affect patients of all ages and is associated with a broad spectrum of clinical manifestations and outcomes. 1,2 Occasionally, patients with multisystem LCH (MS-LCH; ie, LCH involving ≥2 organ systems) develop severe inflammation resembling that observed in patients with hemophagocytic lymphohistiocytosis (HLH), [3][4][5][6][7][8][9][10] a heterogeneous group of disorders typified by excessive activation of the immune system. 11 HLH can be primary Cancer March 15, 2019 (ie, hereditary) or secondary (ie, nonhereditary) in origin.…”

“…Consistent with this idea, case reports and small case series have described patients with LCH who also demonstrate features of HLH. [3][4][5][6][7][8][9][10] In what to our knowledge is the largest study to date, 30 patients were included but the study focused primarily on pathology with little information provided regarding confirmatory testing for HLH, treatment, and outcome. 4 To gain further insights into the association between HLH and LCH, we performed the current comprehensive, retrospective, multicenter study in which we estimated the prevalence and examined the clinical manifestations, timing, risk factors for development, and outcomes of LCH-associated HLH.…”

Sepsis due to Streptococcus pneumoniae associated with secondary hemophagocytic lymphohistiocytosis in a splenectomized patient for spherocytosis

“…Among bacterial infections associated with HLH, there were published associations with Borrelia, [19]-Babesia sp, [20] Bartonella sp, [21] Brucella sp, [22] Q fever, [23] Leptospira sp, [24] Listeria monocytogenes, [25] Mycoplasma pneumoniae, [26] and mycobacteria. [27][28][29][30][31][32] The most frequently described parasitic causes responsible for secondary HLH are: Leishmania sp, [33,34] malaria, [35][36][37] and Toxoplasma gondii. [38,39] Fungal infections are found to be associated with secondary HLH in HIV-infected patients such as Cryptococcus neoformans, [40] Candida spp, [41] or in patients with renal transplantation-association with disseminated histoplasmosis.…”