An update on renal involvement in hemophagocytic syndrome (macrophage activation syndrome)

Abstract

Context: Hemophagocytic syndrome (HPS) is mainly characterized by massive infiltration of bone marrow by activated macrophages and often presents with pancytopenia. Thrombotic microangiopathy (TMA) is also present with thrombocytopenia and renal involvement. Both conditions could coexist with each other and complicate the condition. Evidence Acquisition: Directory of Open Access Journals (DOAJ), EMBASE, Google Scholar, PubMed, EBSCO, and Web of Science with keywords relevant to; Hemophagocytic syndrome, macrophage activation syndrome, interferon-gamma and thrombotic microangiopathy, have been searched. Results: Viral infection, rheumatologic disease and malignancies are the main underlying causes for secondary HPS. calcineurin inhibitors and viral infections are also the main underlying causes of TMA in transplant recipients. In this review, we discussed a 39-year-old male who presented with pancytopenia and renal allograft dysfunction. With the diagnosis of HPS induced TMA his renal condition and pancytopenia improved after receiving intravenous immunoglobulin (IVIG) and plasmapheresis therapy. Conclusions: HPS is an increasingly recognized disorder in the realm of different medical specialties. Renal involvement complicates the clinical picture of the disease, and this condition even is more complex in renal transplant recipients. We should consider the possibility of HPS in any renal transplant recipient with pancytopenia and allograft dysfunction. The combination of HPS with TMA future increases the complexity of the situation.

Secondary hemophagocytic syndrome after renal transplantation: two case-reports

“…5 The first 19 cases were published in 1979 by Risdall et al, 13 of which occurred after renal transplantation,1 was due to SLE, and 5 were idiopathic. 4,5,10,12,14 In 1985, Hadchouel reported the first HLH cases associated with rheumatic pathologies and named the disease macrophage activation syndrome. 3,5 The condition is underdiagnosed, and should always be considered in cases of febrile cytopenia with hepatosplenomegaly.…”

“…Secondary HLH is associated with infections (viral, fungal, bacterial, and parasitic), drugs (methotrexate, non-hormonal anti-inflammatories, anticonvulsants, anti-TNF-α, anti-CD52), autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, Sjögren syndrome, systemic sclerosis, and Kawasaki disease), neoplasms (lymphomas), and immunosuppression (solid organ transplantation). 1,2,5,9,10,12,13,14,16 A diagnostic criteria was proposed in 1991 and revised in 2004 by the International Society of Histiocytosis and includes 8 items of which at least 5 must be present (Chart 1). 1,2,6,8 The two case-reports described post-KTx HLHs secondary to infectious processes with at least 6 diagnostic criteria each.…”

“…Emmenegger et al reported a 59% response with 1.6 g/kg IVIG for 3 days in patients with different Fever (> 38ºC for at least 7 days) Cytopenia affecting 2 or 3 cell types (hemoglobin < 9.0g/dL; neutrophils < 1.000/mm³; platelets < 100.000/mm³) underlying conditions (infection, malignancy, and systemic lupus erythematosus), confirming the effectiveness of this therapeutic strategy, especially with the infectious condition (78% versus 39%). 5,10,12,15,17 The main predictive factor of good clinical response was starting therapy within 2 days of serum ferritin peak. 5,15 Asci et al reported that of the 13 patients with post-KTx HLH analyzed in their study, 6 recovered and received IVIG therapy.…”

Hemophagocytic lymphohistiocytosis secondary to infectious diseases

“…Previous studies showed that high-dose of polyvalent immunoglobulin are beneficial in infection. In fact, the main predictive factor of response was its early administration, especially when ferritin level was high (2). For patients with I-HLH, the suitable antimicrobials targeting suspected or confirmed pathogens were indicated, such as, antiviral, antibiotic or antifungal therapy (13).…”

“…Its incidence is underestimated since its clinical symptoms are non-specific and usually associated with other symptoms of an underlying disease. There are 2 types of HLH: primary HLH (familial) occurs in children with inherited dysfunction of the immune response, whereas secondary HLH (acquired) occurs in association with infections, autoimmune disorder or malignancy (1,2). Infection-associated HLH (I-HLH), noted with both adults and children (3), is most commonly secondary to viral infections such as Epstein-Barr virus, which is the most responsible for severe form of I-HLH (4).…”