Hemophagocytic lymphohistiocytosis (HLH) is a rare inflammatory disorder with a high mortality rate and a wide range of symptoms. Solid organ transplantation, which provides patients with a unique immunosuppressive state, is a less common predisposing factor for HLH. HLH after solid organ transplantation (HLH-SOT) is very rare and fatal. It is hard to diagnose and treat and extremely understudied. The use of immunosuppressants makes the situation of HLH-SOT more complex. This review summarizes the existing literature on HLH after solid organ transplantation and describes its triggers and symptoms, focusing on its diagnosis and treatment. We performed a literature search of case reports, case series, letters to the editor, and clinical quizzes describing patients with HLH after solid organ transplantation (HLH-SOT). We provide recommendations on the diagnosis protocol and treatment strategy based on the existing evidence.

A disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 (ADAMTS-13) is the specific von Willebrand factor-cleaving protease and circulates in a closed and latent conformation due to a spacer/CUB1 domain interaction. ADAMTS-13 is allosterically activated after binding of its substrate or antibodies, inducing an open conformation. Recently, we suggested a potential role of plasmin (fibrinolysin) in hemostasis disorders reported in most patients with hemophagocytic lymphohistiocytosis (HLH), a rare and life-threatening condition related to a severe systemic inflammatory state. Most patients with HLH had a partial ADAMTS-13 deficiency, and plasmin could induce a truncation of the C-terminal part of ADAMTS-13 and thus an open conformation.

To understand the effect of plasmin on ADAMTS-13, our study aimed to investigate ADAMTS-13 conformation in patients with HLH.

Forty-five critically ill patients with HLH were prospectively enrolled between April 2015 and December 2018. ADAMTS-13 activity was measured by fluorescent resonance energy transfer-VWF73 assay, ADAMTS-13 antigen, and conformation with our homemade 3H9-enzyme-linked immunosorbent assay and 1C4-enzyme-linked immunosorbent assay.

ADAMTS-13 activity ranged from <10 to 65 IU/dL, and 41 of the 45 patients had a quantitative deficiency in ADAMTS-13 (activity <50 IU/dL). Twenty patients had a severe ADAMTS-13 deficiency (activity <20 IU/dL). ADAMTS-13 conformation was folded in all patients under normal conditions. Surprisingly, the switch of ADAMTS-13 conformation expected with the monoclonal antibody 17G2 (anti-CUB1) was disturbed in 6 patients (activity <20 IU/dL).

Our study reported that ADAMTS-13 conformation is closed in HLH and provides an indirect proof that plasmin is not able to massively degrade ADAMTS-13. Further studies on glycosylation and citrullination profiles of ADAMTS-13 are needed to understand their role in HLH.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening disorder characterized by systemic inflammation and organ failure as a result of dysregulated immune cell activation. HLH can be induced by a variety of factors including infection, tumours and autoimmune disease and can also occur in patients following solid organ transplantation. Occurrence of HLH and lupus nephritis (LN) successively within a short period of time after renal transplantation is uncommon.

We described an 11-year-old female post-transplant patient who presented with hemocytopenia, fever, elevated serum ferritin, splenomegaly, hyperlipidemia, and hypofibrinemia, and was clinically diagnosed with HLH. After comprehensive treatment with corticosteroids, intravenous immunoglobulin (IVIG), and reducing immunosuppressants, her condition improved, but then hematuria ensued. The transplant kidney biopsy showed LN. She was treated with hydroxychloroquine and methylprednisolone while intensive immunosuppressive agents were given. She has remained in remission for two years until now.

The main inducing factors of HLH should be identified as early as possible, and accurate treatment plans should be taken. The long-course IVIG regimen may be one of the effective treatments for virus-induced HLH. After remission of HLH, we need to be alert to the recurrence of autoimmune diseases in patients with underlying diseases, and timely increase immunosuppressants.

Immunosuppressed patients can contract parvovirus B19, and some may experience hemophagocytic lymphohistiocytosis (HLH). Herein, we describe the first report of hemophagocytic lymphohistiocytosis in a heart-lung transplant patient with concomitant parvovirus B19 infection. The patient was treated with intravenous immune globulin (IVIG) and the features of HLH were remission. This instance emphasizes the significance of parvovirus B19 monitoring in transplant patients with anemia; if HLH complicates the situation, IVIG may be an adequate remedy. Finally, a summary of the development in diagnosing and managing parvovirus B19 infection complicated by HLH is provided.

Parvovirus B19 (B19V) is associated with a wide range of clinical manifestations. The major presentation is erythema infectiosum. However, a persistent infection may cause pure red cell aplasia and chronic anemia in immunocompromized patients. The B19V seroprevalence varies with age and geographical location.

To determine the B19V serological status and DNAemia in kidney, liver, and pancreas transplant candidates.

Patients who underwent kidney, liver, or simultaneous kidney and pancreas/liver transplantation between January 2021 and May 2022 were included in the study. The serum samples were collected before transplantation. For detection of B19V DNA, a LightMix Kit B19V EC (TIB MOLBIOL, Berlin, Germany) was used. B19V IgM and IgG antibodies were detected using a commercial ELISA test (Euroimmun, Lübeck, Germany).

One hundred and thirty-one transplant candidates were included in the study, 71.0% male, with an average age of 53.27 years ± 12.71 years. There were 68.7% liver, 27.5% kidney, 3.0% simul taneous pancreas/kidney transplant (SPKT), and 0.8% simultaneous liver/kidney transplant recipients. No patients had detectable B19V DNA. B19V IgG seroprevalence was 77.1%. No acute or recent infections were detected (IgM antibodies). There was no difference in the mean age of seronegative and seropositive patients (51.8 years ± 12.9 years vs 53.7 years ± 12.7 years, t = -0.603; P = 0.548). Although seropositivity was lower in patients aged less than 30 years (66.6%) compared to the patients aged 30-59 years and > 60 years (80.4% and 78.1%, respectively), this difference was not significant. In addition, there was no difference in seropositivity between male and female transplant candidates, 76.3% and 78.9% (χ 2 = 0.104; P = 0.748). The seroprevalence did not differ among organ recipients, with 77.8%, 80.6%, and 50.0% for liver, kidney, and SPKT, respectively, (χ 2 = 5.297; P = 0.151). No significant difference was found in the seroprevalence in kidney transplant patients according to dialysis modality. Seroprevalence was 71.1% in hemodialysis patients, and 100% in peritoneal dialysis patients (χ 2 = 0.799; P = 0.372).

The B19V seroprevalence is expectedly high among kidney, liver, and pancreas transplant candidates, but there are still 22.9% of seronegative individuals who remain at risk for primary disease and severe manifestations. Further research should elucidate the necessity of B19V screening in peri-transplant management.