tacrolimus and Lymphohistiocytosis--Hemophagocytic

Hemophagocytic syndrome (HPS) is a rare but potentially life-threatening disease in kidney transplant recipients, and is caused by systemic proliferation of macrophages actively phagocytizing other blood cells in the bone marrow, lymph nodes, and the spleen. Here, we report a 40-year-old male kidney transplant recipient who presented with fever, bicytopenia, and elevated liver enzymes 2 months after transplantation. Given that cytomegalovirus antigenemia and real-time polymerase chain reaction tests were positive, liver biopsy was performed under an assumption of cytomegalovirus-induced hepatitis. Hepatic histology revealed multifocal microabscess with cytomegalovirus inclusion bodies, marked Kupffer cell hyperplasia, and erythrophagocytosis by activated macrophages. As laboratory findings such as hyperferritinemia, elevated serum lactate dehydrogenase, low natural killer cell activity, and high soluble interleukin-2 receptor were also compatible with HPS, the recipient was diagnosed as having cytomegalovirus-induced hepatitis combined with reactive HPS. Following intravenous ganciclovir therapy with continuous administration of tacrolimus and corticosteroid, the symptoms resolved and laboratory findings were normalized. As far as we know, this is the first report of cytomegalovirus-induced hepatitis combined with reactive HPS in a kidney transplant recipient that is diagnosed by liver biopsy.

Topics: Adult; Antiviral Agents; Biopsy; Cytomegalovirus; Cytomegalovirus Infections; Humans; Kidney Transplantation; Liver; Lymphohistiocytosis, Hemophagocytic; Male; Tacrolimus; Tomography, X-Ray Computed

Topics: Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Drug Therapy, Combination; Humans; Lymphohistiocytosis, Hemophagocytic; Male; Prostatic Neoplasms; Steroids; Tacrolimus; Treatment Outcome

A 56-year-old Japanese woman with muscle weakness, increased creatine kinase and aldolase levels, and characteristic cutaneous lesions was diagnosed with anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 antibody)-positive dermatomyositis. She also had interstitial lung disease (ILD). After corticosteroid and tacrolimus combination therapy was started, bicytopenia and elevated serum ferritin and transaminase emerged. Because the bone marrow tissues were hypoplastic with hemophagocytes, she was diagnosed with concomitant autoimmune-associated hemophagocytic syndrome (HPS). Intravenous cyclophosphamide pulse therapy and plasmapheresis were performed. The laboratory findings indicated improved abnormalities, and the ILD did not progress. Anti-MDA5 antibody-positive dermatomyositis can be complicated by HPS.

Topics: Adrenal Cortex Hormones; Autoantibodies; Combined Modality Therapy; Cyclophosphamide; Dermatomyositis; Disease Progression; Female; Humans; Immunosuppressive Agents; Interferon-Induced Helicase, IFIH1; Lung Diseases, Interstitial; Lymphohistiocytosis, Hemophagocytic; Methylprednisolone; Middle Aged; Plasmapheresis; Pulse Therapy, Drug; Tacrolimus

Hemophagocytic lymphohistiocytosis (HLH) is a rare but severe and often overwhelming systemic hyper-inflammatory syndrome generally presenting with unexplained fevers, hepatosplenomegaly, and progressive multi-organ dysfunction. Treatment of HLH has two major goals: Halting the triggering event and controlling the overactive immune system. However, patients with primary or recurrent secondary HLH should subsequently undergo allogeneic HCT for long lasting disease remission. Hereby we present the case of a 69 years old man with recurrent HLH who underwent a reduced intensity conditioning of fludarabine, cyclophosphamide and low dose total body irradiation followed by a haploidentical marrow graft and post-transplantation cyclophosphamide (PTCy), tacrolimus and mycophenolate mofetil as GVHD prophylaxis. He achieved a durable remission of HLH symptoms despite persistent myeloid mixed chimerism. The use of haploidentical donors and PTCy as tolerance inducing regimen is feasible in HLH. The achievement of mixed donor chimerism may be enough to control the clinical manifestations and to cure HLH.

Topics: Aged; Allografts; Cyclophosphamide; Hematopoietic Stem Cell Transplantation; Humans; Lymphohistiocytosis, Hemophagocytic; Male; Mycophenolic Acid; Tacrolimus; Transplantation Conditioning; Vidarabine

Topics: Adult; Allografts; Anemia, Aplastic; Bone Marrow Transplantation; Chronic Disease; Graft vs Host Disease; Humans; Immunosuppressive Agents; Influenza Vaccines; Infusions, Intravenous; Lymphohistiocytosis, Hemophagocytic; Male; Methylprednisolone; Prednisolone; Tacrolimus; Treatment Outcome

Hemophagocytic syndrome (HPS) is an unusual disorder associated with systemic lupus erythematosus (SLE). A 64-year-old woman was admitted because of fever and urticarial vasculitis. Laboratory data revealed pancytopenia and immunological abnormalities, suggesting elevated disease activity. Prednisolone monotherapy failed to improve the pancytopenia despite the amelioration of other clinical findings. Because her condition was suggestive of HPS, tacrolimus at 2-3 mg/day was added to the prednisolone regimen. Eventually, the pancytopenia improved and prednisolone could be effectively tapered. Tacrolimus could be an additional or alternative modality for treating refractory HPS.

Topics: Bone Marrow; Dose-Response Relationship, Drug; Female; Fever; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lymphohistiocytosis, Hemophagocytic; Middle Aged; Pancytopenia; Prednisolone; Remission Induction; Tacrolimus; Treatment Failure; Treatment Outcome; Urticaria; Vasculitis

Hemophagocytic lymphohistiocytosis (HLH) is associated with hypercytokinemia in children. Although HLH can be also observed after hematopoietic stem cell transplantation (HSCT), the incidence and clinical features of HLH after HSCT remain obscure.. The clinical features of HLH after HSCT (post-HSCT HLH) were investigated in children with malignancies, immune deficiencies, or aplastic anemia. The HLH/Langerhans Cell Histiocytosis (LCH) Committee of the Japanese Society of Pediatric Hematology (JSPH) sent questionnaires to hospitals with JPSH members asking for details of cases in which HLH occurred after HSCT between 1998 and 2008.. Among 42 children who were diagnosed with post-HSCT HLH between 1998 and 2008 in Japan, 37 fulfilled our inclusion criteria; of these, 26 were classified as early-onset (onset <30 days after HSCT) and 11 were classified as late-onset (onset >30 days after HSCT). In the early-onset group, the presence of respiratory symptoms, high levels of total bilirubin, and triglycerides at onset and the lack of control of GVHD with tacrolimus were significantly associated with non-resolution of HLH (P < 0.05). The survival rate was significantly higher in patients with resolution of HLH than in those without resolution (59% vs. 14%, P < 0.05).. These findings suggest that early-onset post-HSCT HLH is a specific entity of HLH, and appropriate diagnosis and prompt management need to be established.

Topics: Anemia, Aplastic; Bilirubin; Child; Child, Preschool; Common Variable Immunodeficiency; Disease-Free Survival; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Infant; Infant, Newborn; Japan; Lymphohistiocytosis, Hemophagocytic; Male; Neoplasms; Surveys and Questionnaires; Survival Rate; Tacrolimus; Transplantation, Homologous; Triglycerides

Topics: Bone Marrow Transplantation; Graft vs Host Disease; Humans; Immunocompromised Host; Immunosuppressive Agents; Influenza A Virus, H1N1 Subtype; Influenza, Human; Lymphohistiocytosis, Hemophagocytic; Lymphoma, Mantle-Cell; Male; Middle Aged; Neoplasm Recurrence, Local; Pandemics; Tacrolimus

Haemophagocytic syndrome (HPS) is known as a relatively rare complication in autoimmune diseases. Here we analysed the clinical features of HPS in patients with systemic autoimmune diseases.. One thousand and fourteen patients with systemic autoimmune diseases admitted to Hokkaido University Hospital from 1997 to 2007 were recruited [350 SLE, 136 RA, 98 polymyositis/dermatomyositis (PM/DM), 88 SSc, 91 vasculitis syndrome, 37 primary SS, 26 adult onset Still's disease (AOSD) and 188 other diseases]. Clinical features and treatment outcomes were retrospectively analysed.. Thirty cases (3.0%) fulfilled HPS criteria (progressive cytopenia in two or more lineages and haemophagocytosis in reticuloendothelial systems). Underlying diseases were SLE (18), RA (2), PM/DM (2), SSc (2), vasculitis (1), SS (2) and AOSD (3). Nineteen patients were diagnosed as having autoimmune-associated HPS, eight infection-associated, one drug-induced and one developed HPS after haematopoietic stem cell transplantation. For the treatment of HPS, high-dose corticosteroid monotherapy was given in 26 cases, being effective in 12 (46%). Ten out of 15 patients with corticosteroid-resistant autoimmune-associated HPS were treated with CsA, cyclophosphamide or tacrolimus, leading to the remission in 80%. The overall mortality rate was 20%. Multivariate analysis showed that the presence of infections and CRP level >50 mg/l on HPS related with poor prognosis.. The prevalence of HPS among in-hospital patients with systemic autoimmunity is not ignorable. Administration of immunosuppressants was effective in cases with autoimmune-associated HPS, whereas prognosis was poor in infection-associated HPS.

Topics: Adult; Aged; Autoimmune Diseases; Bacterial Infections; Cyclophosphamide; Cyclosporine; Glucocorticoids; Humans; Immunosuppressive Agents; Lymphohistiocytosis, Hemophagocytic; Middle Aged; Prognosis; Retrospective Studies; Tacrolimus; Virus Diseases; Young Adult