title: Acquired haemophilia in HIV negative, HHV-8 positive multicentric Castleman's disease: a case report.
abstract: Multicentric Castleman's Disease (MCD) is an atypical lymphoproliferative disorder, related to human herpesvirus 8 (HHV-8) infection and often associated with autoimmune diseases such as haemolytic anaemia and thrombocytopenia. Acquired haemophilia (AH) is a rare, life-threatening disease, which can occur in association with lymphoproliferative disorders, although only one case of AH in MCD has been described so far. We report the case of a human immuno deficiency virus negative 71-yr-old woman referred to our hospital for prolonged bleeding on surgical site following a lymph node biopsy. Lymph node histology revealed MCD, while the screening for the bleeding disorder showed prolonged activated partial thromboplastin time (APTT) (ratio: 1.89, normal value <1.24), low factor VIII (FVIII:C) levels (6%) with anti-factor VIII antibodies (2.3 Bethesda units), leading to a diagnosis of AH. Virological studies on plasma, lymphocyte and bronchoalveolar wash showed positivity for HHV-8 infection. Treatment with steroids (metilprednisolone 1-1.5 mg/kg/d) and cyclophosphamide (100 mg/d orally) was unsuccessful, and then antiviral therapy with cidofovir (5 mg/kg/wk) was started. A transient normalisation of APTT was seen after two administrations of cidofovir, but then coagulation parameters worsened and a large haematoma of the arm appeared. Bleeding was successfully stopped with two boluses of recombinant activated factor VII (Novoseven 90 microg/kg). Therapy with anti-CD 20 monoclonal antibody rituximab (Mabthera 375 mg/m2 once a week for 4 wk) was started, and following two administrations APTT normalised once again. Cardiological and neurological complications arose before the third dose of rituximab and the patient died shortly afterwards.
authors.affiliation: Department of Oncology and Haematology, Section Haematology, University of Modena and Reggio Emilia, Modena, Italy. marietta@unimo.it
authors.forename: Marco
authors.initials: M
authors.lastname: Marietta
authors.forename: Samantha
authors.initials: S
authors.lastname: Pozzi
authors.forename: Mario
authors.initials: M
authors.lastname: Luppi
authors.forename: Marcello
authors.initials: M
authors.lastname: Bertesi
authors.forename: Cinzia
authors.initials: C
authors.lastname: Cappi
authors.forename: Monica
authors.initials: M
authors.lastname: Morselli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Torelli
mesh_terms: D000368:Aged; D001323:Autoantibodies / Q000097:blood; D005871:Castleman Disease / Q000150:complications* / Q000821:virology; D005169:Factor VIII / Q000032:analysis / Q000276:immunology; D017809:Fatal Outcome; D005260:Female; D018023:HIV Seronegativity; D006467:Hemophilia A / Q000150:complications* / Q000276:immunology / Q000821:virology; D006470:Hemorrhage / Q000209:etiology; D006566:Herpesviridae Infections / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy; D019288:Herpesvirus 8, Human; D006801:Humans; D010314:Partial Thromboplastin Time
chemical_list: D001323:Autoantibodies; D005169:Factor VIII