Multicentric Castleman's disease: prolonged remission with anti CD-20 monoclonal antibody in an HIV-infected patient.

Abstract

We report a case of multicentric Castleman’ s disease (MCD), in an HIV-infected patient successfully treated with anti CD-20 monoclonal antibody Mabthera (rituximab), an agent used for the treatment of patients with relapsed or refractory low-grade or follicular, CD20 positive, B-cell non-Hodgkin's lymphoma [1]. In December 2001, a 61-year-old man was admitted to our hospital because of high-grade fever, profound malaise, fatigue weight loss and, night sweats. Two months before admission the diagnosis of HIV infection and MCD was made at another hospital. The patient started steroids and highly active antiretroviral therapy (HAART) and discharged feeling well. Physical examination revealed cervical lymphadenopathy. Laboratory tests showed a mild Coombs negative normocytic anaemia, a slight lymphocytosis, elevated erythrocyte sedimentaion rate, diffuse hypergammaglobulinaemia, increased serum C-reactive protein and lactate dehydrogenase, and negative PRC test for human herpes virus type 8 (HHV-8) infection. Bone marrow examination revealed the presence of dysplastic myeloid cells and increased proportions of polytypic plasma cells (6%). An abdominal computed tomography scan revealed several homogenous enlarged lymph nodes in the retroperitoneal mesenteric and pelvic region and a chest high resolution computed tomography (HRCT) disclosed several lymph nodes with a diameter greater than 1 cm in the mediastinum and axillary region intraparenchymal nodules and in the subpleural area. Biopsy of a supraclavicular lymph node established once again the diagnosis of MCD. The patient was treated with steroids and discharged 3 weeks later in a good condition. During the next months, the patient presented with generalized pruritus associated with a papulomacular rash, and a steroid induced myopathy for which he refused to continue any treatment. In September 2002, he was readmitted to our department with the same symptomatology as above – high-grade fever, sweats, malaise, fatigue, weight loss and lymphadenopathy. The patient was commenced on rituximab at 375 mg/m2 once a week for 4 consecutive weeks. No adverse reactions were observed. At the end of the first week the patient's condition was significantly improved, all his symptoms had subsided and he was able to restart his HIV medication. The patient received a second course of therapy with rituximab as above 3 months later. At the end of any course the patient was evaluated with a computed tomography scan of the chest and the abdomen. A significant decrease in the lymph nodes size was noted. MCD, also known as multicentric lymphoid angio-follicular hyperplasia, is a distinct lymphoproliferative disorder characterized by polyclonal lymphoid proliferation associated with vascular hyperplasia and plasma cell infiltration [2]. The condition may present either as isolated MCD or as MCD combined with Kaposi's sarcoma or non-Hodgkin's lymphoma [2,3]. Virtually all MCD patients are symptomatic. Systemic signs include fever of varying degree, malaise, fatigue, weight loss, sweating, pulmonary symptoms, skin rash, peripheral oedema, generalized lymphadenopathy and hepato-splenomegaly as in our patient [2,4]. MCD is a rare condition in HIV-infected patients and the outcome is often fatal in the absence of treatment. Treatment options include steroids, chemotherapeutic agents, and monoclonal antibodies neutralizing human interleukin-6 [4,5]. In HIV-infected patients, MCD is frequently associated with Kaposi's sarcoma related to HHV-8 infection. B-cell lymphoma is also found with increased incidence in HIV related MCD [5–7]. Recently, a long-term remission of Kaposi's sarcoma-associated HHV-8 related MCD was reported in an HIV-infected patient with the administration of a chimeric anti-CD20 monoclonal antibody, Rituximab [8]. HIV-related MCD has been considered as a distinct type of MCD associated with the presence of HHV-8 positive Epstein–Barr virus-negative plasma cells in the lymphoid organs. It has been suggested that these cells derive from naive B-cells expressing λ-heavy and λ-light chains (IgMλ) and form sheets of cells in the mantle and interfollicular zones [6,7]. This cell population may proliferate to form non-Hodgkin's lymphoma, or may be controlled by the immune system or low-dose chemotherapy or administration of rituximab. It is notable that MCD may develop and progress in HIV infected patients as in our case, as an independent disorder despite undetectable viral load and high CD4 cell count resulting from HAART [8]. In conclusion, rituximab is effective in the treatment of MCD in HIV-infected patients and should be added to the list of therapeutic means for the otherwise fatal disorder. In our patient, clinical manifestations were completely resolved, and a remarkable reduction in the size of enlarged lymph nodes was documented. No relapse of the disease was noted 1 year after the cessation of treatment. Importantly, the beneficial effect of the drug was documented as early as 1 week after the first course of treatment.