Letter to the Editor
Simultaneous Kaposi's sarcoma and Castleman's disease in a HIV-negative patient. Response to rituximab and doxorubicin
Sarcoma de Kaposi y enfermedad de Castleman simultáneos en un paciente VIH negativo. Respuesta a rituximab y doxorrubicina
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Response to rituximab and doxorubicin" "tieneTextoCompleto" => true "saludo" => "Dear Editor:" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "565" "paginaFinal" => "566" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Mónica García-Arpa, Carmen Calle-Primo, Francisco Martín-Dávila" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Mónica" "apellidos" => "García-Arpa" "email" => array:1 [ 0 => "mgarciaa73@yahoo.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Carmen" "apellidos" => "Calle-Primo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Francisco" "apellidos" => "Martín-Dávila" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Department of Dermatology, Hospital General Universitario de Ciudad Real, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Hematology, Hospital General Universitario de Ciudad Real, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Department of Pathology, Hospital General Universitario de Ciudad Real, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Sarcoma de Kaposi y enfermedad de Castleman simultáneos en un paciente VIH negativo. Respuesta a rituximab y doxorrubicina" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Kaposi's sarcoma (KS) and Castleman's disease (CD) are two human herpesvirus-8 (HHV-8)-related diseases. Dual HHV-8-related diseases are rarely seen in HIV-negative patients.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> We report a HIV-negative patient with simultaneous SK and multicentric (MC) CD treated with rituximab and doxorubicin liposomal (R-Dox) with good response.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A healthy 69-year-old man presented with cutaneous lesions on limbs for one year. On exploration, scant violaceous plaques and nodules were present on his lower limbs and left forearm. Lymphadenopathies or organomegalies were absent. Laboratory exams (blood cell count, CD4 count, coagulation, biochemistry, electrophoresis, immunoglobulins, serology for syphilis, hepatitis B and C, HIV and fecal occult blood) and chest X-ray showed no alterations. Skin biopsy revealed a KS. The diagnosis was classic KS. Due to the limited skin involvement, no therapy was done. However, one month later, he presented an acute episode of severe pain and edema on right leg without systemic symptoms. He was diagnosed of deep vein thrombosis (DVT) of right femoral vein. In anamnesis, no risk factor for deep vein thrombosis or family history of thrombosis were identified. New laboratory tests were performed, including erythrocyte sedimentation rate, C-reactive protein, albuminemia and test for thrombophilia, which were normal. PCR in blood for HHV-8 and HHV-8 Ig G were positive (1:1024, >1:64), whereas HHV-8 Ig M was negative. A TAC body revealed numerous lymphadenopathies in paratracheal chains, axillary region and aortopulmonary window and splenomegaly (15.5<span class="elsevierStyleHsp" style=""></span>cm) which showed increased activity in <span class="elsevierStyleSup">18</span>F-FDGPET-CT. A core needle biopsy of axillary lymphadenopathy revealed follicular hyperplasia with vascular proliferation, hyalinization, and few concentric layers of lymphocytes, arranged in onion skin appearance. Diagnosed of MCCD was made. Bone marrow aspiration was normal. The patient was treated with Rituximab 375<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span> plus Doxorubicin 20<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>. After six cycles of R-Dox, a second PET-CT confirmed complete resolution of lymphadenopathy and splenomegaly without worsening of KS. One year later, the patient remains in complete remission of MCCD with limited cutaneous KS.</p><p id="par0015" class="elsevierStylePara elsevierViewall">CD or giant lymph node hyperplasia is a rare lymphoproliferative disease that most commonly occurs in patients immunosuppressed, HIV-positive and rarely in immunocompetent patients. It can be unicentric or multicentric. MCCD is manifested by constitutional symptoms, fever, generalized lymphadenopathy, hepatosplenomegaly, polyclonal hypergammaglobulinemia, high erythrocyte sedimentation rate and C-reactive protein, hypoalbuminemia, anemia and thrombocytopenia. Histologically, CD is divided into three types (hyaline vascular type or angio-follicular type, plasma cell type and mixed type). Most of multicentric variant are plasma cell type. HHV-8 is an oncogenic virus involved in the pathogenesis of KS, primary effusion lymphoma and CD. HHV-8 infection is linked with MCCD in almost all HIV-positive patients and also in up to 40% of HIV-negative patients.</p><p id="par0020" class="elsevierStylePara elsevierViewall">There is no standard treatment for MCCD. Corticosteroids, chemotherapy and radiotherapy are classic treatments. Currently, rituximab has become the first-line treatment for VIH-positive MCCD. However, rituximab-related KS flare has been reported in these patients, so R-Dox could be a good alternative when KS coexists. In HIV-negative patients, data are scarce regarding treatment of MCCD, with few reports treated with rituximab. Furthermore, there is less information about cases of MCCD and KS treated with rituximabin this subgroup. Nicoli et al. reported a HIV-negative patient with complete remission of MCCD after rituximab without reactivation of previous node KS<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>; another patient treated with rituximab and CHOP showed good response to MCCD without progression of KS.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> However, worsening of KS have been described in one HIV-negative patient with MCCD treated initially with rituximab and various regimens of chemotherapy (including doxorubicin), although finally, addition of valganciclovir improved both diseases.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Moreover, another patient presented extensive cutaneous KS months later after treatment with rituximab, prednisolone and cyclophosphamide for MCCD.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> On the other hand, another patient under treatment with cyclosporin for minimal change nephropathy, presented MCCD and KS; both diseases responded well to doxorubicin.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Furthermore, it's remarkable that a DVT was the first and unique manifestation of MCCD, in a patient with classic KS. Different thrombotic events have been rarely described in CD. They include venous and arterial thrombosis as well as renal thrombotic microangiopathy. Nevertheless, an isolated DVT as initial presentation is exceptional.</p><p id="par0030" class="elsevierStylePara elsevierViewall">R-DOX seems a good treatment for HIV-negative patient with SK and MCCD. 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