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there are some cases in which no associated pathology can been determined&#44; so this group is classified as essential<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> cryoglobulinemia&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Here we present a case of essential mixed cryoglobulinemia not associated with hepatitis C infection&#44; presented with symptoms of lower limb acronecrosis&#44; which required amputation of several distal phalanges of the foot&#44; despite an early diagnosis&#44; as a result a poor response to treatment&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Case Report</span><p id="par0025" class="elsevierStylePara elsevierViewall">A 64-year-old woman with a history of hypertension and type 2 diabetes mellitus treated with torasemide 5<span class="elsevierStyleHsp" style=""></span>mg&#47;day and dietary control&#44; respectively&#44; 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1</a>&#41;&#46; The remainder of the examination was normal&#46; During hospitalization&#44; the analysis showed leukocytosis 13<span class="elsevierStyleHsp" style=""></span>500<span class="elsevierStyleHsp" style=""></span>cells&#47;mm<span class="elsevierStyleSup">3</span> &#40;75&#37; segmented PMN&#44; 15&#37; lymphocytes&#41;&#44; Hb 10&#46;8<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#44; MCV 84&#46;7&#44; platelets 332<span class="elsevierStyleHsp" style=""></span>000&#44; ESR 54<span class="elsevierStyleHsp" style=""></span>mm&#47;h and CRP 48<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#46; Coagulation studies as well as liver and kidney function were within normal limits&#46; Serologic studies for cytomegalovirus&#44; Brucella and Epstein-Barr as well as Mantoux and serial blood cultures were negative&#46; No alterations of tumor markers&#44; antinuclear antibodies&#44; anti-native DNA&#44; ANCA and rheumatoid factor were seen&#46; After measuring cryoglobulins&#44; a 25&#37;&#8211;30&#37; cryocrit was obtained &#40;polyclonal&#8211;monoclonal pattern&#41; in separate determinations&#44; always with negative rheumatoid factor without complement consumption and negative analysis for hepatitis B and C&#46; The protein profile showed a monoclonal gammopathy of uncertain significance&#44; but dismissed the presence of a lymphoproliferative process&#44; because of no significant alterations in the CBC&#44; no alteration in the bone marrow study and finally&#44; imaging studies &#40;computed tomography and ultrasound&#41; ruled out the presence of nodal and hepatosplenic involvement&#46; The electromyogram showed signs compatible to severe sensory-motor polyneuropathy with greater lower limb involvement&#44; but the pathological examination of biopsied parts of nervous tissue and vascular alterations were not found&#46; The remaining studies&#44; gastroscopy&#44; abdominal ultrasound&#44; echocardiogram&#44; visceral arteriography&#44; chest radiography and electrocardiogram&#44; showed no pathological data&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">The patient received corticosteroids and cyclophosphamide and remained without fever and showed slight improvement of the dysesthesia in the legs&#46; After discharge&#44; the outpatient controls were carried out for 4 years&#44; and the patient received 8&#8211;32<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>methylprednisolone&#47;day depending on the clinical situation&#46; Nevertheless&#44; dysesthesia persisted&#44; with stabbing pain and vascular disorders of the lower limbs&#44; with amputation of the second and fourth left toe injury due to chronic ischemic necrosis &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41; becoming necessary&#46; Given the poor clinical improvement&#44; additional treatments were tried with prostaglandins&#44; bosentan and rituximab&#44; without satisfactory results&#46; Finally&#44; we had to resort to plasmapheresis associated with rituximab&#44; which maintained the cryocrit at 10&#37; but with only partial control of dysesthesias and vascular abnormalities of the lower limbs&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0035" class="elsevierStylePara elsevierViewall">MC is a relatively rare disease associated with many infections or immunological diseases&#44; with an etiology not yet fully explained&#46; It is known that HCV infection plays an important causal role&#44; but the contribution of genetic factors and&#47;or environmental factors is unknown&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a> Since the identification of HCV in 1989&#44; it has been recognized as the cause of about 90&#37; of cases of MC and &#60;5&#37; of cases are now considered essential&#44; in which no causal agent can be determined&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> These figures vary a little depending on the prevalence of HCV infection and other demographic aspects&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;8</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Essential MC usually has a more aggressive course than those secondary to other diseases&#44; with prevalence of renal&#44; neuropathic and impaired peripheral circulation&#46; Treatment with corticosteroids and immunosuppressants such as cyclophosphamide is unsatisfactory&#44; so the use of anti-CD20 monoclonal antibodies &#40;rituximab&#41;&#44; plasmapheresis or drugs still under evaluation as lenalidomide&#44; and alternative therapies is under evaluation&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Plasmapheresis usually provides good results&#44; reducing the levels of circulating immune complexes and cryoglobulins&#44; so it is particularly used in severe complications of essential MC&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> This is reflected in this clinical case&#44; where after performing all additional studies to determine any underlying disease&#44; it was concluded that we were dealing with a case of essential MC &#40;type II&#41;&#44; presenting with symptoms&#44; such as anemia&#44; joint involvement&#44; and cutaneous vasculitic&#46; Despite establishing treatment with glucocorticoids&#44; immunosuppressants&#44; vasodilators and rituximab we did not achieve an effective response&#44; as seen in cases of MC associated with HCV infection&#44; so plasmapheresis sessions were begun&#44; associated with rituximab&#44; which achieved partial control of the disease&#46; It was decided that the patient should receive combination therapy with plasmapheresis and rituximab before the winter as a preventive measure of vascular damage&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">In terms of clinical manifestations&#44; these can range from a relatively benign course&#44; to dramatic complications that might endanger the life of the patient&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2&#44;9</span></a> The main ones are palpable purpura&#44; systemic symptoms&#44; arthralgias&#44; lymphadenopathy&#44; hepatosplenomegaly&#44; peripheral neuropathy&#44; hypocomplementemia&#44; bronchiolitis obliterans&#44; glomerulonephritis&#44; Raynaud&#39;s phenomenon&#44; livedo reticularis and acrocyanosis&#44; as well as ulcers and necrosis of the skin&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a> Throughout the progression of our patient&#44; we observed no control of peripheral involvement&#44; which led to necrosis of the second and fourth fingers of the left foot&#44; with subsequent amputation&#46; This severe skin involvement occurs in only about 2&#37; of cases and is due to vasculitis with fibrinoid necrosis and inflammation of the vessel wall and perivascular space&#44; which most often affects the lower limbs&#44; and can evolve to a chronic ulcer and gangrene&#44; as in our patient&#44; as well as cases published in several reviews and case reports&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;10&#44;11</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In conclusion&#44; the particularity of this case is the presentation of one of the few cases of MC associated with no underlying disease &#40;non-HCV&#41;&#44; being therefore essential&#44; and as mentioned in other articles&#44; these cases have an abrupt clinical presentation and poor response to conventional therapy&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of Interest</span><p id="par0055" class="elsevierStylePara elsevierViewall">The authors have no conflict of interest to declare&#46;</p></span></span>"
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        "titulo" => "Abstract"
        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Cryoglobulinemia is a rare disease characterized by the production of monoclonal or polyclonal immunoglobulins that precipitate in cold temperature&#46; While this phenomenon can be observed in a large number of disorders&#44; it has been associated with hepatitis C virus infection in more than 90&#37; of cases&#46; The remaining 10&#37;&#44; called essential cryoglobulinemia&#44; has been characterized by a more severe course and a failure to respond to conventional treatment&#46; This article describes the case of a patient with essential cryoglobulinemia presenting with acronecrosis with a poor outcome&#44; despite treatment&#44; leading to amputation&#46;</p>"
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        "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La crioglobulinemia es una enfermedad rara en la cual se producen inmunoglobulinas monoclonales y&#47;o policlonales que precipitan con el fr&#237;o&#46; Si bien este fen&#243;meno puede observarse en una gran cantidad de trastornos&#44; se ha asociado m&#225;s frecuentemente a la infecci&#243;n por el virus de la hepatitis C en m&#225;s del 90&#37;&#46; El porcentaje restante&#44; llamado crioglobulinemia esencial&#44; se ha caracterizado por curso m&#225;s severo y falta de respuesta al tratamiento convencional&#46; El presente art&#237;culo describe el caso de un paciente con crioglobulinemia esencial que se presenta con acronecrosis&#44; en la que su mala evoluci&#243;n&#44; a pesar del tratamiento&#44; la lleva a la amputaci&#243;n&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara">Please&#44; cite this article as&#58; Ram&#237;rez Huaranga MA&#44; et al&#46; Crioglobulinemia con acronecrosis no asociada a infecci&#243;n por hepatitis C&#58; reporte de un caso&#46; Reumatol Clin&#46; 2012&#59;<span class="elsevierStyleBold">8&#40;2&#41;</span>&#58;84&#8211;6&#46;</p>"
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Case Report
Cryoglobulinemia With Acronecrosis Not Associated With Hepatitis C Infection: A Case Report
Crioglobulinemia con acronecrosis no asociada a infección por hepatitis C: reporte de un caso
Marco A. Ramírez Huarangaa,
Corresponding author
hurauma@hotmail.com

Corresponding author.
, Claudia C. Ramos Rodríguezb, David Bellido Pastranac
a Reumatología, Hospital General de Ciudad Real, Ciudad Real, Spain
b Dermatología, Hospital Daniel Alcides Carrión, Callao, Peru
c Servicio de Medicina Interna, Hospital General de Ciudad Real, Ciudad Real, Spain
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Type I is associated with lymphoproliferative disease and multiple myeloma&#44; while types II and III are associated with connective tissue diseases and infections&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The clinical manifestations of cryoglobulinemia symptoms can vary from only general and non-specific to joint pain&#44; renal&#44; neuropathic and skin involvement&#44; which in a few cases can become acronecrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The association between hepatitis C virus &#40;HCV&#41; and mixed cryoglobulinemia &#40;MC&#41; has been highly evident from the recognition of serological markers for HCV infection&#44; and found in 90&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> However&#44; there are some cases in which no associated pathology can been determined&#44; so this group is classified as essential<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> cryoglobulinemia&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Here we present a case of essential mixed cryoglobulinemia not associated with hepatitis C infection&#44; presented with symptoms of lower limb acronecrosis&#44; which required amputation of several distal phalanges of the foot&#44; despite an early diagnosis&#44; as a result a poor response to treatment&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Case Report</span><p id="par0025" class="elsevierStylePara elsevierViewall">A 64-year-old woman with a history of hypertension and type 2 diabetes mellitus treated with torasemide 5<span class="elsevierStyleHsp" style=""></span>mg&#47;day and dietary control&#44; respectively&#44; came to the clinic&#46; She had started her illness with symptoms of joint pain and Raynaud&#39;s phenomenon in hands and feet almost 1 year prior&#46; Twenty days before admission she presented fever predominantly during the evening&#44; with an average temperature of 38<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; which diminished with metamizole&#44; as well as burning sensation in the legs&#44; fatigue and weight loss of 6&#8211;7<span class="elsevierStyleHsp" style=""></span>kg in the past 10 months&#46; Upon examination&#44; the patient was febrile but other vital signs were in the normal&#44; with a good general condition&#44; focused and well hydrated&#46; A cardiac auscultation showed rhythmic sounds&#44; a I&#8211;II&#47;VI ejection murmur&#44; but no other abnormalities&#59; peripheral pulses were present&#46; On examination of skin there was discoloration of the lower limbs&#44; mainly on the dorsal aspect of the foot &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The remainder of the examination was normal&#46; During hospitalization&#44; the analysis showed leukocytosis 13<span class="elsevierStyleHsp" style=""></span>500<span class="elsevierStyleHsp" style=""></span>cells&#47;mm<span class="elsevierStyleSup">3</span> &#40;75&#37; segmented PMN&#44; 15&#37; lymphocytes&#41;&#44; Hb 10&#46;8<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#44; MCV 84&#46;7&#44; platelets 332<span class="elsevierStyleHsp" style=""></span>000&#44; ESR 54<span class="elsevierStyleHsp" style=""></span>mm&#47;h and CRP 48<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#46; Coagulation studies as well as liver and kidney function were within normal limits&#46; Serologic studies for cytomegalovirus&#44; Brucella and Epstein-Barr as well as Mantoux and serial blood cultures were negative&#46; No alterations of tumor markers&#44; antinuclear antibodies&#44; anti-native DNA&#44; ANCA and rheumatoid factor were seen&#46; After measuring cryoglobulins&#44; a 25&#37;&#8211;30&#37; cryocrit was obtained &#40;polyclonal&#8211;monoclonal pattern&#41; in separate determinations&#44; always with negative rheumatoid factor without complement consumption and negative analysis for hepatitis B and C&#46; The protein profile showed a monoclonal gammopathy of uncertain significance&#44; but dismissed the presence of a lymphoproliferative process&#44; because of no significant alterations in the CBC&#44; no alteration in the bone marrow study and finally&#44; imaging studies &#40;computed tomography and ultrasound&#41; ruled out the presence of nodal and hepatosplenic involvement&#46; The electromyogram showed signs compatible to severe sensory-motor polyneuropathy with greater lower limb involvement&#44; but the pathological examination of biopsied parts of nervous tissue and vascular alterations were not found&#46; The remaining studies&#44; gastroscopy&#44; abdominal ultrasound&#44; echocardiogram&#44; visceral arteriography&#44; chest radiography and electrocardiogram&#44; showed no pathological data&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">The patient received corticosteroids and cyclophosphamide and remained without fever and showed slight improvement of the dysesthesia in the legs&#46; After discharge&#44; the outpatient controls were carried out for 4 years&#44; and the patient received 8&#8211;32<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>methylprednisolone&#47;day depending on the clinical situation&#46; Nevertheless&#44; dysesthesia persisted&#44; with stabbing pain and vascular disorders of the lower limbs&#44; with amputation of the second and fourth left toe injury due to chronic ischemic necrosis &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41; becoming necessary&#46; Given the poor clinical improvement&#44; additional treatments were tried with prostaglandins&#44; bosentan and rituximab&#44; without satisfactory results&#46; Finally&#44; we had to resort to plasmapheresis associated with rituximab&#44; which maintained the cryocrit at 10&#37; but with only partial control of dysesthesias and vascular abnormalities of the lower limbs&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0035" class="elsevierStylePara elsevierViewall">MC is a relatively rare disease associated with many infections or immunological diseases&#44; with an etiology not yet fully explained&#46; It is known that HCV infection plays an important causal role&#44; but the contribution of genetic factors and&#47;or environmental factors is unknown&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a> Since the identification of HCV in 1989&#44; it has been recognized as the cause of about 90&#37; of cases of MC and &#60;5&#37; of cases are now considered essential&#44; in which no causal agent can be determined&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> These figures vary a little depending on the prevalence of HCV infection and other demographic aspects&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;8</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Essential MC usually has a more aggressive course than those secondary to other diseases&#44; with prevalence of renal&#44; neuropathic and impaired peripheral circulation&#46; Treatment with corticosteroids and immunosuppressants such as cyclophosphamide is unsatisfactory&#44; so the use of anti-CD20 monoclonal antibodies &#40;rituximab&#41;&#44; plasmapheresis or drugs still under evaluation as lenalidomide&#44; and alternative therapies is under evaluation&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Plasmapheresis usually provides good results&#44; reducing the levels of circulating immune complexes and cryoglobulins&#44; so it is particularly used in severe complications of essential MC&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> This is reflected in this clinical case&#44; where after performing all additional studies to determine any underlying disease&#44; it was concluded that we were dealing with a case of essential MC &#40;type II&#41;&#44; presenting with symptoms&#44; such as anemia&#44; joint involvement&#44; and cutaneous vasculitic&#46; Despite establishing treatment with glucocorticoids&#44; immunosuppressants&#44; vasodilators and rituximab we did not achieve an effective response&#44; as seen in cases of MC associated with HCV infection&#44; so plasmapheresis sessions were begun&#44; associated with rituximab&#44; which achieved partial control of the disease&#46; It was decided that the patient should receive combination therapy with plasmapheresis and rituximab before the winter as a preventive measure of vascular damage&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">In terms of clinical manifestations&#44; these can range from a relatively benign course&#44; to dramatic complications that might endanger the life of the patient&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2&#44;9</span></a> The main ones are palpable purpura&#44; systemic symptoms&#44; arthralgias&#44; lymphadenopathy&#44; hepatosplenomegaly&#44; peripheral neuropathy&#44; hypocomplementemia&#44; bronchiolitis obliterans&#44; glomerulonephritis&#44; Raynaud&#39;s phenomenon&#44; livedo reticularis and acrocyanosis&#44; as well as ulcers and necrosis of the skin&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a> Throughout the progression of our patient&#44; we observed no control of peripheral involvement&#44; which led to necrosis of the second and fourth fingers of the left foot&#44; with subsequent amputation&#46; This severe skin involvement occurs in only about 2&#37; of cases and is due to vasculitis with fibrinoid necrosis and inflammation of the vessel wall and perivascular space&#44; which most often affects the lower limbs&#44; and can evolve to a chronic ulcer and gangrene&#44; as in our patient&#44; as well as cases published in several reviews and case reports&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;10&#44;11</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In conclusion&#44; the particularity of this case is the presentation of one of the few cases of MC associated with no underlying disease &#40;non-HCV&#41;&#44; being therefore essential&#44; and as mentioned in other articles&#44; these cases have an abrupt clinical presentation and poor response to conventional therapy&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of Interest</span><p id="par0055" class="elsevierStylePara elsevierViewall">The authors have no conflict of interest to declare&#46;</p></span></span>"
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        "titulo" => "Abstract"
        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Cryoglobulinemia is a rare disease characterized by the production of monoclonal or polyclonal immunoglobulins that precipitate in cold temperature&#46; While this phenomenon can be observed in a large number of disorders&#44; it has been associated with hepatitis C virus infection in more than 90&#37; of cases&#46; The remaining 10&#37;&#44; called essential cryoglobulinemia&#44; has been characterized by a more severe course and a failure to respond to conventional treatment&#46; This article describes the case of a patient with essential cryoglobulinemia presenting with acronecrosis with a poor outcome&#44; despite treatment&#44; leading to amputation&#46;</p>"
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        "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La crioglobulinemia es una enfermedad rara en la cual se producen inmunoglobulinas monoclonales y&#47;o policlonales que precipitan con el fr&#237;o&#46; Si bien este fen&#243;meno puede observarse en una gran cantidad de trastornos&#44; se ha asociado m&#225;s frecuentemente a la infecci&#243;n por el virus de la hepatitis C en m&#225;s del 90&#37;&#46; El porcentaje restante&#44; llamado crioglobulinemia esencial&#44; se ha caracterizado por curso m&#225;s severo y falta de respuesta al tratamiento convencional&#46; El presente art&#237;culo describe el caso de un paciente con crioglobulinemia esencial que se presenta con acronecrosis&#44; en la que su mala evoluci&#243;n&#44; a pesar del tratamiento&#44; la lleva a la amputaci&#243;n&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara">Please&#44; cite this article as&#58; Ram&#237;rez Huaranga MA&#44; et al&#46; Crioglobulinemia con acronecrosis no asociada a infecci&#243;n por hepatitis C&#58; reporte de un caso&#46; Reumatol Clin&#46; 2012&#59;<span class="elsevierStyleBold">8&#40;2&#41;</span>&#58;84&#8211;6&#46;</p>"
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      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:11 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cryoglobulinemic vasculitis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "C&#46; Ferri"
                            1 => "M&#46;T&#46; Mascia"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Opin Rheumatol"
                        "fecha" => "2006"
                        "volumen" => "18"
                        "paginaInicial" => "54"
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                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16344620"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The cryoglobulins&#58; an overview"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "F&#46; Dammacco"
                            1 => "D&#46; Sansonno"
                            2 => "C&#46; Piccolli"
                            3 => "F&#46;A&#46; Tucci"
                            4 => "V&#46; Racanelli"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
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                        "tituloSerie" => "Eur J Clin Invest"
                        "fecha" => "2001"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11454019"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatitis C virus&#44; cryoglobulinemia&#44; and vasculitis&#58; immune complex relations"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "D&#46; Sansonno"
                            1 => "F&#46; Dammaco"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S1473-3099(05)70053-0"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Infect Dis"
                        "fecha" => "2005"
                        "volumen" => "5"
                        "paginaInicial" => "227"
                        "paginaFinal" => "236"
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                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15792740"
                            "web" => "Medline"
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                        ]
                      ]
                    ]
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                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical spectrum&#44; treatment and outcome of patients with type II mixed cryoglobulinemia without evidence of hepatitis C infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46; Foessel"
                            1 => "J&#46;F&#46; Besancenot"
                            2 => "G&#46; Blaison"
                            3 => "N&#46; Magy-Bertrand"
                            4 => "R&#46; Jaussaud"
                            5 => "Y&#46; Etienne"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3899/jrheum.100998"
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                        "fecha" => "2011"
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                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21196580"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Review&#58; mixed cryoglobulinemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "C&#46; Ferri"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1750-1172-3-1"
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                        "fecha" => "2008"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mixed cryoglobulinemia&#58; new concepts"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46; Ramos-Casals"
                            1 => "O&#46; Trejo"
                            2 => "M&#46; Garcia-Carrasco"
                            3 => "R&#46; Cervera"
                            4 => "J&#46; Font"
                          ]
                        ]
                      ]
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                  ]
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                    0 => array:1 [
                      "Revista" => array:6 [
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                        "fecha" => "2000"
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                          0 => array:2 [
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                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatitis C virus-induced cryoglobulinemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "E&#46; Charles"
                            1 => "L&#46; Dustin"
                          ]
                        ]
                      ]
                    ]
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                        "fecha" => "2009"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19606079"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cryoglobulins in chronic hepatitis C virus infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46; Trendelenburg"
                            1 => "J&#46;A&#46; Schifferli"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
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Article information
ISSN: 21735743
Original language: English
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Idiomas
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