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    "textoCompleto" => "<span class="elsevierStyleSections"><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p class="elsevierStylePara elsevierViewall">Nephrogenic systemic fibrosis &#40;NSF&#41; is a newly fibrosing skin condition first identified in 1997&#44; and the initial published report of 15 cases appeared in 2000<a class="elsevierStyleCrossRef" href="#bib1"><span class="elsevierStyleSup">1</span></a>&#46; Most cases are described in patients with renal insufficiency undergoing haemodialysis&#44; peritoneal dialysis or after cadaveric renal transplant&#46; Some cases have been described in patients with acute renal failure &#40;ARF&#41;&#46; Numerous reports have been published&#44; some of them in Europe<a class="elsevierStyleCrossRefs" href="#bib2"><span class="elsevierStyleSup">2&#8211;9</span></a>&#46; The cutaneous changes include firm and thickened&#44; indurate skin plaques and papules as well as nodules on the extremities and trunk&#46; Histopathology typically shows an increase in dermal fibroblast-like cells associated with mucin deposition&#46; Differential diagnosis includes scleromyxoedema&#44; systemic or localized sclerodermia&#44; eosinophilic fascitis&#44; eosinophilia-myalgia syndrome&#44; scleredema&#44; lipodermatosclerosis&#44; porphyria cutanea tarda&#44; rheumatism fibroblastic&#44; Spanish toxic oil syndrome&#44; vinyl chloride exposure&#44; dermatofibrosarcoma protuberans and &#946;-2 microglobulin amyloidosis<a class="elsevierStyleCrossRef" href="#bib10"><span class="elsevierStyleSup">10</span></a>&#46; In 2006 Grobner and Marckmann proposed that Gadolinium based contrast agents &#40;Gd-CA&#41; may trigger the development of NFS in patients with underlying metabolic acidosis<a class="elsevierStyleCrossRefs" href="#bib11"><span class="elsevierStyleSup">11&#44;12</span></a>&#46; We described a patient with the clinical and pathologic picture of NSF presented after an ARF in the course of a perinuclear antineutrophil cytoplasmic antibodies &#40;p-ANCA&#41; associated systemic vasculitis&#46;</p></span><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Case report</span><p class="elsevierStylePara elsevierViewall">The patient&#44; a 65-year-old woman was referred to our institution in February 2003&#46; Her medical history included pulmonary tuberculosis at 28 years of age&#44; severe obesity and varicosity and phlebitic disease&#46; The patient had been treated previously with alternative therapies&#46; The family antecedents included a 39-year-old daughter suffering a rheumatoid arthritis and systemic lupus erythematosus overlap syndrome and another 38 year-old daughter diagnosed with a microscopic polyarteritis with positive ANA and p-ANCA that evolved to chronic renal failure requiring haemodialysis&#46; In February 2003 the patient was admitted to another hospital because of a 4-week syndrome with fever&#44; cough&#44; dysnea and myalgias&#46; Three days before being admitted the patient complained of pain&#44; oedema and swelling of the right leg and increased dyspnoea and vomiting together with abdominal pain&#46; On admittance acute renal failure with a creatinine of 2&#44;33<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; a normochromic normocytic anaemia &#40;Hb 9&#46;1<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#41;&#44; an erythrocyte sedimentation rate &#40;ESR&#41; of 128 and a C-reactive protein of 21&#44;7<span class="elsevierStyleHsp" style=""></span>mg&#47;L was reported&#46; Arterial blood gases on air revealed a pa O<span class="elsevierStyleInf">2</span> of 60&#44; a p CO<span class="elsevierStyleInf">2</span> of 35 and an O<span class="elsevierStyleInf">2</span> saturation of 94&#37;&#46; A chest radiography showed bilateral alveolar infiltrates first interpreted as infection&#46; An echography of the right leg showed deep venous thrombosis of the internal saphena&#46; At that point the patient did not accept the performance of a thoracic computed tomography &#40;CT&#41;&#46; Treatment with antibiotics&#44; low weight heparin&#44; and corticoids was instituted but the patient presented a gastric haemorrhage and a haematoma on the right leg and worsening of the anaemia that required blood transfusion and was referred to our hospital&#46; On admittance the laboratory studies revealed an ESR of 13&#44; normochromic normocytic anaemia &#40;Hb 7&#46;8<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#41; with 22500 leucocytes&#44; and platelet count and coagulation tests within normal range&#46; The serum creatinine had increased to 2&#44;8<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#46; A urinalysis revealed 3&#43; leucocytes and 3&#43; blood dipstick but protein or casts were absent&#46; The rheumatoid factor and cryoglobulins were negative&#46; Antinuclear antibodies were positive to 1&#47;640 by indirect immunofluorescence &#40;Hep-2 cells&#41; Anti-DNA and anticardiolipin antibodies were negative &#40;including anti-&#946;-2 glicoprotein I&#41; C3 was 59&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dl and C4 within range&#46; Serologic tests for hepatitis B and C were negative&#46; Anti-SS-A &#40;Ro&#41; antibody was positive&#46; P-ANCAs were positive to 1&#47;320 by indirect immunofluorescence&#46; Antimyeloperoxidase &#40;anti-MPO&#41; antibodies by enzimoimmunoanalysis were positive to 19<span class="elsevierStyleHsp" style=""></span>U&#47;mL &#40;normal &#60;10&#41; C-ANCA&#44; antiproteinase-3 and anti-glomerular basement membrane antibodies were negative&#46; No monoclonal band was detected in serum&#46; Five days later&#44; an ultrasound-guided renal biopsy was performed with the result of glomerulosclerosis affecting 8 of 11 glomeruli &#40;72&#37;&#41; with a focal segmental necrotizing lesion in one of them&#46; The vessels appeared normal and there was no evidence of vasculitis&#46; A moderate inflammatory infiltrate with polimorfonuclear and lymphocytes was observed in the interstitium&#46; Immunoperoxidase staining was negative for IgA&#44; IgG&#44; IgM&#44; C3&#44; or C4&#46; Red Congo stain for amyloid was negative&#46; A bronchoscopy showed data of pulmonary haemorrhage&#46; A thoracic CT showed some areas with ground-glass appearance&#46; An angiomagnetic nuclear resonance showed a right leg haematoma and thrombosis of the internal saphena&#46; A salivary glands gammagraphy showed a marked asymmetry and decreased uptake of right submandibular gland with normal left glands&#46; Schirmer&#39;s test was pathologic &#40;less than 5<span class="elsevierStyleHsp" style=""></span>mm&#41;&#46; An echocardiogram showed a light pericardial effusion with hypertrophy of the left ventricle and preserved function&#46; An electromyogram showed data of myopathy&#46; A diagnosis of p-ANCA associated vasculitis was made and treatment with intravenous methylprednisolone &#40;1<span class="elsevierStyleHsp" style=""></span>gm&#47;day&#41; for 3 days was initiated with normalization of renal function and cessation of pulmonary hemorrhage&#46; She refused treatment with cyclophosphamide&#46; During admittance the patient experienced an atrial fibrillation that was resolved with amiodarone and digoxine&#46; The patient was discharged with a creatinine of 1&#44;3<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#46; Routine visits were performed from this time with normal kidney and pulmonary function testing&#46; Two months later during routine visits the patient complained of the presence of papule-plaques involving the trunk and extremities accompanied by pain in the right hand together with flexion contracture of the 4th and 5th fingers of the right hand&#46; The skin had a brownish appearance&#44; and the arms and the legs were hyperpigmented &#40;<a class="elsevierStyleCrossRefs" href="#fig1">figs&#46; 1 y 2</a>&#41;&#46; A punch biopsy of the skin showed a preserved epidermis with a fibrosed dermis with numerous collagen bundles and numerous fibroblast-like cells and absence of inflammatory infiltrates or plasma cells&#46; Alcian blue stain demonstrates mucin deposits &#40;<a class="elsevierStyleCrossRef" href="#fig3">fig&#46; 3</a>&#41;&#46; A magnetic resonance &#40;MR&#41; of the arm showed an increased signal in the septum of subcutaneous cellular tissue with a &#8220;paved&#8221; appearance &#40;<a class="elsevierStyleCrossRef" href="#fig4">fig&#46; 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig1"></elsevierMultimedia><elsevierMultimedia ident="fig2"></elsevierMultimedia><elsevierMultimedia ident="fig3"></elsevierMultimedia><elsevierMultimedia ident="fig4"></elsevierMultimedia><p class="elsevierStylePara elsevierViewall">At the end of 2004 the patient was readmitted due to a new pulmonary haemorrhage and deteriorated renal function that required corticosteroids and intravenous cyclophosphamide&#46; Skin lesions were unchanged from baseline&#46; She suffered a colonic diverticulitis complicated with perforation and sepsis that ultimately led to death&#46; An autopsy was not carried out&#46;</p></span><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p class="elsevierStylePara elsevierViewall">NSF is basically a fibroplasia-an increase in fibrocytes and dermal collagen&#46; Patients present thickened or oedematous skin with indurated papules and plaques involving the extremities and the trunk&#46; The lesions are typically symmetrical&#46; Occasionally swelling of the hands and feet sometimes associated with bulla is noted&#46; Joints contracture may develop very rapidly&#46; Plantar flexion of the feet may be severe enough to make ambulation impossible&#46; Histological findings may vary depending on the stage of the disease development&#46; These findings include thick collagen bundles&#44; variable mucin deposition&#44; and absence of plasma cells and proliferation of dermal fibroblast&#46; CD34-positive dermal dendrocytes are closely apposed to collagen and elastic fibers<a class="elsevierStyleCrossRef" href="#bib2"><span class="elsevierStyleSup">2</span></a>&#46; MR imaging shows a heterogeneous pattern of the musculature&#44; as seen in myositis&#44; as well as abnormally inflamed subcutaneous adipose tissue<a class="elsevierStyleCrossRef" href="#bib8"><span class="elsevierStyleSup">8</span></a>&#46;</p><p class="elsevierStylePara elsevierViewall">The affected patients were initially identified among recipients of renal transplant&#44; but later cases identified in patients with a variety of different kidney diseases appeared&#46; The severity of NSF is not related to the degree of renal impairment or to the cause of the underlying renal dysfunction&#46; The aetiology and pathogenesis of NSF are unknown&#44; the resemblance to a tissue injury reaction and the presence of myofibroblast&#44; also seen in Spanish toxic olive oil epidemic syndrome&#44; in the tissue specimens suggest that fibrogenic cytokines such as TGF-&#946; may be involved in the evolution of the disease<a class="elsevierStyleCrossRefs" href="#bib6"><span class="elsevierStyleSup">6&#44;13</span></a>&#46; Decreased level of TGF-&#946;1 after plasmapheresis appears to correlate with the amelioration of this clinical condition<a class="elsevierStyleCrossRef" href="#bib4"><span class="elsevierStyleSup">4</span></a>&#46; Hypercoagulability or thrombotic episodes&#44; or both&#44; may precipitate NSF in as many as 12&#37; of the patients<a class="elsevierStyleCrossRef" href="#bib10"><span class="elsevierStyleSup">10</span></a> and anticardiolipin antibodies have been described in some patients<a class="elsevierStyleCrossRefs" href="#bib6"><span class="elsevierStyleSup">6&#44;14</span></a>&#46; Jimenez et al report a marked elevation of acute phase reactants in 6 patients and a reduced diffusion capacity on pulmonary function testing in 5 patients<a class="elsevierStyleCrossRef" href="#bib13"><span class="elsevierStyleSup">13</span></a>&#46; Systemic involvement with fibrosis of diaphragm&#44; psoas muscle or testis<a class="elsevierStyleCrossRef" href="#bib3"><span class="elsevierStyleSup">3</span></a> and increased circulating immune complexes and anti-DNA antibodies have been reported<a class="elsevierStyleCrossRef" href="#bib15"><span class="elsevierStyleSup">15</span></a>&#46;</p><p class="elsevierStylePara elsevierViewall">After 2006 numerous published case series have confirmed a very strong associattion of NSF with exposure to Gd-CA&#46; 93&#37; of the uncounfounded biopsy-proven NSF cases linked to a specific Gd-CA have been associated with gadodiamide &#40;Omniscan<span class="elsevierStyleSup">&#174;</span>&#41;&#46; Trasmetillation of the gadolinium chelate because of prolonged clearance of Gd-CA has been proposed as trigger for NSF<a class="elsevierStyleCrossRef" href="#bib16"><span class="elsevierStyleSup">16</span></a> High-dose erythropoietin therapy has been postulated to contribute to the pathogenesis of NSF but our patient did not received treatment with eytrhopoietin<a class="elsevierStyleCrossRef" href="#bib17"><span class="elsevierStyleSup">17</span></a>&#46;</p><p class="elsevierStylePara elsevierViewall">The ultimate course of NSF has not been defined&#46; Frequently the disease persists and causes varying degrees of disability&#46; Complete resolution is rare&#46; At present&#44; there is no consistently effective therapy for NSF&#46; Therapeutic modalities that have been attempted up to now include oral and topical steroids&#44; intralesional triamcinolone or methotrexate&#44; cyclosporine&#44; tacrolimus&#44; thalidomide&#44; interferon&#44; photopheresis or plasmapheresis<a class="elsevierStyleCrossRefs" href="#bib4"><span class="elsevierStyleSup">4&#44;10&#44;18</span></a>&#46; Intravenous immunoglobulin as used in scleromyxoedema have reported slight improvement in joint motion range<a class="elsevierStyleCrossRef" href="#bib19"><span class="elsevierStyleSup">19</span></a>&#46;</p><p class="elsevierStylePara elsevierViewall">Differential diagnosis includes scleromyxoedema&#44; which the condition resembles in some aspect&#44; but systemic findings are absent&#46; Scleromyxoedema commonly affects the face&#44; an unusual finding in NSF<a class="elsevierStyleCrossRef" href="#bib20"><span class="elsevierStyleSup">20</span></a>&#46; We have not found monoclonal serum paraproteinemia or inflammatory plasma cell infiltrate in the skin biopsy in our patient&#46; Well-circumscribed&#44; indurate&#44; inflamed&#44; hyperpigmented plaques of the lower part of the legs characterize lipodermatosclerosis&#44; usually affecting women who have venous insufficiency and stasis&#46; These features are quiet different from those of our patient&#46; Other disorders to be considered are systemic or localized sclerodermia &#40;morphea&#41;&#44; eosinophilic fascitis or the eosinophilia-myalgia syndrome&#46; Our patient developed the characteristic symmetric lesions involving the trunk and extremities without face or neck involvement&#46; There was no Raynaud&#39;s phenomenon&#44; sclerodactyly&#44; telangiectasias or perioral furrows as in systemic sclerosis&#46; Morphea is characterized by ivory-colored plaques with violaceous borders and histologically there is increased collagen with the absence of mucin&#46; There was no peripheral&#8211;blood eosinophilia&#44; thickening of the deep fascia or infiltrates in the biopsy as seen in eosinophilic fascitis or eosinophilia myalgia syndrome&#46; There was no evidence of amyloid deposition on skin or kidney biopsies&#46; Initially the patient complained of polyarthralgias but arthritis as described in fibroblastic rheumatism was absent&#46; The patient had previously undertaken homeopathic treatment but she did not know the characteristics of the products she had taken&#46; There was no evidence of exposure to toxic oil&#46;</p><p class="elsevierStylePara elsevierViewall">Our patient suffered ARF in the setting of a systemic disease characterized by pulmonary haemorrhage and renal insufficiency together with positive ANA&#44; Ro and p-ANCA antibodies&#46; She suffered a deep venous thrombosis and was treated with subcutaneous heparin and had antecedents of phlebitis but she did not show positive lupus anticoagulant&#44; antiphospholipid antibodies or any abnormal coagulation test&#46; A MR with Gd-Ca &#40;Gadodiamide-Omniscan<span class="elsevierStyleSup">&#174;</span>&#41; was performed 20 days after admision&#46; The cutaneous lesions began two months later&#46; ANCA associated vasculitis was the final diagnosis in view of the pulmonary haemorrhage and positive anti MPO antibodies&#44; although the findings of the kidney biopsy with marked sclerotic findings were not those typically encountered in Wegener&#8242;s granulomatosis or microscopic polyarteritis&#46; The increased prevalence of autoimmune diseases in their family resulted surprising&#46; She had four live daughters&#44; two of them with autoimmune diseases&#44; and other three male pregnancies derived in death in early childhood&#46; No information about the death causes was obtained&#46;</p><p class="elsevierStylePara elsevierViewall">We stress this peculiar case of NSF in a patient with systemic autoimmune disease in an autoimmune family background and the presence of three of the antecedents typically found in NSF&#58; acute renal failure&#44; deep venous thrombosis and exposure to Gd-Ca&#46;</p></span></span>"
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          "identificador" => "xpalclavsec112807"
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          "titulo" => "Introduction"
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          "titulo" => "Case report"
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        6 => array:1 [
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    "fechaRecibido" => "2008-09-12"
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            0 => "Nephrogenic systemic fibrosis"
            1 => "p-ANCA vasculitis"
            2 => "Acute renal failure"
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            0 => "Fibrosis sist&#233;mica nefrog&#233;nica"
            1 => "Vasculitis asociada a p-ANCA"
            2 => "Fracaso renal agudo"
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      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<p class="elsevierStyleSimplePara elsevierViewall">Nephrogenic systemic fibrosis &#40;NSF&#41; is a fibrosing skin condition of unknown origin&#46; Most cases have been described in patients with acute or chronic renal failure&#46; The cutaneous changes include firm and thickened&#44; indurate skin plaques and papules on the extremities and trunk&#46; Histopathology typically shows an increase in dermal fibroblast-like cells associated with mucin deposition&#46; Previous exposition to gadolinium-based contrast agents was closely associated with its onset&#46; We described a patient with the clinical and pathologic picture of NSF presented after an acute renal failure in the course of a perinuclear antineutrophil cytoplasmic antibodies associated systemic vasculitis&#46;</p>"
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      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<p class="elsevierStyleSimplePara elsevierViewall">La fibrosis sist&#233;mica nefrog&#233;nica &#40;FSN&#41; es una entidad de origen desconocido caracterizada por un incremento de la fibrosis cut&#225;nea&#46; La mayor&#237;a de los casos se han descrito en pacientes con fracaso renal agudo o cr&#243;nico&#46; Las alteraciones cut&#225;neas incluyen p&#225;pulas y placas dermicas engrosadas e induradas distribuidas por las extremidades y el tronco&#46; El estudio histol&#243;gico pone de manifiesto un incremento en la dermis del n&#250;mero de c&#233;lulas tipo fibroblasto acompa&#241;ado de dep&#243;sito de mucina&#46; En la mayor&#237;a de los casos existe el antecedente reciente de exposici&#243;n a agentes de contraste tipo gadolinio&#46; Describimos una paciente que presenta los hallazgos cl&#237;nicos y patol&#243;gicos caracter&#237;sticos de la FSN despu&#233;s de un fracaso renal agudo en el contexto de una vasculitis asociada a anticuerpos anticitoplasma de los neutr&#243;filos&#46;</p>"
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          "en" => "<p class="elsevierStyleSimplePara elsevierViewall">Indurate papule-plaques with brownish hyperpigmentation of the arm&#46;</p>"
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          "en" => "<p class="elsevierStyleSimplePara elsevierViewall">Contracture of the fourth and fifth fingers of the right hand&#46;</p>"
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                      "titulo" => "Nephrogenic fibrosing dermopathy after liver transplantation successfully treated with plasmapheresis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
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                            0 => "P&#46;W&#46; Baron"
                            1 => "K&#46; Cantos"
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                      "titulo" => "Nephrogenic fibrosing dermopathy&#58; a novel cutaneous fibrosing disorder in patients with renal failure"
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                        0 => array:2 [
                          "etal" => false
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                            0 => "R&#46;D&#46; Swartz"
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                        0 => array:2 [
                          "etal" => false
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                            0 => "B&#46;N&#46; Streams"
                            1 => "V&#46; Liu"
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                      "titulo" => "Nephrogenic fibrosing dermopathy&#58; a novel&#44; disabling disorder in patients with renal failure"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46; Evenepoel"
                            1 => "M&#46; Zeegers"
                            2 => "S&#46; Segaert"
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                      "titulo" => "Nephrogenic fibrosing dermopathy&#58; An unusual skin condition associated with kidney disease"
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                            0 => "S&#46; Ishibe"
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Case report
Nephrogenic systemic fibrosis in a patient with a p-ANCA systemic vasculitis
Fibrosis sistémica nefrogénica en un paciente con una vasculitis sistémica asociada a p-ANCA
Eduardo Cuendea,
Autor para correspondencia
ecuende.hupa@salud.madrid.org

Autor para correspondencia.
, Mikel Aldamizb, Joseba Portub, R.. Ramón Ruiz de Gaunac, Rosa Zaballad, Juan Carlos Vesgaa
a Rheumatology Service, Hospital Príncipe de Asturias, Alcalá de Henares, Spain
b Internal Medicine Service, Hospital Txagorritxu, Vitoria-Gasteiz, Spain
c Nephrology Service, Hospital Txagorritxu, Vitoria-Gasteiz, Spain
d Pathology Service, Hospital Txagorritxu, Vitoria-Gasteiz, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p class="elsevierStylePara elsevierViewall">Nephrogenic systemic fibrosis &#40;NSF&#41; is a newly fibrosing skin condition first identified in 1997&#44; and the initial published report of 15 cases appeared in 2000<a class="elsevierStyleCrossRef" href="#bib1"><span class="elsevierStyleSup">1</span></a>&#46; Most cases are described in patients with renal insufficiency undergoing haemodialysis&#44; peritoneal dialysis or after cadaveric renal transplant&#46; Some cases have been described in patients with acute renal failure &#40;ARF&#41;&#46; Numerous reports have been published&#44; some of them in Europe<a class="elsevierStyleCrossRefs" href="#bib2"><span class="elsevierStyleSup">2&#8211;9</span></a>&#46; The cutaneous changes include firm and thickened&#44; indurate skin plaques and papules as well as nodules on the extremities and trunk&#46; Histopathology typically shows an increase in dermal fibroblast-like cells associated with mucin deposition&#46; Differential diagnosis includes scleromyxoedema&#44; systemic or localized sclerodermia&#44; eosinophilic fascitis&#44; eosinophilia-myalgia syndrome&#44; scleredema&#44; lipodermatosclerosis&#44; porphyria cutanea tarda&#44; rheumatism fibroblastic&#44; Spanish toxic oil syndrome&#44; vinyl chloride exposure&#44; dermatofibrosarcoma protuberans and &#946;-2 microglobulin amyloidosis<a class="elsevierStyleCrossRef" href="#bib10"><span class="elsevierStyleSup">10</span></a>&#46; In 2006 Grobner and Marckmann proposed that Gadolinium based contrast agents &#40;Gd-CA&#41; may trigger the development of NFS in patients with underlying metabolic acidosis<a class="elsevierStyleCrossRefs" href="#bib11"><span class="elsevierStyleSup">11&#44;12</span></a>&#46; We described a patient with the clinical and pathologic picture of NSF presented after an ARF in the course of a perinuclear antineutrophil cytoplasmic antibodies &#40;p-ANCA&#41; associated systemic vasculitis&#46;</p></span><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Case report</span><p class="elsevierStylePara elsevierViewall">The patient&#44; a 65-year-old woman was referred to our institution in February 2003&#46; Her medical history included pulmonary tuberculosis at 28 years of age&#44; severe obesity and varicosity and phlebitic disease&#46; The patient had been treated previously with alternative therapies&#46; The family antecedents included a 39-year-old daughter suffering a rheumatoid arthritis and systemic lupus erythematosus overlap syndrome and another 38 year-old daughter diagnosed with a microscopic polyarteritis with positive ANA and p-ANCA that evolved to chronic renal failure requiring haemodialysis&#46; In February 2003 the patient was admitted to another hospital because of a 4-week syndrome with fever&#44; cough&#44; dysnea and myalgias&#46; Three days before being admitted the patient complained of pain&#44; oedema and swelling of the right leg and increased dyspnoea and vomiting together with abdominal pain&#46; On admittance acute renal failure with a creatinine of 2&#44;33<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; a normochromic normocytic anaemia &#40;Hb 9&#46;1<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#41;&#44; an erythrocyte sedimentation rate &#40;ESR&#41; of 128 and a C-reactive protein of 21&#44;7<span class="elsevierStyleHsp" style=""></span>mg&#47;L was reported&#46; Arterial blood gases on air revealed a pa O<span class="elsevierStyleInf">2</span> of 60&#44; a p CO<span class="elsevierStyleInf">2</span> of 35 and an O<span class="elsevierStyleInf">2</span> saturation of 94&#37;&#46; A chest radiography showed bilateral alveolar infiltrates first interpreted as infection&#46; An echography of the right leg showed deep venous thrombosis of the internal saphena&#46; At that point the patient did not accept the performance of a thoracic computed tomography &#40;CT&#41;&#46; Treatment with antibiotics&#44; low weight heparin&#44; and corticoids was instituted but the patient presented a gastric haemorrhage and a haematoma on the right leg and worsening of the anaemia that required blood transfusion and was referred to our hospital&#46; On admittance the laboratory studies revealed an ESR of 13&#44; normochromic normocytic anaemia &#40;Hb 7&#46;8<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#41; with 22500 leucocytes&#44; and platelet count and coagulation tests within normal range&#46; The serum creatinine had increased to 2&#44;8<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#46; A urinalysis revealed 3&#43; leucocytes and 3&#43; blood dipstick but protein or casts were absent&#46; The rheumatoid factor and cryoglobulins were negative&#46; Antinuclear antibodies were positive to 1&#47;640 by indirect immunofluorescence &#40;Hep-2 cells&#41; Anti-DNA and anticardiolipin antibodies were negative &#40;including anti-&#946;-2 glicoprotein I&#41; C3 was 59&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dl and C4 within range&#46; Serologic tests for hepatitis B and C were negative&#46; Anti-SS-A &#40;Ro&#41; antibody was positive&#46; P-ANCAs were positive to 1&#47;320 by indirect immunofluorescence&#46; Antimyeloperoxidase &#40;anti-MPO&#41; antibodies by enzimoimmunoanalysis were positive to 19<span class="elsevierStyleHsp" style=""></span>U&#47;mL &#40;normal &#60;10&#41; C-ANCA&#44; antiproteinase-3 and anti-glomerular basement membrane antibodies were negative&#46; No monoclonal band was detected in serum&#46; Five days later&#44; an ultrasound-guided renal biopsy was performed with the result of glomerulosclerosis affecting 8 of 11 glomeruli &#40;72&#37;&#41; with a focal segmental necrotizing lesion in one of them&#46; The vessels appeared normal and there was no evidence of vasculitis&#46; A moderate inflammatory infiltrate with polimorfonuclear and lymphocytes was observed in the interstitium&#46; Immunoperoxidase staining was negative for IgA&#44; IgG&#44; IgM&#44; C3&#44; or C4&#46; Red Congo stain for amyloid was negative&#46; A bronchoscopy showed data of pulmonary haemorrhage&#46; A thoracic CT showed some areas with ground-glass appearance&#46; An angiomagnetic nuclear resonance showed a right leg haematoma and thrombosis of the internal saphena&#46; A salivary glands gammagraphy showed a marked asymmetry and decreased uptake of right submandibular gland with normal left glands&#46; Schirmer&#39;s test was pathologic &#40;less than 5<span class="elsevierStyleHsp" style=""></span>mm&#41;&#46; An echocardiogram showed a light pericardial effusion with hypertrophy of the left ventricle and preserved function&#46; An electromyogram showed data of myopathy&#46; A diagnosis of p-ANCA associated vasculitis was made and treatment with intravenous methylprednisolone &#40;1<span class="elsevierStyleHsp" style=""></span>gm&#47;day&#41; for 3 days was initiated with normalization of renal function and cessation of pulmonary hemorrhage&#46; She refused treatment with cyclophosphamide&#46; During admittance the patient experienced an atrial fibrillation that was resolved with amiodarone and digoxine&#46; The patient was discharged with a creatinine of 1&#44;3<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#46; Routine visits were performed from this time with normal kidney and pulmonary function testing&#46; Two months later during routine visits the patient complained of the presence of papule-plaques involving the trunk and extremities accompanied by pain in the right hand together with flexion contracture of the 4th and 5th fingers of the right hand&#46; The skin had a brownish appearance&#44; and the arms and the legs were hyperpigmented &#40;<a class="elsevierStyleCrossRefs" href="#fig1">figs&#46; 1 y 2</a>&#41;&#46; A punch biopsy of the skin showed a preserved epidermis with a fibrosed dermis with numerous collagen bundles and numerous fibroblast-like cells and absence of inflammatory infiltrates or plasma cells&#46; Alcian blue stain demonstrates mucin deposits &#40;<a class="elsevierStyleCrossRef" href="#fig3">fig&#46; 3</a>&#41;&#46; A magnetic resonance &#40;MR&#41; of the arm showed an increased signal in the septum of subcutaneous cellular tissue with a &#8220;paved&#8221; appearance &#40;<a class="elsevierStyleCrossRef" href="#fig4">fig&#46; 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig1"></elsevierMultimedia><elsevierMultimedia ident="fig2"></elsevierMultimedia><elsevierMultimedia ident="fig3"></elsevierMultimedia><elsevierMultimedia ident="fig4"></elsevierMultimedia><p class="elsevierStylePara elsevierViewall">At the end of 2004 the patient was readmitted due to a new pulmonary haemorrhage and deteriorated renal function that required corticosteroids and intravenous cyclophosphamide&#46; Skin lesions were unchanged from baseline&#46; She suffered a colonic diverticulitis complicated with perforation and sepsis that ultimately led to death&#46; An autopsy was not carried out&#46;</p></span><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p class="elsevierStylePara elsevierViewall">NSF is basically a fibroplasia-an increase in fibrocytes and dermal collagen&#46; Patients present thickened or oedematous skin with indurated papules and plaques involving the extremities and the trunk&#46; The lesions are typically symmetrical&#46; Occasionally swelling of the hands and feet sometimes associated with bulla is noted&#46; Joints contracture may develop very rapidly&#46; Plantar flexion of the feet may be severe enough to make ambulation impossible&#46; Histological findings may vary depending on the stage of the disease development&#46; These findings include thick collagen bundles&#44; variable mucin deposition&#44; and absence of plasma cells and proliferation of dermal fibroblast&#46; CD34-positive dermal dendrocytes are closely apposed to collagen and elastic fibers<a class="elsevierStyleCrossRef" href="#bib2"><span class="elsevierStyleSup">2</span></a>&#46; MR imaging shows a heterogeneous pattern of the musculature&#44; as seen in myositis&#44; as well as abnormally inflamed subcutaneous adipose tissue<a class="elsevierStyleCrossRef" href="#bib8"><span class="elsevierStyleSup">8</span></a>&#46;</p><p class="elsevierStylePara elsevierViewall">The affected patients were initially identified among recipients of renal transplant&#44; but later cases identified in patients with a variety of different kidney diseases appeared&#46; The severity of NSF is not related to the degree of renal impairment or to the cause of the underlying renal dysfunction&#46; The aetiology and pathogenesis of NSF are unknown&#44; the resemblance to a tissue injury reaction and the presence of myofibroblast&#44; also seen in Spanish toxic olive oil epidemic syndrome&#44; in the tissue specimens suggest that fibrogenic cytokines such as TGF-&#946; may be involved in the evolution of the disease<a class="elsevierStyleCrossRefs" href="#bib6"><span class="elsevierStyleSup">6&#44;13</span></a>&#46; Decreased level of TGF-&#946;1 after plasmapheresis appears to correlate with the amelioration of this clinical condition<a class="elsevierStyleCrossRef" href="#bib4"><span class="elsevierStyleSup">4</span></a>&#46; Hypercoagulability or thrombotic episodes&#44; or both&#44; may precipitate NSF in as many as 12&#37; of the patients<a class="elsevierStyleCrossRef" href="#bib10"><span class="elsevierStyleSup">10</span></a> and anticardiolipin antibodies have been described in some patients<a class="elsevierStyleCrossRefs" href="#bib6"><span class="elsevierStyleSup">6&#44;14</span></a>&#46; Jimenez et al report a marked elevation of acute phase reactants in 6 patients and a reduced diffusion capacity on pulmonary function testing in 5 patients<a class="elsevierStyleCrossRef" href="#bib13"><span class="elsevierStyleSup">13</span></a>&#46; Systemic involvement with fibrosis of diaphragm&#44; psoas muscle or testis<a class="elsevierStyleCrossRef" href="#bib3"><span class="elsevierStyleSup">3</span></a> and increased circulating immune complexes and anti-DNA antibodies have been reported<a class="elsevierStyleCrossRef" href="#bib15"><span class="elsevierStyleSup">15</span></a>&#46;</p><p class="elsevierStylePara elsevierViewall">After 2006 numerous published case series have confirmed a very strong associattion of NSF with exposure to Gd-CA&#46; 93&#37; of the uncounfounded biopsy-proven NSF cases linked to a specific Gd-CA have been associated with gadodiamide &#40;Omniscan<span class="elsevierStyleSup">&#174;</span>&#41;&#46; Trasmetillation of the gadolinium chelate because of prolonged clearance of Gd-CA has been proposed as trigger for NSF<a class="elsevierStyleCrossRef" href="#bib16"><span class="elsevierStyleSup">16</span></a> High-dose erythropoietin therapy has been postulated to contribute to the pathogenesis of NSF but our patient did not received treatment with eytrhopoietin<a class="elsevierStyleCrossRef" href="#bib17"><span class="elsevierStyleSup">17</span></a>&#46;</p><p class="elsevierStylePara elsevierViewall">The ultimate course of NSF has not been defined&#46; Frequently the disease persists and causes varying degrees of disability&#46; Complete resolution is rare&#46; At present&#44; there is no consistently effective therapy for NSF&#46; Therapeutic modalities that have been attempted up to now include oral and topical steroids&#44; intralesional triamcinolone or methotrexate&#44; cyclosporine&#44; tacrolimus&#44; thalidomide&#44; interferon&#44; photopheresis or plasmapheresis<a class="elsevierStyleCrossRefs" href="#bib4"><span class="elsevierStyleSup">4&#44;10&#44;18</span></a>&#46; Intravenous immunoglobulin as used in scleromyxoedema have reported slight improvement in joint motion range<a class="elsevierStyleCrossRef" href="#bib19"><span class="elsevierStyleSup">19</span></a>&#46;</p><p class="elsevierStylePara elsevierViewall">Differential diagnosis includes scleromyxoedema&#44; which the condition resembles in some aspect&#44; but systemic findings are absent&#46; Scleromyxoedema commonly affects the face&#44; an unusual finding in NSF<a class="elsevierStyleCrossRef" href="#bib20"><span class="elsevierStyleSup">20</span></a>&#46; We have not found monoclonal serum paraproteinemia or inflammatory plasma cell infiltrate in the skin biopsy in our patient&#46; Well-circumscribed&#44; indurate&#44; inflamed&#44; hyperpigmented plaques of the lower part of the legs characterize lipodermatosclerosis&#44; usually affecting women who have venous insufficiency and stasis&#46; These features are quiet different from those of our patient&#46; Other disorders to be considered are systemic or localized sclerodermia &#40;morphea&#41;&#44; eosinophilic fascitis or the eosinophilia-myalgia syndrome&#46; Our patient developed the characteristic symmetric lesions involving the trunk and extremities without face or neck involvement&#46; There was no Raynaud&#39;s phenomenon&#44; sclerodactyly&#44; telangiectasias or perioral furrows as in systemic sclerosis&#46; Morphea is characterized by ivory-colored plaques with violaceous borders and histologically there is increased collagen with the absence of mucin&#46; There was no peripheral&#8211;blood eosinophilia&#44; thickening of the deep fascia or infiltrates in the biopsy as seen in eosinophilic fascitis or eosinophilia myalgia syndrome&#46; There was no evidence of amyloid deposition on skin or kidney biopsies&#46; Initially the patient complained of polyarthralgias but arthritis as described in fibroblastic rheumatism was absent&#46; The patient had previously undertaken homeopathic treatment but she did not know the characteristics of the products she had taken&#46; There was no evidence of exposure to toxic oil&#46;</p><p class="elsevierStylePara elsevierViewall">Our patient suffered ARF in the setting of a systemic disease characterized by pulmonary haemorrhage and renal insufficiency together with positive ANA&#44; Ro and p-ANCA antibodies&#46; She suffered a deep venous thrombosis and was treated with subcutaneous heparin and had antecedents of phlebitis but she did not show positive lupus anticoagulant&#44; antiphospholipid antibodies or any abnormal coagulation test&#46; A MR with Gd-Ca &#40;Gadodiamide-Omniscan<span class="elsevierStyleSup">&#174;</span>&#41; was performed 20 days after admision&#46; The cutaneous lesions began two months later&#46; ANCA associated vasculitis was the final diagnosis in view of the pulmonary haemorrhage and positive anti MPO antibodies&#44; although the findings of the kidney biopsy with marked sclerotic findings were not those typically encountered in Wegener&#8242;s granulomatosis or microscopic polyarteritis&#46; The increased prevalence of autoimmune diseases in their family resulted surprising&#46; She had four live daughters&#44; two of them with autoimmune diseases&#44; and other three male pregnancies derived in death in early childhood&#46; No information about the death causes was obtained&#46;</p><p class="elsevierStylePara elsevierViewall">We stress this peculiar case of NSF in a patient with systemic autoimmune disease in an autoimmune family background and the presence of three of the antecedents typically found in NSF&#58; acute renal failure&#44; deep venous thrombosis and exposure to Gd-Ca&#46;</p></span></span>"
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        "resumen" => "<p class="elsevierStyleSimplePara elsevierViewall">Nephrogenic systemic fibrosis &#40;NSF&#41; is a fibrosing skin condition of unknown origin&#46; Most cases have been described in patients with acute or chronic renal failure&#46; The cutaneous changes include firm and thickened&#44; indurate skin plaques and papules on the extremities and trunk&#46; Histopathology typically shows an increase in dermal fibroblast-like cells associated with mucin deposition&#46; Previous exposition to gadolinium-based contrast agents was closely associated with its onset&#46; We described a patient with the clinical and pathologic picture of NSF presented after an acute renal failure in the course of a perinuclear antineutrophil cytoplasmic antibodies associated systemic vasculitis&#46;</p>"
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        "resumen" => "<p class="elsevierStyleSimplePara elsevierViewall">La fibrosis sist&#233;mica nefrog&#233;nica &#40;FSN&#41; es una entidad de origen desconocido caracterizada por un incremento de la fibrosis cut&#225;nea&#46; La mayor&#237;a de los casos se han descrito en pacientes con fracaso renal agudo o cr&#243;nico&#46; Las alteraciones cut&#225;neas incluyen p&#225;pulas y placas dermicas engrosadas e induradas distribuidas por las extremidades y el tronco&#46; El estudio histol&#243;gico pone de manifiesto un incremento en la dermis del n&#250;mero de c&#233;lulas tipo fibroblasto acompa&#241;ado de dep&#243;sito de mucina&#46; En la mayor&#237;a de los casos existe el antecedente reciente de exposici&#243;n a agentes de contraste tipo gadolinio&#46; Describimos una paciente que presenta los hallazgos cl&#237;nicos y patol&#243;gicos caracter&#237;sticos de la FSN despu&#233;s de un fracaso renal agudo en el contexto de una vasculitis asociada a anticuerpos anticitoplasma de los neutr&#243;filos&#46;</p>"
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Información del artículo
ISSN: 1699258X
Idioma original: Inglés
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2011 Abril 3 0 3
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2010 Julio 19 0 19
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2010 Febrero 3 0 3
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2009 Diciembre 5 0 5
2009 Noviembre 2 0 2
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