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has been described in HCV patients treated with IFN alfa and ribavirin&#46; It is thought that IFN alfa favors the differentiation of CD4 T cells&#44; promoting a Th1-type immune response with subsequent granuloma formation&#46; This mechanism may be intensified by ribavirin&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">We present the case of an adult woman with chronic hepatitis due to HCV who was treated with telaprevir&#44; IFN alfa&#44; and ribavirin and who developed papular sarcoidosis of the knees&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The patient was a 51-year-old woman with Child class A liver cirrhosis due to HCV genotype 1A&#44; for which she had begun antiviral therapy 6 months earlier with telaprevir&#44; IFN alfa&#44; and ribavirin&#46; She was seen for asymptomatic lesions on the knees that had appeared several months earlier&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Physical examination revealed multiple brownish erythematous papules &#40;2&#8211;5&#8239;mm in diameter&#41;&#44; some of which were oriented linearly&#44; on both knees &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Dermoscopy revealed an area of homogeneous yellow-orange coloration in which linear vessels were evident &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Histology of one of the lesions on the left knee revealed a non-necrotizing granulomatous infiltrate in the superficial dermis consisting of epithelioid histiocytes and multinucleated giant cells that phagocytosed birefringent crystalline material under polarized light microscopy &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; A diagnosis of papular sarcoidosis of the knees induced by antiviral therapy was established&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Additional tests &#40;laboratory tests with complete blood count&#44; biochemistry&#44; serum levels of angiotensin-converting enzyme&#44; calcium levels in urine collected over 24&#8239;h&#44; tuberculin test&#44; and chest x-ray&#41; revealed no findings of note&#46; Thoracic computed tomography &#40;CT&#41; revealed minimal involvement of the parenchyma of the peribronchovascular interstitium in the patient&#8217;s sarcoidosis&#46; The skin lesions on the knees improved a few months after discontinuing antiviral therapy&#44; without the need for treatment&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The prevalence of sarcoidosis is higher in HCV patients &#40;0&#46;12&#37;&#41; than in the general population &#40;1&#8211;40 per 100000&#41;&#46; Moreover&#44; skin lesions are more common in sarcoidosis patients with HCV &#40;56&#37;&#41; than in those without &#40;22&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> In many patients with chronic HCV hepatitis sarcoidosis is triggered by antiviral treatment &#40;IFN alfa administered alone or in combination with ribavirin&#41;&#46; The resulting sarcoidosis is usually pulmonary or cutaneous&#44; and has a favorable prognosis&#46; In fact&#44; with adequate follow-up most patients can complete antiviral treatment&#46; Once treatment is discontinued or completed the sarcoidosis lesions tend to resolve spontaneously&#44;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a> as observed for the cutaneous and pulmonary lesions in our patient&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Papular sarcoidosis of the knees is considered an intermediate clinical form of sarcoidosis&#44; sharing features of scar and papular sarcoidosis&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> It is usually the initial manifestation of systemic sarcoidosis and has a good prognosis&#46; It is characterized by the presence of reddish-brown papular lesions on both knees&#44; in some cases with a lichenoid appearance and linear orientation&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a> In approximately half of all cases papular sarcoidosis is associated with erythema nodosum &#40;L&#246;fgren syndrome&#41;&#46; For many authors&#44; the presence of these lesions on the knees is key for confirmation of sarcoidosis as the underlying cause of erythema nodosum&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a> Papular sarcoidosis lesions on the knees usually resolve spontaneously&#46; Even in the context of systemic sarcoidosis oral corticosteroid treatment is rarely necessary&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Foreign-body particles are present in the lesions in 60&#37; of cases of papular sarcoidosis&#46; The linear distribution of some lesions is suggestive of an exogenous cause&#46; However&#44; patients tend not to report the presence of previous scars in the same location and histology reveals no scar tissue&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> It is possible that microtrauma results in the inclusion of foreign bodies&#44; and that lesions develop years later in predisposed individuals or in response to treatments such as IFN alfa&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">The main differential diagnosis is scar sarcoidosis&#44; a rare clinical form characterized by swelling and reddening of pre-existing scars of many types&#44; including those caused by trauma&#44; tattoos&#44; venipuncture&#44; surgery&#44; hyaluronic acid injection&#44; and burns&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">In conclusion&#44; we describe a case of papular sarcoidosis of the knees in a HCV patient treated with telaprevir&#44; IFN alfa&#44; and ribavirin&#46; Sarcoidosis should be suspected in patients with erythematous&#44; occasionally linear papules located on both knees&#44; especially in patients with erythema nodosum or HCV treated with IFN&#46;</p></span>"
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Case and Research Letters
Papular Sarcoidosis of the Knees Following Treatment with Interferon Alpha and Ribavirin in a Woman with Hepatitis C
Sarcoidosis papulosa de las rodillas tras tratamiento con interferón alfa y ribavirina en paciente con hepatitis C
B. Monteagudoa,
Autor para correspondencia
, M.C. Grueirob, A. Vilas-Sueiroa, F. Campo-Cerecedoc
a Servicio de Dermatología, Complejo Hospitalario Universitario de Ferrol, Xerencia de Xestión Integrada de Ferrol, SERGAS, Ferrol, A Coruña, Spain
b Medicina Familiar y Comunitaria, Centro de Salud de Narón, SERGAS, Narón, A Coruña, Spain
c Servicio de Anatomía Patológica, Complejo Hospitalario Universitario de Ferrol, Xerencia de Xestión Integrada de Ferrol, SERGAS, Ferrol, A Coruña, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Chronic hepatitis caused by the hepatitis C virus &#40;HCV&#41; is associated with skin diseases including lichen planus&#44; mixed cryoglobulinemia&#44; porphyria cutanea tarda&#44; pruritus&#44; and necrolytic acral erythema&#46; Cutaneous adverse effects are also common in patients treated with interferon &#40;IFN&#41;&#44; particularly when combined with ribavirin&#46; These include injection-site reactions&#44; alopecia&#44; xerosis&#44; pruritus&#44; nummular eczema&#44; lichen planus&#44; and psoriasis flares&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Sarcoidosis is a chronic systemic granulomatous disease of possible autoimmune etiology that primarily affects the lungs and lymph nodes&#46; Induction of sarcoidosis&#44; especially pulmonary and cutaneous forms&#44; has been described in HCV patients treated with IFN alfa and ribavirin&#46; It is thought that IFN alfa favors the differentiation of CD4 T cells&#44; promoting a Th1-type immune response with subsequent granuloma formation&#46; This mechanism may be intensified by ribavirin&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">We present the case of an adult woman with chronic hepatitis due to HCV who was treated with telaprevir&#44; IFN alfa&#44; and ribavirin and who developed papular sarcoidosis of the knees&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The patient was a 51-year-old woman with Child class A liver cirrhosis due to HCV genotype 1A&#44; for which she had begun antiviral therapy 6 months earlier with telaprevir&#44; IFN alfa&#44; and ribavirin&#46; She was seen for asymptomatic lesions on the knees that had appeared several months earlier&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Physical examination revealed multiple brownish erythematous papules &#40;2&#8211;5&#8239;mm in diameter&#41;&#44; some of which were oriented linearly&#44; on both knees &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Dermoscopy revealed an area of homogeneous yellow-orange coloration in which linear vessels were evident &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Histology of one of the lesions on the left knee revealed a non-necrotizing granulomatous infiltrate in the superficial dermis consisting of epithelioid histiocytes and multinucleated giant cells that phagocytosed birefringent crystalline material under polarized light microscopy &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; A diagnosis of papular sarcoidosis of the knees induced by antiviral therapy was established&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Additional tests &#40;laboratory tests with complete blood count&#44; biochemistry&#44; serum levels of angiotensin-converting enzyme&#44; calcium levels in urine collected over 24&#8239;h&#44; tuberculin test&#44; and chest x-ray&#41; revealed no findings of note&#46; Thoracic computed tomography &#40;CT&#41; revealed minimal involvement of the parenchyma of the peribronchovascular interstitium in the patient&#8217;s sarcoidosis&#46; The skin lesions on the knees improved a few months after discontinuing antiviral therapy&#44; without the need for treatment&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The prevalence of sarcoidosis is higher in HCV patients &#40;0&#46;12&#37;&#41; than in the general population &#40;1&#8211;40 per 100000&#41;&#46; Moreover&#44; skin lesions are more common in sarcoidosis patients with HCV &#40;56&#37;&#41; than in those without &#40;22&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> In many patients with chronic HCV hepatitis sarcoidosis is triggered by antiviral treatment &#40;IFN alfa administered alone or in combination with ribavirin&#41;&#46; The resulting sarcoidosis is usually pulmonary or cutaneous&#44; and has a favorable prognosis&#46; In fact&#44; with adequate follow-up most patients can complete antiviral treatment&#46; Once treatment is discontinued or completed the sarcoidosis lesions tend to resolve spontaneously&#44;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a> as observed for the cutaneous and pulmonary lesions in our patient&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Papular sarcoidosis of the knees is considered an intermediate clinical form of sarcoidosis&#44; sharing features of scar and papular sarcoidosis&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> It is usually the initial manifestation of systemic sarcoidosis and has a good prognosis&#46; It is characterized by the presence of reddish-brown papular lesions on both knees&#44; in some cases with a lichenoid appearance and linear orientation&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a> In approximately half of all cases papular sarcoidosis is associated with erythema nodosum &#40;L&#246;fgren syndrome&#41;&#46; For many authors&#44; the presence of these lesions on the knees is key for confirmation of sarcoidosis as the underlying cause of erythema nodosum&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a> Papular sarcoidosis lesions on the knees usually resolve spontaneously&#46; Even in the context of systemic sarcoidosis oral corticosteroid treatment is rarely necessary&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Foreign-body particles are present in the lesions in 60&#37; of cases of papular sarcoidosis&#46; The linear distribution of some lesions is suggestive of an exogenous cause&#46; However&#44; patients tend not to report the presence of previous scars in the same location and histology reveals no scar tissue&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> It is possible that microtrauma results in the inclusion of foreign bodies&#44; and that lesions develop years later in predisposed individuals or in response to treatments such as IFN alfa&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">The main differential diagnosis is scar sarcoidosis&#44; a rare clinical form characterized by swelling and reddening of pre-existing scars of many types&#44; including those caused by trauma&#44; tattoos&#44; venipuncture&#44; surgery&#44; hyaluronic acid injection&#44; and burns&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">In conclusion&#44; we describe a case of papular sarcoidosis of the knees in a HCV patient treated with telaprevir&#44; IFN alfa&#44; and ribavirin&#46; Sarcoidosis should be suspected in patients with erythematous&#44; occasionally linear papules located on both knees&#44; especially in patients with erythema nodosum or HCV treated with IFN&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Monteagudo B&#44; Grueiro MC&#44; Vilas-Sueiro A&#44; Campo-Cerecedo F&#46; Sarcoidosis papulosa de las rodillas tras tratamiento con interfer&#243;n alfa y ribavirina en paciente con hepatitis C&#46; Actas Dermosifiliogr&#46; 2019&#59;110&#58;871&#8211;873&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A&#44; Brownish erythematous papules on both knees&#46; B&#44; Detailed image showing lichenoid lesions&#44; some arranged linearly&#44; on the left knee&#46;</p>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Dermoscopic image showing an area of homogeneous yellow-orange coloration within which linear vessels are evident&#46; &#40;A full-color version of this image can be found in the web version of this article&#46;&#41;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Histological images&#46; A&#44; Non-necrotizing granulomatous infiltrate in the superficial dermis &#40;hematoxylin-eosin&#44; original magnification &#215;10&#41;&#46; B&#44; Epithelioid histiocytes and birefringent crystalline material phagocytosed by multinucleated giant cells &#40;hematoxylin-eosin&#44; original magnification &#215;20&#41;&#46;</p>"
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