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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Onset of interstitial granulomatous dermatitis &#40;IGD&#41;&#44; a rare skin disease with a variable clinical presentation and a characteristic pathological pattern&#44; has been associated with various systemic diseases and different drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Tocilizumab is a humanized monoclonal antibody directed against the interleukin-6 &#40;IL-6&#41; receptor&#44; and has been used to treat IGD with good results&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> We present a case of IGD that began while the affected patient was being treated with tocilizumab&#44; and question whether this drug is truly useful for the treatment of this disease&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The patient was a 62-year-old woman who had a history of antisynthetase syndrome with muscle&#44; lung&#44; and joint involvement and had started treatment with tocilizumab at a dose of 8<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;month&#46; She was referred to the dermatology service for slightly itchy&#44; mildly painful skin lesions that had appeared 9 months after beginning tocilizumab treatment&#46; The patient had no medical history of interest and had not been treated with any other drugs&#46; The lesions consisted of well defined&#44; infiltrated&#44; edematous&#44; erythematous plaques with no epidermal component that were prone to central clearing&#44; resulting in an arciform morphology &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The lesions were located on the armpits&#44; the shoulder girdle&#44; and the internal aspects of the arms &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">A skin biopsy revealed an unaltered epidermis&#44; interstitial histiocytic infiltrate with perivascular accentuation along the entire thickness of the dermis&#44; and an absence of mucin deposits&#46; In certain fields&#44; higher magnification revealed some interstitial and intravascular neutrophils &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#44; based on which a histopathological diagnosis of IGD was established&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The patient was prescribed topical mometasone every 12 hours&#44; without discontinuing tocilizumab treatment&#46; Three months later the lesions had disappeared&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">IGD is a rare dermatosis&#44; which most often appears in patients with rheumatologic diseases&#44; especially rheumatoid arthritis&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> although it has also been associated with solid and hematological malignancies &#40;especially myelodysplastic syndromes<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a>&#41;&#44; infections&#44; and treatment with different drugs&#44; including antihypertensives&#44; anticonvulsants&#44; antidepressants&#44; and immunosuppressants&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> Pathologically&#44; it is characterized by interstitial lymphohistiocytic infiltrate with variable presence of neutrophils and eosinophils&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> Leukocytoclastic vasculitis is occasionally observed&#44; and collagen fiber degeneration is a constant finding&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> The clinical spectrum is variable&#44; and consists of usually asymptomatic&#44; infiltrated&#44; pink&#44; erythematous or erythematous-violaceous papules or plaques&#44; generally without an epidermal component and occasionally with annular morphology&#46; Although infrequent&#44; the presence of indurated linear lesions on the lateral aspects of the trunk &#40;known as the <span class="elsevierStyleItalic">rope sign</span>&#41; is considered almost pathognomonic&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Most cases have a good prognosis without treatment&#44; resolving within 3 months to 3 years&#46; Approximately 30&#37; of cases follow a chronic course with flare-ups&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Although there are no definitive treatments for this disease&#44; it has been successfully treated with topical and systemic corticosteroids&#44; methotrexate&#44; ciclosporin&#44; and&#44; more recently&#44; etanercept&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Tocilizumab is a monoclonal antibody primarily used to treat rheumatoid arthritis&#46; Several skin reactions have been associated with tocilizumab administration&#44; including psoriasis-like reactions&#44;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> erythema multiforme-like lesions&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> acute generalized exanthematous pustulosis&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> and rheumatoid neutrophilic dermatosis&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> There are no cases of tocilizumab-induced IGD described in the literature&#46; However&#44; one report describes a satisfactory clinical response to tocilizumab treatment of IGD&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> suggesting a role of IL-6 in the development of granulomatous inflammation&#44; whereby neutrophils act as the main effector cells&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">In our case&#44; it was not possible to determine whether IGD was triggered by tocilizumab treatment&#59; the lesions resolved without discontinuing treatment and the patient had a history of rheumatological disease&#44; which may have contributed to the onset of this dermatosis&#46; However&#44; the fact that the lesions developed while the patient was undergoing tocilizumab treatment casts doubt on its effectiveness as a treatment for IGD and on the role of IL-6 in the pathogenesis of this disease&#46; As noted by Schanz and coworkers&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> the important pathogenic role of IL-6 in acute inflammation is well established&#59; levels of this cytokine are increased in serum and synovial fluid in patients with rheumatoid arthritis and correlate with disease activity&#46; However&#44; the etiological and pathogenic relationship between IL-6 and IGD is unclear&#46; Certain cases of IGD may be mediated by this cytokine&#44; and therefore have more prominent neutrophilic infiltrate&#44; while others may be triggered by distinct molecular pathways&#46; Further basic and clinical research is necessary to uncover these pathways and&#44; most importantly&#44; to identify treatments that can most effectively shorten the natural course of the disease&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">In conclusion&#44; we present a case of IGD in a patient undergoing tocilizumab treatment&#44; and question the proposed utility of this antibody as a treatment for IGD&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0045" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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Case and Research Letters
Interstitial Granulomatous Dermatitis and Tocilizumab: Is This Treatment Useful for This Skin Condition?
Dermatitis granulomatosa intersticial y tocilizumab: ¿es este un tratamiento de utilidad para esta dermatosis?
D. de Perosanz Loboa,
Autor para correspondencia
dario.perosanz@gmail.com

Corresponding author.
, D. Saceda Corraloa, D. Ortega Quijanoa, R. Carrillo Gijónb
a Servicio de Dermatología, Hospital Universitario Ramón y Cajal, Madrid, Spain
b Servicio de Anatomía Patológica, Hospital Universitario Ramón y Cajal, Madrid, Spain
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    "titulo" => "Interstitial Granulomatous Dermatitis and Tocilizumab&#58; Is This Treatment Useful for This Skin Condition&#63;"
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        "titulo" => "Dermatitis granulomatosa intersticial y tocilizumab&#58; &#191;es este un tratamiento de utilidad para esta dermatosis&#63;"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Erythematous&#44; edematous&#44; nonscaling plaque with neat borders and annular morphology on the anterior aspect of the right arm&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Onset of interstitial granulomatous dermatitis &#40;IGD&#41;&#44; a rare skin disease with a variable clinical presentation and a characteristic pathological pattern&#44; has been associated with various systemic diseases and different drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Tocilizumab is a humanized monoclonal antibody directed against the interleukin-6 &#40;IL-6&#41; receptor&#44; and has been used to treat IGD with good results&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> We present a case of IGD that began while the affected patient was being treated with tocilizumab&#44; and question whether this drug is truly useful for the treatment of this disease&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The patient was a 62-year-old woman who had a history of antisynthetase syndrome with muscle&#44; lung&#44; and joint involvement and had started treatment with tocilizumab at a dose of 8<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;month&#46; She was referred to the dermatology service for slightly itchy&#44; mildly painful skin lesions that had appeared 9 months after beginning tocilizumab treatment&#46; The patient had no medical history of interest and had not been treated with any other drugs&#46; The lesions consisted of well defined&#44; infiltrated&#44; edematous&#44; erythematous plaques with no epidermal component that were prone to central clearing&#44; resulting in an arciform morphology &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The lesions were located on the armpits&#44; the shoulder girdle&#44; and the internal aspects of the arms &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">A skin biopsy revealed an unaltered epidermis&#44; interstitial histiocytic infiltrate with perivascular accentuation along the entire thickness of the dermis&#44; and an absence of mucin deposits&#46; In certain fields&#44; higher magnification revealed some interstitial and intravascular neutrophils &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#44; based on which a histopathological diagnosis of IGD was established&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The patient was prescribed topical mometasone every 12 hours&#44; without discontinuing tocilizumab treatment&#46; Three months later the lesions had disappeared&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">IGD is a rare dermatosis&#44; which most often appears in patients with rheumatologic diseases&#44; especially rheumatoid arthritis&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> although it has also been associated with solid and hematological malignancies &#40;especially myelodysplastic syndromes<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a>&#41;&#44; infections&#44; and treatment with different drugs&#44; including antihypertensives&#44; anticonvulsants&#44; antidepressants&#44; and immunosuppressants&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> Pathologically&#44; it is characterized by interstitial lymphohistiocytic infiltrate with variable presence of neutrophils and eosinophils&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> Leukocytoclastic vasculitis is occasionally observed&#44; and collagen fiber degeneration is a constant finding&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> The clinical spectrum is variable&#44; and consists of usually asymptomatic&#44; infiltrated&#44; pink&#44; erythematous or erythematous-violaceous papules or plaques&#44; generally without an epidermal component and occasionally with annular morphology&#46; Although infrequent&#44; the presence of indurated linear lesions on the lateral aspects of the trunk &#40;known as the <span class="elsevierStyleItalic">rope sign</span>&#41; is considered almost pathognomonic&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Most cases have a good prognosis without treatment&#44; resolving within 3 months to 3 years&#46; Approximately 30&#37; of cases follow a chronic course with flare-ups&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Although there are no definitive treatments for this disease&#44; it has been successfully treated with topical and systemic corticosteroids&#44; methotrexate&#44; ciclosporin&#44; and&#44; more recently&#44; etanercept&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Tocilizumab is a monoclonal antibody primarily used to treat rheumatoid arthritis&#46; Several skin reactions have been associated with tocilizumab administration&#44; including psoriasis-like reactions&#44;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> erythema multiforme-like lesions&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> acute generalized exanthematous pustulosis&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> and rheumatoid neutrophilic dermatosis&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> There are no cases of tocilizumab-induced IGD described in the literature&#46; However&#44; one report describes a satisfactory clinical response to tocilizumab treatment of IGD&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> suggesting a role of IL-6 in the development of granulomatous inflammation&#44; whereby neutrophils act as the main effector cells&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">In our case&#44; it was not possible to determine whether IGD was triggered by tocilizumab treatment&#59; the lesions resolved without discontinuing treatment and the patient had a history of rheumatological disease&#44; which may have contributed to the onset of this dermatosis&#46; However&#44; the fact that the lesions developed while the patient was undergoing tocilizumab treatment casts doubt on its effectiveness as a treatment for IGD and on the role of IL-6 in the pathogenesis of this disease&#46; As noted by Schanz and coworkers&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> the important pathogenic role of IL-6 in acute inflammation is well established&#59; levels of this cytokine are increased in serum and synovial fluid in patients with rheumatoid arthritis and correlate with disease activity&#46; However&#44; the etiological and pathogenic relationship between IL-6 and IGD is unclear&#46; Certain cases of IGD may be mediated by this cytokine&#44; and therefore have more prominent neutrophilic infiltrate&#44; while others may be triggered by distinct molecular pathways&#46; Further basic and clinical research is necessary to uncover these pathways and&#44; most importantly&#44; to identify treatments that can most effectively shorten the natural course of the disease&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">In conclusion&#44; we present a case of IGD in a patient undergoing tocilizumab treatment&#44; and question the proposed utility of this antibody as a treatment for IGD&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0045" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; de Perosanz Lobo D&#44; Saceda Corralo D&#44; Ortega Quijano D&#44; Carrillo Gij&#243;n R&#46; Dermatitis granulomatosa intersticial y tocilizumab&#58; &#191;es este un tratamiento de utilidad para esta dermatosis&#63; Actas Dermosifiliogr&#46; 2020&#59;111&#58;343&#8211;345&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Histology&#46; A&#44; Interstitial dermal infiltrate composed predominantly of histiocytes&#44; with some neutrophils &#40;hematoxylin-eosin&#44; original magnification &#215;200&#41;&#46; B&#44; Detail of previous image&#46; Neutrophils and lymphohistiocytic infiltrate are indicated with yellow arrows and red stars&#44; respectively &#40;hematoxylin-eosin&#44; original magnification &#215;400&#41;&#46;</p>"
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