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Physical examination revealed an erythematous&#44; edematous plaque with a livedoid appearance and poorly defined borders&#44; covering the entire shoulder region and extending to the proximal third of the deltoids &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; A 4-mm punch biopsy was diagnostic&#44; showing dilated vessels in the reticular dermis that were positive for CD31&#44; CD34&#44; and D2-40 as well as CD68-positive intraluminal cell aggregates &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; The results of a full blood workup were normal&#44; including levels for complement&#44; immunoglobulins&#44; rheumatoid factor&#44; and C-reactive protein&#46; Magnetic resonance imaging showed signs of advanced joint degeneration and the possible existence of evolved primary synovial osteochondromatosis&#44; although no malignancy has been demonstrated to date&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The second patient was a 77-year-old woman who had been diagnosed with rheumatoid arthritis 20 years earlier and was receiving treatment with nonsteroidal anti-inflammatory drugs&#46; Two months after surgery on the left shoulder &#40;repair of a partial biceps tendon rupture&#41;&#44; she sought care for an asymptomatic patch that had gradually appeared in the weeks following the procedure &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; During rehabilitation treatment&#44; she was diagnosed with contact dermatitis&#44; although no clear causative agent was identified&#46; Topical corticosteroid treatment was prescribed&#44; but no response was achieved&#46; Physical examination revealed an erythematous&#44; edematous plaque with imprecise borders on the anterior surface of the left shoulder&#44; extending to the pectoral area&#46; Skin biopsy&#44; performed on the basis of clinical suspicion of intralymphatic histiocytosis&#44; showed dilated vessels in the reticular dermis that were positive for CD31&#44; CD34&#44; and D2-40 &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#44; CD68-positive cell aggregates inside lymphatic vessels of the reticular dermis&#44; and perivascular lymphohistiocytic inflammatory cellularity&#44; all confirming the diagnosis&#46; Treatment was started with topical tacrolimus&#44; applied once daily&#44; and oral pentoxifylline &#40;400<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#41;&#44; achieving an excellent response and practically complete resolution after 4 months of treatment &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0020" class="elsevierStylePara elsevierViewall">Intralymphatic histiocytosis is a rare entity that appears to be more frequent in older adults and in women&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1&#8211;5</span></a> The most common site is the limbs&#44; including the shoulder and hip areas&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">6</span></a> Intralymphatic histiocytosis has a nonspecific clinical presentation<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">5</span></a> and tends to manifest as a single erythematous plaque and occasionally in the form of papules or nodules&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">3</span></a> Most of the fewer than 60 cases described in the literature<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">3</span></a> are associated with rheumatoid arthritis&#44;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1&#8211;9</span></a> with skin alterations on the affected joints or&#44; less frequently&#44; in patients with prosthetic joint replacements&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1&#44;2&#44;5&#8211;7&#44;10</span></a> There have also been anecdotal reports of intralymphatic histiocytosis in association with surgical scars in patients with breast cancer<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1&#44;5</span></a> and Merkel cell carcinoma&#44;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1&#44;5</span></a> in the pectoral region of a patient with cancer of the colon&#44;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">2&#44;5</span></a> in the chest of a patient who underwent axillary lymphadenectomy to treat lymphatic tuberculosis&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">2</span></a> and in a patient with Crohn disease with involvement of the suprapubic region&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">2&#44;5</span></a> Cases of primary intralymphatic histiocytosis&#44; without association with any underlying disease&#44; have also been reported&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">2</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The etiology and pathogenesis of intralymphatic histiocytosis are not entirely understood&#44; as the disease has been associated with pathologic processes of various kinds&#46; Some authors classify it as a cutaneous reactive angiomatosis&#44; a histopathologic pattern that arises in reaction to various inflammatory processes&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1&#44;3&#44;7</span></a> The most widely accepted hypothesis is that the lymphatic vessels dilate in response to obstruction of lymphatic drainage caused by congenital abnormalities of the vessels&#44; or by acquired damage from trauma&#44; surgery&#44; radiotherapy&#44; or chronic inflammatory processes such as rheumatoid arthritis&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1&#44;7</span></a> Lymphostasis leads to poor antigen clearance&#44; thus chronically stimulating the proliferation and aggregation of histiocytes&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1&#44;2&#44;7</span></a> Chronic inflammation and the release of inflammatory mediators such as TNF and interleukin-6 perpetuate the process&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">3&#44;8</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The clinical differential diagnosis includes processes such as cellulitis&#44; contact dermatitis&#44; dermatomyositis&#44; and neoplastic vascular processes&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">2</span></a> Definitive diagnosis is established by histology and immunohistochemistry and the main entity that must be ruled out is intravascular lymphoma&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1&#44;5</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In both cases reported&#44; surgery performed before the appearance of the skin lesions may have altered lymphatic circulation&#46; A case of intralymphatic histiocytosis associated with severe osteoarthritis of the shoulder and rotator cuff arthropathy has also been reported&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">11</span></a> The magnetic resonance findings in our first patient were consistent with primary synovial osteochondromatosis&#44; a rare entity characterized by the metaplastic formation of multiple cartilaginous nodules in the connective tissue of the synovial membrane of the joints&#44; especially the knee and&#44; less frequently&#44; the hip&#44; with the possibility of malignancy&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">12</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In the management of intralymphatic histiocytosis&#44; systemic diseases&#8212;especially rheumatoid arthritis&#44;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1&#8211;6</span></a> the underlying disease in 1 of our patients&#8212;must be ruled out&#46; Skin lesions usually appear in the vicinity of affected joints&#44; although the clinical course of the disease does not parallel the activity of rheumatoid arthritis&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1&#44;6</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Although spontaneous involution is seen in some cases&#44; with regression occurring after treatment of the associated disease<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">6</span></a> or replacement of the prosthetic joint replacement in cases triggered by this surgery&#44;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1&#44;2</span></a> most cases are chronic and indolent&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">1</span></a> There is no specific treatment for intralymphatic histiocytosis&#46; Oral corticosteroids&#44; topical corticosteroids&#44; cyclophosphamide&#44; radiotherapy&#44; antiplatelet drugs such as salicylic acid plus amoxicillin&#8211;clavulanic acid&#44; pentoxifylline&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">5</span></a> anti-TNF drugs such as infliximab<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">8</span></a> and anti-interleukin-6 agents such as tocilizumab&#44;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">9</span></a> topical tacrolimus&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">13</span></a> etc&#46;&#44; have been used&#44; always in isolated cases&#44; usually with partial results and frequent recurrences&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">2&#44;6</span></a> One of our patients responded satisfactorily to treatment with oral pentoxifylline and topical tacrolimus for 4 months&#44; during which time the lesions resolved completely&#44; and no recurrence was detected 6 months after suspension of treatment&#46; Spontaneous involution cannot be ruled out but has not been common in the cases reported to date&#44; which have generally been refractory to treatment&#46; There have been 2 reports<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">5&#44;10</span></a> of cases with a positive response to pentoxifylline&#44; due to the anti-inflammatory&#44; antiplatelet&#44; and TNF-inhibitory effects of this drug&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">10</span></a> We found only 1 case<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">13</span></a> in which a good response was achieved with topical tacrolimus after 1 month of treatment&#44; although the mechanism of action in this disease is not clear&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conclusions</span><p id="par0050" class="elsevierStylePara elsevierViewall">We have reported 2 new cases of intralymphatic histiocytosis&#44; highlighting the importance of histopathologic and immunohistochemical diagnosis of this rare entity&#46; The first patient is the first case in which intralymphatic histiocytosis has been reported in association with primary synovial osteochondromatosis&#46; Both patients had a history of joint surgery that could have caused lymphatic drainage alterations&#44; triggering the onset of the disease&#46; We would also like to highlight the response to combination therapy with oral pentoxifylline and topical tacrolimus&#44; which is a good option for treating this chronic entity&#46; Given the rarity of intralymphatic histiocytosis&#44; it is difficult to carry out controlled studies to assess therapies and determine the role of isolated treatments in the clinical course of the lesions&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Ethical Disclosures</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Protection of persons and animals</span><p id="par0055" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for the purpose of this study&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Data confidentiality</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors declare that no private patient data appear in this article&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Right to privacy and informed consent</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors declare that no private patient data appear in this article&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conflicts of Interest</span><p id="par0070" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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            0 => "Histiocitosis intralinf&#225;tica"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Intralymphatic histiocytosis is a benign condition characterized by poorly defined erythematous plaques &#40;sometimes forming a reticular pattern&#41; as well as the presence of nodules and vesicles&#46; Its etiology and pathogenesis appear to be related to chronic inflammation in the affected area&#44; prior surgery&#44; or systemic disease&#44; particularly rheumatoid arthritis&#46; We report on 2 new cases&#44; both associated with joint surgery in the affected area and osteoarticular disease &#40;primary synovial osteochondromatosis and rheumatoid arthritis&#41;&#46; This is a chronic disease and there is no specific treatment&#46; Different treatment options were chosen in the 2 cases described&#46; A spectacular response to treatment with oral pentoxifylline and topical tacrolimus was observed in 1 of the patients&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La histiocitosis intralinf&#225;tica es un proceso benigno caracterizado por placas eritematosas mal delimitadas&#44; a veces reticuladas&#44; otras con n&#243;dulos o ves&#237;culas en su interior&#46; Su etiopatogenia parece estar relacionada con procesos inflamatorios cr&#243;nicos en el &#225;rea afectada&#44; cirug&#237;a previa o con enfermedades sist&#233;micas&#44; sobre todo con la artritis reumatoide&#46; Presentamos 2 nuevos casos&#44; ambos asociados a cirug&#237;a articular del &#225;rea afecta y enfermedad osteoarticular &#40;osteocondromatosis sinovial primaria y artritis reumatoide&#41;&#46; Esta entidad tiene un comportamiento cr&#243;nico y no existe un tratamiento espec&#237;fico&#46; En los 2 casos presentados se plantearon distintas opciones terap&#233;uticas&#44; mostrando uno de ellos una respuesta espectacular al tratamiento con pentoxifilina oral junto con tacrolimus t&#243;pico&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; G&#243;mez-S&#225;nchez ME&#44; Aza&#241;a-Defez JM&#44; Mart&#237;nez-Mart&#237;nez ML&#44; L&#243;pez-Villaescusa MT&#46; Histiocitosis intralinf&#225;tica&#44; a prop&#243;sito de 2 casos&#46; Actas Dermosifiliogr&#46; 2018&#59;109&#58;e1&#8211;e5&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Case 1&#46; Edematous plaque with a livedoid appearance and poorly delimited borders covering the entire shoulder region&#44; extending to the proximal third of the deltoids&#46;</p>"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Skin biopsy&#46; A&#44; Panoramic view &#40;hematoxylin-eosin&#44; original magnification &#215;100&#41; showing dilated vessels in the reticular dermis&#44; some with empty lumens and others with mononuclear cell aggregates&#46; B&#44; Positive staining for CD34 &#40;original magnification &#215;100&#41;&#46; C&#44; Positive staining for D2-40 &#40;original magnification &#215;400&#41;&#46; D&#44; Positive staining for CD31 &#40;original magnification &#215;100&#41;&#46; E&#44; Intraluminal cells positive for CD68&#46;</p>"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Case 2&#46; Erythematous&#44; edematous plaque with imprecise borders on the anterior surface of the left shoulder&#44; extending to the pectoral area&#46;</p>"
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                      "titulo" => "Cutaneous intralymphatic histiocytosis associated with rheumatoid arthritis&#58; Report of a case and review of the literature"
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                            2 => "F&#46;C&#46; Martin"
                            3 => "J&#46;J&#46; Fern&#225;ndez-Mera"
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e-Case Report
Intralymphatic Histiocytosis: A Report of 2 Cases
Histiocitosis intralinfática, a propósito de 2 casos
M.E. Gómez-Sáncheza,
Corresponding author
m_gomsanchez@hotmail.com

Corresponding author.
, J.M. Azaña-Defezb, M.L. Martínez-Martíneza, M.T. López-Villaescusac
a Servicio de Dermatología, Hospital General de Villarrobledo, Villarrobledo, Albacete, Spain
b Servicio de Dermatología, Hospital General de Albacete, Albacete, Spain
c Servicio de Dermatología, Hospital General de Almansa, Almansa, Albacete, Spain
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Skin biopsy&#46; Cells positive for D2-40 &#40;specific marker for lymphatic vessels&#41; in the vessel walls &#40;original magnification &#215;100&#41;&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Intralymphatic histiocytosis is a rare entity that was first described by O&#8217;Grady et al<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">1</span></a> in 1994&#46; Some 54 cases have since been reported&#44; most in association with rheumatoid arthritis and in patients with prosthetic joint replacements&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">2&#44;3</span></a> Because the clinical presentation is nonspecific&#44; diagnosis is fundamentally based on histologic findings&#46; Immunohistochemistry demonstrates the presence of dilated lymphatic vessels &#40;positive for D2-40&#44; CD34&#44; and CD31&#41; in the reticular dermis and aggregates of &#40;CD68-positive&#41; intraluminal histiocytes&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">2</span></a> It has been hypothesized that this dilation of the lymphatic vessels is caused by an obstruction of lymphatic drainage arising from either a congenital abnormality or acquired damage in the vessels&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">2</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case Descriptions</span><p id="par0010" class="elsevierStylePara elsevierViewall">The first patient was a 65-year-old woman who had undergone surgery to repair the rotator cuff of the left shoulder 1 year earlier&#46; She had no history of rheumatoid arthritis or other diseases&#46; The patient sought care for an erythematous and slightly pruritic patch on the left shoulder that had appeared 2 months earlier and had not responded to various regimens of oral antibiotics prescribed to treat the initial suspicion of cellulitis&#46; Physical examination revealed an erythematous&#44; edematous plaque with a livedoid appearance and poorly defined borders&#44; covering the entire shoulder region and extending to the proximal third of the deltoids &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; A 4-mm punch biopsy was diagnostic&#44; showing dilated vessels in the reticular dermis that were positive for CD31&#44; CD34&#44; and D2-40 as well as CD68-positive intraluminal cell aggregates &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; The results of a full blood workup were normal&#44; including levels for complement&#44; immunoglobulins&#44; rheumatoid factor&#44; and C-reactive protein&#46; Magnetic resonance imaging showed signs of advanced joint degeneration and the possible existence of evolved primary synovial osteochondromatosis&#44; although no malignancy has been demonstrated to date&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The second patient was a 77-year-old woman who had been diagnosed with rheumatoid arthritis 20 years earlier and was receiving treatment with nonsteroidal anti-inflammatory drugs&#46; Two months after surgery on the left shoulder &#40;repair of a partial biceps tendon rupture&#41;&#44; she sought care for an asymptomatic patch that had gradually appeared in the weeks following the procedure &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; During rehabilitation treatment&#44; she was diagnosed with contact dermatitis&#44; although no clear causative agent was identified&#46; Topical corticosteroid treatment was prescribed&#44; but no response was achieved&#46; Physical examination revealed an erythematous&#44; edematous plaque with imprecise borders on the anterior surface of the left shoulder&#44; extending to the pectoral area&#46; Skin biopsy&#44; performed on the basis of clinical suspicion of intralymphatic histiocytosis&#44; showed dilated vessels in the reticular dermis that were positive for CD31&#44; CD34&#44; and D2-40 &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#44; CD68-positive cell aggregates inside lymphatic vessels of the reticular dermis&#44; and perivascular lymphohistiocytic inflammatory cellularity&#44; all confirming the diagnosis&#46; Treatment was started with topical tacrolimus&#44; applied once daily&#44; and oral pentoxifylline &#40;400<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#41;&#44; achieving an excellent response and practically complete resolution after 4 months of treatment &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0020" class="elsevierStylePara elsevierViewall">Intralymphatic histiocytosis is a rare entity that appears to be more frequent in older adults and in women&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1&#8211;5</span></a> The most common site is the limbs&#44; including the shoulder and hip areas&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">6</span></a> Intralymphatic histiocytosis has a nonspecific clinical presentation<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">5</span></a> and tends to manifest as a single erythematous plaque and occasionally in the form of papules or nodules&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">3</span></a> Most of the fewer than 60 cases described in the literature<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">3</span></a> are associated with rheumatoid arthritis&#44;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1&#8211;9</span></a> with skin alterations on the affected joints or&#44; less frequently&#44; in patients with prosthetic joint replacements&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1&#44;2&#44;5&#8211;7&#44;10</span></a> There have also been anecdotal reports of intralymphatic histiocytosis in association with surgical scars in patients with breast cancer<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1&#44;5</span></a> and Merkel cell carcinoma&#44;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1&#44;5</span></a> in the pectoral region of a patient with cancer of the colon&#44;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">2&#44;5</span></a> in the chest of a patient who underwent axillary lymphadenectomy to treat lymphatic tuberculosis&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">2</span></a> and in a patient with Crohn disease with involvement of the suprapubic region&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">2&#44;5</span></a> Cases of primary intralymphatic histiocytosis&#44; without association with any underlying disease&#44; have also been reported&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">2</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The etiology and pathogenesis of intralymphatic histiocytosis are not entirely understood&#44; as the disease has been associated with pathologic processes of various kinds&#46; Some authors classify it as a cutaneous reactive angiomatosis&#44; a histopathologic pattern that arises in reaction to various inflammatory processes&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1&#44;3&#44;7</span></a> The most widely accepted hypothesis is that the lymphatic vessels dilate in response to obstruction of lymphatic drainage caused by congenital abnormalities of the vessels&#44; or by acquired damage from trauma&#44; surgery&#44; radiotherapy&#44; or chronic inflammatory processes such as rheumatoid arthritis&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1&#44;7</span></a> Lymphostasis leads to poor antigen clearance&#44; thus chronically stimulating the proliferation and aggregation of histiocytes&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1&#44;2&#44;7</span></a> Chronic inflammation and the release of inflammatory mediators such as TNF and interleukin-6 perpetuate the process&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">3&#44;8</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The clinical differential diagnosis includes processes such as cellulitis&#44; contact dermatitis&#44; dermatomyositis&#44; and neoplastic vascular processes&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">2</span></a> Definitive diagnosis is established by histology and immunohistochemistry and the main entity that must be ruled out is intravascular lymphoma&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1&#44;5</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In both cases reported&#44; surgery performed before the appearance of the skin lesions may have altered lymphatic circulation&#46; A case of intralymphatic histiocytosis associated with severe osteoarthritis of the shoulder and rotator cuff arthropathy has also been reported&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">11</span></a> The magnetic resonance findings in our first patient were consistent with primary synovial osteochondromatosis&#44; a rare entity characterized by the metaplastic formation of multiple cartilaginous nodules in the connective tissue of the synovial membrane of the joints&#44; especially the knee and&#44; less frequently&#44; the hip&#44; with the possibility of malignancy&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">12</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In the management of intralymphatic histiocytosis&#44; systemic diseases&#8212;especially rheumatoid arthritis&#44;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1&#8211;6</span></a> the underlying disease in 1 of our patients&#8212;must be ruled out&#46; Skin lesions usually appear in the vicinity of affected joints&#44; although the clinical course of the disease does not parallel the activity of rheumatoid arthritis&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1&#44;6</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Although spontaneous involution is seen in some cases&#44; with regression occurring after treatment of the associated disease<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">6</span></a> or replacement of the prosthetic joint replacement in cases triggered by this surgery&#44;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1&#44;2</span></a> most cases are chronic and indolent&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">1</span></a> There is no specific treatment for intralymphatic histiocytosis&#46; Oral corticosteroids&#44; topical corticosteroids&#44; cyclophosphamide&#44; radiotherapy&#44; antiplatelet drugs such as salicylic acid plus amoxicillin&#8211;clavulanic acid&#44; pentoxifylline&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">5</span></a> anti-TNF drugs such as infliximab<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">8</span></a> and anti-interleukin-6 agents such as tocilizumab&#44;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">9</span></a> topical tacrolimus&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">13</span></a> etc&#46;&#44; have been used&#44; always in isolated cases&#44; usually with partial results and frequent recurrences&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">2&#44;6</span></a> One of our patients responded satisfactorily to treatment with oral pentoxifylline and topical tacrolimus for 4 months&#44; during which time the lesions resolved completely&#44; and no recurrence was detected 6 months after suspension of treatment&#46; Spontaneous involution cannot be ruled out but has not been common in the cases reported to date&#44; which have generally been refractory to treatment&#46; There have been 2 reports<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">5&#44;10</span></a> of cases with a positive response to pentoxifylline&#44; due to the anti-inflammatory&#44; antiplatelet&#44; and TNF-inhibitory effects of this drug&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">10</span></a> We found only 1 case<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">13</span></a> in which a good response was achieved with topical tacrolimus after 1 month of treatment&#44; although the mechanism of action in this disease is not clear&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conclusions</span><p id="par0050" class="elsevierStylePara elsevierViewall">We have reported 2 new cases of intralymphatic histiocytosis&#44; highlighting the importance of histopathologic and immunohistochemical diagnosis of this rare entity&#46; The first patient is the first case in which intralymphatic histiocytosis has been reported in association with primary synovial osteochondromatosis&#46; Both patients had a history of joint surgery that could have caused lymphatic drainage alterations&#44; triggering the onset of the disease&#46; We would also like to highlight the response to combination therapy with oral pentoxifylline and topical tacrolimus&#44; which is a good option for treating this chronic entity&#46; Given the rarity of intralymphatic histiocytosis&#44; it is difficult to carry out controlled studies to assess therapies and determine the role of isolated treatments in the clinical course of the lesions&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Ethical Disclosures</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Protection of persons and animals</span><p id="par0055" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for the purpose of this study&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Data confidentiality</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors declare that no private patient data appear in this article&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Right to privacy and informed consent</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors declare that no private patient data appear in this article&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conflicts of Interest</span><p id="par0070" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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            2 => "Artritis reumatoide"
            3 => "Tratamiento"
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      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Intralymphatic histiocytosis is a benign condition characterized by poorly defined erythematous plaques &#40;sometimes forming a reticular pattern&#41; as well as the presence of nodules and vesicles&#46; Its etiology and pathogenesis appear to be related to chronic inflammation in the affected area&#44; prior surgery&#44; or systemic disease&#44; particularly rheumatoid arthritis&#46; We report on 2 new cases&#44; both associated with joint surgery in the affected area and osteoarticular disease &#40;primary synovial osteochondromatosis and rheumatoid arthritis&#41;&#46; This is a chronic disease and there is no specific treatment&#46; Different treatment options were chosen in the 2 cases described&#46; A spectacular response to treatment with oral pentoxifylline and topical tacrolimus was observed in 1 of the patients&#46;</p></span>"
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      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La histiocitosis intralinf&#225;tica es un proceso benigno caracterizado por placas eritematosas mal delimitadas&#44; a veces reticuladas&#44; otras con n&#243;dulos o ves&#237;culas en su interior&#46; Su etiopatogenia parece estar relacionada con procesos inflamatorios cr&#243;nicos en el &#225;rea afectada&#44; cirug&#237;a previa o con enfermedades sist&#233;micas&#44; sobre todo con la artritis reumatoide&#46; Presentamos 2 nuevos casos&#44; ambos asociados a cirug&#237;a articular del &#225;rea afecta y enfermedad osteoarticular &#40;osteocondromatosis sinovial primaria y artritis reumatoide&#41;&#46; Esta entidad tiene un comportamiento cr&#243;nico y no existe un tratamiento espec&#237;fico&#46; En los 2 casos presentados se plantearon distintas opciones terap&#233;uticas&#44; mostrando uno de ellos una respuesta espectacular al tratamiento con pentoxifilina oral junto con tacrolimus t&#243;pico&#46;</p></span>"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; G&#243;mez-S&#225;nchez ME&#44; Aza&#241;a-Defez JM&#44; Mart&#237;nez-Mart&#237;nez ML&#44; L&#243;pez-Villaescusa MT&#46; Histiocitosis intralinf&#225;tica&#44; a prop&#243;sito de 2 casos&#46; Actas Dermosifiliogr&#46; 2018&#59;109&#58;e1&#8211;e5&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Case 1&#46; Edematous plaque with a livedoid appearance and poorly delimited borders covering the entire shoulder region&#44; extending to the proximal third of the deltoids&#46;</p>"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Skin biopsy&#46; A&#44; Panoramic view &#40;hematoxylin-eosin&#44; original magnification &#215;100&#41; showing dilated vessels in the reticular dermis&#44; some with empty lumens and others with mononuclear cell aggregates&#46; B&#44; Positive staining for CD34 &#40;original magnification &#215;100&#41;&#46; C&#44; Positive staining for D2-40 &#40;original magnification &#215;400&#41;&#46; D&#44; Positive staining for CD31 &#40;original magnification &#215;100&#41;&#46; E&#44; Intraluminal cells positive for CD68&#46;</p>"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Case 2&#46; Erythematous&#44; edematous plaque with imprecise borders on the anterior surface of the left shoulder&#44; extending to the pectoral area&#46;</p>"
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Skin biopsy&#46; Cells positive for D2-40 &#40;specific marker for lymphatic vessels&#41; in the vessel walls &#40;original magnification &#215;100&#41;&#46;</p>"
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Complete resolution of symptoms following treatment with oral pentoxifylline and topical tacrolimus&#46;</p>"
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                          "etal" => false
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                            0 => "B&#46; De Unamuno Bustos"
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Article information
ISSN: 15782190
Original language: English
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Idiomas
Actas Dermo-Sifiliográficas
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