Case Report
Dacryoadenitis Associated With IgG4-related Disease in an Afro-Colombian Adolescent
Dacrioadenitis por enfermedad relacionada con IgG4 en una adolescente afrodescendiente de Colombia
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class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Departamento de Medicina Interna, Universidad del Valle, Cali, Colombia" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Medicina Interna-Reumatología, Universidad del Valle, Cali, Colombia" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Departamento de Microbiología, Universidad del Valle, Cali, Colombia" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Dacrioadenitis por enfermedad relacionada con IgG4 en una adolescente afrodescendiente de Colombia" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1468 "Ancho" => 1500 "Tamanyo" => 217918 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">(A) Right proptosis at the onset of the clinical symptoms. (B) T1-weighted postcontrast cross-sectional magnetic resonance image (MRI) at admission. Note the enlargement of right lacrimal gland, with enhancement after the administration of contrast medium. (C) Decrease in proptosis after 1 year of follow-up. (D) T1-weighted postcontrast cross-sectional MRI after 1 year of follow-up. Note the decrease in the size of right lacrimal gland versus baseline MRI.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Immunoglobulin (Ig) G4-related disease (IgG4-RD) is an immune-mediated inflammatory condition that mimics autoimmune and infectious disorders and malignancies, with specific organ or multisystemic involvement.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> It is most prevalent in Asian men, between the fifth and sixth decades of life, with orbital involvement being the most widespread extrapancreatic manifestation.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> We report a case of dacryoadenitis in an Afro-Colombian adolescent as an uncommon form of IgG4-RD.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case Description</span><p id="par0010" class="elsevierStylePara elsevierViewall">The patient was a 13-year-old Afro-Colombian girl. She presented with ocular pain and proptosis in right eye that had begun 7 days earlier (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A); she mentioned nothing similar in her history. The ophthalmological study found orbital asymmetry and lowered gaze and proptosis in right eye (exophthalmometry in right eye 22<span class="elsevierStyleHsp" style=""></span>mm, left eye 18<span class="elsevierStyleHsp" style=""></span>mm). Orbital magnetic resonance imaging (MRI) showed an increase in the size of right lacrimal gland causing a mass effect, suggestive of an inflammatory or neoplastic process, with no bone involvement.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Chest and abdominal computed tomography, an aspirate, bone marrow biopsy and immunophenotype, infectious markers (enzyme-linked immunosorbent assay for human immunodeficiency virus, anti-hepatitis C virus, hepatitis B surface antigen, anti-hepatitis B core antibody), thyroid-stimulating hormone/free thyroxine, C-reactive protein, erythrocyte sedimentation rate, complement (C3–C4), antinuclear antibodies, extractable nuclear antigens, antineutrophil cytoplasmic antibodies and serum immunoglobulin levels were normal or negative; the latter ruled out the presence of paraproteinemia and humoral immunodeficiencies.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The biopsy of right lacrimal gland revealed storiform fibrosis, stromal sclerosis, obliterative phlebitis and inflammatory infiltrate (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A and B). Inflammatory pseudotumor was considered by the pediatricians, and treatment was begun with prednisone at 50<span class="elsevierStyleHsp" style=""></span>mg/day.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Follow-up MRI performed 9 months later in rheumatology showed a reduction in the size of the lacrimal gland, and serum IgG4 was normal. An immunohistochemical study revealed an extensive infiltrate of IgG4+ plasms cells with an IgG4/IgG ratio<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>40% consistent with dacryoadenitis associated with IgG4-RD (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>C and D). Treatment was begun with azathioprine, as a steroid sparing agent, which achieved sustained clinical and radiological improvement (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C and D).</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0030" class="elsevierStylePara elsevierViewall">IgG4-related disease is a fibroinflammatory, multiorgan, immune-mediated condition,<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> described in 1961 in the context of pancreatitis associated with hypergammaglobulinemia. It was later associated with high serum IgG4 levels and, in 2003, was recognized as a systemic disease when extrapancreatic manifestations were described.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> IgG4 is the least abundant of the subclasses of IgG. It is a poor activator of the classical complement cascade and its production is induced by interleukin (IL) 10 (T regulatory cells and T helper cells [Th2]). Although the physiological mechanism of IgG4-RD is not clearly elucidated, associations with human leukocyte antigen (HLA) polymorphisms (HLA DRB1*0405, DQB1*0401 or DQβ1-57) have been described, molecular mimicry between <span class="elsevierStyleItalic">Helicobacter pylori</span> and proteins of pancreatic acinar cells,<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> just as IgG4 specifies 17 salivary and lacrimal gland antigens (IgG4 complex analysis), which could explain the preferential involvement of these organs<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><p id="par0035" class="elsevierStylePara elsevierViewall">The diagnosis of IgG4-RD is based on clinical and radiological findings, as well as serological evidence (IgG4<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>135<span class="elsevierStyleHsp" style=""></span>mg/dL) and histological manifestations (storiform fibrosis, obliterative phlebitis and tissue infiltration by >10 IgG4+ plasma cells per high-power field with a IgG4:IgG<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>40%).<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> Our patient met all of the criteria except for the serological finding, but IgG4 may not have been detected because she had been taking steroids for 9 months.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Autoimmune pancreatitis is the most common presentation, whether or not it is associated with extrapancreatic involvement. Periorbital tissue is among the regions most frequently involved (in up to 39% of the patients).<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> IgG4-related diseases predominantly affect men over 50 years of age. The majority of the patients are Asian, especially Japanese, and the prevalence is estimated to be 6 cases per 100,000 population.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> We found 1 case of dacryoadenitis reported in Latin America, in a study involving biopsy specimens,<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> but none in Afro-descendant adolescent women or the pediatric population. This is the second case of dacryoadenitis associated with IgG4-RD in a child reported in the literature, preceded only by that of a 13-year-old white North American girl.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Oral corticosteroids, with or without azathioprine or mycophenolate mofetil, are the treatment of choice. Our patient received prednisone as monotherapy for 9 months. The addition of azathioprine on the part of the rheumatology department enabled us to reduce the steroid dose, achieving a satisfactory clinical and radiological response.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Ethical Disclosures</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Protection of human and animal subjects</span><p id="par0050" class="elsevierStylePara elsevierViewall">The authors declare that the procedures followed were in accordance with the regulations of the relevant clinical research ethics committee and with those of the Code of Ethics of the World Medical Association (Declaration of Helsinki).</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Confidentiality of data</span><p id="par0055" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Right to privacy and informed consent</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors have obtained the written informed consent of the patients or subjects mentioned in the article. The corresponding author is in possession of this document.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conflicts of Interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors declare they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres1025204" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec982993" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1025205" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec982992" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Case Description" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Ethical Disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Right to privacy and informed consent" ] ] ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflicts of Interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-06-28" "fechaAceptado" => "2016-11-04" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec982993" "palabras" => array:3 [ 0 => "Dacryoadenitis" 1 => "IgG4-related disease" 2 => "Adolescent" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec982992" "palabras" => array:3 [ 0 => "Dacrioadenitis" 1 => "Enfermedad relacionada con IgG4" 2 => "Adolescente" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">IgG4-related disease (IgG4-RD) is a recently recognized clinical condition with multiple aspects not yet elucidated. It is characterized by a fibrous inflammatory process that involves multiple organs and clinical, serological and histopathological findings, which represent a major challenge for the clinician. Classically described as an expansive tumor lesion with storiform fibrosis, lymphoplasmacytic infiltration (IgG4-positive) and elevated serum IgG4. Clinical features are variable, and pancreatic as well as extrapancreatic involvement has been reported, more frequently in Asian men over 50 years and rarely described in black people. We report the case of an Afro-Colombian teenage woman, who had a unilateral ocular protrusion of unknown cause, with histopathologic findings that revealed infiltration of lymphocyte and plasma cells into the lacrimal gland. It was positive for IgG4, ruling out other conditions, and confirming IgG4-related dacryoadenitis.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La enfermedad relacionada con IgG4 (ER-IgG4) es una condición clínica recientemente reconocida, con múltiples aspectos aún no dilucidados. Se caracteriza por el compromiso fibroinflamatorio de múltiples órganos; con hallazgos clínicos, serológicos e histopatológicos que representa un importante reto para el clínico. Clásicamente descrita como una lesión tumoral expansiva con fibrosis estoriforme, infiltración linfoplasmocítica (IgG4 positiva) e IgG4 sérica elevada. Las características clínicas son variables, se describe tanto compromiso pancreático como extrapancreático, es de predominio en varones asiáticos mayores de 50 años, y rara vez es descrita en personas de raza negra. Presentamos el caso de una mujer, adolescente, afro-colombiana, que presenta protrusión ocular unilateral inexplicable, con hallazgos histopatológicos que revelan infiltración de células linfocíticas y plasmáticas en la glándula lacrimal, con positividad para IgG4, descartándose otras condiciones, lo que confirma una dacrioadenitis por enfermedad relacionada con IgG4.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Díaz-Ramírez GS, Medina-Quintero LF, Salinas-César A, Zea-Vera AF. Dacrioadenitis por enfermedad relacionada con IgG4 en una adolescente afrodescendiente de Colombia. Reumatol Clin. 2018;14:164–167.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1468 "Ancho" => 1500 "Tamanyo" => 217918 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">(A) Right proptosis at the onset of the clinical symptoms. (B) T1-weighted postcontrast cross-sectional magnetic resonance image (MRI) at admission. Note the enlargement of right lacrimal gland, with enhancement after the administration of contrast medium. (C) Decrease in proptosis after 1 year of follow-up. (D) T1-weighted postcontrast cross-sectional MRI after 1 year of follow-up. Note the decrease in the size of right lacrimal gland versus baseline MRI.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1272 "Ancho" => 1500 "Tamanyo" => 576104 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Lacrimal gland biopsy. Hematoxylin–eosin staining: (A) Storiform fibrosis, stromal sclerosis and chronic inflammatory infiltrate (×10); (B) Veins with walls swollen with the infiltration of mononuclear inflammatory cells causing obliteration of the lumen. Immunohistochemical staining (×40). (C) Extensive infiltration of plasma cells expressing CD (cluster of differentiation) 38 (anti-CD38 with 3,3′-diaminobenzidine [DAB] staining, ×40); (D) IgG4-positive plasma cells (anti-IgG4 DAB staining, ×40).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "IgG4-related disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "T. Kamisawa" 1 => "Y. Zen" 2 => "S. Pillai" 3 => "J.H. 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