Letter to the Editor
IgG4 autoimmune sclerosing cholangitis
Colangitis esclerosante autoinmune IgG4
Alejandro Mínguez Sabater
, Pablo Ladrón Abia, M. Dolores Higón Ballester
Corresponding author
Servicio de Gastroenterología y Hepatología, Hospital Universitario Politécnico La Fe, Valencia, Spain
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Dolores Higón Ballester" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Alejandro" "apellidos" => "Mínguez Sabater" "email" => array:1 [ 0 => "alejandromsab11@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Pablo" "apellidos" => "Ladrón Abia" ] 2 => array:2 [ "nombre" => "M. Dolores" "apellidos" => "Higón Ballester" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Gastroenterología y Hepatología, Hospital Universitario Politécnico La Fe, Valencia, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Colangitis esclerosante autoinmune IgG4" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1151 "Ancho" => 1500 "Tamanyo" => 199926 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Irregular bile duct stenosis with retrograde dilatation (yellow arrows). Poor visualization of the major pancreatic duct. Cholelithiasis (yellow asterisks).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Immunoglobulin G4-related disease (IgG4-RD) encompasses different entities characterized by a lymphoplasmacytic infiltrate, a predominance of IgG4<span class="elsevierStyleSup">+</span> plasma cells in the affected tissues, and the likelihood of developing fibrosis in the long term.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Immunoglobulin G4-related sclerosing cholangitis is a rare disease in the differential diagnosis of cholestatic jaundice. Given that no clear diagnostic criteria have been established for this condition, a significant clinical suspicion is required to diagnose it and begin treatment for its clinical improvement.</p><p id="par0010" class="elsevierStylePara elsevierViewall">In this regard, we hereby report the case of a 54-year-old male who was admitted to the Gastroenterology Department due to presenting with a four-day history of epigastric pain, choluria, and acholia, as well as a weight loss of 11 kg over a three-month period. The blood tests performed revealed increased bilirubin (4.32 mg/dl) and transaminase levels. An ultrasound showed signs of dilatation of the intrahepatic bile duct, infundibular cholelithiasis, and a normal common bile duct. A magnetic resonance cholangiopancreatography (MRCP) confirmed the existence of obstructive dilatation of the bile duct in relation to the presence of a mass in the head and uncinate process of the pancreas, thus suggesting a differential diagnosis of either a pancreatic neoplasm or focal pancreatitis. The diagnostic studies were further expanded with a thoracoabdominopelvic computed tomography (CT) in which the pancreatic mass did not seem to correspond to a neoplasm, thus modifying the differential diagnosis to either focal chronic pancreatitis or a systemic process owing to the thoracic findings of a micronodular pulmonary pattern in the upper lung lobes, as well as calcified mediastinal and hilar adenopathies.</p><p id="par0015" class="elsevierStylePara elsevierViewall">An upper endoscopic ultrasound with a fine needle aspiration biopsy (FNAB) was also performed, detecting a hypoechogenic area (2 cm) in the head of the pancreas and a pancreatic duct of normal caliber. In addition, adenopathies were identified in the posterior mediastinum, the gastrohepatic ligament, and the periduodenal region. The pancreatic mass was biopsied and sent for analysis, obtaining an inconclusive result for malignancy.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Because of the above, the diagnostic studies were further expanded with immunohistochemical determinations that revealed IgG4 subclass levels of 733 mg/dl (normal value 140), positivity for antinuclear antibodies (ANAs) 1/160, positivity for anti-neutrophil cytoplasmic antibodies (ANCAs) 1/160, and carbohydrate antigen 19.9 (CA 19-9) levels of 291 U/mL. Given that an IgG4-RD was suspected, the images of the MRCP were reviewed again, observing signs that were highly suggestive of biliary tree involvement of autoimmune etiology (radiological findings shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Based on the above, the patient was diagnosed with IgG4-related autoimmune cholangitis and intravenous (i.v.) corticosteroid therapy at a dosage of 0.6 mg/kg/day was consequently started, achieving a gradual decrease in his bilirubin and cholestasis enzyme levels, as well as of his CA 19-9 levels as of the fourth day of treatment. After two months of treatment with oral corticosteroids at a dosage of 40 mg/day, the patient’s cholestasis parameters had returned to normal levels and his CA 19-9 and IgG levels had decreased significantly.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Immunoglobulin G4-related sclerosing cholangitis is the second most frequent manifestation of IgG-RD after autoimmune pancreatitis (type 1), with which it is associated in 70% of cases.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Serum IgG4 levels are elevated in two out of every three patients with this condition, although these levels can be normal despite detecting the typical histopathological findings of the disease.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The most frequent clinical manifestation of this ailment is obstructive jaundice, which is present at the time of diagnosis in 77% of cases.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The differential diagnosis must include both cholangiocarcinoma and chronic cholestases, such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC).<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Because there are no established diagnostic criteria for IgG4-related sclerosing cholangitis, only its histological findings, increased IgG4 serum levels, and response to corticosteroid therapy can orient the diagnosis of this entity.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Treatment is recommended for all symptomatic patients and for asymptomatic patients presenting with persistent alterations in their imaging tests or biochemical liver function parameters. Involvement of other organs may also be an indication to start treatment.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Consensus guidelines recommend corticosteroid therapy as the first-line treatment to induce remission (0.6 mg/kg), with subsequent dose tapering, although some patients appear to benefit from maintenance therapy. Re-treatment with corticosteroids would be indicated in patients who relapse after successful induction, together with the addition of immunosuppressors with a view to maintain the remission or in the event of corticosteroid toxicity (azathioprine, mycophenolate, or cyclophosphamide).<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> In the event of a contraindication or resistance to corticosteroids, i.v. rituximab at a dose of 1 mg administered twice daily for 15 days would be a valid induction alternative.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The prognosis of this condition is variable, often with a high initial response rate, but with frequent relapses, primarily after treatment discontinuation.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> A higher risk has been described in cases with high IgG4 levels or proximal bile duct involvement.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0065" class="elsevierStylePara elsevierViewall">This study has not received any external funding nor cooperation.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Mínguez Sabater A, Ladrón Abia P, Higón Ballester MD. Colangitis esclerosante autoinmune IgG4. Med Clin (Barc). 2021;156:414–415.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1151 "Ancho" => 1500 "Tamanyo" => 199926 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Irregular bile duct stenosis with retrograde dilatation (yellow arrows). Poor visualization of the major pancreatic duct. Cholelithiasis (yellow asterisks).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Consensus statement on the pathology of IgG4-related disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V. Deshpande" 1 => "Y. Zen" 2 => "J.K. Chan" 3 => "E.E. Yi" 4 => "Y. Sato" 5 => "T. Yoshino" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/modpathol.2012.72" "Revista" => array:5 [ "tituloSerie" => "Mod Pathol." 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