Type 1 AIP is commonly accompanied by sclerosing cholangitis [15]. The histology of IgG4-related sclerosing cholangitis (IgG4-SC) shows obliterative phlebitis and transmural fibrosis with dense infiltration of IgG4-positive plasma cells, which lead to stricture of the bile duct.

IgG4-SC must be differentiated from primary sclerosing cholangitis (PSC). Inflammatory bowel disease (IBD) is frequently seen in PSC patients, whereas it is rare in IgG4-SC. Nakazawa et al. reported that the typical findings of IgG4-SC in ERCP are “segmental stricture,” “long stricture with prestenotic dilatation,” and “stricture of the lower bile duct,” while the typical findings of PSC are “band-like stricture,” “beaded appearances,” “pruned-tree appearance,” and “diverticulum-like appearance” [16]. Whether the limited intrapancreatic bile duct stricture associated with AIP should be regarded as a biliary manifestation of IgG4-related disease is controversial, because such stenosis can be induced by compression from the swollen pancreas [17].

IgG4-SC must be also differentiated from cholangiocarcinoma . Neither serum IgG4 concentrations nor cholangiographic findings differentiate these disorders clearly [18]. Endoscopic transpapillary biopsy is generally performed. Although cholangiocarcinoma can be excluded by endoscopic biopsy, the superficial nature of samples obtained by this procedure limits their usefulness for diagnosis of IgG4-SC [19].

Cholecystitis can occur with sclerosing cholangitis. Thickening of the gallbladder wall is detected on imaging, but it is asymptomatic in most cases [20].

The major duodenal papilla is frequently swollen in patients with type1 AIP. Endoscopic biopsy from the major papilla is a useful adjunctive method because the papilla is often involved pathologically in AIP [21, 22].

Retroperitoneal fibrosis (RF ) is a rare disease characterized by the presence of fibro-inflammatory tissue that develops around the abdominal aorta and iliac arteries. IgG4-related disease is the cause of up to two-thirds of cases of RF [23]. Chiba et al. [24] proposed diagnostic criteria for IgG4-related retroperitoneal fibrosis (IgG4-RF) consisting of three items: typical radiological features, elevation of serum IgG4 levels and the histological finding of an abundant infiltration of IgG4-positive plasma cells at a retroperitoneal mass or extraretroperitoneal sites. In their series of 10 IgG4-RF patients, IgG4-RF showed a predilection for elderly men. Symptoms predominantly related to RF (back pain and edema of the lower extremities) were observed in only two patients, and the remaining patients reported initial symptoms due to associated diseases. Twenty-four other IgG4-related diseases (AIP, sialadenitis, dacryoadenitis, lymphadenopathy, pulmonary pseudotumor, and pituitary pseudotumor) occurred in nine patients. On laboratory examinations, anemia, hypoalbuminemia, increased CRP levels, and antinuclear antigen (ANA) positivity were frequently observed. IgG4-RF responds well to steroids, but malignancies including malignant lymphoma should be ruled out.

Major and minor salivary glands can be affected. This disorder was known for more than a century as Mikulicz’s disease, consisting of dacryoadenitis and enlargement of the parotid and submandibular glands, and it is now recognized as an IgG4-related disease [25]. Isolated enlargement of the submandibular glands is common in IgG4-related disease. In contrast, in Sjogren’s syndrome, parotid enlargement predominates. Xerostomia commonly accompanies IgG4-related disease, but it is generally less severe than in Sjogren’s syndrome, and in contrast to Sjogren’s syndrome, it can improve with immunosuppression.

The typical presentation of orbital involvement is swelling within the ocular region or frank proptosis, generally caused by lacrimal-gland enlargement (dacryoadenitis) [26, 27]. Proptosis can also result from orbital pseudotumors that do not affect the lacrimal gland, from involvement of extraocular muscles (orbital myositis), and from combinations of these abnormalities.

The most characteristic form of IgG4-related renal involvement is tubulointerstitial nephritis. The histology of this disease is the same as in other organs: lymphoplasmacytic infiltration with IgG4 predominance among plasma cells; storiform fibrosis; and moderate tissue eosinophilia [28].

Many patients with IgG4-related tubulointerstitial nephritis have substantial enlargements of the kidneys and hypodense lesions evident on CT. The clinical presentation can show advanced renal dysfunction and even end-stage renal dysfunction. Substantial proteinuria can develop, but concentrations are generally subnephrotic.