Case Presentation: A fifty year old female with no significant past medical history presented with one year of acute on chronic bilateral periorbital swelling and twenty pound unintentional weight loss. She also complained of xerostomia and keratoconjunctivitis sicca. Review of systems was positive for intermittent nausea, vomiting, abdominal pain, pruritis, and neck swelling. The patient appeared jaundiced with scleral icterus, periorbital edema and submandibular lymphadenopathy. Lab tests showed total bilirubin 6.1, direct bilirubin 4.4, ALP 1448, AST 254 and ALT 267. A CT scan showed intra and extra hepatic biliary ductal dilatation with abrupt change in caliber at the mid aspect of the CBD. MRCP imaging showed a diffusely enlarged sausage shaped pancreas. CT of orbits revealed bilateral symmetric, marked enlargement of the lacrimal glands. A quantitative IgG level was 2114mg/dL (upper limit of normal is 1600 in our lab). A breakdown by subsets was surprising: IgG1 1190 (341-894), IgG2 966 (171-632), and IgG3 380 (18.4-106). However, IgG4 was squarely within normal range at 58.1. These values were confirmed with a second lab draw. Pancreas was diffusely hypoechoic on EUS. FNA pathology results showed pancreatic parenchyma with lymphoplasmacytic and eosinophilic infiltration, fibrosis and atrophy, without evidence of carcinoma. IgG4 stain performed at outside laboratory could not be interpreted due to technical failure. Given the histological findings, the characteristic imaging of a “sausage-shaped pancreas,” and the extra-pancreatic involvement seen in the lacrimal glands, a diagnosis of AIP was made and prednisone therapy was initiated. Bilirubin levels were between 7.2 and 9.7 prior to initiation of steroids. After one dose of prednisone, bilirubin was 5.0. After two weeks of treatment, bilirubin had normalized. Paradoxically, on subsequent evaluation of IgG subsets one month later, IgG4 was elevated at 183 and the remainder of the IgG subsets were within normal ranges.
Discussion: This case describes a patient with clinical presentation as well as characteristic histologic and imaging findings of AIP. The diagnostic criteria proposed by the Mayo Clinic include one or more of the following: diagnostic histology, characteristic CT imaging, elevation in IgG4 level, other organ involvement and clinical response to glucocorticoid therapy. Though elevation of serum IgG4 is one of the Mayo Clinic diagnostic criteria, it is not required to make the diagnosis. A 2016 meta-analysis found that a cutoff value of 135 to 144mg/dL conferred a sensitivity of 87 percent and a specificity of 83 percent in making the diagnosis of IgG4-RD. Our patient initially had a normal serum IgG4 level. However, an elevated serum IgG4 level was detected after the patient was treated with prednisone, suggestive of dynamic changes of serum IgG4 levels during the course of AIP. Only one case of delayed elevations of IgG4 levels in a patient with IgG4-related disease has been discussed in the available literature.
Conclusions: This case highlights a typical presentation of AIP with IgG4 elevation lagging behind clinical presentation of IgG4-RD. The incidence of IgG4-RD is likely under-estimated and it is important to maintain a high index of suspicion for IgG4-RD if diagnostic criteria are met, knowing that only one of the five criteria are required for diagnosis. Additionally, IgG4 levels can rise dynamically and should be assessed serially in a patient with suspected disease.