A seven year old girl was referred to our hospital with abdominal pain and nausea, which started two weeks ago, and she also described mild pruritus in the last week. There was slight jaundice, epigastric tenderness, and hepatomegaly on physical examination. Laboratory investigations revealed hypertransaminasemia and marked elevation in alkaline phosphatase and gamma-glutamyl transpeptidase, while total bilirubin, direct bilirubin, lipase and pancreatic amylase were slightly increased. Acute-phase reactants such as white blood cell count, platelet count, C-reactive protein, and erythrocyte sedimentation rate were markedly elevated, which were compatible with a systemic inflammation. Viral hepatitis serology was negative.
The patients had hypergammaglobulinemia (serum IgG 2 710 mg/dL, upper limit of normal for age <1 682 mg/dL), and a significant elevation in serum IgG4 level (143 mg/dL, N: 1.0-108.7 mg/dL) was observed. Antinuclear antibody (ANA) and perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) were positive by indirect immunofluorescence test, whereas liver kidney microsome type 1 antibody (anti-LKM-1), anti-mitochondrial antibody (AMA), anti-smooth muscle antibody (ASMA) were negative. Magnetic resonance imaging (MRI) of the abdomen revealed hepatomegaly with a heterogeneous parenchyma of the liver and a diffuse enlargement of the pancreas, surrounded by a capsule-like rim, and it was compatible with autoimmune pancreatitis (Fig. 1). Further radiologic investigation with magnetic resonance cholangiopancreatography (MRCP) confirmed a narrowing at the bifurcation of the common hepatic duct and mild dilatation of intrahepatic bile ducts (Fig. 1). The histopathologic examination of liver biopsy showed lymphoplasmacytic inflammation around the portal bile ducts with periportal fibrosis and mild bridging necrosis (Fig. 2). Furthermore, immunostaining of the liver biopsy revealed intense IgG, but only scarce IgG4 (+) plasma cells (8 plasma cells/high-power field). The patient was given ursodeoxycholic acid 15 mg/kg/day treatment.
During follow-up, the patient reported bilateral orbital edema around the upper orbital rim and the eyelid with no pain or erythema. Orbital MRI demonstrated enlarged lacrimal glands with contrast enhancement (Fig. 1). On the second month of admission, the patient developed bloody diarrhea and underwent an ileo-colonoscopy. All colonic segments were erythematous and scattered exudative lesions were more pronounced in the distal colon. A histopathologic examination of the colonic biopsies demonstrated lymphoplasmacytic inflammation in lamina propria, cryptitis, destruction of crypts, and vasculitis. Hence, both the endoscopic and the pathologic findings were consistent with IBD, favoring ulcerative colitis. Upper GI tract endoscopy revealed erosions in the duodenum, and histopathology confirmed duodenitis with patchy lymphoplasmacytic inflammation and focally enhanced gastritis.
The patient was investigated for tuberculosis and missing vaccines were completed before commencing long-term immunosuppressive therapy. Later on, treatment with intravenous methylprednisolone 1.5 mg/kg/day, oral mesalazine 60 mg/kg/day was initiated. Methylprednisolone was gradually tapered to 4 mg/day over 10 weeks. Her signs and symptoms improved dramatically, and follow-up imaging of the abdomen at the second week of treatment demonstrated complete resolution of pancreatic enlargement (Fig. 3). The initial peak of total IgG (3 350 mg/dL) and IgG4 (177 mg/dL) levels improved to 1790 mg/dL and 77 mg/dL, respectively 2 weeks later. At the 3rd month of treatment, serum ESR and CRP levels improved and returned to normal. The patient has been asymptomatic while using 4 mg/day methylprednisolone treatment, and laboratory examinations have been normal during the last 12 months of follow-up. A written informed consent of the patient is obtained.