Case of Autoimmune Pancreatitis with Pancreatic Mass with Obstructive Jaundice, Timely Diagnosis Saved from the Major Surgery

Diagnosis

Universally accepted criteria for diagnosis of AIP are HISORt Criteria given by the Mayo clinic based on 5 main diagnostic criteria: histological chracterstics, imaging findings, serology, other organ involvement and response to steroid therapy [4]. H-Histological characteristics, 3 histologic key findings are Lymphoplasmacytic infiltration affecting the tissue either diffusely or patchy and focusing on ducts. For the diagnosis of AIP, the number of IgG4 plasma cells should exceed 50 cells/high-power field (HPF) in surgical specimens and 10 cells/HPF in biopsy samples. Storiform fibrosis composed of thick collagen bundles which form a characteristic “swirling” and focally cartwheel-like (e.g., storiform) pattern. Obliterative phlebitis characterized in its early stage by a mainly lymphocytic perivascular infiltrates and in its later stages by an intravascular infiltration that finally leads to fibro inflammatory obliteration. I-Imaging charterstics [3, 5, 6]. Parenchymal changes suggestive of AIP are Diffuse or (multi-) focal enlargement with loss of the normal multi-lobulated pattern (‘sausage-like’ shape); with diffuse involvement, more frequent in type 1 and focal involvement in AIP type 2. Altered imaging characteristics, such as lower signal intensity (SI)/echogenicity on unenhanced T1-w MRI/(E)US, respectively, moderately higher SI on T2-w MRI, impeded diffusion on MRI, and increased 18F fluorodeoxyglucose(FDG)-uptake on PET-CT [5] compared with normal parenchyma. Post injection of (iodine, gadolinium, or microbubble-based) contrast media, there is dotted/patchy enhancement in the late arterial/ pancreatic phase that progressively increases towards the later vascular phases. Rectangular shape of the tail (‘cut-tail sign’). Thin peripancreatic edematous rim or progressively enhancing true capsule.

Ductal changes suggestive of AIP are Long-segment (i.e. 1/3 of the length) or multifocal main pancreatic duct (MPD) involvement (narrowing or vanishing) without upstream dilatation or other signs of obstructive pancreatitis. Skip lesions, i.e. 2 involved MPD-segments separated by a normal MPD-segment. ‘Duct-penetrating’ (i.e. visible MPD- and/or common bile duct (CBD) lumen) and ‘icicle’ (i.e. a progressive decrease of MPD-diameter) signs within an enlarged parenchymal area. Contrast-enhanced CT shows diffuse enlargement with delayed enhancement and rim- like enhancement in the pancreas. 4 types of IgG4 related sclerosing cholangitis described by Nakazawa, et al. [7]. S-Serology: Significance of serum IgG4 level: 2 or 3 times the upper limit of the reference range of the IgG4 level was a useful marker for the diagnosis of various types of IgG4-RD and the optimal cutoff level was 248 mg/dL [8]. Metanalysis (n = 6048), by Xu, et al. [9], showed Sensitivity of 85%, Specificity value of 93% [9]. IgG4/IgG1, with a cutoff value of 0.24. Doorenspleet, et al. [9] showed that IgG4/IgG RNA in blood, have 94% sensitivity, 99% specificity to differentiate IgG4 pancreatobiliary diseses from other etiologies [6].

O-Other Organ Involvement

Hilar/intrahepatic biliary strictures, persistent distal biliary strictures, parotid or lacrimal gland involvement, mediastinal lymphadenopathy or retroperitoneal fibrosis can be present. Type 1 autoimmune pancreatitis (AIP) is the pancreatic manifestation of a multi-organ disease, named immunoglobulin G4 (IgG4)-related disease while type 2 AIP is a pancreas specific disorder not associated with IgG4 [10].

T-Treatment

Spontaneous resolution of symptoms without medical, interventional endoscopic or surgical treatment occurs in 10- 25% of cases. Treatment required in the following patients:

• All symptomatic patients (e.g. suffering from pancreatic pain, obstructive jaundice).
• Asymptomatic patients in case of: Persistence of a pancreatic mass in imaging to rule out cancer.
• Persistence of liver test abnormalities (cholestasis) in case of associated IgG4-related cholangitis.
• In subclinical situations that could lead to severe or irreversible organ failure [11].

Phases of Treatment

Induction Phase: Steroids, methylprednisolone, Dose of 0.6- 0.8 mg/kg/day , ~30-40 mg/day for 1 month, Response is re- assessed at 2-4 weeks interval with clinical, biochemical, and morphological markers, tapered by 5 mg every two weeks (over 3-6 months), Response rate (~98%) [12]. Maintenance Phase: No high quality evidence, dose of glucocorticoids 10 mg/day. Risk of recurrence [12] was around 40% in patients without prior steroid therapy, ~25% in patients who received steroids previously. Expert recommendations -2.5-10 mg/day prednisolone for 12 months. Some Japanese centers continue low-dose (5 mg) prednisolone for as many as 3 years and beyond [13].

Remission Criteria: Defined as fulfilling each of the following criteria after 6 months of treatment: 50% decline in IgG4 levels, Glucocorticoids tapered to maintenance dose 10 mg/day; and No relapse during glucocorticoid tapering within 6 months [12]. Long-term prognosis of autoimmune pancreatitis with and without corticosteroid treatment.

Relapse: Risk factors for relapse: The relapse rate is high and range from 26% -70%, more common in patients with high baseline serum IgG4 levels [14]. Relapse management: Three common regimens for relapse management are:

• High-dose glucocorticoids followed by maintenance treatment with low dose glucocorticoids or a glucocorticoid-sparing agent.
• High-dose glucocorticoids without maintenance treatment.
• Rituximab induction with or without maintenance rituximab. Glucocorticoids (>95% success rate), first option if tolerated by the patient [11]. Role of immunosuppressant/biological are considered in Disease relapse for
• Maintenance of remission strategy.
• High risk of relapse (multi-organ involvement).
• If no change in disease activity or the disease relapsed during glucocorticoid taper or discontinuation.

Rituximab: If resistant or intolerant to high-dose glucocorticoids to maintain remission, Failed to respond to immunosuppressive therapies , Two dose regimens are: dose is 375 mg/m2 body surface area, weekly for 4 weeks infusions every 2-3 months or Two 1000 mg infusions 15 days apart every 6 months. Role of biliary stenting without cholangitis in patients with increases risk of cholangitis and those where condition may propagate pancreatic stone formation [15]. Serum liver test abnormalities are normalized in 80% and 100% at 15 and 21 days, respectively without stenting [16]. Long term prognosis: Both endocrine and exocrine insufficiency can develop on long term, more than 1/3rd patients, after 3 years of diagnosis. Diabetes mellitus 19-67% and exocrine insufficiency in 36-85% [17]. The outcome of patients with type 2 AIP, a condition often associated with inflammatory bowel disease is not different from that of patients with type 1 AIP, except for diabetes [17].