**5. Treatment**

Once the diagnosis of AIP is established, treatment with steroids should be started. While some tendency to spontaneous improvement can exist in several cases, steroid treatment is far superior, and the recovery of pancreatic involvement is almost always complete after a relatively short, some month of treatment [32, 33]. The widely accepted dose of prednisone is relatively low, about 0.5–0.6 mg/kg/day. Others initiate the treatment with 40 mg prednisone/ day. After 3–4 weeks with this treatment, the steroid dose is tapered, reducing it 5 mg/day every 2 weeks. Finally, the treatment can be stopped after the complete morphological recovery demonstrated by CT scan or magnetic resonance. However, some authors argue in favor of a maintenance treatment with prednisone in a dose as low as 5 mg/day for 2 years, and they found less recurrence with this conduct, but it is impossible to avoid completely the recurrence of the disease in the pancreas or in some other organ. The recurrent disease also responds to steroid treatment. However, in case of recurrence, it is advisable to initiate a longer treatment with some steroid-sparing agent, azathioprine (1.0–1.5 mg/kg/day) or mycophenolate (2 to 3 g/day) for several years. If these treatments fail, rituximab has been shown effective in the treatment of the first episode of the disease and also in its recurrence. In our experience, steroid treatment with or without steroid-sparing agents was effective in all but one cases; we recently used rituximab 1000 mg repeated in 15 days, i.e., 2000 mg as total dose, in one exceptional patient, with a good initial result. The Mayo Clinic experience [34] is in favor to repeat rituximab 1000 mg every 2–6 months and use it as maintenance treatment. Diabetes becomes frequently clinically overt during the acute phase, as a consequence of the disease itself and the effect of corticosteroids. Insulin treatment can be necessary, but it is transitory in the majority of the patients. Close control is mandatory in order to adjust the insulin dose, which changes rapidly during the treatment: insulin requirement initially increases and later on decreases rapidly. Clinically evident pancreatic exocrine insufficiency during the acute phase is not observed; enzyme supplementation is not necessary.

The effect of steroids is uniformly excellent. It means that if steroids fail to induce remission, one must have serious doubts in the diagnosis, whatever was the basis to establish it. In these cases histological diagnosis is mandatory and surgery is probably inevitable. In spite of the growing knowledge about AIP, the differential diagnosis can be difficult, and AIP continues to be a histological finding of some patients operated on with the suspicion of pancreatic cancer. However, surgery is not a good treatment for AIP; the recurrence without prednisone treatment continues to be a real possibility. In addition, pancreatic resection has surgical morbimortality and late metabolic consequences, which are hardly justifiable in a benign medically treatable disease.

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*Autoimmune Pancreatitis: Clinical Presentation and Therapy*

**6. Late prognosis: progression to chronic pancreatitis**

AIP has been considered as a subclass of chronic pancreatitis (CP). There is no doubt that autoimmune factors can have some importance of the pathogenesis of CP and also in some cases of recurrent acute pancreatitis (RAP). There is also a possibility that the idiopathic advanced CP in several cases can be the late consequence of unrecognized and untreated AIP. However, clinical and epidemiological characteristics; morphological alterations in CT, MR, and EUS; images and histology are all quite different when compared to CP [35]. In addition, CP is a progressive damage to the pancreas, while AIP is a reversible disease after an adequate treatment. There are contradictory observations in the literature about the longterm outcome of AIP [36–38]. When we evaluate the published observations, we must be cautious, and we have to remember that AIP was definitively described only in 1995; it means that follow-up of patients for a period longer than 20 years is lacking. Biliary stenting by ERCP [39] and significant focal stenosis of the main pancreatic duct [40] were found as risk factors for formation of pancreatic stones and progression to CP. Exocrine and endocrine insufficiencies were described in a significant number of patients [41], even without detectable changes of advanced pancreatic disease. However, pancreatic enzyme replacement therapy has not been routinely used even in these cases. Our limited experiences are different: while 11 of our 74 patients had diabetes, clinically overt exocrine insufficiency was observed only in 2 of them [18], requiring oral pancreatic enzyme replacement therapy. We can find similar doubts in the literature about the risk of malignancy: higher incidence of pancreatic and extrapancreatic cancer was described by some authors [42] but not confirmed by others [43]. We did not observe malignant

The possibility of AIP to PC requires longer observations. However, we insist that AIP in our opinion is not a simple subclass of CP. The differences are as strong as or even stronger than in the case of obstructive pancreatitis. Both of these entities can be reversible with an adequate timely treatment, and probably both of them can progress to CP if their cause persists unresolved [44]. If it is true, it underlines even

Autoimmune pancreatitis is an increasingly recognized, relatively new disease, identified definitively only in 1995. Two types of the AIP are described, type 1 or lymphoplasmacytic sclerosing pancreatitis (LPSP) and type 2 or idiopathic ductcentric pancreatitis. While type 1 is part of an IgG4-related systemic disease, type 2 is limited to the pancreas and can be associated only with inflammatory bowel disease. The diagnosis is not easy; detection of morphological alterations is the clue in recognizing AIP and distinguishing it from other pancreatic diseases. Once the diagnosis is made, the clinical classification of types 1 and 2 also can be difficult. For this reason, an indeterminate category Not Otherwise Specified (NOS) is useful in the everyday clinical practice. All types of AIP respond rapidly and completely to steroid treatment. The late prognosis is good, but residual morphological and functional pancreatic changes can be present. Progression to advanced CP probably can be prevented with adequate treatment. These characteristics make AIP a unique pancreatic disease: its correct diagnosis avoids unnecessary surgery, and it is the only pancreatic disease when we have the possibility to achieve a complete recovery with noninvasive medical treatment. It is particular also among the autoimmune diseases: an excellent

more the importance of the early diagnosis and proper treatment.

*DOI: http://dx.doi.org/10.5772/intechopen.83349*

disease in our cohort of patients.

**7. Conclusions**

*Chronic Autoimmune Epithelitis - Sjogren's Syndrome and Other Autoimmune Diseases...*

type 2 (**Figure 8**).

**5. Treatment**

possible diagnosis. In these latter cases, pancreatic biopsy is advisable, guided by EUS and taking core biopsy, not cytology. Several cases will show typical histology of type 1 AIP. In others, the absence of significant IgG4-positive lymphoplasmacytic infiltration and the presence of granulocytic epithelial lesions with or without neutrophil infiltration of the pancreatic lobules prove definitively type 2 AIP. However, typical histological features of type 2 can be also absent in the core biopsy: in these cases the diagnosis continues to be NOS or sometimes probable

Once the diagnosis of AIP is established, treatment with steroids should be started. While some tendency to spontaneous improvement can exist in several cases, steroid treatment is far superior, and the recovery of pancreatic involvement is almost always complete after a relatively short, some month of treatment [32, 33]. The widely accepted dose of prednisone is relatively low, about 0.5–0.6 mg/kg/day. Others initiate the treatment with 40 mg prednisone/ day. After 3–4 weeks with this treatment, the steroid dose is tapered, reducing it 5 mg/day every 2 weeks. Finally, the treatment can be stopped after the complete morphological recovery demonstrated by CT scan or magnetic resonance. However, some authors argue in favor of a maintenance treatment with prednisone in a dose as low as 5 mg/day for 2 years, and they found less recurrence with this conduct, but it is impossible to avoid completely the recurrence of the disease in the pancreas or in some other organ. The recurrent disease also responds to steroid treatment. However, in case of recurrence, it is advisable to initiate a longer treatment with some steroid-sparing agent, azathioprine (1.0–1.5 mg/kg/day) or mycophenolate (2 to 3 g/day) for several years. If these treatments fail, rituximab has been shown effective in the treatment of the first episode of the disease and also in its recurrence. In our experience, steroid treatment with or without steroid-sparing agents was effective in all but one cases; we recently used rituximab 1000 mg repeated in 15 days, i.e., 2000 mg as total dose, in one exceptional patient, with a good initial result. The Mayo Clinic experience [34] is in favor to repeat rituximab 1000 mg every 2–6 months and use it as maintenance treatment. Diabetes becomes frequently clinically overt during the acute phase, as a consequence of the disease itself and the effect of corticosteroids. Insulin treatment can be necessary, but it is transitory in the majority of the patients. Close control is mandatory in order to adjust the insulin dose, which changes rapidly during the treatment: insulin requirement initially increases and later on decreases rapidly. Clinically evident pancreatic exocrine insufficiency during the acute phase is not observed; enzyme supplementation is

The effect of steroids is uniformly excellent. It means that if steroids fail to induce remission, one must have serious doubts in the diagnosis, whatever was the basis to establish it. In these cases histological diagnosis is mandatory and surgery is probably inevitable. In spite of the growing knowledge about AIP, the differential diagnosis can be difficult, and AIP continues to be a histological finding of some patients operated on with the suspicion of pancreatic cancer. However, surgery is not a good treatment for AIP; the recurrence without prednisone treatment continues to be a real possibility. In addition, pancreatic resection has surgical morbimortality and late metabolic consequences, which are hardly justifiable in a benign

**102**

not necessary.

medically treatable disease.
