Clin J Gastroenterol (2012) 5:199–203 DOI 10.1007/s12328-012-0298-1
CASE REPORT
Autoimmune pancreatitis that developed over a 3-month observation period for IgG4-related dacryoadenitis and sialadenitis Misato Amaki • Terumi Kamisawa • Taku Tabata • Seiichi Hara • Sawako Kuruma • Kazuro Chiba • Takashi Fujiwara • Go Kuwata • Hideto Egashira • Koichi Koizumi • Keigo Setoguchi • Junko Fujiwara Takeo Arakawa • Kumiko Momma • Noriko Ozaki
•
Received: 17 February 2012 / Accepted: 28 March 2012 / Published online: 20 April 2012 Ó Springer 2012
Abstract Autoimmune pancreatitis (AIP) that developed in a short period in a patient with IgG4-related dacryoadenitis and sialadenitis is reported. A 67-year-old man was diagnosed as having IgG4-related dacryoadenitis and sialadenitis histologically, serologically, and radiologically. At that time, the pancreas was normal on computed tomographic scanning, magnetic resonance imaging, and 18F-fluorodeoxyglucose positron emission tomography. However, AIP occurred in the pancreatic body and tail during the 3-month period of observation of the initial diseases. All IgG4-related lesions improved promptly after steroid therapy. This report emphasizes that, since IgG4related disease can develop in other organs within a short period in a patient with IgG4-related disease, periodic imaging follow-up is necessary. Keywords Autoimmune pancreatitis IgG4-related dacryoadenitis IgG4-related sialadenitis
Introduction Autoimmune pancreatitis (AIP) is a peculiar type of pancreatitis of presumed autoimmune etiology. It is characterized clinically by a preponderance of elderly males, association with various extrapancreatic lesions such as sclerosing cholangitis or sclerosing sialadenitis, and responsiveness to steroid therapy; serologically by elevation of serum IgG or IgG4 levels; radiologically by enlargement of the pancreas and irregular narrowing of the main pancreatic duct; and histopathologically by dense fibrosis with lymphoplasmacytic infiltration in the pancreas [1, 2]. Since most AIP cases are diagnosed from symptoms such as obstructive jaundice or abdominal pain, the initial imaging findings or natural course of AIP is unknown. A case of AIP that developed over a 3-month period of observing IgG4-related dacryoadenitis and sialadenitis is reported.
Case presentation
M. Amaki T. Kamisawa (&) T. Tabata S. Hara S. Kuruma K. Chiba T. Fujiwara G. Kuwata H. Egashira K. Koizumi K. Setoguchi Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan e-mail: [email protected] J. Fujiwara T. Arakawa K. Momma Department of Endoscopy, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan N. Ozaki Department of Ophthalmology, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
A 67-year-old Japanese man noticed swelling of the right upper eyelid in January 2011. The swelling was not painful, but itchy. He visited an ophthalmologist, and an allergic reaction was suspected. He had been previously healthy, with no history of serious diseases, but he had a history of hay fever and food allergy to mackerel. He noticed swelling of the right salivary gland in February. The symptoms developed gradually over 3 months, and he visited another doctor. Computed tomographic (CT) scanning and magnetic resonance imaging (MRI) of the head showed swelling of bilateral lacrimal and salivary glands and enlargement of the right external ocular muscle (Fig. 1). 18F-Fluorodeoxyglucose positron emission tomography
123
200
Clin J Gastroenterol (2012) 5:199–203
Fig. 3 CT scan taken in May showing no abnormality in the pancreas Fig. 1 MRI showing swelling of bilateral lacrimal glands and enlargement of the right external ocular muscle (arrow)
Fig. 2 FDG-PET showing abnormal uptake in bilateral orbital regions (long arrows) and submandibular glands (short arrows)
(FDG-PET) showed abnormal uptake in bilateral orbital regions, submandibular glands, and cervical lymph nodes (Fig. 2). There was no FDG uptake in the pancreas on the FDG-PET and no abnormalities in the pancreas on CT and MRI (Fig. 3). Histopathological examination of the biopsy specimen from the right lacrimal gland performed in May showed diffuse infiltration of lymphocytes and plasma cells, and fibrotic changes around the ducts (Fig. 4a). Immunohistochemically, the number of IgG4-positive plasma cells was 13/per high power field (Fig. 4b), and the
123
Fig. 4 Histopathology of the biopsy specimen from the right lacrimal gland showing a diffuse infiltration of lymphocytes and plasma cells, and fibrotic changes (H&E staining) and b abundant infiltration of IgG4-positive plasma cells (IgG4 immunostaining)
IgG4?/IgG? plasma cell ratio was 40 %. The serum IgG4 level was 790 mg/dl. The patient was diagnosed as having IgG4-related dacryoadenitis and sialadenitis [3]. The patient noticed itchy erythema involving the forearms, and this was treated with a topical steroid agent, but there was no improvement.
Clin J Gastroenterol (2012) 5:199–203
201
Fig. 6 ERCP showing irregular narrowing of the main pancreatic duct of the pancreatic body and tail (arrow)
Fig. 5 a MRI taken in August showing enlargement of the pancreatic body and tail with a capsule-like rim (arrows). b Diffusion-weighted MRI showing a high-intensity area (arrow) in the enlarged pancreatic body and tail. c MRI performed 4 weeks after starting steroid therapy showing reduction of the enlarged pancreas (arrow)
In August, the patient was referred to our hospital for further examination and treatment for the IgG4-related diseases. On admission, his temperature was 35.0 °C, blood pressure was 148/68 mmHg, and pulse rate was 69 per min. His body weight was 55 kg. On physical examination, swelling and ptosis of the right eyelid and swelling
of bilateral submandibular glands were observed. He did not have any other symptoms, including visual loss, double vision, or a visual field defect. Examination of his chest and heart was normal, and no abdominal tumors or hepatosplenomegaly was detected. On laboratory examination, the white blood cell count was 8300/mm3, and the eosinophil count was 750/mm3. There were no abnormalities in hepatobiliary and pancreatic enzymes and tumor markers including CA19.9 and CEA. Immunologically, the serum IgG, IgG4, and IgE levels were elevated at 2117 mg/dl (normal \1700 mg/dl), 824 mg/dl (\135 mg/dl), and 2154 IU/ml (\250 IU/ml), respectively. Autoantibodies such as antinuclear antibody, rheumatoid factor, anti-Ro antibody (SS-A), and anti-La antibody (SS-B) were negative. On abdominal MRI and CT performed in August, the pancreatic body and tail were obviously enlarged with a capsule-like rim, but the pancreatic head was within a normal size (Fig. 5a). On diffusion-weighted MRI, the enlarged pancreas showed a high intensity area (Fig. 5b). Endoscopic retrograde cholangiopancreatography (ERCP) showed irregular narrowing of the main pancreatic duct of the pancreatic body and tail (Fig. 6). The patient was diagnosed as having AIP associated with IgG4-related sclerosing dacryoadenitis and sialadenitis [4]. On histology, the biopsy specimen from an erythematous area showed superficial and deep perivascular dermatitis without infiltration of IgG4-positive cells. The patient was then treated with 30 mg of prednisolone daily for 2 weeks. The dose was tapered by 5 mg every 2 weeks. On MRI performed 4 weeks after starting steroid therapy, the eyelid swellings had shrunken markedly, and the enlargement of the pancreas had also improved (Fig. 5c). His serum IgG,
123
202
IgG4, and IgE levels and peripheral eosinophil count were markedly decreased (965 mg/dl, 245 mg/dl, 641 IU/ml, and 210/mm3, respectively). Five months later, he was on a maintenance dose of prednisolone (5 mg/day) without relapse.
Discussion The histology of various extrapancreatic lesions associated with AIP is quite similar to fibrosis with abundant infiltration of IgG4-positive plasma cells and lymphocytes, and the obliterative phlebitis seen in the pancreas of AIP. Furthermore, dense infiltration of IgG4-positive plasma cells and lymphocytes is detected in various organs of a patient with AIP [5, 6]. AIP and its extrapancreatic lesions show good responsiveness to steroids. Therefore, AIP is currently recognized as a pancreatic lesion of IgG4-related systemic disease (IgG4-related disease). In some cases, only one or two organs are clinically involved, while in others, three or four organs are affected [2, 5]. From this point of view, both AIP and the extrapancreatic lesions of AIP may occur randomly. Mikulicz’s disease (MD) is characterized by bilateral, painless, and symmetrical swelling of the lacrimal, parotid, and submandibular glands [7]. From the findings of high IgG4 concentrations and abundant infiltration of IgG4positive cells in the lacrimal and salivary glands of MD patients, MD is also considered an IgG4-related disease [8]. Salivary gland lesions, that is, IgG4-related sialadenitis, are one of the common locations of other organ involvement in patients with AIP. Lacrimal gland lesions, that is, IgG4related dacryoadenitis [9], are occasionally associated with AIP. Hamano et al. [10] reported that salivary and lacrimal gland swellings were detected in 8 (13 %) and 23 (26 %) of 64 AIP patients, respectively, and both lesions were found in 6 patients. The lesions preceded the AIP by 15 years in one patient. Extrapancreatic lesions with AIP sometimes appear metachronously. In our previous study of 56 AIP patients, swelling of the salivary glands (n = 8), swelling of the lacrimal glands (n = 2), distant lymphadenopathy (n = 5), and retroperitoneal fibrosis (n = 1) were found to be the extrapancreatic lesions preceding AIP, while sclerosing cholangitis occurred synchronously [11]. It is unclear why the onset period of each lesion differs in IgG4-related systemic sclerosing disease. About 74 [12] to 88 % [13] of AIP patients were diagnosed with obstructive jaundice due to associated sclerosing cholangitis. That is, AIP cannot be diagnosed in most cases before the bile duct is involved even if AIP occurs subclinically. Compared with AIP, swelling of the salivary or lacrimal glands can be easily noticed even
123
Clin J Gastroenterol (2012) 5:199–203
without other symptoms. Since radiological imaging of the pancreas is usually not performed when salivary or lacrimal gland lesions occur, it is unclear whether AIP already exists subclinically at that time. In the present case, the pancreas was normal 3 months before the onset of AIP. Thus, AIP may develop over a short time in a patient with IgG4-related disease. Although the pathogenesis of AIP remains unclear, it was recently reported that the expressions of Th2 cytokines and regulatory cytokines, which are closely involved in the pathogenesis of allergic disorders, were upregulated in the affected tissues of AIP [14]. The reported patient had a history of hay fever and food allergy to mackerel, dermatitis, peripheral blood eosinophilia, and marked serum IgE elevation. Allergic mechanisms might be related to the occurrence of AIP in this patient [15]. Recently, AIP has been divided into two types, type 1 and type 2. Type-1 AIP is recognized to be a pancreatic manifestation of IgG4-related disease, and type-2 AIP is usually devoid of IgG4-positive plasma cell and elevated serum IgG4 levels [16]. Accordingly, this patient was diagnosed as having type-1 AIP. In the present case, AIP developed during 3 months of follow-up for IgG4-related sclerosing dacryoadenitis and sialadenitis. IgG4-related lesions can develop in other organs within a short period of time in a patient with IgG4related disease, and the pancreas is frequently involved in IgG4-related disease. Therefore, periodic (every 6–12 months) imaging follow-up for the pancreas by ultrasonography appears to be necessary in MD patients without manifestation of AIP. Acknowledgments This work was supported in part by the Research Committee of Intractable Pancreatic Diseases (Principal investigator: Tooru Shimosegawa) provided by the Ministry of Health, Labour, and Welfare of Japan. Conflict of interest interest.
The authors state that they have no conflict of
References 1. Okazaki K, Kawa S, Kamisawa T, Ito T, Inui K, Irie H, et al. Japanese clinical guidelines for autoimmune pancreatitis. Pancreas. 2009;38:849–66. 2. Kamisawa T, Takuma K, Egawa N, Tsuruta K, Sasaki T. Autoimmune pancreatitis and IgG4-related sclerosing disease. Nat Rev Gastroenterol Hepatol. 2010;7:401–9. 3. Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T, et al. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol. 2012;22:21–30. 4. Otsuki M, Chung JB, Okazaki K, Kim MH, Kamisawa T, Kawa S, et al. Asian diagnostic criteria for autoimmune pancreatitis: consensus of the Japan–Korea Symposium on Autoimmune Pancreatitis. J Gastroenterol. 2008;43:403–8.
Clin J Gastroenterol (2012) 5:199–203 5. Kamisawa T, Funata N, Hayashi Y, Eishi Y, Koike M, Tsuruta K, et al. A new clinicopathological entity of IgG4-related autoimmune disease. J Gastroenterol. 2003;38:982–4. 6. Kamisawa T, Funata N, Hayashi Y, Tsuruta K, Okamoto A, Amemiya K, et al. Close relationship between autoimmune pancreatitis and multifocal fibrosclerosis. Gut. 2003;52:683–7. 7. Mikukicz. Uber eine eigenartige symmetrische erkrankung der tranen und mundspeicheldrusen. Beitr Chir Fortsch Gewidmet Theodor Billroth 1892;610–30. 8. Yamamoto M, Harada S, Ohara M, Suzuki C, Naishiro Y, Yamamoto H, et al. Clinical and pathological differences between Mikulicz’s disease and Sjogren’s syndrome. Rheumatology. 2005;44:227–34. 9. Takahashi M, Kawano M, Zen Y, Minato H, Yamada K, Sugiyama K. IgG4-related chronic sclerosing dacryadenitis. Arch Ophthalmol. 2007;125:1575–8. 10. Hamano H, Arakura T, Muraki T, Ozaki Y, Kiyosawa K, Kawa S. Prevalence and distribution of extrapancreatic lesions complicating autoimmune pancreatitis. J Gastroenterol. 2006;41: 1197–205.
203 11. Takuma K, Kamisawa T, Anjiki H, Egawa N, Igarashi Y. Metachronous extrapancreatic lesions in autoimmune pancreatitis. Int Med. 2010;49:529–33. 12. Kamisawa T, Okamoto A. IgG4-related sclerosing disease. World J Gastroenterol. 2008;14:3948–55. 13. Chari ST, Takahashi N, Levy MJ, Smyrk TC, Clain JE, Pearson RK, et al. A diagnostic strategy to distinguish autoimmune pancreatitis from pancreatic cancer. Clin Gastroenterol Hepatol. 2009;7:1097–103. 14. Zen Y, Fujii T, Harada K, Kawano M, Yamada K, Takahira M, et al. Th2 and regulatory immune reactions are increased in immunoglobulin G4-related sclerosing pancreatitis and cholangitis. Hepatology. 2007;45:1538–46. 15. Kamisawa T, Anjiki H, Egawa N, Kubota N. Allergic manifestations in autoimmune pancreatitis. Eur J Gastroenterol Hepatol. 2009;21:2236–9. 16. Sak RP, Chari ST, Pannala R, et al. Differences in clinical profile and relapse rate of type 1 versus type 2 autoimmune pancreatitis. Gastroenterology. 2010;139:140–8.
123
CASE REPORT
Autoimmune pancreatitis that developed over a 3-month observation period for IgG4-related dacryoadenitis and sialadenitis Misato Amaki • Terumi Kamisawa • Taku Tabata • Seiichi Hara • Sawako Kuruma • Kazuro Chiba • Takashi Fujiwara • Go Kuwata • Hideto Egashira • Koichi Koizumi • Keigo Setoguchi • Junko Fujiwara Takeo Arakawa • Kumiko Momma • Noriko Ozaki
•
Received: 17 February 2012 / Accepted: 28 March 2012 / Published online: 20 April 2012 Ó Springer 2012
Abstract Autoimmune pancreatitis (AIP) that developed in a short period in a patient with IgG4-related dacryoadenitis and sialadenitis is reported. A 67-year-old man was diagnosed as having IgG4-related dacryoadenitis and sialadenitis histologically, serologically, and radiologically. At that time, the pancreas was normal on computed tomographic scanning, magnetic resonance imaging, and 18F-fluorodeoxyglucose positron emission tomography. However, AIP occurred in the pancreatic body and tail during the 3-month period of observation of the initial diseases. All IgG4-related lesions improved promptly after steroid therapy. This report emphasizes that, since IgG4related disease can develop in other organs within a short period in a patient with IgG4-related disease, periodic imaging follow-up is necessary. Keywords Autoimmune pancreatitis IgG4-related dacryoadenitis IgG4-related sialadenitis
Introduction Autoimmune pancreatitis (AIP) is a peculiar type of pancreatitis of presumed autoimmune etiology. It is characterized clinically by a preponderance of elderly males, association with various extrapancreatic lesions such as sclerosing cholangitis or sclerosing sialadenitis, and responsiveness to steroid therapy; serologically by elevation of serum IgG or IgG4 levels; radiologically by enlargement of the pancreas and irregular narrowing of the main pancreatic duct; and histopathologically by dense fibrosis with lymphoplasmacytic infiltration in the pancreas [1, 2]. Since most AIP cases are diagnosed from symptoms such as obstructive jaundice or abdominal pain, the initial imaging findings or natural course of AIP is unknown. A case of AIP that developed over a 3-month period of observing IgG4-related dacryoadenitis and sialadenitis is reported.
Case presentation
M. Amaki T. Kamisawa (&) T. Tabata S. Hara S. Kuruma K. Chiba T. Fujiwara G. Kuwata H. Egashira K. Koizumi K. Setoguchi Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan e-mail: [email protected] J. Fujiwara T. Arakawa K. Momma Department of Endoscopy, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan N. Ozaki Department of Ophthalmology, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
A 67-year-old Japanese man noticed swelling of the right upper eyelid in January 2011. The swelling was not painful, but itchy. He visited an ophthalmologist, and an allergic reaction was suspected. He had been previously healthy, with no history of serious diseases, but he had a history of hay fever and food allergy to mackerel. He noticed swelling of the right salivary gland in February. The symptoms developed gradually over 3 months, and he visited another doctor. Computed tomographic (CT) scanning and magnetic resonance imaging (MRI) of the head showed swelling of bilateral lacrimal and salivary glands and enlargement of the right external ocular muscle (Fig. 1). 18F-Fluorodeoxyglucose positron emission tomography
123
200
Clin J Gastroenterol (2012) 5:199–203
Fig. 3 CT scan taken in May showing no abnormality in the pancreas Fig. 1 MRI showing swelling of bilateral lacrimal glands and enlargement of the right external ocular muscle (arrow)
Fig. 2 FDG-PET showing abnormal uptake in bilateral orbital regions (long arrows) and submandibular glands (short arrows)
(FDG-PET) showed abnormal uptake in bilateral orbital regions, submandibular glands, and cervical lymph nodes (Fig. 2). There was no FDG uptake in the pancreas on the FDG-PET and no abnormalities in the pancreas on CT and MRI (Fig. 3). Histopathological examination of the biopsy specimen from the right lacrimal gland performed in May showed diffuse infiltration of lymphocytes and plasma cells, and fibrotic changes around the ducts (Fig. 4a). Immunohistochemically, the number of IgG4-positive plasma cells was 13/per high power field (Fig. 4b), and the
123
Fig. 4 Histopathology of the biopsy specimen from the right lacrimal gland showing a diffuse infiltration of lymphocytes and plasma cells, and fibrotic changes (H&E staining) and b abundant infiltration of IgG4-positive plasma cells (IgG4 immunostaining)
IgG4?/IgG? plasma cell ratio was 40 %. The serum IgG4 level was 790 mg/dl. The patient was diagnosed as having IgG4-related dacryoadenitis and sialadenitis [3]. The patient noticed itchy erythema involving the forearms, and this was treated with a topical steroid agent, but there was no improvement.
Clin J Gastroenterol (2012) 5:199–203
201
Fig. 6 ERCP showing irregular narrowing of the main pancreatic duct of the pancreatic body and tail (arrow)
Fig. 5 a MRI taken in August showing enlargement of the pancreatic body and tail with a capsule-like rim (arrows). b Diffusion-weighted MRI showing a high-intensity area (arrow) in the enlarged pancreatic body and tail. c MRI performed 4 weeks after starting steroid therapy showing reduction of the enlarged pancreas (arrow)
In August, the patient was referred to our hospital for further examination and treatment for the IgG4-related diseases. On admission, his temperature was 35.0 °C, blood pressure was 148/68 mmHg, and pulse rate was 69 per min. His body weight was 55 kg. On physical examination, swelling and ptosis of the right eyelid and swelling
of bilateral submandibular glands were observed. He did not have any other symptoms, including visual loss, double vision, or a visual field defect. Examination of his chest and heart was normal, and no abdominal tumors or hepatosplenomegaly was detected. On laboratory examination, the white blood cell count was 8300/mm3, and the eosinophil count was 750/mm3. There were no abnormalities in hepatobiliary and pancreatic enzymes and tumor markers including CA19.9 and CEA. Immunologically, the serum IgG, IgG4, and IgE levels were elevated at 2117 mg/dl (normal \1700 mg/dl), 824 mg/dl (\135 mg/dl), and 2154 IU/ml (\250 IU/ml), respectively. Autoantibodies such as antinuclear antibody, rheumatoid factor, anti-Ro antibody (SS-A), and anti-La antibody (SS-B) were negative. On abdominal MRI and CT performed in August, the pancreatic body and tail were obviously enlarged with a capsule-like rim, but the pancreatic head was within a normal size (Fig. 5a). On diffusion-weighted MRI, the enlarged pancreas showed a high intensity area (Fig. 5b). Endoscopic retrograde cholangiopancreatography (ERCP) showed irregular narrowing of the main pancreatic duct of the pancreatic body and tail (Fig. 6). The patient was diagnosed as having AIP associated with IgG4-related sclerosing dacryoadenitis and sialadenitis [4]. On histology, the biopsy specimen from an erythematous area showed superficial and deep perivascular dermatitis without infiltration of IgG4-positive cells. The patient was then treated with 30 mg of prednisolone daily for 2 weeks. The dose was tapered by 5 mg every 2 weeks. On MRI performed 4 weeks after starting steroid therapy, the eyelid swellings had shrunken markedly, and the enlargement of the pancreas had also improved (Fig. 5c). His serum IgG,
123
202
IgG4, and IgE levels and peripheral eosinophil count were markedly decreased (965 mg/dl, 245 mg/dl, 641 IU/ml, and 210/mm3, respectively). Five months later, he was on a maintenance dose of prednisolone (5 mg/day) without relapse.
Discussion The histology of various extrapancreatic lesions associated with AIP is quite similar to fibrosis with abundant infiltration of IgG4-positive plasma cells and lymphocytes, and the obliterative phlebitis seen in the pancreas of AIP. Furthermore, dense infiltration of IgG4-positive plasma cells and lymphocytes is detected in various organs of a patient with AIP [5, 6]. AIP and its extrapancreatic lesions show good responsiveness to steroids. Therefore, AIP is currently recognized as a pancreatic lesion of IgG4-related systemic disease (IgG4-related disease). In some cases, only one or two organs are clinically involved, while in others, three or four organs are affected [2, 5]. From this point of view, both AIP and the extrapancreatic lesions of AIP may occur randomly. Mikulicz’s disease (MD) is characterized by bilateral, painless, and symmetrical swelling of the lacrimal, parotid, and submandibular glands [7]. From the findings of high IgG4 concentrations and abundant infiltration of IgG4positive cells in the lacrimal and salivary glands of MD patients, MD is also considered an IgG4-related disease [8]. Salivary gland lesions, that is, IgG4-related sialadenitis, are one of the common locations of other organ involvement in patients with AIP. Lacrimal gland lesions, that is, IgG4related dacryoadenitis [9], are occasionally associated with AIP. Hamano et al. [10] reported that salivary and lacrimal gland swellings were detected in 8 (13 %) and 23 (26 %) of 64 AIP patients, respectively, and both lesions were found in 6 patients. The lesions preceded the AIP by 15 years in one patient. Extrapancreatic lesions with AIP sometimes appear metachronously. In our previous study of 56 AIP patients, swelling of the salivary glands (n = 8), swelling of the lacrimal glands (n = 2), distant lymphadenopathy (n = 5), and retroperitoneal fibrosis (n = 1) were found to be the extrapancreatic lesions preceding AIP, while sclerosing cholangitis occurred synchronously [11]. It is unclear why the onset period of each lesion differs in IgG4-related systemic sclerosing disease. About 74 [12] to 88 % [13] of AIP patients were diagnosed with obstructive jaundice due to associated sclerosing cholangitis. That is, AIP cannot be diagnosed in most cases before the bile duct is involved even if AIP occurs subclinically. Compared with AIP, swelling of the salivary or lacrimal glands can be easily noticed even
123
Clin J Gastroenterol (2012) 5:199–203
without other symptoms. Since radiological imaging of the pancreas is usually not performed when salivary or lacrimal gland lesions occur, it is unclear whether AIP already exists subclinically at that time. In the present case, the pancreas was normal 3 months before the onset of AIP. Thus, AIP may develop over a short time in a patient with IgG4-related disease. Although the pathogenesis of AIP remains unclear, it was recently reported that the expressions of Th2 cytokines and regulatory cytokines, which are closely involved in the pathogenesis of allergic disorders, were upregulated in the affected tissues of AIP [14]. The reported patient had a history of hay fever and food allergy to mackerel, dermatitis, peripheral blood eosinophilia, and marked serum IgE elevation. Allergic mechanisms might be related to the occurrence of AIP in this patient [15]. Recently, AIP has been divided into two types, type 1 and type 2. Type-1 AIP is recognized to be a pancreatic manifestation of IgG4-related disease, and type-2 AIP is usually devoid of IgG4-positive plasma cell and elevated serum IgG4 levels [16]. Accordingly, this patient was diagnosed as having type-1 AIP. In the present case, AIP developed during 3 months of follow-up for IgG4-related sclerosing dacryoadenitis and sialadenitis. IgG4-related lesions can develop in other organs within a short period of time in a patient with IgG4related disease, and the pancreas is frequently involved in IgG4-related disease. Therefore, periodic (every 6–12 months) imaging follow-up for the pancreas by ultrasonography appears to be necessary in MD patients without manifestation of AIP. Acknowledgments This work was supported in part by the Research Committee of Intractable Pancreatic Diseases (Principal investigator: Tooru Shimosegawa) provided by the Ministry of Health, Labour, and Welfare of Japan. Conflict of interest interest.
The authors state that they have no conflict of
References 1. Okazaki K, Kawa S, Kamisawa T, Ito T, Inui K, Irie H, et al. Japanese clinical guidelines for autoimmune pancreatitis. Pancreas. 2009;38:849–66. 2. Kamisawa T, Takuma K, Egawa N, Tsuruta K, Sasaki T. Autoimmune pancreatitis and IgG4-related sclerosing disease. Nat Rev Gastroenterol Hepatol. 2010;7:401–9. 3. Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T, et al. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol. 2012;22:21–30. 4. Otsuki M, Chung JB, Okazaki K, Kim MH, Kamisawa T, Kawa S, et al. Asian diagnostic criteria for autoimmune pancreatitis: consensus of the Japan–Korea Symposium on Autoimmune Pancreatitis. J Gastroenterol. 2008;43:403–8.
Clin J Gastroenterol (2012) 5:199–203 5. Kamisawa T, Funata N, Hayashi Y, Eishi Y, Koike M, Tsuruta K, et al. A new clinicopathological entity of IgG4-related autoimmune disease. J Gastroenterol. 2003;38:982–4. 6. Kamisawa T, Funata N, Hayashi Y, Tsuruta K, Okamoto A, Amemiya K, et al. Close relationship between autoimmune pancreatitis and multifocal fibrosclerosis. Gut. 2003;52:683–7. 7. Mikukicz. Uber eine eigenartige symmetrische erkrankung der tranen und mundspeicheldrusen. Beitr Chir Fortsch Gewidmet Theodor Billroth 1892;610–30. 8. Yamamoto M, Harada S, Ohara M, Suzuki C, Naishiro Y, Yamamoto H, et al. Clinical and pathological differences between Mikulicz’s disease and Sjogren’s syndrome. Rheumatology. 2005;44:227–34. 9. Takahashi M, Kawano M, Zen Y, Minato H, Yamada K, Sugiyama K. IgG4-related chronic sclerosing dacryadenitis. Arch Ophthalmol. 2007;125:1575–8. 10. Hamano H, Arakura T, Muraki T, Ozaki Y, Kiyosawa K, Kawa S. Prevalence and distribution of extrapancreatic lesions complicating autoimmune pancreatitis. J Gastroenterol. 2006;41: 1197–205.
203 11. Takuma K, Kamisawa T, Anjiki H, Egawa N, Igarashi Y. Metachronous extrapancreatic lesions in autoimmune pancreatitis. Int Med. 2010;49:529–33. 12. Kamisawa T, Okamoto A. IgG4-related sclerosing disease. World J Gastroenterol. 2008;14:3948–55. 13. Chari ST, Takahashi N, Levy MJ, Smyrk TC, Clain JE, Pearson RK, et al. A diagnostic strategy to distinguish autoimmune pancreatitis from pancreatic cancer. Clin Gastroenterol Hepatol. 2009;7:1097–103. 14. Zen Y, Fujii T, Harada K, Kawano M, Yamada K, Takahira M, et al. Th2 and regulatory immune reactions are increased in immunoglobulin G4-related sclerosing pancreatitis and cholangitis. Hepatology. 2007;45:1538–46. 15. Kamisawa T, Anjiki H, Egawa N, Kubota N. Allergic manifestations in autoimmune pancreatitis. Eur J Gastroenterol Hepatol. 2009;21:2236–9. 16. Sak RP, Chari ST, Pannala R, et al. Differences in clinical profile and relapse rate of type 1 versus type 2 autoimmune pancreatitis. Gastroenterology. 2010;139:140–8.
123
