Clinical characteristics and outcome of autoimmune pancreatitis based on serum immunoglobulin G4 level:A single-center,retrospective cohort study

BACKGROUND Autoimmune pancreatitis(AIP)has been linked with elevated immunoglobulin(Ig)G4 levels.The characteristics and outcomes of AIP based on serum markers have not been fully evaluated.AIM To compare clinical features,treatment efficacy,and outcome of AIP based on serum IgG4 levels and analyze predictors of relapse.METHODS A total of 213 patients with AIP were consecutively reviewed in our hospital from 2006 to 2021.According to the serum IgG4 level,all patients were divided into two groups,the abnormal group(n=148)with a high level of IgG4[>2×upper limit of normal(ULN)]and the normal group(n=65).The t-test or Mann-Whitney U test was used to compare continuous variables.Categorical parameters were compared by theχ^(2) test or Fisher’s exact test.Kaplan-Meier curves Zhou GZ et al.Clinical characteristics and outcome of AIP WJG https://www.wjgnet.com 5126 September 21,2023 Volume 29 Issue 35 and log-rank tests were established to assess the cumulative relapse rates.Univariate and multivariate analyses were used to investigate potential risk factors of AIP relapse.RESULTS Compared with the normal group,the abnormal group had a higher average male age(60.3±10.4 vs 56.5±12.9 years,P=0.047);higher level of serum total protein(72.5±7.9 g/L vs 67.2±7.5 g/L,P<0.001),IgG4(1420.5±1110.9 mg/dL vs 252.7±106.6 mg/dL,P<0.001),and IgE(635.6±958.1 IU/mL vs 231.7±352.5 IU/mL,P=0.002);and a lower level of serum complement C3(100.6±36.2 mg/dL vs 119.0±45.7 mg/dL,P=0.050).In addition,a lower number of cases with abnormal pancreatic duct and pancreatic atrophy(23.6%vs 37.9%,P=0.045;1.6%vs 8.6%,P=0.020,respectively)and a higher rate of relapse(17.6%vs 6.2%,P=0.030)were seen in the abnormal group.Multivariate analyses revealed that serum IgG4[(>2×ULN),hazard ratio(HR):3.583;95%confidence interval(CI):1.218–10.545;P=0.020]and IgA(>1×ULN;HR:5.908;95%CI:1.199–29.120;P=0.029)and age>55 years(HR:2.383;95%CI:1.056–5.378;P=0.036)were independent risk factors of relapse.CONCLUSION AIP patients with high IgG4 levels have clinical features including a more active immune system and higher relapse rate.Several factors,such as IgG4 and IgA,are associated with relapse.

Understanding autoimmune pancreatitis: Clinical features, management challenges, and association with malignancies

In this editorial we comment on the article by Jaber et al.Autoimmune pancreatitis(AIP)represents a distinct form of pancreatitis,categorized into AIP-1 and AIP-2,characterized by obstructive jaundice,lymphoplasmacytic infiltrate,and fibrosis.AIP-1,associated with elevated immunoglobulin G4(IgG4)levels,exhibits higher relapse rates,affecting older males,while AIP-2 is less common and linked to inflammatory bowel disease.AIP is considered a manifestation of IgG4-related systemic disease,sharing characteristic histological findings.Steroids are the primary treatment,with emerging biomarkers like interferon alpha and inter-leukin-33.AIP poses an increased risk of various malignancies,and the assoc-iation with pancreatic cancer is debated.Surgery is reserved for severe cases,necessitating careful evaluation due to diagnostic challenges.AIP patients may have concurrent PanINs but display favorable long-term outcomes compared to pancreatic cancer patients.Thorough diagnostic assessment,including biopsy and steroid response,is crucial for informed surgical decisions in AIP.

Unmet needs in biomarkers for autoimmune pancreatitis diagnosis

Autoimmune pancreatitis(AIP)is a rare chronic autoimmune disorder.The diagnosis of AIP mainly depends on histopathology,imaging and response to treatment.Serum immunoglobulin 4(IgG4)is used only as collateral evidence in diagnostic criteria for AIP because of its moderate sensitivity.Serum IgG4 levels are normal in 15%-37%of type 1 AIP and most of type 2 AIP patients.In these patients,the indeterminate imaging and histopathology may lead to the difficulty in definitive diagnosis of AIP.Therefore,discovery of new biomarkers is impor-tant for AIP diagnosis.Here,we provide some views on the progression and challenges in identifying novel serological biomarkers in AIP diagnosis.

Type one autoimmune pancreatitis based on clinical diagnosis: A case report

BACKGROUND Autoimmune pancreatitis(AIP)is a rare form of autoimmune-mediated pancrea-titis,which is easily misdiagnosed as pancreatic cancer and thus treated surgi-cally.We studied the diagnosis and treatment of a patient with type 1 AIP recent-ly admitted to our hospital,and reviewed the literature to provide a reference for clinical diagnosis of AIP.CASE SUMMARY The chief complaint was yellowing of the body,eyes and urine for 21 d.The pa-tient's clinical presentation was obstructive jaundice and imaging suggested pan-creatic swelling.It was difficult to distinguish between inflammation and tumor.Serum immunoglobulin G4(IgG4)was markedly elevated.IgG4 is an important serological marker for type 1 AIP.The patient was diagnosed with AIP,IgG4-related cholangitis,acute cholecystitis and hepatic impairment.After applying hormonal therapy,the patient's symptoms improved significantly.At the same time,imaging suggested that pancreatic swelling subsided,and liver function and other biochemical indicators decreased.The treatment was effective.CONCLUSION In patients with pancreatic swelling,the possibility of AIP should be considered.

Autoimmune pancreatitis:Cornerstones and future perspectives

Autoimmune pancreatitis(AIP)is an autoimmune subtype of chronic pancreatitis resulting from the aberrant immune response against the pancreas,leading to inflammation and fibrosis.Although AIP is rare,its incidence is increasing and is often misdiagnosed as other pancreatic diseases.AIP is commonly classified into two types.Type 1 AIP(AIP-1)is typically associated with elevated serum immunoglobulin G4(IgG4)levels and systemic manifestations,while type 2 AIP is typically a more localized form of the disease,and may coexist with other autoimmune disorders,especially inflammatory bowel diseases.Additionally,there is emerging recognition of a third type(type 3 AIP),which refers to immunotherapy-triggered AIP,although this classification is still gaining acceptance in medical literature.The clinical manifestations of AIP mainly include painless jaundice and weight loss.Elevated serum IgG4 levels are particularly characteristic of AIP-1.Diagnosis relies on a combination of clinical,laboratory,radiological,and histological findings,given the similarity of AIP symptoms to other pancreatic disorders.The mainstay of treatment for AIP is steroid therapy,which is effective in most cases.Severe cases might require additional imm-unosuppressive agents.This review aims to summarize the current knowledge of AIP,encompassing its epidemiology,etiology,clinical presentation,diagnosis,and treatment options.We also address the challenges and controversies in diagnosing and treating AIP,such as distinguishing it from pancreatic cancer and managing long-term treatment,highlighting the need for increased awareness and knowledge of this complex disease.

Clinical and pathological differences between serum immunoglobulin G4-positive and -negative type 1 autoimmune pancreatitis

AIM: To identify clinical and pathological differences between serum immunoglobulin G4 (IgG4)-positive (SIP) and IgG4-negative (SIN) type 1 autoimmune pancreatitis (AIP) in South Korea. METHODS: AIP was diagnosed by the international consensus diagnostic criteria. The medical records and pathology were retrospectively reviewed and IgG4-positive cells were counted in a high power field (HPF). Type I AIP was defined as a high serum level of IgG4or histological finding. SIN type 1 AIP was defined as a histological evidence of type 1 AIP and a normal serum IgG4 level. The clinical and pathological findings were compared between the two groups. The analysis was performed using Student's t test, Fischer's exact test and Mann-Whitney's U test. A P value of < 0.05 was considered statistically significant. As repeated com- parison was made, P values of less than 5% (P < 0.05) were considered significant. RESULTS: Twenty five patients with definite type 1 AIP (19 histologically and six serologically diagnosed cases) were enrolled. The mean tissue IgG4 concentrations were significantly higher in SIP than SIN group (40 cells per HPF vs 18 cells per HPF, P = 0.02). Among eight SIN patients, the tissue IgG4 concentrations were less than 15 cells per HPF in most of cases, except one. The sensitivity of serum IgG4 was 68% (17 SIP and eight SIN AIP). Other organ involvement was more frequent- ly associated with SIP than SIN AIP (59% vs 26%, P = 0.016). However, the relapse rate and diffuse swelling of the pancreas were not associated with serum IgG4 level. The concentrations of IgG4-positive cells per HPF were higher in SIP than SIN AIP (40 vs 18, P = 0.02). CONCLUSION: The sensitivity of serum IgG4 was 68% in type 1 AIP. High serum IgG4 level was associated with other organ involvement and tissue IgG4 concentration but did not affect the relapse rate in type 1 AIP.

Biomarkers in autoimmune pancreatitis and immunoglobulin G4-related disease

Solitary organ autoimmune disorders,formerly known as autoimmune pancreatitis(AIP),autoimmune sialadenitis,and autoimmune sclerosing cholangitis,are now considered organ-specific manifestations of systemic immunoglobulin G4-related disease(IgG4-RD).AIP and IgG4-RD are characterized by elevated serum concentration of IgG4 antibody(Ab),accumulation of IgG4-expressing plasmacytes in the affected organs,and involvement of multiple organs.It is well established that enhanced IgG4 Ab responses are a hallmark of AIP and IgG4-RD for diagnosis and monitoring disease activity.However,a significant fraction of patients with AIP and IgG4-RD who develop chronic fibroinflammatory responses have normal serum concentrations of this IgG subtype.In addition,disease flare-up is sometimes seen even in the presence of normalized serum concentrations of IgG4 Ab after successful induction of remission by prednisolone.Therefore,it is necessary to identify new biomarkers based on the understanding of the pathophysiology of AIP and IgG4-RD.Recently,we found that activation of plasmacytoid dendritic cells producing both interferon-α(IFN-α)and interleukin-33(IL-33)mediate murine AIP and human IgG4-RD.More importantly,we provided evidence that serum concentrations of IFN-αand IL-33 could be useful biomarkers for the diagnosis and monitoring of AIP and IgG4-RD activity after induction of remission in these autoimmune disorders.In this Frontier article,we have summarized and discussed biomarkers of AIP and IgG4-RD,including Igs,autoAbs,and cytokines to provide useful information not only for clinicians but also for researchers.

Usefulness of ultrasonography to assess the response to steroidal therapy for the rare case of type 2b immunoglobulin G4-related sclerosing cholangitis without pancreatitis:A case report

BACKGROUND A type 2b immunoglobulin G4(IgG4)-related sclerosing cholangitis(SC)without autoimmune pancreatitis is a rare condition with IgG4-SC.While the variety of the imaging modalities have tested its usefulness in diagnosing the IgG4-SC,however,the usage of ultrasonography for the assessment of the response to steroidal therapy on the changes of bile duct wall thickness have not been reported in the condition.Therefore,the information of our recent case and reported cases have been summarized.CASE SUMMARY We report the case of an 82-year-old Japanese man diagnosed with isolated IgG4-related SC based on the increase of serum IgG4,narrowing of the bile duct,its wall thickness,no complication of autoimmune pancreatitis,and IgG4 positive inflammatory cell infiltration to the wall with the fibrotic changes.The cholangiogram revealed type 2b according to the classification.Corticosteroid treatment showed a favorable effect,with the smooth decrease in serum IgG4 and the improvement of the bile duct wall thickness.CONCLUSION As isolated type 2b,IgG4-SC is rare,the images,histological findings,and clinical course of our case will be helpful for physicians to diagnose and treat the new cases appropriately.

Immunoglobulin G4 associated autoimmune cholangitis and pancreatitis and nivolumab

This letter to editor discussing on the publication on immunoglobulin G4 associated autoimmune cholangitis and pancreatitis following the administration of nivolumab.Concerns on confounding factors are raised and discussed.

Review of the diagnosis,classification and management of autoimmune pancreatitis

Autoimmune pancreatitis(AIP)is a rare form of chronic pancreatitis,with as yet undetermined incidence and prevalence in the general population.Our understanding of it continues to evolve.In the last few years,2separate subtypes have been identified:type 1 AIP has been recognised as the pancreatic manifestation of a multiorgan disease,named immunoglobulin G4(IgG4)-related disease while type 2 AIP is a pancreas specific disorder not associated with IgG4.International criteria for the diagnosis of AIP have been defined:the HISORt criteria from the Mayo clinic,the Japan consensus criteria and,most recently,the international association of pancreatology"International Consensus Diagnostic Criteria".Despite this,in clinical practice it can still be very difficult to confirm the diagnosis and differenti-ate AIP from a pancreatic cancer.There are no large studies into the long-term prognosis and management of relapses of AIP,and there is even less information at present regarding the Type 2 AIP subtype.Further studies are necessary to clarify the pathogenesis,treatment and long-term outcomes of this disease.Critically for clinicians,making the correct diagnosis and differentiating the disease from pancreatic cancer is of the utmost importance and the greatest challenge.

Diagnosis and treatment of autoimmune pancreatitis: experience with 100 patients

BACKGROUND： Autoimmune pancreatitis （ALP） is increasingly recognized as a unique subtype of pancreatitis. This study aimed to analyze the diagnosis and treatment of AIP patients from a tertiary care center in China. METHODS： One hundred patients with AIP who had been treated from January 2005 to December 2012 in our hospital were enrolled in this study. We retrospectively reviewed the data of clinical manifestations, laboratory tests, imaging examinations, pathological examinations, treatment and outcomes of the patients. RESULTS： The median age of the patients at onset was 57 years （range 23-82） with a male to female ratio of 8.1：1. The common manifestations of the patients included obstructive jaundice （49 patients, 49.0%）, abdominal pain （30, 30.0%）, and acute pancreatitis （11, 11.0%）. Biliary involvement was one of the most extrapancreatic manifestations （64, 64.0%）. Fifty-six （56.0%） and 43 （43.0%） patients were classified into focal- type and diffuse-type respectively according to the imaging examinations. The levels of serum IgG and IgG4 were elevated in 69.4% （43/62） and 92.0% （69/75） patients. Pathological analysis of specimens from 27 patients supported the diagnosis of lymphoplasmacytic sclerosing pancreatitis, and marked （〉10 ceUs/HPF） IgG4 positive cells were found in 20 （74.1%） patients.Steroid treatment and surgery as the main initial treatments were given to 41 （41.0%） and 28 （28.0%） patients, respectively. The remission rate after the initial treatment was 85.0%. Steroid was given as the treatment after relapse in most of the patients and the total remission rate at the end of follow-up was 96.0%. CONCLUSIONS： Clinical manifestations, laboratory tests, imaging and pathology examinations in combination could increase the diagnostic accuracy of AIP. Steroid treatment with an initial dose of 30 or 40 mg prednisone is effective and safe in most patients with AIP.

Autoimmune pancreatitis and pancreatic cancer:Epidemiological aspects and immunological considerations

Ordinary chronic pancreatitis is a well-known risk factor for pancreatic cancer,whereas such an association with autoimmune pancreatitis(AIP)is widely debated.Due to the rarity of the latter disorder,there are few specific clinical and epidemiological studies investigating the relation between AIP and pancreatic cancer,which do not seem to support it.However,these studies are affected by several limitations and,therefore,a link between AIP(and,specifically,type 1 AIP)and pancreatic cancer cannot be ruled out definitively on this basis.Moreover,several immunopathological aspects of type 1 AIP and,in general,immunoglobulin G4-related disease can create an immunological context that may impair the tumoral immunosurveillance and promote the pancreatic carcinogenesis and its progression.In detail,Th2 immunological dominance,type 2 macrophage polarization and basophil infiltration observed in type 1 AIP,may play a permissive role in creating a favorable immunological environment for pancreatic carcinogenesis,in addition to the immunosuppressive therapies that can be used in these patients.

Pathophysiology of autoimmune pancreatitis

Autoimmune pancreatitis(AIP) is a recently discovered form of pancreatitis and represents one of the diseases of the pancreas which can be cured and healed medically. International consensus diagnostic criteria have been developed, and the clinical phenotypes associated with the histopathologic patterns of lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-centric pancreatitis should be referred to as type 1 and type 2AIP, respectively. Most importantly, in type 1 AIP, the pancreatic manifestations are associated with other extrapancreatic disorders, resembling an immunoglobulin G4(IgG4)-related disease. In addition, the pancreas o a patient with AIP is often infiltrated by various types of immune cells; the cluster of differentiation(CD) 4or CD8 T lymphocytes and IgG4-bearing plasma cells have been found in the pancreatic parenchyma and other involved organs in AIP and factors regulating T-cell function may influence the development of AIP From a genetic point of view, it has also been reported that DRB1*0405 and DQB1*0401 mutations are significantly more frequent in patients with AIP when compared to those with chronic calcifying pancreatitis, and that only DQB1*0302 had a significant association with the relapse of AIP. Finally, it has been found that thepolymorphic genes encoding cytotoxic T lymphocyteassociated antigen 4, a key negative regulator of the T-cell immune response, are associated with AIP in a Chinese population. Even if these data are not concordant, it is possible that physiological IgG4 responses are induced by prolonged antigen exposure and controlled by type 2 helper T cells. We reviewed the current concepts regarding the pathophysiology of this intriguing disease, focusing on the importance of the humoral and cellular immune responses.

Localized type 1 autoimmune pancreatitis superimposed upon preexisting intraductal papillary mucinous neoplasms

A 70-year-old woman was found to have 2 cystic lesions in the head of the pancreas on abdominal ultrasonography during a routine medical examination.Endoscopic ultrasonography(EUS)and magnetic resonance cholangiopancreatography showed multilocular cysts in the head of the pancreas without dilation of the main pancreatic duct.The patient was followed-up semiannually with imaging studies for suspected branch duct-type intraductal papillary mucinous neoplasm(IPMN).At 3 years after initial presentation,hypoechoic lesions were observed around each pancreatic cyst by EUS.Diffusion-weighted imaging showed high-intensity regions corresponding to these lesions.Therefore,a diagnosis of invasive carcinoma derived from IPMN could not be excluded,and subtotal stomach-preserving pancreaticoduodenectomy was performed.The macroscopic examination of the surgical specimen showed whitish solid masses in the head of the pancreas,with multilocular cysts within each mass.Microscopically,each solid mass consisted of inflammatory cells such as lymphocytes and plasma cells.Furthermore,immunochemical staining revealed immunoglobulin G4-positive cells,and many obliterating phlebitides were observed.The cysts consisted of mucus-producing epithelial cells and showed a papillary growth pattern.Based on these findings,we diagnosed multiple localized type 1 autoimmune pancreatitis occurring only in the vicinity of the branch ducttype IPMN.

Recent advances in the management of autoimmune pancreatitis in the era of artificial intelligence

Autoimmune pancreatitis(AIP)is a type of immune-mediated pancreatitis subdivided into two subtypes,type 1 and type 2 AIP.Furthermore,type 1 AIP is considered to be the pancreatic manifestation of the immunoglobulin G4(IgG4)-related disease.Nowadays,AIP is increasingly researched and recognized,although its diagnosis represents a challenge for several reasons:False positive ultrasound-guided cytological samples for a neoplastic process,difficult to interpret levels of IgG4,the absence of biological markers to diagnose type 2 AIP,and the challenging clinical identification of atypical forms.Furthermore,60%and 78%of type 1 and type 2 AIP,respectively,are retrospectively diagnosed on surgical specimens of resected pancreas for suspected cancer.As distinguishing AIP from pancreatic ductal adenocarcinoma can be challenging,obtaining a definitive diagnosis can therefore prove difficult,since endoscopic ultrasound fine-needle aspiration or biopsy of the pancreas are suboptimal.This paper focuses on recent innovations in the management of AIP with regard to the use of artificial intelligence,new serum markers,and new therapeutic approaches,while it also outlines the current management recommendations.A better knowledge of AIP can reduce the recourse to surgery and avoid its overuse,although such an approach requires close collaboration between gastroenterologists,surgeons and radiologists.Better knowledge on AIP and IgG4-related disease remains necessary to diagnose and manage patients.

Present state of endoscopic ultrasonography-guided fine needle aspiration for the diagnosis of autoimmune pancreatitis type 1

Autoimmune pancreatitis(AIP)is defined as pancreatitis caused by irregular narrowing of the pancreatic duct accompanied by pancreatic swelling,fibrosis and lymphocyte infiltration,events that are related to autoimmune mechanisms.The 2010 International Consensus Diagnostic Criteria for AIP defined pancreatitis as“type 1”when increased levels of serum IgG4 were present and other organs were involved;lymphoplasmacytic sclerosing pancreatitis was the main histological characteristic.Apart from surgery,endoscopic ultrasonographyguided fine needle aspiration(EUS-FNA)is the only method for the histological diagnosis of AIP;however,this method is difficult.The use of larger-diameter FNA needles and trucut biopsy did not improve the diagnostic performance of EUS-FNA,but it has improved gradually.In this review,we look back at past efforts to improve the diagnostic performance of EUS-FNA and reveal the present state of EUS-FNA for the histological diagnosis of AIP type 1.

Retroperitoneal fibrosis associated with immunoglobulin G4-related disease

Retroperitoneal fibrosis is a rare disease characterized by the development of inflammation and fibrosis in the soft tissues of the retroperitoneum and other abdominal organs.Retroperitoneal fibrosis can be of 2 types:idiopathic and secondary.The recently advocated concept and diagnostic criteria of immunoglobulin G4(IgG4)-related disease,derived from research on autoimmune pancreatitis(AIP),has led to widespread recognition of retroperitoneal fibrosis as a condition caused by IgG4-related disease.We now know that previously diagnosed idiopathic retroperitoneal fibrosis includes IgG4-related disease;however,the actual prevalence is unclear.Conversely,some reports on AIP suggest that retroperitoneal fibrosis is concurrently found in about 10% of IgG4-related disease.Because retroperitoneal fibrosis has no specific symptoms,diagnosis is primarily based on diagnostic imaging(computed tomography and magnetic resonance imaging),which is also useful in evaluating the effect of therapy.Idiopathic retroperitoneal fibrosis can occur at different times with other lesions of IgG4-related disease including AIP.Thus,the IgG4 assay is recommended to diagnose idiopathic retroperitoneal fibrosis.High serum IgG4 levels should be treated and monitored as a symptom of IgG4-related disease.The first line of treatment for retroperitoneal fibrosis is steroid therapy regardless of its cause.For patients with concurrent AIP,i.e.,IgG4-related retroperitoneal fibrosis,the starting dose of steroid is usually 30-40 mg/d.The response to steroid therapy is generally favorable.In most cases,the pancreatic lesion and retroperitoneal fibrosis improve after the initial treatment.However,the epidemiology,treatment for recurring retroperitoneal fibrosis,and long-term prognosis are still largely unknown.Further analysis of such cases and research are necessary.

Immunoglobulin G4-related gastrointestinal diseases, are they immunoglobulin G4-related diseases?

In immunoglobulin G4(IgG4)-related disease(RD),organ enlargement or nodular lesions consisting of abundant infiltration of lymphocytes and IgG4-positive plasma cells and fibrosis are seen in various organs.Although infiltration of many IgG4-positive plasma cells is detected in the gastric and colonic mucosa and major duodenal papilla of patients with autoimmune pancreatitis,it cannot be diagnosed as a gastrointestinal lesion involved in IgG4-RD,because none of the following is observed in these lesions:a mass-like formation;dense fibrosis;or obliterative phlebitis.Based on our review of the literature,there appear to be two types of IgG4-related gastrointestinal disease.One is a gastrointestinal lesion showing marked thickening of the wall of the esophagus and stomach,consisting of dense fibrosis with abundant infiltration of IgG4-positive plasma cells,which usually show submucosal spreading.The other is an IgG4-related pseudotumor occurring in gastrointestinal regions such as the stomach,colon,and major duodenal papilla,showing polypoid or mass-like lesions.Most solitary IgG4-related gastrointestinal lesions that are not associated with other IgG4-RD appear to be difficult to diagnose.It is of utmost importance to rule out malignancy.However,these lesions may respond to steroid therapy.To avoid unnecessary resection,IgG4-related gastrointestinal diseases should be considered in the differential diagnosis.

Differences between diffuse and focal autoimmune pancreatitis

AIM:To investigate differences in clinical features between diffuse-and focal-type autoimmune pancreatitis(AIP).METHODS:Based on radiological findings by computed tomography and/or magnetic resonance imaging,we divided 67 AIP patients into diffuse type(D type) and focal type(F type).We further divided F type into head type(H type) and body and/or tail type(B/T type) according to the location of enlargement.Finally,we classified the 67 AIP patients into three groups:D type,H type and B/T type.We compared the three types of AIP in terms of clinical,laboratory,radiological,functional and histological findings and clinical course.RESULTS:There were 34 patients with D-type,19 with H-type and 14 with B/T-type AIP.Although obstructive jaundice was frequently detected in D-typepatients(88%) and H-type patients(68%),no B/T-type patients showed jaundice as an initial symptom(P < 0.001).There were no differences in frequency of abdominal pain,but acute pancreatitis was associated more frequently in B/T-type patients(36%) than in D-type patients(3%)(P = 0.017).Serum immunoglobulin G(IgG)4 levels were significantly higher in D-type patients(median 309 mg/dL) than in B/T-type patients(133.5 mg/dL)(P = 0.042).Serum amylase levels in B/T-type patients(median:114 IU/L) were significantly greater than in H-type patients(72 IU/L)(P = 0.049).Lymphoplasmacytic sclerosing pancreatitis(LPSP) was histologically confirmed in 6 D-type,7 H-type and 4 B/T-type patients;idiopathic duct-centric pancreatitis was observed in no patients.Marked fibrosis and abundant infiltration of CD20-positive B lymphocytes with few IgG4-positive plasma cells were detected in 2 B/T-type patients.Steroid therapy was effective in all 50 patients(31 D type,13 H type and 6 B/T type).Although AIP relapsed during tapering or after stopping steroids in 3 D-type and 3 H-type patients,no patients relapsed in B/T type.During follow-up,radiological features of 6 B/T-type patients were not changed and 1 B/T-type patient improved naturally.CONCLUSION:Clinical features of H-type AIP were similar to those of D-type,but B/T-type differed from D and H types.B/T-type may involve diseases other than LPSP.

Progressive multi-organ expression of immunoglobulin G4-related disease: A case report

A 63-year-old Caucasian man presented with a cholestatic syndrome, renal failure and arthralgias. A laboratory examination revealed high immunoglobulin G (IgG) and IgG4 levels (5.95 g/L; normal range: 0.08-1.4 g/L), pointing to a diagnosis of systemic IgG4-related disease, with definite radiological evidence of biliary and pancreatic expression, and plausible renal, articular, salivary and lacrimal glands involvement. Due to the rarity of the condition, there are currently no random control trials to point to the optimal therapeutic approach. The patient has been on steroid therapy with the subsequent introduction of azathioprine, with a complete resolution of all symptoms, a rapid reduction to normalization of all blood tests, and a complete regression of the radiological picture. Our experience underlines the complexity of IgG4-related disease and its variable and sometimes progressive presentation, while pointing out the need for a careful and complete assessment for possible multi-organ involvement.