Diagnostic Criteria For IgG4-related Disease Research Articles

Eosinophilic Gastroenteritis with Ascites, Elevated Serum IgG4, and Hypereosinophilic Syndrome: A Manifestation of IgG4-related Disease?

A 76-year-old woman with persistent diarrhea was referred to our hospital. She had purpura, peripheral eosinophilia (18,177/μL), and an elevated serum IgG4 level (819 mg/dL). Abdominal computed tomography revealed massive ascites and bowel edema. A skin biopsy of the purpura revealed leukocytoclastic vasculitis with prominent eosinophilic infiltration. Biopsies of the gastrointestinal mucosa revealed dense eosinophilic infiltration, indicating eosinophilic gastroenteritis (EG) associated with the hypereosinophilic syndrome. The number of IgG4-positive cells increased in the duodenal mucosa; however, the diagnostic criteria for IgG4-related disease (IgG4-RD) were not met. Whether or not EG with ascites is a manifestation of IgG4-RD warrants further investigation.

The 2022 revised diagnostic criteria for IgG4-related respiratory diseases

In 2011, the Comprehensive Diagnostic Criteria for IgG4-related disease was published in Japan. Organ-specific diagnostic criteria based on organ-specific findings were proposed and published by each of the related societies, and the diagnostic criteria for IgG4-related respiratory disease was published in 2015. Based on the revisions to the comprehensive diagnostic criteria in 2020 and the publication of the Classification Criteria, new diagnostic criteria for IgG4-related respiratory disease are presented. Emphasis has been placed on evaluating specific pathological findings and excluding other respiratory diseases. It is mentioned in the commentary that in cases with imaging findings suggestive of interstitial pneumonia with chronic fibrosis or poor response to steroid therapy, other possible diseases should be considered.

Performance of classification and diagnostic criteria for IgG4-related disease and comparison of patients with and without IgG4-related disease

IgG4-related disease (IgG4-RD) was recently described in Japan. It is characterised by extensive organ involvement with tissue fibrosis. We assessed the performance of the 2019 American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) classification criteria and the 2020 revised comprehensive diagnostic (RCD) criteria as well as differences between patients with and without IgG4-RD. In this retrospective, single-centre study of 50 patients admitted with suspected IgG4-RD, we evaluated the sensitivity and specificity of both criteria. We also compared clinical characteristics and laboratory data of patients with IgG4-RD (n = 42) and patients without IgG4-RD (n = 8). The ACR/EULAR classification criteria had 88.1% sensitivity and 87.5% specificity for IgG4-RD diagnosis. The RCD criteria had 100% sensitivity and 50% specificity. Patients with IgG4-RD had significantly more affected organs (p = 0.002). Patients with a single affected organ and IgG4-RD had significantly higher serum IgG4/IgG ratios (p = 0.027), lower serum C-reactive protein levels (p = 0.020), and lower total haemolytic complement activity (p = 0.044) than those without IgG4-RD. The ACR/EULAR classification criteria have high specificity and the RCD criteria have high sensitivity for diagnosing IgG4-RD. The number of affected organs is important for diagnosing IgG4-RD.

Isolated IgG4-related cholecystitis with localized gallbladder wall thickening mimicking gallbladder cancer: a case report and literature review

BackgroundIgG4-related cholecystitis, which is a manifestation of IgG4-related disease in the gallbladder, is associated with autoimmune pancreatitis or IgG4-related sclerosing cholangitis in most cases; isolated gallbladder lesions without systemic manifestations are very rare. Gallbladder wall thickening is often diffuse, but sometimes localized, in which case, differentiation from gallbladder cancer becomes difficult. The characteristic features of IgG4-related cholecystitis on imaging that would enable differentiation from gallbladder cancer remain poorly described.Case presentationWe present a rare case of isolated IgG4-related cholecystitis with localized gallbladder wall thickening that was clinically difficult to distinguish from malignancy before resection. An 82-year-old man was referred to our hospital because of gallbladder wall thickening on abdominal ultrasonography without any symptoms. Dynamic computed tomography of the abdomen showed localized wall thickening from the body to the fundus of the gallbladder that was enhanced from an early stage with a prolonged contrast effect. There were no other findings, such as pancreatic enlargement and bile duct dilatation. Magnetic resonance cholangiopancreatography revealed neither dilatation nor stenosis of the bile duct and pancreatic duct. Endoscopic ultrasonography (EUS) showed a smooth layered thickening of the gallbladder wall with a maximum thickness of 6 mm and a well-preserved outermost hyperechoic layer in the same area. Laparoscopic cholecystectomy was performed because malignancy could not be completely ruled out. Pathological examination of a resected specimen revealed IgG4-positive plasma cell infiltration, fibrosis, and phlebitis. Although the serum IgG4 level measured after resection was normal, the condition was ultimately diagnosed as probable IgG4-related cholecystitis according to the 2020 revised comprehensive diagnostic criteria for IgG4-related disease. The EUS images reflected the pathological findings, in which lymphocytic infiltration was distributed in a laminar fashion in the gallbladder wall.ConclusionsAlthough rare, isolated IgG4-related cholecystitis with localized wall thickening mimicking gallbladder cancer remains a clinical problem. A smooth laminar thickening of the gallbladder wall on EUS imaging could be one of the most informative characteristics for differentiating IgG4-related cholecystitis from gallbladder cancer.

Investigation of IgG4-positive cells in idiopathic multicentric Castleman disease and validation of the 2020 exclusion criteria for IgG4-related disease.

Patients with plasma cell type idiopathic multicentric Castleman disease (PC‐iMCD) often show elevated serum IgG4 levels and IgG4‐positive cell infiltration in tissues due to overproduction of interleukin‐6, and may meet the diagnostic criteria for IgG4‐related disease (IgG4‐RD). Although PC‐iMCD has been listed as a major exclusion disease for IgG4‐RD, distinguishing between these diseases is challenging due to a lack of highly specific diagnostic biomarkers. In 2020, we proposed exclusion criteria of IgG4‐RD mimickers. In this paper, we validated the accuracy of the criteria in excluding one of the mimickers, PC‐iMCD, from IgG4‐RD. Validation was performed on 57 PC‐iMCD patients (39 presenting lymph node lesions and 19 with lung lesions) and 29 IgG4‐RD patients (22 presenting lymph node lesions and seven with lung lesions). According to our results, 20.5% of the PC‐iMCD patients with lymph node lesions and 42.1% of those with lung lesions met the diagnostic criteria for IgG4‐RD. All these patients with PC‐iMCD were excluded from a diagnosis of IgG4‐RD by the proposed criteria. Additionally, 6.9% of IgG4‐RD patients met the exclusion criteria. Thus, if the exclusion criteria are met, diagnosis should be made based on a combination of findings including organ distribution of disease, response to steroid therapy, and other pathological findings.

SIGNIFICANCE OF IgG4 IN IDIOPATHIC RETROPERITONEAL FIBROSIS

(Objective)Retroperitoneal fibrosis is largely divided into the idiopathic and secondary types. Some idiopathic cases include IgG4-related diseases, which are often similar to malignant diseases, such as lymphoma and sarcoma. The diagnostic criteria for IgG4-related disease are used and pathologic examination is necessary for a definitive diagnosis of IgG4-related retroperitoneal fibrosis. The first choice of treatment for IgG4-related retroperitoneal fibrosis is steroid administration, but no consensus has been established regarding its dose and tapering schedule. We investigated the significance of IgG4 in diagnosis and treatment of idiopathic retroperitoneal fibrosis. (Patients and methods)We examined 14 cases diagnosed as idiopathic retroperitoneal fibrosis between April 2013 and March 2019. Serum IgG4 was measured at the time of diagnosis in 13 cases, and changes over time in serum IgG4 before and after the induction of steroid therapy were measured in 6 cases. Computed tomography-guided biopsy was performed on 4 cases. (Results)Of all cases, 1 patient was diagnosed as IgG4-related retroperitoneal fibrosis and 5 patients were classified as possible group. Ten patients were administered steroid therapy. Percutaneous nephrostomy tube was placed in 3 patients and was removed in 2 of these patients after steroid therapy. The serum high levels of IgG4 were confirmed in all 4 patients who were classified into the possible group and who were treated with steroids. (Conclusion)Although histologic examination is necessary for the diagnosis of retroperitoneal fibrosis, tissue collection by open or laparoscopic surgery is highly invasive. CT-guided biopsy may be useful in high-risk cases, such as elderly patients on anticoagulation. After excluding other diseases in high-risk cases, response to empiric steroid therapy may be diagnostic. In the possible group, changes in serum IgG4 levels may reflect the disease condition and might be useful in determining the maintenance dose of steroids.

The 2020 Revised Comprehensive Diagnostic Criteria for IgG4-Related Disease. The Research Program for Intractable Disease by the Ministry of Health, Labour and Welfare (MHLW) Japan

The 2020 Revised Comprehensive Diagnostic Criteria for IgG4-Related Disease. The Research Program for Intractable Disease by the Ministry of Health, Labour and Welfare (MHLW) Japan

Follow-up with serum IgG4-monitoring in 8 patients with IgG4-related disease diagnosed by a lacrimal gland mass.

The diagnostic criteria for IgG4-related disease were previously published and serum IgG4 measurement has been reimbursed by national health insurance in Japan since 2012. Eight patients diagnosed with IgG4-related disease based on lacrimal gland masses were retrospectively reviewed. The 8 patients were 3 men and 5 women ranging in age from 52 to 77 (median, 63) years at the initial visit and their follow-up period ranged from 0.25 to 11 (median, 7) years. Bilateral and unilateral involvement were noted in 4 patients each; 2 on the right side and 2 on the left side in those with unilateral involvement. Serum IgG4 was high in 5 of 8 patients at the initial visit. Five patients with no systemic signs were followed without treatment, whereas oral steroids were administered and tapered in the other 3 patients who exhibited systemic signs. One patient with a history of radiation for MALT lymphoma in bilateral lacrimal glands developed IgG4-related disease in the left lacrimal gland 10 years later and was followed without treatment. Nine years later, her serum IgG4 level increased to 1500 mg/dL and paracardiac lesions, found on positron emission tomography, were confirmed to be MALT lymphoma by needle biopsy, leading to systemic chemotherapy. The other 7 patients had neither local recurrence nor additional systemic signs. Serum IgG4 monitoring may be useful to detect systemic complications in IgG4-related ophthalmic disease and markedly high serum IgG4 levels may indicate new lymphoma at other sites.

IGG4-RELATED DISEASE PRESENTING AS A LUNG MASS

SESSION TITLE: Fellows Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: IgG4 related disease (IgG4-RD) is a fibroinflammatory condition characterized by tumefactive lesions, dense lymphoplasmacytic infiltration rich in IgG4 cells, and fibrosis of multiple organ systems.1 The current cornerstone of diagnosis is the presence of IgG4 positive cells in tissue, regardless of the serum IgG4 level.2 Grossly the tissue appears to have a dense lymphoplasmacytic infiltrate and storiform fibrosis. This infiltration then creates a tumefactive mass that can destroy the affected organ.1 Patients may also experience epithelial damage from inflammation due to immune complex deposition.2 CASE PRESENTATION: Our patient is a 69-year-old male with a known medical history of CAD status post CABG, diabetes, hypertension, who presented to an outside hospital for a 3-month history of hemoptysis. He had an earlier admission for hemoptysis, and interferon release assay was negative, so he was discharged with 1 month of Augmentin. The patient did not undergo bronchoscopy at that time. 3 weeks prior to presentation to our facility he had small amount of hemoptysis that then progressed to small clots. He was a former smoker and had occupation exposure to pesticides. He was also incarcerated for one year. His CT was notable for mediastinal lymphadenopathy and possible obstruction in the anterior segment of the right upper lobe as well as a post-obstructive pneumonia versus dense atelectasis. No abnormalities were noted in the pancreas, biliary tree, or kidneys. Given his risk factors for malignancy he underwent bronchoscopy which did not reveal an endobronchial lesion, and a RUL mass was biopsied with electronavigational guidance. EBUS was also preformed and noted normal lymphoid tissue. Pathology of the RUL mass was notable for >50 IgG4 plasma cells as well as a dense lymphoplasmacytic infiltrate and storiform fibrosis. Microbiology of tissue was unrevealing. The patient’s hemoptysis resolved with time, and he was started on oral steroid therapy per Rheumatology. He was noted to have an elevated IgE at 260 IU/mL, but IgG4 l was within normal limits at 76.5 IU/mL. DISCUSSION: This patient’s case illustrates the varying presentations of IgG4-RD. While patients with this disease can more commonly present with mediastinal lymphadenopathy and intrathoracic lesions, they are usually associated with extra-thoracic lesions. Our patient, however, appears to have isolated thoracic disease. While our initial differential diagnosis included malignancy and infectious etiology, we were quite surprised to find IgG4-RD in this patient. CONCLUSIONS: There are no wildly accepted diagnostic or treatment guidelines for pulmonary IgG4-RD currently. Trial of steroid therapy has been proposed at a dose of 0.6mg/kg of body weight for 2-4 weeks, with a slow taper for up to 3 years.1 Prompt diagnosis is needed to halt further progression of IgG4-RD to the extensive fibrotic stage and multi-organ failure. Reference #1: Stone JH, Zen Y, Deshpande V. IgG4-Related Disease. NEJM 2012;366 (6): 539-551. Reference #2: Strehl JD, Hartmann A, Agaimy A. Numerous IgG4-positive plasma cells are ubiquitous in diverse localised non-specific chronic inflammatory conditions and need to be distinguished from IgG4- related systemic disorders. J Clin Pathol 2011;64:237-43. Reference #3: Matsui S, Yamamoto H, Minamoto S, Waseda Y, Mishima M, Kubo K. Proposed Diagnostic Criteria for IgG4-Related Disease. Res Inv 2016; 54: 130-132. DISCLOSURES: No relevant relationships by Ximena Solis, source=Web Response No relevant relationships by Andres Yepes Hurtado, source=Web Response

A CASE OF IGG4-RELATED INTERSTITIAL LUNG DISEASE MANIFESTING AS RECURRENT NECROTIZING PNEUMONIA

SESSION TITLE: Medical Student/Resident Lung Pathology SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: IgG4-related disease is a newly recognized fibroinflammatory disorder characterized by enlargement of one or more organs with classic histopathologic findings of diffuse lymphoplasmacytic infiltration and IgG4+ plasma cells. Presentation relies on the primary organ affected. Pulmonary disease can be especially difficult to characterize, as its course may mimic various lung pathologies. In this case report, we describe a case of IgG4-related interstitial lung disease (ILD) that manifested as recurrent necrotizing pneumonia. CASE PRESENTATION: A 33-year old female with past medical history of recent Group B Streptococcal bacteremia with aortic valve endocarditis was admitted for severe aortic insufficiency, necessitating aortic valve replacement. She developed hypoxic respiratory failure requiring ventilation support and treatment for pneumonia. After discharge, she was soon readmitted for right sided necrotizing pneumonia. Initial bronchoscopy positive for Streptococcus Viridians and Lactobacillus with repeat bronchoscopy after antibiotics showing normal flora. Patient was ultimately readmitted for left sided chest pain and hypoxia. Initial workup showed elevated inflammatory markers and CT chest with right-sided, multifocal pneumonia with cavitations. Microbiology and immunologic studies unremarkable. The patient did not improve on 1 month of antibiotics so underwent a lung biopsy revealing for interstitial fibrosis, inflammatory lymphoplasmacytic infiltrate, and positive IgG4 staining with elevated serum IgG4 levels- diagnostic for IgG4-related ILD. The patient was started on PO prednisone with complete resolution on most recent follow-up 2 months later. DISCUSSION: IgG4-related disease was first recognized in 2003 and is now understood as a spectrum of related diseases. In particular, the prevalence of pulmonary involvement remains uncertain, and neither diagnostic criteria nor treatment have officially been established. Review of previous cases reveals diverse presentations sharing features of other lung pathologies including pneumonias, cancer, and granulomatous diseases. The current report describes IgG4-related ILD manifesting as recurrent necrotizing pneumonia confirmed via characteristic lung pathology and an elevated serum IgG4 level of 235 mg/dL. Treatment relied on previous cases describing good prognosis from corticosteroids; specifically, prednisone 0.6 mg/kg with plans for slow taper. Patient was successfully weaned from oxygen support without further addition of DMARDs. CONCLUSIONS: IgG4-related disease encompasses a spectrum of fibroinflammatory disorders that can affect multiple organ systems, including the lungs. Given the evolving nature of IgG4-related ILD, diagnosis can be especially difficult given the multitude of presentations mimicking other infectious, neoplastic, and inflammatory disease processes. Larger studies could further understanding of this complex disease. Reference #1: Stone, John H., et al. “Mechanisms of Disease: IgG4-Related Disease.” The New England Journal of Medicine, 9 Feb. 2012. Reference #2: Chen, Chiu-Fan et al. “IgG4-related lung disease presenting as interstitial lung disease with bronchiolitis: A case report.” Medicine vol. 96,49 (2017): e9140. doi:10.1097/MD.0000000000009140 Reference #3: Umehara, Hisanori, et al. “Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD).” Modern Rheumatology, vol. 22, no. 1, 2 Jan. 2014, pp. 21-30. Abstract. DISCLOSURES: no disclosure on file for Duc Ho; No relevant relationships by Larry Jankelowitz, source=Web Response No relevant relationships by Ramier Lehne, source=Web Response

Gastric calcifying fibrous tumor suspected to be complicated with immunoglobulin G4-related disease treated by laparoscopy and endoscopy cooperative surgery: a case report

BackgroundCalcifying fibrous tumor (CFT) is a rare benign soft tissue lesion.Case presentationA 30-year-old woman was admitted to our hospital with complaints of epigastralgia. A 15-mm submucosal tumor was identified in the greater curvature of the superior body of the stomach by upper gastrointestinal endoscopy. Endoscopic ultrasonography revealed a hypoechoic lesion with an acoustic shadow consistent with calcification. Computed tomography showed a gastric tumor with calcification. A gastrointestinal stromal tumor was diagnosed, and gastric wedge resection was performed by laparoscopy and endoscopy cooperative surgery. On pathological examination, the tumor was identified to be a CFT. Postoperative serum IgG4 levels were 26.0 mg/dl, which supported the diagnosis of probable immunoglobulin G (IgG) 4-related disease, according to the comprehensive diagnostic criteria of IgG4-related disease. The patient was discharged on postoperative day 7 and remains well with no evidence of tumor recurrence for 2 years after resection.ConclusionWe herein reported a patient with a gastric CFT suspected to be complicated with immunoglobulin G4-related disease that was successfully treated by laparoscopy and endoscopy cooperative surgery.

Immunophenotype involved in IgG4-related disease

As stated in the comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), IgG4-RD is characterized by elevated serum IgG4 level and pathological findings, characterized by infiltration of IgG4-positive plasma cells. In addition to fibrotic changes, dysregulated activation of lymphocytes is considered as one of major pathogenic events in IgG4-RD. Among lymphocytes, the importance of plasmablast, T follicular helper (Tfh) cells, T type 2 helper (Th2) cells, T regulatory (Treg) cells, and CD4 positive T cells with cytotoxic activity has been reported. Conversely, comprehensive immunophenotyping in patients with IgG4-RD revealed that there are two different axes consisting plasmablast-Tfh cells and Treg cells. There is need for research to seek out molecules associated with these immunocompetent cell interactions. It is believed that this will contribute to the future application to disease-specific treatment for IgG4-RD.

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A 51-year-old woman with a previous history of rheumatoid arthritis experienced painless progressive visual loss in the left eye for 3 weeks. Fundus examination revealed optic disk pallor in her left eye. Magnetic resonance imaging of the brain and orbits showed enhancement of the pachymeninges and hypersignal at the left optic nerve. Meningeal biopsy was performed. Immunohistochemical staining for IgG4 revealed several IgG4-positive plasma cells, which in some areas reached the number of 50 cells/high-power field. In this case, the clinical and histopathological features of the patient met diagnostic criteria for rheumatoid arthritis and IgG4-related disease, respectively. Rheumatoid arthritis sometimes occurs with abundant IgG4 plasma cells and fulfills the histological diagnostic criteria for IgG4-related disease. This case demonstrates that overlapping features of IgG4-RD and rheumatoid arthritis may present in a single patient.

Clinicopathological features of immunoglobulin G4-related pleural lesions and diagnostic utility of pleural effusion cytology.

Immunoglobulin (Ig)G4-related disease is a recently described systemic immune-mediated fibro-inflammatory disease that frequently occurs in tumorous form. Herein, we elucidated the clinicopathological and cytological characteristics of IgG4-related pleural lesions (PLs). Among 22 patients with fibro-inflammatory PLs of idiopathic aetiology, eight cases were diagnosed as IgG4-PL and the remaining 14 as non-IgG4-PL according to comprehensive diagnostic criteria for IgG4-related disease. Cell block examination of pleural effusion (CBPE) was performed in five patients with IgG4-PL and in six with non-IgG4-PL. Both groups were compared in terms of clinical presentation, laboratory data, histopathological features of resected pleura, and cytological features of pleural effusion (PE). PE was the most common (six patients, 75%) clinical presentation of IgG4-PL. IgG4-PL comparatively showed significantly more frequent concomitant allergic disease (P=.021), higher serum IgE levels (P = .012), higher adenosine deaminase levels in pleural fluid (P=.005), and rare spontaneous recovery without treatment (P = .046). The IgG4-PL group was histologically characterised by thicker fibrous pleura, storiform fibrosis, and infiltration of regulatory T cells, eosinophils and basophils. Using CBPE, IgG4-PL was cytologically distinct with numerous IgG4+ cells and eosinophils. The cytology of CBPE positively correlated with the histology of pleural tissue in the number of IgG4+ cells and eosinophils (R=.769 and .803, respectively). IgG4-PL frequently presents with PE and is histologically and cytologically characterised by abundant infiltration of IgG4+ cells and eosinophils. We believe that CBPE with immunohistochemistry/special staining could assist in the auxiliary diagnosis of IgG4-PL.

Evaluation of IgG4+ Plasma Cell Infiltration in Patients with Systemic Plasmacytosis and Other Plasma Cell-infiltrating Skin Diseases

Systemic plasmacytosis is a rare skin disorder characterized by marked infiltration of plasma cells in the dermis. IgG4-related disease is pathologically characterized by lymphoplasmacytic infiltration rich in IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis, accompanied by elevated levels of serum IgG4. Reports of cases of systemic plasmacytosis with abundant infiltration of IgG4+ plasma cells has led to discussion about the relationship between systemic plasmacytosis and IgG4-related disease. This study examined IgG4+/IgG+ plasma cell ratios in 4 patients with systemic plasmacytosis and 12 patients with other skin diseases that show marked infiltration of plasma cells. Furthermore, we examined whether these cases met one of the pathological diagnostic criteria for IgG4-related disease (i.e. IgG4+/IgG plasma cells ratio of over 40%). Only one out of 4 patients with systemic plasmacytosis met the criterion. These results suggest that systemic plasmacytosis and IgG4-related disease are distinct diseases.

A CASE OF IgG4-RELATED DISEASE WITH THICKENING OF THE RENAL PELVIS AT LEFT RENAL HILUM DIAGNOSED BY OBTURATOR LYMPH NODE DISSECTION

IgG4-related kidney disease (IgG4-RKD) is a comprehensive term for renal lesions associated with IgG4-related disease (IgG4-RD), which is a recently recognized clinical entity characterized by a dense lymphoplasmacytic infiltrate rich in IgG4+ plasma cells with fibrosis affecting several organs. A 70-year-old woman was referred to our hospital for an abnormality at the left renal hilum detected by CT scan. Urinalysis was negative, urine cytology was rated as Class IIIa, and contrast-enhanced CT revealed left renal pelvic wall thickening without an irregular lumen and swelling of bilateral obturator lymph nodes. Ureterorenoscopy and biopsy were performed, and results showed no evidence of malignancy. Then, laparoscopic pelvic lymphadenectomy was performed. Plasma cells were the predominant infiltrating inflammatory cells; immunostaining showed marked infiltration of IgG4+ plasma cells with >10 IgG4+ plasma cells per high-power field, and the IgG4+/IgG+ cell ratio was over 40%. Serum IgG4 was extremely high. We made a final diagnosis of possible IgG4-related disease according to Comprehensive diagnostic Criteria for IgG4-related disease 2011. We report a long-term (40-month) follow-up case of IgG4-related kidney disease without therapy because there are no symptoms.

Approach to cutaneous vasculitides with special emphasis on small vessel vasculitis: histopathology and direct immunofluorescence.

The present review will focus on recent publications in cutaneous vasculitides. Some histopathological and clinical features, such as papillary dermal edema, perivascular C3 deposition, clinically evident edema, and lesions above the waist, may point out renal or gastrointestinal involvement in Henoch-Schönlein purpura (HSP). HSP associated with familial Mediterranean fever differs from typical isolated HSP by showing no deposits of IgA, much younger age, and location of the lesions on the face or the trunk. Single-organ cutaneous small vessel vasculitis is a more restricted entity than hypersensitivity vasculitis and HSP. Because cutaneous polyarteritis nodosa and macular lymphocytic arteritis share some clinicopathologic features, the question is raised whether they are not two different entities. Several histopathological features defining IgG4-related disease are found in granuloma faciale and erythema elevatum diutinum, two localized chronic cutaneous vasculitis; however, in a recent series no diagnostic criteria for IgG4-related disease was detected in them. When a patient presents with skin lesions, in which necrotizing or leukocytoclastic vascuitis is confirmed histologically, irrespective of the size of the affected vessel, the possibility of systemic vasculitis, an infection, medication, or a systemic disease such as systemic lupus erythematosus must be searched before reaching definitive diagnosis.

Increased number of IgG4-positive plasma cells in chronic rhinosinusitis

Conclusion: High levels of IgG4-positive plasma cells were observed in tissue samples from ∼30% of patients with chronic rhinosinusitis who satisfied the comprehensive diagnostic criteria for IgG4-related disease. Detection of increased numbers of IgG4-positive plasma cells in the nasal cavity or paranasal sinuses might not be sufficient to make a diagnosis of IgG4-related rhinosinusitis, and a comprehensive evaluation is required.Objectives: This study aimed to clarify the clinicopathological characteristics of IgG4-positive plasma cells in patients with chronic rhinosinusitis.Method: This study examined nasal mucosal specimens from 35 patients and assigned them to high-IgG4 and low-IgG4 groups based on infiltration of IgG4-positive plasma cells. It compared the pathological characteristics of the two groups, including the presence of fibrosis, phlebitis, hyperplasia of the nasal glands and infiltration of inflammatory cells.Results: No cases of chronic rhinosinusitis showed storiform fibrosis or obliterative phlebitis. The mean number of IgG4-positive plasma cells in samples from all patients was 29.8 ± 40.3/high-power field. Eleven of the 35 cases (31.4%) were classified as high-IgG4. Hyperplasia of the nasal glands was observed significantly more frequently in the high-IgG4 group than in the low-IgG4 group (p = .03).

Abdominal Manifestations of IgG4-Related Disease

IgG4-related disease is a recently recognized systemic disorder involving multiple organs throughout the body. The multi-organ involvement of this disease was previously thought to occur as isolated, unrelated autoimmune disorders. Although virtually any part of the body may be involved in IgG4-related disease, abdominal manifestations tend to predominate in most affected individuals. While autoimmune pancreatitis is the most commonly encountered abdominal disorder in the setting of IgG4-related disease, the liver, kidneys, gastrointestinal tract, retroperitoneum, and mesentery may likewise be involved. Various diagnostic criteria for IgG4-related disease have been proposed based on physical exam, serology, and histopathologic confirmation. However, imaging plays an essential role in the diagnosis of this disorder, not only to establish the presence of IgG4-related disease, but to assess the severity and extent of systemic disease involvement.

A case of IgG4-related disease coexisted with rectal cancer.

A 67-year-old man was referred to our hospital with suspicion of rectal tumor, hilar tumor, and urinary tumor. Colonoscopic findings were intermittent nodular lesions with redness which were atypical to primary rectal cancer. Endoscopic retrograde cholangiopancreatography showed narrowing of the bilateral intrahepatic bile duct. However, the findings were improved 1 month later. Blood biochemistry showed high level of serum IgG4 up to 1140 mg/dl. The patient matched to comprehensive diagnostic criteria for IgG4-related disease as a possible diagnostic case. Laparoscopic low anterior resection with creation of ileostomy was performed for rectal cancer. Histological findings revealed cancer cells spread horizontally at submucosal layer and subserosal layer. There was marked infiltration of the plasma cells and lymphocytes at tumor stroma, and more than half of the plasma cells were positive for IgG4. After surgery, the level of serum IgG4 was decreased to 597 mg/dl. Although the association with IgG4-related disease and colorectal disease is unclear, the tumor progression was atypical for rectal cancer. Some report that the disease may rise up the risk of a malignant disease. It is necessary to perform systemic examination keeping in mind for concurrence of malignancy.