Systematic analysis for clinical characteristics and outcomes of IgG4-related disease patients during the COVID-19 pandemic.

BACKGROUND: To systematically describe clinical characteristics and investigate factors associated with COVID-19-related infection, hospital admission, and IgG4-related disease relapse in IgG4-RD patients. METHODS: Physician-reported IgG4-RD patients were included in this retrospective study. Using multivariable logistic regression analysis to determine factors for primary outcome (COVID-19-related IgG4-RD relapse) and secondary outcome (COVID-19-related infection and hospital admission). Covariates included age, sex, body mass index, smoking status, comorbidities, IgG4-RD clinical features, and treatment strategies. RESULTS: Among 649 patients, 530 had a diagnosis of COVID-19, 25 had COVID-19-related hospital admission, and 69 had COVID-19-related IgG4-RD relapse. Independent factors associated with COVID-19 infection were age (OR, 0.98; 95% CI, 0.96-1.00), body mass index (1.10, 1.03-1.18), and tofacitinib (0.34, 0.14-0.79). Further analysis indicated that age (1.10, 1.03-1.16), coronary heart disease (24.38, 3.33-178.33), COVID-19-related dyspnea (7.11, 1.85-27.34), pulmonary infection (73.63, 16.22-4615.34), and methotrexate (17.15, 1.93-157.79) were associated with a higher risk of COVID-19-related hospital admission. Importantly, age (0.93, 0.89-0.98), male sex (0.16, 0.03-0.80), ever/current smoking (19.23, 3.78-97.80), COVID-19-related headache (2.98, 1.09-8.17) and psychiatric symptoms (3.12, 1.07-9.10), disease activity before COVID-19 (1.89, 1.02-3.51), number of involved organs (1.38, 1.08-1.76), glucocorticoid dosage (1.08, 1.03-1.13), and methotrexate (5.56, 1.40-22.08) were strong factors for COVID-19-related IgG4-RD relapse. CONCLUSIONS: Our data add to evidence that smoking and disease-specific factors (disease activity, number of involved organs, and specific medications) were risk factors of COVID-19-related IgG4-RD relapse. The results highlight the importance of adequate disease control with b/tsDMARDs, preferably without using methotrexate and increasing glucocorticoid dosages in the COVID-19 era. Key Points • COVID-19-related infection or hospital admission were associated with known general factors (age, body mass index, specific comorbidities and methotrexate) among IgG4-RD patients. • Smoking and disease-specific factors (disease activity, number of involved organs and specific medications) were associated with higher odds of COVID-19-related IgG4-RD relapse. • The results highlight the importance of adequate disease control with b/tsDMARDs, preferably without using methotrexate or increasing glucocorticoid dosages.

Potential impact of autoimmune diseases family history in IgG4-related disease: a retrospective cohort study.

OBJECTIVE: Autoimmune comorbidities may be associated with IgG4-related disease (IgG4-RD), here we aimed to determine the correlation of autoimmune diseases (AID) family history and IgG4-RD in a Chinese cohort. METHODS: This retrospective cohort study identified 628 cases of IgG4-RD in Peking Union Medical College Hospital. Patients were classified into two groups, with AID family history group (AID-positive) and without AID family history group (AID-negative). We viewed the potential value of AID family history on IgG4-RD by comparing the differences between the two groups. In addition, Cox regression analysis estimated CIs and HR for IgG4-RD risk. RESULTS: 93 (14.8%) IgG4-RD patients had AID family history. Compared with AID-negative group, baseline data analysis revealed that AID-positive group patients had an earlier age of IgG4-RD onset (50.4±14.8 vs 54.2±12.6, p=0.014*), a higher percentage of antinuclear antibody (ANA) positivity (38.9% vs 22.7%, p=0.0277*) and Riedel thyroiditis (10.9% vs 2.4%, p=0.001*), were prone to comorbid with other AID (16.1% vs 6.2%, p=0.0238*). Cox analysis found that younger age (HR 0.97 (95% CI 0.94 to 0.99), p=0.0384*) and higher proportions of baseline peripheral eosinophils (HR 1.1 (95% CI 1.02 to 1.2), p=0.0199*) increased the risk of unfavourable prognosis for AID-positive IgG4-RD patients. CONCLUSIONS: 14.8% of IgG4-RD patients had AID family history, with younger age of disease onset age and higher frequency of ANA positivity in AID-positive group, indicating that IgG4-RD may share genetic background with other AID.

Clinical profiles differ in IgG4-related disease with and without allergy: a large case-control study in China.

OBJECTIVES: This study aimed to elucidate different clinical profiles in IgG4-related disease (IgG4-RD) with and without allergy. METHODS: Four hundred and thirty-four patients diagnosed with IgG4-RD at Peking University People's Hospital were included. Clinical and treatment options-based relapse data were collected and compared between IgG4-RD patients with and without allergy. RESULTS: Among these patients, 214 (49.3%) had allergic diseases. Most of the IgG4-RD patients with allergy had initial involved organs directly exposed to ambient air and their allergic symptoms occurred mostly before or at IgG4-RD disease onset. Compared with IgG4-RD patients without allergy, allergic patients had almost equal sex ratio, more organ involvement, earlier ages of disease onset and diagnosis, longer disease duration, higher incidence of dacryoadenitis, sialadenitis, lymphadenopathy, paranasal sinus and lung lesions. Higher serum IgG4, IgE and IgG4/IgG ratio, lower serum C3 complement 3 (C3) and C4, and higher incidence of eosinophilia were also found in IgG4-RD patients with allergy. Furthermore, allergy may increase relapse rate and shorten relapse-free survival time in IgG4-RD patients treated with glucocorticoids only, whereas combination therapy of glucocorticoids and immunosuppressants could improve treatment outcome. CONCLUSIONS: Allergy leads to disparities in clinical profiles in IgG4-RD patients. Allergy could result in higher relapse rate and shorten relapse-free survival time in patients receiving glucocorticoids only.

Malignancies in Immunoglobulin G4-related ophthalmic disease.

PURPOSE: Clinical phenotypes in Immunoglobulin G4-related disease (IgG4-RD) according to the patterns of affecting organs have different risks of malignancies. We attempt to determine the association of malignancies with IgG4-related ophthalmic disease (IgG4-ROD). DESIGN: Retrospective cohort study. METHODS: Review of medical records, orbital images and histopathology reports in a territory-wide cohort of biopsy proven IgG4-ROD patients from 2005-2019. FINDINGS: Among 122 patients who had biopsies taken from adnexal lesions including lacrimal glands (n = 108), orbital mass (n = 30), infiltrated orbital fat (n = 10), conjunctiva (n = 2) or extraocular muscles (n = 3), 13% (16/122) developed malignancies over 73 ± 48months' follow-up. There were 9 cases of ocular adnexal lymphoma (OAL) and 7 extra-orbital malignancies. Compared with the general population, the incidence of OAL was significantly higher (standardized incidence ratios, SIRs = 10.0, 95%CI = 4.5-17.6) while that of extra-orbital malignancies was similar. The SIRs was highest within the first year (SIR = 46.7, 95%CI = 18.5-87.6) when 7 OAL were concomitantly diagnosed. Patients who developed OAL or extra-orbital malignancies were older than other patients at IgG4-ROD diagnosis (64.9 ± 7.1, 68.3 ± 8.5 versus 55.2 ± 15.0 years, P < 0.05). Asymmetric lacrimal gland enlargement (78% versus 13%), lack of frontal (0% versus 12%) or infraorbital nerve enlargement (0% versus 36%) were associated with OAL (all P < 0.05). Pre-treatment serum IgG4 level or extra-orbital IgG4-RD involvement was similar among patients with or without malignancies. CONCLUSION: In this biopsy-proven IgG4-ROD cohort, 7% developed OAL which was 10 times higher than the general population. Patients with asymmetric lacrimal gland enlargement or without trigeminal nerves involvement radiologically were associated with OAL.

Reducing relapse through maintenance steroid treatment can decrease the cancer risk in patients with IgG4-sclerosing cholangitis: Based on a Japanese nationwide study.

OBJECTIVE: IgG4-related sclerosing cholangitis (IgG4-SC) is recognized as a benign steroid-responsive disease; however, little is known about the risk of development of cancer in patients with IgG4-SC and about how to counter this risk. DESIGN: We conducted a retrospective review of the data of 924 patients with IgG4-SC selected from a Japanese nationwide survey. The incidence, type of malignancy, and risk of malignancy in these patients were examined. Then, the standardized incidence ratio (SIR) of cancer in patients with IgG4-SC was calculated. RESULTS: Relapse was recognized in 19.7% (182/924) of patients, and cancer development was noted in 15% (139/924) of patients. Multivariate analysis identified only relapse as an independent risk factor for the development of cancer. In most of these patients with pancreato-biliary cancer, the cancer developed within 8 years after the diagnosis of IgG4-SC. The SIR for cancer after the diagnosis of IgG4-SC was 12.68 (95% confidence interval [CI] 6.89-8.79). The SIRs of cancers involving the biliary system and pancreas were 27.35 and 18.43, respectively. The cumulative survival rate was significantly better in the group that received maintenance steroid treatment (MST) than in the group that did not; thus, MST influenced the prognosis of these patients. CONCLUSION: Among the cancers, the risk of pancreatic and biliary cancers is the highest in these patients. Because of the elevated cancer risk, surveillance after the diagnosis and management to prevent relapse are important in patients with IgG4-SC to reduce the risk of development of cancer.

Comment on "The risk of malignancy in patients with IgG4-related disease: a systematic review and meta-analysis" by Yu et al.

With great interest, we have read the recent article "The risk of malignancy in patients with IgG4-related disease: a systematic review and meta-analysis" by Yu et al. While we have a great appreciation for the work conducted by the authors there are some methodological issues need to be considered. First, the period of articles included in the study, almost before 2013, implied that most follow-up days in these articles were earlier than the established date of a unified definition of IgG4-RD, 2011. Thus, it may lead to misclassification bias in the study. Second, IgG4-RD is a fibrous-inflammatory process that often involves multiple organs; however, malignant tumors related to IgG4-RD proposed in the study were only confined to four diseases. Therefore, we suggest adding subgroup analysis for more malignancies depending on the prevalence of IgG4-RD involved organs to ensure better clinical practice. Third, the causation between IgG4-RD and malignancy remains obscure currently. The time course for development in different malignancies varies significantly so that we cannot infer that malignancies discovered after IgG4-RD are directly relevant. With problems mentioned above, we recommend solutions to make this article more convincing.

Nationwide epidemiological survey of immunoglobulin G4-related disease with malignancy in Japan.

BACKGROUND AND AIM: To clarify the clinicoepidemiological characteristics of immunoglobulin G4 (IgG4)-related disease (IgG4-RD) with malignancy, a nationwide epidemiological survey was conducted. METHODS: Immunoglobulin G4-related disease patients with malignancy who had visited selected hospitals in Japan were surveyed. The study consisted of two stages: the number of IgG4-RD patients with malignancy was estimated by the first questionnaire and their clinicoepidemiological characteristics were assessed by the second questionnaire. RESULTS: The frequencies of autoimmune pancreatitis (AIP), IgG4-related sialadenitis, IgG4-related eye disease, IgG4-related kidney disease, and IgG4-related retroperitoneal fibrosis were 44.7%, 20.8%, 14.0%, 5.16%, and 5.12%, respectively. The overall prevalence of malignant disease in IgG4-RD cases was estimated to be 10 900 per 100 000 cases, which was significantly higher than that of malignant disease in the general population. The prevalence of malignant lymphoma in IgG4-RD cases was the highest and was estimated to be 1985 per 100 000 cases. IgG4-related kidney disease had the highest frequency of malignant disease (17.1%). In data from 200 patients, 61 (30.5%) cases of cancer were found 2 years or more before the IgG4-RD diagnosis, 92 cases (46%) during the 1 year preceding or following IgG4-RD diagnosis, and 62 cases of cancer (31%) 2 or more years following IgG4-RD diagnosis. CONCLUSIONS: The nationwide survey for IgG4-RD with malignancy in Japan showed that IgG4-RD may be related with malignant diseases.

Differences of clinicopathological features between IgG4-related and non-IgG4-related idiopathic retroperitoneal fibrosis.

OBJECTIVE: To evaluate the clinical and pathological features of IgG4-related and non-IgG4-related idiopathic retroperitoneal fibrosis (IRF) according to the latest classification criteria for IgG4-related disease in 2019. METHODS: Patients with IRF confirmed by histological examination from our hospital between 2000 and 2020 were selected in this study. Medical records of all patients were reviewed by independent researchers. Retroperitoneal specimens were obtained for hematoxylin & eosin staining, elastic-collagenous fiber staining, and immunohistochemical analysis. The clinical and pathological features between IgG4-related and non-IgG4-related IRF were analyzed. RESULTS: A total of 105 patients were included with 77 in the IgG4-related group and 28 in non-IgG4-related group. The ratio of male to female patients and the incidence of acute renal failure were significantly higher in the IgG4-related group than in the non-IgG4-related group. Elevated erythrocyte sedimentation rate and C-reactive protein were more common and the recurrence rate was significantly higher in the IgG4-related group than in the non-IgG4-related group. Radiographically, the ureter was more easily involved by retroperitoneal soft tissue in the IgG4-related group. Histologically, there were no significant differences in the incidence of dense lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis between the two groups except for the IgG4 staining. CONCLUSIONS: Idiopathic retroperitoneal fibrosis can be classified into IgG4-related and non-IgG4-related subtypes. There were no significant pathological differences between the two subtypes of IRF, except for the IgG4 staining. Patients with the IgG4 subtype tended to be more likely to be male, have a higher inflammatory index, and be more likely to have recurrence.

The risk of malignancy in patients with IgG4-related disease: a systematic review and meta-analysis.

BACKGROUND: The relationship between IgG4-related disease (IgG4-RD) and the risk of malignancy is still controversial. This article focused on assessing the risk of cancer in patients with IgG4-RD by meta-analysis. METHODS: We conducted a systematic review of the literature and meta-analysis characterizing the associated risk of overall malignancy and four site-specific malignancies (pancreas, lung, gastric and lymphoma) in patients with IgG4-RD. A search from 2003 to 2020 was performed using specified terms from PubMed, Embase, Web of Science and SinoMed. Random-effects model analysis was used to pool standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were conducted to clarify the heterogeneity of the included studies. Begg's funnel plot and Egger's linear regression test were used to evaluate the bias of the meta-analysis. A P value < 0.05 indicated the existence of publication bias. RESULTS: A total of 10 studies were included in the article. The overall SIR estimates suggested an increased risk of overall cancer in IgG4-RD patients (SIR 2.57 95% CI 1.72-3.84) compared with the general population. The specific SIRs for pancreas and lymphoma were higher than those of the general population in IgG4-RD patients (SIR 4.07 95% CI 1.04-15.92, SIR 69.17 95% CI 3.91-1223.04, respectively). No significant associations were revealed in respiratory and gastric cancer (SIR 2.14 95% CI 0.97-4.75, SIR 0.95 95% CI 0.24-3.95, respectively). Four studies were found to be the major sources of heterogeneity by sensitivity analysis. There was no evidence of publication bias via Egger's test. CONCLUSION: Compared with the general population, patients with IgG4-RD appear to have a higher risk of overall cancer, especially pancreatic and lymphoma. The risk of lung and gastric cancer was not different between IgG4-RD patients and the general population.

IgG4-Related Disease: A Clinical Case Series From a Tertiary Care Center in India.

AIM: Immunoglobulin G4-related disease (IgG4-RD) is often an unrecognized, rare fibroinflammatory condition that can involve various organ systems. This study aimed to identify the different clinical patterns of this disease in a single center in North India. METHODS: Patients were diagnosed on the basis of published diagnostic criteria for IgG4-RD. Patients' presenting complaints; epidemiologic profiles; and laboratory, radiologic, and histologic findings along with the treatment and outcomes were collected and analyzed. RESULTS: In total, 70 patients were diagnosed with the disease. The female-to-male ratio was 0.94:1, and it increased with multiorgan involvement. The mean age of patients was 41.4 years, and the majority of the patients (65.7%) were younger than 50 years. Patients were diagnosed as possible (38.57%), probable (32.85%), and definite (28.57%) IgG4-RD. The incidence of the involvement of orbital and periorbital tissues was the highest (52.9%); however, 13% of the patients had multiple organ involvement. Patients with involvement of the retroperitoneal tissues and the lymph nodes were 8.5% and 5.7%, respectively. Increased serum IgG4 levels were found in 74.3% of the patients with single-organ involvement, whereas all patients with multiorgan involvement had increased IgG4 levels. The majority of patients (94.3%) required immunosuppressive medications along with corticosteroids. Azathioprine was the most commonly used (72.8%) immunosuppressive medication. Rituximab was used in 17.1% of the patients, of whom only one had multisystem involvement. CONCLUSIONS: This study depicts the most common patterns of organ involvement, along with the epidemiologic, laboratory, histologic, and radiologic data and response to treatment, in IgG4-RD, with a definite ophthalmology referral bias.

Lifetime Allergy Symptoms in IgG4-Related Disease: A Case-Control Study.

OBJECTIVE: The etiology of IgG4-related disease (IgG4-RD) is unknown, and there has been controversy over the significance of allergic conditions in IgG4-RD. We examined the prevalence of lifetime allergy symptoms in IgG4-RD and the association between these and IgG4-RD. METHODS: We identified IgG4-RD patients and non-IgG4-RD controls without autoimmune conditions seen at a single center. IgG4-RD patients were classified using the American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria. Allergy symptoms were ascertained by questionnaire. We assessed the association of IgG4-RD features with allergy symptoms. We compared the proportion of cases and controls with allergy symptoms using conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) after matching cases and controls 1:1 by age and sex. RESULTS: Lifetime allergy symptoms were reported by 165 (71%) of 231 IgG4-RD patients. Aeroallergen symptoms were most commonly reported (n = 135, 58%), followed by skin allergy symptoms (n = 97, 42%) and food allergy symptoms (n = 47, 20%). IgG4-RD cases with a history of allergy symptoms were more likely to have head and neck involvement (OR 2.0 [95% CI 1.1-3.6]) and peripheral eosinophilia (OR 3.3 [95% CI 1.2-9.0]) than those without allergy symptoms. The prevalence of any allergy symptoms was similar between cases and controls (OR 0.7 [95% CI 0.4-1.1]); this remained consistent after stratifying by head and neck involvement. CONCLUSION: Lifetime allergy symptoms are common in IgG4-RD but are not reported more often in IgG4-RD compared to non-IgG4-RD patients without autoimmune conditions. These findings suggest that allergies are not uniquely associated with the pathogenesis or presentation of IgG4-RD.

Significance of high serum IgG4 in complete or non-full-fledged IgG4-related disease-a retrospective investigation of 845 patients and its clinical relevance.

OBJECTIVE: Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized heterogeneous, subacute, and usually silent autoimmune disease involving many organs with protean manifestations. However, high IgG4 in serum is not necessarily indicating an IgG4-RD. The aims of this study were to investigate the clinical relevance of high serum IgG4 level in IgG4-RD or non IgG4-RD patients, and to see if IgG4-RD in Taiwan differs from that in other parts of the world. METHODS: Eight hundred forty-five patients with high IgG4 were retrospectively reviewed from January 2002 to May 2020 in Taipei Veteran General Hospital. Two hundred sixty-seven patients fulfilled IgG4-RD criteria and were categorized into pancreato-hepato-biliary disease, retroperitoneal fibrosis and/or aortitis, head/neck-limited disease, classic Mikulicz syndrome with systemic involvement, CNS-limited disease, sclerosing vasculitis, skin-limited disease, and sensorineural hearing disease. These manifestations were correlated to smoking, atopy, hyper-IgE/eosinophilia, aging, malignancies, and hypocomplementemia. Five hundred seventy-eight patients were not fulfilling the criteria but were also analyzed for the prevalence of allergy, malignancy, connective tissue diseases, lung diseases, and infections. RESULTS: In IgG4-RD patients, 124 (46.4%) smoked. Top 4 clinical subtypes included Mikulicz syndrome with systemic involvement (33.3%), pancreato-hepatobiliary disease (31.4%), head/neck disease (19.4%), and retroperitoneal fibrosis/aortitis (12.7%). Top 4 co-morbid conditions included high serum IgE/eosinophilia (46.2%), hypocomplementemia (34%), malignancies (13.4%), and allergy (13.4%). Pancreato-biliary disease was associated with high IgE/eosinophilia (r2 = 0.380, P = 0.025) and malignancy (r2 = 0.211, P = 0.027), Miculicz syndrome with allergy (r2 = 0.396, P < 0.01) and high IgE/eosinophil (r2 = 0.396, P < 0.01), CNS diseases (r2 = 0.973, P = 0.035) and sclerosing vasculitis (r2 = 1, P < 0.01) with advanced age respectively, with the latter being also related to atopy and high IgE/eosinophilia (r2 = 1, p < 0.01). CONCLUSION: Smoking may precipitate IgG4-RD. IgG4-RD with pancreato-hepatobiliary disease is closely related to allergy and neoplasm, and those with Mikulicz syndrome may result from atopy. Elderly IgG4-RD patients tend to develop CNS pathology parallel to advancing of age. The disease may probably be originated from an unknown mechanism that may sporadically evolve into malignancies.

Clinical characteristics of IgG4-related respiratory disease patients: a large Chinese cohort study.

OBJECTIVES: IgG4-related disease (IgG4-RD) is an autoimmune disorder and frequently involves multiple organs. The respiratory tract is one of the most frequently affected sites. In this study, we aimed to compare the demographic and clinical characteristics between IgG4 related respiratory disease (IgG4-RRD+) and extra-thoracic IgG4-related disease (IgG4-RRD-) in a large cohort. METHODS: A total of 448 cases of IgG4-RD (104 IgG4-RRD+ patients and 344 IgG4-RRD- patients) diagnosed at Peking University People's Hospital during 2003 to 2020 were included in our study. Patients' demographic data, clinical characteristics, laboratory parameters and imaging features were analysed. RESULTS: IgG4-RRD+ patients had an older age at disease onset and diagnosis. Multiorgan involvement and hypocomplementaemia were more common in IgG4-RRD+. Besides, the level of ESR, IgG and IgG4 were higher in IgG4-RRD+ patients. In IgG4-RRD+ group, salivary gland, lacrimal gland, lymph nodes, biliary system and kidney were more commonly involved than those in the IgG4-RRD- group. Also, more organ involvement eosinophilia and biliary involvement were independent risk factors for the development of IgG4-RRD+. CONCLUSIONS: Our study revealed demographic, clinical and laboratory differences between the two phenotypes, in addition to describing the imaging features of IgG4-RRD+, which will be helpful for understanding of the disease.

Clinicopathological characteristics of IgG4-related lung disease.

BACKGROUND: Immunoglobulin G4-related lung disease (IgG4-RLD) is a rare entity. We retrospectively analyzed the clinical and histopathological characteristics of patients with pathologically confirmed IgG4-RLD to improve the diagnosis rate and reduce the risk of misdiagnosis. METHODS: We screened the pathological reports of 4838 patients with pulmonary surgery and/or biopsy specimens from April 2017 to April 2021 at Sun Yat-Sen Memorial Hospital affiliated with Sun Yat-Sen University, and specimens from 65 patients with suspected IgG4-RLD were subjected to immunohistochemical staining for IgG4 and IgG. Finally, 10 patients with definite IgG4-RLD that was pathologically confirmed were enrolled and analyzed. RESULTS: The incidence of pathologically confirmed IgG4-RLD was 0.2% (10/4838). The ten patients had an average age of 59.7 years at diagnosis, and the male-to-female ratio was 9:1. The initial clinical manifestations were nonspecific, and cough was the most common symptom (4/10). More than one organ was involved in most patients (8/10), and mediastinal/hilar lymph node involvement was often observed (7/10). Serum IgG4 was analyzed in 6 patients and found to be elevated. Serum tumor marker levels were within the normal range or were slightly elevated. Computed tomography (CT) of the chest and/or 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) imaging revealed that 5 patients had a mixed type, 3 patients had the solid nodular type, and 2 patients had the bronchovascular type. All pulmonary masses and large nodules with solid patterns had spiculated margins and inhomogeneous enhancement with or without pleural indentation and a lobulated appearance. Abundant lymphoplasmacytic cell infiltration and fibrosis were observed in all patients. The expression of IgG4 and IgG was upregulated in the pulmonary sections. Seven patients were treated with glucocorticoids with or without additional immunosuppressants and responded well. CONCLUSIONS: The results of our study suggest that multiple imaging findings, an elevated serum IgG4 concentration, and no significant increase in serum tumor biomarkers could provide diagnostic support for IgG4-RLD, especially for isolated IgG4-RLD or IgG4-RLD that includes other organ involvement that does not aid in establishing the diagnosis.

Ophthalmic involvement disparities in clinical characteristics of IgG4-related disease: a retrospective study of 573 patients.

PURPOSE: To investigate the clinical manifestations of orbital involvement in a large cohort of Chinese patients with IgG4-related disease (IgG4-RD). METHODS: A total of 573 patients with IgG4-related disease were included. We described and compared the demographic, clinical, laboratory and histopathologic findings from 314 patients with IgG4-related ophthalmic disease (IgG4-ROD) and 259 with extra-ophthalmic IgG4-RD. RESULTS: Male predominance was found significant in extra-ophthalmic IgG4-RD only. Patients with IgG4-ROD showed younger age at diagnosis and longer duration from onset till diagnosis. In patients with extra-ophthalmic IgG4-RD, the most commonly involved extra-ophthalmic organ was pancreas; while in IgG4-ROD patients, salivary gland was most frequently affected. Multivariate analysis exhibited IgG4-ROD was associated with allergy history, higher serum IgG4/IgG ratio, multiple organs involvement and sialoadenitis. Orbital images were reviewed in 173 (55.1%) IgG4-ROD patients. Fifty-one (29.5%) patients had multiple lesions. Lacrimal gland involvement was detected in 151 (87.3%) patients, followed by extraocular muscles (40, 23.1%), other orbital soft tissue (40, 23.1%) and trigeminal nerve (8, 4.6%). Biopsy was performed from various organs in 390 cases. A dense lymphoplasmacytic infiltration and fibrosis were the main feature in orbital specimens. Storiform fibrosis and obliterative phlebitis were absent in lacrimal gland. CONCLUSIONS: Lacrimal gland involvement was the most common orbital manifestation of IgG4-ROD. Patients with IgG4-ROD showed different characteristic in demographic, clinical, laboratory findings compared to patients with extra-ophthalmic IgG4-RD. These features might indicate potential differences in the pathogenesis of these two subgroups of IgG4-RD.

Enfermedad relacionada con IgG4: reporte de un caso y revisión de la literatura / IgG4-related disease: a case report and literature review

Immunoglobulin G4 (IgG4-RD) -related disease is a regional or systemic fibroinflammatory disease of unknown etiology. It has a characteristic histopathological appearance of dense lymphoplasmacytic infiltrates with abundant IgG4 positive plasma cells, storiform fibrosis and obliterative phlebitis with the appearance of inflammatory swelling or swollen lesions. This entity frequently affects the pancreas, salivary glands, and lymph nodes, but it can compromise almost any structure in the human anatomy. This new disease entity includes a wide variety of diseases such as Mikulicz disease, autoimmune pancreatitis, Riedel's thyroiditis, interstitial nephritis, and retroperitoneal fibrosis. Glucocorticoid therapy can resolve clinical and pathologic abnormalities and impaired organ function. IgG4-RD was internationally recognized in 2011, and new evidence has accumulated on its pathogenesis, clinical characteristics, and treatment. However, much is still unknown about the behavior of IgG4 in vivo, the participation of this molecule in disease, and whether its role in IgG4-related disease is primary or secondary. The text below is based on a brief review of the most recent literature on this entity in relation to a clinical case.

IgG4-releated disease.

BACKGROUND: IgG4-related disease (IgG4-RD) is a non-malignant, chronic, immune-related disease. It was first recognized as a distinct disease in 2012 and the first classification criteria were published in 2020. This new entity can cause fibroinflammatory lesions in nearly any organ. It often presents as a multi-organ disease and can be confused with malignancy, infection or other immune-mediated conditions. Although the disease could affect virtually any organ, there are strong predilections for certain organs: the major salivary glands, the orbits and lacrimal glands, the pancreas and biliary tree, the lungs, the kidneys, the aorta and retroperitoneum, the meninges and the thyroid gland. PURPOSE: Correlation among clinical, serologic, radiologic and pathologic data is required for establishing IgG4-RD. We sum up the newest information necessary for the dia-gnosis.

The neurology of IGG4-related disease.

PURPOSE OF REVIEW: IgG4-related disease (IgG4-RD) is emerging as a fibro-inflammatory entity affecting multiple organs, including manifold neurologic manifestations. This review discusses general characteristics of IgG4-RD neurologic disease including epidemiology, histology, clinical picture and treatment approaches. RECENT FINDINGS: IgG4-RD is increasingly recognized as an important underlying pathophysiology in multiple disorders of neurologic interest, including orbital inflammation, infundibulo-hypophysitis, hypertrophic pachymeningitis, and even in rare cases CNS parenchymal disease and cranial vascular involvement. These were previously considered idiopathic and unrelated to any systemic disease but now known to share a common histopathology. New knowledge regarding the pathogenesis, clinical features and epidemiology of IgG4 is emerging, and new neurological manifestations continue to be described. Diagnostic progress includes CT-PET imaging, the use of flow cytometry for plasmablast quantification, and the use of reverse passive latex agglutination aiming to overcome the prozone phenomenon. Histopathologic confirmation of IgG4-RD remains the gold standard method of diagnosis but new diagnostic criteria for systemic and organ-specific disease are being proposed. Though glucorticoids remain the mainstay of therapy, relapses and incomplete recovery are frequent. Rituximab is a promising treatment in IgG4-RD that is severe, refractory or glucocorticoid dependent. Initiation of immunosuppression at an early stage of disease should be considered in order to avoid development of refractory fibrosis. SUMMARY: The current review emphasizes the neurologic manifestations of IgG4-RD.