Efficacy and safety of rituximab biosimilar (CT-P10) in IgG4-related disease: an observational prospective open-label cohort study

ObjectiveRituximab is increasingly used in IgG4-related disease (IgG4-RD) but high costs limit its wide off-label administration. European and US regulatory agencies have recently approved rituximab biosimilars for the treatment of different rheumatologic and hematological conditions. No data are available, yet, on the efficacy and safety of rituximab biosimilars for the treatment of IgG4-RD. Scope of the present work is to evaluate the efficacy and safety of the rituximab biosimilar CT-P10 (RTX-B) in patients with IgG4-RD.MethodsPatients with active IgG4-RD, naïve to rituximab or switched from the originator (RTX-O) to the biosimilar were treated with RTX-B and prospectively followed-up for 18 months. Safety and efficacy were assessed at six months. Relapse rate was assessed at 18 months. Disease activity was assessed by means of the IgG4-RD Responder Index (IgG4-RD RI).ResultsThirty-eight patients were included in this study. Thirty-three patients (87%) were naïve to RTX. Five patients (13%) relapsed after RTX-O and were switched to RTX-B. After six months, 21 patients (60%) achieved disease remission. The median serum IgG4 concentration decreased from 1344 to 575 mg/L (p < 0.01), and the median IgG4-RD RI decreased from 7.5 to 0 (p < 0.01). B-cell depletion was observed in all patients. Eight patients (36%) relapsed within 18 months. Side effects related to RTX-B administration were observed in 14 patients (37%). These results are in line with our previous experience with RTX-O.ConclusionsThe (Truxima^TM) rituximab biosimilar CT-P10 represents a safe and effective alternative to rituximab originator for the treatment of IgG4-RD.     

Long-term efficacy of maintenance therapy with Rituximab for IgG4-related disease

BackgroundIgG4-Related Disease (IgG4-RD) promptly responds to glucocorticoids but relapses in most patients. Rituximab (RTX) represents a promising strategy to avoid IgG4-RD flares but its administration for maintaining disease remission has never been assessed in terms of optimal timing of infusion, dosage, and duration of treatment. In the present study we aimed to evaluate the efficacy and safety of RTX for maintenance of IgG4-RD remission.MethodsFourteen patients with IgG4-RD were treated with RTX as induction of remission therapy at the San Raffaele Scientific Institute in Milan, Italy. The cohort was then divided into two study groups: patients re-treated only in case of disease relapse (Group 1, n = 7), and patients regularly re-treated with RTX every 6 months for maintenance therapy (Group 2, n = 7). Data on free-relapse rate and adverse events were collected and retrospectively analysed.ResultsMedian follow-up time and baseline clinical-serological features were similar between Group 1 and 2 (p > 0.05). The free relapse rate 18 months after induction of remission treatment was significantly lower in Group 1 (29%) than in Group 2 (100%) (p = 0.006). Infectious complications developed in 6/14 patients (3 in Group 1 and 3 in Group 2).ConclusionAdministration of RTX every 6 months as maintenance of remission therapy prevents IgG4-RD flares.     

A multicenter phase II prospective clinical trial of glucocorticoid for patients with untreated IgG4-related disease

Objective: Although glucocorticoids are effective for patients with IgG4-related disease, the treatment has not yet been standardized. Therefore, the treatment strategy should be established.

Patients and methods: Patients who fulfilled the comprehensive diagnostic criteria for definite IgG4-related disease were started on prednisolone (0.6?mg/kg body weight) with the dose reduced every two weeks. The subsequent maintenance dose and need for prednisolone were determined for individual patients. The primary endpoint was the complete remission (CR) rate at one year. Secondary endpoints included overall response rate (ORR), the maintenance dose, the relapse rate, and adverse events.

Results: This study enrolled 61 patients. After clinicopathological review, three patients were excluded, and one, 13, and 44 patients were diagnosed with probable, possible, and definite IgG4-related disease, respectively. Of the 44 patients with definite IgG4-RD, 29 (65.9%) achieved CR, and the ORR was 93.2%. No patient was refractory to primary treatment. The most frequent adverse events were glucose intolerance. Six patients relapsed.

Conclusions: Glucocorticoid treatment is usually effective for patients with IgG4-RD, and we should examine the possibility of other disorders when a patient is glucocorticoid refractory. Some patients are misdiagnosed, making central clinicopathological review of diagnosis very important in conducting clinical studies.     

Everyday clinical practice in IgG4-related dacryoadenitis and/or sialadenitis: Results from the SMART database

Abstract

Objective. Immunoglobulin (Ig)G4-related disease (IgG4-RD) is a new disease entity that has only been identified this century. Clinical information is thus lacking. We established the Sapporo Medical University and Related Institutes Database for Investigation and Best Treatments of IgG4-related Disease (SMART) to clarify the clinical features of IgG4-RD and provide useful information for clinicians.

Methods. Participants comprised 122 patients with IgG4-related dacryoadenitis and/or sialadenitis (IgG4-DS), representing lacrimal and/or salivary lesions of IgG4-RD, followed-up in December 2013. We analyzed the sex ratio, mean age at onset, organ dysfunction, history or complications of malignancy, treatments, rate of clinical remission, and relapse.

Results. The sex ratio was roughly equal. Mean age at diagnosis was 59.0 years. Positron emission tomography revealed that the ratio of other organ involvements was 61.4%. Complications of malignancy were observed in 7.4% of cases. Glucocorticoid was used to treat 92.1% of cases, and the mean maintenance dose of prednisolone was 4.8 mg/day. Rituximab was added in three cases, and showed good steroid-sparing effect. The clinical remission rate was 73.8%, and the annual relapse rate was 11.5%. Half of the cases experienced relapses within 7 years of initial treatment.

Conclusion. We analyzed the clinical features and treatments of IgG4-DS using SMART, providing useful information for everyday clinical practice.     

Relapse rate and predictors of relapse in a large single center cohort of type 1 autoimmune pancreatitis: long-term follow-up results after steroid therapy with short-duration maintenance treatment

Background

Type 1 autoimmune pancreatitis (AIP), as a pancreatic manifestation of IgG4-related disease, shows a favorable prognosis in the short term. However, disease relapse is common in long-term follow-up, despite a successful initial treatment response. This study aimed to identify the predictors of relapse and long-term outcomes in patients with type 1 AIP.

Methods

Patients with more than 2 years of follow-up who met the International Consensus Diagnostic Criteria for type 1 AIP were included. Patients who had undergone pancreatic operations associated with AIP or who lacked sufficient clinical data were excluded.

Results

All 138 patients achieved clinical remission with initial steroid therapy, and 66 (47.8%) experienced relapse during a median 60 (range 24–197) months follow-up. Among the relapsed patients, about 74% (49/66) relapsed within 3 years. About 60% (82/138) had other organ involvement (OOI), most commonly in the proximal bile duct (26.8%). At first diagnosis, OOI, and especially OOI of the proximal bile duct, was a significant independent predictor of relapse (hazard ratio 2.65; 95% confidence interval 1.44–4.89; p = 0.002), according to multivariate analysis. During the follow-up period, 16 (11.6%) patients experienced endocrine/exocrine dysfunction and 32 (23.2%) patients developed de novo pancreatic calcifications/stones. No pancreatic cancer occurred in any patients.

Conclusions

Type 1 AIP has common relapses, and patients with OOI, especially OOI of the proximal bile duct, appear to be at increased risk for relapse. Long-term sequelae, including pancreatic insufficiency and pancreatic calcifications/stones, are common in patients with relapse. To reduce the relapse, longer maintenance treatment may be needed especially for patients at high risk for relapse.

     

Utility of the “2019 ACR/EULAR classification criteria” for the management of patients with IgG4-related disease

BackgroundThe 2019 ACR/EULAR Classification Criteria for IgG4-related disease (IgG4-RD) represent a fundamental tool for patient enrollment in research studies and in clinical trials but their usefulness in daily clinical practice remains unknown.ObjectiveTo validate the 2019 ACR/EULAR Classification Criteria for IgG4-RD in a real-life setting and to anticipate their utility for orienting disease diagnosis and patient management.MethodsFour experts were asked to classify 200 patients diagnosed with IgG4-RD according to the 2019 ACR/EULAR Classification Criteria for IgG4-RD. Agreement between experts was calculated and the Classification score of each patient was correlated with the following variables and outcomes: serum IgG4 and IgE; inflammatory markers; eosinophils; plasmablasts; IgG4-RD responder index; diabetes, osteoporosis, relapses; and use of rituximab.ResultsAmong the 157/200 cases equally rated by at least three experts, 94 (59.9%) achieved IgG4-RD classification and 63 (40.1%) did not. Strong agreement among IgG4-RD experts was observed in classifying patients (k = 0.711, p<0.0001). Clinical presentations not included in the classification algorithm and lack of informative histology were the most common reasons for not achieving classification. In patients achieving classification, the Classification score did not correlate with variables of disease activity and was not associated with specific outcomes.ConclusionsThe ACR/EULAR Classification Criteria represent a replicable instrument for classifying patients and a useful framework for orienting diagnosis but are of limited utility for assessing IgG4-RD activity, for predicting disease outcomes, and for defining personalized therapeutic approaches.     

Determination of the duration of glucocorticoid therapy in type 1 autoimmune pancreatitis: A systematic review and meta-analysis

BackgroundThe indications for maintenance glucocorticoid therapy (MGT) and its duration after initial remission of type 1 autoimmune pancreatitis (AIP) remain controversial. In contrast to the Japanese treatment protocol, the Mayo protocol does not recommend MGT after initial remission. This study aimed to evaluate the relapse rate in patients with type 1 AIP according to the duration of glucocorticoid therapy.MethodsWe conducted a systematic literature review up until November 30, 2020, and identified 40 studies reporting AIP relapse rates. The pooled relapse rates were compared between groups according to the protocol and duration of glucocorticoids (routine vs. no MGT; glucocorticoids ≤6 months vs. 6–12 months vs. 12–36 months vs. ≥ 36 months). The pooled rates of adverse events related to glucocorticoids were also evaluated.ResultsMeta-analysis indicated calculated pooled relapse rates of 46.6% (95% confidence interval (CI), 38.9–54.3%) with glucocorticoids for ≤ 6 months, 44.3% (95% CI, 38.8–49.8%) for 6–12 months, 34.1% (95% CI, 28.6–39.7%) for 12–36 months, and 27.0% (95% CI, 23.4–30.6%) for ≥ 36 months. The rate of relapse was also significantly lower in patients with routine-use protocol of MGT (31.2%; 95% CI, 27.5–34.8%) than in patients with no MGT protocol (44.1%; 95% CI, 35.8–52.4%). Adverse events were comparable between groups.ConclusionsThe rate of relapse tended to decrease with extended durations of glucocorticoid therapy up to 36 months. Clinicians may decide the duration of glucocorticoids according to patient condition, including comorbidities and risk of relapse.     

IgG4-related disease as a variable-vessel vasculitis: A case series of 13 patients with medium-sized coronary artery involvement

IntroductionIgG4-related disease (IgG4-RD) is a systemic autoimmune fibroinflammatory disease that can affect multiple organ systems. Although large-vessel vasculitis is a well-recognized manifestation of IgG4-RD, this condition is generally not regarded as a vasculitis. We aimed to describe coronary artery involvement (CAI), a vascular distribution about which little is known in IgG4-RD.Material and methodsPatients with IgG4-related CAI were identified from a large, prospective IgG4-RD cohort. CAI was confirmed by imaging evidence of arterial or periarterial inflammation in any coronary artery. We extracted details regarding demographics, features of IgG4-RD, and manifestations of CAI.ResultsOf 361 cases in the cohort, 13 (4%) patients had IgG4-related CAI. All were male and all had highly-elevated serum IgG4 concentrations, with a median value of 955 mg/dL (interquartile range [IQR]: 510–1568 mg/dL; reference: 4–86 mg/dL). Median disease duration at the time of CAI diagnosis was 11 years (IQR: 8.23–15.5 years). Extensive disease in the coronary arteries was the rule: all three major coronary arteries were involved in 11 patients (85%). The coronary artery manifestations included wall thickening or periarterial soft tissue encasement (85%), stenosis (69%), calcification (69%), and aneurysms or ectasia (62%). Five patients (38%) had myocardial infarctions, 2 (15%) required coronary artery bypass grafting, and 2 (15%) developed ischemic cardiomyopathy.DiscussionCoronary arteritis and periarteritis are important manifestations of IgG4-RD, which should be regarded as a variable-vessel vasculitis that is among the most diverse forms of vasculitis known. Potential complications of CAI include coronary artery aneurysms, myocardial infarction, and ischemic cardiomyopathy.     

Demystifying seronegative autoimmune pancreatitis

BackgroundAutoimmune pancreatitis (AIP) has been classified into type 1 and type 2 subtypes. Serum immunoglobulin G4 (IgG4) elevation characterizes type 1 AIP. Type 2 AIP and a subset of type 1 AIP are seronegative, i.e., have normal serum IgG4 levels.AimWe compared the profiles of the three subsets of AIP to identify the unique characteristics of seronegative type 1 AIP and type 2 AIP.MethodsWe compared the clinical profiles of 69 seropositive type 1 AIP patients, 21 seronegative type 1 AIP patients and 22 type 2 AIP patients.ResultsAmong type 1 AIP, seronegative group had similar clinical profiles when compared to seropositive group except that they were more likely to undergo surgical resection than seropositive patients (p = 0.001). Seronegative type I AIP patients were older (61.9 ± 13.7 vs 45.3 ± 17.4; p = 0.004), and differed in the occurrence of other organ involvement (OOI) (71.4% vs 0%; p < 0.001) and disease relapse (33.3% vs 0%; p = 0.005) when compared with type 2 AIP. All seronegative type 1 AIP patients had at least one of the following –OOI, disease relapse, and age >50 years while none of the type 2 AIP had OOI or disease relapse.ConclusionsSeronegative and seropositive type 1 AIP patients have similar clinical profiles, which are distinct from that of type 2 AIP. Among the seronegative AIP group, patients are more likely to have type 1 AIP rather than type 2 AIP if they are older than 50 years or have OOI or disease relapse.     

Ophthalmic manifestations of IgG4-related disease: Single-center experience and literature review

ObjectivesIgG4-related disease (IgG4-RD) is an inflammatory disorder responsible for fibrosing, tumefactive lesions that can involve the lacrimal gland as well as the extraocular muscles, orbital soft tissues, sclera, and local nerves. We reviewed IgG4-related ophthalmic disease (IgG4-ROD), including the natural history, pathology, and treatment, based on our center's experience and that reported in the literature.MethodsWe identified 27 patients with orbital manifestations from our IgG4-RD registry; six were excluded because no pathology was available for review. All 21 cases included had histopathologically confirmed diagnoses of IgG4-RD, 11 of which were of the orbital tissue. Other data were obtained by a retrospective medical records review. MEDLINE and PubMed literature searches in English were conducted to identify articles for a literature review on the topic.ResultsPatients with IgG4-ROD were predominantly male (57%) and had an average age at symptom onset of 50 years (range: 21–79 years). The lacrimal gland was the most commonly involved structure (62%). Most patients (71%) had bilateral disease and extra-orbital involvement (71%); these patients also had elevated serum IgG4 concentrations compared to those with unilateral disease and no extra-orbital disease. Ten patients improved following rituximab treatment.ConclusionsOphthalmic involvement is a common manifestation of IgG4-RD and can affect nearly every orbital structure. Consideration of IgG4-RD and accurate diagnosis by biopsy have important implications for prognosis and treatment following the distinction of this condition from the Sjögren syndrome (SjS), granulomatosis with polyangiitis (GPA, formerly Wegener's), sarcoidosis, lymphoma, infection, and other disorders. Rituximab holds promise as an effective steroid-sparing agent or therapy for steroid-resistant cases.     

Significance of peripheral eosinophilia for diagnosis of IgG4-related disease in subjects with elevated serum IgG4 levels

ObjectivesIn this study, we aim to assess the diagnostic utility of elevated serum IgG4 (sIgG4) concentration alone and in combination with peripheral eosinophilia (PE) for IgG4-related disease (IgG4-RD).MethodsFrom the Mayo Clinic, Rochester electronic medical record database we identified 409 patients with above normal levels of sIgG4 (reference range 121–140 mg/dL) who had sIgG4 measured to differentiate IgG4-RD from another disease.ResultsAmong 409 patients with any elevation in sIgG4 levels, 129 (31.5%) had a definite diagnosis of IgG4-RD. The prevalence of PE increased with increasing sIgG4 levels and was more likely to be seen in subjects with IgG4-RD vs. non-IgG4-RD at ≥1X (n = 35/120, 29.2% vs. n = 23/258, 8.9%; p < 0.001), ≥2X (n = 23/64, 35.9% vs. n = 5/54,9.3%; p = 0.001) and ≥3X (n = 18/42, 42.9% vs. n = 0/9, 0%; p = 0.015) of sIgG4 upper limit of normal (ULN), respectively. After adjusting for gender and age, sIgG4 levels ≥ 2X ULN with PE as a predictor, had a higher positive predictive value in predicting IgG4-RD (72.2% vs. 65.9%) with an Area Under the Receiver Operatic Characteristic Curve (AUC) of 0.776, compared to sIgG4 ≥ 2X ULN without PE predictor (AUC = 0.74), p = 0.016. PE, sIgG4≥2X ULN, male gender, and age independently predicted the disease with odds ratio of 4.89 (95% CI:2.51–9.54), 3.78 (95% CI:2.27–6.28), 2.78 (95% CI:1.55–4.97), and 1.03 (95% CI:1.02–1.05), respectively.ConclusionEven in subjects in whom IgG4-RD is suspected, only a minority (∼30%) with elevated sIgG4 levels have IgG4-RD. sIgG4 by itself is more specific at higher levels, though never diagnostic. PE increases with increasing sIgG4 and adds diagnostic value at higher sIgG4 levels.     

Clinicopathological features of IgG4-related disease complicated with orbital involvement

Abstract

Objective. IgG4-related disease (IgG4-RD) is characterized by IgG4-positive plasmacytic infiltration and fibrosis in various organs. Orbital involvement in IgG4-RD includes lacrimal glands, extra-ocular muscles, trigeminal nerve and other parts of the orbit. Immunohistochemical staining is used to diagnose IgG4-RD in patients with orbital inflammation. The purpose of this retrospective study was to clarify the clinicopathological features of IgG4-RD complicated with orbital involvement.

Methods. We examined the clinical features, pathological findings and response to treatment in nine patients with IgG4-RD who underwent orbital tissue biopsy between April 2010 and August 2012 at the University of Tsukuba Hospital.

Results. Among the nine patients, eight had dacryoadenitis, one had infraorbital nerve swelling, and another one had IgG4-related orbital inflammation. Involvement of other organs was identified in all patients, including involvement of the salivary glands, lymph nodes, lung, kidney and para-aorta. In all patients, biopsy samples from orbital tissues showed lymphoplasmacytic infiltration and fibrosis, and IgG4-positive/IgG-positive plasmacyte ratio of > 40%. All patients were treated with prednisolone (0.6 mg/kg/day) and responded well in early phase, although relapse was noted in two patients following tapering of prednisolone, evident by swelling of lacrimal glands.

Conclusion. Patients with IgG4-RD complicated with orbital involvement often present with involvement of other organs. The histopathological findings of orbital tissue match the characteristic features of IgG4-RD. Corticosteroid is effective for orbital and systemic involvement in IgG4-RD.     

Clinical characteristics of immunoglobulin IgG4-related sclerosing cholangitis: Comparison of cases with and without autoimmune pancreatitis in a large cohort

BackgroundThe clinical characteristics of IgG4-related sclerosing cholangitis (IgG4-SC) especially without autoimmune pancreatitis (AIP) have not been investigated in a large cohort.AimsTo clarify the clinical characteristics of IgG4-SC and IgG4-SC without AIP.MethodsWe retrospectively reviewed imaging, serology, other organ involvement (OOI) and histology of 872 patients with IgG4-SC who participated in a Japanese nationwide survey in 2019, and compared these items between IgG4-SC with and without AIP.ResultsAIP was present in 83.7% (730/872) of IgG4-SC. In IgG4-SC, bile duct wall thickening was observed on ultrasound (528/650; 81.2%), computed tomography (375/525; 71.4%) and magnetic resonance imaging or cholangiopancreatography (290/440; 65.9%). An elevated serum IgG4 level (≥ 135 mg/dL) was found in 88.0% (322/366). IgG4-related OOI other than AIP was observed in 25.2% (211/836). The proportion of females was significantly higher in IgG4-SC without AIP (28.9% vs. 20.1%; p = 0.025). Hilar stricture was the most common cholangiographic type in IgG4-SC without AIP (39/107; 36.4%).There were no significant differences between IgG4-SC with and without AIP in the rates of bile duct wall thickening, elevated serum IgG4 level, or IgG4-related OOI.ConclusionsThe clinical characteristics of IgG4-SC was similar between IgG4-SC with and without AIP in a large cohort.     

Role of interleukin-32 in the mechanism of chronic inflammation in IgG4-related disease and as a predictive biomarker for drug-free remission

Objectives: In immunoglobulin (Ig) G4-related disease (IgG4-RD), the mechanism of chronic inflammation and predictive factors for drug-free remission is still unclear. To examine the issues, we focused on tuberculosis, a chronic infection, and on the role of interleukin (IL)-32.

Methods: We examined the positive rate of QuantiFERON TB-2G (QFT-2G) in 126 patients with IgG4-RD, and compared with the rate in the general population. Furthermore, specimens of submandibular glands from the maintenance treatment group and drug-free group of IgG4-RD and specimens of small salivary glands from primary Sjögren’s syndrome (SS) were stained with anti-IL-32 antibody and anti-protease-activated receptor 2 antibody, and the number of positive cells was compared between these groups.

Results: The positive rate of QFT-2G was 19.8% in IgG4-RD patients, which is higher than in the general population. The expression of IL-32 and PAR2 in the submandibular glands of the maintenance treatment group of IgG4-RD was significantly greater than that of the drug-free remission group and SS patients.

Conclusions: This study indicates the possibility that IL-32 is associated with chronic inflammation and that it can be a predictive factor for drug-free remission in IgG4-RD.     

Enfermedad relacionada con IgG4: ¿es el rituximab la mejor estrategia terapéutica en los casos refractarios a terapia convencional? Resultados de una revisión sistemática

IntroductionIgG4 related disease is a fibroinflammatory condition characterised by lymphoplasmocytic infiltration with predominance of IgG4+ plasma cells, fibrosis, and in most cases elevated IgG4 serum levels. It can affect any organ and result in varying clinical manifestations. Steroids are the cornerstone of treatment, however there is a high percentage of relapse. Recent studies have demonstrated favourable effects with rituximab.ObjectiveTo evaluate effectiveness related to the response to treatment with rituximab in patients with IgG4 related disease refractory to steroids and other immunosuppressant therapies.Materials and methodsWe undertook a systematic search of the specialist databases EMBASE, LILACS, PUBMED and OVID-Cochrane for publications up until December 2017.ResultsAfter the quality analysis, we selected 27 articles (264 patients in total) for the final review, of which 23 were case reports and case series (105 patients), 3 were observational follow-up cohort studies (129 patients), and there was one clinical trial (30 patients). IgG4 related disease presents predominantly in male patients aged between 50 and 70 years on average. Multiple organs are compromised with an average of 3.5 compromised organs. Orbital, glandular and lymph-node compromise is most frequent. Patients in the different studies we included had received various treatments prior to starting rituximab, including glucocorticoids and disease-modifying anti-rheumatic drugs. There was 90.7% response in the cases where rituximab was used as second line therapy; rituximab was used as first line treatment for 10% of the patients with a 100% response rate.ConclusionThe use of rituximab for patients refractory to first-line treatments was associated with a high response percentage and less dependence on glucocorticoids.     

A rare cause for lower back pain: a case of an IgG4-related periaortitis

IgG4-related disease (IgG4-RD) are a group of autoinflammatory diseases often presenting as tumor-like lesions because of their infiltrative or mass forming behavior. They are characterized by a typical histology consisting of storiform fibrosis, high numbers of infiltrating IgG4-positive plasma cells, obliterative phlebitis, and a moderate presence of eosinophilic cells. Serum IgG4 levels can be elevated. We present a case of a 57 year-old male patient with immobilizing lower back pain, fever, and night sweats. We diagnosed IgG4-related periaortitis using serum IgG4 levels, abdominal ultrasound, PET/CT, and histology. We successfully treated the patient with glucocorticoids (GC) and azathioprine. Periaortitis is a rare presentation of IgG4-RD and therefore noteworthy. It has to be considered in patients with a retroperitoneal mass.     

Ophthalmic manifestations of IgG4-related disease: Single-center experience and literature review

Objectives

IgG4-related disease (IgG4-RD) is an inflammatory disorder responsible for fibrosing, tumefactive lesions that can involve the lacrimal gland as well as the extraocular muscles, orbital soft tissues, sclera, and local nerves. We reviewed IgG4-related ophthalmic disease (IgG4-ROD), including the natural history, pathology, and treatment, based on our center's experience and that reported in the literature.

Methods

We identified 27 patients with orbital manifestations from our IgG4-RD registry; six were excluded because no pathology was available for review. All 21 cases included had histopathologically confirmed diagnoses of IgG4-RD, 11 of which were of the orbital tissue. Other data were obtained by a retrospective medical records review. MEDLINE and PubMed literature searches in English were conducted to identify articles for a literature review on the topic.

Results

Patients with IgG4-ROD were predominantly male (57%) and had an average age at symptom onset of 50 years (range: 21–79 years). The lacrimal gland was the most commonly involved structure (62%). Most patients (71%) had bilateral disease and extra-orbital involvement (71%); these patients also had elevated serum IgG4 concentrations compared to those with unilateral disease and no extra-orbital disease. Ten patients improved following rituximab treatment.

Conclusions

Ophthalmic involvement is a common manifestation of IgG4-RD and can affect nearly every orbital structure. Consideration of IgG4-RD and accurate diagnosis by biopsy have important implications for prognosis and treatment following the distinction of this condition from the Sjögren syndrome (SjS), granulomatosis with polyangiitis (GPA, formerly Wegener's), sarcoidosis, lymphoma, infection, and other disorders. Rituximab holds promise as an effective steroid-sparing agent or therapy for steroid-resistant cases.     

Imaging and pathological features of gastric lesion of immunoglobulin G4-related disease: A case report and review of the recent literature

Abstract

We describe a 67-year-old man with immunoglobulin G4-related disease (IgG4-RD) presenting with optic neuropathy, dacryoadenitis, periaortitis, retroperitoneal fibrosis, and a gastric mass-like lesion. A mass-like lesion measuring 52?×?40?mm in the antrum of the stomach was found incidentally through whole-body screening for other organ involvement of IgG4-RD using contrast-enhanced computed tomography (CT). Histology of the stomach revealed that the lesion was also IgG4-related and was located in the submucosal layer extending to the subserosal region. This case suggests that the stomach can also be a site of involvement of IgG4-RD.     

Cardiac Structural Abnormalities Associated With IgG4-Related Coronary Periarteritis and Inflammation Revealed by Multimodality Imaging

A man presented with shortness of breath, and a globular heart was seen on a chest radiograph. An echocardiogram showed masses at the atrioventricular grooves. Computed tomography (CT) coronary angiography and fluorine-18 (¹⁸F) fluorodeoxyglucose positron emission tomography (FDG-PET)/CT confirmed coronary aneurysms with hypermetabolic perivascular masses at the coronary arteries and right internal iliac artery. Histologic features were highly suspicious for IgG4-related disease (IgG4-RD). IgG4-RD is a recently recognized fibroinflammatory condition, and FDG-PET/CT can provide information about the disease pattern, which may suggest IgG4-RD, as well as the optimal biopsy site.     

The external validation of the 2019 ACR/EULAR classification criteria for IgG4-related disease in a large cohort from China

ObjectiveTo externally validate the performance of the 2019 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for IgG4-related disease (IgG4-RD) within a cohort from China and to compare the criteria with the 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD.MethodsThis study included 875 IgG4-RD and 302 non-IgG4-RD cases (213 mimickers and 89 patients with other diseases). Using expert clinical judgment as the gold standard for diagnosis of IgG4-RD, the performance (sensitivity, specificity, area under the curve (AUC) of the 2019 ACR/EULAR criteria for IgG4-RD was evaluated. We also compared it with the 2020 RCD criteria.ResultsThe 2019 ACR/EULAR classification criteria had a sensitivity of 76.6% (95% CI: 73.8% to 79.4%) and a specificity of 98.0% (96.0%-99.4%), an AUC of 0.873 (0.857–0.889) in the overall cohort. Those false negative cases under the 2019 ACR/EULAR classification criteria had significantly lower levels of serum IgG4, and fewer had pathological information, with a higher frequency in the involvement of those uncommon organs compared with the true positive cases. The cases judged as negative by the 2019 ACR/EULAR classification criteria yet judged as “definite” by the 2020 RCD criteria had more involvement of uncommon organs.ConclusionsThe 2019 ACR/EULAR classification criteria for IgG4-RD show outstanding specificity and good sensitivity in real-world clinical practice. The 2020 RCD criteria are helpful for the diagnosis of IgG4-RD in clinical scenarios where IgG4-RD presents as involving an isolated organ, especially the unusual sites.