Management Of IgG4-related Disease Research Articles

Recommendations for the diagnosis and treatment of IgG4-related disease in China

IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition characterized by tumefactive lesions in multi-organs. It is a novel entity presented by variable manifestations. In recent years, there has been progress toward recognizing IgG4-RD. However, the diagnosis and treatment of IgG4-RD still present challenges due to insufficient experience. To address this, the Chinese Rheumatology Association has developed standardized guidelines for the diagnosis and treatment of IgG4-RD based on domestic and international experience. These guidelines aim to enhance the understanding and management of IgG4-RD, ultimately improving the prognosis for patients with IgG4-RD.

Isolated IgG4-related cholecystitis mimicking an advanced gallbladder cancer: Don't fall into the trap.

A 59-year old women developed spontaneous jaundice without fever and after a progressive loss of 10 kg in 6 months. Iconography showed an enlarged gallbladder with gallstones and thickening walls responsible for an intrahepatic bile duct dilatation with infiltration of the hepatic pedicle and a portal stenosis (Fig. 1). Jaundice spontaneously resolved but cholestasis remained. Surgical and radiological guided biopsy were performed twice without contributive histology. We decided to proceed to a right portal vein embolization in the aim to proceed to an extended right hepatectomy. Fortunately, definitive histology of the last biopsy revealed inflammatory condition with a high IgG4-plasmocytes rate although the patient's serum concentration of IgG4 was moderate (1.39 g/L, normal rate: 0.86–1.35 g/L) and initially considered as not significant. A complete check up was performed and concluded that it was the unique location of an IgG4-related disease [ [1] Lanzillotta M. Mancuso G. Della-Torre E. Advances in the diagnosis and management of IgG4 related disease. BMJ. 2020; 369: m1067https://doi.org/10.1136/bmj.m1067 Crossref PubMed Scopus (97) Google Scholar ]. Corticotherapy was introduced.

Experience from the first UK inter-regional specialist multidisciplinary meeting in the diagnosis and management of IgG4-related disease

Immunoglobulin G4-related disease (IgG4-RD) is a complex multisystem fibro-inflammatory disorder, requiring diagnostic differentiation from malignancy and other immune-mediated conditions, and careful management to minimise glucocorticoid-induced toxicity and prevent progressive organ dysfunction. We describe the experience of the first inter-regional specialist IgG4-RD multidisciplinary team meeting (MDM) incorporating a broad range of generalists and specialists, held 6-weekly via web-link between Oxford University Hospitals NHS Foundation Trust and University College London Hospitals NHS Foundation Trust. Over 3 years, there were 206 discussions on 156 patients. Of these, 97 (62%) were considered to have definite or possible IgG4-RD; 67% had multi-organ involvement and 23% had a normal serum IgG4. The average number of specialist opinions sought prior to MDM was four per patient. Management was changed in the majority of patients (74%) with the treatment escalation recommended in 61 cases, including 19 for rituximab. Challenges arose from delays and misdiagnosis, cross-specialty presentation and the management of sub-clinical disease. Our cross-discipline IgG4-RD MDM enabled important diagnostic and management decisions in this complex multisystem disorder, and can be used as a model for other centres in the UK.

Additive effect of leflunomide and glucocorticoids compared with glucocorticoids monotherapy in preventing relapse of IgG4-related disease: A randomized clinical trial

ObjectivesTo evaluate the efficacy and safety of leflunomide (LEF) and glucocorticoids (GCs) combination therapy compared with GCs monotherapy in preventing relapse of IgG4-related disease (IgG4-RD). MethodsA 12-month, randomized, open-label, controlled trial was conducted at a large academic medical center (ClinicalTrials.gov: NCT02703194). Enrolled patients with active IgG4-RD were randomly allocated to the GCs + LEF (20 mg/day) combination therapy or GCs monotherapy group. All patients received GCs with a predefined taper regimen starting from a dosage of 0.5–0.8 mg/kg/d. The primary outcome was the time to relapse. The secondary outcomes included complete response, remission, GCs dosage, and serum IgG4 level. ResultsSixty-six patients with active IgG4-RD were enrolled (33 patients in each group). The demographic and disease characteristics showed no statistically significant differences between groups. Additionally, the initial GCs dosages were similar (50.00 vs. 50.00 mg/day, P = 0.295). Disease relapses occurred in 6 (18.2%) and 14 (42.4%) patients in the combination therapy group and GCs monotherapy group, respectively (P = 0.032). The combination therapy was significantly superior to GCs monotherapy regarding the primary outcome, the time to relapse (HR, 0.35; 95% confidence interval [CI], 0.13–0.90; P = 0.023), as well as the secondary outcome, the time to complete response (HR, 1.75; 95% CI, 1.01–3.02; P = 0.034). A longer duration of remission was observed in the combination therapy group (7.00 vs. 3.00 months, P = 0.002) and less cumulative dosage of GCs was used (5103.13 vs. 5637.50 mg, P = 0.031). Additionally, a higher proportion of patients in the combination therapy group (54.5%) were able to reach a daily GCs dose of ≤5 mg/day compared with the GCs monotherapy group (18.2%) (P = 0.006). The incidences of adverse events were similar in the 2 groups (P = 0.325). ConclusionLEF in combination with GCs therapy is well-tolerated and significantly superior to GCs monotherapy in preventing the relapse of IgG4-RD. LEF can be used as a steroid-sparing agent in the management of IgG4-RD.

Management of IgG4-related disease.

IgG4-related disease was unrecognised as a unified disease entity until this century, yet in a short period of time the disease has been appreciated to have a worldwide distribution, and its clinical, pathological, and radiological features have been described in considerable detail. The disease has strong organ predilections, and many of the clinical presentations of disease are increasingly familiar to both generalists and specialists. Early recognition of IgG4-related disease is crucial because although the disease is highly treatable, it can lead to serious organ damage and even death if undiagnosed until advanced stages. Its indolent nature often makes diagnosis challenging, and IgG4-related disease is one of the great mimickers of other diseases in the current era. Glucocorticoids are an effective treatment for IgG4-related disease, but their long-term use is problematic in a disease that frequently affects middle-aged to elderly individuals and often leads to pancreatic dysfunction. Our understanding of the pathophysiology of the disease is surprisingly advanced given the relatively recent recognition of this condition. Insights into disease pathophysiology offer the possibility of a variety of targeted treatment approaches. Looking ahead, biological therapies could profoundly alter the way in which IgG4-related disease is managed, permitting the use of specific therapies that are tailored to patients' clinical phenotypes.

Combination therapy of leflunomide and glucocorticoids for the maintenance of remission in patients with IgG4-related disease: a retrospective study and literature review.

Although glucocorticoids are effective in IgG4-related disease (IgG4-RD), patients may relapse during or after glucocorticoid tapering. Immunosuppressive agents, including leflunomide (LEF), are regarded as steroid-sparing agents in other autoimmune disorders and need to be discussed in the management of IgG4-RD. To identify the efficacy and safety of combination therapy of LEF and glucocorticoids in IgG4-RD. We retrospectively summarised data of patients diagnosed with IgG4-RD between November 2012 and November 2015. Only patients treated with LEF plus glucocorticoids and had been followed up for more than three visits and 6 months were analysed with clinical symptoms, laboratory and imaging findings, treatment protocol, LEF-related adverse events and disease activity reflected by IgG4-RD Responder Index (IgG4-RD RI). A total of 18 patients, including 14 untreated patients and 4 relapsing patients, was included. The mean (SD) onset age was 54.0 (9.6) years. The mean (SD) follow-up period was 12.1 (7.4) months. All patients had active disease with mean (SD) IgG4-RD RI of 15.0 (5.6) at baseline and experienced improvements at 1 month. At the last follow up, the mean (SD) IgG4-RD Responder Index declined to 3.1 (1.7) in all patients and to 2.5 (1.2) in patients without relapse. The mean (SD) dose of GC declined to 6.9 (2.7) mg/day. A total of 12 (66.7%) and 11 (61.1%) patients were in remission at 6 months and the last follow up respectively. Three (16.7%) patients relapsed in clinical course. Two reversible adverse events were observed. The combination therapy of LEF and glucocoticoids is effective and safe in IgG4-RD.

Interdisciplinary Management of IgG4-Related Disease: From Dermis to Nephron

Interdisciplinary Management of IgG4-Related Disease: From Dermis to Nephron