Case Of IgG4-related Disease Research Articles

Compromiso gástrico por enfermedad relacionada con IgG4

Introduction: IgG4-related disease (IgG4-RD) is a recently described entity, characterized by IgG4+ infiltration of plasma cells and storiform pattern sclerosis mediated by CD4+ lymphocytes and follicular helper T-cells (Tfhs). Most patients present with adenopathy and weight loss. Among the most affected sites are the pancreas, salivary and lacrimal glands, aorta, and retroperitoneum. Gastric involvement is rare. Diagnosis is based on histopathological examination of the involved organ, clinical manifestations, and serological results. Glucocorticoid therapy is the first line management. Case report: a 38-year-old male patient with symptoms suggestive of upper gastrointestinal (GI) bleeding, upper GI endoscopy revealed a gastric corpus ulcer, suspicious of an ulcerated gastric subepithelial lesion, possibly a gastrointestinal stromal tumor (GIST). Consequently, laparoscopic subtotal gastrectomy was performed. Histology was compatible with an ulcerated IgG4-related fibrosclerosing tumor. Glucocorticoid therapy was started with patient´s favorable response. Conclusion: in this paper, we will review the cases of IgG4-RD with gastric involvement reported in the literature to describe the most important features of this condition.

The clinical outcomes and healthcare resource utilization in IgG4-related disease: a claims-based analysis of commercially insured adults in the United States.

IgG4-related disease (IgG4-RD) can affect nearly any organ and is often treated with glucocorticoids, which contribute to organ damage and toxicity. Comorbidities and healthcare utilization in IgG4-RD are poorly understood. We conducted a cohort study using claims data from a US managed care organization. Incident IgG4-RD cases were identified using a validated algorithm; general population comparators were matched by age, sex, race/ethnicity and index date. The frequency of 21 expert-defined clinical outcomes associated with IgG4-RD or its treatment and healthcare-associated visits and costs were assessed 12 months before and 36 months after the index date (date of earliest IgG4-RD-related claim). There were 524 cases and 5240 comparators. Most cases received glucocorticoids prior to (64.0%) and after (85.1%) the index date. Nearly all outcomes, many being common glucocorticoid toxicities, occurred more frequently in cases vs comparators. During follow-up, the largest differences between cases and comparators were seen for gastroesophageal reflux disease (prevalence difference: +31.2%, P < 0.001), infections (+17.3%, P < 0.001), hypertension (+15.5%, P < 0.01) and diabetes mellitus (+15.0%, P < 0.001). The difference in malignancy increased during follow-up from +8.8% to +12.5% (P < 0.001). Some 17.4% of cases used pancreatic enzyme replacement therapy during follow-up. Over follow-up, cases were more often hospitalized (57.3% vs 17.2%, P < 0.01) and/or had an emergency room visit (72.0% vs 36.7%, P < 0.01); all costs were greater in cases than comparators. Patients with IgG4-RD are disproportionately affected by adverse outcomes, some of which may be preventable or modifiable with vigilant clinician monitoring. Glucocorticoid-sparing treatments may improve these outcomes.

Myofibroblast and pro-fibrotic cytokines in fibrosis of IgG4-related disease (IgG4-RD) patients from South Asia: preliminary data.

Fibrosis is a typical pathological characteristic in IgG4-RD patients and often irreversible. There exists a lack of suitable markers for detection of earlier onset of fibrosis in various organs in IgG4-RD patients. Hence, this study aims at analysing ambispectively the myofibroblasts and the pro-fibrotic cytokines, IFN gamma and IL-33 involved in IgG4-RD associated fibrosis in South Asian patients. Archived biopsy samples of definite/probable/possible cases of IgG4-RD, classified according to diagnostic criteria, taken from patients who attended the OPD and IPD of our tertiary care centre during January 2015-January 2020 were chosen for this study.The paraffin sections were examined qualitatively for fibrosis and the excessive collagen deposition by Hematoxylin & Eosin and Masson's Trichrome staining. Also, the presence of alpha-Smooth muscle actin (α-SMA) expressing myofibroblasts and the involvement of pro-fibrotic cytokines (IFN-gamma, IL-33) were assessed by Immunohistochemistry and scored semi-quantitatively (+mild, ++moderate, +++ severe). Serum IL-33 levels were analysed by indirect Elisa (R & D Systems). Myofibroblasts were present in 10/12 biopsy samples, in moderate levels in 4 (33%) and very high levels (+++) in 3 (25%) of the patients. IFN-gamma was expressed at low levels in 6 (50%) and absent in 6 (50%). All patients showed IL-33 expression with very high levels in tissue (6, 50%), as well as in serum samples. The findings of this study reinforce the role of myofibroblasts and profibrotic cytokines like IL-33 in fibrosis of Ig4-RD patients, pointing to their potential as earlier predictive markers of onset and extent of fibrosis.

Usefulness of 18F-FDG PET-CT for assessing large-vessel involvement in patients with suspected giant cell arteritis and negative temporal artery biopsy

ObjectiveTo investigate the usefulness of 18F-FDG PET-CT for assessing large-vessel (LV) involvement in patients with suspected giant cell arteritis (GCA) and a negative temporal artery biopsy (TAB).MethodsA retrospective review of our hospital databases was conducted to identify patients with suspected GCA and negative TAB who underwent an 18F-FDG PET-CT in an attempt to confirm the diagnosis. The gold standard for GCA diagnosis was clinical confirmation after a follow-up period of at least 12 months.ResultsOut of the 127 patients included in the study, 73 were diagnosed with GCA after a detailed review of their medical records.Of the 73 patients finally diagnosed with GCA, 18F-FDG PET-CT was considered positive in 61 cases (83.5%). Among the 54 patients without GCA, 18F-FDG PET-CT was considered positive in only eight cases (14.8%), which included 1 case of Erdheim-Chester disease, 3 cases of IgG4-related disease, 1 case of sarcoidosis, and 3 cases of isolated aortitis.Overall, the diagnostic performance of 18F-FDG PET-CT for assessing LV involvement in patients finally diagnosed with GCA and negative TAB yielded a sensitivity of 83.5%, specificity of 85.1%, and a diagnostic accuracy of 84% with an area under the ROC curve of 0.844 (95% CI: 0.752 to 0.936). The sensitivity was 89% in occult systemic GCA and 100% in extracranial LV-GCA.ConclusionOur study confirms the utility of 18F-FDG PET-CT in patients presenting with suspected GCA and a negative TAB by demonstrating the presence of LV involvement across different subsets of the disease.

An overlapping case of IgG4-related disease and systemic lupus erythematosus treated with belimumab: a case-based review.

IgG4-related disease (IgG4-RD) is a systemic condition in which IgG4+ plasma cell infiltration and fibrosis cause organ swelling and lead to diverse clinical manifestations. Although IgG4-RD typically responds to glucocorticoids (GCs), relapse during tapering occurs and an early GC-sparing approach might therefore be beneficial. Systemic lupus erythematosus (SLE) is a chronic inflammatory disease with multiple symptoms that is also treated with GCs as a first-line therapy. Recently, belimumab, a recombinant human IgG-1λ monoclonal antibody that inhibits B-cell activating factor, was approved, but reports of use for IgG4-RD are scarce. Here, we present a rare case of IgG4-RD complicated with SLE which was successfully treated with belimumab. A 67-year-old man was diagnosed with IgG4-RD based on a high serum IgG4 level and histopathological findings. Furthermore, he had pericardial effusion on echocardiography, and laboratory tests revealed thrombocytopenia, autoimmune hemolysis, positive anti-nuclear antibodies, positive anti-DNA antibodies, and hypocomplementemia. These data led to an SLE diagnosis. Treatment was started with prednisolone at 40mg/day, plus hydroxychloroquine, which initially improved both the SLE and IgG4-RD symptoms. During the GC tapering, belimumab was added and clinical symptoms resolved completely. Our case and the literature review summarize reported rare overlapping cases of IgG4-RD and SLE and suggest that belimumab is a promising candidate for the treatment of IgG4-RD.

Two cases of igg4 related disease in paediatric and young patients with ocular and ear canal involvement

Two cases of igg4 related disease in paediatric and young patients with ocular and ear canal involvement

A case of IgG4-related disease with laryngeal lesions that was difficult to diagnose

A case of IgG4-related disease with laryngeal lesions that was difficult to diagnose

Long-term efficacy of anti-IL-4 receptor antibody in a patient with aspirin-exacerbated respiratory disease and IgG4-related disease

BackgroundAspirin-exacerbated respiratory disease (AERD) and IgG4-related disease (IgG4RD) share a common pathway of Th2-mediated immune mechanism; there have been several cases of IgG4RD developed in patients with asthma, especially in those comorbid with chronic rhinosinusitis (CRS). IgG4RD has often been treated with systemic corticosteroids, rituximab, or immune-suppressive agents, but frequently failed with relapse.Case presentationHere, we present a case of a 64-year-old male patient with severe AERD with CRS complicated with IgG4RD, who has been successfully treated and maintained with anti-IL-4 receptor antibody, dupilumab after achieving unsatisfactory responses with previous treatments including steroids, rituximab, omalizumab, and reslizumab. The patient’s symptoms (periorbital swelling and asthmatic/nasal symptoms) were remarkably improved; serum levels of IgG4/IgE as well as plasmablast/eosinophil counts progressively decreased without any recurrence sign for over 2 years of dupilumab treatment.ConclusionThese findings demonstrate that blocking the IL-4/IL-13 pathway with dupilumab can be an effective treatment with long-term safety in patients with severe AERD with CRS complicated by IgG4RD.

Frequency, clinical picture, diagnosis, and differential diagnosis of the pathology of the digestive tract (esophagus, stomach, and bowel) in IgG4-related disease (autoimmune pancreatitis)

Despite the publication of European guidelines for the diagnosis and treatment of IgG4-related disease (IgG4-RD), this problem is very complicated from a practical point of view. There are many publications about autoimmune pancreatitis and liver and biliary tract lesions in IgG4-RD, but the data on the digestive tract lesions are not sufficient. Gastrointestinal manifestations of IgG4-RD are considered to be rare or very rare.&#x0D; IgG4-RD presenting as esophageal lesions is rare condition. Only single clinical cases are available. I. Obiorah et al. reported the highest number of cases of IgG4-related esophagitis (8 cases). Interestingly, 7/8 cases reported by I. Obiorah et al. were males (age range: 18 to 79 years), and most patients had dysphagia as the most prominent symptom, with erosions and strictures at endoscopy. Histologically, all patients had a lymphoplasmacytic infiltrate and storiform fibrosis, while obliterative phlebitis was observed in 3/8 patients. Hence, 2 of the 3 major histological “Boston criteria” of IgG4-RD were fulfilled in all patients. Besides, all patients had at least 50 IgG4-positive cells per HPF (range: 50–110), and IgG4/IgG ratios of at least 50% (range: 50–90%). Of I. Obiorah’s patients, s-IgG4 had only been measured in three — all of whom had values in the normal range. Esophageal strictures were identified in three patients, two patients had achalasia.&#x0D; Based on K. Notohara’s series and the other published cases, it can be concluded that gastric IgG4-RD often (but not always) seems to be clinically asymptomatic, that s-IgG4 is elevated in a considerable number of cases, and histologically, that at least two of the Boston criteria often are found. The recommended cut-off of 50 IgG4-positive cells and IgG4/IgG ratios of &gt;40% was often fulfilled in the reported cases of IgG4-RD.&#x0D; There are few reports of IgG4-RD involving the duodenum, duodenal papilla, ileum with small bowel obstruction caused by pseudotumor or sclerosing disease of the small bowel with luminal narrowing.&#x0D; There are case reports of IgG4-RD with lesion of ileocecal area with an obstructing ileocecal mass and appendix, mimicking Crohn’s disease, appendicitis or appendiceal tumor. IgG4-related inflammatory bowel disease may — rarely — also be one of manifestations of IgG4-RD.&#x0D; Treatment should be conducted in accordance with European guidelines.

IgG4 related disease: a novel association with hypertrophic osteoarthropathy

IgG4 related disease (IgG4-RD) is a recently recognized disease that has several associated clinical phenotypes including autoimmune pancreatitis, sclerosing cholangitis, major salivary gland enlargement (Mikulicz disease), orbital pseudotumor, retroperitoneal fibrosis, and inflammatory vascular disease manifesting as aortitis or coronary artery calcification. Histopathology of affected organs shows lymphoplasmacytic infiltrations with a predominance of IgG4-positive plasma cells in the affected tissue and an increased number of eosinophils. Serum IgG4 levels are elevated in two-thirds of patients, and IgE is also often elevated. We report here the first known associated case of presumed IgG4-RD with hypertrophic osteoarthropathy. Hypertrophic osteoarthropathy (HOA) is frequently a paraneoplastic disease of bone, but HOA can be associated with chronic infection, chronic pulmonary disease, cardiac shunts, and cirrhosis. HOA is a clinical diagnosis consisting of arthralgia, digital clubbing, and periostosis of tubular bones seen on imaging with or without synovial effusion. Our 35 yo male LatinX patient presented with typical clinical symptoms of HOA that were confirmed on imaging. During the negative work up for malignancy, disproportionate-for-age coronary artery calcification was identified, which prompted an evaluation for IgG4-RD. The patient also had lung disease (peribronchial thickening), atopic dermatitis, subtle clubbing, elevated IgE, elevated IgG4 (9× normal), and eosinophilia. The patient's symptoms and inflammatory markers improved on prednisone and methotrexate, but a decision to treat with rituximab was made after having to discontinue methotrexate for transaminitis. Rituximab has been used in patients with IgG4-RD with some success, and our patient continues to improve in his skin, respiratory, and bone symptoms with reduction in IgG4, inflammatory markers, and bone turnover markers (alkaline phosphatase).

A Case of IgG4-Related Disease With Sinonasal Involvement Presenting With Decreased Visual Acuity

IgG4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by IgG4-positive plasma cell and T lymphocyte infiltration of multiple organs. It commonly involves the pancreas, lacrimal glands, and salivary glands, and it has been rarely reported in the sinonasal cavity. We herein report the case of a 47-year-old male patient whose chief complaint was decreased visual acuity. A tumefactive mass was found on imaging studies, originating from the sinonasal cavity and invading the orbit, kidney, and meninges. The mass was resected through endoscopic sinus surgery and was pathologically confirmed to be IgG4-RD. The patient was treated with steroid therapy and showed clinical improvement.

IgG4-related disease with kidney and lymph nodes involvement: a case-based review.

IgG4-related disease (IgG4-RD), a rare immune-mediated chronic fibro-inflammatory condition, has various initial symptoms, thus posing diagnostic and therapeutic challenges. Here, we report a case of IgG4-RD in a 35-year-old man with initial clinical symptoms of facial edema and recent onset of proteinuria. It took more than 1year from the onset of clinical symptoms to diagnosis. Pathological examination of renal biopsy revealed significant renal interstitial lymphoid tissue hyperplasia simulating growth pattern of lymphoma. Immunohistochemical (IHC) staining results showed that CD4 + T lymphocyte hyperplasia was dominant. There was no significant deletion of CD2/CD3/CD5/CD7. No monoclone was detected in TCR gene rearrangement. IHC staining showed that the number of IgG4-positive cells was greater than 100/HPF. The ratio of IgG4/IgG was greater than 40%. Combined with clinically examinations, IgG4-related tubulointerstitial nephritis was considered. Further cervical lymph node biopsy results suggested IgG4-related lymphadenopathy. He received methylprednisolone 40mg/day intravenously for 10days, leading to normal results of laboratory tests and clinical manifestations. The patient had a good prognosis without recurrence during 14months of follow-up. This case report can be used as a reference for early diagnosis and treatment of such patients in the future.

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

ObjectiveAutoimmune 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.MethodsThis retrospective cohort...

A case of IgG4-related disease with severe hypereosinophilia

A case of IgG4-related disease with severe hypereosinophilia

The Positive Predictive Value of a Very High Serum IgG4 Concentration for the Diagnosis of IgG4-Related Disease.

Serum IgG4 concentrations are used to evaluate a diagnosis of IgG4-related disease (IgG4-RD), but the positive predictive value (PPV) of a very high IgG4 level is uncertain. This study evaluated the PPV of a very high IgG4 concentration for diagnosing IgG4-RD. The data warehouses of 2 large academic healthcare systems were queried for IgG4 concentration test results. Cases with serum IgG4 concentrations > 5× the upper limit of normal (ULN) were included. Cases of IgG4-RD were determined using the American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria. The PPV for IgG4-RD of an IgG4 concentration > 5× ULN was estimated. Other conditions associated with very high IgG4 concentrations and specific features of IgG4-RD cases were characterized. IgG4 concentrations were available in 32,206 cases. Of these, 3039 (9.4%) had elevated IgG4 concentrations, and a final cohort of 191 (0.6%) cases had IgG4 concentrations > 5× ULN (median age 66 yrs, 72% male). The PPV of an IgG4 concentration > 5× ULN for a diagnosis of IgG4-RD was 75.4% (95% CI 68.7-81.3). In the remaining cases, elevated IgG4 concentrations were observed among patients with malignancies, autoimmune diseases, and infections. The majority of cases with serum IgG4 concentrations > 5× ULN in this study had IgG4-RD. These data support the high weight placed on very high serum IgG4 concentrations in the ACR/EULAR classification criteria. However, 25% of cases with very high IgG4 concentrations had an alternative diagnosis, underscoring the importance of considering the broad differential of etiologies associated with an elevated IgG4 concentration when evaluating a patient.

AN ATYPICAL CAUSE OF EOSINOPHILIA AND HYPOCOMPLEMENTEMIA

<h3>Introduction</h3> IgG4-related disease (IgG4-RD) is a multiorgan immune-mediated fibroinflammatory condition. Patients with IgG4-RD develop symptoms related to the tumor-like enlargement of affected tissues. Histopathologic studies demonstrate a lymphoplasmacytic infiltrate enriched in IgG4-positive plasma cells and a variable degree of storiform pattern fibrosis. <h3>Case Description</h3> A 76-year-old female patient with a history of hypergammaglobulinemia, lymphadenopathy, and Sjogren's syndrome was referred to our division due to low complement levels. She had no history of angioedema or urticaria. Laboratory studies showed hypocomplementemia with low levels of C3 (63 mg/dL), C4 (4 mg/dL), and CH50 (8 U/mL). Also hypergammaglobulinemia (3030 mg/dL) with elevated IgG4 (434 mg/dL), and an increased absolute eosinophil count (790 cells/µL). Skin biopsy on her left calf revealed granular deposition of IgG4. <h3>Discussion</h3> Here we present the case of IgG4-RD as an atypical cause of eosinophilia and hypocomplementemia. The presence of these findings in older patients with unexplained swelling in one or more organs that is responsive to corticoid therapy should raise the suspicion for IgG4-RD. It is important to note that approximately one third of patients diagnosed with IgG4-RD have hypocomplementemia. Interestingly, a case series of patients with IgG4-RD described an association of hypocomplementemia with increased severity and higher risk of relapse. Additionally, hypocomplementemia is related to renal involvement, specifically tubulointerstitial nephritis (TIN). In this regard, a case series reported that up to 56% of patients with IgG4-TIN have decreased C3 and C4.

Sinonasal IgG4-related sclerosing disease: A rare entity and challenging diagnosis.

To describe the rare presentation, imaging and histological findings, and treatments in patients with IgG4-related disease (IgG4-RD) and diagnostic pitfalls and difficulties. Cases of sinonasal IgG4-RD were retrieved, and clinicopathological features were reviewed. Seven cases of sinonasal IgG4-RD were identified over an 11-year period, including four males and three females, with an age range of 19-66 years (median 58 years). Patients presented with symptoms related to the mass effect of the lesions or the destructive nature of the disease including fullness, swelling, obstruction, and pain. Serum IgG and IgG4 levels, IgG/IgG4 ratios, storiform fibrosis, obliterative phlebitis, and plasma cell infiltration were seen in varying proportions. Bony erosion and tissue inflammation were present in some cases. Sinonasal IgG4-RD is exceedingly rare among other IgG4-RD and varied in its clinical presentation thus posing as a clinically difficult disease to diagnosis. Proper clinical, pathological, and immunohistopathological analysis is required for accurate diagnosis. Such disease should be considered in all cases of similar presentation to those in this study.Level of Evidence: 4.

A Case of IgG4-Related Disease with an Invaginated Small Intestine

A Case of IgG4-Related Disease with an Invaginated Small Intestine

Otologic Manifestations of IgG4-Related Disease: Literature Review and Report of Two Cases

Background: IgG4-related disease (IgG4-RD) is an inflammatory process. The literature on IgG4-RD is rather limited, with mastoid involvement being uncommon. In such cases, presentation may mimic other middle ear and mastoid cavity pathologies. Objective: To summarize findings of patients with IgG4-RD involving the mastoid. Methods: Description of two new cases and summary of findings with previous reports. Results: Nineteen cases of IgG4-RD with mastoid bone involvement were reported in the literature, the earliest appearing at the beginning of the previous decade. Most frequent symptoms included hearing deterioration, tinnitus and otalgia. In 58% of the cases, the process was restricted to otologic manifestations. In 7 out of 19 cases, tissue IgG4 levels were elevated. In all histopathologic samples taken from the operative sites, a dense lymphoplasmacytic cell infiltration was observed. Following definitive pathological diagnosis, the most common treatment was corticosteroids. Generally, the time from onset to final diagnosis was usually more than six months. The treatment is corticosteroids, followed by immunosuppressive agents such as rituximab, cyclophosphamide, and methotrexate. Conclusions: IgG4-RD involving the mastoid is a challenging condition, both in diagnosis and treatment. Hence, IgG4-RD should be included in the differential diagnosis of middle ear pathologies and include a multi-disciplinary team for treatment.

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

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. 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. 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. 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.