Risk of Misdiagnosis in Spinal Hypertrophic Pachymeningitis: A Report of Two Cases.

Hypertrophic pachymeningitis (HP) is a rare inflammatory disease of the central nervous system. It typically manifests in the cranium; cases involving the spinal cord are rare (8.6%). This report includes two cases of spinal HP encountered among 666 spinal operative cases. The purpose of this study is to present the initial imaging findings, final diagnosis, and course of treatment in these two cases of spinal HP and to present the possible risk of misdiagnosis with a literature review. In case 1, a 69-year-old female presented with back pain. The initial radiological diagnosis with magnetic resonance imaging (MRI) was a meningioma. However, her blood test showed a mild elevation of C-reactive protein level (3.16 mg/dL), with positive IgG4 and myeloperoxidase anti-neutrophil cytoplasmic antibody results, suggesting an autoimmune disease. We performed a biopsy of the thickened dura and an expansive duraplasty. Serological and pathological diagnosis suggested IgG4-related HP. In case 2, a 67-year-old male presented with bilateral thigh pain. MRI revealed a mass resembling a disc hernia at the L2/3 intervertebral level. The mass was surgically removed. Pathological examination and cerebrospinal fluid analysis confirmed the diagnosis of HP associated with IgG4-related disease. In both cases, immunosuppressive therapy was administered, and follow-up MRI scans revealed the disappearance of the mass. The study concludes that a spinal HP can potentially be misdiagnosed when its images resemble those of tumors or disc hernias owing to its rarity.

Transudative pleural effusion in pleuritis associated with immunoglobulin G4-related disease diagnosed by thoracoscopy under local anaesthesia.

Immunoglobulin G4 (IgG4)-related disease is a chronic inflammatory condition often characterized by exudative pleural effusions. However, transudative pleural effusions, like in the presented case of an 80-year-old man with multiple comorbidities, are less common but possible. Despite initial treatment with diuretics, the effusion persisted, prompting further investigation. Medical thoracoscopy revealed lymphatic follicle hyperplasia and an abundance of IgG4-positive plasmacytoid cells, confirming IgG4-related pleuritis. This case underscores the importance of considering inflammatory etiologies, such as IgG4-related disease, when faced with unresponsive transudative pleural effusions. Thoracoscopy serves as a valuable diagnostic tool in such scenarios, allowing for precise diagnosis and appropriate management.

Surgical Treatment for Giant Multiple Coronary Artery Aneurysms Caused by an IgG4-Related Disease.

Coronary artery aneurysms (CAAs) due to an immunoglobulin G4 (IgG4)-related disease (IgG4-RD) are relatively rare, and there is no consensus on the choice of treatment method. In the present study, we report the results of the surgical treatment for multiple giant CAAs caused by IgG4-RD. A 71-year-old man was diagnosed with severe aortic regurgitation and CAAs. A blood test showed high IgG4 levels, and computed tomography revealed four giant coronary artery aneurysms: two in the right coronary artery (RCA) (proximal RCA and posterior descending artery (PDA)), one in the left anterior descending (LAD), and one in the diagonal branch (Dx). We planned aortic valve replacement, coronary aneurysm resection, and coronary artery bypass grafting (CABG). After finishing aortic valve replacement, the CAAs in proximal RCA, LAD, and Dx were resected. The proximal and distal tracts of the aneurysm were closed with a pericardial bovine patch and ligation. However, since the distal PDA was too calcified to be anastomosed, and the PDA aneurysm was smaller than the others, it was decided to leave the PDA aneurysm. The anastomoses of SVG-RCA and Dx, as well as the left internal thoracic artery to LAD, were performed. Histopathological examination of the aneurysm wall showed a high IgG4-positive cell/IgG-positive cell ratio, and a diagnosis of IgG4-RD was made. In the treatment of CAAs due to IgG4-RD, it is essential to select a procedure that takes into account the size, location, and nature of the aneurysm, and comorbidities. To ensure resection of the aneurysm and blockade of blood flow, closure of the inflow and outflow tracts with a pericardial bovine patch and CABG are effective.

Clinicopathological features of immunoglobulin G4-related constrictive pericarditis.

AIM: Constrictive pericarditis (CP) is characterised by scarring fibrosis and a loss of pericardial elasticity, which causes heart failure. IgG4 (immunoglobulin G4)-related disease (IgG4-RD) is a systemic fibro-inflammatory disease characterised by the infiltration of IgG4-immunopositive plasmacytes and high serum IgG4 levels that frequently shape tumorous lesions. Although pericardial involvement of IgG4-RD is rare, with indications of CP, pericardial effusion and irregular masses, the clinical and pathological features remain unclear. In this study, we examined the relationship between CP and IgG4-RD. METHODS: Among 35 thick-walled CP cases (histologically pericardial thickening ≥2 mm), eight cases were aetiology identified. Using the diagnostic criteria for IgG4-RD, 11 cases were classified as IgG4-CP, whereas the remainder were considered true idiopathic CP (16 cases) and the clinical pathological features were evaluated. RESULTS: Compared with the other groups, the IgG4-CP group was more common in men and associated with low-grade fever and massive pericardial effusion with frequent recurrence. Deaths resulting from heart failure occurred in a few cases of the IgG4-CP group, but not in other groups. An increase in C-reactive protein and a high positivity rate of anti-nuclear antibodies frequently occurred in the IgG4-CP group. Histologically, the IgG4-CP group included lymphoid follicle, eosinophil infiltration and few calcifications. CONCLUSIONS: Pericardial IgG4-RD occurs not only as nodular lesions, but also as thick-walled CP, and accounts for approximately 40% of thick-walled CP cases of unknown cause. The predominant clinical characteristic was refractory and recurrent pericardial effusion. Recognising IgG4-RD as a cause of CP is important to initiate appropriate therapy.

Efficacy and safety of rituximab induction therapy and effect of rituximab maintenance for IgG4-related disease: a systematic review and meta-analysis.

BACKGROUND: Previous studies have reported that rituximab (RTX) therapy might be beneficial in reducing relapse rates in patients with IgG4-related disease (IgG4-RD). Therefore, we aimed to systematically assess the efficacy and safety of RTX induction treatment and the effect of RTX maintenance in patients with IgG4-RD. METHODS: The protocol was registered in the PROSPERO (CRD42023427352). PubMed, Embase, the Cochrane database, Scopus, and the Web of Science were interrogated to identify studies that evaluated the impact of RTX on prognosis in IgG4-RD. We explored the impact of various subgroups of factors on relapse outcomes and focused on the possible role of maintenance therapy in reducing relapse rates. The pooled incidence of adverse events of RTX therapy and the influencing factors have also been evaluated. RESULTS: Eighteen studies comprising 374 patients (mean age 56.0 ± 8.7 years; male 73.7 %) with a mean follow-up duration of 23.4 ± 16.3 months were included. The pooled estimate of the response rate, complete remission rate, overall relapse rate, adverse event rate, and serious adverse event rate of RTX induction therapy were 97.3 % (95 % CI, 94.7 %-99.1 %), 55.8 % (95 % CI, 39.6 %-71.3 %), 16.9 % (95 % CI, 8.7 %-27.1 %), 31.6 % (95 % CI, 16.7 %-48.9 %) and 3.9 % (95 % CI, 0.8 %-8.9 %), respectively. In subgroup analysis, the pooled relapse rate was significantly lower in studies with maintenance than without maintenance (2.8% vs 21.5 %, p < 0.01). Pooled Kaplan-Meier relapse curves also demonstrated that RTX maintenance therapy provided a better prognosis. CONCLUSIONS: RTX induction therapy appears to have satisfactory efficacy in the induction of remission in IgG4-RD. In addition, prophylactic RTX maintenance therapy after induction may be beneficial in preventing relapse of IgG4-RD.

A Rare Case of Immunoglobulin G4-Related Constrictive Pericarditis Diagnosed Via Multimodality Imaging.

Constrictive pericarditis (CP) presents as a pathophysiological state where the pericardium becomes inelastic due to fibrotic changes, most commonly secondary to a protracted inflammatory process. The disease is characterized by compromised diastolic cardiac function due to loss of pericardial compliance. Immunoglobulin G4 (IgG4)-related disease, an entity marked by the insidious proliferation of IgG4-positive plasma cells and subsequent fibrosis within various organs, is an infrequent but recognized cause of CP. A case of a 55-year-old male patient with clinical manifestations of dyspnea and edema in the lower extremities elucidates the diagnostic complexity inherent to CP. Echocardiography revealed a constellation of signs, including annulus reversus, septal bounce, and a congested inferior vena cava; cardiac magnetic resonance imaging (MRI) demonstrated diffuse pericardial thickening with delayed gadolinium enhancement, suggestive of a long-term inflammatory state; and right heart catheterization confirmed the hemodynamic hallmark of CP-equalization of diastolic pressures across the cardiac chambers. The serological analysis elicited elevated serum levels of IgG4 and IgE, pointing to the differential diagnosis of IgG4-related disease. Given the nonspecific clinical presentation of IgG4-related CP, a heightened index of suspicion combined with a systematic approach to imaging and serological evaluation is paramount.

Mikulicz's disease combined with IgG4-related hypophysitis: a case report.

BACKGROUND: IgG4-related diseases are very uncommon, and its diagnosis and treatment are complicated as it encompasses multiple disciplines. CASE PRESENTATION: A 77-year-old woman was admitted with a jaw mass and nausea and vomiting. Laboratory tests showed elevated serum IgG4, pituitary MRI suggested thickening of the pituitary stalk, and head and neck CT suggested orbital and mandibular masses. Patients with mandibular mass were diagnosed with Mikulicz's disease with IgG4-related hypophysitis. We found no other evidence of causing thickening of the pituitary stalk. She was given oral prednisolone 30 mg daily, and her nausea and vomiting improved significantly, and the mandibular and ocular masses decreased in size. CONCLUSION: Mikulicz's disease combined with IgG4-related hypophysitis is a rare case of IgG4-RD in elderly women. IgG4-RD is one of the causes of head and neck exocrine gland mass and pituitary stalk thickening in the elderly.

Duodenal stricture secondary to IgG4-related chronic sclerosing duodenitis-A case report with review of the literature.

Key Clinical Message: This case highlights the importance of a definite diagnosis of an IgG4-related chronic sclerosing duodenitis based on histological and radiological findings to rule out any malignancy in the mass. While dealing with patients having concentric duodenal thickening resulting in stricture formation, one should think of inflammatory etiology as well. IgG4-related disease is one of these inflammatory disorders where we see soft tissue thickening without a large mass or any associated lymphadenopathy as in our case. Abstract: Immunoglobulin G4-related disease (IgG4-RD) is distinguished as an infiltration of IgG-4-positive plasmacytes involving inflammatory lesions across multiple organs which is accompanied by raised IgG4 levels in the serum. Several inflammatory disorders are recognized as part of the IgG4-RD family based on shared histopathological features, which include Mikulicz's disease, chronic sclerosing sialadenitis, or Riedel's thyroiditis. Our case highlights a distinctive presentation of IgG4-related diseases; a 58-year-old man presenting with duodenal stricture highly suspicious of a duodenal mass/ampullary mass later found to be due to IgG4-related sclerosing duodenitis with negative malignancy on biopsy. We present the diagnostic challenges faced and relevant findings noted.

Rituximab and pericardiectomy with waffle procedure in constrictive pericarditis due to IgG4-related disease: A case report.

We should consider IgG4-related disease (IGRD) as one of the potential causes of constrictive pericarditis. In patients with constrictive pericarditis due to IGRD, the combination of surgical treatment and immunosuppressive therapy may be an effective strategy.

Lateral micro-orbitotomy as the technique of choice for orbital pseudotumor in IgG4-RD. Case report and review of the literature.

Immunoglobulin G4-related disease (IgG4-RD) is characterized by a systemic fibroinflammatory infiltrate that often involves the orbit in addition to other tissues. Thus it has to be considered in the differential diagnosis of orbital tumors. We report the clinical case of a 64-year-old woman who presented with right mydriasis, progressive proptosis and paralysis of the third cranial nerve of 1 year of evolution. Cranial MRI identified an intraconal lesion of the right orbit, located between the external and inferior rectus muscles and the optic nerve, and she was scheduled for surgery by transcranial approach with lateral micro-orbitomy. A satisfactory macroscopic excision was achieved with no remarkable complications and a definitive deferred histological result of pseudotumor by IgG4-RD. Follow-up for 24 months showed no tumor recurrence, and the patient clinically improved from ophthalmoplegia. This case highlights the efficacy of lateral orbitotomy in the etiologic diagnosis and successful therapeutic outcome of complex orbital lesions associated with IgG4-RD pseudotumor.

Combined paraganglioma and IgG4-related retroperitoneal fibrosis.

A paraganglioma is a neuroendocrine tumor that may secrete catecholamines and present with symptoms of sympathetic overload such as hypertension and diaphoresis. It is important that paragangliomas are identified, as they must often be treated by surgical excision. IgG4-related retroperitoneal fibrosis (IgG4-RPF) is a systemic inflammatory disease that results in the infiltration of IgG4-positive plasma cells in the retroperitoneum. Such fibrosis may adversely affect nearby organs and tissues. Here, we describe a case of combined paraganglioma and IgG4-RPF in a 47-year-old female patient. This case demonstrates the deleterious effect of these two conditions when they occur simultaneously.

Clinical manifestations of chronic pancreatitis in English cocker spaniels.

BACKGROUND: Chronic pancreatitis (CP) is common in English cocker spaniels (ECS). It is histologically similar to IgG4-related disease (IgG4-RD) in humans and is characterized by duct destruction, interlobular fibrosis, and dense periductular and perivenous lymphocytic aggregates. However, the clinical manifestations of CP in ECS have not been previously described. OBJECTIVES: Characterize the clinical manifestations of CP in a group of ECS, including similarities and differences to IgG4-RD in humans. ANIMALS: One-hundred four ECS with CP and 44 client owned control ECS without CP (both healthy and diseased controls). METHODS: Affected dogs were divided into 2 groups according to the methods used to diagnose CP. Case records were searched for signalment, clinical, and clinicopathological findings, and evidence of keratoconjunctivitis sicca (KCS), proteinuria, other immune-mediated diseases, and anal sacculitis. RESULTS: Involvement of other organs was common. Affected ECS presented with a high frequency of KCS (n = 49), proteinuria (n = 47), anal gland disease (n = 36), atopy (n = 21), and other immune-mediated diseases (n = 16). Those with parti-color hair coats, particularly blue roan, had a strong association with CP, suggesting a link between coat color and autoimmune conditions in this breed. CONCLUSIONS AND CLINICAL IMPORTANCE: English cocker spaniels with CP show clinical similarities to humans with IgG4-RD and common involvement of other organs. Clinicians should evaluate affected Cocker Spaniels for proteinuria, keratoconjunctivitis sicca, and other potential immune-mediated diseases.

Pulmonary manifestations, treatments and outcomes of IgG4-related disease-a systematic literature review.

Immunoglobulin G4-related disease (IgG4-RD) is a multisystem fibroinflammatory condition. A consistent feature of many cases is pulmonary infiltrates, or respiratory failure. This systematic literature review aims to summarise the pulmonary manifestations of IgG4-RD, including clinical outcomes and treatment. This review was registered on PROSPERO (CRD42023416410). Medline, Embase and Cochrane databases were searched for articles discussing IgG4-RD syndrome. Information was extracted on demographics, type and prevalence of pulmonary manifestations, treatment and clinical outcomes. Initially, after deduplication, 3123 articles were retrieved with 18 ultimately included. A pooled total of 724 patients with IgG4-RD were included, 68.6% male, mean age 59.4 years (SD 5.8) at disease onset. The most frequently described pulmonary manifestation was mediastinal lymphadenopathy (n = 186, 48.8%), followed by pulmonary nodules (n = 151, 39.6%) and broncho-vascular thickening (n = 85, 22.3%). Where treatment was reported, the majority of patients received glucocorticoids (n = 211, 93.4%). Other immunosuppressive therapy included cyclophosphamide (n = 31), azathioprine (n = 18), with mycophenolate mofetil (n = 6), rituximab (n = 6), methotrexate (n = 5) and other unspecified immunomodulators (50). Clinical outcomes were reported in 263 patients, where 196 patients had remission of their disease, 20 had relapse, 35 had stable disease, four had progression and eight patients died from complications of IgG4-RD. This systematic review summarises pulmonary manifestations, treatments and outcomes in patients with IgG4-RD. Pulmonary involvement in IgG4-RD is relatively common, leading to high levels of morbidity and mortality. Glucocorticoids remain the mainstay of treatment, but further work is required to explore the management of patients with pulmonary manifestations in association with IgG4-RD.

IgG4-related disease: Case report and 6-year follow-up of an elusive diagnosis mimicking malignancy.

Key Clinical Message: IgG4-related disease is a rare and emerging pathology, characterized by the appearance of pseudotumors. Due to the ability to mimic other pathologies, it is essential to consider it as a differential diagnosis in multisystemic processes. The diagnosis is challenging, requiring a multidisciplinary approach, to minimize the associated morbidity and mortality. Abstract: IgG4-related disease (IgG4-RD) is a rare, emerging, systemic and chronic pathology, characterized by the appearance of pseudotumors resulting from tissue infiltration by IgG4-positive plasma cells that promote eosinophilic inflammation of the tissue with subsequent fibrosis. We present the case of a male, 45-year-old patient, with marked weight loss and skin pallor detected by his family doctor during a child health consultation of his daughter. When questioned, the patient referred complaints of postprandial discomfort in the left hypochondrium with a feeling of fullness, weight loss, chronic fatigue and hyperhidrosis that had lasted for a month. On physical examination, he was pale, and had pain at palpation of the left hypochondrium. Laboratory data showed increased inflammation markers, abdominal ultrasound and CT demonstrated numerous enlarged lymph nodes in the upper quadrants, raising concern for a malignant lymphoproliferative process. Serological, imaging, clinical and laparoscopic excisional biopsy revealed features of IgG4-related disease and excluded malignant lymphoproliferative disease. The immediate response to treatment with oral prednisolone 30 mg/day also contributed for diagnosis confirmation. Due to refractory disease after gradual prednisolone reduction, second-line therapy with rituximab was initiated. Over the 6 years of follow-up, the patient presented multiple exacerbations characterized by the emergence of systemic symptoms, being maintained under close clinical and imaging follow-up by reumathology, infectious diseases, and family medicine specialists.

A case report of IgG4-related hepatic inflammatory pseudotumor in a 3-year old boy.

Background: Hepatic Inflammatory Pseudotumor (IPT) is an infrequent condition often masquerading as a malignant tumor, resulting in misdiagnosis and unnecessary surgical resection. The emerging concept of IgG4-related diseases (IgG4-RD) has gained widespread recognition, encompassing entities like IgG4-related hepatic IPT. Clinically and radiologically, corticosteroids and immunosuppressive therapies have proven effective in managing this condition. Case Presentation: A 3-year-old Chinese boy presented to the clinic with an 11-month history of anemia, fever of unknown origin, and a tender hepatic mass. Blood examinations revealed chronic anemia (Hb: 6.4 g/L, MCV: 68.6 fl, MCH: 19.5 pg, reticulocytes: 1.7%) accompanied by an inflammatory reaction and an elevated serum IgG4 level (1542.2 mg/L). Abdominal contrast-enhanced computed tomography unveiled a 7.6 cm low-density mass in the right lateral lobe, while magnetic resonance imaging demonstrated slight hypointensity on T1-weighted images and slight hyperintensity on T2-weighted images, prompting suspicion of hepatic malignancy. A subsequent liver biopsy revealed a mass characterized by fibrous stroma and dense lymphoplasmacytic infiltration. Immunohistochemical analysis confirmed the presence of IgG4-positive plasma cells, leading to the diagnosis of IgG4-related hepatic IPT. Swift resolution occurred upon initiation of corticosteroid and mycophenolate mofetil therapies. Conclusion: This study underscores the diagnostic approach to hepatic IPT, utilizing histopathology, immunostaining, imaging, serology, organ involvement, and therapeutic response. Early histological examination plays a pivotal role in clinical guidance, averting misdiagnosis as a liver tumor and unnecessary surgical interventions.

A case of IgG4-related disease associated with ulcerative colitis that was successfully treated with a JAK inhibitor.

Glucocorticoids (GC) are the standard of care for the induction and maintenance of remission in immunoglobulin G4 (IgG4)-related diseases. However, IgG4-related diseases often relapse with GC dose reduction, not only making GC dose reduction difficult but also necessitating GC dose escalation in many cases. Therefore, other immunosuppressive drugs are required to maintain remission. Here, we report a 39-year-old man with ulcerative colitis and IgG4-related disease who experienced a relapse of both diseases despite treatment with tacrolimus and 6-mercaptopurine. Following the initiation of tofacitinib, a Janus-associated kinase inhibitor, it was possible to reduce the GC dose while maintaining remission of both diseases. This case highlights the potential utility of Janus-associated kinase inhibitors in managing complex cases of IgG4-related disease, especially those with concurrent conditions such as ulcerative colitis.

Isolated IgG4 related disease of the trachea.

IgG4 related disease (IgG4-RD) is a multisystem inflammatory disease and can affect several organs including salivary glands, orbits, lungs, pancreas, kidneys and lymph nodes. Up to 40 % of patients have allergic manifestations including asthma, chronic rhinosinusitis, eczema and asthma. Commonly pulmonary manifestations include pulmonary nodules ranging from <1 to 5 cm in diameter, interstitial opacities and mediastinal lymphadenopathy. Rarely, IgG4-RD presents as isolated tracheal disease. Symptoms include dyspnea and stridor due to airway narrowing. Diagnosis of IgG4-RD including tracheal IgG4-RD requires a biopsy. The histologic specimen is characterized by lymphoplasmacytic infiltrate with high density of IgG4 positive plasma cells, and storiform fibrosis (a cartwheel appearance of fibroblasts and inflammatory cells). Up to 30 % of patients with IgG4-RD have normal serum IgG4 levels. The mainstay of therapy is glucocorticoids for those with systemic disease. Rituximab is an alternative for those who cannot tolerate glucocorticoids or those with disease recurrence. Patients with tracheal disease often require balloon dilation. Recurrence is common in patients and up to two thirds of patients have residual disease despite treatment. These patients often require surgical resection of affected area for symptomatic relief.