IgG4-related Ophthalmic Disease Research Articles

IgG4-Related Ophthalmic Disease. Part II: Clinical Aspects.

To review the current state of knowledge of IgG4-related ophthalmic disease (IgG4-ROD). A review of the literature and personal experience of the authors. IgG4-related disease is a recently recognized fibroinflammatory disorder that may affect 1 or more organs. It is characterized by lymphoplasmacytic infiltrates with large numbers of IgG4 positive plasma cells, storiform fibrosis, obliterative phlebitis, and eosinophil infiltration as well as peripheral eosinophilia, and in some cases, elevated serum levels of IgG4. These features are not always seen, and the diagnosis should be made by integrating clinical, imaging, and histopathological data, with reference to recently defined diagnostic criteria. IgG4-ROD forms a significant proportion of what has previously been labeled "idiopathic orbital inflammation" or reactive lymphoid hyperplasia. Orbital disease may occur alone, at the same time as disease elsewhere, or metachronously with systemic disease. Although almost any ocular adnexal tissue may be affected, there are several commoner recognizable patterns of IgG4-ROD: (1) sclerosing dacryoadenitis; 2) enlargement of orbital nerves (most commonly the infraorbital nerve) associated with orbital myositis and lacrimal gland disease, often in combination with paranasal sinus disease, eosinophilia, and systemic involvement; and 3) sclerosing orbital inflammation. Patients with IgG4-ROD should be investigated and monitored for other organ involvement. Some patients with IgG4-related disease may develop lymphoma, usually marginal zone lymphoma of mucosa-associated lymphoid tissue type. Treatment of IgG4-ROD includes the use of corticosteroids and other immunosuppressants. Rituximab has been shown to be very effective. Longer term studies on the natural course and treatment of IgG4-ROD are needed. Patients presenting with orbital inflammatory lesions should have biopsies obtained whenever possible. The examining pathologist should routinely look for features of IgG4-ROD, and if found, the patient should be investigated for other organ involvement. Early treatment may prevent destructive changes in affected tissues.

Diagnosis and treatment of IgG4-related ophthalmic disease

Purpose: To further characterize the clinical presentation, diagnosis, and current treatment strategies of IgG4-related ophthalmic disease. Methods: Review and analysis of seven cases orbital inflammatory syndrome found to be biopsy positive for IgG4. Results: We present seven cases of IgG4-related ophthalmic disease, a previously unknown entity that has only recently been identified as a treatable systemic disorder. Management included surgical excision, systemic steroids, steroid-sparing immunosuppression, and radiotherapy. Conclusions: These cases illustrate the importance of including IgG4-related ophthalmic disease in the differential diagnosis of periorbital or orbital masses. Prompt recognition of this entity by clinicians can allow for effective treatment with corticosteroids. Treatment with steroid-sparing immune suppressants and radiotherapy has shown promise in chronic or refractory disease, nonetheless tumor excision may ultimately be necessary.

IgG4-related ophthalmic disease. Part I: background and pathology.

To review the current state of knowledge of IgG4-related ophthalmic disease (IgG4-ROD). A review of the literature and personal experience of the authors. IgG4-related disease is a recently recognized fibroinflammatory disorder that may affect 1 or more organs. It is characterized by lymphoplasmacytic infiltrates with large numbers of IgG4 positive plasma cells, storiform fibrosis, obliterative phlebitis, and eosinophil infiltration as well as peripheral eosinophilia, and in some cases, elevated serum levels of IgG4. These features are not always seen, and the diagnosis should be made by integrating clinical, imaging, and histopathological data, with reference to recently defined diagnostic criteria. IgG4-ROD forms a significant proportion of what has previously been labeled "idiopathic orbital inflammation" or reactive lymphoid hyperplasia. Orbital disease may occur alone, at the same time as disease elsewhere, or metachronously with systemic disease. Although almost any ocular adnexal tissue may be affected, there are several more common recognizable patterns of IgG4-ROD: 1) sclerosing dacryoadenitis; 2) enlargement of orbital nerves (most commonly the infraorbital nerve) associated with orbital myositis and lacrimal gland disease, often in combination with paranasal sinus disease, eosinophilia, and systemic involvement; and 3) sclerosing orbital inflammation. Patients presenting with orbital inflammatory lesions should have biopsies obtained whenever possible. The examining pathologist should routinely look for features of IgG4-ROD, and if found, the patient should be investigated for other organ involvement. Early treatment may prevent destructive changes in affected tissues.

IgG4関連眼疾患の10年と今後の課題について

IgG4関連眼疾患の10年と今後の課題について

IgG4-Related Disease

Immunoglobulin G4-related disease (IgG4-RD) is a multifocal inflammatory disorder that causes tumefactive lesions with a dense lymphoplasmacytic infiltrate rich in IgG4 plasma cells and storiform-pattern fibrosis. The clinical symptoms are relatively mild, and the condition is usually recognized by organ swelling and damage. When referring to the ophthalmic manifestations of IgG4-RD, the term IgG4-related ophthalmic disease (IgG4-ROD) is used. IgG4-ROD is characterized by bilateral lacrimal gland enlargement accompanied by 3 distinctive features: infraorbital nerve enlargement, extraocular myositis, and compressive optic neuropathy. IgG4 implies an underlying systemic disease process requiring evaluation to detect other systemic involvement. This includes hypophysitis and hypertrophic pachymeningitis, entities of neuro-ophthalmic interest. IgG4-ROD usually responds favorably to systemic corticosteroids but may be complicated by relapse during steroid taper. Rituximab has been shown to be effective for controlling steroid-refractory IgG4-RD. In contrast to IgG4-RD, an increasing number of cases of extranodal marginal B-cell lymphoma (MALT type) associated with IgG4-ROD have been described. IgG4 may be a risk factor for later emergence of low-grade B-cell lymphoma.

Diagnostic criteria for IgG4-related ophthalmic disease.

Immunoglobulin G4 (IgG4)-related disease is a novel clinical entity characterized by infiltration of IgG4-immunopositive plasmacytes and elevated serum IgG4 concentration accompanied by enlargement of and masses in various organs, including the lacrimal gland, salivary gland, and pancreas. Recent studies have clarified that conditions previously diagnosed as Mikulicz disease as well as various types of lymphoplasmacytic infiltrative disorders of the ocular adnexa are consistent with a diagnosis of IgG4-related disease. Against this background, the diagnostic criteria for IgG4-related ophthalmic disease have recently been established, based on both the clinical and the histopathologic features of the ocular lesions. This article reviews these new criteria with reference to the comprehensive diagnostic criteria for IgG4-related disease for all systemic conditions reported in 2012.

Bilateral Optic Nerve Involvement in Immunoglobulin G4–Related Ophthalmic Disease

To describe a presumptive case of immunoglobulin G4-related ophthalmic disease (IgG4-ROD) with bilateral optic nerve involvement and to review the clinical features of this entity. Case report. A 62-year-old man presented with bilateral blurred vision. He had a history of sinus surgery, and a biopsy specimen showed dense infiltration of IgG4-positive plasma cells. His visual acuity was 20/25, right eye, and 20/125, left eye. Serologies demonstrated elevated serum levels of IgG and IgG4, and computed tomography showed masses surrounding both optic nerves at the orbital apices and bilaterally enlarged infraorbital nerves. The patient underwent 2 cycles of intravenous pulse steroid therapy followed by a taper of oral steroids Three months later, vision was 20/20 in each eye and, while the serum level of IgG was within normal limits, the IgG4 level remained elevated. IgG4-ROD may involve the optic nerves resulting in vision loss. Although steroid administration is the primary treatment for this entity, slow tapering is essential to avoid relapse.

Location and frequency of lesions in patients with IgG4-related ophthalmic diseases

It is well-known that the lacrimal gland (LG) may be affected in IgG4-related ophthalmic disease (IgG4ROD). Recently, IgG4-related ophthalmic lesions other than those of the lacrimal gland have been reported. However, no study to date has revealed the details of these lesions. This study was conducted to evaluate the location and frequency of lesions found in conjunction with IgG4ROD using radiological imaging. Radiological images and clinical records of 65 patients collected from seven institutions in Japan were reviewed retrospectively. All patients had been pathologically diagnosed with IgG4ROD. Patients of mucosa-associated lymphoid tissue lymphoma associated with IgG4-related lesions were excluded. Orbital magnetic resonance imaging or computed tomography findings were evaluated. Of the 65 patients, 31 (47.7%) had lesions involving the LG alone, whereas 34 (52.3%) had lesions involving the areas other than LG, including eight patients who had lesions without any LG involvement. IgG4-related ophthalmic lesions included LG enlargement in 57 patients (87.7%), trigeminal nerve branch enlargement in 25 (38.5%), extraocular muscle enlargement in 16 (24.6%), diffuse orbital fat lesions in 15 (23.1%), orbital mass lesions in 11 (16.9%), eyelid lesions in eight (12.3%), and nasolacrimal duct lesion in one (1.5%). Six patients (9.2%) presented with visual disturbance due to optic nerve disturbance, eight (12.3%) with a restriction of ocular movement, and 19 (29.2%) with exophthalmos. Thirty-four (52.3%) of the 65 IgG4ROD patients had lesions in areas other than LG. Lesions were found in the trigeminal nerve branch including pterygopalatine fossa, extraocular muscles, orbital fat, eyelid, and nasolacrimal duct.

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.

A prevalence study of IgG4-related ophthalmic disease in Japan

Immunoglobulin (Ig)G4-related ophthalmic disease belongs to a category of ocular adnexal lymphoproliferative disorders, the most frequent group of orbital tumors and simulating lesions. The aim of this study was to elucidate the number of IgG4-related diseases of orbital lymphoproliferative disorders and correlate ages and sex of such patients from 18 centers in Japan. One thousand and fourteen patients with orbital lymphoproliferative disorders were enrolled in this study. All had pathologically diagnosed lymphoproliferative disorders with surgical samples of ocular adnexal tissue. Patients with conjunctival lesions and intraocular lymphoma were excluded. Of the 1,014 cases of orbital lymphoproliferative disorders 404 (39.8%) had extranodal mucosa-associated lymphoid tissue (MALT) lymphoma, 156 (15.4%) had other malignant lymphomas, 191 (18.8%) had non-IgG4 orbital inflammation, 219 (21.6%) had IgG4-related orbital inflammation, and 44 (4.3%) had IgG4-positive MALT lymphoma. Median age of the IgG4-related orbital inflammation group was 62years, which is significantly lower than that of the MALT lymphoma group (median 66years) and higher than the non-IgG4 orbital inflammation group (median 57years). The male/female ratio was 105/114 in the IgG4-related orbital inflammation group. Nearly a quarter of orbital lymphoproliferative disorders in Japan are related to IgG4.

Pathological findings of infraorbital nerve enlargement in IgG4-related ophthalmic disease

We report a case of bilateral infraorbital nerve enlargement (IONE) associated with immunoglobulin (Ig)G4-related ophthalmic disease and describe the associated histopathologic findings. An otherwise healthy 59-year-old man presented with bilateral exophthalmos and right visual disturbance. Orbital magnetic resonance imaging showed bilateral IONE and a soft tissue mass in the right orbit. Excisional biopsy in the left infraorbital canal was performed. Histopathologic assessment revealed IgG4-related disease involving the epineurium of the infraorbital nerve. The patient received systemic steroid therapy, to which he responded well. IONE in IgG4-related ophthalmic disease is due to IgG4-related disease involving the epineurium.