Case Report: Orbital Myositis and Myasthenia Gravis as Symptoms of Immune Reconstitution Inflammatory Syndrome in a Patient With Human Immunodeficiency Virus Infection.

We present a case of a 37-year-old man with HIV infection who had been on antiretroviral therapy for one year. He was admitted to our hospital with red and swollen eyes, acute onset progressive exophthalmos, and intermittent diplopia endured for 7 days. His symptoms, exam, and imaging led to a diagnosis of immune reconstitution inflammatory syndrome associated orbital myositis. His symptoms improved considerably after glucocorticoid therapy. Following a reduction in the oral prednisone dose, he re-presented with left ptosis, which rapidly progressed to bilateral ptosis. Diagnostic testing led to the diagnosis of immune mediated myasthenia gravis. Treatment with pyridostigmine bromide, prednisone, and tacrolimus was initiated. One month later, the patient's symptoms improved significantly. There was a probable association between his symptoms and autoimmune immune reconstitution inflammatory syndrome. This report highlights the importance of recognizing autoimmune disorders in human immunodeficiency virus-infected patients undergoing antiretroviral therapy. Orbital myositis and myasthenia gravis in human immunodeficiency virus-infected patients correlate closely with immunity status following a marked increase in CD4+ T cell counts.

Idiopathic inflammatory diseases of orbit and ocular adnexa: Histopathological and immunochemical analysis.

Purpose: : To present histopathological and immunohistochemical analysis of idiopathic inflammatory diseases of orbit and ocular adnexa. Methods: Design- A retrospective laboratory-based study. The study was carried out in an ocular pathology laboratory in a tertiary institute of northeast India where analysis of 93 cases was done in 5 years, during the period from 2011 to 2016. Hematoxylin--eosin and special stains were done for the diagnoses. Immunohistochemistry (IHC) panel was also carried out. For infectious pathology, Grocott's methenamine silver (GMS) stain for fungus, tissue Gram's stain for bacteria's, and acid-fast stains for tubercular bacilli were done. IHC panels were done for CD 20 (B-cells), CD-3 (T-cells), CD-45 (Leukocyte common antigen, LCA), BCL-2, CD-138 (Plasma cells), Kappa, Lambda, IgG-4 in tissue, IgG-4 in serum, etc. IHCs were done using kit methods (standardized) and adequate controls were taken for each sample. Results: 93 cases of nonspecific orbital inflammation were reported out of 1,467 specimens. Orbital pseudotumors (idiopathic orbital inflammatory disease, IOID) were seen in 27 cases (sclerosing variety-6); benign lymphoid hyperplasia in two cases; reactive lymphoid hyperplasia in 10 cases; atypical plasma lymphoproliferative reactive (polyclonal immunophenotypically, IgG4 negative) lesions in four cases; IgG-4 related disease in one case; nonspecific inflammatory reactions (conjunctiva, sclera, and lid) in 49 cases. In all the diagnoses, infections and lymphomas were excluded. Conclusion: Biopsy supported study on nonspecific orbital inflammation was important to know the pattern.

IgG4-related Ophthalmic Disease in Idiopathic Sclerosing and Non-Sclerosing Orbital Inflammation: A 25-Year Experience.

Purpose: To determine the prevalence, clinical manifestations, and treatment outcomes of IgG4-related ophthalmic disease (IgG4-ROD) in previously diagnosed idiopathic orbital inflammation (IOI).Materials and Methods: Thirty one surgically treated patients with IOI between 1990 and 2015 were divided into sclerosing (SIOI) and non-sclerosing (NSIOI) to identify IgG4-ROD. Preserved pathological specimens were immunostained for IgG4 cells. Changes in clinical features were evaluated before and after treatment.Results: Out of the 31 patients, 15 (48.4%) had IgG4-ROD, consisting of 7 of the 16 SIOI (43.8%) and 8 of the 15 NSIOI patients (53.3%). Among 15 patients with IgG4-ROD, 4 (26.7%) achieved complete remission, which was significantly less than among IgG4-unrelated patients (11/16, 68.8%, p = .03). Furthermore, 3 out of 15 IgG4-ROD patients (20%) experienced recurrence, all of whom had SIOI, compared to 0% among IgG4-unrelated patients (p = .1).Conclusions: IgG4-ROD is common among previously identified IOI in our study. Treatment response is modest in IgG4-ROD patients.

[New insights of myositis-specific and -associated autoantibodies in juvenile and adult type myositis]. / Újabb adatok a myositisspecifikus és -asszociált antitestekrol juvenilis és felnottkori myositisekben.

Myositis, which means inflammation of the muscles, is a general term used for inflammatory myopathies. Myositis is a rare idiopathic autoimmune disease. It is believed that environmental factors such as virus, bacteria, parasites, direct injuries, drugs side effect can trigger the immune system of genetically susceptible individuals to act against muscle tissues. There are several types of myositis with the same systemic symptoms such as muscle weakness, fatigue, muscle pain and inflammation. These include dermatomyositis, juvenile dermatomyositis, inclusion-body myositis, polymyositis, orbital myositis and myositis ossificans. Juvenile and adult dermatomyositis are chronic, immune-mediated inflammatory myopathies characterized by progressive proximal muscle weakness and typical skin symptoms. The aim of the authors was to compare the symptoms, laboratory and serological findings and disease course in children and adult patients with idiopathic inflammatory myopathy. Early diagnosis and aggressive immunosuppressive treatment improve the mortality of these patients. Myositis-specific autoantibodies have predictive and prognostic values regarding the associated overlap disease, response to treatment and disease course. The authors intend to lighten the clinical and pathogenetic significance of the new target autoantigens. Orv. Hetil., 2016, 157(29), 1179-1184.

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

PURPOSE: To review the current state of knowledge of IgG4-related ophthalmic disease (IgG4-ROD). METHODS: A review of the literature and personal experience of the authors. RESULTS: 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. CONCLUSIONS: 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-Related Ophthalmic Disease. Part II: Clinical Aspects.

PURPOSE: To review the current state of knowledge of IgG4-related ophthalmic disease (IgG4-ROD). METHODS: A review of the literature and personal experience of the authors. RESULTS: 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. CONCLUSIONS: 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.

Clinicopathologic features of orbital immunoglobulin G4-related disease (IgG4-RD): a case series and literature review.

BACKGROUND: Involvement of orbital structures by immunoglobulin G4-related disease (IgG4-RD) is not uncommon. We conducted this study to evaluate the clinicopathologic features of orbital IgG4-RD. MATERIAL/METHODS: This was a retrospective, clinicopathologic study. Clinical records, light microscopic features, results of immunostaining with IgG & IgG4 and laboratory findings were reviewed in 16 patients diagnosed with orbital IgG4-RD. RESULTS: Eleven patients had a bilateral disease, and the lacrimal gland was involved in 14. Dense sclerosis, plasma cell aggregates and dense lymphoplasmacytic infiltrate were seen in all patients. Serum IgG4 titre was elevated in 12 patients. Nine patients responded completely to glucocorticoid treatment. Five patients had a relapse on discontinuation of treatment. CONCLUSION: Orbital IgG4-RD is a distinct clinicopathologic entity requiring increased awareness and needs to be differentiated from other orbital lymphoproliferative lesions.

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.

IgG4-related orbital disease: a meta-analysis and review.

IgG4-related orbital disease (IgG4-ROD) is a recently described condition that may account for a significant proportion of idiopathic lymphoplasmacytic or sclerotic orbital lesions. This study is the first meta-analysis of published cases and reveals several differences between IgG4-related disease affecting the orbit and that affecting the pancreas. IgG4-ROD affects a slightly younger group of patients, affects men and women approximately equally, is commonly associated with salivary gland lesions, is associated with a relatively higher serum IgG4 and may confer an increased risk of non-Hodgkin Lymphoma. Its pathogenesis may involve an immune response to antigen exposure in the upper aerodigestive tract.

IgG4-related systemic disease as a cause of "idiopathic" orbital inflammation, including orbital myositis, and trigeminal nerve involvement.

IgG4-related systemic disease (IgG4-RD) is an inflammatory condition of unknown etiology that has been identified as the cause of tumefactive lesions in a number of tissues and organs. The role of the IgG4 remains to be clarified fully, but the histopathologic diagnosis hinges upon the finding of IgG4-bearing plasma cells in addition to characteristic morphologic features, with or without elevated seum IgG4. We present a 56-year-old man with orbital pseudotumor in whom, after 30 years of intractable disease, biopsy showed IgG4-RD involving the lacrimal gland, extraocular muscles, intraconal fat, and trigeminal nerve. Six months after initiating treatment with rituximab, his disease remained dormant, with improvement in his proptosis and normalization of serum IgG4 levels. We review the differential of idiopathic orbital inflammatory disease, including IgG4-RD, and emphasize the need for biopsy for accurate diagnosis and to guide appropriate treatment.