Orbital inflammatory pseudotumor: new advances in diagnosis, pathogenesis, and treatment.

Orbital inflammatory pseudotumor (OIP) is a benign, non-specific inflammatory disorder that commonly occurs in middle-aged adults and is usually unilateral but can occur bilaterally. Its clinical manifestations have tremendous clinical heterogeneity and vary according to the site of infiltration and the degree of lesions, including orbital pain, swelling, diplopia, proptosis, restricted eye movement, and decreased visual acuity. Clinical features, Image characteristics and pathological examinations often need to be evaluated to confirm the diagnosis. Currently, there is no systematic research on the pathogenesis of OIP, which may be related to immunity or infection. The first-line treatment is glucocorticoids. Radiotherapy, immunosuppressants, and biologics can be considered for treatment-resistant, hormone-dependent, or intolerant patients. In this review, we aim to summarize and focus on new insights into OIP, including new diagnostic criteria, pathogenesis, and discoveries in new drugs and treatment strategies. In particular, we highlight the literature and find that T cell-mediated immune responses are closely related to the pathogenesis of OIP. Further exploration of the mechanism and signaling pathway of T cells in the immune process will help to identify their therapeutic targets and carry out targeted therapy to treat refractory OIP and reduce the side effects of traditional treatments.

Single Institutional Experience on Orbital Inflammatory Pseudotumor: Diagnostic and Management Challenge.

AIMS: Orbital inflammatory pseudotumor is considered a non-neoplastic inflammatory process. The finding of clonality of B or T-cell receptors in cases pathologically diagnosed as orbital inflammatory pseudotumor has unknown clinicopathologic significance. We sought to investigate potential B and T-cell clonality and concomitant diseases in cases pathologically diagnosed as orbital inflammatory pseudotumor. METHODS: Cases diagnosed as orbital inflammatory pseudotumor at our institution were retrospectively analyzed. Hematoxylin and eosinstained slides, immunohistochemically stained slides and polymerase chain reactions on cell block material for the investigation of clonality of B and T-cell receptors were evaluated, to confirm the diagnosis and investigate the prevalence of concomitant diseases. RESULTS: A total of 13 cases showing characteristic histopathologic features of orbital inflammatory pseudotumor were identified. CD138, IgG, and IgG4 showed varying numbers of plasma cells in each case, with 5 cases (5/13, 38%) exhibiting relative increase in the presence of IgG4 plasma cells. However, no cases showed diagnostic findings of IgG4-related disease (IgG4-RD). polymerase chain reactions analysis showed clonal B-cell populations in 2 cases (2/13, 15%). No cases showed anaplastic lymphoma kinase expression by immunohistochemistry. There were no clinical reports of progression to lymphoma or development of systemic IgG4-RD in any of the patients (average follow-up of 300 days), with 38% of patients showing systemic autoimmune conditions. CONCLUSION: A small but significant percentage of typical orbital inflammatory pseudotumor on histology showed B-cell clonality on polymerase chain reactions analysis of B-cell receptors, or features suggestive, but not diagnostic of IgG4-RD. Close follow-up of these patients to identify development of lymphoma, systemic IgG4-RD, or other rheumatologic conditions may be clinically warranted.

Enfermedad inflamatoria orbitaria idiopática. Presentación de un caso / Idiopathic orbital inflammatory disease. Case presentation

RESUMEN El pseudotumor orbitario es la tercera causa de oftalmoplejía dolorosa; constituye un desafío diagnóstico pues obliga a descartar enfermedades de etiología muy diversa que lo provocan. Se presenta el caso de una paciente femenina, de color de piel blanca, de procedencia urbana, ama de casa, fumadora, que no practica ejercicios ni lleva dieta, con antecedentes de hipertensión arterial y artritis reumatoidea, que acudió al Servicio de Oftalmología por presentar síntomas inflamatorios anexiales: edema palpebral, quemosis conjuntival, vasos conjuntivales dilatados, que se acompañaban de proptosis, oftalmoplejía dolorosa con diplopía y de una masa tumoral palpable a nivel de la porción supero-externa de la órbita. Se ingresó y se le realizaron estudios imagenológicos e histológicos, que solo aportaron signos inflamatorios y una pansinusitis. Se concluyó como un pseudotumor orbitario en su forma aguda de aparición, asociada a la artritis reumatoidea, cuyo diagnóstico se realizó por exclusión sobre la base de los resultados negativos de los estudios imagenológicos y de la biopsia. Llevó tratamiento con antibióticos parenterales y altas dosis de esteroides orales con regresión del cuadro y mejoría clínica. Se decidió la presentación del caso porque en la provincia no existen reportes sobre esta entidad, y por el énfasis en cómo llegar al diagnóstico y su correcto manejo, evitando con ello secuelas en el órgano visual.

ABSTRACT Orbital pseudotumor is the third cause of painful ophthalmoplegia; it constitutes a diagnostic challenge as it forces us to rule out diseases of very diverse etiology that cause it. A female patient, of white skin color, of urban origin, housewife, smoker, who does not practice exercises or is not on a diet, with a history of high blood pressure and rheumatoid arthritis, who attended the Ophthalmology service for presenting Adnexal inflammatory symptoms: eyelid edema, conjunctival chemosis, dilated conjunctival vessels, which were accompanied by proptosis, painful ophthalmoplegia with diplopia and a palpable tumor mass at the level of the superior-external portion of the orbit was presented. She was admitted and imaging and histological studies were performed, which only revealed inflammatory signs and pansinusitis. It was concluded as an orbital pseudotumor in its acute onset form, associated with rheumatoid arthritis, the diagnosis of which was made by exclusion on the basis of the negative results of imaging studies and biopsy. She was treated with parenteral antibiotics and high doses of oral steroids with regression of the symptoms and clinical improvement. The presentation of the case was decided because in the province there are no reports on this entity, and because of the emphasis on how to reach the diagnosis and its correct management, thereby avoiding effects in the visual organ.

[Management of orbital inflammatory disorders in internal medicine: New findings resulting from a retrospective study of 31 consecutive patients]. / Prise en charge des orbitopathies inflammatoires en médecine interne : nouvelles données issues de l'étude d'une série de 31 patients consécutifs.

PURPOSE: To describe a case series of patients investigated in internal medicine for orbital inflammation (OI) since the individualization of the clinical entity of the IgG4-related orbital disease (IgG4 ROD). PATIENTS AND METHODS: Thirty four patients were consecutively referred by a specialized center where orbital biopsy was performed when the lesion was surgically accessible. Fourteen patients were excluded in case of missing data or lymphoma, periocular xanthogranuloma or Graves' orbitopathy. Patients with systemic or auto-immune disease according to the international criteria, or presenting with idiopathic orbital inflammation syndrome (IOIS), were included. Knowing the histological similarities between IOIS and IgG4 ROD, immunohistochemical assessment of plasma cells for IgG4 positivity was performed for every patient with available biopsy. Clinical and biological characteristics, treatment and response to treatment of included patients are reported. RESULTS: Among 22 included patients, 10 presented with orbital manifestation of a systemic or autoimmune disease including 2 sarcoidosis (9%) and 8 (36%) cases of non specific OI which were reclassified in IgG4 ROD. Finally, IOIS of various clinicopathological presentation was diagnosed for 12 patients including 10 with histological documentation. Whereas relapse and resistance were not found to be related to IgG4 positivity (50% in both IOIS and IgG4 ROD groups), another treatment in addition to corticosteroids was more often necessary in IgG4 ROD patients (50%) than in IOIS patients (25%). CONCLUSION: After ruling out auto-immune orbital diseases, especially IgG4 ROD, IOIS should be discussed. Factors conditioning the corticosteroid response are yet to be determined.

Treatment of recalcitrant orbital inflammatory syndrome with plasmapheresis therapy.

Refractory idiopathic orbital inflammation (IOI) represents a management challenge due to its significant proportion of treatment failures. Currently, there are no established guidelines for recalcitrant IOI and majority of immunosuppressive agents have resulted in variable outcomes. Advancements of plasmapheresis therapy can play a significant role in ophthalmological diseases. This treatment has shown to produce a satisfactory therapeutic response in immune-mediated neurological conditions. In this case report, we share our successful experience with the use of plasmapheresis therapy in a patient with recalcitrant IOI.

Neurofibromatose tipo 1 com acometimento do nervo infraorbital: relato de caso / Neurofibromatosis type 1 with infraorbital nerve involvement: a case report

A neurofibromatose tipo 1 é uma doença autossômica dominante rara, com manifestações clínicas diversas. Sua apresentação mais marcante é a presença de neurofibromas (tumores da bainha neural) cutâneos ou internos, que também podem ocorrer de forma esporádica, associados a outras manifestações sistêmicas, como manchas café com leite e lesões oculares. Por serem tumores da bainha de mielina, os neurofibromas podem acometer diversos nervos periféricos, incluindo nervos da face. Apresentamos o caso de um paciente de 1 ano, portador de neurofibromatose tipo 1, com neurofibroma em nervo infraorbital direito, com o acesso proposto para tratamento cirúrgico que fornecesse ampla visualização e acesso a lesão, sem comprometimento estético importante, permitindo preservação de partes moles e adequado crescimento facial.

Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disease with multiple clinical manifestations. Its most significant presentation is cutaneous or subcutaneous neurofibromas (myelin sheath tumors), which may be associated with other systemic manifestations such as caféau- lait spots and eye involvement. Neurofibromas can affect several peripheral nerves, including the facial nerves. This report presents a case of a 1-year-old patient with NF1 with right infraorbital nerve neurofibroma in which the proposed access for surgical treatment allowed adequate visualization of the tumor with good aesthetic results, preservation of the soft tissues, and normal facial growth.

The impact of IgG-4-ROD on the diagnosis of orbital tumors: A retrospective analysis.

This study was to determine the prevalence of immunoglobulin G4 (IgG4)-related orbital disease (IgG4-ROD) among patients who have previously undergone biopsy and were diagnosed to have idiopathic orbital inflammatory disease (IOID) or orbital lymphoproliferative disease (OLD), namely, lymphoma and benign reactive lymphoid hyperplasia (BRLH). This is a retrospective cross-sectional study. The charts and slides of all patients who underwent biopsies and were histopathologically diagnosed to have either IOID or OLD were reviewed. Demographics, clinical features, initial histopathological diagnoses, treatment received, and final outcome were noted. Using the diagnostic criteria for diagnosis for IgG4 disease, those cases that would classify as "possible IgG4-related disease (IgG4-RD)" were reviewed, reclassified, and reassigned a diagnosis of IgG4-ROD. We reviewed 105 patients' clinical charts. Of these 105 patients, upon reviewing the histopathology, 18 (17.15%) patients were found to fit the diagnostic criteria for possible IgG4-ROD. Of these 18 patients who were now reassigned the diagnosis of IgG4-ROD, the most common previous histopathological diagnosis was found to be IOID, for eight patients (44%), then BRLH, which was noted in five patients (27.8%), followed by lymphoma, which was noted in two patients (11.1%). Previously diagnosed cases of IOID and OLD were found to fulfill the criteria for IgG4-ROD. Given the advent of recent diagnostic and histopathological techniques, all cases of suspected IOID and OLD should be screened for IgG4-ROD and all previously diagnosed cases must be closely followed up, given the systemic implication of IgG4-RD. Histopathological reassessment of previously diagnosed cases may be considered.

IgG4-related disease in idiopathic sclerosing orbital inflammation.

AIMS: To investigate the frequency of IgG4-related disease (IgG4-RD) among patients previously diagnosed with idiopathic sclerosing orbital inflammation (ISOI), and to compare the clinical features and treatment outcomes of patients with ISOI associated with IgG4-RD and those without IgG4. METHODS: Retrospective clinicopathological series of 24 patients with ISOI diagnosed between June 2001 and June 2010. Biopsy specimens were immunostained for IgG-expressing and IgG4-expressing cells. Clinical data of patients with IgG4-RD and ISOI unrelated to IgG4 were obtained from patient records. RESULTS: Of 24 patients, 11 patients (45.8%) were identified with IgG4-RD. 10 patients (10/11, 90.9%) presented with bilateral lacrimal gland enlargement, and seven of those also had submadibular gland enlargement. One patient (1/11, 9.1%) presented with a superior orbital mass. All patients were successfully treated with steroids and/or radiotherapy or had an indolent clinical course. 13 patients (54.2%) were identified with ISOI unrelated to IgG4. Eight patients (8/13, 61.5%) showed unilateral orbital involvement, and nine patients (9/13, 69.2%) had orbital lesions not involving the lacrimal glands. Treatment modalities for ISOI unrelated to IgG4 were varied and less effective: eight patients (61.5%) relapsed following initial treatment with steroids or radiation, and additional therapies were required to enter remission. CONCLUSIONS: IgG4-RD may be identified frequently in patients with ISOI, and distinguishing features may be bilateral lacrimal gland enlargement with associated submandibular gland enlargement. Patients with IgG4-RD may have better treatment outcomes with less aggressive treatment modalities than those with ISOI unrelated to IgG4. An additional workup for IgG4-RD should be considered in all histopathological biopsy specimens suspicious of ISOI.

Good response to surgical treatment and mycophenolate in woman with inflammatory pseudotunor secondary to ANCA positive vasculitis.

We present the case of a young woman with ANCA positive vasculitis and infammatory pseudotumor as a granulomatous manifestation, who had a good response to surgical removal and mycophenolate mofetil.

[Orbital inflammation]. / Inflammation orbitaire.

Orbital inflammation is a generic term encompassing inflammatory pathologies affecting all structures within the orbit : anterior (involvement up to the posterior aspect of the globe), diffuse (involvement of intra- and/or extraconal fat), apical (involvement of the posterior orbit), myositis (involvement of only the extraocular muscles), dacryoadenitis (involvement of the lacrimal gland). We distinguish between specific inflammation and non-specific inflammation, commonly referred to as idiopathic inflammation. Specific orbital inflammation corresponds to a secondary localization of a "generalized" disease (systemic or auto-immune). Idiopathic orbital inflammation corresponds to uniquely orbital inflammation without generalized disease, and thus an unknown etiology. At the top of the differential diagnosis for specific or idiopathic orbital inflammation are malignant tumors, represented most commonly in the adult by lympho-proliferative syndromes and metastases. Treatment of specific orbital inflammation begins with treatment of the underlying disease. For idiopathic orbital inflammation, treatment (most often corticosteroids) is indicated above all in cases of visual loss due to optic neuropathy, in the presence of pain or oculomotor palsy.

Aggressive inflammatory pseudotumor of the maxillary sinus and orbit.

Inflammatory pseudotumor (IPT) is a rare, locally aggressive, benign neoplasm of unknown etiology. It is uncommon in the head and neck region, particularly in the paranasal sinuses. We present an unusual case of IPT of the maxillary sinus and orbit in a 27-year-old woman who presented with cheek swelling, right orbital swelling, double vision, and associated fever and trismus. Computed tomography identified a mass with radiologic features suggestive of a malignancy of the maxillary sinus and orbit; the mass extended into the infratemporal fossa, parapharyngeal space, anterior antral wall, and surrounding soft tissue. A diagnosis of IPT was established on the basis of histologic and immunohistochemical analysis, which identified a proliferation of bland spindle cells and a mixed inflammatory cell infiltrate. Despite its aggressive appearance, IPT is associated with a good prognosis. Our patient was treated successfully with a combination of surgery, steroid therapy, and methotrexate. Chemotherapeutic agents are generally reserved for recalcitrant cases.

Inflammatory modulators and biologic agents in the treatment of idiopathic orbital inflammation.

PURPOSE OF REVIEW: To review the diagnosis and treatment of idiopathic orbital inflammation (IOI), with an emphasis on the development and use of inflammatory mediators and biologic agents. RECENT FINDINGS: Use of targeted biologic immunomodulatory therapy is becoming widespread and proving effective against many inflammatory and autoimmune conditions. Although corticosteroids remain the mainstay of care for IOI, their use is fraught with complications and side-effects, suggesting the need for novel therapies. Evidence for the successful implementation of nonsteroidal inflammatory mediators in IOI is accumulating. SUMMARY: The treatment of IOI with traditional methods, particularly corticosteroids, is often inadequate and accompanied by recurrences, medication dependence, and intolerability. Many of these issues may be avoided with the use of existing and novel pharmaceutical agents targeting specific inflammatory mediators. The literature on these agents and their use in IOI is in its infancy but shows tremendous promise in the treatment of this often-recalcitrant illness.

Idiopathic sclerosing orbital inflammation: a review of demographics, clinical presentation, imaging, pathology, treatment, and outcome.

PURPOSE: To characterize clinical features, diagnostics studies, treatments, and outcomes of patients with histologically proven idiopathic sclerosing orbital inflammation (ISOI), to define optimal management for this recalcitrant disease, and to determine changes in characterization and management by comparing our results with the last significant literature review. METHODS: A search of the U.S. National Library of Medicine: National Institutes of Health's electronic database for cases and case series in the English literature of biopsy-proven ISOI published between March 1994 and September 2010 was conducted. A cross-literature review was performed to tabulate demographics, clinical findings, studies, treatments, and outcomes, which were compared with the ISOI data published by Rootman et al. (1994). RESULTS: Sixty-one cases, 71 eyes from 17 published reports, met inclusion criteria. No ethnic, sex, or comorbidity predilection was established. Patients typically presented in the fourth decade with proptosis (73%), pain (49%), and normal vision (44%). Orbital imaging and histopathology were sparsely reported. Most common treatments involved systemic corticosteroids either alone (34%) or combined with other modalities (51%). CONCLUSIONS: Characteristics of the disease remain unchanged, and best management was not determined due to inconsistent reporting methods across the literature. Collaboration with established groups (i.e., European Group On Graves Orbitopathy (EUGOGO), International Thyroid Eye Disease Society (ITEDS)) or the formation of a new group of physicians and scientists to help develop a systematic approach for future reporting and evaluation was proposed.

Orbital pseudotumor after an upper respiratory infection: a comprehensive review.

BACKGROUND: Idiopathic orbital inflammation (IOI), also known as orbital pseudotumor, is a nonspecific orbital inflammation of unknown etiology. IOI can clinically mimic many other orbital pathologies, some of which can be life-threatening, as in the case of orbital cellulitis. Thus, it is imperative for the clinician to emergently arrive at the correct diagnosis. In many cases, however, IOI presents as a clinical and therapeutic challenge, and conclusive diagnosis is only confirmed after all other etiologies have been ruled out. CASE REPORT: A 63-year-old man presented urgently with a red, proptotic, painful eye. After history, blood tests, radiologic testing, and ruling out other emergent etiologies, such as orbital cellulitis, the patient was placed on oral steroids. He responded immediately to the steroid treatment. However, the patient did have a recurrence. With the second IOI episode, the patient noted, as previously, a preceding upper respiratory infection. This case may possibly show an association between an infectious trigger leading to a nonspecific aberrant immune response in the orbit. CONCLUSION: IOI is a difficult condition to diagnose and treat. After ruling out other orbital pathologies, it is appropriate to begin treatment with oral steroids. In this case report, the patient noted an upper respiratory infection before each episode of IOI. Although there is no proof of cause, there is a strong case for the consideration of a viral respiratory infection leading to IOI.

[Idiopathic orbital inflammation syndrome in childhood--case report and literature review]. / Idiopathische orbitale Entzündung im Kindesalter--Fallbericht und Literaturreview.

BACKGROUND: Idiopathic orbital inflammation syndrome (IOIS) is a rare disease in childhood. There are only ca. 70 case reports in the scientific literature. METHOD: We present a case report and review of literature. CASE REPORT: A 6-year-old girl developed within one week beginning with a discrete, non-traumatic haemorrhage of the lower palpebra a painful proptosis, periorbital swelling, conjunctival chemosis and injection and motility restriction to lateral gaze of the right eye. MRI showed a retrobulbar and eyelid mass with enhancement and signs of haemorrhage without optic nerve involvement. A rapidly performed biopsy excluded malignancies and confirmed the diagnosis of non-specific inflammation. With high-doses of intravenous and later oral prednisolone the symptoms improved significantly. Because of an impairment under tapering of prednisolone an interim elevation of the dose was necessary, but with very slow tapering over 4.5 months the girl became symptom-free except for a minimal, non-relevant abduction deficit. There has been no recurrence in the last 1.5 years. DISCUSSION: In comparison to the clinical features of adults the rarely reported childhood cases show no relevant differences in orbital signs, frequency of bilaterality and pain, recurrence rate and success of therapy. Only iritis and papilloedema seem to be special features of childhood IOIS, these cases tend to a higher rate of recurrences. Histopathological examination is much more necessary than in adults because of the need for exclusion of rhabdomyosarcoma. Our case shows that haemorrhages can also be a sign for an IOIS.

Idiopathic sclerosing orbital inflammation with intranasal extension.

INTRODUCTION: To report a case of idiopathic orbital sclerosing inflammation (ISOI) with intranasal extension. MATERIAL AND METHODS: The patient presented with a 6-month history of epiphora, upper eyelid swelling, ptosis and mild orbital pain. Ophthalmologic examination, CT, MRI and biopsy with surgical debulking were performed. RESULTS: MRI revealed a homogeneously enhancing diffuse right orbital mass in the inferonasal quadrant of the orbit, which extended to the nasal cavity up to inferior nasal concha, maxillary and ethmoid sinuses. Histological analysis showed dense collagenous tissue with sparse infiltration of mixed inflammatory cells. Inmunohistochemical analysis confirmed polyclonality. The diagnosis of idiopathic sclerosing orbital inflammation was made and 80 mg/day of oral prednisolone was prescribed. At last follow up, one year later, there was no clinical evidence of recurrent orbital disease. CONCLUSION: ISOI can present with extraorbital extension. Corticosteroids are a reasonable first-line treatment, until the pathogenesis is better understood.

Otolaryngologists and orbital pseudotumor: a case report.

Orbital pseudotumor (idiopathic orbital inflammation) is the third most common orbital disease, accounting for 5 to 6% of orbital disorders. It often presents in a manner very similar to inflammatory or neoplastic sinus disease. In addition, sinus disease is often a cause of orbital pseudotumor, although the etiology of this entity has yet to be defined. Treatment with steroids is usually successful early on, but long-term treatment-failure and recurrence rates are high. Despite otolaryngologists' intimate knowledge of sinus pathology, we have generally not been heavily involved in researching the causes and treatment of orbital pseudotumors. In this article, we report the case of an affected patient who presented with an orbital mass on radiography. The mass was likely the result of sinus disease in the setting of an untreated orbital floor fracture. We describe the clinical, radiographic, and operative features of this case, and we discuss the otolaryngologist's role in the management of orbital pseudotumors.