Progress in etiology, diagnosis, and therapy of idiopathic orbital inflammatory disease

Abstract

Idiopathic orbital inflammation (IOI) is a disease with signs and symptoms of an orbital inflammatory lesion with after local and systemic evaluation no apparent cause. Little is known about the etiology of the disease. This study aimed to answer three questions: a) what etiologic factors are involved in the pathogenesis of IOI, b) what diagnostic approach should be taken to diagnose IOI and how can IOI be classified into subtypes, and c) what therapies are effective in treating IOI. A case control study showed that the risk of IOI was increased in participants who had a higher BMI or who used bisphosphonates. The risk was decreased in participants with a higher socio-economic status and in women older at first childbirth. An almost significant association was found between IOI and autoimmune disease. IOI biopsy specimens were tested for presence of infectious entities using PCR techniques and Parvo-B19, Epstein-Barr, and Human Herpesvirus-6 were detected. Viral presence was statistically significant more often present in orbital biopsies of IOI patients compared to controls. A small case series described patients in whom diagnoses of both Graves and IOI were made in the same patient, at different times. It was concluded that Graves’ disease should not by default be an exclusion criterion for IOI. A stepwise diagnostic IOI algorithm was evaluated and demonstrated to be efficient and safe. The study advocates the reservation of a therapeutic trial of corticosteroids for patients with low suspicion of malignancy with muscular and apical mass localizations, or with optic nerve compression. Evaluation of another diagnostic algorithm to differentiate Wegener’s granulomatosis from IOI showed that diagnostic findings indicating orbital WG were ear/nose/throat involvement, multiple organ system involvement, a positive ANCA, and vasculitis on histology, whereas granulomatous inflammation without signs of vasculitis was more indicative of other orbital disease. After evaluation of classification systems for IOI, a new, combined histopathology and localization-based classification system was suggested. This combination was shown to provide a repeatable, easy to apply, plausible, and complete IOI classification system. Such a classification system is crucial in furthering our understanding of non-specific idiopathic orbital inflammatory diseases through research. The use of intravenous methylprednisolone (IVMP) in the treatment of severe IOI was evaluated by comparing patients with severe IOI who had been treated with IVMP and oral prednisone or only oral prednisone. The group of intravenously treated patients did not show shorter treatment duration, nor any significant differences in symptom-free outcome and treatment-related complications. These results suggest that the benefit of additional intravenous methylprednisolone to oral prednisone in IOI is limited. Treatment of adult periocular and orbital xanthogranulomatous disease was evaluated and the combination of prednisone and azathioprine was shown to be most effective in aggressive orbital inflammation. Overall, it was concluded that IOI is likely a multifactorial autoimmune disease, that biopsies have a pivotal role in the diagnosis and classification of IOI, and that treatment of severe IOI is still unsatisfactory.