Intravenous immunoglobulins for rheumatic disorders and thromboembolic events-a case series and review of the literature.

To report the temporal association between a series of thromboembolic events and intravenous immunoglobulin infusion in patients with rheumatic diseases, and to review the literature on the subject. The clinical presentation, course, and outcome of thromboembolic events occurring post-immunoglobulin infusion in nine patients is described. A web-based literature review using the PubMed database from 1996 to 2017 was performed, searching for the keywords: thrombosis, thromboembolism, intravenous immunoglobulin, pulmonary embolism, deep vein thrombosis, cerebrovascular event, and acute myocardial infarction. Nine patients who had suffered a thromboembolic event within a week after receiving an intravenous immunoglobulin infusion (Omr-IgG-am™, OMRIX) were identified among our joint cohort. All patients except one were female ranging in age from 22 to 69 years. Five had progressive systemic sclerosis (one of them had progressive systemic sclerosis with antiphospholipid syndrome, and another had an overlap of progressive systemic sclerosis with systemic lupus erythematosus), the sixth had monoclonal IgM autoimmune neuropathy, the seventh had systemic lupus erythematosus with antiphospholipid syndrome, the eighth had granulomatosis with polyangiitis (GPA) and the ninth had overlap autoimmune syndrome. Six of the patients had an arterial thrombosis: an acute myocardial infarction in four, a brachial artery thrombosis in the fifth, and a cerebrovascular attack in the sixth. Three patients sustained a venous thrombosis and/or an acute pulmonary embolism (one of them had a DVT with the PE). Two events occurred during the IVIG infusion, three within an hour after the last infusion of the 5-day course, one occurred a few hours after the initiation of the IVIG therapy, another occurred 3 days after receiving the final infusion of the 10th course, and two events occurred a week after the treatment course has ended. Fifty-five percent of the patients had no thrombogenic risk factors other than their rheumatic condition, and most of them had received numerous, uneventful IVIG treatment courses before sustaining the thromboembolic event. No immediate deaths occurred among this cohort. Thromboembolic events after IVIG infusions, although infrequent, may occur in rheumatic patients, even in the absence of other recognizable risk factors for thromboembolism. The reported events had occurred despite complying with recommended guidelines for IVIG administration, which include a lengthy 8-h infusion and division of the total dose. No correlation was found between the number and frequency of the infusions to the thromboembolic events. Heightened awareness of possible thromboembolic events in rheumatic patients is encouraged for at least a week following IVIG administration.

Spontaneous Bilateral Femoral Fractures After High-Dose Zoledronic Acid.

The authors report a case of spontaneous bilateral diaphyseal femoral fractures believed to be caused by oversuppression of bone remodeling as a result of long-term, high-dose treatment with bisphosphonate. The patient reported pain in both thighs before the fractures. Typical pathologic changes appeared on both femoral radiograph and bone scan before the fractures. Several hours after admission to the emergency department of the authors' institution, the patient underwent closed reduction and internal fixation with intramedullary nails for the bilateral femoral diaphyseal fractures. Treatment with zoledronic acid was immediately discontinued. In recent years, low-energy femoral diaphyseal fractures in patients undergoing long-term bisphosphonate treatment have been reported. It is believed that the prolonged treatment causes long-term suppression of bone remodeling and accumulation of microdamage. It is important to observe patients who are undergoing bisphosphonate treatment carefully. In this case study, the authors report the patient's unique medical history.

Response of vasculitic peripheral neuropathy to intravenous immunoglobulin.

Peripheral neuropathy is a prominent feature of the systemic and secondary vasculitides. Usually, it responds to corticosteroids therapy, but in certain cases it may resist corticosteroid or immunosuppressive treatment, or both. The objective of this study is to present case reports of patients who exhibited various inflammatory diseases, accompanied with vasculitic peripheral neuropathies, for which intravenous immunoglobulin (IVIg) was used for treatment. The study included 10 patients with the following: Sjögren's syndrome (1), systemic lupus erythematosus (2), vaccination-induced vasculitis (1), Churg-Strauss vasculitis (1), mixed cryoglobulinemia (2), polyarteritis nodosa (1), sarcoidosis (1), and scleroderma (1). All developed vasculitic peripheral neuropathy and were treated with 1-13 cycles of high-dose IVIg (2 g/kg body weight). The patients were followed up for 1-5 years after this treatment. Results showed that in all but two patients (mixed cryoglobulinemia associated with hepatitis C and sarcoidosis), neuropathy improved or completely resolved after IVIg treatment. In conclusion, IVIg may be beneficial in cases of resistant vasculitic peripheral neuropathy. IVIg should probably be considered as a sole or adjuvant treatment in patients for whom conventional treatment is contraindicated, or for patients in whom conventional treatment has failed.