This review of IVIG-induced aseptic meningitis over a 6-year period identifies a more robust estimate of incidence and risk of 0.60% and 0.067% for all patients and infusions, respectively. Given that this complication can mimic infectious meningitis and cause considerable morbidity, physicians need to be aware of this rare but important condition.

Chronic venous disease encompasses a spectrum of disorders caused by an abnormal venous system. They include chronic venous insufficiency, varicose veins, lipodermatosclerosis, postthrombotic syndrome, and venous ulceration. Some evidence suggests a genetic predisposition to chronic venous disease from gene polymorphisms associated mainly with vein wall remodeling. The literature exploring these polymorphisms has not been reviewed and compiled thus far. In this narrative and systematic review, we present the current evidence available on the role of polymorphisms in genes involved in vein wall remodeling and other pathways as contributors to chronic venous disease. We searched the EMBASE, Medline, and PubMed databases from inception to 2013 for basic science or clinical studies relating to genetic associations in chronic venous disease and obtained 38 relevant studies for this review. Important candidate genes/proteins include the matrix metalloproteinases (extracellular matrix degradation), vascular endothelial growth factors (angiogenesis and vessel wall integrity), FOXC2 (vascular development), hemochromatosis (involved in venous ulceration and iron absorption), and various types of collagen (contributors to vein wall strength). The data on associations between these genes/proteins and the postthrombotic syndrome are limited and additional studies are required. These associations might have future prognostic and therapeutic implications.

Corneal crystal deposition due to multiple myeloma is a rare ocular manifestation caused by elevated

Background: Aseptic meningitis is a rare and significant complication of intravenous immunoglobulin (IVIg) therapy. The true incidence is unknown as there are a number of case reports and few thorough reviews. Some have suggested the incidence being 0-1% with one reported exception of 11% in the literature. It is important to recognize this condition clinically, as it often mimics infectious meningitis. To determine the true incidence and natural history of IVIg-induced aseptic meningitis, we conducted a retrospective review and case series at a single tertiary care centre by two separate methods. For this study, IVIg-induced aseptic meningitis was defined as: headache with meningismus or a deterioration in mental status after receiving IVIg, with or without accompanying fever, nausea, vomiting, pharyngitis, photophobia, and/or diarrhea (as per the Transfusion Transmitted Injuries Surveillance System of the Public Health Agency of Canada). IVIg headaches alone were not included in our review. Method: We performed a retrospective review of all cases of IVIg-induced aseptic meningitis at London Health Sciences Centre (LHSC) from January 1, 2008 to December 31, 2013. During the study period, the initial method was to evaluate all reported transfusion reactions (as per the Transfusion Reaction Course [TRAC] system for reporting) to identify possible or probable aseptic meningitis due to IVIg. Subsequently, in our second method, we reviewed and cross-referenced all documented IVIg infusions and all lumbar punctures performed at LHSC during the study period. All patients with both IVIg infusions and lumber punctures were identified and further chart review was performed to determine if these patients had aseptic meningitis due to IVIg. We report on our identified cases of IVIg-induced aseptic meningitis, identify the true incidence, and speculate on the natural history of this condition. Results: During our study period, a total of 1921 IVIg infusions (554,566 g) were administered, with major indications being: chronic inflammatory demyelinating polyneuropathy (25.7%), primary immune deficiency (14.1%), other (primarily rheumatologic indications – 13.9%), multifocal motor neuropathy (10.4%), and adult immune thrombocytopenia (7.4%). 8 cases of aseptic meningitis were reported to the transfusion laboratory by the first method, with no additional cases identified by the second method, which gave us an overall incidence of 0.42%. Indications included: aplastic anemia (1/8), immune thrombocytopenia (3/8), chronic inflammatory demyelinating polyneuropathy (1/8), autoimmune hemolytic anemia (1/8), primary immune deficiency (1/8), and myasthenia gravis (1/8). As per our case series, IVIg-induced aseptic meningitis is an uncommon complication of unknown etiology that seems to affect all ages, with no relation to the underlying indication for IVIg. The only predisposing factor seen in our cohort may be a prior exposure to blood products, but other risk factors such as migraines, immune dysregulation, and dose and rate of infusion have been reported in the literature. In this study, patients presented with symptoms within 24-48 hours of IVIg infusion, and were treated with antibiotics initially due to the clinical resemblance and suspicion of bacterial meningitis. However, symptoms self-resolved within 5-7 days. This condition appears to be non-fatal; therefore, treatment is purely supportive, with subsequent IVIg infusions likely requiring premedication or possibly a switch in formulation. Conclusion: In this review of IVIg-induced aseptic meningitis over a 6 year period in a tertiary care centre, we identify a more robust incidence of 0.42% for this condition (consistent with most previous reports). Though this condition can be under-recognized, all possible cases were identified with a rigorous TRAC system for reporting reactions and by using two different methods. Furthermore, we speculate on the natural history of this condition based on our 8 identified cases. Given that this complication can mimic infectious meningitis and cause considerable morbidity, we hope that physicians will be aware of, and recognize, this rare but important complication of IVIg therapy. Disclosures No relevant conflicts of interest to declare.

A 51-year-old white woman with a history of pernicious anemia developed increasing lethargy and shortness of breath without neurologic or B symptoms. Investigations revealed the following: white blood cells 2.8 3 10 9 /L, hemoglobin 62 g/L (mean cell volume 126.3 fL), platelets 82 3 10 9 /L, and evidence of hemolysis (unconjugated bilirubin 58 mmol/L, lactate dehydrogenase .2500 U/L, reticulocytes 45 3 10 9 /L, and haptoglobin ,0.07 g/L) with negative direct antiglobulin test. Red cell folate was normal, but total vitamin B 12 level was decreased at ,22 pmol/L; homocysteine and methylmalonic acid were elevated (21.5 mmol/L and 16.6 mmol/L, respectively). Peripheral blood film showed macrocytes and mild fragmented erythrocytes. Bone marrow (BM) aspirate revealed a hypercellular marrow with megaloblastic and dysplastic features in myeloid and erythroid lineages (panels A-B), along with 10% to 15% ring sideroblasts (panels C-E). Marrow cytogenetics revealed a normal female karyotype.A month after receiving intramuscular vitamin B 12 injections daily for 1 week, then weekly, the patient became asymptomatic. Her blood counts and vitamin B 12 level normalized, thus arguing against an alternative diagnosis of myelodysplasia (BM aspirate was not repeated). This is a rare presentation of vitamin B 12 deficiency with striking megaloblastic features and ring sideroblasts. Rather than presumptively diagnosing myelodysplasia, timely recognition and vitamin B 12 supplementation lead to resolution of symptoms and blood work abnormalities.For additional images, visit the ASH IMAGE BANK, a reference and teaching tool that is continually updated with new atlas and case study images. For more information visit http://imagebank.hematology.org.

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