Uriel Katz

Intravenous immunoglobulin: adverse effects and safe administration.

Intravenous immunoglobulin (IVIg) is administered for various indications and generally considered a safe therapy. Most of the adverse effects (AEs) associated with IVIg administration are mild and transient. The immediate AEs include headache, flushing, malaise, chest tightness, fever, chills, myalgia, fatigue, dyspnea, back pain, nausea, vomiting, diarrhea, blood pressure changes, tachycardia, and anaphylactic reactions, especially in IgA-deficient patients. Late AEs are rare and include acute renal failure, thromboembolic events, aseptic meningitis, neutropenia, and autoimmune hemolytic anemia, skin reactions, and rare events of arthritis. Pseudohyponatremia following IVIg is important to be recognized. Renal failure, usually oliguric and transient, occurs mostly on using sucrose-containing products owing to osmotic injury. Among high-risk patients who have a previous renal disease, dehydration, diabetes mellitus, advanced age, hypertension, hyperviscosity, or are treated by other nephrotoxic medications, administration of a non-sucrose-containing IVIg product after accomplishing hydration, in a low concentration and a slow infusion rate while supervising urine output and kidney function, is recommended. Thromboembolic complications occur because of hyperviscosity especially in patients having risk factors including advanced age, previous thromboembolic diseases, being bedridden, diabetes mellitus, hypertension, dyslipidemia, or those receiving high-dose IVIg in a rapid infusion rate. Immediate AEs can be treated by the slowing or temporary discontinuation of the infusion and symptomatic therapy with analgesics, non-steroidal anti-inflammatory drugs, antihistamines, and glucocorticoids in more severe reactions. Slow infusion rate of low concentration of IVIg products and hydration, especially in high-risk patients, may prevent renal failure, thromboembolic events, and aseptic meningitis.

Drug-induced lupus: an update.

PURPOSE To review and update drug-induced lupus (DIL) with emphasis on the characteristics of anti-TNF-induced lupus. RESULTS DIL is an autoimmune phenomenon triggered by a given drug and resulting in a syndrome sharing several features of systemic lupus erythematosus (SLE). Drugs like procainamide and hydralazine have been strongly associated with the development of DIL. During the past years several cases of DIL related to biologic therapy with anti-TNF drugs were reported. From the analysis of the unusual characteristics of these cases some conclusions may be drawn: anti-TNF-induced DIL may present with classical SLE dermatologic symptoms, hypocomplementemia, an increased frequency of significant anti-dsDNA antibody titers and a decreased incidence of anti-histone antibodies, all these atypical findings in classical DIL. CONCLUSIONS Anti-TNF-induced DIL may be a unique form of the disease or may possibly result from the unmasking of latent idiopathic SLE.

Evidence for the Use of Intravenous Immunoglobulins—A Review of the Literature

Intravenous immunoglobulins (IVIg) were first introduced in the middle of the twentieth century for the treatment of primary immunodeficiencies. In 1981, Paul Imbach noticed an improvement of immune-mediated thrombocytopenia, in patients receiving IVIg for immunodeficiencies. This opened a new era for the treatment of autoimmune conditions with IVIg. Since then, IVIg has become an important treatment option in a wide spectrum of diseases, including autoimmune and acute inflammatory conditions, most of them off-label (not included in the US Food and Drug Administration recommendation). A panel of immunologists and internists with experience in IVIg therapy reviewed the medical literature for published data concerning treatment with IVIg. The quality of evidence was assessed, and a summary of the available relevant literature in each disease was given. To our knowledge, this is the first all-inclusive comprehensive review, developed to assist the clinician when considering the use of IVIg in autoimmune diseases, immune deficiencies, and other conditions.

Update on Intravenous Immunoglobulins (IVIg) Mechanisms of Action and Off- Label use in Autoimmune Diseases

Intravenous Immunoglobulins (IVIg) are administered both as replacement therapy for certain immunodeficiencies and as immunomodulatory therapy for some autoimmune diseases. While the treatment with IVIg is approved in only a few autoimmune diseases, the number of off-label indications is increasing. The varied mechanisms by which IVIg attains its beneficial effect are diverse. There is much evidence for the beneficial and safety profile for IVIg in low as well as high-dose protocols. Patients prone to develop thrombotic events should be advised about the risk of IVIg therapy especially at high doses. This paper updates the mechanisms of action of IVIg as well as recent off-label indications.

Long term safety of IVIg therapy in multiple sclerosis: 10 years experience

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system. The majority of MS patients have a relapsing–remitting course with progressive neurological disability that accumulates over the years. Intravenous Immunoglobulin (IVIg) has demonstrated benefit in the treatment of some patients with relapsing–remitting MS. Concerns about adverse events of IVIg, mainly acute renal failure and thromboembolic events have been raised in the medical literature. We examined the adverse events profile of IVIg treatment in a large cohort of 293 relapsing–remitting MS patients treated with an initial loading dose of IVIg (0.4 g/Kg body weight/day, for 5 consecutive days) and additional booster dose infusions (0.4 g/Kg body weight/booster dose, every 6 weeks) as a maintenance treatment. A total of 9281 IVIg infusions were administered within a mean treatment period of 3.8 ± 3.5 years (3 months–10 years). The main adverse event during the loading dose period was headache, occurring in 12.6% of the patients. The annual rate of any adverse event during the IVIg maintenance period was 4.4% during the first year and had a trend to decrease with every passing year of treatment. Adverse events during the loading dose did not predict adverse events during the maintenance phase. No severe adverse events were recorded. We conclude that IVIg is a safe therapy in MS either for short or for long-term periods.

Chronic Idiopathic Granulomatous Mastitis

Abstract:  We describe four women with idiopathic granulomatous mastitis, a rare benign disease. Age range was 32–40 years. Disease duration was less than 1 year in three patients and long term in the fourth. The diagnosis was based on histological findings, after extensive work‐up ruled out malignancy and known causes of granulomatous mastitis. Treatment with prednisone with gradual tapering yielded a good response. Clinicians should consider the possibility of idiopathic granulomatous mastitis in young women with inflammatory breast processes and negative findings on relevant biopsy, laboratory, and imaging studies. Glucocorticoids are the treatment of choice; surgery is not recommended. Some patients require a glucocorticoid‐sparing drug.

Efficacy and Safety of Intravenous Immunoglobulin in Patients with Metastatic Melanoma

Abstract:  We have previously reported studies performed both in vitro and in laboratory animals, as well as a case study in humans, suggesting that intravenous immunoglobulin (IVIG) may be beneficial in the treatment of malignancies, including metastatic melanoma. As part of a phase II open label trial, we have administered IVIG to nine patients with metastatic melanoma who had been heavily treated. In two of nine (22%) patients treated every 3 weeks with IVIG (1 g/kg body weight), the disease stabilized. One patient had stable disease for 8 months; the other for 3 months. No serious adverse events (AEs) attributable to IVIG were observed. We conclude that IVIG therapy may be useful for the treatment of metastatic melanoma. Furthermore, we suggest that the effects of IVIG therapy might be enhanced by its use as an adjuvant in patients without evidence of disease following surgery.

Echocardiographic Abnormalities in Familial Dysautonomia

Sudden death accounts for up to 43% of all deaths in patients with familial dysautonomia (FD). The classic features of FD, namely, autonomic dysfunction, high blood pressure, and blood pressure labiality, are all risk factors for cardiac remodeling and hypertrophy. Myocardial remodeling and hypertrophy are independent risk factors for arrhythmias, cardiovascular events, and sudden death. An extensive review of the medical literature found no documentation of structural heart defects or myocardial remodeling in patients with FD. Sixteen patients with FD underwent physical examination, in-clinic blood pressure measurements, and echocardiographic study. On the basis of the findings, the patients were categorized by left ventricular geometric pattern. Twenty-four-hour ambulatory blood pressure monitoring was recommended to all participants. The majority of FD patients were found to have very high blood pressure values both during in-clinic measurements and during ambulatory blood pressure monitoring. Echocardiographic abnormalities were found in 43.75% of the study group; 18.75% of the study group had concentric hypertrophy, among which severe hypertrophy was found in 2 patients. Unknown previously, cardiac remodeling or hypertrophy is common in FD. We recommend that routine cardiac echocardiography be performed in this population, and attempts to treat high blood pressure should begin earlier in life.

Animal Models of Vasculitides

The vasculitides are a group of diseases in which the common denominator is the immune attack to components of the vascular wall. Vasculitides may attack large vessels like the aorta, medium-sized vessels like the coronary arteries or small vessels like the glomeruli. We review in this paper the animal models that have been developed to study these diseases.

The Utilization of an Insertable Cardiac Monitor in a Child With Pallid Breath-Holding Spells

BACKGROUND Pacing can be a successful treatment for pallid breath-holding spells, primarily in individuals with severe bradycardia. PATIENT DESCRIPTION We describe an 18-month-old girl experiencing severe pallid breath-holding spells in whom repeated electrocardiographic, Holter, and electroencephalographic monitoring tests were all normal. RESULTS Using a subcutaneous insertable cardiac monitor, severe bradycardia was detected during one of this girls episodes. This finding led to a pacemaker implantation. Subsequently, her breath-holding spells completely resolved. CONCLUSION This child illustrates the ability of the insertable cardiac monitor to help and diagnose arrhythmias in children with unresolved clinical findings. The ability to implant it with a minimal scar makes it ideal for uncooperative individuals with relative few and unexpected episodes that are hard to diagnose.