Steroid induced osteonecrosis: An analysis of steroid dosing risk.

Osteonecrosis is a serious condition involving bone destruction that frequently requires surgical treatment to rebuild the joint. While there is an abundance of literature documenting corticosteroid related osteonecrosis, there is no consensus as to the relative risk of osteonecrosis after administration of steroids via parenteral, oral, topical, inhaled and other routes. This risk is an important prognostic indicator because identification and conservative intervention can potentially reduce morbidity associated with aggressive surgical treatment of osteonecrosis. This paper provides insight into establishing guidelines related to the risk of developing osteonecrosis as a result of corticosteroid use. Case studies, retrospective studies and prospective studies in humans on different corticosteroids and varied dosages were assessed. Most cases of osteonecrosis are secondary to systemically administered corticosteroids and/or high dose daily therapy, particularly in patients with underlying comorbidities including connective tissue diseases, hyperlipidemia, or previous trauma. Previous case reports of osteonecrosis related to inhaled or topical use of steroids are complicated by the fact that in the great majority of cases, the patients are also treated with systemic steroids prior to the development of osteonecrosis. Based on the literature, a set of recommendations regarding the risk of osteonecrosis in patients on steroids was formulated

Suppression of Leukotriene B4 Generation by Ex-vivo Neutrophils Isolated from Asthma Patients on Dietary Supplementation with Gammalinolenic Acid-containing Borage Oil: Possible Implication in Asthma

Dietary gammalinolenic acid (GLA), a potent inhibitor of 5-lipoxygenase (5-LOX) and suppressor of leukotriene B(4) (LTB(4)), can attenuate the clinical course of rheumatoid arthritics, with negligible side effects. Since Zileuton, also an inhibitor of 5-LOX, attenuates asthma but with an undesirable side effect, we investigated whether dietary GLA would suppress biosynthesis of PMN-LTB(4) isolated from asthma patients and attenuate asthma. Twenty-four mild-moderate asthma patients (16–75 years) were randomized to receive either 2.0 g daily GLA (borage oil) or corn oil (placebo) for 12 months. Blood drawn at 3 months intervals was used to prepare sera for fatty acid analysis, PMNs for determining phospholipid fatty acids and for LTB4 generation. Patients were monitored by daily asthma scores, pulmonary function, and exhaled NO. Ingestion of daily GLA (i) increased DGLA (GLA metabolite) in PMN-phospholipids; (ii) increased generation of PMN-15-HETrE (5-LOX metabolite of DGLA). Increased PMN-DGLA/15-HETrE paralleled the decreased PMN generation of proinflammatory LTB(4). However, the suppression of PMN-LTB4 did not reveal statistically significant suppression of the asthma scores evaluated. Nonetheless, the study demonstrated dietary fatty acid modulation of endogenous inflammatory mediators without side effects and thus warrant further explorations into the roles of GLA at higher doses, leukotrienes and asthma

Steroid induced osteonecrosis: An analysis of steroid dosing risk.

Osteonecrosis is a serious condition involving bone destruction that frequently requires surgical treatment to rebuild the joint. While there is an abundance of literature documenting corticosteroid related osteonecrosis, there is no consensus as to the relative risk of osteonecrosis after administration of steroids via parenteral, oral, topical, inhaled and other routes. This risk is an important prognostic indicator because identification and conservative intervention can potentially reduce morbidity associated with aggressive surgical treatment of osteonecrosis. This paper provides insight into establishing guidelines related to the risk of developing osteonecrosis as a result of corticosteroid use. Case studies, retrospective studies and prospective studies in humans on different corticosteroids and varied dosages were assessed. Most cases of osteonecrosis are secondary to systemically administered corticosteroids and/or high dose daily therapy, particularly in patients with underlying comorbidities including connective tissue diseases, hyperlipidemia, or previous trauma. Previous case reports of osteonecrosis related to inhaled or topical use of steroids are complicated by the fact that in the great majority of cases, the patients are also treated with systemic steroids prior to the development of osteonecrosis. Based on the literature, a set of recommendations regarding the risk of osteonecrosis in patients on steroids was formulated

Safety issues and concerns of new immunomodulators in rheumatology

INTRODUCTION: The development of biologic therapies has been an enormous leap in the management of patients with rheumatoid and psoriatic arthritis. Since the first anti-TNF-α therapies, numerous molecules have been identified as targets of immunomodulatory therapies, such as IL-1 (anakinra, canakinumab), IL-6 (tocilizumab), CD20(+) B cells (rituximab), CTLA4 (abatacept) and two additional anti-TNF-α therapies (certolizumab pegol, golimumab). AREAS COVERED: In the present review, we will describe the safety issues related to the immunosuppressive action of these biologic drugs that are mainly represented by infection and malignancy. The risk of infection should be identified before initiating a biologic treatment and markers checked over time, in particular for tuberculosis and hepatitis B and C viruses. Other infections (bacterial, viral, parasitic; opportunistic; surgery-related) and safety issues may require temporary interruption of the treatment until complete resolution. No significantly increased risk of malignancy, both hematological and solid, has been associated with the use of biologic agents. In all cases, it is difficult to dissect the risks related to biologics from those related to baseline treatments. EXPERT OPINION: Detailed medical history and laboratory screening should be performed before starting biologic therapies. Clinicians should be aware of the different safety profiles associated with different molecules and they should follow up data coming out of the existing registries for biologics in regard to new or old side effects

Common Variable Immunodeficiency: Etiological and Treatment Issues

One of the great advances in clinical medicine was the recognition of the pleomorphism of the immune response and the multiple afferent and efferent limbs of antigen processing and responsiveness. A significant contribution to this understanding was derived from studies of human immunodeficiency states, including both inherited and acquired syndromes. Amongst these syndromes, one of the most common, and least understood, is common variable immune deficiency (CVID). CVID is a syndrome that leads to a reduction in serum immunoglobulins and complications including recurrent infections. Management includes immunoglobulin replacement therapy; however, patients with CVID are at risk for complications of exogenous immunoglobulin administration as well as CVID-associated diseases such as autoimmune processes and malignancies. To assess the current state of knowledge in the field, we performed a literature review of a total of 753 publications covering the period of 1968 until 2008. From this list, 189 publications were selected for discussion. In this review, we demonstrate that while the molecular basis of CVID in many cases remains incompletely understood, significant strides have been made and it is now clear that there is involvement of several pathways of immune activation, with contributions from both T and B cells. Furthermore, despite the current gaps in our knowledge of the molecular pathogenesis of the syndrome, there have been dramatic advances in management that have led to improved survival and significantly reduced morbidity in affected patients