DOCSLIB.ORG

Immediate Type I Hypersensitivity Response Implicated in Worsening Injection Site Reactions to Adalimumab

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Immediate Type I Hypersensitivity Response Implicated in Worsening Injection Site Reactions to Adalimumab OBSERVATION Immediate Type I Hypersensitivity Response Implicated in Worsening Injection Site Reactions to Adalimumab Michael Paltiel, MD; Laura M. Gober, MD; April Deng, MD, PhD; Jamal Mikdashi, MD; Irena Alexeeva, MD; Sarbjit S. Saini, MD; Anthony A. Gaspari, MD Background: Tumor necrosis factor (TNF) inhibitors an immediate type I hypersensitivity reaction to adali- such as adalimumab, etanercept, and infliximab play an mumab. A histamine release assay performed on periph- increasingly important role in the management of a va- eral blood leukocytes from both patients demonstrated sig- riety of chronic inflammatory disorders. With their in- nificant histamine release on exposure to adalimumab. creasing use, a wide spectrum of dermatological adverse Furthermore, passive transfer of serum from one of the effects, including injection site reactions and the devel- allergic patients to basophils from a nonatopic, healthy do- opment of dermatitis, have been recognized. Previous nor sensitized those cells to release significant amounts studies have implicated the role of the delayed-type hy- of histamine with exposure to adalimumab. persensitivity reaction in mediation of injection site re- actions to etanercept. To our knowledge, there have been Conclusion: This study demonstrates that an IgE- no published studies on immunologic mechanism of in- mediated immediate type I hypersensitivity reaction plays jection site reactions to adalimumab to date. a role in the mediation of worsening injection site reac- tions in some patients receiving adalimumab. Observations: We describe 2 patients with a history of worsening injection site reactions to adalimumab. Find- ings from skin testing in both patients were suggestive of Arch Dermatol. 2008;144(9):1190-1194 HE ADVENT OF TUMOR rienced etanercept-induced ISRs by per- necrosis factor (TNF) forming an immunohistological analysis of inhibitors has dramatically reaction sites in 3 patients with rheuma- changed the therapeutic toid arthritis. The authors observed an in- approach to an increasing flammatory infiltrate composed largely of number of immune-mediated inflamma- T cells bearing an activated cytotoxic phe- T ϩ ϩ ϩ tory disorders including psoriasis notype (HLA-DR /CD3 /CD4−/CD8 ), 1 and psoriatic arthritis, rheumatoid with a minor contribution of cells bearing arthritis,2-4 juvenile idiopathic arthritis,5 6,7 an activated helper/inducer T-cell pheno- ankylosing spondylitis, ulcerative coli- ϩ ϩ ϩ − 8 9 type (HLA-DR /CD3 /CD4 /CD8 ), tis, and Crohn disease. Currently avail- CD14ϩ monocytes, CD1ϩ Langerhan cells, able anti-TNF agents include 1 soluble eosinophils, and neutrophils. The authors p75 TNF receptor (etanercept) and 2 speculated that their findings were most monoclonal anti-TNF antibodies (inflixi- consistent with a T-cell–mediated delayed mab and adalimumab). While generally hypersensitivity reaction, mediated by well tolerated and safe, a variety of ϩ 12 adverse effects including a wide spec- CD8 T cells. As with etanercept, pa- trum of dermatological conditions are tients receiving adalimumab therapy com- Author Affiliations: increasingly being recognized in the set- monly experience ISRs. To our knowl- Departments of Dermatology ting of TNF inhibitors. edge, however, no studies have been (Drs Paltiel, Deng, and In clinical trials, a variety of skin con- conducted to assess the immunologic Gaspari), Rheumatology ditions have been reported, including cu- mechanism of ISRs with adalimumab (Dr Mikdashi), and Neurology taneous eruptions and injection site reac- therapy to date. We describe 2 patients with (Dr Alexeeva), University of 4,10 prominent and worsening ISRs to adali- Maryland, and Department of tions (ISRs) during adalimumab therapy, Allergy and Clinical urticarial reactions and stomatitis during in- mumab and present evidence demonstrat- 11 Immunology, Johns Hopkins fliximab therapy, and ISRs during etaner- ing that immediate-type hypersensitivity re- University (Drs Gober and cept therapy.3 Zeltser et al12 conducted a action plays a role in the mediation of ISRs Saini), Baltimore, Maryland. retrospective study of patients who expe- in both patients. (REPRINTED) ARCH DERMATOL/ VOL 144 (NO. 9), SEP 2008 WWW.ARCHDERMATOL.COM 1190 ©2008 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 REPORT OF CASES tients’ forearm, and skin was lightly pricked with a 27-gauge needle. A reading was performed 15 minutes after the pin prick. In addition, 0.1 mL (40 mg/0.8 mL) of adalimumab, 0.1 mL of CASE 1 vehicle, and 0.1 mL of normal saline were injected intrader- maly in the attempt to reproduce ISRs in both patients. Similar A 41-year-old Asian woman with a history of HLA-B27– testing was performed on 1 patient (patient 3), who had no his- positive spondyloarthropathy was treated with adali- tory of ISR to adalimumab after 9 months of therapy. mumab, 40 mg subcutaneously injected every other week, for arthritis involving both knees and the left ankle. The BASOPHIL ISOLATION patient’s arthritic symptoms improved considerably; how- AND HISTAMINE RELEASE ever, after 5 injections she began to develop ISRs consist- ing of prominent edema, erythema, and pruritus at the in- Venous blood samples for basophil studies were collected into jection sites on the abdomen and thighs. The initial syringes containing 5mM EDTA from 2 patients with a history reactions were localized to a small area within approxi- of ISRs to adalimumab, 1 patient (patient 3) with no history of mately 3 cm of injection site and appeared several hours ISRs to adalimumab, and 1 healthy, nonatopic control patient after an injection, and subsequent ISRs developed more with no history of exposure to adalimumab. Mixed blood leuko- cytes were isolated by dextran sedimentation and then stimu- rapidly (within minutes) and involved an increasingly lated for histamine release with adalimumab (0.5-50 000 ng/ greater area. Edema and erythema around the injection site mL) (Humira; Abbott Laboratories, Abbott Park, Illinois), human lasted 2 to 3 days after injection before gradual and com- ␥-globulin (50-50 000 µg/mL) (Sigma-Aldrich, St Louis, Mis- plete resolution. After 2 months of therapy, the patient de- souri), polyclonal goat antihuman IgE (0.1 µg/mL), and N- veloped multiple pruritic erythematous scaly patches in formyl-methionine-leucine-phenylalanine (1µM) at 37°C for a generalized distribution and discontinued the therapy. 45 minutes. Assays were performed in duplicate in standard buff- The dermatitis subsequently resolved with initiation of topi- ers containing calcium as previously described.13 Histamine was cal corticosteroids (clobetasol propionate, 0.05%, oint- quantified from supernatants using an automated fluorometric ment applied to the body and hydrocortisone, 2.5%, cream assay. Results are presented as the percentage of total histamine applied to the face) and narrow-band UV-B therapy. content minus the subject’s spontaneous histamine release. CASE 2 BASOPHIL SENSITIZATION A 60-year-old white woman with a history of irritable bowel In a separate experiment, basophils from the same nonatopic, healthy control patient were isolated by dextran sedimenta- syndrome, psoriasis, and psoriatic arthritis, attended our tion. Basophil surface IgE was stripped by incubating the cells dermatology clinic for treatment of persistent psoriasis and with lactic acid (pH 3.9) in normal saline for 3.5 minutes at psoriatic arthritis. The patient was being treated with etaner- room temperature.14,15 Following lactic acid stripping, serum cept, 25 mg every week for 4 years, with incomplete clear- from patient 1 was incubated with cells from the nonatopic do- ance of psoriasis and persistent arthritic symptoms. The nor at 37°C for 60 minutes in buffers containing heparin and patient had been previously treated with methotrexate and EDTA. Then the cells were stimulated for histamine release to phototherapy with limited success. Etanercept therapy was adalimumab (500-50 000 ng/mL) as described in the previous discontinued, and adalimumab therapy, 40 mg weekly for subsection. As a control to confirm removal of surface-bound the first 4 weeks, was initiated. The patient initially expe- IgE, cells were stimulated for histamine release by polyclonal rienced notable improvement of her arthritic symptoms goat antihuman IgE (0.1 µg/mL) and showed a 59% decrease in response after stripping (14%) vs before stripping (34%), with and psoriasis but developed edema and erythema around subsequent recovery of response (42%) following incubation the injection site within several hours after the second in- with serum from patient 1. jection. Gradually, each subsequent injection of adali- mumab resulted in a more prominent edema and ery- STATISTICAL ANALYSES thema around the injection site and developed more rapidly. Each ISR lasted 2 to 3 days before gradual resolution. The Quantitative data were analyzed for statistically significant dif- patient subsequently experienced decreased efficacy of the ferences between control and treatment groups using the Graph- drug in the treatment of psoriasis and psoriatic arthritis Pad Instat Software Program (GraphPad Software, San Diego, and discontinued the therapy. California). Because multiple comparisons were examined, a 1-way analysis of variance was applied to the quantitative data. PϽ.05 was considered statistically significant. METHODS RESULTS PIN-PRICK TESTING Pin-prick testing resulted in the development of wheal Pin-prick testing was used to
Load more

Recommended publications
  • Clinical Policy: Baricitinib (Olumiant) Reference Number: ERX.SPA.291 Effective Date: 07.24.18 Last Review Date: 11.18 Revision Log
    Clinical Policy: Baricitinib (Olumiant) Reference Number: ERX.SPA.291 Effective Date: 07.24.18 Last Review Date: 11.18 Revision Log See Important Reminder at the end of this policy for important regulatory and legal information. Description Baricitinib (Olumiant®) is Janus kinase (JAK) inhibitor. FDA Approved Indication(s) Olumiant is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies. Limitation(s) of use: Use of Olumiant in combination with other JAK inhibitors, biologic disease-modifying antirheumatic drugs (DMARDs), or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria. It is the policy of health plans affiliated with Envolve Pharmacy Solutions™ that Olumiant is medically necessary when the following criteria are met: I. Initial Approval Criteria A. Rheumatoid Arthritis (must meet all): 1. Diagnosis of RA; 2. Prescribed by or in consultation with a rheumatologist; 3. Age ≥ 18 years; 4. Member meets one of the following (a or b): a. Failure of a ≥ 3 consecutive month trial of methotrexate (MTX) at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced; b. If intolerance or contraindication to MTX (see Appendix D), failure of a ≥ 3 consecutive month trial of at least ONE conventional DMARD (e.g., sulfasalazine, leflunomide, hydroxychloroquine) at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced; 5.
    [Show full text]
  • Immunosuppressant Drugs Therapy with COVID-19
    Immunosuppressant Drugs Therapy with COVID-19: Associated Risks, Drug-Drug Interactions & Contraindications Debjyoti Talukdar1, Diane Ignacio2, and Madan Mohan Gupta2 1Teerthanker Mahaveer University 2The University of the West Indies at St Augustine September 24, 2020 Abstract Immunosuppressant drugs like Etanercept, Mycophenolate mofetil, Sirolimus, Cyclosporine and Rituximab can weaken the immune system and make patients susceptible to SARS nCoV-2 virus. These drugs make immunocompromised persons more vulnerable to complications associated with COVID-19. Moreover, it can also increase the mortality and morbidity, as a weakened immune system can lead to longer duration of infection. This study discusses the guidelines on immunosuppressant drugs and its associated risk factors with COVID-19, issued by the U.S CDC (Centers for Disease Control and Prevention), WHO (World Health Organisation), U.S FDA (Food and Drug Administration) and other accredited global health organisa- tions. Moreover, it also includes information about pharmaceutical properties, mechanism of action, COVID-19 associated risk factors, adverse drug reactions, contraindications and drug-drug interactions. Our study will help government partners and international health organisations to better understand COVID-19 health risks associated with immunosuppressants. Increased public awareness about effective drug therapy for autoimmune diseases, cancer treatment, immunocompromised and organ transplant patients will help lower the mortality and morbidity associated with the disease amid COVID-19 pandemic. 1. INTRODUCTION As per the U.S Department of Health and Human Services and U.S FDA, immunosuppressant drugs can cause susceptibility to viruses leading to infection with increase in morbidity of the disease. It can cause severe risk of illness from COVID-19 due to a weakened immune system.
    [Show full text]
  • Benlysta® (Belimumab)
    UnitedHealthcare Pharmacy Clinical Pharmacy Programs Program Number 2021 P 1227-6 Program Prior Authorization/Notification Medication Benlysta® (belimumab)* *This program applies to the subcutaneous formulation of belimumab P&T Approval Date 9/2017, 9/2018, 9/2019, 9/2020, 2/2021, 7/2021 Effective Date 10/1/2021; Oxford only: 10/1/2021 1. Background: Benlysta® is a B-lymphocyte stimulator (BLyS)-specific inhibitor indicated for the treatment of patients aged 5 years and older with active, autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy and adult patients with active lupus nephritis who are receiving standard therapy. Limitations of Use: The efficacy of Benlysta has not been evaluated in patients with severe active central nervous system lupus. Benlysta has not been studied in combination with other biologics. Use of Benlysta is not recommended in these situations. 2. Coverage Criteria: A. Systemic Lupus Erythematosus 1. Initial Authorization a. Benlysta will be approved based on all of the following criteria: (1) Diagnosis of systemic lupus erythematosus -AND- (2) Laboratory testing has documented the presence of autoantibodies [e.g., ANA, Anti-dsDNA, Anti-Sm, Anti-Ro/SSA, Anti-La/SSB] -AND- (3) Patient is currently receiving standard immunosuppressive therapy [e.g., hydroxychloroquine, chloroquine, prednisone, azathioprine, methotrexate] -AND- (4) Patient does not have severe active central nervous system lupus -AND- (5) Patient is not receiving Benlysta in combination with either of the following: (a) Biologic DMARD [e.g., Enbrel (etanercept), Humira (adalimumab), Cimzia (certolizumab), Kineret (anakinra)] © 2021 UnitedHealthcare Services, Inc. 1 (b) Lupkynis (voclosporin) Authorization will be issued for 12 months.
    [Show full text]
  • Attachment: Extract from Clinical Evaluation: Etanercept
    AusPAR Attachment 2 Extract from the Clinical Evaluation Report for etanercept Proprietary Product Name: Erelzi Sponsor: Novartis Pharmaceuticals Australia Pty Ltd First round report: June 2017 Second round report: August 2017 Therapeutic Goods Administration About the Therapeutic Goods Administration (TGA) · The Therapeutic Goods Administration (TGA) is part of the Australian Government Department of Health and is responsible for regulating medicines and medical devices. · The TGA administers the Therapeutic Goods Act 1989 (the Act), applying a risk management approach designed to ensure therapeutic goods supplied in Australia meet acceptable standards of quality, safety and efficacy (performance) when necessary. · The work of the TGA is based on applying scientific and clinical expertise to decision- making, to ensure that the benefits to consumers outweigh any risks associated with the use of medicines and medical devices. · The TGA relies on the public, healthcare professionals and industry to report problems with medicines or medical devices. TGA investigates reports received by it to determine any necessary regulatory action. · To report a problem with a medicine or medical device, please see the information on the TGA website <https://www.tga.gov.au>. About AusPARs · An Australian Public Assessment Report (AusPAR) provides information about the evaluation of a prescription medicine and the considerations that led the TGA to approve or not approve a prescription medicine submission. · AusPARs are prepared and published by the TGA. · An AusPAR is prepared for submissions that relate to new chemical entities, generic medicines, major variations and extensions of indications. · An AusPAR is a static document; it provides information that relates to a submission at a particular point in time.
    [Show full text]
  • Heart Failure and Drug-Induced Lupus
    Unusual toxicities with TNF inhibition: Heart failure and drug-induced lupus J.J. Cush John J. Cush, MD, Chief, Rheumatology ABSTRACT demyelinating disease, cytopenias, auto- and Clinical Immunology, Presbyterian Serious and unexpected adverse events, immune disorders, and heart failure. Hospital of Dallas, Clinical Professor of such as heart failure and drug-induced Other essays in this volume address the Internal Medicine, The University of Texas lupus, have been reported in patients subject of infection (10), demyelination Southwestern Medical School, Dallas, Texas, USA. receiving TNF inhibitor therapy. These (11), and lymphoma (12). This review events generally are easily recogniz- will focus on heart failure and lupus- Please address correspondence to: John J. Cush, MD, Presbyterian Hospital able, although they cannot be predicted like disease, which are rarely seen in of Dallas, 8200 Walnut Hill Lane, Dallas, nor avoided, other than by drug avoid- association with TNF inhibitor therapy Texax 75231-4496, USA. ance altogether. Many patients have and are currently without explanation. Clin Exp Rheumatol 2004; 22 (Suppl. 35): great benefit from anti-TNF therapies. S141-S147. Their intelligent use requires a firm Sources of data © Copyright CLINICAL AND EXPERIMENTAL understanding of these rare toxicities, As a consequence of drug approval, RHEUMATOLOGY 2004. so as to minimize the morbidity associ- manufacturers have a responsibility to ated with their uncommon occurrence. collect safety data actively and report Key words: TNF inhibitors, conges- these data to the appropriate agencies. tive heart failure, drug-induced lupus, Introduction For example, in the USA a manufactur- rheumatoid arthritis. The introduction of biologic agents to er must submit periodic safety reports specifically inhibit the pro-inflammato- to the FDA twice yearly (March and ry cytokine, tumor necrosis factor (TNF), September).
    [Show full text]
  • New Biological Therapies: Introduction to the Basis of the Risk of Infection
    New biological therapies: introduction to the basis of the risk of infection Mario FERNÁNDEZ RUIZ, MD, PhD Unit of Infectious Diseases Hospital Universitario “12 de Octubre”, Madrid ESCMIDInstituto de Investigación eLibraryHospital “12 de Octubre” (i+12) © by author Transparency Declaration Over the last 24 months I have received honoraria for talks on behalf of • Astellas Pharma • Gillead Sciences • Roche • Sanofi • Qiagen Infections and biologicals: a real concern? (two-hour symposium): New biological therapies: introduction to the ESCMIDbasis of the risk of infection eLibrary © by author Paul Ehrlich (1854-1915) • “side-chain” theory (1897) • receptor-ligand concept (1900) • “magic bullet” theory • foundation for specific chemotherapy (1906) • Nobel Prize in Physiology and Medicine (1908) (together with Metchnikoff) Infections and biologicals: a real concern? (two-hour symposium): New biological therapies: introduction to the ESCMIDbasis of the risk of infection eLibrary © by author 1981: B-1 antibody (tositumomab) anti-CD20 monoclonal antibody 1997: FDA approval of rituximab for the treatment of relapsed or refractory CD20-positive NHL 2001: FDA approval of imatinib for the treatment of chronic myelogenous leukemia Infections and biologicals: a real concern? (two-hour symposium): New biological therapies: introduction to the ESCMIDbasis of the risk of infection eLibrary © by author Functional classification of targeted (biological) agents • Agents targeting soluble immune effector molecules • Agents targeting cell surface receptors
    [Show full text]
  • BCMA-Targeted Immunotherapy for Multiple Myeloma Bo Yu1, Tianbo Jiang2 and Delong Liu2*
    Yu et al. Journal of Hematology & Oncology (2020) 13:125 https://doi.org/10.1186/s13045-020-00962-7 REVIEW Open Access BCMA-targeted immunotherapy for multiple myeloma Bo Yu1, Tianbo Jiang2 and Delong Liu2* Abstract B cell maturation antigen (BCMA) is a novel treatment target for multiple myeloma (MM) due to its highly selective expression in malignant plasma cells (PCs). Multiple BCMA-targeted therapeutics, including antibody-drug conjugates (ADC), chimeric antigen receptor (CAR)-T cells, and bispecific T cell engagers (BiTE), have achieved remarkable clinical response in patients with relapsed and refractory MM. Belantamab mafodotin-blmf (GSK2857916), a BCMA-targeted ADC, has just been approved for highly refractory MM. In this article, we summarized the molecular and physiological properties of BCMA as well as BCMA-targeted immunotherapeutic agents in different stages of clinical development. Keywords: B cell maturation antigen, BCMA, Belantamab mafodotin, CAR-T, Antibody-drug conjugate, Bispecific T cell engager Introduction B cell maturation antigen (BCMA) Recent advances in novel therapeutics such as prote- BCMA is encoded by a 2.92-kb TNFRSF17 gene located asome inhibitors (PI) and immunomodulatory drugs on the short arm of chromosome 16 (16p13.13) and (IMiD) have significantly improved the treatment out- composed of 3 exons separated by 2 introns (Fig. 1). comes in patients with multiple myeloma (MM) [1–8]. BCMA is a 184 amino acid and 20.2-kDa type III trans- However, most MM patients eventually relapse due to membrane glycoprotein, with the extracellular N the development of drug resistance [9]. In addition, terminus containing a conserved motif of 6 cysteines many of the current popular target antigens, such as [18–21].
    [Show full text]
  • JAK-Inhibitors for the Treatment of Rheumatoid Arthritis: a Focus on the Present and an Outlook on the Future
    biomolecules Review JAK-Inhibitors for the Treatment of Rheumatoid Arthritis: A Focus on the Present and an Outlook on the Future 1, 2, , 3 1,4 Jacopo Angelini y , Rossella Talotta * y , Rossana Roncato , Giulia Fornasier , Giorgia Barbiero 1, Lisa Dal Cin 1, Serena Brancati 1 and Francesco Scaglione 5 1 Postgraduate School of Clinical Pharmacology and Toxicology, University of Milan, 20133 Milan, Italy; [email protected] (J.A.); [email protected] (G.F.); [email protected] (G.B.); [email protected] (L.D.C.); [email protected] (S.B.) 2 Department of Clinical and Experimental Medicine, Rheumatology Unit, AOU “Gaetano Martino”, University of Messina, 98100 Messina, Italy 3 Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Pordenone, 33081 Aviano, Italy; [email protected] 4 Pharmacy Unit, IRCCS-Burlo Garofolo di Trieste, 34137 Trieste, Italy 5 Head of Clinical Pharmacology and Toxicology Unit, Grande Ospedale Metropolitano Niguarda, Department of Oncology and Onco-Hematology, Director of Postgraduate School of Clinical Pharmacology and Toxicology, University of Milan, 20162 Milan, Italy; [email protected] * Correspondence: [email protected]; Tel.: +39-090-2111; Fax: +39-090-293-5162 Co-first authors. y Received: 16 May 2020; Accepted: 1 July 2020; Published: 5 July 2020 Abstract: Janus kinase inhibitors (JAKi) belong to a new class of oral targeted disease-modifying drugs which have recently revolutionized the therapeutic panorama of rheumatoid arthritis (RA) and other immune-mediated diseases, placing alongside or even replacing conventional and biological drugs.
    [Show full text]
  • Enbrel) Reference Number: CP.PHAR.250 Effective Date: 08.16 Last Review Date: 02.21 Coding Implications Line of Business: Medicaid Revision Log
    Clinical Policy: Etanercept (Enbrel) Reference Number: CP.PHAR.250 Effective Date: 08.16 Last Review Date: 02.21 Coding Implications Line of Business: Medicaid Revision Log See Important Reminder at the end of this policy for important regulatory and legal information. Description Etanercept (Enbrel®) is a tumor necrosis factor (TNF) blocker. FDA Approved Indication(s) Enbrel is indicated for the treatment of: • For reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis (RA). Enbrel can be initiated in combination with methotrexate (MTX) or used alone. • For reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis (JIA) in patients ages 2 and older • For reducing signs and symptoms, inhibiting the progression of structural damage of active arthritis, and improving physical function in patients with psoriatic arthritis (PsA). Enbrel can be used with or without methotrexate. • For reducing signs and symptoms in patients with active ankylosing spondylitis (AS) • For the treatment of patients 4 years or older with chronic moderate to severe plaque psoriasis (PsO) who are candidates for systemic therapy or phototherapy Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria. It is the policy of health plans affiliated with Centene Corporation® that Enbrel is medically necessary when the following criteria are met: I. Initial Approval Criteria A. Ankylosing Spondylitis (must meet all): 1. Diagnosis of AS; 2. Prescribed by or in consultation with a rheumatologist; 3.
    [Show full text]
  • Hypersensitivity Reactions (Types I, II, III, IV)
    Hypersensitivity Reactions (Types I, II, III, IV) April 15, 2009 Inflammatory response - local, eliminates antigen without extensively damaging the host’s tissue. Hypersensitivity - immune & inflammatory responses that are harmful to the host (von Pirquet, 1906) - Type I Produce effector molecules Capable of ingesting foreign Particles Association with parasite infection Modified from Abbas, Lichtman & Pillai, Table 19-1 Type I hypersensitivity response IgE VH V L Cε1 CL Binds to mast cell Normal serum level = 0.0003 mg/ml Binds Fc region of IgE Link Intracellular signal trans. Initiation of degranulation Larche et al. Nat. Rev. Immunol 6:761-771, 2006 Abbas, Lichtman & Pillai,19-8 Factors in the development of allergic diseases • Geographical distribution • Environmental factors - climate, air pollution, socioeconomic status • Genetic risk factors • “Hygiene hypothesis” – Older siblings, day care – Exposure to certain foods, farm animals – Exposure to antibiotics during infancy • Cytokine milieu Adapted from Bach, JF. N Engl J Med 347:911, 2002. Upham & Holt. Curr Opin Allergy Clin Immunol 5:167, 2005 Also: Papadopoulos and Kalobatsou. Curr Op Allergy Clin Immunol 7:91-95, 2007 IgE-mediated diseases in humans • Systemic (anaphylactic shock) •Asthma – Classification by immunopathological phenotype can be used to determine management strategies • Hay fever (allergic rhinitis) • Allergic conjunctivitis • Skin reactions • Food allergies Diseases in Humans (I) • Systemic anaphylaxis - potentially fatal - due to food ingestion (eggs, shellfish,
    [Show full text]
  • Hypersensitivity Mechanisms: an Overview
    Hypersensitivity Mechanisms: An Overview Stephen Canfield, MD, PhD Asst. Prof. Medicine Pulmonary, Allergy, and Critical Care Medicine 1 Origins of Hypersensitivity “Hypersensitivity” first used clinically in 1893: • attempting to protect against diphtheria toxin • test animals suffered enhanced responses, even death following second toxin exposure Emil von • at miniscule doses not harmful to untreated Behring animals The term “Allergy” is coined in 1906: • postulated to be the product of an “allergic” response • from Greek allos ergos (altered reactivity) Clemens von Pirquet os from Silverstein, AM. 1989. A History of Immunology. Academic Press, San Diego 2 First Task of the Immune System Dangerous Innocuou ? s? 3 Modern Use • Hypersensitivity: • Aberrant or excessive immune response to foreign antigens • Primary mediator is the adaptive immune system • T & B lymphocytes • Damage is mediated by the same attack mechanisms that mediate normal immune responses to pathogen 4 Mechanisms of Hypersensitivity Gell & Coombs Classification G&C Common Term Mediator Example Class Type I Immediate Type IgE monomers Anaphylaxis IgG/IgM Drug-induced Type II Cytotoxic Type monomers hemolysis Immune Complex IgG/IgM Type III Serum sickness Type multimers PPD rxn Type IV Delayed Type T cells Contact Dermatitis 5 Common to All Types Adaptive (T & B Cell) Immune Responses • Reactions occur only in sensitized individuals • Generally at least one prior contact with the offending agent • Sensitization can be long lived in the absence of re-exposure (>10 years)
    [Show full text]
  • Diseases of the Immune System 813
    Chapter 19 | Diseases of the Immune System 813 Chapter 19 Diseases of the Immune System Figure 19.1 Bee stings and other allergens can cause life-threatening, systemic allergic reactions. Sensitive individuals may need to carry an epinephrine auto-injector (e.g., EpiPen) in case of a sting. A bee-sting allergy is an example of an immune response that is harmful to the host rather than protective; epinephrine counteracts the severe drop in blood pressure that can result from the immune response. (credit right: modification of work by Carol Bleistine) Chapter Outline 19.1 Hypersensitivities 19.2 Autoimmune Disorders 19.3 Organ Transplantation and Rejection 19.4 Immunodeficiency 19.5 Cancer Immunobiology and Immunotherapy Introduction An allergic reaction is an immune response to a type of antigen called an allergen. Allergens can be found in many different items, from peanuts and insect stings to latex and some drugs. Unlike other kinds of antigens, allergens are not necessarily associated with pathogenic microbes, and many allergens provoke no immune response at all in most people. Allergic responses vary in severity. Some are mild and localized, like hay fever or hives, but others can result in systemic, life-threatening reactions. Anaphylaxis, for example, is a rapidly developing allergic reaction that can cause a dangerous drop in blood pressure and severe swelling of the throat that may close off the airway. Allergies are just one example of how the immune system—the system normally responsible for preventing disease—can actually cause or mediate disease symptoms. In this chapter, we will further explore allergies and other disorders of the immune system, including hypersensitivity reactions, autoimmune diseases, transplant rejection, and diseases associated with immunodeficiency.
    [Show full text]