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ITE Review: Allergy and Immune Disorders Angela M. Pugliese MD Henry Ford Hospital Department of Emergency Medicine ALLERGY Allergy • 4 types of hypersensitivity reactions • 1. Anaphylactic • IgE mediated with degranulation from mast cells • 2. Cytotoxic • IgG or IgM antibiodies react with cell antigens and activate complement • ie: autoimmune hemolytic anemia, goodpasture’s • 3. Immune Complex • immune complex deposition resulting in complement activation • ie: serum sickness, SLE, RA • 4. Cell-mediated • activated T-cells against cell surface bound antigens • ie: contact dermatitis Angioedema • edema of deeper layers of skin that is non-pruritic • can cause burning, pain or numbness • Drug induce vs Hereditary • Drug induced • ACE inhibitors: not IgE mediated • anti-histamines and steroids haven’t shown clear benefit • tx includes airway protection and possible racemic epi • Hereditary • C1-esterase inhibitor deficiency • tx is also airway protection, but can also give frozen plasma • consider high dose epi, danazol and stanozolol Anaphylaxis • IgE mediated, immediate hypersensitivity reaction to antigen • abrupt onset of symptoms to SENSITIZED patient involving 2 or more organ systems • pts on beta-blockers have more severe reactions • Presenting Symptoms: rash, “lump” in throat, wheezing, N/V/D, hypotension, pulmonary edema • most serious reactions tend to occur within minute but can have relapse of symptoms within 4-8 hours Anaphylaxis Treatment • EPINEPHRINE – MUST KNOW DOSES • stop or remove offending agent, protect airway • also give H1 blockers, steroids, nebs and consider glucagon for patients on b-blockers who are refractory Anaphylaxis Disposition • Usually admission for observation or continued treatment • Consider discharge only in mild cases • • • • no hemodynamic instability no airway involvement complete resolution of symptoms to ED treatment no relapse after 6 hour observation Anaphylactoid Reaction • Direct release of mediators, do not require prior exposure like anaphylaxis (but otherwise can think of as the same) • Treatment is same as anaphylaxis • Most common offending agents • • • • IV dye ASA NSAIDs codeine Erythema Multiforme • more severe variant of an urticarial reaction • Iris or target Lesions • Common Drug Offenders • • • • • PCN Sulfa Cephalosporins tetracycline phenytoin Stevens-Johnson Syndrome • severe, potentially fatal form of erythema multiforme • Characterized by bullae, mucus membrane lesions and multisystem involvement • Bactrim and Herpes Simplex are common causes Jarish-Herxheimer Reaction • febrile reaction to parasitic or bacterial antigens that are release when organism is killed • occurs 2-12 hours after initiation of antibiotics, lasts less than 48 hours • Tx is supportive: give antipyretics and consider steroids occasionally Adverse Food Reactions • DIRECT HISTAMINE RELEASE: causes flushing, bronchospasm, urticarial rash and hypotension • Preservatives, food enhancers, dyes and allergens cause this • Sulfites (preservatives): asthmatics are more sensitive, commonly found in packaged salad, shrimp, pickles, dried fruit, sausages, cheese, wine and fruit juices • Scombroidosis: food toxin from spoiled salt water fish, has peppery taste, usually doesn’t have bronchospasm or hypotension Immunology General Priciples • Innate vs Adaptive immunity • Antibodies • IgM: first to appear, serves as marker for early acute infection • IgA: predominates in secretions and GI fluid, inhibits cell adherence to pathogens • IgE: found in mast cells and basophils, responsible for hypersensitivity responses • IgG: 75% of total immunoglobulin mass, crosses placenta and provide fetal immunity for first 6 months of life, deficiencies lead to infections with encapsulated organisms • Cell Mediate Immunity • T-cells, natural killer cells and macrophages • vital to control intracellular infections • CD4 vs CD8 cells SPECIFIC IMMUNOCOMPROMISED STATES • • • • • • • Transplant Cancer Diabetes Alcoholism and cirrhosis Renal Failure Splenectomy/Hyposplenia/Functional Asplenia Pts on Immunosuppressive therapy Transplant Patients • Think – Rejection, infection, toxicity (to immunosuppressive drugs) • Infection is leading cause of death • First month: mainly bacterial related to surgery, also think about candida and HSV • 1-6 months: think mainly CMV, also worry about EBV, hepatitis, listeria and aspergillosis • After 6 months: mainly chronic viral infections, can have disseminated varicella-zoster, low threshold for IV acyclovir Transplant Rejection • 3 categories for rejection • hyperacute: happens minutes to hours after surgery, irreversible • acute: 1-12 weeks post-op, may be reversed • chronic: progressive, insidious and irreversible • Immunosuppressant (focus on toxicity) • Cyclosporine: toxicity can cause vasoconstriction and renal ischemia • Cellcept (mycophenolate): side effects N/V/D, leukopenia • Prograf: can be nephrotoxic or cause seizures and neuropathy • Failure of transplant to take immunosuppressive meds should be considered an emergency Renal Transplant • make sure to check for tenderness over allograft • subtle elevation in creatinine can mean rejection • Renal US with vascular flow analysis for evaluation • tx is methylprednisolone Lung Transplant • search for infection, CXR can be non specific • symptoms of subtle fever > 0.5 C above baseline should not be ignored • Can also have cough, dyspnea, chest tightness • tx of rejection is methylprednisolone Heart Transplant • remember transplanted heart is DENERVATED • no anginal chest pain • no response to atropine • Use isoproterenol • watch closely for signs of heart failure, Mis present this way………or with death • Tx of rejection also methylprednisolone, can use dopa and dobutamine for hypotension, ISOPROTERENOL for bradydysrhythmias Liver Transplant • can present with fever, anorexia, abdominal pain, ascites, color changes • also consider vascular thrombosis, biliary leak or obstruction and drug toxicity • get hepatic US with vascular • tx of rejection is methylprednisolone Cancer Patients • frequently have multiple immune defects • neutropenia, impaired B & T cell function • induced by chemo or the CA itself • infection is much more common in acute leukemia, lymphoma and multiple myeloma • Listeria is common in CA patients with impaired cell mediated immunity • Pneumonia in neutropenic CA pts is usually from gram neg bacteria early and fungal infections late Neutropenia • Definition • neutrophil count less than 500 cell/mL • Febrile neutropenia: above and fever of 38.3 • Usually from cytotoxic chemotherapy or radiation • Incidence and Severity • inversely proportional to neutrophil count • directly proportional to duration • Most common sites of infection • lung, mouth and pharynx • Bacteremia can occur without obvious source Neutropenia • Pneumonia and anorectal infections are more likely to associated with bacteremia • Gram positive bacteria are leading cause of infection • Aspergillosis and candida are most common fungal infections • Fever is frequently the only sign of infection • Treatment: • broad spectrum antibiotics in setting of fever or obvious infection without fever • Ampho B for fungal infections • granulocyte colony-stimulating factor for high risk patients Diabetes • predisposed to infection from defects in immune functions, vascular insufficiency and neuropathy (leads to wound neglect) • Neutrophil and macrophage functions are impaired • Cellular and humoral immunity are normal • Infections with increased frequency • • • • • malignant otitis externa (pseudomonas) rhinoncerbral zygomycosis (mucormycosis) emphysematous cystitis fournier’s foot infections with osteo Alcoholism and Cirrhosis • predisposed to infection through….. • direct immune suppression • alterations in blood flow • depression of mental status and delay in seeking care • Cirrhotics have impaired hepatic clearance and killing of bacteria as well as splenic hypofunction • Common infections include spontaneous bacteremia • also think sepsis from e. coli, klebsiella and salmonella Renal Failure • Infections are the 2nd most common cause of death after CAD in CKD/ESRD patients • Vascular access site infections and multiple defects in immunity are the cause • have generalized immune hyporesponsiveness • humoral immunity affected: deficient IgG production • have poor response to vaccinations • Watch for peritonitis with PD patients • 2/3 will have an episode within 1st year Splenectomy/Hyposplenia/Functio nal Asplenia • primary site of IgM synthesis • principle clearing site for strep pneumo • higher rate of disseminated pneumococcal infections • Overhwelming infections…. • from encapsulated organisms • h. influenzae, n. meningitidis, gram neg bacilli • more common in children, esp <2 • pts with underlying heme disorder (less so in trauma) • usually have no obvious source • Infections with babsia microti from ticks leads to severe and usually fatal hemolysis • Vaccination is very important in these patients Immunosuppressives • Steroids and company • high dose steroids alter neutrophil, monocyte and lymphocyte functions • Suppress inflammation • Cause profound depression of cell mediated immunity • Most common infections from pyogenic bacteria • ie. s. aureus, strep, gram neg bacilli IMMUNE RELATED DISORDERS • • • • • Rheumatoid Arthritis Lupus Reiter’s Syndrome Raynaud’s Disease Vasculitis Rheumatoid Arthritis • associated with polyarticular joint pain • Most common in women: related to HLA-DR haplotype • Most commonly affects the hand (MCP and PIP joint), then wrist and elbow Lupus • multisystem inflammatory disorder mediated by autoantibodies • associated with symmetric polyarticular joint pain • small and large joints • Women 15-40 mainly affected • Diagnosis: 4/11 of DOPAMINE RASH • Can be drug induced; this is usually reversible • HIPPS: hydralazine, INH, phyntoin, procainamide, sulfa • Treatment • Nsaids for joint pain, steroids for acute flare and immunosuppressive therapy Lupus Diagnosis • DOPAMINE RASH • • • • • • • • • • • Discoid rash Oral ulcers Photosensitive rash Arthritis Malar rash Immunologic criteria (positive anti-dsDNA, anti-Sm) NEurologic or psych symptoms Renal disease Ana + Serositis Hematologic disorders Reiter’s Syndrome • Can’t see, can’t pee, can’t climb a tree • classic triad: conjunctivitis, urethritis, arthritis • Young males 15-35: with HLA-B27 antigen • Usually proceeded by chlamydia, shigella or salmonella infections • Oligoarthritis develops 1-6 weeks after chlamydial urethritis, affects weight bearing joints of lower extremities • Treatment: Abx for urethritis, NSAIDS for arthritis, immunosuppressives for recurrent ocular inflammation Raynaud’s Disease • Vasospasm of distal small arteries • Bilateral triphasic response to cold or emotion • fingers become white, blue, then red • Resolves spontaneously, benign course • avoid cold exposure Vasculitis • Inflammation and necrosis of blood vessels leading to tissue damage • Temporal Arteritis: • • • • involves branches of the carotid artery presents with temporal HA, vision changes, scalp tenderness Diagnose with temporal artery biopsy ESR > 50 in pt with concerning symptoms should be started on steroids • leads to irreversible blindness if untreated • Takayasu’s : • • • • involves aorta and major branches presents with finger ischemia and arm claudication Diagnose with aortic arteriogram Tx is steroids Vasculitis • Bechet Disease • recurrent painful oral and genital ulcers • diagnosis by biopsy • tx: steroids and immunosuppression • Polyarteritis Nodosa • skin ulcers, nephritis, mesenteric ischemia • diagnosis with biopsy of kidney or skin lesions • tx: steroids and immunosuppression Questions???