Download ITE Review: Must Know Immune Disorders

ITE Review: Must Know Immune Disorders
The Immunocompromised Patient
Perspective –
-
Increasing numbers of immunocompromised patients present to ED must be able to
recognize and treat possible infectious complications of cancer, DM, renal failure, cirrhosis,
asplenism, HIV, transplant patients
Principles of Disease –
-have innate (natural) and acquired (adaptive) immune responses
- innate is activated immediately and occurs at the same extent to every exposure
-adaptive immunity takes time to develop initially but improves after each exposure
Antibodies
-IgM : first to appear and respond to new antigen, less affinity for binding, but begins B-cell
proliferation, detected earlier and serves as marker for early response to acute infection
-Secretory IgA: predominant in GI fluids, and most fluid secretions, inhibits cell adherence to
pathogens
-IgE: high concentrations on mast cells and basophils, responsible for immediate hypersensitivity
responses
-IgG: 75% of total immunoglobulin mass, crosses placenta and provides fetal immunity for first 6
months of life, deficiencies lead to infections from encapsulated organisms
Cell-Mediated Immunity
-immune responses that are mediated by T lymphocytes, natural killer cells and mononuclear
phagocytes
-vital to control infections that survive and replicate intracellularly
-only 5% of lymphocytes are in circulating blood; most mature and are active in the marrow,
thymus, spleen and lymph nodes
-the spleen and lymph nodes expose T cells to circulating antigens
-2 types of T cells: CD4 and CD8
-CD4: the helper cell, initiated the production of cytokines and enhanced B-cell antibody
production
-CD8: the suppressor cell, generally cytotoxic and mediate eradication of virally infected target
cells and certain tumors
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-without cell mediate immunity patients are at increased risk for disseminated infections from
intracellular bacteria (mycobacterium, listeria, salmonella) and more severe infections from viral
infections (CMV, herpes, varicella) as well as other fungal and protozoa infections (candida,
Cryptococcus, PCP, toxoplasma)
-Natural Killer Cells: important for innate immunity, not B or T cells, recognize and kill infected
cells, also secrete cytokines that activate macrophages
-salmonella and listeria infections are common in patients with impaired cell mediated immunity
Granulocytic Phagocytes
-neutrophils, macrophages, eosinophils and basophils
-neutrophils and macrophages bind to and ingest bacteria, can detect invaders from self, also
modulate immune response by presenting antigens to lymphocytes and releasing cytokines and
complement components
-eosinophils: less involved in digestion and mediate destruction of certain parasitic helminths
-basophils: high affinity for IgE, release histamine, prostaglandins and leukotrienes
Specific Immunocompromised States
Solid Organ Transplants
-Main complications: think Rejection, Infection, toxicity (to immunosuppressant drugs)
-infection is leading cause of death in transplant patients and must be suspected any time they
present with signs of rejection
-infections in the first month post transplant: mainly bacterial, related to surgery, also think HSV
and candida
-infections from 1 to 6 months: think mainly CMV, also worry about EBV, hepatitis, listeria,
pneumocystic and aspergillosis
-infections after 6 months: mainly chronic viral infections, think Varicella-zoster and can be
disseminated, have low threshold to start IV acyclovir
Transplant Rejection
-immunosuppressants: Cyclosporine acute toxicity can cause vasoconstriction and renal
ischemia, Cellcept (mycophenolate) has side effects including diarrhea, N/V, leukopenia, Prograf
toxicity include nephrotoxicity, seizures and neuropathy
-failure for transplant to take their immunosuppressant meds should be considered an
emergency
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-3 categories of Rejection: 1. hyperacute; happens few minutes to hours after surgery and is
irreversible; 2. Acute; occurs 1-12 weeks after and may be reversed; 3. Chronic; is progressive,
insidious and usually irreversible
Renal Transplant
-make sure to check for tenderness over allograft
-subtle elevation in creatinine can be only sign of rejection, get renal US
-treatment is with methylprednisolone, 500 mg IV
Lung Transplant
-search for infection, CXR may be non specific
-symptoms include subtle fever >0.5 C above baseline, cough, dyspnea, chest tightness
-treatment is again methylprednisolone
Heart Transplant
-rejection can be asymptomatic, remember won’t have angina chest pain, transplants hearts are
denervated, MIs will presents with heart failure or death
-watch for signs of heart failure
-atropine will not work to increase HR
-treatment includes methylprednisolone, isoproterenol for bradydysrhythmias and dopamine or
dobutamine for hypotension
Liver Transplant
-can present with fever, anorexia, abdominal pain or ascites, decreased bile output or change in
color
-consider vascular thrombosis, biliary leak or obstruction, infection and drug toxicity in
differential, get liver US
-treatment for rejection again is methylprednisolone
Cancer
-frequently have multiple immune defects; such as neutropenia and impaired T & B cell
functions
-induced by chemo or the CA itself
-infections much more common acute leukemia, lymphoma and multiple myeloma
-listeria is a common bacterial infection in CA patients with impaired cell mediated immunity
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-neutropenic CA patients pneumonia is often caused by gram neg bacteria early and fungal
infections (aspergillus) late
Neutropenia
-defined as neutrophil count less than 500 cells/ml, febrile neutropenia is defined as fever above
38.3 and neutropenia
-usually results from cytotoxic chemotherapy or radiation
-incidence and severity of infection is inversely proportional to the absolute neutrophil count
and directly proportional to the duration of neutropenia
-most common site of infection are lung, mouth and pharynx
-pneumonia and anorectal infections are more likely to have associated bacteremia
-bacteremia can occur without obvious source
-gram positive organisms are now the leading cause of bacterial infection in these patients
-aspergillus and candida are most common fungal infections in CA patients with fever and
neutropenia
-fever is frequently the only sign of infection in neutropenic patients
-work up of febrile neutropenia should include meticulous search for infection
-Management: initiate broad spectrum antibiotics with fever or in afebrile neutropenic patients
with any sign or symptom of infection
-amphotericin B is drug of choice for treatment of invasive fungal infection
-limit use of cell stimulation therapy (granulocyte colony-stimulating factor) to high risk
neutropenic patients: ie elderly, patient with severe sepsis, multiorgan failure or recurrent
febrile neutropenia
-disposition based on high risk vs low risk patients: high risk patients include inpatient when
fever occurs, comorbid medical conditions, uncontrolled cancer, acute leukemia, organ failure,
hemodynamically unstable, pneumonia
Diabetes
-predisposed to infection because of defect in immune functions, vascular insufficiency,
neuropathy that leads to wound neglect and excess substrate for bacterial and fungal growth
-neutrophil and macrophage functions are impaired, exacerbated in hyperglycemia and
improved with tight glycemic control
-cellular and humoral immunity normal or only minimally affected
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-infections with increased frequency include rhinoncerbral zygomycosis (formerly
mucormycosis), malignant otitis externa from pseudomonas, emphysematous cystitis,
fournier’s, and foot infections with osteo
Alcoholism and Cirrhosis
-predisposes to infection through direct suppression, alterations in blood flow, depression of
mental status and delay in seeking medical care
-in cirrhosis there is deficient hepatic clearance and killing of bacteria and splenic hypofunction
-alcoholics have increased incidence of oropharyngeal colonization with gram negative bacteria
and are more likely to aspirate
-common infections include spontaneous bacteremia and sepsis by e. coli, klebsiella, salmonella
Renal Failure
-infections cause up to 20% of all deaths among renal failure patients and 2nd most common
cause of mortality after CAD
-vascular access sites and numerous immune system defects are responsible
-CKD leads to generalized immune hyporesponsiveness; humeral immunity is affected and
results in deficient production of certain IgG and poor response to vaccinations
-watch for peritonitis in patients getting peritoneal dialysis; 2/3 of patients have this in the first
year of PD
Splenectomy/Hyposplenia/Functional Asplenia
-most important organ in the reticuloendothelial system and primary site of IgM synthesis
-also results in decreased production of neutrophils, natural killer cells and immunomodulating
cytokines
-principle site of clearance of strep pneumoniae from blood; so predisposes to overwhelming
pneumococcal infections
-also fulminating infection with other encapsulated organisms (h. influenzae, n. meningitidis and
canocytophaga canimorsus after dog bites) and gram neg bacilli
-infections with babesia microti transmitted by tick bites in US usually result in severe and often
fatal hemolysis
-overwhelming sepsis in post-splenectomy patients is rare but more common in children,
greatest risk in children younger than 2
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-patients with splenectomy from hematologic disorders are at higher risk for infection than
patients with splenectomy from trauma
-overwhelming post splenectomy infections usually have no obvious source
-pneumococcal vaccination is very important as well as H. influenzae, N. meningitidis, and flu
Immunosuppressive Therapy
-include steroids and other immunosuppressive medications
-high dose steroids alter function of neutrophils, monocytes and lymphocytes as well as
suppress inflammation
-also cause profound depression of cell mediated immunity
-most common infections occurring in patients on steroids are usually by pyogenic bacteria (s.
aureus, streptococci and gram neg bacilli)
Immune Related Diseases/Disorders
Rheumatoid Arthritis
-associated with polyarticular joint pain
-most commonly affects women: related to HLA-DR 4 haplotype
-most commonly affects the hand (MCP and PIP joint), then wrist and elbow
Lupus
-associated with symmetric polyarticular joint pain
-multisystem inflammatory disorder mediated by autoantibodies, course is highly variable, drug
induced lupus is usually reversible
-mainly women 15-40, small and large joints affected
-associated with the butterfly rash
-diagnosis: 4/11 criteria from pneumonic 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
-drugs that induce lupus: HIPPS: hydralazine, INH, phenytoin, procainamide, sulfonamides
-treatment: nsaids for pain, steroids for acute flares, immunosuppressive therapy
Reiter’s Syndrome – Can’t see, can’t pee, can’t climb a tree
-asymmetric polyarticular joint pain
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-usually proceeded by infection with chlamydia, shigella or salmonella
-young males 15-35: with HLA-B27 antigen
-Classic triad: urethritis, conjunctivitis and arthritis
-oligoarthritis develops usually 1-6 weeks following urethritis usually chlamydia infections
-weight bearing joints of lower extremity most commonly affected, must differentiate from
gonococcal arthritis
-treatment: Abx for urethritis targeted against chlamydia and gonorrhea, recurrent ocular
inflammation may require immunosuppressants, NSAIDs for arthritis
Raynaud’s Disease
-vasospasm of distal small arteries
-characteristic 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 headache, scalp
tenderness, vision changes, jaw claudication, diagnosis is from temporal artery biopsy, person
with symptoms and ESR >50 start steroids to prevent irreversible blindness
-Takayasu’s arteritis: involves aorta and major branches, presents with finger ischemia and arm
claudication, diagnosis is aortic arch arteriogram, treatment is prednisone
-polyarteritis nodosa: skin ulcers (shin), nephritis, mesenteric ischemia, diagnosis can be biopsy
of ulcers or kidneys, treatment prednisone or cyclophosphamide
-Bechet disease: recurrent painful oral and genital ulcers, diagnosis is biopsy, treatment
prednisone or immunosuppressants
Allergy
-4 types of hypersensitivity reactions
1. anaphylactic: IgE mediated degranulation of mast cells, ie anaphylaxis
2. cytotoxic: IgG or IgM antibodies react with cell antigens and activate complements
ie. Autoimmune hemolytic anemia, goodpasture
3. Immune complex: immune complex deposition and subsequent complement
activation, ie: serum sickness, SLE, RA
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4. cell-mediated: activated T-cells against cell surface bound antigens, ie contact
dermatitis
Angioedema
-edema of deeper layers of skin that is nonpruritic but can cause burning, numbness or pain
-drug induced angioedema
-ACE-inhibitors: not IgE associated, antihistamines and steroids haven’t shown clear
benefit, treatment includes possible racemic epi and airway establishment
-Hereditary angioedema (HAE): C1-esterase inhibitor deficiency, treatment is once again
airway management but also frozen plasma, possible high dose epi and danazol and
stanozolol
Anaphylaxis and Anaphylactoid Reactions
-IgE mediated, immediate hypersensitivity reaction to antigen
-abrupt onset of symptoms with release of chemical mediators in sensitized patient and
involving two or more organ systems
-patients on beta-blockers tend to have more severe reactions
-symptoms include: lump in throat, urticaria or warm flushing to skin, N/V/D and crampy
abdominal pain, full blown anaphylaxis includes hypotension, wheezing and pulmonary edema
-most serious reactions occur within minutes of exposure to antigen but can reoccur within 4-8
hours
-anaphylactoid reactions: direct release of mediators (IV dye, ASA, NSAIDs, codeine are
commonly implicated agents), do not require prior exposure to agent and not immunologically
mediated, treatment is the same as anaphylaxis
-treatment: stop or remove offending agent, protect airway, GIVE EPI, H1 blockers, steroids and
consider glucagon for patients on b-blockers who a refractory to fluids and epi, nebs for
wheezing
-EPI dose: 0.3 ml IM 1:1000 concentration for mild to moderate may repeat doses up to 3 times,
for severe reactions 1-5 mL of 1:10,000 concentration IV over 10 minutes
-disposition is usually admission, if mild can discharge with 3 day course of steroids, Benadryl
and epipen
-mild anaphylaxis: no hypotension or signs of upper airway involvement, rapid and complete
response to ED treatment, 6 hour observation without reoccurrence, safe discharge with
responsible caretaker who can closely observe
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Erythema Multiforme
-more severe variant of an urticarial reaction
-Iris or target lesions: red, raised and multi-shaped with clear centers, non-pruritic
-drugs that are frequently the cause: PCN, sulfa, cephalosporins, tetracyclines, phenytoin
Stevens-Johnson Syndrome
-severe, potentially fatal form of erythema multiforme
-characterized by bullae, mucus membrane lesions and multisystem involvement
-long acting sulfonamindes have been implicated (Bactrim), herpes simplex is another common
cause
Jarish-Herxheimer Reaction
-febrile reaction to parasitic or bacterial antigens that are liberated when the organisms are
destroyed from antibiotic therapy
-occurs 2-12 hours after antibiotic initiation, lasts less than 48 hours
-treatment is supportive, including antipyretics and occasionally steroids
Adverse Food Reactions – Direct Histamine Release
-can cause flushing, bronchospasm, urticarial and hypotension
-Sulfites (preservatives): found in packaged salads, shrimp, dried fruit, gelatin, pickles, sausages,
cheeses, wine and fruit juices, 5-10% of asthmatics are sensitive
-Tartrazine dye (yellow dye #5) and Monosodium glutamate (flavor enhancer) also can cause
hypersensitivity reactions
-Scombroidosis: food toxins from spoiled salt water fish, have peppery taste at time of ingestion,
cause flushing, urticarial, HA, vomiting/diarrhea, but usually not bronchospasm or hypotension
-“Chinese restaurant syndrome” most common cause because food contains most or all of
inciting agents (allergens, preservatives, color additives, flavor enhancers and toxins)
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