Immunologic and Rheumatologic Disorders
Anaphylaxis
Kimberly L. DiMaria
Cheryl N. Bartke
Background
Anaphylaxis occurs most commonly among children and adolescents.
Although the incidence of allergies and severe allergic reactions is on the rise, the estimated lifetime prevalence of anaphylaxis rate remains low at 0.05% to 2%.
Fatal cases of anaphylaxis are rare.
Definition
A potentially life-threatening systemic reaction to an allergen or trigger that primarily affects the mucocutaneous, hemodynamic, and respiratory systems.
Etiology
Most common triggers are food (e.g., eggs, shellfish, nuts), medications (e.g., antibiotics, nonsteroidal anti-inflammatories), and stinging.
Can occur through a variety of mechanisms, which are classified into the following categories:
Immunologic IgE-mediated/IgE-dependent/type I hypersensitivity reaction.
Immunologic non-IgE-mediated/IgE-independent.
Nonimmunologic/direct mast cell activation.
Idiopathic.
An allergen, such as radiocontrast, can precipitate an anaphylactic response through more than one mechanism, either an IgE-mediated response or a direct mast cell activation (i.e., causing histamine release).
Regardless of the mechanism, the clinical manifestations and initial management are identical.
Pathophysiology
Antigen-specific IgE is formed when an individual who is genetically susceptible is exposed to an allergen or trigger.
When that person is subsequently exposed to the same allergen, mast cell activation occurs rapidly because the antigen-specific IgE has already bound to the mast cells via IgE receptors, making the cascade of inflammatory reactions rapid.
Activation of mast cells and basophils triggers a rapid release of various inflammatory and newly formed mediators, including histamine, tryptase, leukotrienes, prostaglandins, platelet-activating factor, and various cytokines.
Mediators affect various target organs, including the heart, lungs, vasculature, gastrointestinal tract, and skin.
Heart rate, myocardial contractility, coronary blood flow, and electrical conduction through the sinoatrial and atrioventricular nodes are affected by the release of histamine and platelet-activating factor, causing decreased cardiac output and possible myocardial ischemia.
Bronchospasm and increased mucus production in the lungs can occur as a result of mediator release.
Vasodilation and increased vascular permeability lead to hypotension, distributive shock, and eventually impaired oxygen delivery.
Increased vascular permeability of the airways and intestinal tract causes laryngeal edema and gastrointestinal upset.
Mucocutaneous symptoms of flushing, angioedema, urticaria, and pruritus occur as a result of histamine release.
Clinical Presentation
Rapid onset: minutes to hours.
Hives, itching, abdominal pain, emesis, stridor, wheezing, shortness of breath, laryngeal edema, hypotension, and shock.
If not treated promptly, can lead to cardiorespiratory collapse and death.
Diagnostic Evaluation
Clinical diagnosis based on pathopneumonic symptomology.
No specific laboratory test can confirm the diagnosis of anaphylaxis.
However, plasma histamine levels, serum total tryptase levels, and serum IgE levels, if measured during or following an anaphylactic episode, are all elevated.
Skin testing is indicated to confirm allergens or triggers.
Care should be taken to ensure that testing is carried out in a health care facility that can manage anaphylaxis, should the patient develop a reaction to a trigger.
Management
ABC assessment.
Additional key examination components include pulmonary, neurologic, and skin examinations, and frequent vital signs.
Discontinue exposure to trigger/allergen if possible (e.g., a patient receiving intravenous [IV] chemotherapy).
Epinephrine administration, intramuscular/subcutaneous; should not be delayed if anaphylaxis is suspected.
Delays in administration are associated with worse outcomes.
Administration should occur promptly on recognition of mild anaphylaxis symptoms; it is not necessary to wait until potentially life-threatening symptoms develop.
0.01 mg/kg of 1:1,000 (1 mg/mL) into vastus lateralis muscle.
Maximum dose: 0.3 mg for children; 0.5 mg for adults.
If possible, inject with an autoinjector.
Epinephrine is the only effective treatment for anaphylaxis. It will decrease laryngeal edema, treat hypotension and shock, cause bronchodilation, and increase cardiac output by increasing heart rate and myocardial contraction.
There is no absolute contraindication of epinephrine administration for treatment of anaphylaxis.
Repeat the dose every 5 to 15 minutes as needed.
An estimated 20% of patients will require multiple doses of epinephrine.
May consider initiating IV epinephrine infusion.
Place patient in a recumbent or supine position with lower extremities elevated above the heart.
Administer oxygen; secure airway if necessary.
Obtain IV access and administer 0.9% normal saline.
30 to 40 mL/kg often required to treat hypotension.
Consider administration of adjunctive medications after epinephrine administration.
H1-antihistamine: diphenhydramine.
Nebulized β-agonist: albuterol.
Glucocorticoids: methylprednisolone IV or prednisone PO.
H2-antihistamine: ranitidine.
PEARLS
The key to successful management of anaphylaxis is the prompt recognition of the signs and symptoms and the administration of epinephrine.
If in doubt about whether or not a patient is experiencing an allergic/anaphylactic reaction, administer epinephrine.
Symptoms of anaphylaxis are variable, depending on the individual. Additionally, the same person may have different manifestations of anaphylaxis from one episode to another.
Providers should consider mastocytosis or clonal mast cell disorder as an underlying diagnosis for idiopathic anaphylaxis.
Immunodeficiencies
Megan Trahan
Definition
A group of genetic disorders that affect components of innate and adaptive immune systems and ultimately lead to susceptibility to infection.
Etiology/Types
Humoral.
Isolated immunoglobulin deficiency (IgM, IgA, or IgG subclass).
X-linked agammaglobulinemia.
Common variable immunodeficiency.
Transient hypogammaglobulinemia of infancy.
Hyper-IgM syndrome.
Cellular.
22q11.2 Deletion syndrome.
Combined antibody and cellular defects.
Severe combined immunodeficiency (SCID).
Wiskott-Aldrich syndrome.
Ataxia telangiectasia syndrome.
Phagocytic.
Chronic granulomatous disease (CGD).
Hyper-IgE syndrome.
Leukocyte adhesion deficits.
Complement.
Early complement defect (C2, C3, or C5).
Late complement defect.
Pathophysiology
Humoral: antibody production or function.
X-linked, autosomal recessive, or autosomal dominant inheritance, if known.
Cellular.
22q11.2 Deletion: t-cell deficiency secondary to thymic aplasia or hypoplasia.
Combined antibody and cellular.
SCID: multiple subtypes, some deficiency of T cells, B cells, and/or natural killer cells.
Autosomal recessive inheritance.
Phagocytic.
Oxidative dysfunction of polymorphonuclear leukocytes and monocytes, leading to inability to kill phagocytosed bacteria and fungi.
Complement.
Complement proteins may be absent or reduced in number.
Clinical Presentation
Common warning signs of primary immunodeficiency (Table 17.1).
In addition to infection, it may present with autoimmune diseases or lymphoid malignancy.
Evaluate for syndromes associated with primary immunodeficiency (e.g., 22q11 deletion [DiGeorge syndrome] or ataxia telangiectasia).
TABLE 17.1 Warning Signs of Primary Immunodeficiency
10 Warning Signs of Primary Immunodeficiency
≥4 new ear infections within 1 y
Recurrent, deep skin or organ abscesses.
≥2 sinus infections within 1 y
Persistent thrush in mouth or fungal infection on skin.
≥2 mo on antibiotics with little effect
Need for IV antibiotics to clear infections.
≥2 pneumonias within 1 y
≥2 deep-seated infections including septicemia.
Failure of an infant to gain weight or grow normally
A family history of primary immunodeficiency.
Adapted from Jeffery Modell Foundation. (2013). 10 warning signs of primary immunodeficiency. Retrieved from http://www.info4pi.org/aboutPI/index.cfm?section=aboutPI&content=warningsigns
Evaluate immune organs: tonsils, spleen, and lymph nodes.
Specific disease types and common presentations.
Humoral: sinopulmonary infections with encapsulated organisms.
Combined (SCIDs): failure to thrive, respiratory tract or gastrointestinal infections, candidal skin infections, Pneumocystis jiroveci pneumonia.
Phagocytic (CGD): infection with catalase-positive organisms (Escherichia coli, Pseudomonas, Klebsiella, Serratia, Salmonella, Candida, and Aspergillus).
Complement.
Early complement defects: sepsis.
Late complement defects: Neisseria infections.
Diagnostic Evaluation
Complete blood count (CBC): evaluate for anemia, thrombocytopenia, lymphopenia, or neutropenia.
Quantitative immunoglobulins (IgG, IgA, IgM, IgE).
Total protein and albumin.
Low total protein with normal albumin suggests immunoglobulin deficiency.
Antibody titers to vaccinations.
Complement activity (CH50, C3, and C4).
Nitroblue tetrazolium dye test: evaluate for CGD.
Management
Depends on specific immunodeficiency.
Treat infection with appropriate antimicrobial based on suspected or confirmed organism.
Administer leukocyte-poor Cytomegalovirus (CMV)-negative blood when blood product administration is necessary.
Consider postexposure prophylaxis for varicella zoster.
Avoid live virus vaccines.
General Treatment
Humoral.
IV immunoglobulins (IVIG) or subcutaneous immunoglobulin.
Antibiotic prophylaxis.
Do not require vaccines as they cannot make antibodies.
Cellular: bone marrow transplant depending on severity.
Combined antibody and cellular.
Strict isolation.
Bone marrow transplant.
IV immunoglobulin (IVIG).
Pneumocystis prophylaxis (e.g., trimethoprim-sulfamethoxazole).
Phagocytic.
Treat infection.
Trimethoprim-sulfamethoxazole prophylaxis.
Recombinant gamma interferon.
Complement.
Prevention of infection with vaccines.
Prompt treatment of infection.
Juvenile Idiopathic Arthritis
Jan A. Odiaga
Background
Juvenile idiopathic arthritis (JIA) encompasses a complex group of disorders comprising several clinical entities with the common feature of arthritis.
Each subtype of JIA is characterized by a different mode of presentation, disease course, and outcome.
Definition
The diagnosis of JIA requires the persistence of arthritis for >6 weeks in a child <16 years of age in whom there is no other identified cause for arthritis.
Currently, seven subtypes have been identified by stratification criteria.
Pathophysiology
Underlying cause and pathogenesis of JIA remain unclear.
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