IMMUNE SYSTEM
Primary lymphoid organs—development of lymphocytes: Bone marrow, fetal liver, and spleen. Thymus: maturation of T cells.
Secondary lymphoid tissue—sites of antigen recognition: Lymph nodes, spleen, mucosal-associated lymphoid tissues (MALT), and gut-associated lymphoid tissues (GALT).
Maternal serum antibodies (immunoglobulin G [IgG]) transferred across the placenta protect the infant from birth until approximately 6 months of age, and totally disappear by 12–18 months of age.
Maternal antibodies (IgA) are transferred to the child’s intestinal tract through breast milk.
A child’s IgG antibodies begin developing between 6 months and 1 year of age.
Children under the age of 2 years develop strong immune response to polysaccharide antigens in a vaccine (Haemophilus influenzae, pneumococcal) if they are conjugated to a protein carrier.
Transplacental antibodies protect neonates against chickenpox, measles, mumps, and rubella, but not chlamydia, gonorrhea, or group B Streptococcus.
First immunoglobulin to appear in the bloodstream after the initial exposure to an antigen (primary antibody response): IgM
Secretory antibody response: IgA
Major antibody to protein antigens: IgG
HYPERSENSITIVITY REACTIONS
See Table 9-1 for types of hypersensitivity reactions.
Urticaria (hives): Pale or reddened irregular, elevated itchy patches of skin.
Angioedema: Giant wheals caused by localized dilatation and ↑ permeability of the capillaries in the deep dermis.
Vesicle: A collection of fluid underneath epidermis = blister < 5 mm in diameter
Bulla: Blister > 5 mm in diameter with thin walls.
Anaphylaxis
DEFINITION
A severe and potentially life-threatening systemic allergic IgE-mediated reaction caused by release of mediators from tissue mast cells and blood basophils.
TABLE 9-1. Types of Hypersensitivity Reactions
ETIOLOGY
Foods: Milk, egg, peanuts, shellfish.
Drugs: β-lactam antibiotics, sulfa.
Vaccine, immune globulin, blood products.
Latex (gloves, Foley catheters, and endotracheal tubes).
Insect stings.
SIGNS AND SYMPTOMS
Abrupt onset and rapid progression within 5–30 minutes.
Generalized pruritus, urticaria, tearing, angioedema.
Flushing, dizziness.
Vomiting, abdominal cramps.
Respiratory symptoms: Upper airway obstruction (laryngeal angioedema), bronchospasm.
Hypotension, shock.
Anaphylactoid Reaction
Clinically similar to anaphylaxis
Not IgE mediated
Does not require previous exposure
DIAGNOSIS
History of exposure.
Clinical presentation.
Serum tryptase (at 1, 4, and 8 hours).
See Figure 9-1 for National Institute of Allergy and Immunologic Disease/Food Allergy and Anaphylaxis Network diagnostic criteria.
Risk factors for severe anaphylactic reaction:
Asthma
β blockade
Adrenal insufficiency
TREATMENT
Airway, breathing, circulation (ABC).
Epinephrine (1:1000–0.01 mL/kg subcutaneously). Minimum dose: 0.1 mL. Maximum dose: 0.3. mL.
Diphenhydramine 1–2 mg/kg IV, IM, or PO q4–6h.
Cimetidine 5–10 mg/kg IV q6h (refractory cases).
Admit if upper airway obstruction, significant bronchospasm, blood pressure instability.
Prophylaxis:
Avoid
ID bracelet
Self-injectable epinephrine (Epi-pen).
Urticaria (Hives)
DEFINITION
Allergic (IgE-mediated), or nonallergic (nonimmunological: physical, chemical)–mediated skin lesions.
ETIOLOGY
Infections:
Viruses (influenza, enterovirus, infectious mononucleosis, hepatitis).
Bacteria (group A β-hemolytic streptococci).
Medications (penicillin, cephalosporin, phenytoin, barbiturate, aspirin).
Foods.
Insect stings.
Autoimmune diseases.
Malignancies.
Viral infections are the most common causes of urticaria in children.
SIGNS AND SYMPTOMS
Raised pale and pink pruritic areas of annular or serpiginous pattern.
Rash is often migratory, waxing and waning.
FIGURE 9-1. Visual representation of National Institute of Allergy and Immunologic Disease/Food Allergy and Anaphylaxis Network diagnostic criteria.
(Reproduced, with permission, from Manivannan V, Decker WW, Stead LG, Li JT, and Campbell R. Intl J Emerg Med, 2009.)
DIAGNOSIS
Clinical; no tests needed.
TREATMENT
Avoiding the precipitating cause.
Epinephrine (1:1000 at 0.01 mg/kg) if urticaria is severe.
Diphenhydramine.
Serum Sickness
For the past 2 weeks, a 6-year-old boy has had puffy eyelids on awakening and swelling of the feet and abdomen in the afternoon. He complains of joint aches and on-and-off fever. His history includes a sting by a yellow jacket. Physical examination is significant for generalized lymphadenopathy. Urinalysis shows protein 3+ and ESR is 35. Think: Serum sickness.
DEFINITION
Type III hypersensitivity reaction; does not require prior sensitization.
PATHOPHYSIOLOGY
Antigen-antibody complexes form deposits in blood vessels, particularly in joints and glomeruli of the nephrons, where they activate the classical complement pathway, resulting in vasculitis.
ETIOLOGY
Antigout medications: Allopurinol, gold salts.
Antimicrobials: Cefaclor, penicillin, griseofulvin, sulfonamides.
Antiarrhythmics: Quinidine, procainamide.
Antihypertensives: Captopril, hydralazine.
Thyroid medications: Thiouracil, iodides.
Other medications: Barbiturates, phenytoin.
Serum/blood products, venoms.
SIGNS AND SYMPTOMS
Onset 1–3 weeks after initial exposure to an offending agent.
Fever, arthralgia, lymphadenopathy, and rash (serpiginous and urticarial or polymorphous).
Frequent facial edema.
Rare arthritis, cardiovascular and renal involvement.
Symptoms persist 7–10 days and resolve spontaneously.
DIAGNOSIS
Clinical.
Low levels of C3, C4 (complement components), and CH50.
TREATMENT
Withdrawal of the offending agent.
Drug Reaction
DEFINITION
Abnormal immunologically mediated hypersensitivity responses.
Relatively rare.
ETIOLOGY
Potentially any drug can cause drug reaction.
PATHOPHYSIOLOGY
Type I (IgE mediated): Penicillin, cephalosporin.
Type II (cytotoxic antibody mediated): Penicillin—hemolytic anemia; quinidine—thrombocytopenia.
Type III (immune complex mediated): Penicillin, sulfonamides, cephalosporin.
Type IV (cell mediated): Contact dermatitis—Neosporin.
Most common causes of drug reactions: penicillin, sulfonamide.
CLINICAL CRITERIA
Reactions do not resemble pharmacologic action of the drug.
Similar to those that may occur with other allergens.
Timing: 7–10 days.
Reproduced by minute doses.
Discontinuation may result in resolution.
SIGNS AND SYMPTOMS
Mild rash to anaphylaxis.
Fixed drug eruptions: Recur at the same site after each administration of causative drug (sulfonamides are the most common).
Drug Reactions
Most are afebrile.
Eruption may worsen before improving after discontinuation of the drug.
DIAGNOSIS
Eosinophilia is a clue but is not diagnostic.
Skin test is available for penicillin. It is indicated for the patients with a history of penicillin-associated anaphylaxis, urticaria, or serum sickness.
Radioallergosorbent test (RAST).
The most common site for the manifestation of drug reactions is the skin.
DISPOSITION
Discontinue likely offending agent.
Admit if:
Stevens-Johnson syndrome.
Toxic epidermal necrolysis.
Severe drug reaction.
Respiratory distress.
Penicillin Allergy
TYPES
Wide variety of allergic reactions:
Type I: Anaphylaxis.
Type II: Hemolytic anemia.
Type III: Serum sickness.
AMPICILLIN/AMOXICILLIN RASH
Not urticaria, seen with infectious mononucleosis.
Hyperuricemia.
Food Allergy/Sensitivity
PATHOPHYSIOLOGY
Most of the true hypersensitivities to food products are IgE mediated. IgE binds to mast cells, resulting in the release of histamine and other mediators. Most common triggers are peanuts, shellfish, and eggs.
Early presentation in life. Only ∼5% of children under the age of 4 years have food hypersensitivity. It is seen even less frequently in older children.
Most adverse reactions to food do not have an immunologic basis.
Nonimmunologic food intolerances are common, like enzyme deficiencies (lactase deficiency, vomiting, diarrhea).
Most common food allergies:
Peanut
Shellfish
Eggs
SIGNS AND SYMPTOMS
IgE-mediated hypersensitivity reactions start within minutes of the responsible food intake, and often are associated with urticaria, edema, and anaphylaxis (see below).
Allergic enterocolitis of infancy with vomiting and diarrhea (becomes bloody) represents hypersensitivity to cow’s milk proteins, but is not IgE mediated. It → failure to thrive. Half of infants reacting to the cow’s milk protein also react to soy protein. Note early presentation in the first month of life.
Gluten-sensitive enteropathy is also a non-IgE-mediated food hypersensitivity (celiac disease), and also → failure to thrive. Gradual onset of symptoms in the second half of infancy, when the child starts to eat grains (cereal) containing gluten protein.
TREATMENT
Avoidance of offending agent.
Stevens-Johnson Syndrome (SJS; Erythema Multiforme Major)
DEFINITION
Extreme variant of erythema multiforme (EM) with systemic toxicity and involvement of the mucous membranes.
ETIOLOGY
Drugs: Sulfonamides and anticonvulsants.
Mycoplasma pneumoniae, herpes simplex virus.
Mild EM does not progress to SJS.
SIGNS AND SYMPTOMS
Prodromal phase (1–14 days): Fever, headache, malaise.
Mucosal involvement:
Exudative conjunctivitis.
Oral erosions on the palate and gingivae.
Urethritis, vaginitis.
Skin involvement: Target lesions—annular, with pink halo surrounding a pale halo and erythematous center. May have central blistering. Palms and soles are involved.
Nikolsky’s sign: Separation of normal epidermis at the basal layer caused by sliding finger pressure (“rubbed off” line).
See Dermatologic Disease chapter.
The oral cavity is almost always involved in erythema mulitforme major.
DIAGNOSIS
Clinical criteria: Cutaneous lesion plus at least two mucosal surfaces involved.
Skin biopsy is not indicated (would show perivascular mononuclear cell infiltrate).
TREATMENT
Hospitalization for supportive care.
Intravenous (IV) hydration.
Topical steroids and anesthetics as needed.
IMMUNODEFICIENCIES
Primary (congenital) immune deficiencies (Table 9-2) present at different ages, depending on category of disorder.
When evaluating a child with recurrent infections, pay attention to the following:
Age of onset: T-cell deficiency presents in the first 3–4 months of life, whereas B-cell disorders present after 6 months of age, when maternal antibodies disappear.
TABLE 9-2. Combined and Primary T-Cell Immune Deficiencies
X-linked inheritance: Similar case in a male relative (Bruton’s, Wiskott-Aldrich, chronic granulomatous disease [CGD]).
Clinical features:
Failure to thrive (FTT): Severe combined immunodeficiency (SCID).
Hypertelorism, hypocalcemia, truncus arteriosus: DiGeorge syndrome.
Absence of tonsils and lymphatic nodes: Bruton’s agammaglobulinemia.
Coarse features, eczema, lax joints, scoliosis: Job syndrome.
Workup: Thymus shadow on chest x-ray, antibody titers (response to vaccination), absolute lymphocyte count (ALC).
Sites of infection:
Phagocytes (CGD): Sinopulmonary and soft tissues.
Immunoglobulin deficiencies: Sinopulmonary and gastrointestinal (Giardia).
T cells: Disseminated (mycobacteria, varicella-zoster virus).
Types of microorganisms: Intracellular infections in T-cell disorders (viruses, mycobacteria, Pneumocystis); Neisseria infections in late complement deficiency.
Severe Combined Immunodeficiency (SCID)
A 4-month-old female just diagnosed with failure to thrive (FTT) presents with respiratory distress. On physical examination, she has a temperature of 101°F (38.3°C), RR 70 breaths/min, and oxygen saturation 91% (on room air). Oral thrush and bilateral rhonchi were present. There is no lymphadenopathy. Her white blood cell count is 16.2, 83% neutrophils, 11% monocytes. Chest x-ray shows diffuse bilateral interstitial infiltrates. Think: PCP.
Infection with opportunistic organisms such as PCP is common in infants with SCID. Absence of lymph nodes in an infant with FTT in the first few months of life is suggestive of SCID. Oral thrush, extensive diaper rash, and failure to thrive are the prominent features.
Onset of SCID at 3 months of age:
No palpable lymph nodes
Opportunistic infections
Failure to thrive
DEFINITION
Abnormalities of both humoral and cellular immunity.
ETIOLOGY
A group of genetic abnormalities that result in severe T-cell depletion (or dysfunction) and B-cell dysfunction (eg, enzyme deficiencies → defect in stem cell maturation).
Adenosine deaminase (ADA) deficiency: One third of all SCID cases.
SIGNS AND SYMPTOMS
Presents within first 3 months with diarrhea, pneumonia, otitis, sepsis, FTT, and skin rashes.
Frequency and severity of infections.
Persistent infection with opportunistic organisms (Candida, mycobacteria, herpes viruses, CMV, PCP).
Absent lymphatic nodes, hypoplastic thymus.
DIAGNOSIS
Lymphopenia: ALC (absolute lymphocyte count) < 500.
↓ serum IgG, IgA, and IgM.
Low or no T and B cells.
TREATMENT
Aggressive antimicrobial treatment of even mild infections.
Recombinant ADA is available for replacement therapy.
Bone marrow transplantation (BMT).
PROGNOSIS
Death within first 2 years if untreated.
Measures to be taken in SCID:
Protective isolation
Irradiation of all blood products
Letterer-Siwe Disease
An 18-month-old female presents with two “bumps on the head.” Physical examination shows weight below 3rd percentile; two palpable masses on the scalp; and scaly, greasy patches of rash over the scalp, eyebrows, neck, and in the ear canals; generalized lymphadenopathy; and hepatosplenomegaly. WBC: 5.6, Hb 8.4, platelet count 76. Lateral skull radiograph shows two well-defined lytic lesions. Think: Letterer-Siwe disease.
Letter-Siwe disease is the most severe form of Langerhans’ cell histiocytosis. Patients with this disease typically present with a scaly seborrhea and eczematous rash that involves the scalp, ear canals, abdomen, and intertriginous areas of the neck and face. Typical age of presentation is under 2 years. There is a potential for pancytopenia because of hematopoietic involvement.
DEFINITION
The most severe form of Langerhans’ cell histiocytosis (LCH).
Manifestation of complex immune dysregulation.
SIGNS AND SYMPTOMS
Skeleton involved (80%): Skull, vertebrae (eosinophilic granuloma, lytic lesions).
Skin (50%): Seborrheic or eczematoid dermatitis in a child of < 2 years of age
Lymphadenopathy (33%).
Hepatosplenomegaly (20%).
Letterer-Siwe disease:
Lytic lesions
Lymphadenopathy
Eczema
Anorexia, FTT
Exophthalmos.
Pituitary dysfunction: Growth retardation, diabetes insipidus.
Systemic manifestations: Fever, weight loss, irritability, FTT.
Bone marrow suppression: Anemia, thrombocytopenia, neutropenia.
LAB
Complete blood count (CBC).
Liver function tests (LFTs).
Coagulation profile.
Chest x-ray.
Skeletal survey.
Urine osmolality.
Tissue biopsy (skin or bone lesions).
TREATMENT
Treatment directed at arresting the progression of lesion (low-dose local radiation).
Systemic multiagent chemotherapy.
Spontaneous remission.
DiGeorge Syndrome
A 2-month-old infant with congenital heart disease and cleft palate is hospitalized with cough and tachypnea. He has a history of a seizure episode. Chest x-ray shows diffuse infiltrates and no thymic shadow. Serum calcium is 6.5 mg/dL. Think: DiGeorge syndrome.
DiGeorge syndrome is a T-cell deficiency that results from failure of development of the third and fourth pharyngeal pouches, which are responsible for the development of thymus and parathyroid glands. These result in lack of T-cell-mediated immunity, tetany, and congenital defects of the heart and great vessels. It is important to recognize this diagnosis because without treatment it is fatal.
PATHOPHYSIOLOGY
Deletion in chromosome 22, resulting in a defect of development of the third and fourth pharyngeal pouches.
Phenotypical translation into midline defects of the heart, head, parathyroids, and thymus.
SIGNS AND SYMPTOMS
Dysmorphic features: Hypertelorism, cleft palate.
Congenital heart disease: Truncus arteriosus, interrupted aortic arch.
Hypoparathyroidism presents as hypocalcemic seizures (“tetany”).
Recurrent infections: depending on T-lymphocyte counts. Opportunistic infections (OIs) in severe cases.
CATCH 22
Cardiac abnormality (tetralogy of Fallot)
Abnormal facies
Thymic aplasia
Cleft palate
Hypocalcemia
(22 abmormality on the 22 chromosome)
DIAGNOSIS
Calcium level and parathyroid hormone.
T-cell count (variable).
Chest x-ray: No thymic shadow.
Echocardiogram.
Fluorescent in situ hybridization (FISH) test detects the 22q11.2 deletion.
TREATMENT
Thymic transplant if ALC < 100.
BMT is not an option because of high risk for graft-versus-host disease (GVHD).
Use irradiated blood products only.
Ataxia-Telangiectasia (AT)
DEFINITION
Autosomal-recessive disorder of DNA repair that presents as telangiectasias, ataxia, and variable extent of T-cell deficiency, with progressive loss of T helpers. Both humoral and cellular immunodeficiency.
Ataxia-telangiectasia:
Injected sclera
Ataxia
Lymphoma
SIGNS AND SYMPTOMS
Usually presents during first 6 years, wheelchair confinement by 10–12 years.
Earliest sign: Telangiectasias on the sclerae (misdiagnosed as “pink eye”).
Progressive cerebellar ataxia.
Chronic sinusitis, bronchiectases.
OIs.
↑ risk of malignancy (lymphomas, leukemia).
LAB
Absence of antibodies after vaccination.
Low IgA and IgM.
T4 lymphocytes decline over time.
↑ serum α-fetoprotein.
TREATMENT
Supportive therapy.
Improve pulmonary function.
Prophylaxis of OIs.
Chronic Mucocutaneous Candidiasis (CMC)
DEFINITION
T-cell dysfunction: Inability to recognize candidal antigens.
A heterogeneous group of disorders characterized by recurrent or persistent superficial candidal infections of the skin, nails, and mucous membranes.
SIGNS AND SYMPTOMS
Refractory thrush may extend to the esophagus.
Refractory severe diaper rash.
Angular cheilitis.
Nails thickened, significant edema and erythema of the surrounding periungual tissue.
Often associated with endocrinopathy: Hypo/hyperthyroidism, polyendocrinopathy.
TREATMENT
Systemic antifungals
Skin care
Wiskott-Aldrich Syndrome
A 10-month-old boy presents with oral thrush despite 10 days of treatment with nystatin. He had 4 episodes of otitis media. Physical examination shows oral thrush and multiple patches of eczema. Both tympanic membranes are dull. CBC shows the following: WBC 7.6, Hb 11.3, platelet count 97. His uncle died in infancy of infection. Think: Wiskott-Aldrich syndrome.
Wiskott-Aldrich syndrome is an X-linked recessive syndrome characterized by the triad of eczema, thrombocytopenia, and immunodeficiency. The initial manifestation usually is petechiae or bleeding in the first few months of life. Classic presentation is thrombocytopenia, eczema, and recurrent otitis media.
Wiskott-Aldrich syndrome:
Eczema
Thrmobocytopenia
↑ IgA/IgE
DEFINITION
X-linked-recessive disorder of cell cytoskeleton, presenting as eczema, thrombocytopenia (TCP), and ↑ susceptibility to infection.
SIGNS AND SYMPTOMS
Atopic dermatitis/eczema.
Thrombocytopenic purpura.
Recurrent infections in infancy: Pneumococcal (otitis, pneumonia), persistent thrush.
OIs: Pneumocystis jiroveci pneumonia (PCP).
Oral candidiasis at > 6 months of age should arouse suspicion for the presence of an immunodeficiency.
LAB
↓ gM.
↑ IgA and IgE.
Absence of antibodies after vaccination.
Common Variable Immunodeficiency (CVID)
DEFINITION
A group of disorders of T- and B-cell interaction and cytokine production, resulting in impaired IgM to IgG switch and in the absence of protective antibody titers (see Table 9-3).
Often (one fourth) familial.
Involves the formation of autoantibodies.
TABLE 9-3. B-Cell Disorders and Immunoglobulin Deficiencies
SIGNS AND SYMPTOMS
Two peak ages of onset: Children aged 1–5 years and 16–20 years old.
Lymphadenopathy, splenomegaly.
Association with autoimmune diseases: Inflammatory bowel disease (IBD), sprue-like syndrome, arthritis.
Lymphoid interstitial pneumonitis, granulomas on various organs.
↑ risk of malignancies: Non-Hodgkin lymphoma, gastric carcinoma.
Sinopulmonary infections: Pneumococcal, Mycoplasma.
Gastrointestinal (GI) infections: Giardia.
Bruton’s Congenital Agammaglobulinemia
DEFINITION
X-linked tyrosine kinase deficiency resulting in the arrest of B-cell maturation. Gene defect in Xq22.
Severe hypogammaglobulinemia.
Bruton’s agammaglobulinemia:
Male
No palpable lymph nodes
No tonsil
Respiratory and gastrointestinal infections
SIGNS AND SYMPTOMS
No tonsils.
No palpable lymphatic nodes.
Recurrent/chronic sinopulmonary (pneumococcal), GI (Giardia) infections.
↑ susceptibility to enteroviral meningoencephalitis.
DIAGNOSIS
Very low or absent mature B lymphocytes and all classes of immunoglobulins. No production of protective antibodies (negative titers).
Infants with Bruton’s agammaglobulinemia remain well for the first 6 months due to the presence of maternal IgG antibodies.
Selective IgA Deficiency
DEFINITION
Deficiency of IgA-predominant immunoglobulin on mucosal surfaces.
EPIDEMIOLOGY
Most common of the primary antibody deficiencies.
Selective IgA deficiency can → fatal anaphylaxis with blood (IVIG) infusion. IVIG is contraindicated.
SIGNS AND SYMPTOMS
Mostly respiratory tract infections.
Allergies.
Autoimmune diseases: IBD, arthritis.
DIAGNOSIS
IgA < 5 mg/dL.
Normal levels of other immunoglobulins and normal response to vaccination.
Normal cell-mediated immunity.
IgA is the major immunoglobulin within the upper airway.
Chédiak-Higashi Syndrome
DEFINITION
Autosomal-recessive syndrome caused by mutations of the lysosomal trafficking regulator gene, resulting in abnormal chemotaxis and fusion of intracellular granules.
Thymic hypo- or aplasia → a deficiency of functional T cells.
SIGNS AND SYMPTOMS
Recurrent skin infections and pneumonias (Staphylococcus aureus).
Partial oculocutaneous albinism.
Progressive peripheral neuropathy.
DIAGNOSIS
Giant gray granules in the cytoplasm of nucleated cells.
Leukopenia, neutropenia.
Chemotaxis test.
TREATMENT
Ascorbic acid has no effect.
Antibiotics for acute infections.
BMT (does not prevent or cure peripheral neuropathy).
Chronic Granulomatous Disease (CGD)
A 10-month-old male presents with a temperature of 101.6°F (38.7°C) and a 3 × 4-cm abscess of the left buttock. His WBC count is 19.9, 77% neutrophils. At the age of 5 months he had staphylococcal cervical lymphadenitis that required drainage. His uncle also had recurrent abscesses. Think: CGD.
Recurrent infections in the first year of life are usually the first symptom. Granulomatous lesions in the lungs, skin, and liver are common.
PATHOPHYSIOLOGY
Most common inherited disorder of phagocytosis, X-linked or auto-somal recessive.
Oxidase deficiency in neutrophils and macrophages = defect in generation of oxygen metabolites.
Chemotaxis and phagocytosis intact.
Inability to kill catalase-positive microorganisms: S aureus.
Impaired intracellular bactericidal activity is the definitive test for chronic granulomatous disease.
SIGNS AND SYMPTOMS
Presents in the first years of life.
Recurrent deep soft tissue abscesses and lymphadenitis.
Severe staphylococcal and Burkholderia cepacia pneumonia and lung abscess, pneumatoceles.
Osteomyelitis.
Hepatosplenomegaly (granulomas).
DIAGNOSIS
Nitroblue tetrazolium test.
Leukocytosis.
Hypergammaglobulinemia.
TREATMENT
Aggressive antimicrobial treatment of infection.
Surgical excision of abscesses.
Job Syndrome (Hyper-IgE)
A 10-year-old boy has a history of severe pneumonia with empyema at the age of 5 years. He is also allergic to pollens and animal dander. Now he has fever of 102.3°F (39.1°C). On examination, coarse facial features, eczematous patches on the extremities, and a tender 4 × 3-cm right anterior cervical lymphatic node is present. WBC is 24.7. Think: Job syndrome.
Job syndrome is hyperimmunoglobulinemia E with impaired chemotaxis. IgE level should be obtained. Characteristic findings include eczema, recurrent “cold,” staphylococcal skin abscesses, sinusitis, and otitis media.
Job syndrome:
Eczema
Eosinophilia
Lax joints
Staph infections
DEFINITION
Neutrophil chemotactic defect.
Autosomal dominant.
SIGNS AND SYMPTOMS
Recurrent staphylococcal infections.
Eczema.
Coarse facial features, lax joints.
DIAGNOSIS
IgE > 10,000 IU/mL.
Eosinophilia.
TABLE 9-4. Phagocytic and Chemotactic Disorder
TREATMENT
Penicillinase-resistant antibiotics.
BMT.
Complement Deficiency
A 16-year-old female presents with a second episode of meningococcal meningitis. Her CH50 is 78%. Think: C5–C9 deficiency.
Patients with complement deficiency are uniquely susceptible to meningococcal infection. Defects in terminal complement are associated with recurrent infections with Neisseria.
Meningococcal vaccination is the best way to protect a patient with complement deficiency.
COMPLEMENT
Complex system of nine serum proteins (C1–C9).
FUNCTIONS OF COMPLEMENT
Opsonization.
Bacteria cell lysis.
Facilitating chemotaxis.
ASSOCIATED DISEASES
C1q deficiency: Systemic lupus erythematosus (SLE).
C1 esterase inhibitor (C1 INH) deficiency: Hereditary angioedema.
C2 deficiency: Pneumococcal infections.
C5–C9 terminal complement deficiency: Neisserial infection.
Hypocomplementemia occurs in patients with lupus nephritis and poststreptococcal glomerulonephritis, but not in Henoch-Schönlein purpura or minimal change disease.
TABLE 9-5. Complement Deficiencies
DIAGNOSIS
CH50 screening test.
Asplenia
A 7-year-old African-American girl who just immigrated from Togo presents with fever of 104°F (40°C). Physical examination did not reveal any source of fever. There is no palpable spleen. Her WBC count is 28.2, Hct 27.1, and there are Howell-Jolly bodies in RBCs. Blood culture grew Streptococcus pneumoniae. Think: Sickle cell disease.
Patients with asplenia are at increased risk for the development of sepsis, most commonly due to S pneumoniae. Patients with sickle cell disease develop functional asplenia. Howell-Jolly bodies indicate hyposplenism.
Asplenia:
Howell-Jolly bodies
Encapsulated organism
DEFINITION
Absence of the functional spleen.
ETIOLOGY
Associated with some congenital syndromes.
Functional asplenia may be secondary to sickle cell disease (SCD) or other hemoglobinopathies.
Hyposplenia may be secondary to SLE, rheumatoid arthritis (RA), IBD, GVHD, nephrotic syndrome, or prematurity.
Splenectomy due to trauma, Hodgkin’s lymphoma, and hereditary spherocytosis.
DIAGNOSIS
↓ IgM antibodies, alternate complement pathway, and tuftsin.
↑ requirement for opsonic antibodies.
Howell-Jolly bodies in erythrocytes.
COMPLICATIONS
Sepsis with encapsulated organisms:
0–6 months: Gram-negative enteric (Klebsiella, Escherichia coli).
> 6 months of age: S pneumoniae, Haemophilus influenzae type B. Malaria and babesiosis are more severe.
TREATMENT
Penicillin prophylaxis.
Pneumococcal immunization, also H influenzae and meningococcal (vaccinations against encapsulated organisms).
Graft-versus-Host Disease (GVHD)
DEFINITION
Donor lymphocytes detect host as foreign.
Complication of BMT.
ETIOLOGY
Engraftment by immunocompetent donor lymphocytes in an immunologically compromised host.
PATHOPHYSIOLOGY
Donor T-cell activation by antibodies against host major histocompatibility complex antigens.
SIGNS AND SYMPTOMS
Acute: < 100 days:
Erythroderma.
Cholestatic hepatitis—abnormal LFTs.
Enteritis—diarrhea and cramps.
↑ susceptibility to infections.
Chronic: > 100 days:
Either:
Generalized skin involvement, or
Localized skin involvement and/or hepatic dysfunction and liver histologic evidence of chronic aggressive hepatitis, bridging necrosis, or cirrhosis
Or:
Involvement of the eye (“keratoconjunctivitis sicca” = dry eye).
Involvement of minor salivary glands or oral mucosa (dryness).
Involvement of any other target organ.
Requirements for the diagnosis of graft-versus-host disease:
Graft must contain immunocompetent cells.
Host must be immunocompromised.
Histocompatibility differences must exist.
TREATMENT
High-dose glucocorticoids.
Immunosuppressive therapy.
