First Aid for the Pediatrics Clerkship, 3 Ed.

Immunologic Disease

IMMUNE SYSTEM

Image Primary lymphoid organs—development of lymphocytes: Bone marrow, fetal liver, and spleen. Thymus: maturation of T cells.

Image Secondary lymphoid tissue—sites of antigen recognition: Lymph nodes, spleen, mucosal-associated lymphoid tissues (MALT), and gut-associated lymphoid tissues (GALT).

Image 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.

Image Maternal antibodies (IgA) are transferred to the child’s intestinal tract through breast milk.

Image A child’s IgG antibodies begin developing between 6 months and 1 year of age.

Image 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.


Image

Transplacental antibodies protect neonates against chickenpox, measles, mumps, and rubella, but not chlamydia, gonorrhea, or group B Streptococcus.

Image First immunoglobulin to appear in the bloodstream after the initial exposure to an antigen (primary antibody response): IgM

Image Secretory antibody response: IgA

Image Major antibody to protein antigens: IgG


HYPERSENSITIVITY REACTIONS

See Table 9-1 for types of hypersensitivity reactions.

Image Urticaria (hives): Pale or reddened irregular, elevated itchy patches of skin.

Image Angioedema: Giant wheals caused by localized dilatation and ↑ permeability of the capillaries in the deep dermis.

Image Vesicle: A collection of fluid underneath epidermis = blister < 5 mm in diameter

Image 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

Image

ETIOLOGY

Image Foods: Milk, egg, peanuts, shellfish.

Image Drugs: β-lactam antibiotics, sulfa.

Image Vaccine, immune globulin, blood products.

Image Latex (gloves, Foley catheters, and endotracheal tubes).

Image Insect stings.

SIGNS AND SYMPTOMS

Image Abrupt onset and rapid progression within 5–30 minutes.

Image Generalized pruritus, urticaria, tearing, angioedema.

Image Flushing, dizziness.

Image Vomiting, abdominal cramps.

Image Respiratory symptoms: Upper airway obstruction (laryngeal angioedema), bronchospasm.

Image Hypotension, shock.


Image

Anaphylactoid Reaction

Image Clinically similar to anaphylaxis

Image Not IgE mediated

Image Does not require previous exposure


DIAGNOSIS

Image History of exposure.

Image Clinical presentation.

Image Serum tryptase (at 1, 4, and 8 hours).

Image See Figure 9-1 for National Institute of Allergy and Immunologic Disease/Food Allergy and Anaphylaxis Network diagnostic criteria.


Image

Risk factors for severe anaphylactic reaction:

Image Asthma

Image β blockade

Image Adrenal insufficiency


TREATMENT

Image Airway, breathing, circulation (ABC).

Image Epinephrine (1:1000–0.01 mL/kg subcutaneously). Minimum dose: 0.1 mL. Maximum dose: 0.3. mL.

Image Diphenhydramine 1–2 mg/kg IV, IM, or PO q4–6h.

Image Cimetidine 5–10 mg/kg IV q6h (refractory cases).

Image Admit if upper airway obstruction, significant bronchospasm, blood pressure instability.


Image

Prophylaxis:

Image Avoid

Image ID bracelet

Image Self-injectable epinephrine (Epi-pen).


Urticaria (Hives)

DEFINITION

Allergic (IgE-mediated), or nonallergic (nonimmunological: physical, chemical)–mediated skin lesions.

ETIOLOGY

Image Infections:

Image Viruses (influenza, enterovirus, infectious mononucleosis, hepatitis).

Image Bacteria (group A β-hemolytic streptococci).

Image Medications (penicillin, cephalosporin, phenytoin, barbiturate, aspirin).

Image Foods.

Image Insect stings.

Image Autoimmune diseases.

Image Malignancies.


Image

Viral infections are the most common causes of urticaria in children.


SIGNS AND SYMPTOMS

Image Raised pale and pink pruritic areas of annular or serpiginous pattern.

Image Rash is often migratory, waxing and waning.

Image

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

Image Avoiding the precipitating cause.

Image Epinephrine (1:1000 at 0.01 mg/kg) if urticaria is severe.

Image Diphenhydramine.

Serum Sickness

Image

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

Image Antigout medications: Allopurinol, gold salts.

Image Antimicrobials: Cefaclor, penicillin, griseofulvin, sulfonamides.

Image Antiarrhythmics: Quinidine, procainamide.

Image Antihypertensives: Captopril, hydralazine.

Image Thyroid medications: Thiouracil, iodides.

Image Other medications: Barbiturates, phenytoin.

Image Serum/blood products, venoms.

SIGNS AND SYMPTOMS

Image Onset 1–3 weeks after initial exposure to an offending agent.

Image Fever, arthralgia, lymphadenopathy, and rash (serpiginous and urticarial or polymorphous).

Image Frequent facial edema.

Image Rare arthritis, cardiovascular and renal involvement.

Image Symptoms persist 7–10 days and resolve spontaneously.

DIAGNOSIS

Image Clinical.

Image Low levels of C3, C4 (complement components), and CH50.

TREATMENT

Withdrawal of the offending agent.

Drug Reaction

DEFINITION

Image Abnormal immunologically mediated hypersensitivity responses.

Image Relatively rare.

ETIOLOGY

Potentially any drug can cause drug reaction.

PATHOPHYSIOLOGY

Image Type I (IgE mediated): Penicillin, cephalosporin.

Image Type II (cytotoxic antibody mediated): Penicillin—hemolytic anemia; quinidine—thrombocytopenia.

Image Type III (immune complex mediated): Penicillin, sulfonamides, cephalosporin.

Image Type IV (cell mediated): Contact dermatitis—Neosporin.


Image

Most common causes of drug reactions: penicillin, sulfonamide.


CLINICAL CRITERIA

Image Reactions do not resemble pharmacologic action of the drug.

Image Similar to those that may occur with other allergens.

Image Timing: 7–10 days.

Image Reproduced by minute doses.

Image Discontinuation may result in resolution.

SIGNS AND SYMPTOMS

Image Mild rash to anaphylaxis.

Image Fixed drug eruptions: Recur at the same site after each administration of causative drug (sulfonamides are the most common).


Image

Drug Reactions

Image Most are afebrile.

Image Eruption may worsen before improving after discontinuation of the drug.


DIAGNOSIS

Image Eosinophilia is a clue but is not diagnostic.

Image Skin test is available for penicillin. It is indicated for the patients with a history of penicillin-associated anaphylaxis, urticaria, or serum sickness.

Image Radioallergosorbent test (RAST).


Image

The most common site for the manifestation of drug reactions is the skin.


DISPOSITION

Image Discontinue likely offending agent.

Image Admit if:

Image Stevens-Johnson syndrome.

Image Toxic epidermal necrolysis.

Image Severe drug reaction.

Image Respiratory distress.

Penicillin Allergy

TYPES

Wide variety of allergic reactions:

Image Type I: Anaphylaxis.

Image Type II: Hemolytic anemia.

Image Type III: Serum sickness.

AMPICILLIN/AMOXICILLIN RASH

Image Not urticaria, seen with infectious mononucleosis.

Image Hyperuricemia.

Food Allergy/Sensitivity

PATHOPHYSIOLOGY

Image 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.

Image 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.

Image Most adverse reactions to food do not have an immunologic basis.

Image Nonimmunologic food intolerances are common, like enzyme deficiencies (lactase deficiency, vomiting, diarrhea).


Image

Most common food allergies:

Image Peanut

Image Shellfish

Image Eggs


SIGNS AND SYMPTOMS

Image IgE-mediated hypersensitivity reactions start within minutes of the responsible food intake, and often are associated with urticaria, edema, and anaphylaxis (see below).

Image 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.

Image 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

Image Drugs: Sulfonamides and anticonvulsants.

Image Mycoplasma pneumoniae, herpes simplex virus.


Image

Mild EM does not progress to SJS.


SIGNS AND SYMPTOMS

Image Prodromal phase (1–14 days): Fever, headache, malaise.

Image Mucosal involvement:

Image Exudative conjunctivitis.

Image Oral erosions on the palate and gingivae.

Image Urethritis, vaginitis.

Image Skin involvement: Target lesions—annular, with pink halo surrounding a pale halo and erythematous center. May have central blistering. Palms and soles are involved.

Image Nikolsky’s sign: Separation of normal epidermis at the basal layer caused by sliding finger pressure (“rubbed off” line).

Image See Dermatologic Disease chapter.


Image

The oral cavity is almost always involved in erythema mulitforme major.


DIAGNOSIS

Image Clinical criteria: Cutaneous lesion plus at least two mucosal surfaces involved.

Image Skin biopsy is not indicated (would show perivascular mononuclear cell infiltrate).

TREATMENT

Image Hospitalization for supportive care.

Image Intravenous (IV) hydration.

Image Topical steroids and anesthetics as needed.

IMMUNODEFICIENCIES

Image Primary (congenital) immune deficiencies (Table 9-2) present at different ages, depending on category of disorder.

Image When evaluating a child with recurrent infections, pay attention to the following:

Image 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

Image

Image X-linked inheritance: Similar case in a male relative (Bruton’s, Wiskott-Aldrich, chronic granulomatous disease [CGD]).

Image Clinical features:

Image Failure to thrive (FTT): Severe combined immunodeficiency (SCID).

Image Hypertelorism, hypocalcemia, truncus arteriosus: DiGeorge syndrome.

Image Absence of tonsils and lymphatic nodes: Bruton’s agammaglobulinemia.

Image Coarse features, eczema, lax joints, scoliosis: Job syndrome.

Image Workup: Thymus shadow on chest x-ray, antibody titers (response to vaccination), absolute lymphocyte count (ALC).

Image Sites of infection:

Image Phagocytes (CGD): Sinopulmonary and soft tissues.

Image Immunoglobulin deficiencies: Sinopulmonary and gastrointestinal (Giardia).

Image T cells: Disseminated (mycobacteria, varicella-zoster virus).

Image Types of microorganisms: Intracellular infections in T-cell disorders (viruses, mycobacteria, Pneumocystis); Neisseria infections in late complement deficiency.

Severe Combined Immunodeficiency (SCID)

Image

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.


Image

Onset of SCID at 3 months of age:

Image No palpable lymph nodes

Image Opportunistic infections

Image Failure to thrive


DEFINITION

Abnormalities of both humoral and cellular immunity.

ETIOLOGY

Image 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).

Image Adenosine deaminase (ADA) deficiency: One third of all SCID cases.

SIGNS AND SYMPTOMS

Image Presents within first 3 months with diarrhea, pneumonia, otitis, sepsis, FTT, and skin rashes.

Image Frequency and severity of infections.

Image Persistent infection with opportunistic organisms (Candida, mycobacteria, herpes viruses, CMV, PCP).

Image Absent lymphatic nodes, hypoplastic thymus.

DIAGNOSIS

Image Lymphopenia: ALC (absolute lymphocyte count) < 500.

Image ↓ serum IgG, IgA, and IgM.

Image Low or no T and B cells.

TREATMENT

Image Aggressive antimicrobial treatment of even mild infections.

Image Recombinant ADA is available for replacement therapy.

Image Bone marrow transplantation (BMT).

PROGNOSIS

Death within first 2 years if untreated.


Image

Measures to be taken in SCID:

Image Protective isolation

Image Irradiation of all blood products


Letterer-Siwe Disease

Image

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

Image The most severe form of Langerhans’ cell histiocytosis (LCH).

Image Manifestation of complex immune dysregulation.

SIGNS AND SYMPTOMS

Image Skeleton involved (80%): Skull, vertebrae (eosinophilic granuloma, lytic lesions).

Image Skin (50%): Seborrheic or eczematoid dermatitis in a child of < 2 years of age

Image Lymphadenopathy (33%).

Image Hepatosplenomegaly (20%).


Image

Letterer-Siwe disease:

Image Lytic lesions

Image Lymphadenopathy

Image Eczema


Image Anorexia, FTT

Image Exophthalmos.

Image Pituitary dysfunction: Growth retardation, diabetes insipidus.

Image Systemic manifestations: Fever, weight loss, irritability, FTT.

Image Bone marrow suppression: Anemia, thrombocytopenia, neutropenia.

LAB

Image Complete blood count (CBC).

Image Liver function tests (LFTs).

Image Coagulation profile.

Image Chest x-ray.

Image Skeletal survey.

Image Urine osmolality.

Image Tissue biopsy (skin or bone lesions).

TREATMENT

Image Treatment directed at arresting the progression of lesion (low-dose local radiation).

Image Systemic multiagent chemotherapy.

Image Spontaneous remission.

DiGeorge Syndrome

Image

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

Image Deletion in chromosome 22, resulting in a defect of development of the third and fourth pharyngeal pouches.

Image Phenotypical translation into midline defects of the heart, head, parathyroids, and thymus.

SIGNS AND SYMPTOMS

Image Dysmorphic features: Hypertelorism, cleft palate.

Image Congenital heart disease: Truncus arteriosus, interrupted aortic arch.

Image Hypoparathyroidism presents as hypocalcemic seizures (“tetany”).

Image Recurrent infections: depending on T-lymphocyte counts. Opportunistic infections (OIs) in severe cases.


Image

CATCH 22

Cardiac abnormality (tetralogy of Fallot)

Abnormal facies

Thymic aplasia

Cleft palate

Hypocalcemia

(22 abmormality on the 22 chromosome)


DIAGNOSIS

Image Calcium level and parathyroid hormone.

Image T-cell count (variable).

Image Chest x-ray: No thymic shadow.

Image Echocardiogram.

Image Fluorescent in situ hybridization (FISH) test detects the 22q11.2 deletion.

TREATMENT

Image Thymic transplant if ALC < 100.

Image BMT is not an option because of high risk for graft-versus-host disease (GVHD).

Image 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.


Image

Ataxia-telangiectasia:

Image Injected sclera

Image Ataxia

Image Lymphoma


SIGNS AND SYMPTOMS

Image Usually presents during first 6 years, wheelchair confinement by 10–12 years.

Image Earliest sign: Telangiectasias on the sclerae (misdiagnosed as “pink eye”).

Image Progressive cerebellar ataxia.

Image Chronic sinusitis, bronchiectases.

Image OIs.

Image ↑ risk of malignancy (lymphomas, leukemia).

LAB

Image Absence of antibodies after vaccination.

Image Low IgA and IgM.

Image T4 lymphocytes decline over time.

Image ↑ serum α-fetoprotein.

TREATMENT

Image Supportive therapy.

Image Improve pulmonary function.

Image Prophylaxis of OIs.

Chronic Mucocutaneous Candidiasis (CMC)

DEFINITION

Image T-cell dysfunction: Inability to recognize candidal antigens.

Image A heterogeneous group of disorders characterized by recurrent or persistent superficial candidal infections of the skin, nails, and mucous membranes.

SIGNS AND SYMPTOMS

Image Refractory thrush may extend to the esophagus.

Image Refractory severe diaper rash.

Image Angular cheilitis.

Image Nails thickened, significant edema and erythema of the surrounding periungual tissue.

Image Often associated with endocrinopathy: Hypo/hyperthyroidism, polyendocrinopathy.

TREATMENT

Image Systemic antifungals

Image Skin care

Wiskott-Aldrich Syndrome

Image

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.


Image

Wiskott-Aldrich syndrome:

Image Eczema

Image Thrmobocytopenia

Image ↑ IgA/IgE


DEFINITION

X-linked-recessive disorder of cell cytoskeleton, presenting as eczema, thrombocytopenia (TCP), and ↑ susceptibility to infection.

SIGNS AND SYMPTOMS

Image Atopic dermatitis/eczema.

Image Thrombocytopenic purpura.

Image Recurrent infections in infancy: Pneumococcal (otitis, pneumonia), persistent thrush.

Image OIs: Pneumocystis jiroveci pneumonia (PCP).


Image

Oral candidiasis at > 6 months of age should arouse suspicion for the presence of an immunodeficiency.


LAB

Image ↓ gM.

Image ↑ IgA and IgE.

Image Absence of antibodies after vaccination.

Common Variable Immunodeficiency (CVID)

DEFINITION

Image 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).

Image Often (one fourth) familial.

Image Involves the formation of autoantibodies.

TABLE 9-3. B-Cell Disorders and Immunoglobulin Deficiencies

Image

SIGNS AND SYMPTOMS

Image Two peak ages of onset: Children aged 1–5 years and 16–20 years old.

Image Lymphadenopathy, splenomegaly.

Image Association with autoimmune diseases: Inflammatory bowel disease (IBD), sprue-like syndrome, arthritis.

Image Lymphoid interstitial pneumonitis, granulomas on various organs.

Image ↑ risk of malignancies: Non-Hodgkin lymphoma, gastric carcinoma.

Image Sinopulmonary infections: Pneumococcal, Mycoplasma.

Image Gastrointestinal (GI) infections: Giardia.

Bruton’s Congenital Agammaglobulinemia

DEFINITION

Image X-linked tyrosine kinase deficiency resulting in the arrest of B-cell maturation. Gene defect in Xq22.

Image Severe hypogammaglobulinemia.


Image

Bruton’s agammaglobulinemia:

Image Male

Image No palpable lymph nodes

Image No tonsil

Image Respiratory and gastrointestinal infections


SIGNS AND SYMPTOMS

Image No tonsils.

Image No palpable lymphatic nodes.

Image Recurrent/chronic sinopulmonary (pneumococcal), GI (Giardia) infections.

Image ↑ susceptibility to enteroviral meningoencephalitis.

DIAGNOSIS

Very low or absent mature B lymphocytes and all classes of immunoglobulins. No production of protective antibodies (negative titers).


Image

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.


Image

Selective IgA deficiency can → fatal anaphylaxis with blood (IVIG) infusion. IVIG is contraindicated.


SIGNS AND SYMPTOMS

Image Mostly respiratory tract infections.

Image Allergies.

Image Autoimmune diseases: IBD, arthritis.

DIAGNOSIS

Image IgA < 5 mg/dL.

Image Normal levels of other immunoglobulins and normal response to vaccination.

Image Normal cell-mediated immunity.


Image

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.


Image

Thymic hypo- or aplasia → a deficiency of functional T cells.


SIGNS AND SYMPTOMS

Image Recurrent skin infections and pneumonias (Staphylococcus aureus).

Image Partial oculocutaneous albinism.

Image Progressive peripheral neuropathy.

DIAGNOSIS

Image Giant gray granules in the cytoplasm of nucleated cells.

Image Leukopenia, neutropenia.

Image Chemotaxis test.

TREATMENT

Image Ascorbic acid has no effect.

Image Antibiotics for acute infections.

Image BMT (does not prevent or cure peripheral neuropathy).

Chronic Granulomatous Disease (CGD)

Image

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

Image Most common inherited disorder of phagocytosis, X-linked or auto-somal recessive.

Image Oxidase deficiency in neutrophils and macrophages = defect in generation of oxygen metabolites.

Image Chemotaxis and phagocytosis intact.

Image Inability to kill catalase-positive microorganisms: S aureus.


Image

Impaired intracellular bactericidal activity is the definitive test for chronic granulomatous disease.


SIGNS AND SYMPTOMS

Image Presents in the first years of life.

Image Recurrent deep soft tissue abscesses and lymphadenitis.

Image Severe staphylococcal and Burkholderia cepacia pneumonia and lung abscess, pneumatoceles.

Image Osteomyelitis.

Image Hepatosplenomegaly (granulomas).

DIAGNOSIS

Image Nitroblue tetrazolium test.

Image Leukocytosis.

Image Hypergammaglobulinemia.

TREATMENT

Image Aggressive antimicrobial treatment of infection.

Image Surgical excision of abscesses.

Job Syndrome (Hyper-IgE)

Image

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.


Image

Job syndrome:

Image Eczema

Image Eosinophilia

Image Lax joints

Image Staph infections


DEFINITION

Image Neutrophil chemotactic defect.

Image Autosomal dominant.

SIGNS AND SYMPTOMS

Image Recurrent staphylococcal infections.

Image Eczema.

Image Coarse facial features, lax joints.

DIAGNOSIS

Image IgE > 10,000 IU/mL.

Image Eosinophilia.

TABLE 9-4. Phagocytic and Chemotactic Disorder

Image

TREATMENT

Image Penicillinase-resistant antibiotics.

Image BMT.

Complement Deficiency

Image

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.


Image

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

Image Opsonization.

Image Bacteria cell lysis.

Image Facilitating chemotaxis.

ASSOCIATED DISEASES

Image C1q deficiency: Systemic lupus erythematosus (SLE).

Image C1 esterase inhibitor (C1 INH) deficiency: Hereditary angioedema.

Image C2 deficiency: Pneumococcal infections.

Image C5–C9 terminal complement deficiency: Neisserial infection.


Image

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

Image

DIAGNOSIS

CH50 screening test.

Asplenia

Image

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.


Image

Asplenia:

Image Howell-Jolly bodies

Image Encapsulated organism


DEFINITION

Absence of the functional spleen.

ETIOLOGY

Image Associated with some congenital syndromes.

Image Functional asplenia may be secondary to sickle cell disease (SCD) or other hemoglobinopathies.

Image Hyposplenia may be secondary to SLE, rheumatoid arthritis (RA), IBD, GVHD, nephrotic syndrome, or prematurity.

Image Splenectomy due to trauma, Hodgkin’s lymphoma, and hereditary spherocytosis.

DIAGNOSIS

Image ↓ IgM antibodies, alternate complement pathway, and tuftsin.

Image ↑ requirement for opsonic antibodies.

Image Howell-Jolly bodies in erythrocytes.

COMPLICATIONS

Sepsis with encapsulated organisms:

Image 0–6 months: Gram-negative enteric (Klebsiella, Escherichia coli).

Image > 6 months of age: S pneumoniae, Haemophilus influenzae type B. Malaria and babesiosis are more severe.

TREATMENT

Image Penicillin prophylaxis.

Image Pneumococcal immunization, also H influenzae and meningococcal (vaccinations against encapsulated organisms).

Graft-versus-Host Disease (GVHD)

DEFINITION

Image Donor lymphocytes detect host as foreign.

Image 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

Image Acute: < 100 days:

Image Erythroderma.

Image Cholestatic hepatitis—abnormal LFTs.

Image Enteritis—diarrhea and cramps.

Image ↑ susceptibility to infections.

Image Chronic: > 100 days:

Image Either:

Image Generalized skin involvement, or

Image Localized skin involvement and/or hepatic dysfunction and liver histologic evidence of chronic aggressive hepatitis, bridging necrosis, or cirrhosis

Image Or:

Image Involvement of the eye (“keratoconjunctivitis sicca” = dry eye).

Image Involvement of minor salivary glands or oral mucosa (dryness).

Image Involvement of any other target organ.


Image

Requirements for the diagnosis of graft-versus-host disease:

Image Graft must contain immunocompetent cells.

Image Host must be immunocompromised.

Image Histocompatibility differences must exist.


TREATMENT

Image High-dose glucocorticoids.

Image Immunosuppressive therapy.

Image



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