Allergy and Endocrine Disorders - Doc Ge

7/28/2019 Allergy and Endocrine Disorders - Doc Ge

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ALLERGYDr. Geraldine Anne S. RamirezDepartment of Pediatrics


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Allergy

- Untoward physiological event where there is anacquired specific change in the reactivity of the host,mediated by an immune system.

IgE antibody

role in immediate hypersensitivity Rxn

- detected clinically in atopic individual by the whealand flare formation

- Ascariasis and occupational allergens


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Immunologic Basis of Allergic

Diseases

Immunologic system

detect and eliminate anything foreign to the body

Immunitybeneficial

Allergyharmful

Foreign material external environment

- Internal environment


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Component of host vs. foreign

substances

1. Environment

2. Target cells ( B lymphocytes and T lymphocytes )


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Immunologic Response of the Host

in Eliminating Foreign Material

1. Primary (Non-specific) the most primitiveresponse; phagocytosis and inflammation

2. Secondary (specific) 2 possible mechanisms:

a. B cell response with elaboration of antibodies

(IgE, IgM, IgG, IgA, IgD)b. T- cell response of cell-mediated or delayed

hypersensitivity


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In patient with genetic defect in processing Ag,and the Ag persists-host is immunologicallyimbalance


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Genetics

Chromosome autosomal dominant

Both parent atopic 33% risk

One parent atopic (24%-29%)


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Allergy and Infection

- Most common infection viral RSV, parainfluenzaand corona virus


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Emotional Factors

- trigger or exacerbate an allergic attack

(autonomic nervous system)


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Physical Factors

- cold, heat, exercise, changes in barometricpressure (parasympathetic ns)


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Characteristics of the Allergic Child

- Hay fever

- Urticaria

- Asthma

- Others: diarrhea, headache, conjunctivitis

Diagnosis

- RAST

- Skin test


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Lab. Exam

- CBC increase eosinophilia (3-7%)

- ESR

- Radiography

- Stool Exam- Urinalysis

- Total IgE (PRIST)

- Provocation or Challenge test- Patch Test


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Principles of Therapy in Allergic

Disease

- Based on effect of adequate identified causativeallergens (hx taking and skin testing)


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Non-IgE Mechanism of Allergy

Complement Pathway

C3a }anaphylaxis can induce histaminerelease from Basophiles and from mast cellsin the skin, producing wheal and flare rxns.

C5a } may result in Urticaria


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Neurogenic Pathway

- Non-adrenergic, non cholinergic (NANC) Pwregulates upper and lower airway function through thesecretion of small neuropeptides that have pro-inflammatory activities.

- Stimulation of exposed norepinephrine in the airwaytriggers cause increased nasal activity and secretion ofneuropeptides as reflex response.

- May cause bronchoconstriction, airway edema, andmucus production

ex. Asthma


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Modern Concept of Allergy

Allergic diseasesabnormal intense immunologicalreaction to the usual environment allergens.

Signs and Symptoms

1st month vomiting, diarrhea, bloody stools

2nd and 3rd monthskin eruptions

4 mos. yr. sneezing or wheezing

Initial exposure to allergen elicits a temporaryinflammatory response

Repeated exposure chronic inflamed with tissue damage,

hypersensitivity of the affected organ


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1st Allergy at about 6 mos. of life

Food allergy

Atopic dermatitis upper airway allergies

Bronchial hypersensitivity Lower airway allergies


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3. Tissue damaging responses (tertiary) will comeinto play

- these responses are no longer beneficial tothe host

If the tertiary response is ineffective, the Ag stillpersists then a more harmful or deleteriousand self-perpetuating response will be sustained(Autoimmune disease)


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4 Types of Immunologic or

Hypersensitivity Rxn

Type I or Anaphylaxis IgE mediated or anaphylacticreaction: e.g. rhinitis, sinusitis, asthma, hypersensitivitypneumonitis, urticaria, eczema, dermatitis, angioedema

Type II or Cytotoxic

Type III or Immune complex

Type IV or Granulomatous rxn


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Mediators of Allergy

Rapidly released mediators:

1. Mast cellsPreformed mast cells mediators vasoactiveamine (histamine and serotonin), adenosine,

proteases (kinase, tryptase), proteoglycans


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* Most significant biologic activity of thesemediators:

Vasodilatation with vascular leakage, smoothmuscle contraction, goblet and glandularsecretion as well as stimulation of the irritant

(itch and sneeze) nerve receptors.


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2. PAF- platelet activating factor a peptide that isproduced with pro-inflammatory

properties

- Isolated in the bronchial airway and skin

- ability to aggregate and degranulate platelets, a

feature of allergic immunity

- Acts pro anti-inflammatory mediators inallergy


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3. Cytokine very patent pro-inflammatory

mediators


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Pharmacotherapy

1. Antihistaminesprevent symptoms of IgE-mediatedallergic diseases, atropine like effect, asthmaprophylaxis

HI receptor antagonist useful in allergic disorders complete or block the action of histamine byreversible competitive antagonism at HI receptor

H2 receptor antagonist ex. Cimetidine, ranitidine-can inhibit cell-mediated immune skin responses


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2 Types of Histamines

1. Classical rapidly absorbs after oral orparenteral administration relief appreciatedwithin 15-30 min. e.g. meclizine- 12-24 hrs.,

mequitazine 36 hrs.- passed BBB and placenta, metabolized inthe liver

SE: sedation, nausea and vomiting,suppression of parkinsonismlikesyndrome


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2 Types of Histamines

2. Newer Nonclassical HI anatagonists

Terfenadine, astemizole lack of sedationand anti-cholinergic effects

- long acting, good compliance


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2. Adrenergic Agents

- relax airway smooth muscle, inhibit release of

chemical mediators from mast cells causingbronchoconstriction, increase mucociliarytransport by ciliary activity

Beta 2 adrenergic agents e.g. salbutamol,terbutaline, tolbuterol

Epinephrine stimulate alpha B1 and B2receptors given SQ 0.1 ml/kg of 1:1 dil, Rapid

onset, counteracts asthmaticbronchospasm


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3. Methylxanthine

- Theophylline- relaxes bronchial smooth

muscle, stimulate ciliary motility, acts as CNSrespiratory stimulant, improve diaphragmaticand other respiratory muscle contractility in thedistressed asthmatic

- phosphodiesterase inhibition which increasethe tissue levels of cyclic AMP

- inhibition of neural transmission at certainsynapses


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SE: narrow range between clinically effected bloodlevels and levels producing side effects which

include:anorexia, nausea, vomiting, heartburn,diarrhea, neurologic

effects: headache, restlessness, insonia,muscle spasm, seizure, cardiovascular

effects: (palpitations, tachycardia, arrhythmia),allergy


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4. Corticosteroid

- anti-inflammatory, potentiate the effects of

beta adrenergic drugs decrease airwayobstructions

- long term side effects: adrenal suppressionleading to inhibition of linear growth andposterior subscapsular cataract

- long term use inhaled corticosteroid safeand effective e.g. Budesonide


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5. Muscarinic Antagonist

- obviates the systemic atropine effects

- competitively inhibit the effect of acetylcholineat muscarinic receptor causing relaxation of theairway smooth muscles and dec. secretion of

mucus ex. Ipatropium bromide


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6. Cromolyn Sodium

- non-steroidal, inhaled anti-inflammatory drug,prevents both antibody-mediated mast celldegranulation and the transmembrane influx ofCa provoked by IgE antibody-antigen mediator-

selective suppressive effect on anti-inflammatorycells like macrophages, eosinophils, neutrophilsand monocytes.


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7. Ketotifen

- prophylaxis for asthma, a potent anti -anaphylactic activity, inhibit release and effect ofmediators, acts as Ca channel antagonists andoptimizes the beta adrenergic responses.


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ENDOCRINE DISORDERS


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Disorders of the Pituitary Glands

Hypothalamic and Pituitary hormones

Pituitaryloc at sella turcica

Ant. Pituitarysecrete trophic hormones

1. ACTH2. TSH

3. GH

4. LH5. FSH

6. PRL

7. Betalipotropin


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Primary hormone defwhen failure is due toorgan failure

Secondary hormone def lack of stimulationby the pituitary, which may result fromeither def. of hypothalamic releasinghormone or to an intrinsic pituitary disease


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Hypopituitarism

- Growth hormone defgrowth failure

EtiologyCongenital

Acquired

P ibl C f Pit it r nd r


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Possible Causes of Pituitary and or

hypothalamic dysfunction leading to

Growth failure:

1. Developmental Defects2. Idiopathic Hypopituitarism3. Tumors and Infiltrative lesions

4. Psychosocial Dwarfism5. Unresponsive to GH6. Empty Sella Syndrome7. Iatrogenic

8. Infections9. Vascular lesions10. Autoimmune causes


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Clinical Manifestations

- Short, growth velocity is subnormal, BW andlength are normal

- Doll like, cherubic

- External genitalia in boys are underveloped,penis is small

- Delay in skeletal and dental devt.

- Hypoglycemia


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Differential Diagnosis

- Proportionate Dwarfism

- Gonodal dysgenesis

- Turner syndrome- Constitutional short stature


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Diagnosis

- History and PE, Measurements

- Abnormal GH and other Pituitary function tests

- Investigation of other target organs like:

Thyroid functionserum thyroxine andTSH

Gonodal function measure serum LH,FSH, estradiol and

testosterone, prolactin

Adrena glandsplasma or serum cortisol


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Roentgenography and Imaging

studies:

Skull X-ray

MRI

CT Scans


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Treatment

Organic lesions treat primary cause

Surgery

Growth hormone defHigh Growth Hormone

Di b I i id


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Diabetes Insipidus

- Disorder characterized by extreme thirst, polydipsia,

polyuria, and episodes of dehydration is due toabsence of ADH

- Etiology: idiopathic

- Takes 95% of the post. lobe of pituitary to cause DI

- Craniopharyngiomamost common cause inchildren up to 14 yrs.


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- Hereditaryautosomal dominant

- Differential Diagnosis:

Chronic Renal Disease - hypoplastic or polycystickidney, Chronic GN, Pyelonephritis


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Causes of Central or Neurogenic DI

Hypophysectomy

Tumors

Surgery to remove suprasellar tumors

Granuloma

Infiltrative disorder like leukemia andhistiocytosis x

Infections like encephalitis

Trauma Autoimmune causes

Hereditary/familial


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Laboratory Dx:

History and PE

Monitor I and O

Urine specific gravity1.001 1.005

Urine osmolality and plasma are taken

MRI

CT Scans


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Treatment

Central DIDDAVP a synthetic analogue ofVasopressin Chlorpropamide.

Nephrogenic DI treat underlying cause prevent dehydration, inc. water intake,Chlorthiazide, Indomethacin

S d f I i S i


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Syndrome of Inappropriate Secretion

of ADH

- Condition wherein ADH concentration isinappropriately high for the level of plasmaosmolality


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Diagnostic Criteria

1. Hyponatremia with hypo-osmolality

2. Urine inappropriately concentrated to greaterthan 100 mosm/kg

3. Euvolemia and absence of CHF, cirrhosis,Nephrotic syndrome

4. Absence of renal, adrenal or thyroidinsufficiency


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Etiology

Condition involving CNS: Trauma, infectiousand surgery for pituitary tumors

The following can produce S/S of SIADH:

- TB, Lung tumors, lymphomas, sarcomas ofduodenim, pancreas, prostate, thymus

- intake of drugs like Clofibrate,chlorpropamide, thiazide


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Clinical Manifestations

S/S of hypotonicity of body fluids and waterintoxication

N/V, irritability, and personality changes


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Treatment

Restrict fluids

Correct electrolytes imbalance

Demeclocycline


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Thyroid Disorders in Children

Congenital Hypothyroidism

- One of the most common preventable causes ofmental retardation


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Etiology

1. Thyroid dysgenesis

2. Thyroid dyshormogenesis

3. Hypothalamic or pituitary dysfunction

4. Maternal anti-thyroid drug ingestion

5. Maternal autoimmunity

6. Immaturity

D f t i C it l N d i


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Defects in Congenital Non endemic

Hypothyroidism

1. TSH receptor abnormality

2. Iodide trapping defect

3. Organification defect

4. Iodotyrosine deiodinase def.

5. Defects in thyroglobulin synthesis or transport leadsto failure of T3 and T4 release into the circulation

6. Failure of proteolytic enz. to digest the thyroglobulin- T4 complex

7. Peripheral thyroid hormone receptor defect

Cli i l M if t ti


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Clinical Manifestation Common S/S in Neonates:

Constipation, prolonged jaundice, lethargy, poorfeeding, hypothermia, good babies unusuallyquiet and seldom cry when wet

Other features:

Prolonged gestation with large birth size, large ant

fontanel and a post. fontanel > 1 cm, RDS,peripheral cyanosis, delayed onset of stooling,abdominal distention, vomiting and edema


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Long Term untreated CH-CRETIN

- Hollow empty eyes which appear far apart

- Swollen eyelids, broad nose with depressedbridge, open mouth with thick broad tongue,narrow chest with curved back


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Lab Dx

Low to nil serum thyroxin (T4), TSH assay

Newborn screening

Thyroid scanning

Radioactive iodine uptake

CBC with Periph smear, Bilirubin levels

EKG Bone Age


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Treatment

Early institution of treatment is the dictum

Na Levothyroxine


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Prognosis

Time of treatment is correlated withneurodevelopmental outcome. Treat within the1st 4-6 weeks of life augurs a very good mental

prognosis.


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Goiters in Children

Any enlargement of the lobe or lobes of thethyroid gland to at least the patients terminalphalanx of the thumb


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Endemic Goiter

- Iodine deficiency, endemic in the mountains

- Intake of goitrogens and a genetic metabolicdefects

- Compensatory hypertrophy of the glands in itseffort to produce adequate amounts of thyroidhormone


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Treatment

- Levothyroxin

- Potassium iodide or iodized oil

- Iodized salt as prophylaxis


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Hashimoto Thyroditis

CLTchronic lymphocytic thyroiditis

- autoimmune, inflammatory condition causing55-65% of all euthyroid goiters

- common in female more than male

- occurs frequently with chromosomalabnormality or syndromes


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Diagnosis

Increase titers of thyroid antibodies

RAI scan


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Simple Colloid Goiter

- Adolescent goiter, on toxic goiter, autoimmune,gland is normal

- Thyroid function test is normal

- Regression of goiter size with thyroxine therapy


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Congenital Goiter

- Occur in areas of iodine deficient

- Anti thyroid substances ingested by pregnantmothers


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Solitary Nodule

- Assoc. with malignancy

- Rare in children


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Etiology

Irradiation most common implicated


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Clinical Manifestation

Thyroid Ca - painless cervical amass in thethyroid area

- Cervical lymph node enlargement

- Majority are euthyroid


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Lab Dx

Normal thyroid function

USG

Radionuclide scan

FNAB


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Allergy and Endocrine Disorders - Doc Ge

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