Highlights of some pediatric topics Neonatal medicine - Neonatal reflexes - Neonatal metabolic disorders - Neonatal hematological disorders Growth

- Factors affecting growth - Growth curves and percentiles - Aspects of physical growth Nutrition - Nutritional requirements - Weaning - Kwashiorkor and marasmus - Rickets and Hypervitaminosis D Infection - Fever without a focus (Non-localizing febrile illness) - Fever of unknown origin - Scarlet fever - Immunization Cardiac disorders - Rheumatic fever - Infective endocarditis Respiratory disorders - Suppurative lung disorders Gastroenterology - Painful oral lesions - Diarrheal Disorders - Dehydration and Rehydration - Persistent diarrhea Liver disorders - Viral hepatitis Hematological disorders - Parasitic anemias Page 2 3 5

6 6 7 8 11 12 15 18 20 21 22 27 31 32 34 35 36 38 39 42

Neonatal reflexes
There are several reflexes that can be normally elicited in the newborn. Eliciting these reflexes is important for evaluation of the general condition, evaluation of vision and detection of focal neurological signs. The reflexes can be classified as tendon reflexes and primitive reflexes. Primitive reflexes are peculiar to newborn and they usually disappear by 4-6 months. Persistence of these reflexes indicates a neurological problem.

1. Moro reflex
How to elicit it? Dropping the head, with the examiners hand supporting the shoulders or Making a loud noise near the baby's ear or Sudden withdrawal of the blanket from underneath the infant.

The response
Abduction of the arms at the shoulders and extension of the forearm at the elbow. The hands and fingers are held wide-open. The arms are then moved as in an embrace. A cry follows these movements and should be vigorous. There is a generalized extension of the trunk. Clinical significance of the reflex Absence: It may be due to intracranial birth injury, cerebral depression by narcotics or anaesthesia given to the mother just before delivery or, prematurity.. Asymmetrical response: It may be due to brachial palsy or fracture clavicle. Persistence of the reflex: If it persists after 6 months of age it indicates cerebral palsy or mental retardation.

2. Tonic neck reflex

How to elicit it? It is elicited by placing the infant in a supine position and perform a lateral rotation of the head to one side. The response - Extension of the arm and leg towards which the head is turned and flexion of the limbs on the opposite side. The response is obtained in infants from 1-7 months. Clinical significance of the reflex - Absence: It may due to spinal cord disease. - Abnormal response: Indicates neuromotor disorder of cerebral origin. -Persistence of the reflex: If it persists, cerebral disease is a possibility.

3. Rooting and suckling reflexes

Rooting reflex: The reflex is elicited in 4 areas, at both comers of the mouth and on the upper and lower lips and at the midline. The mouth opens or the head turns towards the side of the stimulus. Suckling reflex: If you introduce the nipple or a finger in the infant mouth, he sucks it. The reflex is important for feeding. Good suckling indicates a good general condition. Absent reflex indicates a serious brain lesion or serious infection.

4. Blinking and papillary reflexes

Sudden exposure of the eyes to bright light leads to blinking. The reflex is important for evaluation of vision. Again, exposure to bright light leads to papillary constriction while exposure to dim light leads to papillary dilatation. The reflex is present since birth and does not disappear.

5. Grasp reflex
If you put your finger in the infant palm, he grasps it. The reflex disappears by 4 months of age. Unilateral absence indicates a focal neurological lesion. Persistence of the reflex indicates an upper motor neurone lesion.

6. Landau reflex
When the infant is held prone in a horizontal position the body forms a convex arc upwards with head, trunk and hips flexed and the shoulders drawn back. Extension of the head occurs after a month of age.

7. Stepping reflex
When the infant is held in an upright position and lowered until the feet touch the table, stepping movements are made.

8. Placing reflex
When the dorsal surface of the foot touches the edge of the table, the foot is elevated, and placed on the table.

9. Babinski reflex
It is positive and disappears at about 1 year. Unsustained ankle clonus (5-6 beats) may .normally be present until 2-4 months of age

Neonatal Metabolic Disorders

I. Hypoglycemia
Hypoglycemia is defines as blood glucose level of 40/mg/dl in the first 72 hours of life regardless the gestational age. Causes: The main causes are: 1. Infant of diabetic mother 2. Intrauterine growth retardation. 3. Serious illness (sepsis, shock, and asphyxia). 4. Errors of metabolism. Clinical Picture: It may be asymptomatic or symptomatic. Symptoms include jittery, cyanosis, R.D., convulsions, apnea Treatment: This condition needs continuous monitoring of blood glucose since birth for early detection and management. No convulsions (asymptomatic): 10% dextrose (2 ml/kg)... l.V. Convulsions (symptomatic): 10% dextrose (4 ml/kg)... l.V. Maintenance in the form of IV dextrose 10 % 6-8 mg/kg /minute.

II. Hypocalcemia
Hypocalcemia is defined as blood calcium level of less than 7Jmg/dl. Causes: It can be early or late. - Early hypocalcemia (during the first 3 days) occurs in preterm, infant of diabetic mothers and birth asphyxia. - Late hypocalcemia (during the next days to weeks) occurs due to high phosphate load (cow milk) and hypoparathyroidism. Clinical Picture: Convulsions, hyper-reflexia, cyanosis and apnea. Treatment -Early onset (Ca< 6.5 mg/dl): l.V. infusion of calcium gluconate (5 ml/kg/day). -Seizures, apnea, tenancy (Ca< 5 mg/dl): 1-2 ml/kg of calcium gluconate 10% over 5minutes, slow l.V infusion.

III. Hypomagnesemia
Hypomagnesemia is defined as blood magnesium level of fess than 1.5 mg/dl. Causes: The main causes are insufficient stores, iatrogenic (as exchange transfusion), with hypocalcemia and infant of diabetic mother. Clinical Picture: Same picture of hypocalcemia (convulsions, cyanosis, apnea).

Treatment
0.25ml/kg of magnesium sulfate (MgSO4 50%), I.M only (not l.V).

IV. Hypothermia (cold injury)

Hypothermia is defined as lowering of the body temperature below 35.5 C. Causes: The main causes are: - Cold environment. - Inadequate drying of clothing. - Sepsis. Clinical Picture - Initial signs include cold skin, weak sucking, lethargy, weak cry, skin color changes, tachycardia, tachypnea. - Late signs are Lethargy, apnea and bradycardia. Treatment Gradual warming of the infant (rapid warming is serious).

V. Hyperthermia
Hyperthermia is defined as elevation of the body temperature (38-39 C) in the first 2-3 days. Causes: The main causes are: - Infections. - Dehydration. - High environmental temperature. Clinical Picture - The skin is warm, flushed or pink initially and pale later. - Other findings as Dehydration, intracranial hemorrhage, heat stroke. - Death may occur in severe cases. Treatment - Lowering environmental temperature. - Oral or parenteral fluids.

Neonatal Hematological Disorders

I. Neonatal bleeding
Causes of neonatal bleeding
Bleeding in healthy newborn Hemorrhagic disease in the newborn (most common). Neonatal thrombocytopenia (maternal lupus, maternal IIP, maternal drugs). Bleeding in sick newborn Disseminated intravascular coagulation (DIG). Neonatal septicemia, neonatal liver disease, hemophilias. Investigations of neonatal bleeding include Complete blood picture. Prothrombin time, prothrombin concentration, partial thromboplastin time. Liver function tests. Fibrinogen and fibrinogen degradation products (in DIC).

Hemorrhagic disease of the newborn

- It is the most common cause of bleeding in the neonate. It commonly presents between 2-7 days of life by bleeding from GIT, intracranial hemorrhage, or bleeding following circumcision or from injection sites. - It occurs due to depletion of Vitamin K dependant coagulation factors, II,VII, IX, X due to transient deficiency of free vitamin K (due to absence of bacterial intestinal flora normally responsible for its synthesis). - Prophylactic I.M. vitamin K should be administered at birth. - Treatment of the disease is by vitamin K administration, transfusion of fresh frozen plasma or whole blood if needed.

II. Neonatal anemia

Causes of neonatal anemia
Physiologic anemia of the newborn. Congenital anemias. Hemolytic anemias. Hemorrhagic anemias. Abruptio placenta. Twin to twin transfusion or fetomaternal transfusion. Birth trauma or hemorrhage during delivery. Anemia of prematurity.

Growth and Development

Growth and development is a continuous process, which starts with the fertilization of ovum and extends till the end of adolescence. Evaluation of growth and development is an essential step in examination of every patient and it aims to distinguish between what is normal and what is abnormal. Growth is an increase in the mass and dimension of the body and it includes aspects that can be measured as weight, length and head circumference. Development is the functional maturation and acquisition of skills and it includes aspects as motor development, mental development and sexual development.

Factors affecting physical growth

There is a wide range of variations in physical growth among normal infants and children ". The factors that explain these variations are: 1. Genetic and hereditary factor: Children inherit their height and body frame from their parents. It is observed that some families are short and others are tall. 2. Race: There is a racial difference in rate and pattern of growth so it is better for every country to use its own growth charts. 3. Sex: Girls grow faster than boys from 7 months to 4 years and also they start and end their puberty at younger age. There are growth curves for boys and others for girls. 4. Nutrition: Under-nutrition leads to growth failure and over-nutrition leads to obesity. The first sign in protein energy malnutrition is deceleration of growth. 5. Socioeconomic factors: Children of low socioeconomic classes have poor nutrition, poor hygiene and poor heath compared to those of high socioeconomic classes. Chronic illness: Chronic systemic diseases as renal, cardiac, gastrointestinal and endocrinal .6 .diseases cause growth failure

Growth curves (or growth charts)

Growth charts are standards for growth of normal infants, children and adolescents. They are available in percentile values where: 50th percentile represents the average or the mean. 25th, 10th and 5th percentiles are low normal values. 75th, 90th and 95th are high normal values. Types: There are available charts for weight, height and head circumference. For each parameter, there are charts for boys and others for girls. There are also charts in relation to age, charts for the first 3 years (see opposite chart) and charts for 2-20 years (see short stature). - Uses: Growth curves are useful in two ways: 1. With single measurement, values below 5th or above 95th percentile are abnormal. 2. With repeated or serial measurements, the growth rate can be assessed. Any normal child should follow his own percentile on serial measurements. So, any deviation from the own percentile is abnormal. Acceleration of growth (catch up) occurs with therapy.

Physical growth
Average weight for age At birth: 3 kg During the first 4 months, weight gain is about 750 gm/month. 1 month: 3.750kg 2 months: 4.500 kg 3 months: 5.250 kg 4 months: 6.000 kg (2 times birth weight) During the second 4 months, weight gain is about 500 gm/month. 5 months: 6.500 kg 6 months: 7.000 kg 7 months: 7.500kg 8 months: 8.000 kg During the third 4 months, weight gain is about 250 gm/month. 9 months: 8.250 kg 10 months: 8.500kg 11 months: 8.750 kg 12 months: 9.000 kg (3 times birth weight) During early childhood, weight gain is about 2 kg/year. 2years: 12 kg 3 years: 14 kg 4 years: 16 kg 5 years: 18 kg 6 years: 20 kg During late childhood, weight gain is about 2.5 kg/year. 7 years: 22.5 kg 8 years: 25 kg 9 Years: 27.5 kg 10 years: 30 kg (10 times birth weight) Average length or height for age At birth: 50cm During the first 4 years 6 months: 68 cm 1 year: 75 cm 2 years: 87 cm 3 years: 94 cm 4 years: 100 cm (2 times birth length) Between 4- 8 years, the height increases about 7 cm/year. 5 years: 107 cm 6 years: 114 cm 7 years: 121 cm 8 years: 128 cm Between 9-12 years, the height increases about 5 cm/year. 9 years: 135 cm 10 years: 140 cm 11 years: 145 cm 12 years: 150 cm (3 times birth length)

Average head circumference for age At birth: 35 cm 6 months: 43cm 1 year: 47 cm (12 cm more) 2 years: 49 cm 6 years: 51 cm 12 years: 53 cm (6 cm more)

Weight is doubled at 4 months and tripled at 12 months. Height is doubled at 4 years and tripled at 12 years.

Head circumference increases 12 cm during the first year and only 6 cm during the next 11 years. This demonstrates the importance of brain growth in the first year.

The anterior fontanel closes at 14-18 months

Nutritional Requirements
Any diet must be nutritionally adequate for growth and development. An adequate diet should supply: (1) adequate amount of Water, (2) adequate Calories, (3) adequate Macronutrients (carbohydrates, lipids and proteins), (4) adequate Micronutrients (vitamins, minerals and trace elements) and (5) adequate amount of fiber.

1. Water requirements
Water is essential for existence. A lack of it results in death in a matter of days. Water content in infants is relatively higher (75-80% of body weight) than that of adults (55-60%). This explains why infants are more susceptible to dehydration. Water requirements in various age groups (ml/kg/ day) Infancy 120 2-6 years 100 7-1 2 years 90-80 13-1 8 years 80-70 Adults 50-40

2. Energy requirements
Children need calories for several reasons: 1. Maintenance of basal metabolism (50% of total caloric intake). 2. Physical activity (25% of total caloric intake). 3. Growth (12% of total caloric intake). 4. Fecal losses (8%) and specific dynamic action of food (5%). The proper relationship of caloric supply from each of the three macronutrients is: Carbohydrates: Lipids: Proteins = 3: 2: 1 (or 50%: 35%: 15%). Energy requirements in various age groups (kCal /kg /day) Infancy 100 2-6 years 90 7-1 2 years 80-70 13-1 8 years 60-50 Adults 40

Under and over-nutrition are the 2 major nutritional disorders related to energy intake.

3. Protein requirements
Proteins are needed for: 1. Growth, development and repair of tissues. 2. Formation of cells and cellular elements (cytoplasm and nucleoproteins). 3. Formation of enzymes and hormones. 4. Many vital properties of the blood (hemoglobin, coagulation system, antibodies, viscosity, buffering system, osmotic pressure, iron, calcium and iodine). Protein needs are highest during periods of rapid growth in infancy and childhood, during infections and injuries.

Protein requirements in various age groups (gm/ kg / day) Infancy 2-2.5 2-6 years 1.8-1.6 7-1 2 years 1.2 13-1 8 years 1,0 Adults 0.8

Proteins are made of 20 amino acids in varying proportions (9 amino acids are considered essential for man and must be provided in the diet). Proteins are considered to be either of high or low biological value:

Proteins of high biological value are the proteins of animal origin (e.g. milk, eggs, meat and liver). They contain all the essential amino acids in adequate amounts. Proteins of low biological value are the proteins of vegetable origin (e.g. cereals, legumes .. .etc). They are deficient in one or more of the essential amino acids. When high biological value proteins are the main source of protein, less amounts will be needed than if the source is a low biological value protein.

4. Carbohydrate requirements
Carbohydrates supply the necessary bulk of the diet and most of the body's energy needs. An infant should receive daily no less than 1% of his body weight of carbohydrates (i.e. 10 gm/kg/day).

5. Lipid requirements:
Lipids should supply the rest of the daily caloric requirement not supplied by proteins and carbohydrates. Lipids are essential to provide energy (1 gm of lipid gives 9 calories), essential fatty acids and fat-soluble vitamins. They are also important for insulation against variations in environmental temperature, support of body structures and making foods more palatable.

intake.

Recommended fat intake: Total fat intake should be 35% of the total caloric

6. Vitamins and minerals

Vitamins and minerals are essential for several metabolic events. Vitamins and iron requirements Vitamin A 2000 lU/day Vitamin D 400 lU/day Vitamin B1 1 mg/day Vitamin B2 1 mg/day Vitamin C 50 mg/day Iron 10-15 mg/day

7. Fibers
Dietary fiber is useful in increasing fecal output (bulking effect) and prevention of constipation. Whole grain cereals, fruits and vegetables are sources of dietary fiber.

Nutrition
1- Balanced diet should contain Carbohydrate Fat Protein 3 2 1 50% 35% 15% of caloric intake 2- Difference between colostrums & mature breast milk Colostrum Mature breast milk Timing 1st 3 days After 2 week Color Yellowish White Consistency Thick Thin PH Alkaline Acidic Specific gravity 1040 1060 1020 - 1040 Protein content 8 gm% 1.3 gm% CHO content 5.5 gm% 6.7 gm% Fat content 3 gm% 3.6 gm% Minerals 4 gm% 0.25 gm% Amount 40 - 60 ml/day I - 2 liters /day 3- Assessment of breast-feeding attachment & positioning A- Good attachment should fulfill all the following: *Infants mouth widely opened. *His chin is touching mother's breast. *More areola visible above than below his mouth. * His lower lip turned outward. B- Good positioning should fulfill all the following: *Infant's neck is straight or bent slightly back. *Infant's body is turned towards the mother. *Infant's body is close to mother's body. *Infant's whole body supported. 4- Factors influencing milk secretion a- Hormonal factor: *Prolactin. *Thyroxin. *Oxytocin. b- Psychic state: *Emotions. *Tension. *Anxiety. c- Nutritional state of the mother: Adequate diet with good fluid intake d- Physical activity: Out-door activity is needed. e- Complete emptying of the breast: At least every other feed 5- Difficulties in breast feeding A- Maternal:*Engorgement. *Scanty milk. *Retracted nipple. *Painful nipple conditions. B- Infantile:*Nasal obstruction. *Cleft palate. *Weak suckling. *Painful oral condition 6- Special formulae A- Lactose free formulae: Lactose is usually replaced by sucrose. It is used in: *Lactose intolerance (congenital or acquired). *Galactosemia. B-Phenylalanine free Formula: It is low in phenylalanine. Used for Phenylketonuria.

10

Weaning
Weaning means gradual introduction of food other than milk in the infant's diet.

Time of weaning
Current recommendation is to introduce such foods between 4-6 months of age. This time is suitable for several reasons: 1. The baby is able to support his head and neck while sitting (6 months). 2. The baby has increased levels of digestive enzymes. 3. The baby requires more calories than can be provided by milk alone. 4. The iron stores (that were obtained from the mother), are depleted. 5. Loss of extrusion reflex: If you attempt to spoon-feed a very young infant, the infant's tongue will push the spoon and food back out. This is the extrusion reflex and it denotes that the infant is not ready for solid foods. It disappears by 4-6 months of age and the infant becomes ready to transfer food from front of the mouth to the back and swallow. 6. The infant can attempt at self-feeding (purposefully bring his hand to his mouth).

General rules of weaning

1. New foods are introduced one at a time, at intervals of about 2-3 week. 2. New foods should be freshly prepared, properly mixed and have a good taste. 3. New foods are given by spoon. 4. If the infant appears disinterested in a food, try it again another time. 5. The infant's appetite is the best index of the proper amount. 6. Common food allergens (as cow's milk, egg whites) should be delayed until after the first year.

Suggested schedule of weaning

1. At 4 months old, the first food introduced is usually an iron-fortified, hypoallergenic infant cereal (rice cereal). It should be mixed with human milk, formula or water. It is given using an appropriately sized spoon. 2. At 5 months old, vegetable soup is given. 3. At 6 months old, yogurt and fruits can be introduced. 4. At 7 months old, egg yolk can be given. 5. At 8-9 months, he can start to share the ordinary food. Now he can use his fingers to pick up smaller items (watch to avoid chocking). 6. At 9-12 months, self-feeding is under way. Most table foods (provided soft and in small pieces) are appropriate.

Some precautions and foods to avoid

1. Do not leave the baby alone during feeding (choking). 2. Avoid salt and spices. 3. Avoid egg whites in the first year (food allergies). 4. Avoid cow's milk, as it is not well tolerated until one year. It may lead to milk allergy, iron deficiency anemia and vitamin D deficiency rickets.

11

5. Avoid excessive amounts of breast milk or formula after 6 months of age (interfere with the introduction of sufficient amounts of foods needed for energy). 6. Avoid high risk chocking foods: As peanuts, nuts, raw carrots, hard candy and gum.

Protein Energy Malnutrition

Classification (types)
Nutritional Dwarfism: Mild to moderate form of chronic under-nutrition - early infancy no wasting/edema. Marasmus: Severe form of chronic caloric deficiency Kwashiorkor: Protein deficiency with good caloric supply Marasmic KWO: Mixed

Contributing Factors
*Ignorance & poverty. *Urbanization *Environmental degradation *Infections *Natural disasters

Marasmus
Insufficient caloric supply to meet the minimum daily requirement. (both energy & protein are deficient). Nutritional marasmus: usually occur between 6 ms - 18 ms

Etiology:
*Nutritional. *Non-Nutritional. Nutritional marasmus: *Dietetic error. Over diluted or infrequent formula. *Scanty breast milk. *Infections (repeated GE). *Loss of nutritional elements. *Anorexia *Prolonged dietary restriction. Non nutritional marasmus:

12

*Congenital anomalies: Cong. hypertrophic pyloric stenosis, congenital heart & renal anomalies. *Chronic infection: Empyema, TB & urinary tract infection *Chronic illness: DM, cystic fibrosis, cerebral palsy & mental retardation.

Clinical Picture of marasmus

*Loss of weight (Growth failure & retardation). First degree: weight loss is about 15-25 % of expected weight. Second degree: weight loss is about 25-35 % of expected weight. Third degree: weight loss is > 35% of expected weight . *Loss of SC fat (skin on bone). 1st degree: Abdominal wall 2nd degree: Buttocks & thighs 3rd degree: Senile face *Muscle wasting. *Hypothermia *Vitamin deficiency: Vitamin A & B complex deficiency *Mineral deficiency: Iron deficiency anemia, copper & zinc *Hungry: Anxious, continuous crying with starvation diarrhea (scanty-dark green)

Complications & Death in marasmus

*Infections: GE Dehydration & electrolyte imbalance. *Hypothermia. *Hypoglycemia.

Kwashiorkor
Severe protein deficiency + adequate caloric intake (high CHO diet) Age: Usually occur between 18 - 24 ms

Etiology
*Dietetic error: Decrease breast milk & give high CHO diet. *Infections: Post measles (anorexia, mouth infections & enterocolitis) & post gastro-enteritis. *Maternal deprivation: Pregnancy or birth of another baby

Clinical Picture of Kwashiorkor

A- Constant Features: *Edema (Albumin ADH Aldosterone). *Growth failure & growth retardation. B- Variable Features: *Hair changes. *Hepatomegaly. *Anemia (dyshemopoeitic - hemorrhagic). *Infections (acquired immunodefeciency). *Mental changes (apathy & misery) *Disturbed muscle to fat ratio *Skin changes. *Anorexia, vomiting & diarrhea. *Vitamin deficiency (Vit. A, K, B complex). *Mineral deficiency: Iron, copper & zinc.

Complications & Death in Kwashiorkor

*Hypoglycemia. *Water & electrolyte imbalance. *Hypothermia. *Serious infections.

13

Investigations
A- Laboratory: *CBC: Anemia - leucocytosis in infection *Plasma proteins: Total proteins. *Albumin. * & globulins but globulins. *Glucose: Hypoglycemia *Electrolytes: K - dilutional hyponatremia (but total body Na). * Mg Imaging: Chest X-ray

Marasmic kwashiorkor
Mixed form: Marasmic patient is fed on CHO diet only without protein. Kwashiorkor is subjected to CHO restriction (marked anorexia) Diagnosis: * Edema or hair changes in marasmic patient *Loss of subcutaneous fat in KWO patient

14

Marasmus Main feature Behavior, appetite Electrolyte disturbances Complications Less common wasting Alert, hungry Minimal

Kwashiorkor Edema Apathetic, anorexia Severe More common Worse, difficult

Prognosis, treatment Better, easier

Prevention of PEM:
*Breastfeeding promotion. *Nutritional education of the mother. *Nutritional assessment of infants & toddlers every visit.

Management of PEM
A- Hospital managment: Indicated in: 3rd degree marasmus, KWO, Marasmic KWO or Infections (pneumonia & diarrhea) B- Treatment of life threatening conditions: *Antibiotics. *Shock, dehydration & electrolyte imbalance. *Anemia by blood or packed RBCs 10-15 cc/kg. *Prevention of hypothermia. C-Nutritional management: Marasmus: Type: Milk for non-weaned infants. *Balanced diet for weaned infants Amount: 150 Kcal/kg/day (actual body wt) gradually (5-10 Kcal/kg/day) every day or every other day according to tolerance. Kwashiorkor Dietetic management is more difficult due to anorexia Type: a- Milk: Start with soy based lactose free formula, gradually standard formulas b- Other food: *Animal protein: eggs, chicken, meat & yogurt. *Plant protein: lentils, beans. *Fresh vegetables & fruits Amount: 4-6 gram protein/kg/day Route: Oral or by naso-gastric tube in severe anorexia D- Treatment of vitamin & mineral deficiency: *Single dose of Vitamin A. *Folic acid *Iron: 6mg/kg/day. *Others: Vitamin D, C. and B complex- minerals as K and zinc. E- Treatment of parasitic infestations: If parasites are present.

Vitamin D Deficiency Rickets

15

Sources of Vitamin D:
*Ultraviolet light. *Fish liver oil. *Egg yolk. *Fortified infant formulas. *Requirement 400 IU/day. NB:- *Breast milk is deficient in Vitamin D, so it must be given from 4-6 mo onwards. *Premature infants need earlier (at 1 mo) and higher supplementation (up to 800 IU/day.

Metabolism:
Vitamin D is hydroxylated in liver to 25 (OH) D A second hydroxylation in kidney to 1, 25 di (OH) D (the active form of vitamin D).

Functions:
* Absorption of Ca & Ph from intestine. *Bone mineralization by deposition of Ca. * Reabsorption of Ph from kidney.

Etiology:
*Prolonged breast feeding without vitamin D supplementation. *Diet poor in vitamin D, as milk, fruits & vegetables. *Lack of exposure to sunlight. Normal Bone Formation: Four layers are arranged in epiphyseal region Zone of resting cartilage. Zone of proliferating cartilage (6-8 rows of cartilage cells). Zone of degenerating cartilage (zone of provisional calcification). Zone of ossification.

Pathology in Rickets:
Cartilage proliferation without degeneration. Newly formed osteoid tissue fails to calcify skeletal deformities. Defective mineralization in subperiosteal bone shaft rarefaction green stick fractures

Clinical Features:
- Skeletal Manifestations a- Head:- *Box like skull *Delayed closure of ant. fontanel. *Delayed dentition. b- Thorax:- *Rosary beads. *Harrisons sulcus, and longitudinal sulcus *Chest deformities (pigeon chest & flaring out) c- Extremities:- *Enlarged lower ends of long bone. *Marfan sign. *Deformities. d- Spine:- *scoliosis. *Correctable kyphosis - Muscular Manifestations (Hypotonia) Generalized hypotonia & laxity of ligaments: *Delayed sitting, standing and walking. *Rachitic kyphosis *Abdominal distension. *Visceroptosis - Neurological Manifestations:-

16

*Early: irritability, anorexia, excessive sweating *Late: hypocalcemic tetany Latent tetany (serum Ca 7-9 mg/dl); elicited by provocation Manifest tetany (serum Ca < 7 mg/dl) carpopedal spasm, laryngospasm, convulsions.

Complications:
Respiratory infections is the main complication

Radiological Findings: Appear at wrist & ankle Joints (3 stages)

a- Active rickets: *Broad epiphysis. *Cupping & fraying of distal ends of long bones *Wide joint space. *Rarefaction ( bone density) *Deformity and fractures b- Healing rickets (after 2 wks of treatment): Concave dense transverse line of calcification at lower end of long bone c- Healed rickets (after 4 wks treatment): Straight dense white transverse line at lower end of long bone

Biochemical Findings:
*Normal serum calcium (N 9 -11 mg %) *Low serum phosphorus (N 4.5 -5.5 mg %) *High alkaline phosphatase (Early finding)

Treatment of Vitamin D Deficiency Rickets:

*Exposure to sunlight *Vitamin D rich food as egg yolk and liver *Vitamin D therapy: either Oral : 2000 - 5000 IU/day vitamin D3 for 2 - 4 wks. Oral: 0.5 2 ug/day one-alpha (1, 25 dihydroxy D3) for 2-4 wks (very expensive drug) Single intramuscular injection 200.000 IU *Calcium supplementation *Treatment of infections *Treatment of tetany with: IV calcium gluconate10%, 1ml/kg slowly.

Non-Vitamin D Deficiency Rickets

17

A- Renal Rickets:
1- Renal osteodystrophy (renal glomerular rickets): It is due to chronic renal failure. Pathophysiology: a- Phosphorus retention with increased serum phosphorus & decreased serum calcium. b- Decreased activity of one alpha hydroxylase. 2- Renal tubular rickets: a- Familial hypophosphatemic rickets: (X-linked dominant). Due to failure of the kidney tubules to reabsorb phosphorus. b- Vitamin D resistant hypocalcemic rickets: Due to failure of the kidney tubules to reabsorb calcum. c- Multiple renal tubular defects: 1- Fanconi syndrome: Phosphaturia, glucosuria & amino-aciduria 2- Lowe syndrome: Fanconi syndrome + mental retardation + ocular manifestation (cataract & glaucoma).

B- Hepatic rickets:
In chronic liver disease or obstructive jaundice. Pathophysiology: a- Decreased activity of 25 hydroxylase activity. b- Decreased vitamin D absorption from intestine due to decreased bile acids.

C- Intestinal malabsorption

Hypervitaminosis D (Vitamin D Toxicity)

- Causes: It is caused by high supplement doses of vitamin D. Prolonged administration of
daily doses of 2000 IU has been reported to result in vitamin D toxicity. - Clinical manifestations and complications: They include the following: Anorexia, nausea and vomiting. Polyuria and polydipsia. Soft tissue deposits may occur in kidneys (nephrocalcinosis), blood vessels and heart. - Laboratory findings: Hypercalcemia. (Above 11 mg/dl) is the main finding. - Treatment: It necessitates immediate stoppage of vitamin D administration together with oral corticosteroids to decrease absorption.

Causes of fever in children

18

Short febrile illness (duration less than 7 days) Simple focal infections Respiratory: Nasopharyngitis, tonsillitis, otitis media, sinusitis, and bronchitis. Digestive: Stomatitis, gastroenteritis. Urinary: Urinary tract infections (cystitis). Cutaneous: Cellulitis, abscess. Serious focal infections Meningitis, pneumonia, peritonitis, pyelonephritis, osteomyelitis and arthritis. Simple fever (fever without a focus) Viremia, bacteremia and septicemia. Prolonged fever (duration more than 10-14 days) Infections (most common) Bacterial: Systemic infections or hidden focal infections Systemic infections: Salmonellosis, brucellosis, listeriosis, tuberculosis. Hidden focal: Abdominal abscess (liver, perinephric, pelvic), endocarditis pyelonephritis, osteomyelitis Viral: Infectious mononucleosis, cytomegalovirus infection, hepatitis. Parasitic: Malaria, toxoplasmosis, visceral larva migrans. Rheumatic diseases Rheumatic fever, systemic rheumatoid arthritis, systemic lupus erythematosus (SLE). Malignancy Leukemia, lymphoma, neuroblastoma.

Fever without a focus

After exclusion of focal infections, the diagnosis of simple fever can be made and because of absence of any other specific features it can be also called "isolated fever" or "nonspecific febrile illness". - In case of simple fever, the most important clinical problem is how to differentiate between viral and bacterial infections. Evaluation of the general condition by the "general clinical assessment" is very useful. With this simple assessment, physician can often differentiate between 3 clinical entities; viremia, bacteremia and septicemia. General clinical assessment History 1. 2. 3. Appetite and thirst. Activity and playfulness. Reaction to parents (the mood).

Examination 1. Level of consciousness. 2. Appearance: normal or sick. 3. Reaction to social stimulation: smiles or looks anxious and irritable.

a) Viremia:

19

Fever is not high and the general condition (by the general clinical assessment) is fair. - In this case, prescribing an antipyretic and re-examination after 24-48 hours is important because re-examination may reveal a focus of infection in up to 40% of cases. b) Bacteremia - Fever can be high and the general clinical assessment reveals that the patient looks sick. - In this case, simple investigations as CBC, CRP and ESR are useful to confirm the bacterial infection. Leukocytosis (above 15.000 cells/mm3) or bandemia (above 10%) are highly suggestive. Also, CRP level between 20-30 mg/liter suggests bacterial infection. - When investigations are not available, it is reasonable to prescribe an oral broadspectrum antibiotic (as ampicillin or amoxicillin) and to re-examine after 24-48 hours. c) Septicemia - The general clinical assessment reveals that the patient is seriously ill. - High fever or hyperpyrexia is suggestive especially when combined with persistent vomiting, pallor, toxic look, cold extremities, mottled skin or disturbed consciousness.

Management of septicemia 1. Urgent hospitalization: This is important for urgent investigations and immediate
parenteral combined antibiotic therapy. 2. Investigations: They should include simple tests (CBC, ESR, CRP), chest x-ray, CSF examination and blood and urine cultures. Polymorphonuclear leukocytosis (abovelS.OOO cells/mm3), bandemia (above 10%), toxic granulations, elevated CRP (above 20 mg/liter) or elevated ESR (above 20 in first hour) are confirmatory findings. 3. Combined parenteral antibiotic therapy: It is made with a broad-spectrum penicillin and an aminogycoside. 4. Close observation: Septicemia is a serious condition with high morbidity and mortality rate. During the course of illness in the hospital, attention should be given to the complications or the manifestations of advanced disease. Early detection of these complications and their prompt management can save lives of many patients.

Fever with a purpuric rash Serious bacterial infection: It is the cause in up to 20% of cases. Meningococcal septicemia is the most common but several other organisms as hemophilus influenza type b, staphylococcal, streptococcal or listeria may be responsible. Management should include urgent hospitalization, blood and CSF cultures and parenteral antibiotic therapy. Viral infections: They are responsible in up to 80% of cases. Enterovirus infection (especially echovirus type 9) is probably the most common. Other viral hemorrhagic fevers are black measles, Dengue fever, and cytomegalovirus infection.

Management of unexplained prolonged fever

20

(fever of unknown origin)

Hospitalization Documentation of fever: The complaint may be false or the fever may subside. Observation: For general condition and appearance of new symptoms or signs. Drugs should be avoided as much as possible to exclude drug fever. Investigations Initial investigations CBC, ESR, and CRP: Positive findings indicate that the illness is significant. Urine and blood cultures. Chest x-ray: May reveal pneumonia or lung infiltrate. Tuberculin test may be done. Serological tests: Widal test (typhoid fever) and monospot test (infectious mononucleosis). Further investigations (if above tests are unrevealing) Abdominal and cardiac ultrasound: May reveal liver abscess, pelvic abscess or endocarditis. Bone marrow examination: May reveal malignant cells. Lymph node biopsy. Blind empirical drug therapy It should be generally avoided as it may mask the condition and make the diagnosis difficult. Exceptions to this rule are: 1. Blind antibiotic therapy: It is indicated in patients with the clinical diagnosis of septicemia but the organism could not be isolated (remember that the diagnosis of septicemia is a clinical and not laboratory one and the causative organism can be identified in only 50% of cases). 2. Blind antituberculous therapy: It is indicated in sick patients with cachexia and weight loss and when the possibility of tuberculosis is strongly standing in spite of the negative laboratory findings.

Management of a febrile infant or child

1. General measures
Bed rest, easily digested food and excess fluids. Supplementation with multivitamins in cases with prolonged dietary restriction.

2. Antipyretic measures Sponging with tap water: It can be effective in lowering the body temperature.
Cold compresses with iced water should be avoided as it increases the peripheral vasoconstriction. Antipyretic drugs: One of several antipyretic drugs can be prescribed orally or rectally every 4-6 hours (see below). In case of hyperpyrexia (temperature above 41C), I.V acetylsalicylic acid can be used.

3. Specific treatment In simple infections (as tonsillitis, otitis media, sinusitis and bronchitis), one oral
antibiotic can be used for about 5-7 days. In serious infections (as pneumonia, meningitis, peritonitis, and septicemia), parenteral combined antibiotic therapy (to cover both gram-positive and gram-negative infections) is essential. Duration of therapy is for at least 7-10 days.

21

Scarlet fever
It is a bacterial disease caused by erythrogenic toxin-producing strain of group A beta hemolytic streptococcus. Epidemiology: It is most common between 2-10 years, but no age is exempted. Both sexes are equally affected. The disease occurs more often during late winter and early spring. It is endemic in most large cities.

Clinical manifestations: start after an incubation period of 2 - 4 days.

Onset: Sudden by high fever (39-40C), sore throat, vomiting and abdominal pain. Rash: Two types Enanthem: Redness and edema over the tonsils, pharynx, tongue and palate. White strawberry tongue: The tongue is at first covered with a white coat with red edematous papillae emerging through this coat. Red strawberry tongue: When the white coat peels off, the tongue becomes red Exanthem: It appears on the first or the second day at the base of the neck and axillae. The rash soon becomes generalized and it fades on pressure. It is a red punctate or finely papular rash (gooseflesh or sandpaper appearance). The cheeks are flushed with a ring of pallor around the mouth (circumoral pallor). The rash fades in 3 to 7 days by brawny desquamation that begins on the face, proceeds over the trunk and finally to the hands and feet. * Complications: They include the following: 1. Spread of the infection: Cervical adenitis, sinusitis, otitis media, mastoiditis and lateral sinus thrombosis, bronchitis, bronchopneumonia, septicemia, and osteomyelitis. 2. Late complications: Occur as a result of an autoimmune process 2-3 weeks after the acute illness. They include rheumatic fever, glomerulonephritis, and erythema nodosum. Diagnosis: It depends mainly on the characteristic clinical picture. Confirmatory investigations include the following: Throat culture: May be positive for group A beta hemolytic streptococcus. Serologic tests: A significant rise of antistreptolysin O titer (ASO titer). Blood picture: There is polymorphonuclear leukocytosis (10.00020.000). Eosinophilia 4 - 20% may be observed. There is usually secondary anemia. Prognosis: It is excellent for recovery and death is rare. The occurrence of rheumatic fever and acute glomerulonephritis has no relation to the severity of the disease.

Treatment

22

Antibiotic therapy: Penicillin is the drug of choice. Oral penicillin V is given in a dose of 400. 000 lU/dose, 4 times/day for 10 days. Erythromycin (50 mg/kg/day) can be used in penicillin sensitive patients and is given for 10 days. Antipyretics for the high fever. Re-examination 2-3 weeks later for detection of late complications as rheumatic fever and glomerulonephritis.

Vaccination (Immunization)
Artificial active immunity (or vaccination) is the specific measures that may be used to protect the individual against infections by raising his resistance. The resistance to infections (or immunity) can be natural or artificial and each can be passive or active. Types of immunity Natural immunity Natural passive immunity: Transplacental immunity from the mother to the fetus. Natural active immunity: Acquired immunity following infections with certain organisms. Artificial immunity Artificial passive immunity: Antisera and immunoglobulins. Artificial active immunity: Vaccination against diseases.

1. Natural passive immunity It is the transplacental immunity from the mother to the fetus.
It gives immunity against infections as poliomyelitis and measles, which form antibodies of the IgG fraction. These antibodies are small and cross the placental to give protection to the newborn. Immunity against these diseases depends on the presence of their antibodies in the maternal circulation. On the other hand, other infections as pertussis form antibodies in the IgM fraction of immunoglobulins. These antibodies are large and do not cross the placenta. Therefore, the newborn is susceptible to these infections. This type of immunity disappears almost completely by the 4th month.

2. Natural active immunity It is the acquired immunity following infections with certain organisms.
Some infections produce a long-standing immunity as measles and chickenpox. On the other hand, some diseases such as poliomyelitis and influenza, in which different strains are identified, may affect the individual more than one time because there is no cross immunity between the different strains.

3. Artificial passive immunity It is the immunity acquired by administration of antisera or immunoglobulins. It

is used in serious infections as tetanus, diphtheria and septicemia. The main examples are: Anti-tetanic serum and antidiphtheritic serum. Immunoglobulins (intramuscular or intravenous forms) in septicemia.

23

4. Artificial active immunity (vaccination) It is the immunity acquired by vaccination (where the subject produces his own
antibodies). The basic goal of this type of immunization is to provide safe, effective protection against diseases, particularly at the time most needed. The early decline of maternally transferred antibodies and the ability of the newborn to produce antibodies make the basis of active immunization. Routine active immunization in Egypt is performed against tuberculosis, diphtheria, pertussis, tetanus, poliomyelitis, hepatitis B, measles, mumps and rubella.

Compulsory vaccination in Egypt

Time At birth or during 1st month At the age of 2 months At the age of 4 months At the age of 6 months 12 months 11/2-2 years 41/2 years Vaccine B.C.G. Oral poliomyelitis. DPT vaccine. Hepatitis B vaccine. Oral poliomyelitis. DPT vaccine. Hepatitis B vaccine. Oral poliomyelitis. DPT vaccine. Hepatitis B vaccine. MMR vaccine. Oral poliomyelitis. DPT vaccine. Oral poliomyelitis. DT vaccine. Dose 0.1 ml (inradermal) In the left deltoid region 2 drops (oral) 0.5 ml (intramuscular). 0.5 ml (intramuscular). 2 drops (oral) 0.5 ml (intramuscular). 0.5 ml (intramuscular). 2 drops (oral). 0.5 ml (intramuscular). 0.5 ml (intramuscular). 0.5 ml (subcutaneous). 2 drops (oral). 0.5 ml (intramuscular). 2 drops (oral). 0.5 ml (intramuscular).

Other vaccines 1. DT vaccine: 2. Meningococcal vaccine: 3. Hemophilus influenza type b 4. Hepatitis A vaccine: 5. Chickenpox vaccine: 6. Rabies vaccine: 7. Influenza vaccine:

0.5 ml I.M. 0.5 ml subcutaneous 0.5 ml I.M.... or subcutaneous, 3 doses 0.5 ml I.M. ... 2 doses 0.5 ml... I.M.... or subcutaneous 1.0 ml I.M.... 5 doses (days: 0,3,7,14,28) 0.5 ml... I.M.... or subcutaneous.

A) Compulsory vaccination
1. T.B. immunization (B.C.G vaccine) Type of vaccine: It is a live-attenuated vaccine. It produces incomplete protection
against tuberculosis but it prevents fatal conditions such as military tuberculosis and tuberculous meningitis.

24

Schedule of vaccination: it is given at 1-2 days of age or during the first month. If vaccination is carried out after the first year, prior tuberculin testing is essential. The dose is 0.1 ml of the vaccine, injected intradermal in the left deltoid region. Booster vaccination: Booster dose is given at the age of 6 years. Complications of vaccination: Localized lymphadenopathy in the axillary region, which necessitates antituberculous treatment. Contraindication of BCG Vaccination: Immunodeficiency or in patients on immuno-suppressive drugs.

2. Diphtheria-tetanus-pertussis vaccine (D.P.T vaccine) Type of vaccine: It contains diphtheria toxoid, tetanus toxoid and killed pertussis. The value of this combination is to reduce the number of injections. Older children above 6 years and adults should not receive pertussis vaccine to minimize untoward reactions, so booster doses are of diphtheria-tetanus vaccine (DT vaccine). Schedule of vaccination: Three successive I.M injections are given at 2 monthly intervals at the age of 2, 4 and 6 months. The dose is 0.5 ml/time. Booster vaccination: Booster doses are given at the age of one and half year and then at the age of 4 and half years. Contraindications: During acute illness, during convalescence from disease, C.N.S. damage and epilepsy and severe reaction (e.g. fever greater than 40.5C). Side Effects: Mild fever within 12 to 24 hours and local reaction at the site of injection. Pertussis vaccine is contraindicated in presence of convulsions.

3. Poliomyelitis vaccine Type of vaccine: The oral Sabin vaccine is a live-attenuated poliovirus vaccine. It has the advantage of easy administration, low cost, no systemic or local reaction, immunity as high as 95% starting few days after the vaccination and of long lasting duration. It provides both humoral immunity and cellular immunity of the gut. Schedule of vaccination: Three successive doses are given at 2 monthly intervals at the age of 2, 4 and 6 months (as D.P.T vaccine). The dose is 2 drops/time. Booster vaccination: At one and half year and at 4 and half years (as D.P.T vaccine). Precautions: The following precautions are important: 1. The vaccine should not be given during diarrhea episodes or during acute infections. 2. In breast-fed infants, the vaccine is to be given one hour before or after feeding to avoid the effect of local immunity of the gastrointestinal tract against poliovaccine. 3. The live attenuated vaccine is contraindicated in cases of immune deficiency and in immune suppressed individuals. The killed vaccine (Salk vaccine) may be used instead.

25

4. Hepatitis B vaccine Ag. Type of vaccine: It is recombinant DNA vaccine prepared from coding of Hbs

Schedule of vaccination: Three successive I.M injections are given at 2 monthly intervals at the age of 2, 4 and 6 months. The dose is 0.5 ml/time. Side Effects: They include transient erythema and induration at the site of injection. Mild low-grade fever may also occur.

5. Measles vaccine Type of vaccine: It is a live attenuated virus. Antibody level produced by the
vaccine is lower than that produced by natural infection. Schedule of vaccination: In developing countries, the vaccine was given at 9 months. (not available alone now in Egypt) The dose is 0.5 ml given subcutaneous. Contraindications: Before the age of eight months of life, during febrile illness or during convalescence from disease. It is also contraindicated in diseases as leukemia or immune deficiencies and with corticosteroid and immunosuppressive therapy. Side Effects: It is generally safe. Short febrile reaction for 2-3 days may occur.

6. Measles-Mumps-Rubella vaccine (MMR Vaccine) Type of vaccine: It is a mixture of 3 vaccines (live attenuated vaccines of
measles, mumps and rubella). Schedule of vaccination: It is given to children at the age of 12 months. The dose is 0.5 ml subcutaneous (single dose). A booster dose at the age of 4-6 years is currently recommended. It can be also given to older children. Side Effects: The vaccine is safe. Fever and coryza-like symptoms may occur 610 days after injection.

B) Non compulsory vaccines

1. DT vaccine Type of vaccine: It is a mixture of toxoids of diphtheria and tetanus. Indications: It is given to children above the age of 6 years. The dose is 0.5 ml
intramuscular. Pertussis vaccine is contraindicated after this age.

2. Meningococcal vaccine Type of vaccine: It is a capsular polysaccharide vaccine. 26

Indications: It is indicated during epidemics of meningococcal meningitis. It gives immunity for about 2-3 years. The dose is 0.5 ml subcutaneous (single dose). A booster dose may be given every 2 -3 years especially in school age children.

3. Hemophilus influenza type b vaccine (Hib vaccine) Type of vaccine: It is a capsular polysaccharide vaccine of Hemophilus influenza
type b.

Indications: It is indicated for prevention of invasive bacterial diseases caused by hemophilus influenza type b especially meningitis, septicemia, cellulitis, arthritis and epiglottitis. It is particularly important in infants and young children below the age of 5 years where the incidence of infection with Hemophilus influenza type b is most prominent. Schedule of vaccination: It is recommended to infants in 3 doses at 2, 4 and 6 months. The dose is 0.5 ml I.M or subcutaneous. A booster dose is given at the age of 18 months.

4. Hepatitis A vaccine Type of vaccine: It is a sterile suspension containing inactivated hepatitis A virus. Indications: It is given to adults and children above the age of one year
especially in areas where hepatitis A infection is common. Schedule of vaccination: It consists of 2 doses. The second dose is given 6 months after the first. The dose in children between 1-15 years of age is 0.5 ml, intramuscular. In adults, the dose is 1.0 ml, intramuscular.

5. Chickenpox vaccine Type of vaccine: It is a varicella virus live-attenuated vaccine. Indications: It can be given to children above the age of one year in a dose of 0.5
ml, I.M or subcutaneous. The second dose at age 4-6 years

6. Rabies vaccine Type of vaccine: It is a live-attenuated vaccine. Indications: Vaccination against rabies is directed to individuals who are
subjected to unprovoked bite of a domestic or wild animal. Dogs and cats are the main offenders. When the offending animal is under observation, vaccination can be withheld until the animal acts abnormally. On the other hand, if the biting animal ran away after an unprovoked bite, immediate vaccination is indicated. Schedule of vaccination: Human diploid cell vaccine (HDCV) is available. It is given in 5 doses (each is 1 ml intramuscular) at 0, 3, 7, 14 and 28 days. Local treatment of the puncture wound is equally important.

7. Seasonal influenza vaccine

27

Type of vaccine: It is an inactivated vaccine, usually trivalent against influenza virus serotypes that are expected in the relevant season. Indications: It is indicated in children, above the age of 6 months, and adults who are at risk especially those with cardiac disease, pulmonary, metabolic disease and immune-deficiency. Schedule of vaccination: The dose is 0.5 ml intramuscular or subcutaneous for children above 3years old and only 0.25 ml for children between 1-3 years.

8. Rota virus vaccine

- Type of vaccine: live attenuated vaccine (monovalent or pentavalent) - Route of administration: oral. - Schedule: 2 doses at age 2 and 4months (for monovalent). 3 doses at age 2,4 and 6 months (for pentavalent). The first dose should not be given after age of 15 weeks and the series of vaccins should be completed before 8 months.

9. Pneumococcal vaccine
- Type of vaccine: capsular polysaccharide - Dosage & Route of administration: 0.5 ml I.M. - Schedule: 3 doses at age 2, 4, 6 months. Booster dose at age 12-18 months

Rheumatic Fever
Rheumatic fever is a systemic disease involving more frequently the joints and the heart and less frequently the central nervous system, skin, and subcutaneous tissues. Rheumatic heart disease (RHD) is a permanent cardiac damage due to severe initial attack or recurrent attacks of rheumatic fever. In developing countries like Egypt, this disease remains a major health problem.

A) Rheumatic fever
Etiology: Rheumatic fever is an autoimmune disease following Group A streptococcal infection of the upper respiratory tract. A latent period of 2-3 weeks between the upper respiratory infection and the onset of rheumatic fever is usually present. Age: It occurs at all ages except infancy, with apeak incidence between 5-15years. Sex: Both sexes are equally affected, but rheumatic chorea is commoner in females.

Diagnosis of rheumatic fever

Diagnosis of rheumatic fever depends on a combination of clinical and laboratory findings. The revised Jones criteria are used as a guide for diagnosis. These criteria include (1) major manifestations, (2) minor manifestations and (3) evidence of recent streptococcal infection. Modified Jones criteria for diagnosis of rheumatic fever
Major manifestations Minor manifestations Evidence of recent

28

Polyarthritis Carditis Chorea Erythema marginatum Subcutaneous nodules

Fever Arthralgia Previous rheumatic fever Acute phase reactants Leukocytosis Raised ESR Raised CRP

streptococcal infection Recent scarlet fever Positive throat culture Antistreptococcal antibodies Antistreptolysin O (ASO) Antihyaluronidase Antistreptokinase

Diagnosis of rheumatic fever depends on the presence of 2 major manifestations or one major and 2 minor manifestations in presence of evidence of recent streptococcal infection.

Some precautions are important: 1. Diagnosis based on 2 major manifestations is stronger than that based on 1 major and 2 minor manifestations. 2. Arthralgia cannot be considered a minor manifestation if arthritis is a major manifestation. 3. Fever (minor manifestation) is usually present at the onset of an acute attack. It ranges from 38.5-40C without characteristic pattern. 4. Acute phase reactants (leukocytosis, raised ESR and CRP) are all one minor manifestation. 5. Evidence of recent streptococcal infection is essential for diagnosis. Antistreptolysin O (ASO) is elevated above 400 Todd units in 80% of cases (normal level is below 150 Todd units). When it is negative, other antistreptococcal antibodies should be tested. 6. Exceptions to the above rules are chorea and rheumatic recurrence (in patients with documented previous rheumatic fever).

Major manifestations of rheumatic fever

29

Polyarthritis It occurs in 75% of cases. It is the most common presenting complaint. The affected joint is red, hot, tender, swollen with limitation of movements. Arthritis in rheumatic fever has the following characters Polyarticular: Affecting more than one joint. Affecting large joints: As knees, ankles, elbows and wrists and less commonly hips. Migratory: Affects a joint for few days and leaves it to affect another joint. Dramatic response to salicylates within 48 hours. If left untreated, symptoms usually disappear spontaneously in 3-4 weeks Carditis It occurs in 50% of initial attacks. It is the most serious manifestation (can be fatal or cause permanent valvular damage). It can be detected on initial examination or appears 1-2 weeks later. Symptoms are evident if pericarditis or heart failure is present. Cardiac manifestations include the following. Myocarditis: Disproportionate tachycardia (to the degree of fever), cardiomegaly, muffled heart sounds or prolonged P-R interval on ECG. Endocarditis: Mitral and aortic valve affection. Mitral valve affection is usually detected by: Apical high-pitched, holosystolic murmur (mitral regurgitation). Apical low-pitched mid-diastolic (Carey-Coombs) murmur. Aortic valve affection is much less frequent. Decrescendo diastolic murmur along the left sternal border (aortic regurgitation). Pericarditis: chest pain and Friction rubs may be detected by auscultation. Congestive heart failure may be present at the onset or occurs during the course of illness. Sydenham chorea It occurs in about 10% of cases. It is a self-limited condition with a variable course (Average duration 3 months up to 6 months). It is characterized by involuntary movements, hypotonia and emotional lability. The movements are semipurposeful and exaggerated by anxiety. Hypotonia can be tested by: Speech changes due to tongue hypotonia. Inability to maintain any movement for a long while e.g. tongue flicking, Inability to maintain extended arms and wrists or hand grip. Pendular knee jerk and abnormal gait (dancing gait) can be demonstrated. Erythema marginatum It occurs in less than 5% of patients. It is the characteristic skin rash of rheumatic fever. It is a red wavy lines or rings with sharp margins, mainly on the trunk. These lesions may come and go for several months. Subcutaneous nodules They occur in 1 % of cases, usually several weeks after onset of the attack. They are round, hard, freely movable, painless swellings, and usually overlying bone prominences, from 2-20mm in size.
Polyarthritis should be differentiated from other causes of arthritis (see arthritis). Carditis should not be confused with innocent murmurs, congenital heart disease or viral myocarditis. Systemic lupus erythematosus may produce a similar picture of pancarditis. Rheumatic chorea should not be confused with other abnormal movements (as tics) or with other less common causes of chorea.

Treatment
30

1. Bed rest: It should continue till activity disappears. Daily examination is important to detect carditis, which almost always appears within 2 weeks of onset. 2. Anti-inflammatory agents: The chosen drugs and the duration of therapy depend on the nature of involvement. Anti-inflammatory agents in rheumatic fever Arthritis only and/or carditis without cardiomegaly Salicylates: 100 mg/kg/24 for 2 weeks, then 75 mg/kg/24 for 4-6 weeks Carditis with cardiomegaly or heart failure Prednisone: 2 mg/kg/24 hours for 2 weeks and taper over 2 weeks. Salicylates: 75mg/kg/24 hours at 2 weeks and continue for 6 weeks. 3. Heart failure: Treatment depends on the severity of failure. Mild cases: Complete bed rest, oxygen therapy, fluid restriction and steroids. Severe cases: - Diuretics: Furosemide (Lasix): 1-2 mg/kg/24 hours. Digoxin: 0.03 mg/kg/24 hours. 4. Chorea: Drugs as barbiturates or chlorpromazine. Haloperidol can be used only in patients over 12 years.

Prevention of recurrence
Benzathine penicillin (1.2 million units, I.M) every 2-3 weeks is the drug of choice. Oral phenoxymethyl penicillin is also effective in a dose of 200,000 units twice daily. Duration of prophylaxis is at least 5 years even in patients with no residual heart disease. In patients with rheumatic valvular disease, prophylaxis continues for life. Initial attacks of rheumatic fever can be prevented by proper treatment of streptococcal pharyngitis (see upper respiratory infections).

B) Rheumatic heart disease (RHD)

Chronic rheumatic heart disease results from permanent valvular damage due to severe initial attack or recurrent attacks of rheumatic fever. Mitral valve is the most commonly affected valve followed by the aortic valve.

Clinical diagnosis
Diagnosis of chronic rheumatic heart disease should include the following: 1. Evidence of rheumatic origin. 2. Detection of valvular lesions. 3. Assessment of cardiac size. 4. Detection of possible associated complications: Acute or chronic

31

Acute: Heart failure, infective endocarditis, rheumatic activity and digitalis toxicity. Chronic: Chronic congestive heart failure and pulmonary hypertension. 1. Evidence of rheumatic origin: The following criteria are suggestive of rheumatic origin, (1) age above 5 years, (2) history of recurrent attacks of tonsillitis, (3) documented previous history of rheumatic fever, and (4) multiplicity of valvular lesions with predominant affection of the mitral valve. 2. Detection of valvular lesions: Valvular lesion can be detected by auscultation of the different cardiac areas. Each valvular lesion has its own characteristic murmur. Characteristic murmurs of valvular lesions in rheumatic heart disease
Mitral regurgitation: Apical harsh pansystolic murmur propagating to axilla. Mitral stenosis: Apical rumbling mid-diastolic murmur. Aortic regurgitation: Soft early diastolic murmur over the aortic area. Aortic stenosis: Rough, loud ejection systolic murmur over the aortic area propagating to neck.

3. Assessment of cardiac size: Mild cardiac enlargement is usually difficult to detect clinically. Moderate enlargement can be detected by inspection and palpation. Huge longstanding cardiomegaly is associated with precordial bulge. 4. Detection of complications: The presence and severity of complications depend on the severity of valvular lesions and the duration of illness. Complications of rheumatic heart disease can be acute or chronic. Acute complications: Acute congestive heart failure is the most important and should not be missed (see pediatric emergencies). Other important acute complications are rheumatic activity (or recurrence), infective endocarditis and digitalis toxicity. Chronic complications: Chronic congestive heart failure and pulmonary hypertension.

Investigations
Some investigations are usually required to determine the cardiac size and to detect the valvular lesions. Other investigation to confirm rheumatic activity or infective endocarditis should be considered in case of clinical suspicion.

Investigations in rheumatic heart disease

Heart x-ray: To detect cardiomegaly. Electrocardiogram (ECG): To detect ventricular hypertrophy (right, left or biventricular). Echocardiography: To detect ventricular hypertrophy and valvular lesions. ESR, CRP and ASO titer: To detect rheumatic activity. Blood culture: With suspected infective endocarditis.

Treatment
Treatment is both medical and surgical.

32

1. Medical treatment: Treatment of acute complications as acute congestive heart failure,

rheumatic activity, infective endocarditis and digitalis toxicity. Patients with chronic heart failure need oral digoxin therapy. 2. Surgical treatment: Valve replacement is indicated in those with moderate to severe valvular lesions.

Infective Endocarditis
Infective endocarditis is a well-recognized complication of congenital as well as rheumatic heart disease. The risk is higher with lesions, which result in a turbulent jet of blood, such as a ventricular septal defect, coarctation and patent ductus.

Causative organisms
The endocardium becomes infected in the presence of a bacteremia, which may occur during dental treatment or cardiac surgery. Two organisms are responsible: Streptococcus viridans. Staphylococcus aureus: It has become increasingly more common. In approximately 10 % of cases, blood cultures are negative. Clinical features include one or more of the following: Toxic manifestations: 1Pale, toxic appearance. 2- Tachycardia out of proportion to fever 3- Splenomegaly in 70 % of cases. 4- Clubbing of fingers. 5- Cutaneous manifestations: Oslers nodes (purplish, pea sized, painful nodules in pads of fingers and toes), Splinter hemorrhage: linear hemorrhage beneath the nails. Janeway spots: painless erythmatous lesions in the palms and soles Embolic manifestations: 1Cerebral infarction: hemiplegia / aphasia / blindness. 2Renal infarction: hematuria even microscopic. 3- GIT, pulmonary infarction. 4- Mycotic aneurysm as a result of occlusion of vasa vasorum of cerebral vs. it may rupture and ends in intracranial hemorrhage. Cardiac manifestations: 1Appearance of new murmurs or change of already present murmurs. 2Rupture of the cusps with appearance of sea gull murmur. 3Heart failure

Investigations
1. 2. 3. Repeated blood culture: Diagnosis depends on positive blood cultures. Echocardiography to detect valvular vegetations. Acute phase reactants (Leukocytosis, raised ESR and CRP).

Treatment
1. Parenteral antibiotic therapy: it is given in large doses for a period of 6 weeks. The choice of antibiotics depends on the causative organism: - Streptococcus viridans: The combination of benzylpenicillin (300 000 unit/kg/day) and gentamicin (4-6 mg/kg/day) is useful. - Staphylococcal infection: Antistaphyococcal drugs as cloxacillin (200 mg/kg/day) should be added. Gentamicin can be substituted with amikacin (15 mg/kg/day).

33

2.

Heart failure, if present, should be treated.

Prevention
Antibiotic prophylaxis: Any child with a heart lesion, congenital or rheumatic (no matter how trivial) needs antibiotic prophylaxis with dental treatment (extraction, fillings) or before surgery (involving the middle ear, tonsils or adenoids). The usual practice is to give oral amoxicillin as a single large dose 1 hour before the treatment.

Suppurative lung diseases

a) Purulent pleurisy (empyema)
Empyema means accumulation of pus in the pleural spaces. Causes: The main causes are: 1. Complication of bacterial pneumonias: Especially pneumococcal, staphylococcal and hemophilus influenza pneumonia. 2. Contamination introduced from trauma or thoracic surgery. 3. Mediastinitis or an intra-abdominal abscess. Clinical picture: Symptoms consist mainly of dyspnea, fever and pain exaggerated by deep breathing, cough or straining. The child often lies on the affected side. Chest signs include dullness on percussion, diminished breath sounds, shifts of the trachea and mediastinum to the opposite side. Investigations: Chest x-ray shows unilateral massive opacity in the affected side with obliterated costophrenic angle and mediastinal shift to the opposite side. Thoracocentesis and culture of pus may reveal the causative organism. Treatment: It includes the following 1. Immediate closed drainage of pus: By an underwater seal or by continuous suction. 2. Systemic antibiotic therapy: For 3-4 weeks according to culture- sensitivity studies.

b) Lung abscess
A lung abscess is a suppurative process resulting in destruction of the pulmonary parenchyma with formation of a cavity containing purulent material. Causes: The main causes of lung abscess in children are: 1. Aspiration of infected material or foreign body. 2. Complicated pneumonia: It may complicate pneumonia caused by aerobic pyogenic organisms such as staphylococcus and klebsiella. 3. Metastatic lung abscess: Uncommon in children and may occur secondary to septic emboli from right-sided bacterial endocarditis and septic thrombophlebitis. 4. Amebic lung abscess: Rare cause in children.

34

Clinical picture: It is characterized by an insidious onset with fever,

anorexia, weight loss and cough often associated with hemoptysis and copious amounts of foul smelling or purulent sputum followed by marked relief of symptoms. Chest x-ray reveals a cavity with or without a fluid level surrounded by consolidation. Treatment: It includes the following: 1. Prolonged antibiotic therapy: For 6 weeks according to culture - sensitivity studies. 2. Resection of the affected lobe: It is indicated in children with recurrent hemoptysis. 3. Bronchoscopy: It is indicated only to identify and remove a foreign body.

c) Branchiectasis
Bronchiectasis is a condition characterized by dilatation of the bronchi with inflammatory destruction of the bronchial and peribronchial tissues and accumulation of exudative material in the dependent bronchi and sometimes their distension. Causes: Bronchiectasis can be congenital or acquired. Congenital bronchiectasis: It occurs due to an arrest in bronchial development leading to cyst formation. It is less common than acquired bronchiectasis. Acquired bronchiectasis is more common and usually occurs due to chronic pulmonary infection. Predisposing factors include (1) foreign body aspiration, (2) enlarged broncho-pulmonary nodes due to TB, (3) lung abscess or localized cysts, (4) asthma, (5) immune deficiency, (6) immotile cillia syndrome, (7) cystic fibrosis, (8) gastroesophageal reflux. Pathological changes: They include the following: 1. Destruction of the ciliated epithelium with loss of elastic tissue. 2. Thickening of the bronchial walls due to interstitial edema and fibrosis. 3. Distortion of the bronchial walls with formation of spherical, cylindrical or fusiform cavitary spaces, which become full of stagnant pus resulting from infection. The mainly affected areas are the basal segments of the lower lobes, the right middle lobe and the lingular segment of the left upper lobe.

1. 2.

Clinical Manifestations: They include the following: Chronic cough with expectoration of copious fetid mucopurulent sputum, usually changing with posture. Hemoptysis may occur. Anorexia, fever and poor weight gain are common.

35

3. 4. 5.

Clubbing of fingers is usually seen. Chest signs: Moist or musical rales may be heard over the affected area as well as signs of consolidation or fibrosis. With extensive bronchiectasis, there is persistent dyspnea and delayed physical growth.

Investigations: Chest x-ray may show honeycomb or soap bubble appearance. CT scan of the chest confirms the diagnosis.

1. 2. 3. 4.

Treatment: It includes the following: Effective postural drainage and physiotherapy. Antibiotic therapy (oral, parenteral or aerosol) according to culture-sensitivity studies. Bronchodilators and symptomatic management. In cases of localized bronchiectasis, lobar resection should be considered.

Painful Oral Lesions

Stomatitis (inflammation of oral mucosa) is a common clinical problem especially in infants and young children. Gingivitis means inflammation of gums with no or minimal affection of the oral mucosa. When inflammation involves oral mucosa and gums, the term gingivostomatitis can be used.

1. Monilial stomatitis (Thrush or oral candidiasis)

- Cause: It is an acute fungal infection of oral cavity caused by Candida albicans. - Age: It is most common in neonatal period and early infancy (where the infection can be acquired at birth or from infected nipple in breast-fed infants). The condition is also common with prolonged antibiotic therapy, malnutrition and T-cell immunodeficiency. - Clinical picture: There is a white flaky plaques covering all or part of the tongue, gingiva and oral mucosa. These plaques when removed leave a bright inflamed base. The condition is mildly painful and may cause feeding difficulty. - Treatment: Antifungal oral drugs as nystatin (Mycostatin suspension) or miconazole (Daktarin oral gel). The condition usually subsides within one week. - Persistent oral moniliasis for more than 10 days in spite of the effective therapy or frequently recurrent lesions should suggest T-cell immunodeficiency.

2. Herpetic gingivostomatitis (ulcerative stomatitis)

36

- Cause: It is an acute viral infection of the oral cavity caused by herpes simplex virus. It is the most common cause of gingivitis and mouth ulceration. - Age: It is most common in children between the ages of 1 - 3 years. - Clinical picture: The condition starts with high fever, severe mouth pain and refusal of feeding. Examination of oral cavity reveals small ulcers (2-10 mm in diameter) over the tongue, gingiva and oral mucosa. In severe cases, ulcers may involve all oral mucosa. The condition usually lasts for 4 - 8 days. Pain usually disappears few days before complete healing of ulcers. - Treatment: It is symptomatic and includes local analgesics and antipyretics. Antiviral agents are not recommended for this simple infection.

3. Herpangina
- Cause: It is an acute viral infection of the oral cavity caused by coxsackievirus. - Age: It is most common in children below the age of 5 years. - Clinical picture: The illness starts with fever, sore throat and refusal of feeding. Examination of oral cavity reveals discrete vesicles and ulcers mainly located on the anterior tonsillar pillars. The ulcers are small in size (1-5 mm in diameter) and few in number (usually 1-5) and each one is surrounded by an erythematous ring. In severe cases, the ulcers may involve the soft palate, uvula, tonsils and posterior pharyngeal wall and their number may reach up to 15. The condition usually subsides over 3-6 days. - Treatment: It is symptomatic and includes local analgesics and antipyretics.

Diarrheal Disorders
Incidence: Deaths from infective diarrhea have been dramatically reduced in the last 2 decades
in Egypt. But diarrhea remains an important cause of morbidity in children < 5 yrs age. Definition: Increase fluidity, frequency and or amount of the stools. Etiology: Infective diarrhea may be bacterial, viral or parasitic. Bacterial diarrhea may be due to: - Shigella. - Salmonella. - E. Coli. - Campylobacter jejuni. - Yersinia enterocoliticus. - Cholera. Viral diarrhea may be due to rotavirus, adenovirs, calicivirus, coronavirus, astrovirus.

Parasitic diarrhea is due to Entameba histolytica or Giardia lamblia. Non Infective diarrhea is due to 1- Dietetic error. 2- Lienteric diarrhea. 3- Antibiotic induced. 4- Disaccharide intolerance. 5- Gastro-intestinal allergy. 6- Rare causes. Pathophysiology of Entero-invasive organisms: The organisms penetrate the entrocyte leading to decrease absorptive function & exudation of serum & blood. Pathophysiology of Entro-toxogenic organisms: The organisms produce toxins which stimulate the entrocyte leading to excess secretion of water & electrolytes 37

Biochemical changes
Vomiting leads to loss of acids, water & electrolytes. Diarrhea leads to loss of H2CO3, K, H2O & electrolytes. :Net results - Loss of H2CO3 more than acids Acidosis. .Loss of K Hypokalaemia - Loss of H2O & electrolytes Dehydration decrease ECF volume (may be shock) decrease renal blood flow ++ Renin- Angiotensin Aldosterone system & oliguria. .Aldosterone H2O & Na absorption with K loss Oliguria increased urea & creatinine & retention of acid metabolites acidosis Shift of .H ion intracellular & Shift of K extacellular more intracellular hypokalemia

Clinical picture of Gastro-entritis

Anorexia, nausea & vomiting. Manifestations of Dehydration or shock. Manifestations of hypokalaemia. Others e.g. DIC & hyperthermia - Diarrhea. - Manifestations of acidosis. - CNS manifestations.

Manifestations of Shock Cold cyanotic extremities. Tachycardia.

- Collapsed superficial veins.

- Severe oliguria

Manifestations of Hypokalaemia Abdominal distension. Flaccidity & hyporeflexia. CNS manifestations Irritability. Apathy.

- General weakness. - Cardiac arrhythmia. - Drowsiness. - Coma.

Management Drug therapy

Medications for the vomiting or diarrhea:
Ineffective May prolong the excretion of bacteria in stools Side-effects Unnecessarily to cost Focus attention away from oral rehydration.

Antibiotics or anti-parasitics

Only for specific bacterial or protozoal infections (e.g. cholera, shigellosis, giardiasis).

38

Dehydration & rehydration

Definition: Dehydration: is the loss of water & electrolytes from extracellular fluid & the intracellular fluid will suffer secondarily. Susceptibility to dehydration: Infants are at particular risk of dehydration because they have: *Greater surface area to weight ratio greater insensible water losses. *No access to fluids when thirsty. *Higher basal fluid requirements (10-12% of body weight). *Immature renal tubular re-absorption processes. Manifestations of Dehydration *Weight loss. *Thirsty. *Depressed fontanels. *Sunken eyes. * Lack tears. *Dry tongue. *Loss of skin turger. *Oliguria. * Prolonged capillary refill time. *CNS manifestations: see before. *Manifestations of Shock: see before

Types of Dehydration

39

Isotonic
W & E Loss ICF Cell size Fluid movement ECF Serum Na Skin turger Tongue CNS Equal No change No change Non Normal Poor Dry Lethargy

Hypotonic
E>W Swollen ECF-to- ICF <130mEq/L Very poor Moist Coma

Hypertonic
W>E Shrunken ICF-to-ECF >150mEq/L Fair Woody Convulsion

* W = water * E. = electrolyte *ECF = extra-cellular fluid. *IECF = intra-cellular fluid.

NB;- 1- Hypernatremic dehydration is dangerous as water is drawn out of the brain cerebral shrinkage multiple, small cerebral hemorrhages and convulsions. 2- Transient hyperglycemia occurs in some patients with hypernatremic dehydration but does not require insulin WHO recommendation for assessment of Dehydration:
The child should be assessed for the following 1- Childs general condition: Lethargic or unconscious; restless or irritable. 2- Sunken eyes 3- Offer him fluid: Not able to drink or drinking poorly. Thirsty (drinking eagerly). 4- Skin pinch: It goes back slowly. It goes back very slowly (> 2 sec.) To Classify Severe Dehydration, you need at least two of the following: - Lethargic or unconscious. - Sunken eyes - Not able to drink or drinking poorly. - Skin pinch goes back very slowly (> 2 sec.) To Classify Some Dehydration, you need at least two of the following: - Irritability. - Sunken eyes.

- Thirsty (drinking eagerly). - The skin pinch goes back slowly. Classify No Clinical Signs of Dehydration: If there is no enough signs to classify as some or severe dehydration. Management of dehydration 1-Mild dehydration: <5% body weight loss Few, if any, clinical signs of dehydration. Treated by: Short-term (< 24 hr.) substitution of normal feeds with a maintenance type of glucose-electrolyte solution, followed by normal diet immediately. 40

Rehydration solutions may be rice-based. 2- Moderate dehydration: 5-10% body weight loss 4- 6 hours trial ORS (75 - 100 ml/kg over this period - orally or by naso-gastric tube). If no improvement IV rehydration 3- Severe dehydration: >10% body weight loss IV rehydration to replace fluid loss. 20 ml/kg in hour (normal saline) to correct shock. Followed by 100 ml/kg normal saline + 5% dextrose in ratio 1:1 (the fluid contain 0.45% NaCl & 2.5% glucose) over 8 hours to correct dehydration Monitor: The child's weight and plasma electrolytes. Acute renal failure may complicate it oliguria. NB: - Persistence of oliguria or anuria, while you are giving IV fluid over-hydration & pulmonary edema. Hypernatremic dehydration: (Difficult to treat). Correction of dehydration should be very gradual over long duration. As rapid reduction in plasma sodium concentration cerebral edema and possible convulsions. Slow reduction in plasma sodium over 48 hr. or more in order not to exceed a reduction in plasma sodium of 10 mmol/L per 24 hours.

Post-enteritis (persistent) diarrhea

Definition: Persistence of diarrhea for more than 2 weeks, caused by:
Sugar intolerance. Cows milk allergy. 3. Bacterial colonization. 1) Sugar intolerance Destruction of the brush border with loss disaccharidases increased disaccharide e.g. lactose in the intestine osmotic diarrhea & acidic stools. 1.

2.

2) Cows milk allergy Damage of intestinal cells by diarrhea intestinal allergy more diarrhea &
persistence of the diarrhea.

3) Bacterial colonization
Bacterial colonization of the upper part of the small intestine intestinal injury & mal absorption due to: 1. Direct bacterial invasion. 2. Toxin production. 3. Bacterial deconjugation of bile salts.

Viral Hepatitis

41

Six hepatotropic viruses are known to cause hepatitis as their primary disease manifestation (see below). These viruses are a heterogeneous group of viruses that cause similar acute clinical illness, except HGV, which appears to cause no or mild disease. - Other non-hepatotropic viruses that can cause hepatitis as part of their clinical course include cytomegalovirus (CMV), rubella, Epstein-Barr virus (EBV), etc.

Comparison between hepatitis viruses

Type of virus Transmission routes Incubation P. Diagnostic test Mortality rate (acute) Carrier state Vaccine Treatment HAV Enterovius (RNA) Feco-oral 15-40 days Anti-HAV IgM 0.1-0.2% HBV Hepadnavirus (DMA) Parenteral, sexual, vertical 50-1 50 days HBsAg, antiHBc Ig M 0.5-2% HCV flavivirus (RNA) Parenteral, sexual 1-5 months Anti-HCV HCV-RNA by PCR 1-2% HDV incomplete (RNA) Parenteral, sexual 20-90 days Anti-HDV 2-20% HEV Calcivirus (RNA) Feco-oral 2-9 weeks Anti-HEV 1-2% (20% in pregnant women) No NO None

No Yes None

Yes Yes Interferon-alpha lamivudine

Yes No Interferonalpha plus ribavirin

Yes Yes (HBV) Interferonalpha

Viral hepatitis markers (antigens and antibodies)

Hepatotropic Viruse Hepatitis A virus (HAV) Hepatitis B virus (HBV) Antigens HAV HBsAg HBcAg HBeAg -HDV Ag --Identified Antibodies Anti-HAV Anti-HAV IgM Anti-HBs Anti-HBc Anti-HBc IgM Anti-HBe Anti-HCV Anti-HDV Anti-HEV, Anti-HEV IgM Anti-HGV

Hepatitis C virus (HCV) Hepatitis D virus (HDV) Hepatitis E virus (HEV) Hepatitis G virus (HGV)

Diagnosis of viral hepatitis

42

Diagnosis of viral hepatitis should include (1) the clinical form, (2) confirmatory investigations of acute liver injury and (3) identification of the causative agent.

1. Clinical forms of acute hepatitis

Acute hepatitis presents with one of four clinical forms or types: a) Icteric hepatitis: It is the most common form. Clinical, manifestations can be divided into 3 stages (preicteric, icteric and convalescent stages). Preicteric stage: It is characterized by mild fever, anorexia, vomiting and abdominal pain. This stage usually lasts for 4 - 6 days and the urine usually becomes dark (bilirubinuria) during the last 1-3 days. Icteric stage: Jaundice appears and the liver is enlarged and tender. The early manifestations as fever, vomiting and abdominal pain disappear but anorexia may continue. This stage usually lasts for 2-4 weeks. Convalescent stage: During this stage, gradual decline of jaundice and reduction of liver size occur. b) Cholestatic hepatitis: In some cases, obstruction to biliary flow occurs. In addition to jaundice, pruritis and clay-colored stool are prominent. c) An icteric hepatitis: This form is commoner in infants. It is mainly characterized by gastrointestinal manifestations as vomiting, diarrhea, colics and anorexia. d) Fulminant hepatitis: It is the least common but the most serious form. Clinical manifestations of acute hepatic failure occur (progressive jaundice, bleeding and rapidly developing coma) and mortality rate is high (around 70%).

2. Confirmatory investigations of acute liver injury

Investigations to confirm the presence of acute liver injury include serum bilirubin level, serum transferases, serum albumin and prothrombin time. Blood ammonia and serum electrolytes are also important.

Laboratory evidence of acute liver injury

Direct or mixed hyperbilirubinemia Mild (2 - 6 mg/dl), moderate (6-10 mg/dl) or severe (more than 10 mg/dl). In fulminant hepatitis, peak levels above 20 mg/dl occur. Raised serum transferases Raised aspartate aminotransferase (AST). Formerly known as (SCOT). Raised alanine aminotransferase (ALT). Formerly known as (SGPT). (Levels between hundreds and thousands are common). Evidence of acute hepatic failure (in fulminant hepatitis) Rising bilirubin level (above 10 mg/dl). Low serum albumin level (below 3 gm/dl). Prolonged prothrombin time (more than 20 seconds). High blood ammonia level (above 150 mcg/dl). Hypokalemia, hyponatremia and metabolic acidosis.

3. Identification of the causative agent 43

a) Clinical differentiation: Accurate clinical differentiation between different viral agents is

almost impossible. However, the following characteristics of different agents could be useful to suggest the causative virus: Hepatitis A: It is the most common form. The onset is acute and course is rather short. Fulminant hepatitis is rare and carrier state or chronic liver disease does not occur. Hepatitis B: It is characterized by insidious onset and prolonged course. Fulminant hepatitis may occur; carrier state and chronic liver disease are possible. Hepatitis C: It is similar to hepatitis B with the difference of being more insidious and more prolonged. Fulminant hepatitis is rare but chronicity occurs in 85% of cases. Hepatitis D: It cannot produce infection without concurrent hepatitis B infection. The illness is severer than hepatitis B but chronicity is less. Hepatitis E: It is similar to A with no chronicity or carrier state. It produces fulminant hepatitis in pregnant females (20%).

b) Laboratory differentiation: Hepatitis markers (antigens and antibodies) of different agents

are the only reliable way for differentiation (see above). Hepatitis A: Anti-HAV antibodies belonging to the Ig M class indicate acute disease, whereas anti HAV Ig G antibodies persist after recovery. Hepatitis B: Acute hepatitis B is heralded by appearance of HBsAg, followed by anti-HBc Ig M. Recovery and development of immunity is noted by appearance of antiHBs. In chronic infections, HBsAg persists and anti-HBc Ig G develops. Hepatitis C: Anti-HCV antibody denotes exposure to infection but does not denote recovery or development of immunity.

Prevention 1. Health precautions Hepatitis A: Isolation of acute cases from day care, school or work during the
contagious period, which lasts 7 days after onset of jaundice. Strict hand washing, particularly after changing diapers and before preparing or serving food is also important. Hepatitis B: Prevention of parenteral transmission by (1) strict screening of blood and blood products, (2) strict regulations and instrument sterilization for all rocedures. Hepatitis C: Same precautions as hepatitis B.

2. Vaccination Hepatitis A: A potent inactivated hepatitis A vaccine is available. Hepatitis B: Routine vaccination of all newborns. Vaccination of high risk
groups e.g. thalassemics and hemophilics receiving repeated blood and blood products and blood and blood products and bilharzial patients, who are prone to develop chronic hepatitis B. Hepatitis C: No available vaccine Hepatitis D: Vaccination against hepatitis B.

44

Anemia with malnutrition and parasites

a) Anemia in protein energy malnutrition
Anemia is a common feature in kwashiorkor. It is usually multifactorial Protein deficiency is the main contributing factor. Iron deficiency and other deficiencies (such as folic acid and vitamin B deficiencies). Red cell hypoplasia in the bone marrow. Shortening of the red cell life span. Associated infections. - Treatment of the anemia involves the following: 1. Adequate amounts of proteins. 2. Iron and folic acid. 3. Treatment of associated bacterial and parasitic infections, if present.

b) Ankylostoma anemia
Patients with heavy hookworm infestation may lose up to 250 ml. of blood daily in the gastro-intestinal tract, thus leading to iron deficiency anemia. The blood loss can be compensated if the number of worms is small, but frequently when the number of worms is high, decompensation occurs with a resultant microcytic hypochromic anemia. Severe hookworm anemia is often associated with edema and hypoalbuminemia. In severe forms, heart failure may occur. The anemia of ankylostomiasis is similar to other iron deficient hypochromic anemia in morphology of blood and its response to iron therapy. - Treatment includes the following: 1. Specific treatment of ankylostoma (flubendazole or albendazole: 100 mg/dose, oral, twice daily for 3 days). 2. Iron therapy (6 mg/kg/day of elemental iron, oral, for 4-6 weeks). 3. A well-balanced nutritious diet. 4. Infrequent blood transfusions may be indicated in severe cases.

c) Schistosomiasis anemia
Patients with chronic intestinal schistosomal infestation lose up to 125 ml. of blood daily leading to iron deficiency anemia. Blood loss in urinary schistosomiasis, however, is intermittent and not constant. Secondary hypersplenism may also account for the anemia accompanying chronic schistosomiasis with hepatosplenomegaly in older children. Treatment of schistosoma anemia includes the following: 1. Specific treatment of schistosoma (praziquentel: 40-60 mg/kg, oral, single dose). 2. Iron therapy (6 mg/kg/day of elemental iron, oral, for 4-6 weeks). 3. A well-balanced nutritious diet. 45

46