Rickets - Short Note - Paediatrics

Vitamin D deficiency

    • Bony deformity and rickets.
    • Without bone abnormalities but with symptoms of hypocalcaemia, i.e. seizures, neuromuscular irritability (tetany), apnoea, stridor. (common before 2 years of age and in adolescence-high demand for calcium in rapidly growing bone results in hypocalcaemia before rickets develops)

Rickets

    • Rickets signifies a failure in mineralisation of the growing bone or osteoid tissue.
    • Failure of mature bone to mineralise is osteomalacia.

Aetiology

Nutritional (primary) rickets

Risk factors

• Living in northern latitudes
• Dark skin
• Decreased exposure to sunlight
• Maternal vitamin D deficiency
• Diets low in calcium, phosphorus and vitamin D, e.g. exclusive breast-feeding into late infancy
• Macrobiotic, strict vegan diets
• Prolonged parenteral nutrition in infancy

Intestinal malabsorption
• Small bowel enteropathy (e.g. coeliac disease)
• Pancreatic insufficiency (e.g. cystic fibrosis)
• Cholestatic liver disease
• High phytic acids in diet (e.g. chapattis)

Defective production of 25(OH)D2
• Chronic liver disease

Increased metabolism of 25(OH)D3
• Enzyme induction by anticonvulsants (e.g. phenytoin, phenobarbital)

Defective production of 1,25(OH)2D3
• Hereditary type I vitamin D-resistant (or dependent) rickets (mutation which abolishes activity of renal hydroxylase)
• Familial (X-linked) hypophosphataemic rickets (renal tubular defect in phosphate transport)
• Chronic renal disease
• Fanconi syndrome (renal loss of phosphate)

Target organ resistance to 1,25(OH)2D3
• Hereditary vitamin D-dependent rickets type II
(due to mutations in vitamin D receptor gene).

Clinical manifestations

• Misery
•  Failure to thrive/short stature
•  Frontal bossing of skull
•  Craniotabes (ping-pong ball sensationof the skull elicited by pressing firmly over the occipital or posterior parietal bones)- Earliest sign
•  Delayed closure of anterior fontanelle
•  Delayed dentition
•  Rickety rosary (palpable or visible costochondral junctions)
•  Harrison sulcus (a horizontal depression on the lower chest corresponding to attachment of the softened ribs and with the diaphragm)
    • Pigeon chest / violin case deformity
    • Pot belly
    • Kyphoscoliosis
•  Expansion of metaphyses (especially wrist in crawling individuals, in ankle in walking infants)
•  Bowing of weight-bearing bones
    • Knock knees
•  Hypotonia
    • Proximal myopathy resulting waddling gait
    • Bone pain- axial skeleton, spine, shoulders, ribs & pelvis
    • Localized pain due to green stick fractures
•  Seizures & tetani due to hypocalcaemia

Diagnosis

• Dietary history for vitamin and calcium intake
• Blood tests – serum calcium is low or normal, phosphate low, plasma alkaline phosphatase activity greatly increased, 25-hydroxyvitamin D may be low and parathyroid hormone elevated.

• X-ray of the wrist joint – shows cupping and fraying of the metaphyses and a widened epiphyseal plate, looser’s zone

Management

Nutritional rickets is managed by,
    • Balanced diet,
    • Correction of predisposing risk factors
    • Administration of vitamin D3 (cholecalciferol).

Healing occurs in 2–4 weeks and can be monitored from the,
    • Lowering of alkaline phosphatase,
    • Increasing vitamin D levels
    • Healing on X-rays (but complete reversal of bony deformities may take years)

Jaundice - Short Note - Paediatric

Jaundice in Children

Babies become clinically jaundiced when the bilirubin level reaches about 80 μmol/L.

Management varies according to

• Infant’s gestational age

• Age at onset

• Bilirubin level and rate of rise

• Overall clinical condition

Age at onset

1. Jaundice <24 h of age

2. Jaundice at 2 days to 2 weeks of age

3. Jaundice at >2 weeks of age

1. Jaundice <24 h of age

Usually results from haemolysis

a. Haemolytic disorders

Rhesus haemolytic disease

• Unconjugated bilirubin

• Antibodies may develop to rhesus anti­gens other than D and to the Kell and Duffy blood groups, but haemolysis is usually less severe.

ABO incompatibility

• Unconjugated bilirubin

• More common than rhesus haemolytic disease

• Most ABO antibodies are IgM so do not cross the placenta, but some group O women have an IgG anti-A-haemolysin effect blood group A infant.

• Occasionally, group B infants are affected by anti-B haemolysins.

• Can cause severe jaundice but it is usually less severe than in rhesus disease.

• The Hb level normal or only slightly reduced

• No hepatosplenomegaly

• Direct Coombs’ test positive

• The jaundice usually peaks in the first 12–72 h.

G6PD deficiency–

• Unconjugated bilirubin

• X linked recessive inheritance

• some females develop significant jaundice

Spherocytosis –

• Unconjugated Bilirubin

• 
  

b. Congenital infection

• Conjugated bilirubin

• Abnormal clinical signs, such as growth restriction, hepatosplenomegaly and thrombocyto­penic purpura.

2. Jaundice at 2 days to 2 weeks of age

a. Physiological jaundice

• Mildly or moderately jaun­diced

• Unconjugated bilirubin

• Term ‘physiological jaun­dice’ can only be used after other causes have been considered.

• Due to high Hb concentration at birth, Short RBC life span (70 days), less efficient hepatic bilirubin metabolism

b. Breast milk jaundice

• Common and more prolonged in breast-fed infants.

• Unconjugated bilirubin

• May be due to increased enterohepatic circulation of bilirubin.

c. Dehydration/ Breast feeding jaundice

• Unconjugated bilirubin

• Due to poor milk intake or delay in establishing breast-feeding

• The infant becomes dehydrated

• Breast-feeding should be continued, some times IV fluid are needed to correct dehydration.

d. Infection

• Unconjugated hyper­bilirubinaemia due to poor fluid intake, haemolysis, reduced hepatic function and an increase in the enterohepatic circulation.

• In particular, urinary tract infection may present in this way.

e. haemolysis usually presents in the first day of life, it may occur during the first week.

f.  Extravascular blood

Bruising

cephal haematoma

IVH

Maternal blood in babies GIT

g. polycythaemia (venous haematocrit is >0.65) will exacerbate the infant’s jaundice

h. Crigler–Najjar syndrome- enzyme glu­curonyl transferase is deficient or absent, may result in extremely high levels of unconjugated bilirubin.

3. Jaundice at >2 weeks of age

Jaundice in babies more than 2 weeks old (3 weeks if preterm), is called persistent or prolonged neonatal jaundice.

Unconjugated hyperbilirubinaemia ( commonest cause)

• Breast milk jaundice’ is the most common cause, affecting up to 15% of healthy breast-fed infants; the jaundice gradually fades and disappears by 4–5 weeks of age.

• Infection, particularly of the urinary tract, needs to be considered.

• Congenital hypothyroidism may cause prolonged jaundice before the clinical features of coarse facies, dry skin, hypotonia and constipation become evident. Affected infants should be identified on routine neonatal biochemical screening (Guthrie test).

Conjugated hyperbilirubinaemia (>_25 μmol/L)

• neonatal hepatitis syndrome

• biliary atresia

sug­gested by the baby passing dark urine and unpig­mented pale stools. Hepatomegaly and poor weight gain are other clinical signs that may be present.

Severity of jaundice

• Blanching the skin with one’s finger.

• The jaundice tends to start on the head and face and then spreads down the trunk and limbs.

• If clinically jaundiced, the bilirubin should be checked with a transcutaneous bilirubin meter or blood sample.

Rate of change & bilirubin level (Neonatal Guideline page 29)

• The rate of rise tends to be linear until a plateau is reached, so serial measurements can be plotted on a chart and used to anticipate the need for treatment before it rises to a dangerous level.

Gestation(Neonatal Guideline page 28,27)

• Preterm infants are more susceptible to damage from raised bilirubin, so the intervention threshold is lower.

Clinical condition

• Infants who experience severe hypoxia, hypothermia or any serious illness may be more susceptible to damage from severe jaundice.

• Drugs which may dis­place bilirubin from albumin, e.g. sulphonamides and diazepam, are therefore avoided in newborn infants.

Management of Jaundice

• Breast-feeding & avoid dehydration (but studies have failed to show that routinely supplementing breast-fed infants with water or dextrose solution reduces jaun­dice)

• Phototherapy -Only given for unconjugated hyperbilirubinaemia

Preparation for phototherapy

• This involves exposure of the naked baby to blue light / CFL/LED of wave length 450-460nm

• Keep babies at the distance recommended by the manufacturer for the phototherapy lights to be maximally effective and safe (avoid hyperthermia). In case of fluorescent light phototherapy machines baby should be kept about 18 inches away from the light.

• Ideal irradiance: Use of intensive phototherapy with irradiance in blue-green spectrum of at least 20-30μW/cm2/nm and delivered to as much of the infant’s surface area as possible.

• The light waves convert the bilirubin to water soluble nontoxic forms which are then easily excreted.

• Advantages of phototherapy: non-invasive, effective, inexpensive and easy to use

• Frequent feeding, every 2-3 hours and change of posture should be promoted in an infant receiving phototherapy.

• Eyeshades should be fixed., External genitalia should be covered to prevent soiling from urine and stools. The nappy should cover only a minimum area of body surface of the baby.

Side effects of phototherapy

• Increased insensible water loss when providing phototherapy in cots: breastfeed more frequently / provide adequate fluids to avoid dehydration

• Loose green stools: weigh often and compensate with breast milk.

• Skin rashes (macular popular): harmless, no need to discontinue phototherapy;

• Bronze baby syndrome: occurs if baby has conjugated hyperbilirubinaemia. If so, discontinue phototherapy

• Hypo or hyperthermia: monitor temperature frequently.

All the side effects are reversible & no long term consequences noted.

Exchange transfusion

• Exchange transfusion is required if the bilirubin rises to levels which are considered potentially dangerous. Blood is removed from the baby in small aliquots, (usually from an arterial line or the umbilical vein) and replaced with donor blood (via peripheral or umbilical vein).

• Twice the infant’s blood volume (2 × _80 ml/kg) is exchanged.

• Donor blood should be as fresh as possible

• Intravenous immunoglobulin reduces the need for exchange transfusion.

• There is no bilirubin level known to be safe or which will definitely cause kernicterus. In rhesus haemolytic disease, it was found that kernicterus could be pre­vented if the bilirubin was kept below 340 μmol/L (20 mg/dl).

Biliary Atresia - Short Note - Paediatrics

Biliary atresia is not very common. However it's the major differential diagnosis of Obstructive jaundice in a neonate. Here are the common DD for obstructive jaundice,

• Biliary atresia
• Neonatal hepatitis
• Choledocal cyst
• Tyrosinaemia
• Alpha 1 antitrypsin deficiency
  

Biliary atresia

    • This occurs in 1 in 14 000 live births.
    • It is a progressive disease, in which there is destruction or absence of the extra-hepatic biliary tree and intrahepatic biliary ducts.
    • This leads to chronic liver failure and death unless surgical intervention is performed.

Clinical features

    • Normal birth weight but fail to thrive as the disease progresses.
    • They are usually mildly jaundiced
    • Pale stools
    • Dark Urine
    • Hepatomegaly
    • Splenomegaly (secondary to portal hypertension)
    • Features of cirrhosis may be present in advance cases (clubbing, palmar erythema, spider nevi, gynaecomastia, caput medusa)

Investigations

    • Liver function tests - little value in the differential diagnosis.

    • Fasting abdominal ultrasound may demonstrate a contracted or absent gallbladder

    • Radioisotope scan with TIBIDA shows good uptake by the liver, but no excretion into the bowel.

    • Liver biopsy demonstrates features of extrahepatic biliary obstruction

    • Diagnosis is confirmed at laparotomy
 

Management

Surgical bypass of the fibrotic ducts, hepatoportoenterostomy (Kasai procedure)  -loop of jejunum is anastomosed to the cut surface of the porta hepatis, facilitating drainage of bile from any remaining patent ductules.

(If surgery is performed before the age of 60 days, 80% of children achieve bile drainage. The success rate diminishes with increasing age)

Postoperative complications  -cholangitis
                                               -malabsorption of fats and fat-soluble vitamins

                                               -cirrhosis and portal hypertension can occur even after Kasai procedure

If the operation is unsuccessful, liver transplantation  (Biliary atresia is the single most common indication for liver transplantation in the paediatric age group.)

Answer the following question.

01. A 3 week old breast fed infant has deep jaundice. On physical examination the liver is 3cm below the costal margin. What is the most important laboratory test in this child to diagnose the condition at this time?

a. Serum ceruloplasmin level

b. Direct and total bilirubin levels

c. Hepatic ultasonography

d. Full blood count

e. Urine urobilinogen level

Comment your answer.