PEDIATRIC NURSING SEMINAR

SUBMITTED TO,MRS RAJALEKSMI. KASSO PROFESSORGOVT COLLEGE OF NURSING, ALAPPUZHASUBMITTED BY, MRS. DIVYA RAJII YR MSC NURSING GOVT COLLEGE OF NURSING, ALAPPUZHA

OBJECTIVES

Central objectives

At the end of the seminar the group will gain adequate knowledge regarding Indian childhood cirrhosis, Wilson's disease and Reye syndrome.

Specific objectives

On completion of the seminar the group will be able to,

Define the disease Explain the etiological factors of the disease Describe the pathophysiology of the disease Discuss the diagnostic tests for the disease Explain the management of the disease Illustrate the nursing diagnosis and nursing interventions for the disease.

INDIAN CHILDHOOD CIRRHOSIS

INTRODUCTION

Indian childhood cirrhosis (ICC), a disease considered to have been endemic in and unique to India has now been documented in children of non-Indian origin from other countries. The onset is insidious with nonspecific complaints such as abdominal distention, irregular fever, excessive crying and altered appetite. The disease is typical of young children (12 to 36 months of age) with hepatomegaly and even greater splenomegaly and death within 3 to 33 months. A common killer disease in the past, Indian Childhood Cirrhosis (ICC) which became preventable and treatable in the early 1990s is now rare.

DEFINITION

Indian childhood cirrhosis is an auto immune disorder characterized by fever, abdominal distension and hepato-spleenomegaly and most often seen in Indian children between the age of 6 month to 4 years.

EPIDEMEOLOGY

Indian childhood cirrhosis is more common in the age group of 6 month to 4 years. It is more affected in male child than female child (1 : 4), the first born is at greater risk. Among twins, the member of the pair on mixed or artificial feeding in predisposed families was

reported to have developed cirrhosis of liver. If the other twin was purely breast-fed for first six months, he or she escaped the illness.

A definite family predisposition is the hallmark of ICC. Siblings and twins are affected. An increased prevalence of peptic ulcer, asthma, diabetes and migrane in the pedigrees affected by ICC has been observed. .

A large majority of cases belongs to middle class families. Majority of the patients have vegetarian dietetic background.

Recently, a significant decline in the incidence of Indian Childhood Cirrhosis has been observed in all parts of India since the use of copper and brass utensils for boiling milk is reduced.

ETIOPATHOGENESIS

ICC continues to be a disease of obscure etiology. The following factors may predispose to the illness:

Toxic (copper intoxication): Studies reported that there is an evidence of excess of copper binding proteins (orcein) in the liver of patient with ICC.

if the baby is weaned earlier and if the milk supplements were added to the breast milk often before 3 months of age.

use of copper or copper alloy pots for boiling milk and cooking food. During boiling of milk, copper is released from the copper pots and this is probably absorbed in excess from the gut by infant.

Viral infection of the liver: It is a consequence of neonatal or infective hepatitis.

Immunologic factors: A variety of immunological disturbances were reported in patients with Indian Childhood Cirrhosis. High levels of circulating immune complexes may indicate that an environmental insult might alter the hepatocyte or tissue proteins and initiate an immune mediated injury to the liver.

Nutritional factors: - it is believed that malnutrition is an important cause of cirrhosis. The objections to this hypothesis are:

Cirrhosis is rare in children suffering from kwashiorkor. Cirrhosis is rare in Africa, the home of kwashiorkor. Cirrhosis is uncommon in poor in whom malnutrition is common. On the contrary, the

incidence of ICC is high in the middle class families. Fatty changes of liver in kwashiorkor is either absent or very insignificant in ICC.

So, nutrition does not have clear role in its pathogenesis. All children are equally affected. Good nutrition does not protect the child from the disease.

Hepatotoxic agents: Some hepatotoxic agents like Aflatoxin, produced by Aspergillus flavus that grows on ground nuts, maize, and rice can predispose to this disease. But the actual cause effect relationship is not established.

Familial history of the disease: A definite family predisposition is the hallmark of ICC. An increased prevalence of peptic ulcer, asthma, diabetes and migrane in the pedigrees affected by ICC has been observed.

Metabolic factors: A child with inborn error of tryptophan metabolism, aminoaciduria, aminoacidemia, disturbed lactose, zinc, copper and magnesium metabolism can predispose to the disease. So a child at risk should be put on low tryptophan diet.

To conclude, no single factor seems to be the cause of ICC. It is possible that a genetically prone child suffers from one or more of the superadded factors (viral, toxic, metabolic and autoimmune) leading to the overt picture of ICC.

PATHOPHYSIOLOGY

ICC manifests with jaundice, pruritus, lethargy, and hepatosplenomegaly. Histologically, it is characterized by hepatocyte necrosis, Mallory bodies, intralobular fibrosis, and inflammation. There is an increased hepatic copper content, usually >700microgram per gram dry weight.

CLINICAL FEATURES

The onset is generally vague and ill defined, ranging from no symptoms to an icteric onset. Some infants show pre cirrhotic symptoms.

Two modes of presentation are known: a) Insidious which occurs in a large majority of the cases and b) Acute which is less common.

Insidious onset: In this, the disease will last for 6 months to 3years. Symptoms are grouped under 2 headings.

Pre-cirrhotic symptoms Cirrhotic symptoms Irritability Disturbed appetite Chalky, pasty stools and

distension of abdomen. Constipation or diarrhea Often slight irregular

fever.

Cirrhotic symptoms are grouped under 3 stages:Stage I

Slight fever Liver is enlarged to 3-5cm, edges become sharp

and giving an appearance of leafy boarder. Children exhibits jaundice Poor growth Anorexia Constipation/ diarrhea. Clay colored stools. Growth failure

Stage II Diffuse hepatomegaly Splenomegaly Ascites Esophageal varices Hematemesis Anemia Muscle weakness Lethargy GI bleeding.

Stage III: It is the terminal stage of the disease Restlessness Confusion Dyspnea and cyanosis on exertion. Evidences of hepatocellular failure in the form of

palmar erythema and spider nevi appearance on the upper torso

A peculiar garlic odor is present in patients with impending liver cell failure.

Enlarged and hard spleen Terminally, there is jaundice and hepatic coma

and is often associated with gastro intestinal bleeding. Child may die at this stage either from hepatic failure or intercurrent infections.

DIAGNOSTIC EVALUATION

1. History collection 2. Complete physical examination:

Liver can be palpable, very firm in consistency and its boarders will be sharp. On auscultation hepatic bruit in severe cases. If there is ascites, fluid thrill test can be done.

3. Liver function test:

increased ALT(alanine transaminase, an enzyme present in hepatocytes.) increased GGT( gama glutamyl transpeptidase)

4. Prothrombin time, clotting time and bleeding time should be assessed. PT will be prolonged 5. Liver biopsy: to find out the sclerosis of liver. It is a reliable method of arriving at a foolproof of

diagnosis. 6. Cupriuresis: testing the presence of copper in urine after administration of d-penicillamine.

TREATMENT

Until recently, ICC was dubbed as a “frustrating situation” for which no specific treatment was available. If the diagnosis is made at an early stage (before the development of jaundice and ascites), ICC is potentially treated.

1. Initial stage: Adequate diet with enough of good quality proteins, vitamins and minerals is desirable. Antibiotics should be given to treat the intercurrent infections / infestations. The drug of choice is d- pencillamine (which chelate copper) in a dose of 20- 40 mg/kg/day

for 12 to 18 months, leads to marked improvement and even total reversal in the histopathologic picture.

Symptomatic treatment should be given. Immuno modulators such as levamisole can be used Corticosteroids and gammaglobulins are also helpful. administer IV fluids if there is dehydration Prevention of infection: follow aseptic techniques Prophylactic antibiotics can be given to prevent infection

2. Terminal stage: If the patient has entered precoma or coma, the protein intake should be reduced. administration of neomycin by gavage and 20% IV glucose drip are helpful. oxygen can be administered if necessary. exchange transfusion to remove the circulating toxins.

SURGICAL MANAGEMENT

No specific surgical correction. The only successful treatment for end stage liver disease is liver transplantation.

If there is portal hypertension with hematemesis, Sengstaken tube may help to control the esophageal bleed.

A portocaval anastamosis may be done to relieve the portal hypertention and complications of hypersplenism

NURSING MANAGEMENT

Provide symptomatic treatment to the child. Provide adequate rest and semi fowler’s position. Check and record the abdominal girth every 4th hourly. Administer IV fluids if needed. Provide small and frequent diet. Provide protein rich food and massive doses of vitamin B6. Follow aseptic techniques to prevent infection. Intake and output chart should be maintained. Provide parental education:

explain the cause, symptoms and management of the disease avoid food rich in copper like dry nuts, chocolates, liver etc provide small and frequent diet to the child. Advise the mother to breast feed their baby for longer period and not to introduce food

supplements beyond the age of 6 months. Milk used for infant should not be boiled and stored in copper and copper alloy pots. reduce the use of brass and copper vessels. Use aluminium and steel utensils. foods rich in tryptophan ( milk, eggs, meat, nuts, beans, fish, and cheese) should be reduced. provide more vitamin B6 foods like potato, banana, spinach, soya bean, fruits and

vegetables.( vitamin B6 help to convert tryptophan to niacin)

Nursing diagnosis

1. Hyperthermia related to inflammatory process in the liver. 2. Impaired breathing pattern related to pressure on diaphragm secondary to ascites. 3. Imbalanced nutrition less than body requirement related to anorexia. 4. Diarrhoea or constipation related to acute abdominal condition. 5. Parental anxiety related to management of the disease condition.

WILSON DISEASE

INTRODUCTION

Wilson’s disease is an inborn error of metabolism due to toxic accumulation of copper in liver, brain, cornea and other tissues which manifest as neurological or psychiatric symptoms.

Wilson disease (WD), also known as hepatolenticular degeneration, was first described by American neurologist, Kinnear Wilson, in 1912.

DEFINITION

Wilson disease (hepatolenticular degeneration) is an autosomal recessive disorder that can be associated with degenerative changes in the brain, liver disease, and Kayser-Fleischer rings in the cornea.

EPIDEMIOLOGY

The incidence is 1/50,000 to 1/100,000 births. It is progressive and potentially fatal if untreated; specific effective treatment is available.

WD may present with hepatic, hematologic, neurologic, or psychiatric symptoms. WD presents as liver disease more commonly in children and younger adults than older adults. Its most typical presentation is that of hepatic or hematologic symptoms in the second decade of life. Neurologic and psychiatric presentations are more common in the third and fourth decades.

PATHOGENESIS

Copper is an essential metal which acts as a cofactor for many proteins. In normal human copper metabolism, the dietary intake of copper exceeds physiologic needs and is therefore excreted. Copper is absorbed in the stomach and proximal small intestine relatively efficiently; therefore, to avoid copper toxicity, the amount of copper absorbed and stored in the body must be finely regulated. The main system for achieving such regulation is the hepatic excretion of copper into bile. Up to 80% of absorbed copper is actually excreted in bile to maintain this homeostasis.

WD is transmitted by autosomal recessive inheritance. It is caused by a mutation in the ATP7B gene. The ATPB7 gene normally codes for a metal-transporting P-type adenosine triphosphatase (ATPase), mainly expressed on hepatocytes. In healthy, this ATPase functions in the transmembrane transport of

Schematic diagram of copper storage and excretion

copper within hepatocytes. In WD, the absent or reduced function of this ATPase results in the decreased hepatocellular excretion of copper into bile and defective incorporation of copper into ceruloplasmin. This in turn leads to the progressive accumulation of copper in the liver, and subsequent hepatic injury. Over time, copper may be released into the bloodstream and deposited in secondary organs, such as the brain, cornea, and kidneys. Clinical disease therefore may range over a variable spectrum including abnormal liver function tests to fulminant hepatic failure and cirrhosis, to seizures, psychosis, and other neurologic manifestations.

CLINICAL MANIFESTATIONS

Disease presentations are variable. The younger the patient, the more likely hepatic involvement will be the predominant manifestation. Girls are 3 times more likely than boys to present with acute hepatic failure. After 20 yr of age, neurologic symptoms predominate. Clinical symptoms of liver involvement in WD typically do not occur prior to 3–5 years of life.

Patients less than 20 years old tend to present with liver dysfunction whereas older patients typically present with psychiatric and neurologic manifestations.

Forms of Wilsonian hepatic disease include asymptomatic hepatomegaly (with or without splenomegaly), subacute or chronic hepatitis, and acute hepatic failure (with or without hemolytic anemia).

From a hepatic perspective, signs and symptoms may include:

asymptomatic elevation of aminotransferases asymptomatic hepatomegaly isolated splenomegaly acute hepatitis fatty liver portal hypertension with possible associated gastrointestinal (variceal) bleeding ascites edema other effects of hepatic dysfunction (delayed puberty, amenorrhea, coagulation defect) cirrhosis, and/or fulminant hepatic failure.

From a neurologic or psychiatric perspective, signs and symptoms may include:

changes in behavior deterioration in school performance movement disorders lack of motor coordination rigid dystonia dysarthria drooling seizures

migraine headaches anxiety depression insomnia, personality changes, and/or psychosis

Other manifestations include:

Kayser-Fleischer rings may be absent in young patients with liver disease but are always present in patients with neurologic symptoms.

Menstrual irregularities (e.g. amenorrhea, infertility), Coombs-negative hemolytic anemia (possibly related to the release of large amounts of copper from

damaged hepatocytes) Copper deposition in the kidneys may lead to nephrocalcinosis, hematuria, or aminoaciduria. Cardiac manifestations may include cardiomyopathy and arrhythmias. Unusual manifestations include arthritis, infertility or recurrent miscarriages and endocrinopathies

(hypoparathyroidism).

DIAGNOSIS

Wilson disease should be considered in children and teenagers with unexplained acute or chronic liver disease, neurologic symptoms of unknown cause, acute hemolysis, psychiatric illnesses, behavioral changes, Fanconi syndrome, or unexplained bone (osteoporosis, fractures) or muscle disease (myopathy, arthralgia).

Serum ceruloplasmin: Most patients with Wilson disease have decreased ceruloplasmin levels ( < 20 mg/dL).

Serum copper level: may be elevated in early Wilson disease Urinary copper excretion: Urinary copper excretion (usually < 40 μ g/day) is increased to > 100 μ

g/day and often up to 1,000 μ g or more per day. Response of urinary copper output to chelation: Estimation of urinary copper after a d-

penicillamine challenge (During the 24 hr urine collection patients are given two 500 mg oral doses of d –penicillamine 12 hr apart) help differentiate WD from other causes of raised urinary copper; excretion >1,600 μ g/24 hr. is characteristic of WD.

Demonstration of Kayser-Fleischer rings, which might not be present in younger children, requires a slit-lamp examination by an ophthalmologist.

Liver biopsy is of value for determining the extent and severity of liver disease and for measuring the hepatic copper content (normally < 10 μ g/g dry weight). In Wilson disease, hepatic copper content exceeds 250 μ g/g dry weight. In later stages of Wilson disease hepatic copper content can be unreliable because cirrhosis leads to variable hepatic copper distribution and sampling error.

TREATMENT

WD is fatal without treatment. Treatment modalities for WD include diet modification, chelation, zinc, antioxidants, tetrathiomolybdate, and liver transplantation. Choice of specific therapy is dependent upon clinical presentation.

Dietary modification

Dietary modification with restriction of consumed copper is nearly universally recommended for WD patients for at least their first year of therapy.

A major attempt should be made to restrict dietary copper intake to < 1 mg/day. Foods such as liver, shellfish, nuts, mushroom and chocolate should be avoided. If the copper content of the drinking water exceeds 0.1 mg/L, it may be necessary to demineralize the water.

Copper-chelating agents

Copper chelation is the mainstay of treatment, which leads to rapid excretion of excess deposited copper. Currently, D-penicillamine and trientine are the typical chelation medications utilized in treating WD.

oral administration of d -penicillamine ( β , β -dimethylcysteine) in a dose of 1 g/day in 2 doses before meals for adults and 20 mg/kg/day for pediatric patients

or

triethylene tetramine dihydrochloride at a dose of 0.5-2.0 g/day for adults and 20 mg/kg/day for children.

In response to chelation, urinary copper excretion markedly increases, and with continued administration, urinary copper levels can become normal, with marked improvement in hepatic and neurologic function and the disappearance of Kayser-Fleischer rings.

Pyridoxine (25 mg/ day) should be co-administered with both D-penicillamine and trientine.

Severe adverse reactions can occur and have been reported to occur at a frequency of approximately 30% of patients treated with D-penicillamine and 5% of patients treated with trientine. These reactions may include hypersensitivity reactions, thrombocytopenia, neutropenia, proteinuria, and autoimmune diseases.

Efficacy of treatment is determined by following 24-hour urine copper measurements that is followed every 3 months for the first 2 years and then annually. Drug toxicity needs to be followed closely with a complete blood count, hepatic panel, creatinine, and urinalysis serially.

Ammonium tetrathiomolybdate is another alternative chelating agent under investigation for patients with neurologic disease; initial results suggest that significantly fewer patients experience neurologic deterioration with this drug compared to penicillamine. The initial dose is 120 mg/day (20 mg between meals tid and 20 mg with meals tid). Side effects include anemia, leukopenia, thrombocytopenia, and mild elevations of transaminases.

Zinc therapy

Zinc has also been used as adjuvant therapy, maintenance therapy, or primary therapy in presymptomatic patients, owing to its unique ability to impair the gastrointestinal absorption of copper.

Zinc acetate is given in adults at a dose of 25-50 mg of elemental zinc 3 times a day, and 25 mg 3 times a day in children > 5 yr of age.

Side effects are mostly limited to gastric upset.

Liver transplantationIn hepatic failure, liver transplantation is the most appropriate therapy. Plasmapheresis or kidney

dialysis may be used as temporizing measures to bridge to transplant. It is also indicated in the absence of liver failure in patients with neurological WD in whom chelation therapy has proved ineffective.

SCREENING FOR WD

Screening for WD in asymptomatic relatives should begin at 3 years of age. This screen should include a history and physical examination, hepatic function panel, prothrombin time and INR, slit lamp examination by a pediatric ophthalmologist, 24-hour urine copper, and consideration of genetic testing.

PROGNOSIS

Untreated patients with Wilson disease can die of hepatic, neurologic, renal, or hematologic complications. The prognosis for patients receiving prompt and continuous penicillamine is variable and depends on the time of initiation of and the individual response to chelation. Liver transplantation should be considered for patients with fulminant liver disease, decompensated cirrhosis, or progressive neurologic disease; the last indication remains controversial. Liver transplantation is curative, with a survival rate of ∼ 85-90%. In asymptomatic siblings of affected patients, early institution of chelation or zinc therapy can prevent expression of the disease.

REYE SYNDROMEINTRODUCTION

Reye syndrome is characterized by acute non-inflammatory encephalopathy and fatty degenerative liver failure. The syndrome was first described in 1963 in Australia by RDK Reye and described a few

months later in the United States by GM Johnson. Reye syndrome typically occurs after a viral illness, particularly an upper respratory tract infection, influenza, varicella, or gastroenteritis, and is associated with the use of aspirin during the illness. A dramatic decrease in the use of aspirin among children, in combination with the identification of medication reactions, toxins, and inborn errors of metabolism (IEMs) that present with Reye syndrome–like manifestations, have made the diagnosis of Reye syndrome exceedingly rare.

DEFINITION

Reye syndrome is a disorder defined as acute encephalopathy associated with other characteristic organ involvement. It is characterized by fever, profoundly impaired consciousness, and disordered hepatic function.

ETIOLOGY

The etiology of RS is not well understood, but most cases follow a common viral illness, typically influenza or varicella. Etiological factors include:

Pathogens

Influenza virus types A and B and varicella-zoster virus are the pathogens most commonly associated with Reye syndrome. Other pathogens include parainfluenza virus, adenovirus, coxsackievirus, measles, cytomegalovirus, Epstein-Barr virus, HIV, retrovirus, hepatitis virus types A and B, mycoplasma, chlamydia, pertussis, shigella, and salmonella.

Salicylates

The association of Reye syndrome with salicylates, particularly aspirin, was demonstrated in several epidemiologic studies around the world. Less than 0.1% of children who took aspirin developed Reye syndrome, but more than 80% of patients diagnosed with Reye syndrome had taken aspirin in the past 3 weeks. Recommendations by government health agencies that children not be treated with salicylates led to an immediate and dramatic decrease in the incidence of Reye syndrome.

Other agents

Acetaminophen, outdated tetracycline, valproic acid, warfarin, zidovudine didanosine, and some neoplastic drugs have been associated with Reye syndrome or Reye-like syndrome. Nonsteroidal anti-inflammatory drugs, including sodium diclofenac and mefenamic acid, are thought to produce or worsen Reye syndrome. An association with antiemetics, such as phenothiazines, has been postulated but not substantiated.

Reye syndrome or Reye-like syndrome may also be associated with insecticides; herbicides; isopropyl alcohol; paint; paint thinner; hepatotoxic mushrooms etc

Inborn errors of metabolism

IEMs that produce Reye-like syndromes include fatty-acid oxidation defects, particularly medium-chain acyl dehydrogenase (MCAD) and long-chain acyl dehydrogenase deficiency (LCAD) inherited and acquired forms, urea-cycle defects, amino and organic acidopathies, primary carnitine deficiency, and disorders of carbohydrate metabolism.

EPIDEMIOLOGY

Incidence peaks between age 5 and 14 years; 13.5% were younger than 1 year. Reye syndrome rarely occurs in newborns or in children older than 18 years. Reye syndrome is equally distributed between the sexes.

PATHOPHYSIOLOGY

RS is a condition characterized pathologically by cerebral edema and fatty changes of the liver. The onset of RS is notable for profuse effortless vomiting and varying degrees of neurologic impairment, including personality changes, seizures, and coma, that lead to increase ICP, herniation, and death

The pathogenesis of Reye syndrome, while not precisely elucidated, appears to involve mitochondrial injury (induced by various viruses, drugs, exogenous toxins, and genetic factors) resulting in dysfunction that inhibits oxidative phosphorylation and fatty-acid beta-oxidation in a virus-infected, sensitized host. The host has usually been exposed to mitochondrial toxins, most commonly salicylates (>80% of cases).

Histologic changes include cytoplasmic fatty vacuolization in hepatocytes, astrocyte edema and loss of neurons in the brain, and edema and fatty degeneration of the proximal lobules in the kidneys. All cells have pleomorphic, swollen mitochondria that are reduced in number, along with glycogen depletion and minimal tissue inflammation. Hepatic mitochondrial dysfunction results in hyperammonemia (elevated serum ammonia), which is thought to induce astrocyte edema, resulting in cerebral edema and increased intracranial pressure (ICP).

CLINICAL PRESENTATION

History:

Most patients had at least 1 viral illness (viral upper respiratory illness or influenza, varicella, gastroenteritis) in the 3 weeks preceding the onset of Reye syndrome.

Salicylates were detectable in the blood of 82% of patients. Reye syndrome can occur after vaccination with live viral vaccines.

Physical Examination

Signs and symptoms of Reye syndrome include protracted vomiting, with or without clinically significant dehydration; hepatomegaly in 50%; minimal or absent jaundice; and lethargy progressing to encephalopathy,

Cardinal Symptoms Reye’s Syndrome

Persistent vomiting Diarrhea Lethargy Restlessness and irritability Hydrocephalus Hyperammonimia Hyperglycemia

obtundation, coma, seizures, and paralysis. Notably, patients are afebrile.

HURWITZ CLASSIFICATIONStage 0 Alert, abnormal history and laboratory findings consistent with Reye

syndrome, and no clinical manifestationsStage 1 Vomiting, sleepiness, and lethargy

Stage 2Restlessness, irritability, combativeness, disorientation, delirium, tachycardia, hyperventilation, dilated pupils with sluggish response, hyperreflexia, positive Babinski sign, and appropriate response to noxious stimuli

Stage 3 Obtunded, comatose, decorticate rigidity, and inappropriate response to noxious stimuli

Stage 4 Deep coma, decerebrate rigidity, fixed and dilated pupils, loss of oculovestibular reflexes, and dysconjugate gaze with caloric stimulation

Stage 5 Seizures, flaccid paralysis, absent deep tendon reflexes (DTRs), no pupillary response, and respiratory arrest

Stage 6 Patients who cannot be classified because they have been treated with curare or another medication that alters the level of consciousness

DIAGNOSIS

Workup to exclude inborn errors of metabolism (IEMs) must be performed and should include evaluation for defects of fatty-acid oxidation, amino and organic acidurias, urea-cycle defects, and disorders of carbohydrate metabolism.

Computed tomography (CT) of the head may reveal cerebral edema, but the results are usually normal.

Electroencephalography (EEG) may reveal slow-wave activity in the early stages and flattened waves in advanced stages.

MRI characteristics of Reye syndrome are symmetric thalamic, white matter and basal ganglia lesions, in children with recent history of salycilates or immunosuppressive drugs intake.

Laboratory Studies

An ammonia level as high as 1.5 times normal 24-48 hours after the onset of mental status changes is the most frequent laboratory abnormality. Ammonia tends to peak 56-60

DIAGNOSTIC CRITERIA

Acute non-inflammatory encephalopathy with an altered level of consciousness

Hepatic dysfunction with a liver biopsy showing fatty metamorphosis without inflammation or necrosis or a greater than 3-fold increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), or ammonia levels

hours after the onset of symptoms. The ammonia level may return to normal in stages 4 and 5.

Levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increase to 3 times normal but may return to normal by stages 4 or 5. Bilirubin levels are higher than 2 mg/dL (but usually lower than 3 mg/dL) in 10-15% of patients. If the direct bilirubin level is more than 15% of total or if the total bilirubin level exceeds 3 mg/dL, consider other diagnoses.

Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are prolonged more than 1.5-fold in more than 50% of patients. Levels of factors I (fibrinogen), II, VII, IX, and X may be low because of the disruption of synthetic activities in the liver. Consumption may also contribute to low levels of coagulation factors. Platelet counts are usually normal.

Lipase and amylase levels are elevated. The serum bicarbonate level is decreased secondary to vomiting. Blood urea nitrogen (BUN) and creatinine levels are elevated.

Glucose, while usually normal, may be low, particularly during stage 5 and in children younger than 1 year.

Lactic dehydrogenase (LDH) levels may be high or low. Levels of free fatty acids and amino acids (eg, glutamine, alanine, and lysine) may be elevated. Determine the anion gap and venous blood gas level to evaluate for metabolic acidosis. Urine specific gravity is increased; 80% of patients have ketonuria. Cerebral spinal fluid WBC count, by disease definition, does not exceed 8 cells/µL. Opening pressure

is usually normal but may be elevated, particularly in stages 3-5.

Invasive Procedures

The following procedures may be helpful in treatment, workup, and monitoring:

Vascular access (arterial, central venous, or both) Lumbar puncture if the patient is hemodynamically stable and shows no signs of increased

intracranial pressure (ICP) – Opening pressure may or may not be increased; the white blood cell (WBC) count in the cerebrospinal fluid (CSF) is 8/µL or fewer

Intubation to maintain airway and ventilation and to manage ICP Nasogastric tube placement to decompress the abdomen Bladder catheterization to monitor urine output Percutaneous liver biopsy (if indicated) to exclude an IEM or toxic liver disease Placement of an intracranial device for ICP monitoring in patients with increased ICP

DIAGNOSTIC CRITERIA

Acute non-inflammatory encephalopathy with an altered level of consciousness

Hepatic dysfunction with a liver biopsy showing fatty metamorphosis without inflammation or necrosis or a greater than 3-fold increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), or ammonia levels

Coagulopathy must be corrected before invasive procedures are performed.

COMPLICATIONS

Brain herniation, status epilepticus, syndrome of inappropriate secretion of antidiuretic hormone (SIADH), and diabetes insipidus

Acute respiratory failure and aspiration pneumonia Cardiac arrhythmias Myocardial infarction Cardiovascular collapse Gastrointestinal bleeding and pancreatitis Acute renal failure Sepsis Death

TREATMENT

No specific treatment exists for Reye syndrome; supportive care is based on the stage of the syndrome.

Continue careful monitoring. Establish and maintain the patient’s airway, breathing, and circulation. Check the glucose level, particularly if the patient is younger than 1 year and/or has altered mental

status. Administer dextrose to correct hypoglycemia. Admission to the intensive care unit (ICU) is warranted for continued monitoring and treatment. Consider consultation with a neurologist for electroencephalography (EEG). Consider consultation with a neurosurgeon for monitoring and treatment of increased intracranial

pressure (ICP). Consider consultation with a gastroenterologist or surgeon for liver biopsy. Consider consultation with a metabolic disease specialist if an inborn error of metabolism (IEM) is

a possibility. Monitor and treat long-term neurologic sequelae. Prescribe outpatient anticonvulsants if ongoing

seizures occur.

Stage-Specific Management

Supportive care is based on the clinical stage of the syndrome, with aggressive treatment provided to correct or prevent metabolic abnormalities, particularly hypoglycemia and hyperammonemia, and to prevent or control cerebral edema.

Stages 0-1 Keep the patient quiet. Frequently monitor vital signs and laboratory values. Correct fluid and electrolyte abnormalities, hypoglycemia, and acidosis.

If the patient is hypoglycemic, administer dextrose 25% as an intravenous (IV) bolus in a dose of 1-2 mL/kg.

The use of bicarbonate to correct acidosis is controversial because of potential paradoxical cerebrospinal fluid (CSF) acidosis. If the initial pH is less than 7.0-7.2, consider administering sodium bicarbonate 0.5-2 mEq/kg/h to correct it to 7.25-7.3, with the dosage based on the deficit, calculated as follows:Deficit in HCO3– (mEq) = weight (kg) × base excess × 0.3Avoid rapid correction or overcorrection. Recognize that administration of sodium bicarbonate results in a significant sodium load.

Maintain electrolytes, serum pH, albumin, serum osmolality, glucose, and urine output in normal ranges.

Consider restricting fluids to two thirds of maintenance. Overhydration may precipitate cerebral edema. Use colloids (eg, albumin) as necessary to maintain intravascular volume. Dehydration may compromise cardiovascular volume and reduce cerebral perfusion.

Glucose should be maintained in the 100-125 mg/dL range; this will require administration of D10 or D20.

Place a Foley catheter to monitor urine output. Consider giving ondansetron 1-2 mg IV every 8 hours to decrease vomiting. Antacids may also be administered for gastrointestinal (GI) protection.

Stage 2 The standard of care consists of continuous cardiorespiratory monitoring, placement of central

venous lines or arterial lines to monitor hemodynamic status, urine catheters to monitor urine output, ECG to monitor cardiac function, and EEG to monitor seizure activity.

Endotracheal intubation may be required at this stage to maintain the airway, control ventilation, and prevent increased ICP. Use rapid-sequence agents that minimize the chance of increasing ICP. Place a nasogastric tube to decompress the abdomen.

Hyperammonemia can contribute to cerebral edema and therefore must be corrected aggressively. sodium phenylacetate–sodium benzoate is FDA-approved for the treatment of acute hyperammonemia and associated encephalopathy in patients with deficiencies in enzymes of the urea cycle.

Administer ondansetron 1-2 mg IV during the first 15 minutes of the initial dose of sodium phenylacetate–sodium benzoate. If the ammonia level is higher than 500 µg/dL or if the patient’s condition fails to respond to the initial dose of sodium phenylacetate–sodium benzoate, start dialysis, preferably hemodialysis.

Prevent increased ICP. Elevate the head to 30°, keep the head in a midline orientation, use isotonic rather than hypotonic fluids, avoid overhydration, and administer furosemide 1 mg/kg as often as every 4-6 hours to control fluid overload.

Stages 3-5

Continuously monitor ICP, central venous pressure, arterial pressure, or end-tidal carbon dioxide. Perform endotracheal intubation if the patient is not already intubated.

Treat increased ICP by following standard guidelines, which, in addition to correction of hyperammonemia, proper positioning of the head, and appropriate fluid management (see above), include the following:

Ventilation to maintain the partial pressure of carbon dioxide in the normal range Aggressive management of fever to prevent the increased cerebral metabolism and

increased cerebral blood flow resulting from hyperpyrexia Analgesia and sedation to alleviate agitation or prepare for painful interventions Paralytic agents to control shivering If other measures fail, mannitol 20% solution dosed at 0.25-0.5 g/kg IV infused over 10-20

minutes as often as every 6-8 hours, or hypertonic saline 3% dosed at 3-5 mL/kg over 3-30 minutes.

Induced barbiturate coma and hypothermia are controversial Treat seizures with phenytoin 10-20 mg/kg IV as a loading dose, followed by 5 mg/kg/day

IV divided every 6 hours or fosphenytoin dosed as 10-20 mg/kg phenytoin equivalents. Correct coagulopathy (prothrombin time >16 seconds). The data on treatment of coagulopathy in

Reye syndrome, like those on most etiologies of coagulopathy in children, are limited. Options include fresh frozen plasma (FFP), cryoprecipitate, platelets, vitamin K, and exchange transfusion.

FFP 10-15 mL/kg every 12-24 hours provides rapid correction and volume expansion and should be administered, particularly if active bleeding is present or if invasive procedures (eg, ICP monitoring device placement or liver biopsy) are required. If the fibrinogen level is lower than 100 mg/dL, cryoprecipitate 10 mL/kg every 6 hours should be considered instead of FFP because cryoprecipitate has a higher concentration of fibrinogen.

If invasive procedures are to be performed, platelets should also be given as needed to restore the platelet count to a value higher than 50,000/µL. Vitamin K 1-10 mg IV may be administered instead of FFP or cryoprecipitate if the need for correction is not an emergency. Exchange transfusion is rarely required.

Reye syndrome has been successfully treated with liver transplantation

TREATMENT OF REYE’S SYNDROME - IN SHORT

The Goal of Treatment for the Child with Reye’s Syndrome: Promoting Effective Cerebral Perfusion and Controlling Intracranial Pressure

Treatment of Increased Intracranial Pressure and Impaired Cerebral Profusion

Elevate the head of the bed by 30 degrees Maintain the head a neutral, midline position Limit suctioning interventions to a minimum as this may increased intracranial pressure An intracranial pressure monitoring device may be placed Surgical management may include a craniotomy Cerebrospinal fluid may be drained

Treating Renal Failure in Reye’s Syndrome

Dialysis may be indicated to reduce ammonia levels or residual salicylate Exchange transfusions may be necessary

PREVENTION Salicylates should be avoided in children, except in those who have conditions for which salicylates

are a mainstay of therapy (eg, Kawasaki disease). It is critical to be alert for and recognize early symptoms of Reye syndrome. It is also important to

be mindful of the possibility that an IEM may be the actual cause of the symptoms and, if this is the case, to be prepared to treat the IEM. Appropriate management of IEMs dramatically decreases morbidity and mortality.

Influenza vaccine is recommended by the Centers for Disease Control and Prevention (CDC) for everyone older than 6 months.

TREATMENT OF REYE’S SYNDROME - IN SHORT

The Goal of Treatment for the Child with Reye’s Syndrome: Promoting Effective Cerebral Perfusion and Controlling Intracranial Pressure

Treatment of Increased Intracranial Pressure and Impaired Cerebral Profusion

Elevate the head of the bed by 30 degrees Maintain the head a neutral, midline position Limit suctioning interventions to a minimum as this may increased intracranial pressure An intracranial pressure monitoring device may be placed Surgical management may include a craniotomy Cerebrospinal fluid may be drained

Treating Renal Failure in Reye’s Syndrome

Dialysis may be indicated to reduce ammonia levels or residual salicylate Exchange transfusions may be necessary

PROGNOSIS

Recovery from RS is rapid and usually without sequelae if the diagnosis is determined early and therapy is initiated promptly. Patients who survive have full liver function recovery; however, approximately one third may have subtle neuropsychological deficits.

NURSING CARE MANAGEMENT

Care and observations are implemented as for any child with an altered state of consciousness and increasing ICP.

Potential Nursing Diagnoses

Ineffective breathing pattern Impaired gas exchange Impaired physical mobility Risk for ineffective cerebral tissue perfusion Risk of injury from convulsions Risk for impaired skin integrity and infection related to impaired mobility (possibly from

coma)

Possible Nursing Interventions

Maintain hydration by administering fluids intravenously Institute and maintain seizure precautions Preventing skin breakdown from immobility: pad bony prominences, range of motion

exercises, turning and position changes Monitor intake and output, as the patient may be taking diuretics and may experience renal

impairment from the condition Maintain nothing-by-mouth status of ordered Provide care for endotracheal tube and mechanical ventilator; ensure patency Initiate intravenous access and ensure patency Administer medications as ordered; such as glucose, vitamin K, diuretics, and paralytics Care for intracranial pressure monitoring device Provide a quiet environment to reduce risks of increasing the intracranial pressure Position the head at midline and raise the head of the bed to 30 degrees Administer blood products as ordered Administer vitamin K, fresh frozen plasma, and

platelets as necessary to reduce the risk of bleeding; institute bleeding precautions Because of related liver dysfunction, laboratory studies to determine impaired coagulation,

such as prolonged bleeding time, should be monitored. Support the patient and family and provide teaching for coping mechanisms related to

situational crises.

Parents of children with RS need to be kept informed of the child’s progress, to have diagnostic procedures and therapeutic management explained, and to be given concerned and sympathetic support.

Families need to be aware that salicylate, the alleged offending ingredient in aspirin, is contained in other products. They should refrain from administering any product for influenza-like symptoms without first checking the label for “hidden” salicylates.

Nursing Outcomes

Maintenance of adequate ventilation and oxygenation Maintenance of range of motion and joint mobility Maintenance of respiration rate Remain oriented to environment Maintenance of skin integrity without any signs of skin breakdown

RESEARCH STUDIES

Role of copper in Indian childhood cirrhosis.Tanner MS1.

Author information

1Department of Paediatrics, University of Sheffield, United Kingdom. m.s.tanner@sheffield.ac.uk

Abstract

Of the cirrhoses that affect Indian children, Indian childhood cirrhosis (ICC) is a discrete clinical and histologic entity in which large amounts of copper are deposited in the liver. The evidence linking copper deposition to increased dietary copper intake in infancy was reviewed. Prevention of this feeding pattern prevents ICC, and the disease has now largely disappeared from many parts of India. Penicillamine, if given before the terminal clinical stage of ICC, reduces mortality from 92% to 53%. Long-term survivors show a sequence of histologic resolution, resulting either in inactive micronodular cirrhosis or in virtually normal histologic appearance. Twenty-nine treated ICC patients reexamined at 8.8 y of age (range: 6.3-13 y), 5-12 y after diagnosis, were well and had normal results from liver function tests. Clinical and epidemiologic evidence show that there must be excessive copper ingestion for ICC to develop, but the lack of an animal model, the inconstant relation between liver copper concentrations and liver damage, and the rarity of liver disease in adults suggests that other etiologic factors contribute. Two mechanisms are discussed: 1) that copper may be acting in synergy with a hepatotoxin, or 2) that there may be a genetic predisposition to copper-associated liver damage, as suggested recently for Tyrollean childhood cirrhosis. Although ICC is now rare, sporadic cases of an ICC-like disorder in infants continue to occur. There should be a greater awareness among pediatricians of this disease to enable early diagnosis. Penicillamine

should be used early and adverse prognostic factors recognized as indications for early transplantation and unregulated water supplies should not be used to prepare infant feeds

Is Indian childhood cirrhosis an extinct disease now?--An observational study.

Patra S1, Vij M, Kancherala R, Samal SC.

Indian J Pediatr. 2013 Aug;80(8):651-4. doi: 10.1007/s12098-012-0935-1. Epub 2012 Dec 22.

Author information

1Department of Pathology, Global Health City, Chennai, Tamil Nadu 600100, India. wususama@gmail.com

Abstract

OBJECTIVE:

Indian childhood cirrhosis (ICC), an unique liver disease that has been endemic in most parts of India and advocated by some to be caused by hepatotoxic effect of excess dietary copper is generally believed now to have virtually disappeared from the country. In the face of this the authors report here five cases of ICC encountered in one children hospital over the last 10 y period.

METHODS:

Cases histologically categorized as ICC were initially picked up from the records of the department of Pathology. Their clinical, investigational and follow up information retrieved from hospital data base along with pathologic features of liver biopsies were reviewed in detail.

RESULTS:

The age range of the three male and two female children were from 1 ½ to 12 y and on clinical and investigational features all 5 cases were labeled as non-Wilsonian liver disease of uncertain etiology. Histopathologic findings in each case however, was characteristic of accepted established phase of ICC. Three of the five children died in hospital while the other two left the hospital and were lost to follow up. None of the children had exposure to excess dietary copper.

CONCLUSIONS:

Cases of ICC continue to occur in Andhra Pradesh and very likely in other parts of India. Established and non-typical cases are possibly being missed because of no histologic confirmation and unawareness of the protean manifestation and natural history of this disease. Dietary copper overload is unlikely to play a causal role in ICC.

Simultaneous Presentation of Wilson's Disease and Autoimmune Hepatitis; A Case Report and Review of Literature.

Dara N1, Imanzadeh F1, Sayyari AA1, Nasri P1, Hosseini AH1.

Author information

1Department of Pediatric Gastroenterology, Mofid Children Hospital, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.

Abstract

INTRODUCTION:

Coexistence of Wilson's disease and autoimmune hepatitis has been rarely reported in English literature. In this group of patients, there exist features of both diseases and laboratory and histopathological studies may be misleading. Medical treatment for any of these entities, per se, may result in poor response. Therefore, by considering the acute hepatitis resembling Wilson's disease and autoimmune hepatitis, simultaneous therapy with immunosuppressive and penicillamine may have a superior benefit.

CASE PRESENTATION:

We present the case of a 10-year-old boy with nausea, vomiting, yellowish discoloration of skin and sclera, abdominal pain and tea-color urine. Physical examination showed mild hepatomegaly and right upper quadrant tenderness. Laboratory and histochemical studies and atomic absorption test were done and the results were highly suggestive of both Wilson's disease and autoimmune hepatitis, in him.

CONCLUSIONS:

This case study highlights, although rare, the coexistence of Wilson's disease and autoimmune hepatitis and the need to maintain a high level of awareness of this problem. Therefore, it is reasonable to consider this type of hepatitis in rare patients, with dominant features of both diseases at the same time.

Aspirin and Reye syndrome: a review of the evidence.Schrör K1.

Author information

1Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany. kschroer@uni-duesseldorf.de

Abstract

Reye syndrome is an extremely rare but severe and often fatal disease. Death occurs in about 30-40% of cases from brainstem dysfunction. The disease typically is preceded by a viral infection with an intermediate disease-free interval of 3-5 days. The biochemical explanation for Reye-like symptoms is a generalized disturbance in mitochondrial metabolism, eventually resulting in metabolic failure in the liver and other tissues. The etiology of 'classical' Reye syndrome is unknown. Hypothetically, the syndrome may result from an unusual response to the preceding viral infection, which is determined by host genetic factors but can be modified by a variety of exogenous agents. Thus, several infections and diseases might present clinically with Reye-like symptoms. Exogenous agents involve a number of toxins, drugs (including aspirin [acetylsalicylic acid]), and other chemicals. The 'rise and fall' in the incidence of Reye syndrome is still poorly understood and unexplained. With a few exceptions, there were probably no new Reye-like diseases reported during the last 10 years that could not be explained by an inherited disorder of metabolism or a misdiagnosis. This may reflect scientific progress in the better understanding of cellular and molecular dysfunctions as disease-determining factors. Alternatively, the immune response to and the virulence of a virus might have changed by alteration of its genetic code. The suggestion of a defined cause-effect relationship between aspirin intake and Reye syndrome in children is not supported by sufficient facts. Clearly, no drug treatment is without side effects. Thus, a balanced view of whether treatment with a certain drug is justified in terms of the benefit/risk ratio is always necessary. Aspirin is no exception.

BIBLIOGRAPHY

1. Robert M. Kliegman, Stanton, “NELSON TEXTBOOK OF PEDIATRICS”, 19th edn,2011, Elsevier publishers, Philadelphia, page no: 1390-1395

2. John F. Pohl, Christopher Jolley, “Pediatric Gastroenterology A Color Handbook”,2014, CRC Press, USA, Page no 342-350

3. Marilyn J Hockenberry, David Wilson. Wong’s Nursing Care of infants and children. 9th edition. Elsevier publishers.USA.2011

4. www.medscape.com 5. N.C. Nayak & A.R. Chitale, Indian childhood cirrhosis (ICC) & ICC-like diseases: The changing

scenario of facts versus notions, Indian J Med Res 137, June 2013, pp 1029-1042