Objectives

• Case report-problem

• Defining the clinical condition

• Pathogenesis

• Diagnosis

• Clinical staging of RS

• Case report-solving the problem

Undiagnosed death till…• Off and on fever-antipyretics taken• Progressive pallor and weakness developed• epistaxsis• Recommended to PIMS

• Enlarged liver • APTT prolonged ( activated partial thromboplastin time)• LDH increased Keeping in view of possibility of tuberculosis and other infections, she was started on

injectable steroids, transamine, zantac and Leflox. She was transfused three packs of red cell(against pancytopenia) concentrates but still her condition did not improve.

• Urinary incontinence( involuntary leakage of urine) developed;• Conditions deteriorated further and oxidative stress developed, transferred to ICU

CONTND…

However her condition continued to decline with persistent low blood pressure and weak pulse. Her right pupil became fixed and dilated while left was semi dilated and reactive. The patient went into cardiac arrest and died on the same day of being transferred To ICU.

Liver biopsy taken and sent for fungal and tuberculosis culture as well as for histopathology

• surprisingly both were negative.

• histopathological findings and other lab work rendered the diagnosis as compatible with Reye’s syndrome.

•Reye’s syndrome is a very rare condition that causes serious liver and brain damage. If it is not treated promptly it may result in permanent brain injury or death.

•Reye’s syndrome is characterized by acut non-inflammatory encephalopathy and fatty degeneration of viscera was first described as a distinct entity in 1963 by R. D. Reye

Pathogenesis•Precise reason still not known BUT links with use of aspirin in children after the viral infection has been linked with it (biphasic disease )• It is now not recommended to give ASA to kids 18 and under without doctor’s approval However 4 concepts are prominent1. An intrinsic toxin that affects mitochondrial metabolism 2. An extrinsic toxin that alters the host's response during recovery from a viral illness.3.A genetic susceptibility to Reye's syndrome following exposure to a specific viral or viral-like disease.4. A primary defect in lipid and ammonia metabolism that results in cerebral edema and coma following viral or viral-like exposure.

Current studies have demonstrated the transient disturbances in mitochondrial function in Reye's syndrome.(mitochondrial permeability transition ) The pathogenesis is unclear, but it appears to involve mitochondrial dysfunction that inhibits oxidative phosphorylation and fatty-acid beta-oxidation in a virus-infected, genetically sensitized host.

Diagnosis

• Diagnosis can’t be established w/o a liver biopsy• Centers for Disease Control and Prevention (CDC) have developed

criteria for diagnosis of Reye’s syndrome and include Firstly, the presence of an acute non inflammatory encephalopathy

with an altered level of consciousness with no signs in CSF or in brain histology to indicate infection or inflammation

. The second criteria is hepatic dysfunction with a liver biopsy showing fatty change or a more than 3-fold increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and/or ammonia levels

Thirdly there should be no other explanation for the condition

The answers ??? Case report

Off and on fever-antipyretics taken

The answers ??? Case report

Epistaxsis?

The answers ??? Case report

•Enlarged liver ??

• APTT prolonged ( activated partial thromboplastin time)

•LDH increased??

The answers??Case report

• Oxidative stress ??

Hint

cellular respiration…

Reye’s result of PIMS’ patient: mystery solved• Suspected clinical diagnosis of T.B could not be proven on

thorough investigations• The fact that favored the diagnosis of Reye’s syndrome is the

sudden onset of the symptom complex that lead to death within a week of presentation

• It can be speculated that the child had suffered from a viral infection which was probably superimposed on an inborn metabolic defect that was never suspected and hence never investigated as is usually the case.

• Also the child had off and on history of intake of antipyretics and as everyone has an easy access to aspirin, this may have been the triggering event.

• Finally, the liver biopsy showed marked micro vesicular fatty change that further supported this diagnosis.

• As mentioned earlier, the Reye’s syndrome is a diagnosis of exclusion and as no other explainable cause of hepatic dysfunction was found.

References

• Reyc's syndrome: a clinical review John F.S. Crocker, Md, Frci4c]; Philip C. Bagnell, Md, Frcp[c]

• Reye’s Syndrome: Diagnosed on a PostmortemNeedle Liver Biopsy in an Unexplained Death Ambreen Moatasim, Anwar Ul Haque and Humeira RizwanDepartment of Pathology, Pakistan Institute of Medical Sciences, Islamabad.

• Reye RDK, MorganG, Baral J. Encephalopathy and fatty degeneration of the viscera, a disease entity in childhood. Lancet 1963; ii: 749-52.

• Reye Syndrome and Reye-Like Syndrome Jayaprakash A. Gosalakkal, MD and Vishwanath Kamoji, MD