Question 24.1

a)

Interpret the abnormalities.

Mild hyponatraemia and hyperkalaemia

AKI: Rise in creatinine out of proportion to rise in urea (ratio urea: creatinine < 100:1) – due to intrinsic renal dysfunction or associated severe liver injury

Reduced bicarbonate and normal anion gap metabolic acidosis Hyperbilirubinaemia – mostly conjugated

Acute hepatocellular liver injury: ratio AST:ALT increased but not quite 2:1 indicative of alcoholic hepatitis (also not supported by only slightly elevated GGT) but suggestive other acute liver injury Other synthetic liver dysfunction: INR 1.8; Ammonia mildly elevated

Mildly elevated CK - ? muscle injury

Severely elevated ferritin with normal iron levels. Normal Hb/ Wcc

Markedly deranged coagulation: severe thrombocytopaenia, low fibrinogen, markedly elevated APTT and severely elevated D-Dimer – Suggestive of DIC type pathology

b)

What is the most likely diagnosis?

Given    the   severity    of   the    elevated    ferritin   and   multiorgan   involvement,              Haemphagocytic lymphohistioctyosis (haemophagocytic syndrome)

c)

What are precipitants of this condition?

Viral infections particularly EBV/CMV/HSV/VZC/Parvovirus Malignancy especially lymphoma and leukaemia Rheumatologic conditions

Discussion

First, let's list the abnormalities, and briefly digress on their meaning: 

• Hyponatremia
• Hyperkalemia
• Acidosis
• Renal failure (the lower urea suggests that something other than pre-renal failure is responsible)
• The magnesium is raised
• Albumin and portein are low
• The bilirubin is very elevated, and it is mainly conjugated bilirubin
• The transaminases are elevated, which suggests a noncholestatic cause of the raised bilirubin
• There is hypocalcemia
• CK is elevated, but only trivially so
• The transferrin is low and the iron levels are essentially normal
• The ammonia is raised, which is not unexpected given the degree of hepatic damage
• In the haematology, there is substantial thrombocytopenia, but the counts are otherwise normal
• The coags are deranged, but not spectacularly so.
• The ferritin level is abominably elevated, to the point that the lab technician would recoil in horror from the analyser, and ring you directly.

So, the only thing this could be is haemophagocytic syndrome. The causes of this rare disease can be found in the review article by Gritta Janka (2008):

Congenital:

• familial HLH (FHLH)
• Chediak-Higashi syndrome (CHS 1)
• Griscelli syndrome (GS 2)
• X-linked proliferative syndrome (XLP)
• The UpToDate article has whole pages listing obscure-sounding loci of mutation.

Acquired causes

• Infectious
  • EBV
  • CMV
  • HIV
  • Leishmania
• Neoplastic
  • Lymphoma, especially T and NK-cell
• Autoimmune
  • SLE
  • Kawasaki disease