Here are the differential diagnosis and aetiologies of hyperferritinemia (high ferritin). In the acute setting, infection and malignancy are by far the most common causes of elevated ferritin.

Introduction to ferritin

What is ferritin? Ferritin is a very large spherical protein molecule that looks like a “beach ball”. It is an ubiquitous and highly conserved molecule that can be found in virtually all forms of life, from bacteria, to plants, to animals and humans. Its job is to store iron in a safe manner. Iron, while indispensable to life, is toxic when it is not bound to ferritin or hemosiderin, as it can cause the formation of free radicals from reactive oxygen species. Each ferritin can hold about 4,500 Fe3+ ions.

Infection

Any kind of infection should cause ferritin to be acutely and significantly elevated. The presence of iron significantly enhances the ability of pathogens such as bacteria to multiply. Therefore when there is an acute infection, the body tries to “hide” its iron stores in part by releasing large quantities of ferritin.

  • Viral infections (e.g. Epstein-Barr virus, cytomegalovirus, hepatitis B, hepatitis C)
  • Bacterial infection
  • Fungal or protozoan infection
  • Bacteremia
  • Sepsis

Hematological malignancy

  • B-cell lymphoma
  • NK-cell lymphoma
  • T-cell lymphoma
  • Intravascular lymphoma
  • Solid tumors

Autoimmune

  • Hemophagocytic lymphohistiocytosis (HLH)—especially when the ferritin is very high (in the thousands)
  • Juvenile idiopathic arthritis (Still’s disease)
  • Adult-onset Still’s disease
  • Other autoimmune diseases

Genetic disorders

  • Hemochromatosis
  • Benign hyperferritinemia
  • Hereditary hyperferritinemia with cataract syndrome (HHCS)
  • Dominant hyperferritinemia (Kannengiesser’s disease)

Organ dysfunction

  • Nephrotic syndrome
  • End stage renal disease
  • Protein-losing enteropathy
  • Chronic liver disease