June 2014: Post summaries and take home points

Cutaneous mastocytosis

  • CM is mastocytosis limited to the skin.
  • About 90% of mastocytosis patients have CM.
  • 2/3 of CM cases are found in children.
  • Many children “grow out” of their CM.
  • Adult onset CM tends to develop into SM.
  • All types of CM are positive for Darier’s sign.
  • Darier’s sign is a wheal and flare response when touching mast cell lesions due to histamine release.
  • CM is diagnosed by biopsy.
  • Urticaria pigmentosa (UP) is also called maculopapullar cutaneous mastocytosis (MPCM).
  • UP is the most common form of CM.
  • UP is marked by tan or red/brown lesions that usually start on the trunk.
  • UP lesions are very itchy.
  • UP accounts for 65-90% of CM cases in children and 47-75% overall.
  • UP can cause systemic symptoms.
  • Mastocytomas are benign mast cell tumors.
  • Solitary mastocytomas are often grouped with CM because they usually occur on the skin.
  • Mastocytomas can also occur internally.
  • 10-35% of CM cases are single mastocytomas.
  • Multiple mastocytomas are unusual but can occur.
  • Diffuse cutaneous mastocytosis (DCM) is rare, accounting for 1-5% of CM in children.
  • DCM is the most severe presentation of CM.
  • DCM usually presents in early infancy and is almost always diagnosed before three years of age.
  • DCM lesions can cover much of the body and may blister and bleed.
  • DCM can cause thickening of the skin.
  • Telangiectasia macularis eruptiva perstans (TMEP) is relatively rare and found almost exclusively in adults.
  • TMEP lesions are usually smaller than UP and do not itch.  (Note added on 7/26/15 – a few patients have reached out to let me know that they have TMEP and it does sometimes itch, especially when triggered.  I’m going to look back at the previous source and see if the author of that article was incorrect or if I misunderstood.  I will add my findings into both this post on the original June 2014 post.  Thanks!)
  • The only way to distinguish UP from TMEP is biopsy.
  • Blistering can occur with any form of CM.
  • Patients with frequent blistering are more likely to have systemic symptoms and anaphylaxis.

Histamine: intended functions and mast cell symptoms

  • Histamine is produced mostly by mast cells and basophils.
  • It can be stored inside cells or immediately released and used.
  • A breakdown product of histamine is n-methylhistamine. This is what we test for in 24 hour urine samples.
  • Histamine performs its functions by interacting with four known histamine receptors, H1, H2, H3 and H4.
  • H1 receptors are present in the nervous system including the brain.
  • H1 activity helps regulate the sleep-wake cycle, body temperature, appetite, mood, pain levels and other hormones.
  • H1 activity also causes airway constriction, difficulty breathing, hives and itching.
  • Histamine increases wakefulness.
  • H2 receptors are mostly found in the GI tract and vascular tissues, but some are present in the skin.
  • H2 activity can cause vessels to dilate, decreasing blood pressure.
  • H2 activity induces acid release in the stomach.
  • H3 receptors are in the nervous system.
  • H3 activity regulates release of neurotransmitters, including histamine, acetylcholine, norepinephrine and serotonin.
  • H4 receptors are found in many parts of the body and are involved in inflammation.

Effect of mast cell mediators on sleep

  • About half of histamine in the brain released by mast cells.
  • Histamine increases wakefulness.
  • Histamine activity increased during food deprivation or starvation, so regular meals can help sleep.
  • Chronic fight or flight type stress can increase the number of mast cells in the brain.
  • Prostaglandin D2 induces deep sleep.
  • Mild to moderate inflammation increases production and release of PGD2, making you tired.
  • Severe inflammation induces release of PGE2, which stimulates mast cells to release histamine.
  • Sleep in patients with high PGE2 is fragmented and not deep.

Gene expression and the D816V mutation

  • DNA is a molecule that contains the genetic code for all living organisms and some viruses.
  • DNA in humans is two strands wrapped around each other in a double helix.
  • RNA is similar to DNA but not the same.
  • RNA helps to express certain genes using the code from DNA.
  • Genes tell the cell how to make proteins or RNA that has a specific function.
  • D816V means that at codon 816 (a location in the CKIT gene), a mutation changed the code from making one amino acid (aspartic acid) to another one (valine).
  • Some people with mast cell disease don’t have the D816V mutation, but may have other CKIT mutations.