Mastocytosis, Mast Cell Disorders and/or Severe Allergy

In our bodies we have a type of white blood cell called mast cells and are all around our bodies protecting us from infections and other foreign invaders.

Mast cells function

• Have a chemical called histamine, this is released when you have an allergic reaction.
• They also contain heparin, a chemical which stops the blood from clotting.
• Mast cells are hard-working cells that have many functions, including helping to fight infection and healing wounds.

However if one has too many mast cells (all over the body or in a particular part of the body or the mast cells number are normal but are too over active they can cause very distressing  severe allergy type symptoms known as mastocytosis and mast cell disorders.

There are many types pending on location of mast cells and  a wide range of symptoms may occur  whether the mast cell activation are local or widespread.

Mastocytosis

• This is the term used when too many mast cells are produced. There are many different types of mastocytosis. The most common types are:
  • Those involving the skin (cutaneous).
  • Those which involve lots of different tissues of the body (systemic).
• Much less commonly there is a localised type in which clumps of mast cells gather in one place.

Mast cell activation syndrome

• You may also see mast cell activation syndrome (MCAS) called mast cell activation disorder (MCAD). The mast cells are present in normal numbers but they are triggered to release their chemicals more readily than usual.
• The symptoms are generally the same as mastocytosis.

Localised mast cell disorder

• Rarely, clumps of mast cells can develop in one area of the body.

Patient.Uk 

Types of Mastocytosis and Mast cell disorders

Cutaneous mastocytosis/Diffuse cutaneous mastocytosis

• When larger than normal numbers of mast cells are present in the skin they commonly cause a condition called urticaria pigmentosa.
• Another less common condition called diffuse cutaneous mastocytosis is also sometimes seen where one has symptoms of large areas of rash, headaches , heart palpitation and diarrhoea.
•  A rare condition when Telangiectasia is involved [(Telangiectasia macularis eruptiva perstans (TMEP)]

Localised mastocytosis

• Rarely, clumps of mast cells can form a nodule in the skin, which is usually red, brown or yellow in colour.
• This is called a mastocytoma.
• Even more rarely, a cancerous (malignant) lump called a mast cell sarcoma can develop.

Systemic mastocytosis

• This can cause a whole range of symptoms depending on the parts of the body where large numbers of mast cells are found and pending on the area affected can shorten ones life.

Mast cell leukaemia (very rare).

• A quick-progressing condition that leads to the buildup of mast cells in your bone marrow and other tissues that lead to a short life.

Outlook

• Cutaneous mastocytosis in children often settles down with time.
• Adults can go on to develop the systemic form.
• Systemic mastocytosis tends to be persistent and the outlook (prognosis) depends on which parts of the body are involved.
• In most cases, it just keeps going at a low level for decades, requiring treatment to control symptoms.
• Occasionally, however, it can become aggressive and even life-threatening.
• Most cases of localised mastocytosis cause lumps that are nothing to worry about but occasionally cancers do occur which invade the surrounding tissue

Patient.uk (Authored by Dr Laurence Knott, Reviewed by Dr John Cox | Last edited 9 Jul 2017)

Diagnosis Criteria

The Mast Cell Disease Society advocates the following diagnostic criteria:

• Criterion 1: the patient exhibits symptoms involving two or more organ systems in parallel, which recur, or are chronic, are found not to be caused by any other condition or disorder other than mast cell activation, and require treatment or therapy.
• Criterion 2: documented evidence that mast cells are directly involved in the symptomatology. This is best demonstrated by an increase in the serum level of tryptase, above baseline and within a narrow (generally accepted as one to two hour) window of time after a symptomatic episode. If tryptase estimation is not available or is equivocal, other mediator tests can be used – eg, 24-hour urinary n-methyl histamine, prostaglandin-D2, or its metabolite, 11β-prostaglandin-F2α.
• Criterion 3: a response to medications that inhibit the action of histamine, in addition to a complete or major response to drugs that inhibit other mediators produced by mast cells or block mast cell mediator release.

Overview and Diagnosis of MCAS; The Mast Cell Disease Society, 2021

Diagnosis Tests

• Skin biopsy (with analysis of KIT mutations).
• Blood tests:
  • FBC (anaemia, thrombocytopenia and leukocytosis), clotting studies, renal function tests and LFTs.
  • Serum tryptase – almost all patients with systemic mastocytosis have serum tryptase >20 ng/mL.

Koenig M, Morel J, Reynaud J, et al; An unusual cause of spontaneous bleeding in the intensive care unit – mastocytosis: a case report. Cases J. 2008 Aug 181(1):100.

• Urinary histamine metabolite levels (eg, 11β-prostaglandinF2α or N-methyl histamine) may be elevated.

Divekar R, Butterfield J; Urinary 11beta-PGF2alpha and N-methyl histamine correlate with bone marrow biopsy findings in mast cell disorders. Allergy. 2015 Oct70(10):1230-8. doi: 10.1111/all.12668. Epub 2015 Jun 24.

• If there is suspected systemic involvement (including most adults with suspected mast cell disorders) then complete staging is needed. This includes:
  • CXR (or chest CT scan) for lymphadenopathy.
  • Gastrointestinal investigations – eg, endoscopy and ultrasound of abdomen.
  • Bone density scan and skeletal X-rays.
  • Bone marrow biopsy/aspirate.
• Other tests include:
  • Chromosomal analysis: 20% of patients with systemic mastocytosis have an abnormal karyotype.
  • Molecular testing for KIT D816V mutation is always positive but JAK2 V617F is rarely positive.
  • The mast cell clone is CD-117 positive and CD-25 and/or CD-2 positive. Expression of CD-25 on mast cells is seen in systemic mastocytosis but not in reactive states of mast cell hyperplasia.

Diagnosis Results

There is a suggested diagnostic protocol. The diagnostic criteria are:

• Major criteria:
  • Biopsy finding of multiple dense accumulations of mast cells (greater than 15% of mast cells in clusters) in bone marrow or in other non-skin tissue.
• Minor criteria:
  • Detection of a point mutation at codon 816 in the KIT receptor gene. This may be found in bone marrow or blood or other internal organs.
  • Abnormal mast cell CD25 expression.
  • Serum total tryptase level persistently greater than 20 ng/mL.
  • Presence of KITD 816V mutation.
  • Presence of greater than 25% atypical mast cells.
• The diagnosis of systemic mastocytosis may be made if one major and one minor criterion are present, or if three minor criteria are fulfilled.

Horny HP, Sotlar K, Valent P; Mastocytosis: state of the art. Pathobiology. 200774(2):121-32.

Gangireddy M, Ciofoaia GA; Systemic Mastocytosis