UK

Irene Wilson

UK Mastocytosis Support Group

Irene Wilson

Web site: http://www.ukmasto.co.uk/

Email:

Introduction

The purpose of this website is to offer patients from different countries a common platform to seek and share information about mastocytosis.

The aim is to provide a general introduction about the disease as well as links to various European patient support websites to facilitate human networking.

Mast Cells

Mast cells are part of our immune system. They are produced in the bone marrow and travel to the tissues where they reside near blood vessels or nerves. Normally mast cells are not found in the peripheral blood; therefore, the presence of mast cells is determined exclusively by means of tissue biopsy (e.g. skin or bone marrow) and not by blood sample. Mast cells produce and store substances (i.e. histamine), which can be released and may result in symptoms.

Mastocytosis

As explained, mast cells are part of every single person's immune system. The difference in patients with mastocytosis is that they have an abnormal growth and accumulation of mast cells in one or more organ systems (e.g. skin, bone marrow, liver, spleen). Mastocytosis is a disorder which can present in many different ways.

Symptoms

Symptoms are often caused by degranulation or the release of substances (granules) stored in the mast cells. Mast cells contain packets (or granules) of chemicals including histamine which can be released outside the mast cell. This chemical release can lead to symptoms such as flushing, pruritis, diarrhoea, indigestion, nausea, abdominal pain, muscle/bone pain, osteoporosis, changes in blood pressure (usually a fall known as hypotension), anaphylaxis, high heart rates, headaches, concentration problems, fatigue, brain fog, dizziness, irritation, anger, depression and fear. In every type of mastocytosis symptoms can be acute or chronic. The severity of symptoms may be mild or life threatening and may rely on triggers which can vary greatly from patient to patient. In the rare case of aggressive systemic mastocytosis and in mast cell leukaemia, symptoms arise due to the change and destruction of organs through mast cell infiltration.

WHO-Classification of Mastocytosis

Cutaneous Mastocytosis (CM)

  • Maculopapular cutaneous mastocytosis (MPCM) (formerly: Urticaria Pigmentosa(UP))
  • Diffuse cutaneous mastocytosis (DCM)
  • Mastocytoma

Systemic Mastocytosis (SM)

  • Indolent Systemic Mastocytosis (ISM), (most common form of Systemic Mastocytosis)
    • Isolated Bone Marrow Mastocytosis (BMM)
    • Smouldering Systemic Mastocytosis (SSM)
  • Systemic Mastocytosis with an associated clonal hematological non-mast-cell-lineage disease (SM-AHNMD)
  • Aggressive Systemic Mastocytosis (ASM)
  • Mast Cell Leukaemia (MCL)
  • Mast Cell Sarcoma
  • Extracutaneous Mastocytoma

The World Health Organization has classified Mastocytosis into two different diseases: Cutaneous Mastocytosis and Systemic Mastocytosis.

I. Cutaneous Mastocytosis (CM), which is an exclusively dermatological disease, though mediator symptoms may be systemic.

In cutaneous mastocytosis mast cell accumulation is isolated in the skin. It is ALWAYS a benign disease. Cutaneous mastocytosis is primarily found in children and in most children regresses around puberty. In most cases cutaneous mastocytosis is not inherited.

a) Different types of cutaneous mastocytosis

Maculopapular Cutaneous Mastocytosis (MPCM) (formerly: Urticaria Pigmentosa (UP)) is the most common pattern. Many small pink, or brown marks or swellings occur on the body but not usually on the face.

Telangiectasia macularis eruptiva perstans (TMEP) is a rare subform of MPCM. It shows as persistent pink patches of skin on the body in adults. Flushing and itching with fine blood vessels may be seen.

Diffuse cutaneous mastocytosis (DCM): a very rare form present at birth where the skin is thickened and easily blistered.

Mastocytoma: rare and seen in infancy; It can present as a single or multiple raised nodule.

b) Diagnosis criteria of cutaneous mastocytosis

The diagnosis of cutaneous mastocytosis is based on clinical and histological skin lesions and absence of definitive criteria of systemic involvement:

II. Systemic Mastocytosis (SM) is a haematological disease

Systemic mastocytosis is a myeloproliferative neoplasm. Mast cell proliferation is found in at least one organ (normally in the bone marrow) and must be confirmed by biopsy. Skin involvement can be – but does not have to be present. Systemic mastocytosis is normally found in adults. It has a chronic course and is not curable. The prognosis of systemic mastocytosis is usually favourable. Rarely one form of systemic mastocytosis progresses into another. In most cases, systemic mastocytosis is not inherited.

a) Different types of Systemic Mastocytosis

Indolent Systemic Mastocytosis (ISM): the most common pattern. It may remain unchanged throughout life and rarely progresses into another type. One subvariant is Bone Marrow Mastocytosis, which is never accompanied by skin involvement. Another subvariant is Smouldering Systemic Mastocytosis, which shows a higher mast cell burden.

Systemic Mastocytosis associated with a blood disorder (SM-AHNMD): several types of blood disorders may develop in a few patients. They are found by a routine blood test or by bone marrow biopsy.

Aggressive Systemic Mastocytosis (ASM): this disease is accompanied by an impairment of at least one organ. Skin involvement is rare.

Mast Cell Leukaemia (MCL): this is an exceptionally rare haematological disease. Skin lesions are never present.

There are two different and very rare solid mast cell tumours. Mast Cell Sarcoma, which is malignant and Extracutaneous Mastocytoma, which is a benign tumour found elsewhere in the body and not the skin.

b) Diagnostic criteria of Systemic Mastocytosis

The diagnosis of systemic mastocytosis is established in patients whose biopsy of an internal organ (normally bone marrow) fulfils at least one major and one minor or at least three minor criteria.

Major criterion

Multifocal dense infiltrates of mast cells (> 15 mast cells per aggregate)

Minor criteria

  1. more than 25% of the mast cells show an abnormal morphology (spindle-shaped or elongated)
  2. detection of a KIT mutation at codon 816
  3. mast cells express CD2 and/or CD25
  4. serum tryptase > 20ng/ml

c) Further testing may include: full blood count, ultrasound, DEXA scan and endoscopies.

Treatment

The treatment of indolent systemic mastocytosis is symptom orientated and consists of avoiding individual triggers which may cause mast cell degranulation. Treatment is with histamine receptor antagonists. More aggressive forms of systemic mastocytosis are treated with specific cytoreductive medications (chemotherapy). Rarely polychemotherapy, radiation or stem cell transplant may be necessary.

Literature

European Competence Network on Mastocytosis. Information On Mastocytosis. http://www.ecnm.net/

Horny. HP. Mastocytosis: an unusual clonal disorder of bone marrow-derived hematopoietic progenitor cells. Am J Clin Pathol. 2009 Sep;132(3):438–47.

Valent P, Horny HP, Escribano L, Longley BJ, Li CY, Schwartz LB, Marone G, Nunez R, Akin C, Sotlar K, Sperr WR, Wolff K, Brunning RD, Parwaresch RM, Austen KF, Lennert K, Metcalfe DD, Vardiman, JW, Bennett JM. Diagnostic criteria and classification of mastocytosis: a consensus proposal. Leuk Res. 2001 Jul;25(7):603–626.

Valent P, Akin C, Sperr W, Horny HP, Arock M, Lechner K, Bennett JM, Metcalfe D. Diagnosis and treatment of systemic mastocytosis: state of the art. Br J Haematol. 2003 Sep;122(5):695–717.

Valent P, Akin C, Sperr WR, Mayerhofer M, Födinger M, Fritsche-Polanz R, Sotlar K, Escribano L, Arock M, Horny HP, Metcalfe DD. Mastocytosis: pathology, genetics, and current options for therapy. Leuk Lymphoma. 2005 Jan;46(1):35-48.

Valent P, Akin C, Escribano L, Födinger M, Hartmann K, Brockow K, Castells M, Sperr WR, Kluin-Nelemans HC, Hamdy NA, Lortholary O, Robyn J, van Doormaal J, Sotlar K, Hauswirth AW, Arock M, Hermine O, Hellmann A, Triggiani M, Niedoszytko M, Schwartz LB, Orfao A, Horny HP, Metcalfe DD.

Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment recommendations and response criteria. Eur J Clin Invest. 2007 Jun;37(6):435–53.