Mastocytosis

Classification according to ICD-10
C94.3	Mast cell leukemia
C96.2	Malignant mast cell tumor Malignant mastocytosis
Q82.2	congenital mastocytosis (of the skin) urticaria pigmentosa
D47.0	Histiocyte and mast cell tumor of uncertain or unknown behavior Indolent systemic mastocytosis
ICD-10 online (WHO version 2019)

The mastocytosis is a rare disorder caused by accumulation of mast cells in the skin is characterized or in the internal organs. In addition to the predominantly benign courses with frequent spontaneous remissions , especially in childhood mastocytosis, malignant forms have also been described.

Causes and Triggers

The cause of the disease is unclear. For most people, symptoms are caused by one or more of the following factors:

• alcohol
• hot spices
• certain foods and additives
• (emotional) stress
• Infectious diseases
• Medicines: morphine derivatives, anesthetics, anesthetic gases, codeine, local anesthetics, quinine, amphotericin B, acetylsalicylic acid (ASA) etc.
• Insect venom (bee, wasp), snake and jellyfish venom, and others
• allergic disease (allergens of all kinds)
• physical triggers: exertion, sunlight, cold, heat, friction

Cutaneous mastocytosis

In cutaneous mastocytosis, which predominantly affects children and adolescents, only the skin is affected. It shows reddish-brown pigment spots that occasionally form blisters and which can cause swelling and reddening due to the release of histamine from the mast cells when rubbing them ( Darier's sign ). The diagnosis is made on the basis of the typical picture and, if necessary, confirmed by a biopsy of a focus, which shows a diffuse mast cell infiltration in the dermis upon histological processing . Cutaneous mastocytosis occurs in different variants. The mastocytoma is a collection of mast cells that is present at birth or develops within the first few weeks of life. In contrast, the pigment spots in urticaria pigmentosa are distributed over the entire body, with an emphasis on the trunk. The time of manifestation of this variant lies between childhood and middle adulthood. This can lead to spontaneous regression in children under 10 years of age.

Systemic mastocytosis

Systemic mastocytosis, which usually affects adults, also affects internal organs such as the intestines, liver and spleen. It is still considered a rarity, although some authors suspect a high number of unreported cases. After all, systemic mastocytosis is said to be the cause of 1.25% of all secondary osteoporosis diseases .

diagnosis

The diagnosis of systemic mastocytosis is made when the main and a secondary criterion or three secondary criteria of the so-called WHO consensus criteria are met. The main criterion is

• the detection of multifocal, dense mast cell infiltrates (more than 15 mast cells lying together) in the bone marrow biopsy or in biopsies from organs other than the skin.

Diagnostic secondary criteria are

• a proportion of atypical mast cells of more than 25% of the mast cells in the bone marrow smear or in other organs,
• a c-kit point mutation in codon 816 in mast cells from bone marrow or from organs other than skin,
• an expression of the antigens CD2 or CD25 by mast cells from the bone marrow or organs other than the skin and
• a basal tryptase concentration of more than 20 ng / ml in the blood serum, only in patients without myeloid neoplasia.

As the first tests in suspected cases of Tryptasengehalt in the blood and excretion of may histamine - metabolites N-methyl histamine and 1,4-Methylimidazolessigsäure in urine can be determined. The diagnosis is confirmed by the histological evidence of mast cell infiltration in the bone marrow or in an organ other than the skin.

therapy

The treatment of systemic mastocytosis is mainly symptomatic. The data on which most therapy recommendations are based is sparse. The focus is on avoiding food, medication and situations that, in individual cases, experience has shown to lead to symptoms due to the release of histamine. Older antihistamines , whose sedative effect is deliberately used to reduce the release of histamine, are mostly used as medication . Low doses of benzodiazepines are often used for the same reason . Today, the aggressive forms are often treated “experimentally” with ciclosporin , corticosteroids and interferon α-2b, analogous to other malignant diseases , without their effectiveness being proven.

Another therapeutic approach is PUVA , a treatment with psoralen , a photosensitizing substance, and subsequent exposure of the skin to UV-A radiation.

In a study on more than 100 patients with severe forms of mastocytosis, an international group of doctors and scientists demonstrated the effectiveness of a new, targeted drug: the tyrosine kinase inhibitor midostaurin (PKC412) from Novartis , which selectively inhibits KIT -activated cells 60 percent of the patients get a significant improvement. There was a regression of the organ changes, a decrease in the mast cell infiltrates and there was a prolonged progression-free survival. The main side effects of the drug were nausea and changes in the blood count.

The tyrosine kinase inhibitors masitinib and toceranib are approved for the treatment of mast cell tumors in dogs .

Web links

• Gerhard J. Molderings: Mast cell function in physiology and pathophysiology. (PDF; 205 kB) In: Biotrend Reviews , No. 5, January 2010, BIOTREND Chemicals AG
• mastozytose-info.de - Information on mastocytosis and patient representation in the Federal Joint Committee
• Hans-Peter Horny et al .: Mastocytosis: A disease of the hemopoietic stem cell . In: Deutsches Ärzteblatt . No. 105 (40) , 2008, pp. 686-692 ( aerzteblatt.de - review article).
• Mastocytosis Guideline. (PDF) German Dermatological Society (DDG)
• Mastocytosis guideline of the German Society for Hematology and Medical Oncology eV

Individual evidence

1. ↑ Easily understandable, medically up-to-date information on the subject of mastocytosis. ( Memento of the original from September 9, 2015 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. Allergy portal of the ECARF foundation 
2. ↑ Wolfram Sterry: Kurzlehrbuch Dermatologie . Georg Thieme Verlag, 2011.
3. ↑ ^{a b} G. J. Molderings et al .: Systemic mastocytosis as a reason for chronic gastrointestinal complaints. In: Deutsches Ärzteblatt , 2005, 102, pp. A1744 – A1749.
4. ↑ P. Valent et al .: Mastocytosis (mast cell disease). In: ES Jaffe et al. (Ed.): World Health Organization (WHO) Classification of tumors. Pathology & Genetics. Tumors of Haematopietic and Lymphoid Tissues . WHO (2001); 1, pp. 291-302.
5. ↑ Rüdiger Labahn: New targeted therapy for mastocytosis developed. University of Lübeck , press release from June 30, 2016 at the Informationsdienst Wissenschaft (idw-online.de), accessed on October 18, 2016.
6. ↑ rme / aerzteblatt.de: Midostaurin alleviates systemic mastocytosis. In: Deutsches Ärzteblatt . July 1, 2016, accessed October 18, 2016 . 
7. ↑ Novartis receives FDA approval for Rydapt® in newly diagnosed FLT3-mutated acute myeloid leukemia (AML) and three types of systemic mastocytosis (SM) , PM Novartis April 28, 2017, accessed May 11, 2017
8. ↑ Sven Siebenand: Midostaurin A new multitarget kinase inhibitor. In: Pharmaceutical newspaper. Retrieved October 18, 2016 (edition 30/2016). 
9. ↑ Olivier Hermine et al .: Masitinib for treatment of severely symptomatic indolent systemic mastocytosis: a randomized, placebo-controlled, phase 3 study. In: The Lancet . January 6, 2017, accessed January 28, 2017 . 

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