Skin lesions are observed in about 80% of patients with mastocytosis. They are characteristic of CM and very common in indolent SM [1]. Patients may present with solitary or multiple hyperpigmented macules, papules or nodules, with generalized erythroderma, or peau d'orange-like skin. In infants and young children, skin blistering may be noted. When lesions are stroked, mast cell degranulation may occur and urticaria may be triggered. This phenomenon has been named after the dermatologist who first described it and is known as Darier's sign. Dermatographism, pruritus, and flushing may also be observed in response to the secretion of mast cell mediators.

It is important to note that the more aggressive subtypes of SM rarely present with cutaneous symptoms. These patients may show symptoms related to organ function impairment, may display systemic responses to mast cell degranulation, or suffer from constitutional symptoms [1]. The latter comprise fatigue, fever, and weight loss, among others. Mast cell granules contain histamine, heparin, prostaglandins, leukotrienes, and other vasoactive and proinflammatory mediators, which may induce headaches and abdominal pain, hypotension, tachycardia, and respiratory distress if they reach the circulation. Patients may experience syncopes and life-threatening complications such as anaphylaxis, particularly upon exposure to Hymenoptera venoms.

Extracutaneous tissues most frequently involved in SM are the bone marrow, lymph nodes, liver, spleen, and gastrointestinal mucosa. Bone marrow failure may lead to anemia, leukopenia, and thrombocytopenia. These conditions are accompanied by symptoms such as pallor, loss of energy, and poor performance, recurrent infections, and hemorrhagic diathesis. Lymphadenopathy, hepatomegaly, and splenomegaly may be diagnosed during the clinical examination, while gastrointestinal complications frequently result in nausea, pyrosis, abdominal pain, bloating, and diarrhea. In this context, it may not always be feasible to clinically distinguish between the effects of mast cell degranulation and the direct consequences of mast cell infiltration.

Additionally, mastocytosis predisposes to myalgia, arthralgia, and bone pain. Affected individuals are at higher risks of developing osteopenia, osteoporosis, and pathological fractures.

• Splenomegaly

  Non-indolent disease was more likely to present with hepatomegaly (p=0.0004), splenomegaly (p=0.0097), and lymphadenopathy (p=0.0079). CT, was the most common initial imaging modality, ordered to stage disease in 20 of 29 patients (69%). [ncbi.nlm.nih.gov]

  Diagnosis of mastocytosis was confirmed by histology, and apart from splenomegaly, no signs of systemic spread or associated hematologic disorders were detected. [content.sciendo.com]

  Diagnosis of mastocytosis was confirmed by histology, and apart from splenomegaly, no signs of systemic spread or associated hematologic disorders were detected… CONTINUE READING Create an AI-powered research feed to stay up to date with new papers like [semanticscholar.org]

  Splenomegaly attributable to SM is thought to be due to mast cell infiltration that may accompany hepatomegaly[ 20, 21 ]. Marked splenomegaly was found to be more common in aggressive SM[ 22 ]. [doi.org]

  […] condition include: • Anemia and bleeding disorders; • Gastrointestinal symptoms such as abdominal pain, diarrhea, nausea, or vomiting; • Itching, hives, or flushing of the skin; • Anaphylactoid reactions; • Enlarged liver (hepatomegaly); • Enlarged spleen (splenomegaly [secure.ssa.gov]

• Weight Loss

  loss, hepatomegally and ascitis, splenomagally and hypersplenism B findings: BM MCs count >30% and / or tryptase > 200 ng/mL BM hypercellularity Dysmyelopoiesis without cytopenia Organomegally without functional impairment Diagnosis Clinical manifestations [pathologyoutlines.com]

  Synonym: urticaria pigmentosa. (05 Mar 2000) diffuse mastocytosis Infiltration of many organ systems by mast cells with varied clinical manifestations that can include fever, weight loss, flushing, bronchospasm, rhinorrhoea, palpitations, dyspnea, diarrhoea [kmle.co.kr]

  loss, respiratory functions, diarrhea, lesions, and allergic reactions (some of these general terms may describe more than 1 assessment). [clinicaltrials.gov]

  Some of those patients may have extensive gastrointestinal tract infiltration resulting in low albumin, malabsorption, weight loss, and extensive diarrhea. [onclive.com]

  The dyspnea, weight loss and fevers, as well as the bilateral hilar lymphadenopathy and pulmonary infiltrates, are consistent with both sarcoid and pulmonary involvement of mastocytosis. [ispub.com]

• Fever

  They can have infection, bleeding, and fevers from bone marrow failure engendered by too many mast cells. So, there can be a lot of different ways a person can come to medical attention with a mast cell disease. [onclive.com]

  In patients with SM, mast cells produce high levels of these mediators, causing symptoms that range from mild to life-threatening, including pain, nausea, hives, bleeding, fever and anaphylaxis. [blueprintmedicines.com]

  Case 2 Male infant aged 6 months, with no history of interest, with repeated episodes of diarrhoea, urticarial rashes and fever. [analesdepediatria.org]

  Synonym: urticaria pigmentosa. (05 Mar 2000) diffuse mastocytosis Infiltration of many organ systems by mast cells with varied clinical manifestations that can include fever, weight loss, flushing, bronchospasm, rhinorrhoea, palpitations, dyspnea, diarrhoea [kmle.co.kr]

• Dyspnea

  The patient still had complaints of cognitive clouding, headaches, fatigue, dyspnea, mild abdominal cramping and pruritis. [ispub.com]

  Synonym: urticaria pigmentosa. (05 Mar 2000) diffuse mastocytosis Infiltration of many organ systems by mast cells with varied clinical manifestations that can include fever, weight loss, flushing, bronchospasm, rhinorrhoea, palpitations, dyspnea, diarrhoea [kmle.co.kr]

  […] urticaria pigmentosa Systemic mastocytosis A potentially aggressive condition characterized by mast cell proliferation in the skin, liver, lymph nodes, BM, GI tract Clinical Histamine hyperproduction with flushing, vertigo, palpitations, pruritus, colic, dyspnea [medical-dictionary.thefreedictionary.com]

  The most frequent Grade 3 or greater adverse reactions (incidence greater than or equal to 5%), excluding laboratory terms, were fatigue, sepsis, gastrointestinal hemorrhage, pneumonia, diarrhea, febrile neutropenia, edema, dyspnea, nausea, vomiting, [novartis.com]

  We also found that pulmonary symptoms (i.e., cough and dyspnea/bronchoreactivity) are significantly associated with mastocytosis. [doi.org]

• Respiratory Distress

  In this line, patients may complain about headaches, hypotension, palpitations, and respiratory distress. They may also experience anaphylaxis. [symptoma.com]

  After the fourth cycle of omalizumab, she experienced an immediate multisystem reaction with respiratory distress and tongue swelling. [hindawi.com]

• Abdominal Cramps

  Patients with all forms of mastocytosis can experience urticaria, abdominal cramps, nausea, diarrhea, or hypotension due to release of mediators by mast cells. [ncbi.nlm.nih.gov]

  When triggered, these mast cells release substances that can overwhelm your body and result in signs and symptoms such as facial flushing, itching, a rapid heartbeat, abdominal cramps, lightheadedness or even loss of consciousness. [mayoclinic.org]

  In rare cases chemicals released by mast cells cause changes in the immune system leading to typical allergy symptoms such as: itching, abdominal cramping, or anaphylaxis (shock from allergic or immune causes). [seattlecca.org]

  He had occasional abdominal cramping and diarrhea. Pulmonary function tests demonstrated mild reversible obstruction. [ispub.com]

• Pyrosis

  Lymphadenopathy, hepatomegaly, and splenomegaly may be diagnosed during the clinical examination, while gastrointestinal complications frequently result in nausea, pyrosis, abdominal pain, bloating, and diarrhea. [symptoma.com]

• Hepatosplenomegaly

  Clinical manifestations were predominantly mast cell activation symptoms (75.5%), poor performance status (50.9%), hepatosplenomegaly (50.9%), skin involvement (49.1%), osteoporosis (47.2%), and portal hypertension and ascites (26.4%). [ncbi.nlm.nih.gov]

  [MAST (CELL) + O + CYTE + OSIS] … Useful english dictionary mastocytosis syndrome — an episodic syndrome occurring in certain patients with systemic mastocytosis, usually those with skin lesions, bone lesions, and hepatosplenomegaly, presumably associated [translate.academic.ru]

  Abdominal peptic ulcer disease diffuse small bowel thickening omental and mesenteric thickening 9 hepatosplenomegaly ascites lymphadenopathy Pulmonary pulmonary nodules (rare) 2,8 differential diagnosis of diffuse bony sclerosis Promoted articles (advertising [radiopaedia.org]

  출처: www.mercksource.com/pp/us/cns/cns_health_library.j... mastocytosis s. an episodic syndrome occurring in certain patients with systemic mastocytosis, usually those with skin lesions, bone lesions, and hepatosplenomegaly, presumably associated with [kmle.co.kr]

• Hepatomegaly

  Non-indolent disease was more likely to present with hepatomegaly (p=0.0004), splenomegaly (p=0.0097), and lymphadenopathy (p=0.0079). CT, was the most common initial imaging modality, ordered to stage disease in 20 of 29 patients (69%). [ncbi.nlm.nih.gov]

  Signs and symptoms of this condition include: • Anemia and bleeding disorders; • Gastrointestinal symptoms such as abdominal pain, diarrhea, nausea, or vomiting; • Itching, hives, or flushing of the skin; • Anaphylactoid reactions; • Enlarged liver (hepatomegaly [secure.ssa.gov]

  Systemic symptoms (including flushing, hypotension, severe anaphylaxis, hepatomegaly, diarrhea and gastrointestinal bleeding) appear to be more common in DCM than in other forms of CM with systemic symptoms. [orpha.net]

  Hepatomegaly was found in 41%-72% of patients[ 12, 17 ]. Mast cells are known to infiltrate the liver diffusely with or without portal fibrosis and rarely cirrhosis in 4% of patients[ 12 ]. [doi.org]

• Hypotension

  Patients with all forms of mastocytosis can experience urticaria, abdominal cramps, nausea, diarrhea, or hypotension due to release of mediators by mast cells. [ncbi.nlm.nih.gov]

  2000) diffuse mastocytosis Infiltration of many organ systems by mast cells with varied clinical manifestations that can include fever, weight loss, flushing, bronchospasm, rhinorrhoea, palpitations, dyspnea, diarrhoea, gastrointestinal bleeding, and hypotension [kmle.co.kr]

• Fracture

  The fracture‐risk was only slightly increased. Am. J. Hematol. 91:1069–1075, 2016. © 2016 Wiley Periodicals, Inc. [doi.org]

  We report a case of isolated bone marrow mastocytosis in an 87-year-old woman who presented with a fall resulting in proximal femur fracture. [ncbi.nlm.nih.gov]

  In some patients, there is generalized osteoporosis with the risk of pathological fractures. [radiopaedia.org]

  Increased fracture rate Increased fractures Multiple fractures Multiple spontaneous fractures Varying degree of multiple fractures [ more ] 0002757 Splenomegaly Increased spleen size 0001744 Sudden cardiac death Premature sudden cardiac death 0001645 [rarediseases.info.nih.gov]

• Muscle Spasm

  Toxicity profile was acceptable, with mostly nausea and vomiting (52%), edema (44%), muscle spasms (28%), and rash (28%); however, one patient experienced reversible agranulocytosis (108). [frontiersin.org]

• Chronic Urticaria

  AK002 has completed phase 1 studies in healthy volunteers, indolent systemic mastocytosis, and a Phase 2 trial in patients with chronic urticaria. [globenewswire.com]

  This therapy was licensed for use in patients with severe asthma and chronic spontaneous urticaria. [hindawi.com]

  Interferon treatment of patients with chronic urticaria and mastocytosis. J Am Acad Dermatol1994;30:500–1. ↵ Kolde G, Sunderkotter C, Luger TA. Treatment of urticaria pigmentosa using interferon alpha. [adc.bmj.com]

  Unna showed mast cells in skin lesions of urticaria pigmentosa (UP)16; and, in 1949, systemic mastocytosis was recognized by Ellis while finding mast cell in the necropsy of a child with diffuse chronic infiltration.12 LITERATURE REVIEW Human mast cells [scielo.br]

• Skin Thickening

  When mastocytosis affects the skin (cutaneous mastocytosis), patients may experience Tan or red-brown spots on the skin Thickening of the skin Blisters Small lesions that do not itch When mastocytosis, affects areas other than the skin, it is call Systemic [cancer.columbia.edu]

  thickening in late generalized disease [ 6 ]. [em-consulte.com]

  Phototherapy can also be used to decrease refractory pruritus in urticarial pigmentosa and decrease dermographism and leathery skin thickening in diffuse cutaneous mastocytosis (Le et al, 2017). [atlasgeneticsoncology.org]

  Diffuse papules and nodules occur making the skin thickened, lichenified, and doughy. [23], [24] DCM can present with minimal blistering with erythema evolving into erythroderma. [25] Pseudoxanthomatous mastocytosis is a variant of DCM characterized by [ijpd.in]

  The skin is frequently thickened, lichenified and has a softened texture with a large number of yellowish papules. [scielo.br]

• Kidney Failure

  failure grade 1; dermatographism; longitudinal ridging in all nails; mood disturbances; recurrent impaired vision Mast cell clusters (>15 MCs) in gastro-intestinal biopsies; 14% were stained CD25-positive; somatic KIT D816V mutation and alterations in [f1000research.com]

  The baby born at 26 weeks of gestation (580 g) died at 22 days of life due to extreme prematurity, circulatory failure, grade 3 intraventricular hemorrhage, kidney failure, cardiopulmonary failure (no. 1). [journals.plos.org]

• Headache

  The most common adverse event was mild to moderate infusion-related reactions (flushing, feeling of warmth, headache, nausea, and dizziness) which occurred mostly during the first infusion. [globenewswire.com]

  Flushing Diarrhea Cardiac valvular disease-pulmonic stenosis, tricuspid insufficiency Bronchoconstriction Hypotension Mild and typically asymptomatic Rarely hypertension Precipitated by: anxiety, ethanol, catecholamines, chocolate Pheochromocytoma Pain -headache [errolozdalga.com]

  Medications for diffuse and systemic mastocytosis may include antihistamines, drugs to reduce stomach acid, migraine headache drugs for headache, and cromolyn for bowel symptoms. [medicinenet.com]

• Seizure

  Pehlivanidis C, Fotoulaki M, Boucher W, Kempuraj D, Pang X, et al. (2002) Acute stress-induced seizures and loss of consciousness in a ten-year-old boy with cutaneous mastocytosis. J Clin Psychopharmacol 22: 221–224. View Article Google Scholar 20. [doi.org]

• Vertigo

  […] be cutaneous or extracutaneous and urticaria pigmentosa Systemic mastocytosis A potentially aggressive condition characterized by mast cell proliferation in the skin, liver, lymph nodes, BM, GI tract Clinical Histamine hyperproduction with flushing, vertigo [medical-dictionary.thefreedictionary.com]

The diagnosis of CM is based on clinical and histopathological findings and the exclusion of SM. Skin biopsy samples need to be examined and typically reveal prominent mast cell infiltration in the dermis. Mast cells tend to aggregate around blood vessels and are readily recognized by their dense granular cytoplasm containing numerous metachromatic vesicles.

SM is characterized by the involvement of at least one extracutaneous organ, and the suspicion of systemic complications may be based on observations like organ dysfunction, organomegaly, severe clinical symptoms, and elevated serum tryptase levels. While it is generally recommended to carry out a bone marrow biopsy and to obtain tissue specimens from the organs assumed to be infiltrated by mast cells, molecular testing of peripheral blood cells for the KIT D816V mutation may constitute a less invasive approach to diagnosis. This is particularly the case for pediatric patients who are unlikely to suffer from the systemic variant and where serum tryptase levels may be associated with extensive skin involvement without underlying SM [2] [3].

If the suspicion of systemic involvement is substantiated, biopsy samples as described above have to be obtained. The multifocal presence of dense infiltrates of mast cells in the bone marrow and/or other extracutaneous organs is the single most important feature and major criterion of SM [4]. According to the World Health Organization, one major and one minor diagnostic criterion must be fulfilled for the diagnosis of SM. This same diagnosis may be established in the presence of three minor criteria. In this line, the following minor criteria should be considered:

• Presence of atypical mast cells in affected tissues
• Presence of KIT D816V mutation
• Aberrant expression of CD25 with or without CD2 on neoplastic mast cells
• Persistently elevated serum tryptase levels (> 20 ng/ml)

Since serum tryptase levels reflect the actual mast cell burden, they are also determined during follow-ups [4].

• Cytopenia

  lymphadenopathy, hepatosplemomegally C-findings: cytopenia, pathological fracture, malabsorption, hypoalbuminemia, weight loss, hepatomegally and ascitis, splenomagally and hypersplenism B findings: BM MCs count >30% and / or tryptase > 200 ng/mL BM [pathologyoutlines.com]

  Cytopenia is a “sine qua non” for any MDS diagnosis and in prior classifications, MDS nomenclature included references to “cytopenia” or to specific types of cytopenia (eg, “refractory anemia”). [doi.org]

  Haematological and bones: Anaemia or other cytopenias (if bone marrow involvement). Hypersplenism. Lymphadenopathy. Fractures (if bone marrow involved). [patient.info]

  In patients with very heavy mast cell involvement of the bone marrow, we see cytopenias, neutropenias, and anemias requiring transfusion; platelet problems; and thrombocytopenia requiring platelet transfusions. [onclive.com]

  Grade 3 or 4 myelosuppression during treatment occurred more commonly among patients who had had cytopenias at baseline; distinguishing whether new cases of cytopenias are related to midostaurin or disease progression is often difficult. [nejm.org]

• Decreased Platelet Count

  absolute monocytosis, decreased platelet count, anemia, and elevated alkaline phosphatase and transaminase levels. [jamanetwork.com]

Treatment of mastocytosis is mostly symptomatic and tailored on an individual basis [5]:

• Treating physicians should work in close cooperation with the patient to identify potential triggers leading to the exacerbation of symptoms. Common triggers include physical stimuli, emotional stress, spicy and hot foods, alcohol, drugs, and pathogens.
• The use of antihistamines, steroids, and cromolyn is recommended to alleviate symptoms related to mast cell degranulation. While adults may require lifelong treatment, medical therapy may be ceased eventually in the majority of pediatric patients.
• Cytoreductive drugs are generally reserved for those suffering from aggressive SM, whereby the decision in favor or against chemotherapy should be based on the recommendations of the World Health Organization. Here, B and C findings have been defined that indicate a high mast cell burden, possible dysplasia or excess proliferation of non-mast cell lineages, bone marrow dysfunction, and the involvement of liver, spleen, digestive tract, or skeleton [1]. Chemotherapeutic agents available for the management of mastocytosis include imatinib, masitinib, nilotinib, dasatinib, midostaurin, cladribine, and interferon α, but KIT D816V mutation may confer resistance to drug therapy [6].
• Hematopoietic stem cell transplantation may be considered as a viable and potentially curative therapeutic option for advanced SM [6] [7].
• Mastocytosis-related anaphylaxis should be treated in the same way as other cases of anaphylaxis. Beyond that, CM patients with extensive skin involvement, those diagnosed with SM, and every patient with a history of anaphylaxis should be provided an emergency kit containing an epinephrine autoinjector, corticosteroids, and antihistamines.

The prognosis for cutaneous and indolent SM is excellent. With regard to CM, regression is common in children and typically occurs before puberty. According to a retrospective study based on a long term clinical follow-up of childhood mastocytosis, complete regression may be achieved by 67% of all patients, major regression by 20%, and partial regression by 13% [8]. The persistence of skin lesions is to be expected in adult patients, but the disease can usually be managed with symptomatic treatment, and affected individuals have a normal life expectancy. On the other end of the spectrum are the most aggressive subtypes of SM, namely mast cell leukemia, SM with an associated hematological neoplasm, and aggressive SM. Median survival times of 2, 24, and 41 months, respectively, have been reported [9].

Under circumstances yet to be clarified, mild mastocytosis may aggravate and transform into a more aggressive type. Distinct factors have been identified that allow for a more reliable, yet not infallible risk stratification, and these factors include the type and subtype of mastocytosis, clinical findings, and molecular features [10]. For instance, the presence of KIT D816V mutation has been related to an increased likelihood of CM patients developing systemic complications during the course of the disease, but the parameter is lacking sensitivity [2]. Furthermore, up to 3% of patients who present with indolent SM, the least aggressive subtype of the disease, eventually develop mast cell leukemia. Predictors of disease progression are elevated serum β2‐microglobulin levels and the presence of KIT D816V mutation in multiple lineages [10].

SM is related to spontaneous mutations of the KIT proto-oncogene, which is located on the long arm of chromosome 4 and encodes for a receptor tyrosine kinase. The latter is activated by stem cell factor, a cytokine otherwise known as mast cell growth factor, and plays a key role in the regulation of mast cell differentiation, maturation, and survival. Gain-of-function mutations underlie the increase of mast cell numbers observed in mastocytosis, with mutation D816V being the most prevalent variant in these patients. Apart from KIT mutations, other gene defects, gene polymorphisms, and chromosomal aberrations may account for SM [11].

Little is known about the etiology of CM. Mutations as described in the previous paragraph can rarely be confirmed in patients diagnosed with CM.

The overall incidence of mastocytosis has been estimated at 1 in 10,000 inhabitants, but the underdiagnosis is still assumed [9]. CM is most commonly diagnosed in pediatric patients. While children of all ages may be affected, the majority of cases develops during the first year of life. CM may even be present at birth. By contrast, SM is generally an adult disease, with a peak incidence between the third and fifth decade of life. Slight preference for males or females has been reported for some subtypes of mastocytosis, but the gender distribution may be considered approximately equal at a general level.

With regards to the subtypes of mastocytosis, urticaria pigmentosa and indolent SM predominate in pediatric and adult patients, respectively [9].

Mast cells derive from progenitor cells in the bone marrow, circulate in the peripheral blood and eventually home to distinct tissues. Here, they undergo differentiation and maturation, which are complex processes that are regulated by a variety of mediators and feedback mechanisms. In this context, one of the most important cytokines is stem cell factor. It binds to specific, membrane-bound tyrosine kinase receptors expressed by mast cells. These receptors are encoded by the KIT proto-oncogene, and any mutation of this gene may have a profound impact on the development and survival of mast cells. In line with this, loss-of-function mutations of the KIT gene may result in mast cell deficiency, as has been observed in KIT mutant mice. Gain-of-function mutations, however, may promote mast cell growth and survival, giving rise to mastocytosis [11].

Interestingly, KIT mutations can be confirmed in the majority of patients with SM, but have rarely been identified in those suffering from CM. The mechanisms accounting for the abnormal accumulation and distribution of mast cells in the skin of CM patients have yet to be clarified [11].

No recommendations can be given to prevent the onset of mastocytosis. KIT mutations arise spontaneously, with familial cases of mastocytosis being increasingly rare [5].

Mastocytosis has initially been considered a type of myeloproliferative disease but is listed as a separate major disease entity with distinctive clinical and pathological features in the most recent WHO classification of tumors of hematopoietic tissues [1]. This same classification considers three types of mastocytosis, namely the cutaneous and systemic variants of mastocytosis and mast cell sarcoma. Subtypes have been defined as follows:

• Cutaneous mastocytosis: urticaria pigmentosa/maculopapular cutaneous mastocytosis, diffuse cutaneous mastocytosis, mastocytoma of skin
• Systemic mastocytosis: indolent systemic mastocytosis (including the bone marrow mastocytosis subtype), smoldering systemic mastocytosis, systemic mastocytosis with an associated hematological neoplasm, aggressive systemic mastocytosis, mast cell leukemia
• Mast cell sarcoma without subtypes

It is beyond the scope of this article to provide detailed information on all of these subtypes, which vary with regards to pathogenesis and clinical presentation, which require specific diagnostic measures and treatment strategies. Furthermore, they preferentially affect distinct patient groups and are associated with different outcomes. This article merely aims at giving an overview, and the interested reader is referred to the respective entries on this platform in order to obtain more specific information.

Mastocytosis is a general term referring to a heterogeneous group of disorders that are characterized by an abnormal accumulation and distribution of mast cells. Nearly all children and most adults suffering from mastocytosis present with cutaneous symptoms. They may show hyperpigmented macules, papules or nodules, or other skin lesions that give rise to hives when being stroked. Notwithstanding, mastocytosis may also affect other organs, such as the bone marrow, liver, spleen, or digestive tract. This is more commonly seen in adults and results in a broad spectrum of symptoms, from fatigue to the propensity to infection and bleeding, to abdominal pain and diarrhea. Additional symptoms may be triggered by mast cell-related mediators like histamine and heparin. In this line, patients may complain about headaches, hypotension, palpitations, and respiratory distress. They may also experience anaphylaxis.

The diagnosis of a specific type of mastocytosis is based on a thorough workup and should be considered an indispensable prerequisite for the preparation of an individual treatment plan. Furthermore, the patient's prognosis largely depends on the type of mastocytosis.

1. Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4 ed. Lyon, France: IARC Press; 2017.
2. Carter MC, Bai Y, Ruiz-Esteves KN, et al. Detection of KIT D816V in peripheral blood of children with manifestations of cutaneous mastocytosis suggests systemic disease. Br J Haematol. 2018; 183(5):775-782.
3. Lange M, Zawadzka A, Schrörs S, et al. The role of serum tryptase in the diagnosis and monitoring of pediatric mastocytosis: a single-center experience. Postepy Dermatol Alergol. 2017; 34(4):306-312.
4. Gotlib J, Gerds AT, Bose P, et al. Systemic Mastocytosis, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2018; 16(12):1500-1537.
5. Wagner N, Staubach P. Mastocytosis - pathogenesis, clinical manifestation and treatment. J Dtsch Dermatol Ges. 2018; 16(1):42-57.
6. Valent P, Akin C, Metcalfe DD. Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts. Blood. 2017; 129(11):1420-1427.
7. Ustun C, Reiter A, Scott BL, et al. Hematopoietic stem-cell transplantation for advanced systemic mastocytosis. J Clin Oncol. 2014; 32(29):3264-3274.
8. Uzzaman A, Maric I, Noel P, Kettelhut BV, Metcalfe DD, Carter MC. Pediatric-onset mastocytosis: a long term clinical follow-up and correlation with bone marrow histopathology. Pediatr Blood Cancer. 2009; 53(4):629-634.
9. Brockow K. Epidemiology, prognosis, and risk factors in mastocytosis. Immunol Allergy Clin North Am. 2014; 34(2):283-295.
10. Pardanani A. Systemic mastocytosis in adults: 2019 update on diagnosis, risk stratification and management. Am J Hematol. 2019; 94(3):363-377.
11. Valent P. Diagnostic evaluation and classification of mastocytosis. Immunol Allergy Clin North Am. 2006; 26(3):515-534.