View source for Mastocytosis

{{Infobox medical condition (new)
| name            = Mastocytosis
| image           = Mastocytosis - cropped - very high mag.jpg
| caption         = [[Micrograph]] of mastocytosis. Skin biopsy. [[H&E stain]].
| field           = [[Clinical Immunology|Clinical Immunology and Allergy]], [[Oncology]], [[hematology]]
| synonyms        = '''Clonal bone marrow disorder'''
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'''Mastocytosis''', a type of [[mast cell]] disease, is a [[Rare disease|rare disorder]] affecting both children and adults caused by the accumulation of functionally defective mast cells (also called ''mastocytes'') and [[CD34]]+ mast cell precursors.<ref name="pmid17587883">{{Cite journal |vauthors=Horny HP, Sotlar K, Valent P |title=Mastocytosis: state of the art |journal=Pathobiology |volume=74 |issue=2 |pages=121–32 |year=2007 |pmid=17587883 |doi=10.1159/000101711|doi-access=free }}</ref>

People affected by mastocytosis are susceptible to a variety of symptoms, including [[itch]]ing, [[hives]], and [[Anaphylaxis#Diagnosis|anaphylactic shock]], caused by the release of [[histamine]] and other pro-inflammatory substances from mast cells.<ref>{{Cite web|url=http://www.mastocytosis.ca/masto.htm |title=Mastocytosis & mast cell disorders |access-date=2017-11-02|archive-url=https://web.archive.org/web/20131228172813/http://www.mastocytosis.ca/masto.htm |archive-date=2013-12-28 |publisher=Mastocytosis Society Canada}}</ref>

== Signs and symptoms ==
[[File:Mastocytosis2019.jpg|thumb|upright=1.4|Mastocytosis]]

When mast cells undergo [[degranulation]], the substances that are released can cause a number of symptoms that can vary over time and can range in intensity from mild to severe. Because mast cells play a role in allergic reactions, the symptoms of mastocytosis often are similar to the symptoms of an allergic reaction. They may include, but are not limited to<ref>{{cite journal |last1=Hermine |first1=Olivier |last2=Lortholary |first2=Olivier |last3=Leventhal |first3=Phillip S. |last4=Catteau |first4=Adeline |last5=Soppelsa |first5=Frédérique |last6=Baude |first6=Cedric |last7=Cohen-Akenine |first7=Annick |last8=Palmérini |first8=Fabienne |last9=Hanssens |first9=Katia |last10=Yang |first10=Ying |last11=Sobol |first11=Hagay |last12=Fraytag |first12=Sylvie |last13=Ghez |first13=David |last14=Suarez |first14=Felipe |last15=Barete |first15=Stéphane |last16=Casassus |first16=Philippe |last17=Sans |first17=Beatrice |last18=Arock |first18=Michel |last19=Kinet |first19=Jean Pierre |last20=Dubreuil |first20=Patrice |last21=Moussy |first21=Alain |last22=Soyer |first22=H. Peter |title=Case-Control Cohort Study of Patients' Perceptions of Disability in Mastocytosis |journal=PLOS ONE |date=28 May 2008 |volume=3 |issue=5 |article-number=e2266 |doi=10.1371/journal.pone.0002266 |pmid=18509466 |pmc=2386235 |bibcode=2008PLoSO...3.2266H |doi-access=free }}</ref>
* Fatigue
* Skin lesions (''[[urticaria pigmentosa]]''), [[itch]]ing, and [[dermatographic urticaria|dermatographic ''urticaria'']] (skin writing)
* [[Darier's sign|"Darier's Sign"]], a reaction to stroking or scratching of urticaria lesions.
* [[Abdominal pain|Abdominal discomfort]]
* [[Nausea]] and [[vomiting]]
* [[Diarrhea]]
* Olfactive intolerance
* Ear/nose/throat inflammation
* [[Anaphylaxis]] ([[shock (circulatory)|shock]] from allergic or immune causes)
* Episodes of [[hypotension|very low blood pressure]] (including shock) and [[Syncope (medicine)|faintness]]
* [[Bone pain|Bone]] or [[Myalgia|muscle pain]]
* Decreased bone density or increased bone density ([[osteoporosis]] or [[osteosclerosis]])
* Headache
* Depression<ref name=pmid22031830>{{cite journal |last1=Moura |first1=Daniela Silva |last2=Sultan |first2=Serge |last3=Georgin-Lavialle |first3=Sophie |last4=Pillet |first4=Nathalie |last5=Montestruc |first5=François |last6=Gineste |first6=Paul |last7=Barete |first7=Stéphane |last8=Damaj |first8=Gandhi |last9=Moussy |first9=Alain |last10=Lortholary |first10=Olivier |last11=Hermine |first11=Olivier |last12=Hashimoto |first12=Kenji |title=Depression in Patients with Mastocytosis: Prevalence, Features and Effects of Masitinib Therapy |journal=PLOS ONE |date=21 October 2011 |volume=6 |issue=10 |article-number=e26375 |doi=10.1371/journal.pone.0026375 |pmid=22031830 |pmc=3198767 |bibcode=2011PLoSO...626375M |doi-access=free }}</ref>
* Ocular discomfort
* Increased stomach acid production causing [[Peptic ulcer disease|peptic ulcers]] (increased stimulation of [[enterochromaffin cell]] and direct histamine stimulation on [[parietal cell]])
* [[Malabsorption]] (due to inactivation of pancreatic enzymes by increased acid)<ref>{{Cite journal|last=Lee|first=JK|author2=Whittaker, SJ |author3=Enns, RA |author4= Zetler, P |title=Gastrointestinal manifestations of systemic mastocytosis|journal=World Journal of Gastroenterology|date=Dec 7, 2008|volume=14|issue=45|pages=7005–8|pmid=19058339|doi=10.3748/wjg.14.7005 |pmc=2773867 |doi-access=free }}</ref>
* Hepatosplenomegaly

There are few qualitative studies about the effects of mastocytosis on daily life. However, a Danish study from 2018 describes the multidimensional impact of the disease on everyday life.<ref>{{cite journal |last1=Jensen |first1=Britt |last2=Broesby-Olsen |first2=Sigurd |last3=Bindslev-Jensen |first3=Carsten |last4=Nielsen |first4=Dorthe S. |title=Everyday life and mastocytosis from a patient perspective-a qualitative study |journal=Journal of Clinical Nursing |date=April 2019 |volume=28 |issue=7–8 |pages=1114–1124 |doi=10.1111/jocn.14676 |pmid=30230078 |s2cid=52298220 |url=https://portal.findresearcher.sdu.dk/da/publications/2490058c-e342-4e1f-aa34-0f626673817f }}</ref>

== Pathophysiology ==
[[Mast cell]]s are located in [[connective tissue]], including the [[skin]], the linings of the stomach and intestine, and other sites. They play an important role in the immune defence against bacteria and parasites. By releasing chemical "alarms" such as [[histamine]], mast cells attract other key players of the [[Immune system|immune defense system]] to areas of the body where they are needed.{{citation needed|date=March 2021}}

Mast cells seem to have other roles as well. Because they gather together around [[wound]]s, mast cells may play a part in wound healing. For example, the typical itching felt around a healing scab may be caused by [[histamine]] released by mast cells. Researchers also think mast cells may have a role in the growth of [[blood vessel]]s ([[angiogenesis]]). No one with ''too few'' or no mast cells has been found, which indicates to some scientists we may not be able to survive with too few mast cells.{{citation needed|date=March 2021}}

Mast cells express a [[cell surface receptor]], ''c-kit''<ref name="pmid17555444">{{Cite journal |vauthors=Orfao A, Garcia-Montero AC, Sanchez L, Escribano L |title=Recent advances in the understanding of mastocytosis: the role of KIT mutations |journal=Br. J. Haematol. |volume=138 |issue=1 |pages=12–30 |year=2007 |pmid=17555444 |doi=10.1111/j.1365-2141.2007.06619.x|hdl=10261/62846 |s2cid=12120327 |doi-access=free }}</ref> ([[CD117]]), which is the [[Receptor (biochemistry)|receptor]] for stem cell factor (''scf''). In laboratory studies, ''scf'' appears to be important for the proliferation of mast cells. Mutations of the gene coding for the ''c-kit'' receptor (mutation KIT(D816V)), leading to constitutive signalling through the receptor is found in >90% of patients with systemic mastocytosis.<ref name="pmid28254862">{{Cite journal | vauthors = Valent P, Akin C, Hartmann K, Nilsson G, Reiter A, Hermine O, Sotlar K, Sperr WR, Escribano L, George TI, Kluin-Nelemans HC, Ustun C, Triggiani M, Brockow K, Gotlib J, Orfao A, Schwartz LB, Broesby-Olsen S, Bindslev-Jensen C, Kovanen PT, Galli SJ, Austen KF, Arber DA, Horny HP, Arock M, Metcalfe DD|display-authors = 6 | title = Advances in the Classification and Treatment of Mastocytosis: Current Status and Outlook toward the Future | journal = Cancer Research | volume = 77 | issue = 6 | pages = 1261–1270 | date = March 2017 | pmid = 28254862 | pmc = 5354959 | doi = 10.1158/0008-5472.CAN-16-2234}}</ref>

== Diagnosis ==
Diagnosis of ''urticaria pigmentosa'' (cutaneous mastocytosis, see above) can often be done by seeing the characteristic lesions that are dark brown and fixed. A small skin sample ([[biopsy]]) may help confirm the diagnosis.{{Citation needed|date=February 2018}}

In case of suspicion of systemic disease the level of serum tryptase in the blood can be of help. If the base level of s-tryptase is elevated, this implies that the mastocytosis can be systemic. In cases of suspicion of SM help can also be drawn from analysis of mutation in KIT(D816V) in peripheral blood using sensitive PCR-technology{{citation needed|date=August 2020}}

To set the diagnosis of systemic mastocytosis, certain criteria must be met. Either one major + one minor criterion '''or''' three minor criteria has to be fulfilled:<ref name="pmid27069254" />

===Major criterion===
* Dense infiltrates of >15 mast cells in the bone marrow or an extracutaneous organ

=== Minor criteria ===
* Aberrant phenotype on the mast cells (pos. for CD2 and/or CD25)
* Aberrant mast cell morphology (spindle-shaped)
* Finding of mutation in KIT(D816V)
* S-tryptase >20&nbsp;ng/ml

=== Other mast cell diseases ===
Other types of mast cell disease include:
* Monoclonal mast cell activation, defined by the World Health Organization definitions 2010, also has increased mast cells but insufficient to be systemic mastocytosis (in World Health Organization Definitions)
* [[Mast cell activation syndrome]] – has normal number of mast cells, but all the symptoms and in some cases the genetic markers of systemic mastocytosis<ref name="Akin-Valent-Metcalfe">{{Cite journal|vauthors=Akin C, Valent P, Metcalfe DD|year=2010|title=Mast cell activation: proposed diagnostic criteria|journal=The Journal of Allergy and Clinical Immunology|volume=126|issue=6|pages=1099–104|doi=10.1016/j.jaci.2010.08.035|pmc=3753019|pmid=21035176}}</ref>
* Another known but rare mast cell proliferation disease is [[mast cell sarcoma]].<ref>National Organization for Rare Disorders (NORD) [https://rarediseases.org/rare-diseases/mastocytosis/ "Mastocytosis"], 2017</ref>

=== Classification ===
Mastocytosis can occur in a variety of forms:

==== Cutaneous mastocytosis (CM) ====
* The most common cutaneous mastocytosis is maculopapular cutaneous mastocytosis, previously named papular ''urticaria pigmentosa'' (UP), more common in children, although also seen in adults. ''[[Telangiectasia macularis eruptiva perstans]]'' (TMEP) is a much rarer form of cutaneous mastocytosis that affects adults.<sup>[2]</sup> MPCM and TMEP can be a part of indolent systemic mastocytosis. This should be considered if patients develop any systemic symptoms<ref>{{Cite journal |author=Ellis DL |title=Treatment of telangiectasia macularis eruptiva perstans with the 585-nm flashlamp-pumped dye laser |journal=Dermatol Surg |volume=22 |issue=1 |pages=33–7 |year=1996 |pmid=8556255 |doi= 10.1016/1076-0512(95)00388-6}}</ref>
* Generalized eruption of cutaneous mastocytosis (adult type) is the most common pattern of mastocytosis presenting to the dermatologist, with the most common lesions being macules, papules, or nodules that are disseminated over most of the body but especially on the upper arms, legs, and trunk<ref>{{cite journal |last1=Noack |first1=F. |last2=Escribano |first2=L. |last3=Sotlar |first3=K. |last4=Nunez |first4=R. |last5=Schuetze |first5=K. |last6=Valent |first6=P. |last7=Horny |first7=H.-P. |title=Evolution of Urticaria Pigmentosa into Indolent Systemic Mastocytosis: Abnormal Immunophenotype of Mast Cells without Evidence of c-kit Mutation ASP-816-VAL |journal=Leukemia & Lymphoma |date=July 2009 |volume=44 |issue=2 |pages=313–319 |doi=10.1080/1042819021000037967 |pmid=12688351 |s2cid=30459720 }}</ref>
* Diffuse cutaneous mastocytosis has diffuse involvement in which the entire [[Integumentary system|integument]] may be thickened and infiltrated with mast cells to produce a peculiar orange color, giving rise to the term ''homme orange''.<ref name="Andrews">James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews' Diseases of the Skin: Clinical Dermatology''. (10th ed.). Saunders. {{ISBN|0-7216-2921-0}}.{{page needed|date=June 2020}}</ref>
Cutaneous mastocytosis in children usually presents in the first year after birth and in most cases vanishes during adolescence.

==== Systemic mastocytosis (SM) ====
[[File:Immunohistochemistry of c-KIT in small intestine, highlighting mast cells.jpg|thumb|[[Immunohistochemistry]] for [[KIT (gene)|c-KIT]] highlights mast cells (darkly stained) in the mucosa of the small intestine.]]
Systemic mastocytosis involves the bone marrow in the majority of cases and in some cases other internal organs, usually in addition to involving the skin. Mast cells collect in various tissues and can affect organs where mast cells do not normally inhabit such as the [[liver]], [[spleen]] and [[lymph node]]s, and organs which have normal populations but where numbers are increased. In the bowel, it may manifest as mastocytic [[enterocolitis]].<ref>{{cite journal |last1=Ramsay |first1=David B. |last2=Stephen |first2=Sindu |last3=Borum |first3=Marie |last4=Voltaggio |first4=Lysandra |last5=Doman |first5=David B. |title=Mast Cells in Gastrointestinal Disease |journal=Gastroenterology & Hepatology |date=December 2010 |volume=6 |issue=12 |pages=772–777 |pmid=21301631 |pmc=3033552 }}</ref> However, normal ranges for mast cell counts in the gastrointestinal tract mucosa are not well established in the literature, and depend upon the exact location (e.g. right versus left colon), gender, and patient populations (such as asymptomatic patients versus patients with chronic diarrhea of unknown etiology).  Quantitative mast cell stains may yield little diagnostic information, and further research studies are warranted to determine whether "mastocytic enterocolitis" truly represents a distinct entity.<ref name="Sethi Jain Roland Kinzel pp. 225–232">{{cite journal | last1=Sethi | first1=Aisha | last2=Jain | first2=Dhanpat | last3=Roland | first3=Bani Chander | last4=Kinzel | first4=Jason | last5=Gibson | first5=Joanna | last6=Schrader | first6=Ronald | last7=Hanson | first7=Joshua Anspach | title=Performing Colonic Mast Cell Counts in Patients With Chronic Diarrhea of Unknown Etiology Has Limited Diagnostic Use | journal=Archives of Pathology & Laboratory Medicine | publisher=Archives of Pathology and Laboratory Medicine | volume=139 | issue=2 | date=2015-02-01 | issn=1543-2165 | doi=10.5858/arpa.2013-0594-oa | pages=225–232| pmid=25611105 }}</ref>

There are five types of systemic mastocytosis:<ref name=pmid27069254>{{cite journal |last1=Arber |first1=Daniel A. |last2=Orazi |first2=Attilio |last3=Hasserjian |first3=Robert |last4=Thiele |first4=Jürgen |last5=Borowitz |first5=Michael J. |last6=Le Beau |first6=Michelle M. |last7=Bloomfield |first7=Clara D. |last8=Cazzola |first8=Mario |last9=Vardiman |first9=James W. |title=The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia |journal=Blood |date=19 May 2016 |volume=127 |issue=20 |pages=2391–2405 |doi=10.1182/blood-2016-03-643544 |pmid=27069254 |doi-access=free }}</ref>
* Indolent systemic mastocytosis (ISM). The most common SM (>90%)
* Smouldering systemic mastocytosis (SSM)
* Systemic mastocytosis with associated [[hematological neoplasm]] (SM-AHN)
* Aggressive systemic mastocytosis (ASM)
* [[Mast cell leukemia]] (MCL)
{{Further|topic=the investigational new drug|Bezuclastinib}}

== Treatment ==
There is no cure for mastocytosis, but there are a number of medicines to help treat the symptoms:<ref>{{cite web |title=Mastocytosis - Treatment Options |url=https://www.cancer.net/cancer-types/mastocytosis/treatment-options |website=Cancer.Net |date=25 June 2012 }}</ref>

=== Anti-mediator therapy ===
* [[Antihistamine]]s block receptors targeted by histamine released from mast cells. Both H<sub>1</sub> and H<sub>2</sub> blockers may be helpful, often in combination.<ref>{{cite journal |last1=Cardet |first1=Juan Carlos |last2=Akin |first2=Cem |last3=Lee |first3=Min Jung |title=Mastocytosis: update on pharmacotherapy and future directions |journal=Expert Opinion on Pharmacotherapy |date=October 2013 |volume=14 |issue=15 |pages=2033–2045 |doi=10.1517/14656566.2013.824424 |pmid=24044484 |pmc=4362676 }}</ref>
* [[Leukotriene]] antagonists block receptors targeted by leukotrienes released from mast cells.
* [[Mast cell stabilizer]]s help prevent mast cells from releasing their chemical contents. [[Cromoglicic acid]] is the only medicine specifically approved by the FDA for the treatment of mastocytosis. [[Ketotifen]] is available in Canada and Europe and more recently in the U.S. It is also available as eyedrops (Zaditor).
* [[Proton-pump inhibitor]]s help reduce production of gastric acid, which is often increased in patients with mastocytosis. Excess gastric acid can harm the stomach, esophagus, and small intestine.
* [[Adrenaline|Epinephrine]] constricts blood vessels and opens airways to maintain adequate circulation and ventilation when excessive mast cell degranulation has caused [[anaphylaxis]].
* [[Salbutamol]] and other beta-2 agonists open airways that can constrict in the presence of histamine.
* [[Corticosteroid]]s can be used topically, inhaled, or systemically to reduce inflammation associated with mastocytosis.
* Drugs to prevent/treat osteoporosis include Calcium-Vitamine D, bisphosphonates and in rare cases inhibitors of RANK-L

[[Antidepressant]]s are an important and often overlooked tool in the treatment of mastocytosis. Depression and other neurological symptoms have been noted in mastocytosis.<ref name=pmid22031830/><ref>{{cite journal |last1=Rogers |first1=M P |last2=Bloomingdale |first2=K |last3=Murawski |first3=B J |last4=Soter |first4=N A |last5=Reich |first5=P |last6=Austen |first6=K F |title=Mixed organic brain syndrome as a manifestation of systemic mastocytosis. |journal=Psychosomatic Medicine |date=July 1986 |volume=48 |issue=6 |pages=437–447 |doi=10.1097/00006842-198607000-00006 |pmid=3749421 |s2cid=37335288 }}</ref> Some antidepressants, such as [[doxepin]] and [[mirtazapine]], are themselves potent antihistamines and can help relieve physical as well as cognitive symptoms.{{citation needed|date=June 2022}}

=== Cytoreductive therapy ===
In cases of advanced systemic mastocytosis or rare cases with indolent systemic mastocytosis with very troublesome symptoms, cytoreductive therapy can be indicated.<ref name=pmid27762455>{{cite journal |last1=Pardanani |first1=Animesh |title=Systemic mastocytosis in adults: 2017 update on diagnosis, risk stratification and management |journal=American Journal of Hematology |date=November 2016 |volume=91 |issue=11 |pages=1146–1159 |doi=10.1002/ajh.24553 |pmid=27762455 |doi-access=free }}</ref>
* ɑ-[[interferon]]. Given as subcutaneous injections. Side effects include fatigue and influenza-like symptoms
* [[Cladribine]] (CdA). Chemotherapy which is given as subcutaneous injections. Side effects include immunodeficiency and infections.
* [[Tyrosine kinase inhibitors]] (TKI)
** [[Midostaurin]]. TKI acting on many different tyrosine kinases, approved by FDA and EMA for advanced mastocytosis
** [[Imatinib]]. Can have effect in rare cases without mutation in KIT(D816V)
** [[Masitinib]]. Is being tested in trials. Not approved.
** [[Midostaurin]] - 60% respond.<ref name=pmid31372066>{{cite journal |last1=Gilreath |first1=JA |last2=Tchertanov |first2=L |last3=Deininger |first3=MW |title=Novel approaches to treating advanced systemic mastocytosis |journal=Clinical Pharmacology: Advances and Applications |date=July 2019 |volume=11 |pages=77–92 |doi=10.2147/CPAA.S206615 |pmid=31372066 |pmc=6630092 |doi-access=free }}</ref>
** [[Avapritinib]] in trials; currently being tested but showing promise in reduction of tryptase levels.<ref name=pmid31372066/>

[[Allogeneic stem cell transplantation]] has been used in rare cases with aggressive systemic mastocytosis in patients deemed to be fit for the procedure.

=== Other ===
Treatment with [[Ultraviolet|ultraviolet light]] can relieve skin symptoms, but may increase the risk of skin cancer.<ref>{{cite journal |last1=Broesby-Olsen |first1=Sigurd |last2=Farkas |first2=Dóra Körmendiné |last3=Vestergaard |first3=Hanne |last4=Hermann |first4=Anne Pernille |last5=Møller |first5=Michael Boe |last6=Mortz |first6=Charlotte Gotthard |last7=Kristensen |first7=Thomas Kielsgaard |last8=Bindslev-Jensen |first8=Carsten |last9=Sørensen |first9=Henrik Toft |last10=Frederiksen |first10=Henrik |title=Risk of solid cancer, cardiovascular disease, anaphylaxis, osteoporosis and fractures in patients with systemic mastocytosis: A nationwide population-based study |journal=American Journal of Hematology |date=November 2016 |volume=91 |issue=11 |pages=1069–1075 |doi=10.1002/ajh.24490 |pmid=27428296 |s2cid=24088671 |doi-access=free }}</ref>

== Prognosis ==
Patients with indolent systemic mastocytosis have a normal life expectancy. The prognosis for patients with advanced systemic mastocytosis differs depending on type of disease with MCL being the most serious form with short survival.<ref name=pmid27762455/>

== Epidemiology ==
The true incidence and prevalence of mastocytosis is unknown, but mastocytosis generally has been considered to be an "[[Rare disease|orphan disease]]"; orphan diseases affect 200,000 or fewer people in the United States. Mastocytosis, however, often may be misdiagnosed, as it typically occurs secondary to another condition, and thus may occur more frequently than assumed.{{Citation needed|date=December 2013}}

==Research==
[[National Institute of Allergy and Infectious Diseases]] scientists have been studying and treating patients with mastocytosis for several years at the [[National Institutes of Health]] (NIH) Clinical Center.{{Citation needed|date=December 2013}}

Some of the most important research advances for this rare disorder include improved diagnosis of mast cell disease and identification of growth factors and genetic mechanisms responsible for increased mast cell production.<ref>Garde, Damian, ''[https://www.statnews.com/2020/03/16/unpredictable-allergic-reactions-experimental-drug-takes-blueprint-medicines/ To quell unpredictable allergic reactions, an experimental drug takes aim at a genetic cause, not symptoms]'', Stat, March 16, 2020</ref> Researchers are currently evaluating approaches to improve ways to treat mastocytosis.{{Citation needed|date=December 2013}}

Scientists also are focusing on identifying disease-associated mutations (changes in genes). NIH scientists have identified some mutations, which may help researchers understand the causes of mastocytosis, improve diagnosis, and develop better treatments.{{Citation needed|date=December 2013}}

In Europe the European Competence Network on Mastocytosis (ECNM) coordinates studies, registries and education on mastocytosis.{{citation needed|date=August 2020}}

== History ==
''Urticaria pigmentosa'' was first described in 1869.<ref>{{Cite journal |vauthors=Nettleship E, Tay W |title=Reports of Medical and Surgical Practice in the Hospitals of Great Britain |journal=Br Med J |volume= 2|issue=455 |pages=323–4 |year=1869 | pmc=2260962 |pmid=20745623 |doi=10.1136/bmj.2.455.323}}</ref> The first report of a primary mast cell disorder is attributed to Unna, who in 1887 reported that skin lesions of ''urticaria pigmentosa'' contained numerous mast cells.<ref>{{cite book |last1=Unna |first1=Paul Gerson |last2=Unna |title=Beiträge zur Anatomie und Pathogenese der Urticaria simplex und Pigmentosa |trans-title=Contributions to the anatomy and pathogenesis of urticaria simplex and pigmentosa |language=de |date=1887 |publisher=Verlag von Leopold Voss |oclc=840287852 }}</ref> Systemic mastocytosis was first reported by French scientists in 1936.<ref>{{Cite journal |vauthors=Sézary A, Levy-Coblentz G, Chauvillon P |title=Dermographisme et mastocytose |journal=Bulletin de la Société Française de Dermatologie et de Syphiligraphie |volume=43 |pages=359–61 |year=1936 }}</ref>

==See also==
* [[Mastocytoma]]

==References==
{{Reflist|30em}}

==Further reading==
* {{cite journal |last1=Gruchalla |first1=Rebecca S. |title=Mastocytosis: Developments During the Past Decade |journal=The American Journal of the Medical Sciences |date=June 1995 |volume=309 |issue=6 |pages=328–338 |doi=10.1097/00000441-199506000-00007 |pmid=7771504 }}

{{Myeloid malignancy|us=y}}
{{Congenital malformations and deformations of integument}}
{{Medical resources
| DiseasesDB      = 7864
| ICD10           = {{ICD10|Q|82|2|q|80}}, {{ICD10|C|96|2|c|81}}
| ICD9            = {{ICD9|757.33}}, {{ICD9|202.6}}
| ICDO            = 9741/3
| OMIM            = 154800
| eMedicineSubj   = derm
| eMedicineTopic  = 258
| eMedicine_mult  = {{EMedicine2|med|1401}}
| Orphanet        = 98292
| ICD11           = {{ICD11|2A21}}
| MeshID          = D008415
| NORD            = mastocytosis
| GARDNum         = 6987
| GARDName        = mastocytosis
}}
{{Authority control}}

[[Category:Dermal and subcutaneous growths]]
[[Category:Immune system disorders]]
[[Category:Rare diseases]]