Mastocytosis - Rare Rheumatology News

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Disease Profile

Mastocytosis

1-5 / 10 000

US Estimated

Europe Estimated

Age of onset

All ages

ICD-10

C96.2 D47.0 Q82.2

Inheritance

Most cases of mastocytosis are not inherited. The change (variation or mutation) in the KIT gene that causes many cases of mastocytosis is typically a somatic mutation. Somatic mutations occur after the egg and sperm join (conception) and are only present in certain cells of the body. Typically, affected cells do not include the egg and sperm (germ cells). Therefore, the genetic change associated with mastocytosis typically only occurs in one person in a family, and the disease is not passed on to the next generation.^[2]

Mastocytosis can rarely affect more than one person in the same family. This is known as familial mastocytosis and occurs when a person does have the KIT mutation in the egg or sperm (germ cells). In these cases, the mastocytosis is inherited in an autosomal dominant manner.^[3]^[4]^[5]. This means that to be have mastocytosis, a person only needs a disease-causing genetic change in one copy of the KIT gene. A person with familial mastocytosis has a 50% chance with each pregnancy of passing along the changed gene to his or her child.

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

Mast cell disease

Summary

Mastocytosis occurs when too many mast cells accumulate in the skin and/or internal organs such as the liver, spleen, bone marrow, and small intestines. Mast cells are a type of white blood cell in the immune system. Mast cells are responsible for protecting the body from infection and releasing chemicals to create inflammatory responses.^[1] The signs and symptoms of mastocytosis vary based on which parts of the body are affected. There are two main forms of mastocytosis. Cutaneous mastocytosis only affects the skin and is more common in children. Systemic mastocytosis affects more than one part of the body and is more common in adults.^[1]^[2]

Mastocytosis is usually caused by changes (known as variations or mutations) in the KIT gene. Most cases are caused by somatic mutations, meaning they only occur in certain parts of the body and are not inherited or passed on to the next generation. However, mastocystosis can rarely affect more than one person in a family.^[1]^[3]^[4] Mastocysotis may be suspected when a doctor sees a person has signs and symptoms of the disease. Diagnosis may be confirmed with a skin biopsy or bone marrow biopsy.^[2] Treatment of mastocytosis is based on the signs and symptoms present in each person and can include antihistamines, mast cell stabilizers, corticosteroids, and oral psoralen plus UV-A therapy.^[2]

Symptoms

The signs and symptoms of mastocytosis vary based on which parts of the body are affected. Signs and symptoms of mastocytosis are more likely to occur after a “trigger” such as a change in temperature, certain medications, emotional stress, or irritation of the skin.^[2] There are two main forms of mastocytosis:^[1]

Cutaneous mastocytosis: This form only affects the skin. The most common signs and symptoms include small tan-red macules that develop on the body, especially on the upper and lower extremities and on the thorax and abdomen. Another common feature is known as Darier’s sign, which is the development of lesions in a new area shortly after irritation to the skin such as scratching. When cutaneous mastocytosis occurs in children, signs and symptoms tend to improve or go away completely by the time the child reaches puberty.
Systemic mastocytosis: This form affects more than one part of the body such as the bone marrow, liver, and GI system. Signs and symptoms may include the skin findings associated with cutaneous mastocytosis, as well as symptoms such as low blood pressure (hypotension) abdominal pain, vomiting, diarrhea, fatigue, and frequent headaches. These symptoms may be episodic, meaning they only occur once in a while, or chronic, meaning symptoms are present during a long time. People with systemic mastocytosis may also present to the doctor with an enlarged liver and spleen (hepatosplenomegaly), anemia, or osteoporosis.

Many people affected by mastocytosis, especially systemic mastocytosis, also have symptoms of anxiety and depression. It is unknown if this is due to the stress of having these symptoms as part of daily life, or if the accumulation of mast cells may also affect the chemicals in a person’s brain, causing anxiety and depression.^[1]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Abnormality of skin pigmentation	Abnormal pigmentation Abnormal skin color Abnormal skin pigmentation Abnormality of pigmentation Pigmentary changes Pigmentary skin changes Pigmentation anomaly [ more ]	0001000
Macule	Flat, discolored area of skin	0012733
Mastocytosis		0100495
Pruritus	Itching Itchy skin Skin itching [ more ]	0000989
Urticaria	Hives	0001025
30%-79% of people have these symptoms
Abnormal blistering of the skin	Blistering, generalized Blisters [ more ]	0008066
Diarrhea	Watery stool	0002014
Impaired temperature sensation	Abnormality of temperature sensation Loss of temperature sensation [ more ]	0010829
Nausea and vomiting		0002017
5%-29% of people have these symptoms
Acute leukemia		0002488
Angioedema		0100665
Anorexia		0002039
Arrhythmia	Abnormal heart rate Heart rhythm disorders Irregular heart beat Irregular heartbeat [ more ]	0011675
Asthma		0002099
Chronic leukemia		0005558
Cough	Coughing	0012735
Fatigue	Tired Tiredness [ more ]	0012378
Gastrointestinal hemorrhage	Gastrointestinal bleeding	0002239
Hepatomegaly	Enlarged liver	0002240
Hypercalcemia	High blood calcium levels Increased calcium in blood [ more ]	0003072
Hypotension	Low blood pressure	0002615
Osteoporosis		0000939
Recurrent fractures	Increased fracture rate Increased fractures Multiple fractures Multiple spontaneous fractures Varying degree of multiple fractures [ more ]	0002757
Respiratory insufficiency	Respiratory impairment	0002093
Sarcoma	Cancer of connective tissue Malignant connective tissue tumor [ more ]	0100242
Splenomegaly	Increased spleen size	0001744
Telangiectasia of the skin		0100585
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance		0000006
Cutaneous mastocytosis		0200151
Edema	Fluid retention Water retention [ more ]	0000969
Erythema		0010783
Hypermelanotic macule	Hyperpigmented spots	0001034
Telangiectasia macularis eruptiva perstans		0007583

Cause

Most cases of mastocytosis are caused by a change (known as variation or mutation) in the KIT gene. This gene provides instructions to the body to make a protein that helps control many important cellular processes such as cell growth and division, survival, and movement. This protein is also important for the development of certain types of cells, including mast cells. Mast cells are cells of the immune system that protect the body against infections and produce an inflammatory response when it senses that the body is being attacked.^[2]

Mutations in the KIT gene can lead to an overproduction of mast cells. In mastocytosis, mast cells accumulate in the skin and/or internal organs, leading to the many signs and symptoms of the disease.^[1]

Diagnosis

Mastocytosis is often first suspected by a doctor when a person has signs and symptoms of the disease. A diagnosis of mastocytosis that causes skin lesions may be confirmed by a skin biopsy of the lesion. During a skin biopsy, a sample of skin tissue is taken and looked at under a microscope for the presence of dense areas of mast cells. If there are no cutaneous lesions or if the skin biopsy reveals uncertain results, a bone marrow biopsy may be performed. This procedure can also be useful in differentiating between cutaneous and systemic mastocytosis.^[2]

Blood and/or urine tests may also be used to measure the levels of specific chemicals or substances related to mast cells. High levels of certain substances support the diagnosis of mastocytosis. Some substances may be elevated in systemic mastocytosis but not in cutaneous mastocytosis. Other evaluations or tests used to confirm a diagnosis may include a bone scan, gastrointestinal workup, or genetic testing to confirm there is a mutation in the KIT gene.^[6]

Additional tests may be ordered to rule out other diseases that may cause similar symptoms, such as anaphylaxis, pheochromocytoma, carcinoid syndrome, or Zollinger-Ellison syndrome.^[6]

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment

The treatment for mastocytosis depends on the particular symptoms of each person. Treatment for symptoms that affect the skin include antihistamines and oral psoralen plus UVA (PUVA) therapy. If the symptoms are not responsive to other treatments, a doctor may prescribe steroid creams, ointments, or solutions applied to the skin (topical corticosteroids treatment).^[1] Proton pump inhibitors can be used to treat gastrointestinal symptoms and bone pain. Different treatments work better for some people than others.^[1]

Many specialists recommended that people with mastocytosis have injectable epinephrine they can use in case of anaphylactic shock. Other recommendations include trying to avoid known triggers of symptoms of mastocytosis.^[7]

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

Cromolyn sodium(Brand name: Gastrocrom® (oral)) Manufactured by Azur Pharma
FDA-approved indication: Treatment of mastocytosis.
National Library of Medicine Drug Information Portal
Midostaurin(Brand name: Rydapt) Manufactured by Novartis Oncology
FDA-approved indication: Treatment of adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL).
National Library of Medicine Drug Information Portal

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

The Mast Cell Disease Society
P.O. Box 416
Sterling, MA 01564
E-mail: info@tmsforacure.org
Website: https://tmsforacure.org/
UK Mastocytosis Support Group
E-mail: jess.hobart@gmail.com
Website: https://www.ukmasto.org/

Social Networking Websites

RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

The Merck Manuals Online Medical Library provides information on this condition for patients and caregivers.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
The Mast Cell Disease Society provides information about mast cell diseases, including Mastocytosis.

In-Depth Information

Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
The Merck Manual for health care professionals provides information on Mastocytosis.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Mastocytosis. Click on the link to view a sample search on this topic.

References

Castells MC and Akin C. Mastocytosis (cutaneous and systemic): Epidemiology, pathogenesis, and clinical manifestations. UpToDate. December 5, 2016; https://www.uptodate.com/contents/mastocytosis-cutaneous-and-systemic-epidemiology-pathogenesis-and-clinical-manifestations.
Bundra K and Akin C. Mastocytosis. National Organization for Rare Disorders. 2017; https://rarediseases.org/rare-diseases/mastocytosis/.
Fett NM, Teng J, and Longley BJ. Familial urticaria pigmentosa: report of a family and review of the role of KIT mutations. Am J Dermatopathol. February 2013; 35(1):113-116. https://www.ncbi.nlm.nih.gov/pubmed/22892471.
de Melo Campos P, Machado-Neto JA, Scopim-Ribeiro R, Visconte V, Tabarroki A, Duarte AS, Barra FF, Vassalo J, Rogers HJ, Lorand-Metze I, Tiu RV, Costa FF, Olalla Saad ST, and Traina F. Familial systemic mastocytosis with germline KIT K509I mutation is sensitive to treatment with imatinib, dasatinib and PKC412. Leuk Res. October 2014; 38(10):1245-1251. https://www.ncbi.nlm.nih.gov/pubmed/25139846.
Mast Cell Disease. Online Mendelian Inheritance in Man (OMIM). January 24, 2012; https://omim.org/entry/154800.
Delves PJ. Mastocytosis. Merck Manual. June 2016; https://www.merckmanuals.com/professional/immunology-allergic-disorders/allergic-autoimmune-and-other-hypersensitivity-disorders/mastocytosis.
Habashy J and Robles DT. Mastocytosis. Medscape Reference. May 15, 2017; https://emedicine.medscape.com/article/1057932-overview.
Theoharides TC, Valent P, and Akin C. Mast Cells, Mastocytosis, and Related Disorders. N Engl J Med. July 9, 2015; 373(2):163-172. https://www.ncbi.nlm.nih.gov/pubmed/26154789.

Rare Rheumatology News

Rare Rheumatology News

Rare Rheumatology News

All ages

C96.2 D47.0 Q82.2

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

Summary

Symptoms

Cause

Diagnosis

Testing Resources

Treatment

FDA-Approved Treatments

Organizations

Organizations Supporting this Disease

Social Networking Websites

Learn more

Where to Start

In-Depth Information

References

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.