Background

Systemic mastocytosis is a rare disorder characterized by the abnormal accumulation of mast cells in various tissues throughout the body. Mast cells are a type of white blood cell involved in the immune system. In systemic mastocytosis, these cells accumulate in organs such as the bone marrow, liver, spleen, and gastrointestinal tract.

Mast cells are part of the immune system and are primarily associated with allergic reactions and inflammatory responses. They contain granules filled with substances such as histamine, heparin, and various enzymes. The mutations cause the mast cells to multiply uncontrollably and accumulate in various tissues.

Epidemiology

Systemic mastocytosis is a rare disease, and the exact prevalence is not well-established. It is estimated to affect fewer than 1 in 10,000 people. Systemic mastocytosis can occur at any age, but it is most diagnosed in adults. It is rare in children.

The prevalence of different subtypes of systemic mastocytosis can vary. Indolent forms, which are more common, generally have a better prognosis compared to aggressive forms.

Anatomy

Pathophysiology

Systemic mastocytosis is a clonal disorder, meaning that all affected mast cells are derived from a single abnormal progenitor cell. This leads to the presence of a monoclonal population of mast cells.

The accumulation of mast cells can lead to bone marrow dysfunction, affecting the production of other blood cells. Mast cells can infiltrate various tissues and organs, including the skin, liver, spleen, gastrointestinal tract, lymph nodes, and bone.

When activated, mast cells release these mediators, leading to the characteristic symptoms of systemic mastocytosis, such as itching, flushing, abdominal pain, and anaphylaxis.

Bone marrow is a primary site of mast cell production. In systemic mastocytosis, there is an increased number of abnormal mast cells in the bone marrow.

Etiology

Systemic mastocytosis is a clonal disorder, meaning that all the abnormal mast cells present are derived from a single progenitor cell that has acquired the genetic mutations.

This clonal expansion leads to the presence of a monoclonal population of mast cells in affected individuals. Different mutations may contribute to variations in the clinical presentation and severity of the disease.

The mutations in the gene are typically somatic, meaning they occur in non-germline cells. Somatic mutations are acquired during a person’s lifetime and are not inherited from parents.

Genetics

Prognostic Factors

Different subtypes of systemic mastocytosis exist, ranging from indolent forms with a relatively stable course to aggressive forms associated with organ damage and systemic complications. The specific subtype influences the prognosis, with indolent forms generally having a better prognosis compared to aggressive forms.

Certain cytogenetic abnormalities, such as additional chromosomal abnormalities or mutations in specific genes, may be associated with a poorer prognosis. The involvement of organs and tissues can significantly impact prognosis. Systemic mastocytosis affecting only the skin (cutaneous mastocytosis) may have a more favorable prognosis than forms that involve internal organs.

Clinical History

Age Group:

Systemic mastocytosis is more frequently diagnosed in adults, with most cases occurring in individuals over the age of 18.

The median age at diagnosis is typically in adulthood, with many cases diagnosed in middle-aged or older individuals.

While systemic mastocytosis is rare in children, it can occur in pediatric age groups. Pediatric cases are less common than adult cases, and the disease may present differently in children compared to adults.

Physical Examination

Skin Examination: Inspect the skin for characteristic lesions associated with mastocytosis, such as reddish-brown macules or patches, known as urticaria pigmentosa.

Cardiovascular Examination: Assess for signs of cardiovascular involvement, such as tachycardia or hypotension, which may be indicative of mast cell mediator release.

Neurological Examination: Evaluate neurological function, as some individuals with systemic mastocytosis may experience symptoms such as headaches, dizziness, or cognitive impairment.

Abdominal Examination: Palpate the abdomen to assess for hepatomegaly (enlarged liver) and splenomegaly (enlarged spleen), which can occur in systemic mastocytosis.

Respiratory Examination: Inquire about and evaluate respiratory symptoms, as mast cell activation can contribute to bronchoconstriction and respiratory distress.

Age group

Associated comorbidity

Systemic mastocytosis can be associated with other myeloid disorders, such as myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN).

There is an increased risk of developing certain types of leukemia in individuals with systemic mastocytosis, particularly in cases with aggressive forms of the disease.

Mast cell activation can contribute to bone loss, and individuals with systemic mastocytosis may be at an increased risk of osteoporosis. This risk is further compounded by the potential impact of systemic mastocytosis on bone marrow function.

Mast cells are present in the gastrointestinal tract, and their abnormal activation in systemic mastocytosis can lead to gastrointestinal symptoms. Conditions such as peptic ulcer disease, irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD) may be more prevalent in individuals with systemic mastocytosis.

Associated activity

Acuity of presentation

Individuals with indolent forms may have mild symptoms or even be asymptomatic for an extended period.

Systemic mastocytosis may have a slow and insidious onset, with symptoms developing gradually over time. These symptoms may include skin lesions, itching, flushing, and gastrointestinal disturbances.

Aggressive systemic mastocytosis represents a more severe presentation, characterized by extensive organ involvement, rapid disease progression, and severe symptoms.

This form may include significant bone marrow infiltration, hepatosplenomegaly, and potentially life-threatening complications such as anaphylaxis or organ dysfunction.

Differential Diagnoses

Cutaneous Mastocytosis: Cutaneous mastocytosis refers to mast cell accumulation in the skin without systemic involvement. It includes conditions such as urticaria pigmentosa, diffuse cutaneous mastocytosis, and solitary mastocytoma.

Urticaria and Angioedema: Conditions characterized by recurrent hives (urticaria) and swelling of deeper tissues (angioedema) can mimic some symptoms of mastocytosis.

Allergic Reactions: Immediate hypersensitivity reactions to allergens, medications, or insect stings can cause symptoms like mastocytosis, including flushing, itching, and anaphylaxis.

Gastrointestinal Disorders: Gastrointestinal conditions such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), or peptic ulcer disease may present with abdominal pain and gastrointestinal symptoms.

Autoimmune Disorders: Autoimmune diseases, including lupus, rheumatoid arthritis, may have overlapping symptoms with systemic mastocytosis.

Mast Cell Activation Syndrome (MCAS): MCAS is a condition characterized by symptoms related to mast cell activation but without the criteria for systemic mastocytosis.

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Mast Cell Stabilizers: Cromolyn sodium is a medication that may be used to stabilize mast cells and prevent the release of inflammatory mediators.

Use of Proton Pump Inhibitors (PPIs): PPIs may be prescribed to manage symptoms related to increased gastric acid secretion, which can occur in systemic mastocytosis.

Tyrosine Kinase Inhibitors: In cases of aggressive systemic mastocytosis or mast cell leukemia, tyrosine kinase inhibitors (TKIs) such as imatinib may be prescribed to target the abnormal KIT receptor.

Stem Cell Transplantation: Stem cell transplantation may be considered for individuals with very aggressive forms of systemic mastocytosis, although this is a complex and high-risk procedure.

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

use-of-non-pharmacological-approach-for-systemic-mastocytosis

• Avoid the Triggers: Identify and avoid specific triggers that can activate mast cells. Triggers can vary among individuals but may include certain foods (e.g., high-histamine foods), medications, insect stings, and environmental factors. 
• Avoid Environmental Allergens: Minimize exposure to environmental allergens, such as pollen, dust mites, and animal danger, which can contribute to allergic reactions. 
• Temperature Control: Extreme temperatures, both hot and cold, can trigger mast cell activation. Dressing appropriately for the weather and maintaining a comfortable indoor temperature can be helpful. 
• Reduce Stress: Stress can exacerbate symptoms in some individuals. Stress reduction techniques, such as meditation, deep breathing exercises, and yoga, may be beneficial. 
• Proper Clothing and Bedding: Choose clothing made from natural, breathable fabrics, and consider using hypoallergenic bedding to reduce potential irritants. 
• Personal Care Products: Select personal care products, such as lotions, soaps, and shampoos, that are hypoallergenic and free from potential triggers. 

Role of Tyrosine Kinase Inhibitors (TKIs)

• Midostaurin: It is a multi-targeted TKI that inhibits various kinases, which is commonly mutated in systemic mastocytosis. By inhibiting these kinases, midostaurin can reduce the abnormal proliferation and activation of mast cells. 

• Imatinib: Imatinib is a TKI that specifically targets the KIT receptor, among other kinases. It works by inhibiting the activity of mutated KIT, which is a common driver mutation in systemic mastocytosis. 

Use of Sympathomimetics

Sympathomimetic agents, which include drugs that stimulate the sympathetic nervous system, are more commonly used in other medical conditions. 

• Epinephrine: Epinephrine is a sympathomimetic agent commonly used in emergency situations, such as anaphylaxis. It acts on adrenergic receptors to counteract life-threatening symptoms, including airway constriction, low blood pressure, and increased vascular permeability. 

Use of Mast Cell Stabilizers

Cromolyn sodium: It is a medication that stabilizes mast cells, preventing the release of inflammatory substances. It can be used to reduce symptoms associated with mast cell activation. 

Role of corticosteroids

Corticosteroids have potent anti-inflammatory properties and can help reduce inflammation associated with mast cell activation. They work by suppressing the immune response and inhibiting the release of inflammatory mediators. 

• Prednisone: It is a commonly used oral corticosteroid that may be prescribed in systemic mastocytosis for short-term relief of symptoms. 

use-of-intervention-with-a-procedure-in-treating-systemic-mastocytosis

• Bone Marrow Biopsy: A bone marrow biopsy is a key diagnostic procedure for systemic mastocytosis. It involves the removal of a small sample of bone marrow from the hip or another large bone.  

• Skin Biopsy: Skin biopsy may be performed to evaluate skin lesions associated with cutaneous mastocytosis. The biopsy helps confirm the presence of mast cells in the skin and assess the extent of involvement. 
• Aspiration of Ascites or Pleural Effusion: In cases where systemic mastocytosis affects organs such as the liver or spleen, procedures like paracentesis (aspiration of ascitic fluid) or thoracentesis (aspiration of pleural fluid) may be performed to relieve symptoms and assess for mast cell involvement. 

use-of-phases-in-managing-systemic-mastocytosis

• Clinical Evaluation: The process begins with a thorough clinical evaluation, including a detailed medical history and physical examination.  
• Laboratory Tests: Blood tests, such as complete blood count (CBC) and serum tryptase levels, may be conducted to assess for abnormalities. 
• Bone Marrow Biopsy: A bone marrow biopsy is often performed to confirm the presence of abnormal mast cells and establish a definitive diagnosis. 
• Lifestyle Modifications: Identification and avoidance of triggers that can activate mast cells are important aspects of management.  

Medication

Future Trends

Media Gallary

References

Systemic Mastocytosis – StatPearls – NCBI Bookshelf (nih.gov)

Systemic Mastocytosis Symptoms, Diagnosis, Treatment & Management (aaaai)