Mastocytosis is a rare condition characterized by the abnormal accumulation of mast cells, a type of white blood cell. These cells are present in tissues like the skin, bone marrow, and the lining of the intestine and lungs. As part of the immune system, mast cells are involved in allergic reactions. When triggered, they release chemicals like histamine that cause swelling and itching. In mastocytosis, an excessive number of these cells release these chemicals without a proper trigger, leading to a range of symptoms.
Types of Mastocytosis
Mastocytosis is divided into two main categories based on the location of the excess mast cells. The first, Cutaneous Mastocytosis (CM), is largely confined to the skin and is the form most commonly seen in children. The accumulation of mast cells in the skin leads to the formation of characteristic lesions, which often appear as reddish-brown spots.
The second category is Systemic Mastocytosis (SM), which predominantly affects adults and involves the infiltration of mast cells into one or more internal organs, such as the bone marrow, spleen, liver, or gastrointestinal tract. SM is classified into several subtypes that reflect the condition’s severity. The most common is Indolent Systemic Mastocytosis (ISM), which accounts for the vast majority of adult cases and follows a slow-progressing course with mild to moderate symptoms.
More advanced and less common forms of SM show the condition’s potential severity. Aggressive Systemic Mastocytosis (ASM) is characterized by a high burden of mast cells in various organs, leading to impaired organ function. Another subtype is Systemic Mastocytosis with an Associated Hematological Neoplasm (SM-AHN), where the disease coexists with a separate blood disorder. The rarest form is Mast Cell Leukemia, where immature mast cells are found in the bone marrow and blood.
Symptoms and Triggers
The symptoms of mastocytosis are a direct result of the chemicals released from the large population of mast cells. The signs experienced depend on where in the body the mast cells have accumulated. Skin-related symptoms are common and include urticaria pigmentosa, which are small, pigmented lesions that become itchy and swollen when rubbed—a reaction known as Darier’s sign. Widespread flushing of the skin and persistent itching are also frequently reported. Gastrointestinal problems are another frequent complaint, with individuals often experiencing abdominal pain, nausea, vomiting, and chronic diarrhea.
Beyond the skin and gut, systemic symptoms can include fatigue, bone and muscle pain, and headaches. In some individuals, the massive release of mast cell chemicals can trigger anaphylaxis, a severe and potentially life-threatening allergic reaction. This reaction can cause a sharp drop in blood pressure and difficulty breathing, and can be set off by various triggers. Common triggers include:
- Physical stimuli like friction, heat, or exercise
- Emotional stress
- Certain medications like NSAIDs and opioids
- Insect stings
- Some foods
Underlying Causes and Diagnosis
The majority of mastocytosis cases are linked to a specific genetic mutation in the KIT gene. This gene provides instructions for a receptor protein on the surface of mast cells, which helps regulate their growth and activation. The most common mutation, known as D816V, causes the KIT receptor to become permanently switched on, leading to the uncontrolled production and accumulation of mast cells. This is an acquired mutation, meaning it is not typically inherited but occurs randomly.
Diagnosing mastocytosis involves a multi-step process to confirm the presence of excess mast cells and identify the specific type of the disease. Physicians start with a physical examination of the skin lesions. A blood test is used to measure the level of tryptase, an enzyme released by mast cells, as elevated levels can indicate a high burden of mast cells in the body.
To confirm the diagnosis, a biopsy is necessary. For suspected cutaneous mastocytosis, a small sample of skin is taken and examined under a microscope to identify the number and appearance of mast cells. In cases where systemic mastocytosis is suspected, a bone marrow biopsy is the standard procedure. This involves analyzing a sample of bone marrow for mast cell aggregates and the characteristic KIT mutation.
Management and Treatment Approaches
The management of mastocytosis is highly individualized and focuses on controlling symptoms and avoiding known triggers. A foundational aspect of care involves identifying and steering clear of specific factors that provoke symptom flare-ups. This proactive approach helps to minimize the sudden release of chemicals from mast cells.
Medications form the core of symptom management. H1 and H2 antihistamines are commonly used to counteract the effects of histamine, helping to relieve skin symptoms like itching and flushing, as well as gastrointestinal issues. Mast cell stabilizers and leukotriene inhibitors are also prescribed to manage symptoms. For individuals at risk of anaphylaxis, carrying an epinephrine auto-injector is an important safety measure.
For more advanced forms of the disease, such as Aggressive Systemic Mastocytosis, treatments are aimed at reducing the number of mast cells. Targeted therapies, including KIT inhibitors like midostaurin or avapritinib, may be used. These medications work by blocking the signaling from the mutated KIT protein, thereby controlling the overproduction of mast cells. Treatment plans are tailored to the specific subtype and severity of symptoms.