Indolent Systemic Mastocytosis Symptoms: Their Effects

Indolent systemic mastocytosis is a type of mastocytosis, a rare form of blood cancer. It occurs when mast cells (white blood cells produced in bone marrow) build up in your skin and/or other organs. Mastocytosis is linked with a mutation in the KIT D816V gene.

Mastocytosis can be either cutaneous, with extra mast cells only in your skin, or systemic, with extra mast cells throughout your body in one of five subtypes. Indolent systemic mastocytosis is the most common and least severe subtype of systemic mastocytosis in adults. It can affect many organs, which may or may not include your skin.

Problems arise when a buildup of mast cells affects the bone marrow, liver, spleen, gastrointestinal tract, and/or skin. Symptoms vary depending on where the extra mast cells develop. Since symptoms can mimic other ailments, a biopsy (removing sample tissue for analysis in a lab) and blood test are used to confirm this disease.

This article describes how indolent systemic mastocytosis symptoms start and how they affect your skin and other organs. It also explains how the disease is found and its impact on long-term health.

How Do Indolent Systemic Mastocytosis Symptoms Start?

Indolent systemic mastocytosis symptoms start in different ways, depending on where in the body the excessive amounts of abnormal mast cells are.

Mast cells are important in helping your immune system respond to allergic reactions, heal wounds, and defend your body against diseases and infections. When mast cells are activated, they release the compound histamine, which triggers an allergic response.

Normal mast cells reduce their activity when their work is done. However, with systemic mastocytosis, abnormal mast cells operate in overdrive and exist in excess numbers. When these abnormal mast cells respond to perceived threats with substances called mediators, the effect can cause systemic and local symptoms. Mediators like histamine cause inflammatory responses.

Mast cell disease symptoms occur in mastocytosis due to the release of mediators, which produce symptoms associated with an allergic reaction. There are numerous potential triggers for mast cells to release mediators. These triggers can include:

• Allergens, pollen, dust mites, pet dander
• Food or beverages, including alcohol
• Heat, cold, or sudden changes in temperature
• Weather changes, odors, chemicals, and other environmental triggers
• Venom from bees, waps, and other biting insects and animals
• Viral, bacterial, or fungal infections
• Certain drugs (nonsteroidal anti-inflammatory drugs (NSAIDs) such as Advil (ibuprofen) and Aleve (naproxen), antibiotics, and others)
• Exercise
• Fatigue

Indolent systemic mastocytosis symptoms start slowly. They can often begin as problems that seem unrelated or mimic other conditions that include:

• Frequent diarrhea and stomachaches that resemble any general gastrointestinal disorder
• Symptoms that appear to be an unexplained allergic reaction, that occur due to a wide range of triggers, or that suddenly change from neutral to intense
• Long-lasting facial flushing and heartburn that resembles a food sensitivity

Indolent Mastocytosis Skin Symptoms

Indolent mastocytosis can occur with or without skin symptoms since this disorder can affect everyone differently. When indolent mastocytosis skin symptoms do occur, they can include:

• Urticaria pigmentosa: This mastocytosis rash causes raised patches of brownish skin that itch or sting with contact or temperature changes. It is the most common cutaneous (skin) symptom of systemic mastocytosis, affecting 56% to 100% of those who have this disorder.
• Pruritus: This irritating condition triggers a reaction to scratch your skin. It can occur either all over your body or in just one area, with or without a rash or hives.
• Facial flushing: This condition occurs as episodes of redness with a sensation of burning or warmth on your face and neck. It can sometimes involve your upper trunk too.
• Maculopapular rash: This type of rash consists of a combination of macules (flat discolored areas of skin) and papules (small raised bumps up to 1 centimeter in diameter) that join to cover a large area.

Generally, skin symptoms of indolent systemic mastocytosis can look different in darker skin tones than in lighter skin tones and include the following variations:

• Purple or violet tone to urticaria and blistering of the skin in darker skin tones and reddish blisters on lighter skin tones
• Macules and papules of a maculopapular rash that appear darker than your natural skin tone in darker skin tones and red or pink in lighter skin tones
• Less visible but still existent lesions that have a positive reaction to Darier’s sign (a reaction that involves itching, redness, and welt formation within two to five minutes of gentle rubbing or stroking a lesion, common in mastocytosis) in darker skin tones than in lighter skin tones

Effects of Indolent Systemic Mastocytosis on Organs

The effects of indolent systemic mastocytosis on organs can range in severity and predictability. Symptoms can be episodic and seemingly unexplained. Since the disorder affects everyone differently, it can be hard to know which organs will be affected.

In addition to your skin, the following organs can be affected when mast cells accumulate in organ tissue and/or mast cells release mediators in these organs:

Brain (neuropsychiatric) symptoms include:

Heart (cardiovascular) symptoms include:

Lung and airway (respiratory) symptoms include:

Muscle and bone (musculoskeletal) symptoms include:

Stomach/gut (digestive) symptoms include:

Whole-body (systemic) symptoms include:

Ruling Out ISM Symptoms

Ruling out ISM symptoms can be a complex procedure. Many symptoms of ISM are often attributed to other causes before an accurate diagnosis is achieved. In addition, factors such as disease rarity and provider unfamiliarity with ISM can contribute to a delayed diagnosis.

A diagnosis of ISM typically starts with a visit to your primary care provider for diagnosis and treatment of symptoms that may seem unrelated. The path to a diagnosis typically involves the following process:

Physical exam and history: Your healthcare provider will examine skin symptoms for signs of disease. They will also review your health history, family history, duration and extent of symptoms, and your history of food and medication allergies.

Differential diagnosis: Based on your symptoms, your healthcare provider may recommend tests to rule out the following disorders that have similar symptoms as ISM, though other disorders may also be considered:

• Inflammatory bowel disease (IBD): A gastrointestinal syndrome that can cause changes in bowel habits and abdominal pain
• Irritable bowel syndrome (IBS): A functional gastrointestinal disorder that can cause constipation, diarrhea, or a combination of abnormal bowel movements
• Malabsorption syndrome: A disorder in which your small intestine stops absorbing nutrients properly
• Myeloproliferative disease: A group of disorders in which your body produces too many red blood cells
• Chronic urticaria
• Endocrine disorders: Diseases and conditions that affect the glands and organs that secrete hormones
• Idiopathic mast cell activation syndrome (MCAS) and idiopathic anaphylaxis: A disorder involving abnormal mast cells that cause symptoms from excess mediator release without an increased accumulation of mast cells
• Hereditary alpha tryptasemia (HαT): A genetic condition that causes extra inherited copies of the gene TPSAB1 that makes extra alpha tryptase and leads to symptoms of mast cell activation and mediators

Diagnostic testing: Given the rarity of indolent systemic mastocytosis, it is not uncommon for a primary care provider to refer you to an allergist/immunologist or hematologist/oncologist if they are unfamiliar with the condition.

When ISM is suspected, the following diagnostic tests are necessary to retrieve the results used to diagnose this condition:

• Serum tryptase test: This test measures the amount of tryptase (an enzyme released by mast cells) in your blood. A tryptase test given after an allergic reaction may provide more accurate results.
• Biopsies: These tests involve removing tissue samples from affected organs to determine the number of mast cells present. While a bone marrow biopsy is necessary for diagnosis, biopsies of your skin or other affected organs may also be used.

Other diagnostic tests, such as a bone scan or GI evaluation may be used to provide additional information.

Speed of ISM Symptom Progression

As a medical term, “indolent” describes a condition that progresses slowly and does not present an immediate threat. Symptoms of indolent systemic mastocytosis, therefore, move gradually. ISM rarely worsens to a more advanced form.

It also is rare for symptoms of ISM rarely pose an immediate threat or interfere with organ function. Indolent systemic mastocytosis treatment typically involves treating symptoms and reducing the risk of triggers. People with ISM often have low morbidity (chance of becoming ill) and a normal life expectancy, similar to their peers.

Summary

Indolent systemic mastocytosis is the most common subtype of systemic mastocytosis. It occurs when excess abnormal mast cells build up in your skin, bone marrow, or other organs.

Normal mast cells release histamines and other mediators when triggered. However, damaged mast cells build up in organ tissue and release too much histamine, causing symptoms. Common triggers include insect stings, certain drugs, alcohol, and spicy foods. While this form of the disease seldom becomes severe, symptoms can involve pain and discomfort.

Because this disease is rare and has symptoms that mimic other ailments, getting a diagnosis can be delayed. Getting blood tests and biopsies and/or working with a specialist may help you get a faster diagnosis.