Indolent Systemic Mastocytosis (ISM) Treatment Options

Indolent systemic mastocytosis is a usually benign (noncancerous) form of mastocytosis, a genetic blood cancer caused by abnormal mast cells. Mast cells are white blood cells produced in bone marrow.

As its name implies, “indolent” systemic mastocytosis progresses slowly and does not present an immediate threat. Treatment for this form of the disease aims to identify and avoid symptom triggers.

This disease causes excess abnormal mast cells that build up in organ tissue. When a trigger arises, these cells overreact and release too much of a chemical mediator, such as histamine, to fight off a perceived threat. The effect causes symptoms like an allergic reaction in the organs involved. Treatment mostly includes self-management and certain drugs.

This article describes treatment for indolent systemic mastocytosis when it affects your skin or other organs. It also explains what to expect from flares and how to control treatment side effects.

When to Treat Indolent Systemic Mastocytosis

The timing and type of treatment you receive for indolent systemic mastocytosis can vary by individual since the disease affects everyone differently.

Indolent systemic mastocytosis has a better prognosis than other forms of mastocytosis. The disease typically spares organs from damage and rarely progresses to the more severe forms. People with this condition generally live a normal lifespan, comparable to their peers.

However, it can be highly symptomatic. In addition to physical symptoms, psychological and neurological symptoms that lead to reduced performance can also occur. Symptoms that interfere with physical and or emotional well-being warrant treatment.

Even if symptoms are minor and medical treatment is not needed, guidelines from the National Comprehensive Cancer Network (NCCN) advise that people with indolent systemic mastocytosis should receive the following:

• Counseling about the signs and symptoms of mast cell activation and the importance of avoiding known triggers of mast cell activation that can activate symptoms
• Counseling about the increased risk of anaphylactic reactions
• Instruction on the use and importance of carrying two EpiPens (epinephrine) auto-injectors to manage anaphylaxis
• Education on the need for pre-medication before surgery due to the increased risk of mast cell activation and anaphylaxis during invasive and radiologic procedures

Treatment for Indolent Systemic Mastocytosis Limited to Skin

There is no single treatment for indolent systemic mastocytosis limited to the skin. The specific treatment you receive will depend on many factors, including the extent and severity of your disease, your age, medical history, and other health conditions.

The primary goal of treating ISM limited to the skin is to control symptoms caused by mast-cell mediators. When therapy is needed to control symptoms, common treatments include:

First-Line Therapy

First-generation and second-generation H1 (histamine 1) antihistamines are the cornerstone of first-line therapy for indolent systemic mastocytosis limited to the skin. These drugs often succeed in relieving symptoms of pruritus (itching), facial flushing, and burning of the skin.

Common first-generation H1 antihistamines include:

• Atarax (hydroxyzine hydrochloride)
• Benadryl (diphenhydramine)
• Chlor-Trimeton (chlorpheniramine)
• Doxepin, Sinequan (doxepin hydrochloride)
• Tavist (clemastine)

Second-generation antihistamines may tend to cause less drowsiness than first-generation drugs. Common second-generation H1 antihistamines include:

For persistent symptoms, treatment may be expanded to include the following medications:

H2 (histamine 2) antihistamines:

Leukotriene inhibitors:

Other Therapies:

• Short-term use of topical glucocorticoids including Hytone (hydrocortisone) 2.5% cream, hydrocortisone 1% (over-the-counter creams, lotions, and ointments), Desonate (desonide) 0.05% gel, and Synalar (fluocinolone acetonide)
• Injection of the lesion with crystalline steroid solution
• Surgical removal of the skin lesion

Second-Line Therapy:

Second-line therapy is used for skin symptoms that are not responsive to first-line therapy:

• Phototherapy (Long-wave ultraviolet radiation and narrowband ultraviolet B phototherapy irradiation)
• Psoralen plus ultraviolet A (PUVA) photochemotherapy (psoralens are a medication that makes your skin more sensitive to ultraviolet light)

Treatment for Indolent Systemic Mastocytosis

There is no single treatment plan for indolent systemic mastocytosis because this disease affects everyone differently. Treatment for this disorder is mostly based on expert opinion rather than evidence from controlled clinical trials. This is partly because it is a heterogeneous disease that can affect a combination of body systems, but only involves about 1 per 10,000 people.

Indolent systemic mastocytosis involves at least one organ system other than the skin. Since few cases progress to advanced forms of the disease, treatment focuses on improving and preventing symptoms related to mediators such as histamine. Other treatments may be used for more advanced forms of the disease.

Some common treatments for indolent systemic mastocytosis include:

Neuropsychiatric System

The following treatments may help with brain fog:

Cardiovascular System includes the use of EpiPens, which treat low blood pressure that may be spontaneous or observed after an insect bite or other trigger.

Respiratory System

The following treatments can help with respiratory symptoms such as wheezing and shortness of breath:

Leukotriene inhibitors:

Musculoskeletal System

The following treatments center on treating symptoms of osteoporosis (loss of bone density) and bone pain:

Digestive System

The following medications may be helpful in treating gastrointestinal symptoms:

• Gastrocrom
• H2 antihistamines, including Axid, Pepcid, Tagamet, and Zantac
• Leukotriene inhibitors, including Singulair and Accolate
• Proton pump inhibitors (for increased stomach acid production) including Prilosec (omeprazole), Nexium (esomeprazole), Prevacid (lansoprazole), Zegerid (omeprazole/sodium bicarbonate), and Dexilant (dexlansoprazole)

Whole-Body System

The following treatments can provide benefits for your entire body:

• Ayvakit (avapritinib) inhibits the KIT D816V mutation, the primary underlying gene of indolent systemic mastocytosis.
• EpiPen is used at the first sign of anaphylaxis.
• Gastrocom is used to prevent mast cells from releasing too many mediator substances.
• Xolair (omalizumab) is effective in controlling recurrent anaphylaxis in indolent systemic mastocytosis.

Managing Symptoms and Secondary Conditions

Symptoms and secondary conditions of indolent systemic mastocytosis can range in severity due to the heterogeneous nature of the disease.

Many symptoms are episodic, becoming intense in unpredictable, recurrent flares that occur in response to triggers or for seemingly no reason at all. Since the disorder affects everyone differently, you may not known which organs will be affected or how you will react until symptoms begin.

In addition to treatments specific to symptoms, some people succeed in working to avoid known triggers at home, at work, and in their social lives. However, since triggers can range from temperature variations to the development of new allergies, avoiding triggers can often affect how you live your life.

You may be able to help control flares by following a strict low-histamine diet. This diet restricts eating foods high in histamine or foods that may increase mast cell histamine release. This can help avoid adding to your body’s existing levels of histamine.

High-histamine foods include those that are overly processed, fermented, or spoiled. Examples of high-histamine foods include:

• Aged/hard cheese
• Canned or smoked fish
• Eggs
• Spinach
• Soy-fermented products
• Tomatoes
• Wine and beer
• Yogurt

Managing symptoms can also help reduce your risk of complications and secondary conditions. Common comorbidities (co-occurring conditions) with ISM include:

• Anaphylactic (allergic) reactions that are potentially life-threatening and result in rapid heartbeat, loss of consciousness, and shock
• Blood disorders such as anemia, cytopenia, and poor blood-clotting
• Bone fractures
• Peptic ulcer disease, including ulcers and bleeding in your digestive tract
• Osteoporosis and other bone problems
• Swollen liver
• Inflammation and damage to your organs
• Cancer, including mast cell leukemia or mast cell sarcoma (cancer of the body’s soft tissue)

How to Treat ISM Treatment Side Effects

Limiting or avoiding ISM treatment side effects requires communicating with your care team so they can help you manage these issues. Finding the right treatment regimen can be a complex process.

Factors such as the rarity of the disease and a provider’s unfamiliarity with it can complicate treatment. In some cases, it can contribute to a delayed or hindered diagnosis, impacting side effects and treatment outcomes.

While an allergist or immunologist may help you get a proper diagnosis of indolent systemic mastocytosis, the NCCN advises that treatment of all types of mastocytosis ideally includes a multidisciplinary approach involving the following specialists:

• Dermatologists (specialists in treating conditions of the skin, hair, and nails)
• Hematologists (specialists in blood disorders and the lymphatic system)
• Pathologists (specialists in the study of body tissues and fluids)
• Gastroenterologists (specialists in conditions of the digestive tract and the liver)
• Allergists (specialists in allergies, asthma, and immunological disorders)
• Immunologists (specialists in immune system disorders)

This team of specialists works together to address side effects and treatment changes from all aspects of the disease.

Side effects of ISM treatments can vary by type and disease. Common side effects include:

• Flu-like symptoms
• Gastrointestinal problems
• Headaches
• Joint pain
• Muscle pain
• Nausea
• Vomiting

Side effects of ISM treatment add to the unpredictability of the disease and the wide range of invisible and visible symptoms it can cause. While your healthcare team can help you manage many side effects of treatment, research indicates that people with systemic mastocytosis have also used the following strategies to face these challenges:

• Having have spare time
• Exercising regularly
• Eating healthful meals
• Being kind to yourself to avoid reactions
• Finding new interests not affected by the disease or symptoms
• Forging healthy relationships with healthcare professionals, family members, and friends to promote a climate of wellness

Summary

Indolent systemic mastocytosis can present with many types of symptoms. These can range from mostly skin-centered to systemic problems such as flushing and bone pain. The risk of anaphylaxis is also higher than normal.

Treatment for indolent systemic mastocytosis centers on easing mast cell mediators and their impact on affected organs. Most people with this disease can expect to live a normal lifespan with little risk of severe disease. However, symptoms need proper treatment to maintain comfort and a normal life.

Finding the right treatment can be challenging for this rare and heterogeneous disease. While an allergist or immunologist may manage your care, having a multidisciplinary treatment team is advised.