Treatment Options For Mastocytosis

Mastocytosis is a rare disorder characterised by an abnormal accumulation of mast cells in the skin or internal organs.1 So, what are mast cells? Mast cells are a type of white blood cell that plays a critical role in our immune system, especially regarding allergic responses and defence against pathogens.¹ Normally, mast cells function by releasing chemicals to combat infections and facilitate inflammatory responses. However, if you have mastocytosis, these mast cells multiply excessively and can release large amounts of chemicals known as "mast cell mediators" like histamine.^1,2 This can result in a variety of symptoms ranging from chronic itching, and skin lesions to severe allergic reactions that can affect your quality of life.¹

So how can you treat mastocytosis? Managing mastocytosis requires a multi-faceted approach, and this article will provide everything you need to know to treat mastocytosis effectively!

Understanding mastocytosis

Mastocytosis is a condition characterised by the growth and buildup of mast cells in one or more organ systems. It is generally associated with a KIT gene mutation on the 4q12 chromosome.³

Mastocytosis is of two types: cutaneous and systemic. 

Cutaneous mastocytosis: This type is marked by an increase in mast cells in your skin.⁴ Skin lesions are the typical presentation of this type, which may be red, raised blistered.⁴ It mostly affects children.²

Systemic mastocytosis: Systemic mastocytosis mainly affects internal organs (eg, lymph nodes, gastrointestinal tract, liver, spleen, and bone marrow). It occurs mainly in adults.²

How is mastocytosis treated?

Effective management of mastocytosis requires customised treatment strategies and routine medical supervision. Treatment for mastocytosis differs depending on the kind of mastocytosis and the severity of symptoms. However, most medicines used for mastocytosis are unlicensed and the decision to use these medicines is carefully considered in order to provide the best possible symptom relief, control complications, and quality of life improvement for patients.¹ This is partly because mastocytosis is a heterogeneous and uncommon condition with an estimated frequency of 1 per 10,000.⁵

Treatment of cutaneous mastocytosis

First-line therapy for cutaneous mastocytosis

The main objective of cutaneous mastocytosis treatment is the control of symptoms associated with mast cell mediators.

• Antihistamines are a class of medication that inhibits histamine's actions and is frequently used to address allergy-related issues
• The treatment mainly starts with non-sedating H1 antihistamines for symptoms like itching, flushing, and burning sensations, with increasing doses if initial treatment doesn't fully control symptoms. Nevertheless, if symptoms do not improve, H2 antihistamines and montelukast are suggested.
• If you have gastrointestinal symptoms, oral disodium cromoglycate or proton pump inhibitors (reduce the acid in your stomach) are considered, especially if you experience abdominal pain, diarrhoea, or gastric hypersecretion.^5,6 

Special considerations

• Pediatric Cases: For children, symptom control is usually done with non-sedating H1 antihistamines. potent treatments like systemic glucocorticoids are only used for severe cases or symptomatic mastocytomas.
• Skin Treatments: Topical glucocorticoids can help with skin symptoms temporarily but should be used cautiously due to potential side effects. These steroid creams minimise the number t of mast cells that have the ability to produce histamine. Powerful steroid creams can be applied to the skin to treat mild to moderate cutaneous mastocytosis.^5,6 

Second-line therapy for cutaneous mastocytosis

These options are explored if initial antihistamine therapy does not sufficiently reduce your symptoms. These include:

Photochemotherapy and phototherapy

• Treatments such as narrow-band UVB (NB-UVB) and PUVA therapy (UVA plus psoralen treatment) have demonstrated potential in minimising skin lesions and easing itching in adult mastocytosis patients and have been found to be effective in severe symptoms.⁶ 
• PUVA therapy involves taking psoralen ( a photosensitizing drug) to make the skin more sensitive to ultraviolet light, followed by exposure to UVA light to help reduce skin lesions.⁶

Note: While these therapies provide some comfort, they ought to be monitored closely for any long-term concerns, such as the possibility of developing cancer from UV radiation.

*Since childhood-onset mastocytosis is self-limiting, phototherapy is typically not advised for children.

• Nd: YAG laser treatment may be helpful for localised skin lesions, especially those on the face⁵

Treatment of systemic mastocytosis

• Acute episodes of anaphylaxis ( severe allergic reactions ) are treated with epinephrine/adrenaline. Adrenaline relieves respiratory problems and counteracts the negative effects of excessive histamine. For the initial stages of treatment, antihistamines (H1 and H2 antihistamines) are crucial.
• Itching and flushing can be treated with non-sedating antihistamines (e.g., cetirizine, desloratadine) for daytime and sedating ones (e.g., diphenhydramine, hydroxyzine) for nighttime.
• Proton pump inhibitors and H2 antihistamines work well to treat gastrointestinal issues like peptic ulcer disease and gastric hypersecretion.
• Midostaurin is used to treat advanced systemic mastocytosis by reducing the growth of mast cells. It can significantly alleviate symptoms, thereby enhancing overall quality of life^6,7

Advanced therapies

• Omalizumab can be used to reduce recurrent anaphylaxis in treatment-resistant cases.
• Leukotriene antagonists (medications that block substances causing inflammation) like zafirlukast and montelukast, can be used to manage symptoms.
• Anticholinergics (medications that block certain nerve impulses) could be used to treat diarrhoea associated with systemic mastocytosis.
• If you suffer from a severe allergic response, malabsorption, bone pain, or persistent skin problems, corticosteroids (anti-inflammatory medications)  are suggested
• Oral corticosteroids, often known as corticosteroid tablets, may be used temporarily for really severe symptoms like itching, even though it is uncommon
• For osteoporotic fractures (bone breaks due to weakened bones), which are common in mastocytosis patients, regular monitoring and treatment with bisphosphonates like zoledronic acid is needed. Bisphosphonates slow bone breakdown and support new bone production, improving bone density.
• Calcium supplements may also be provided to help strengthen bones
• For advanced forms of systemic mastocytosis, chemotherapy is considered^.6,7 

Potential therapeutic strategies for mastocytosis

These strategies represent evolving approaches to managing mastocytosis, aiming to alleviate symptoms and improve overall well-being, while research is ongoing to understand their long-term efficacy and safety.

Omalizumab

Omalizumab is a monoclonal antibody that targets IgE (a protein that is involved in allergic responses) and has shown promise in treating recurrent anaphylaxis associated with mastocytosis. In many patients, it can result in full relief of severe symptoms.^{5, 7,8}

Imatinib Mesylate

 Imatinib mesylate has been licensed for the treatment of aggressive systemic mastocytosis without the D816V KIT mutation. It is also showing benefits in certain cases of cutaneous mastocytosis. However, imatinib may increase your susceptibility to infection. Infection may be suspected if you exhibit any of these symptoms:

• Headache with a fever 
• Soreness in the muscles
• Diarrhoea and fatigue^5,6

Masitinib

 This drug is found to be effective in both systemic and cutaneous mastocytosis, with promising results in clinical trials for symptomatic patients^.5,8

Nilotinib or dasatinib anaesthetics

If imatinib therapy does not work, nilotinib or dasatinib may be suggested. However, due to the increased susceptibility to infection caused by the drug, notify your general practitioner as soon as you suspect an infection.⁶ 

Cladribine

Cladribine, initially designed for treating leukaemia (cancers of the blood cells), has also shown effectiveness in treating aggressive systemic mastocytosis, though it is not officially approved for this use.⁶ 

Interferon alpha

Since interferon alpha was first developed to treat cancer, it has also been found to be useful in treating some cases of aggressive mastocytosis by lowering the bone marrow's production of mast cells. When therapy starts, injection-based interferon alpha may induce flu-like symptoms like fever, chills, and joint discomfort. Therefore, you should contact your general practitioner right away if you suspect an infection.^5,6,7 

Prevention and management strategies for mastocytosis

Patients with mastocytosis must stay away from anything that might cause an allergic response.² Patients should take extra precautions to avoid triggers such as:

• Allergens like pollen, animal dander, and dust mites 
• Insect stings
• Certain drugs (eg. NSAIDs, opiates, and antibiotics) 
• Stress
• Alcohol
•  Spicy meals, foods like shellfish and cheese
• Cold or flu
• Extremely cold or hot conditions.^5,2,⁶
• It is recommended that patients always have an adrenaline auto-injector (EpiPen, Jext, Emerade) on hand and be trained to use it in an emergency. 
• Because of the risk of allergy during procedures such as laparoscopy, bone marrow biopsy laparoscopy, bone marrow biopsy, and occasionally endoscopy, patients with systemic mastocytosis must be closely monitored.
• In surgical settings, beta-blockers, alpha-blockers, and cholinergic antagonists should be avoided since they may disrupt the body's natural adrenaline levels and cause anaphylactic responses. 
• It is recommended to avoid using some anaesthetics, such as rocuronium, mivacurium, atracurium, morphine, codeine, thiopental, and succinylcholine. The recommended opioids in cases of necessity include fentanyl and alfentanil.^5,.6,7

Consultations

Patients may need to see immunologists, dermatologists, and haematologists if they are suspected of having severe systemic mastocytosis that needs treatment. In certain situations, a bone marrow biopsy is required, and haematology/oncology expert monitoring may be required.

Severe gastrointestinal problems may require biopsies and endoscopic treatments to rule out alternative conditions.⁷

Summary

• Mastocytosis is a rare disorder characterised by an abnormal accumulation of mast cells in the skin or internal organs
• There are two varieties: systemic mastocytosis, which affects internal organs, and cutaneous mastocytosis, which affects the skin 
• Managing mastocytosis requires a comprehensive and individualised approach
• A combination of therapies can effectively manage symptoms and improve quality of life
• Treatment for cutaneous mastocytosis mainly includes antihistamines, topical steroids, and phototherapy
• Treatment for systemic mastocytosis includes antihistamines, leukotriene antagonists, corticosteroids, bisphosphonates and anticholinergics
• Evolving treatments include omalizumab, imatinib, masitinib, cladribine, and interferon alpha. 
• Avoiding recognised triggers and keeping an adrenaline auto-injector on hand are some common effective prevention strategies.