Introduction

It can be excruciating when your closest friend turns into your greatest enemy. In addition to being a social phenomenon, it is also a biological tragedy. Occasionally, your closest friend, your immune system, turns itself into a humongous adversary and starts orchestrating situations to damage your body in disorderly responses that may be autoimmune disorders or mastocytosis - a genetic immune disorder. 

Definition and overview of mastocytosis

Mastocytosis was first reported in a 2-year-old patient of urticaria pigmentosa (UP) by Nettleship and Tay in 1869. It is a genetic immune disorder in which there is the aggregation of mast cells in body tissues that are responsible for the release of histamine, protease, prostaglandins and leukotrienes in response to their activation by cross-linking of Immunoglobulin E (IgE).

Definition and overview of allergic reactions

Allergic reactions, which we also call hypersensitivity, are conditions in which there is an exaggerated and inappropriate response of the immune system to foreign substances. The immune system responds to harmless substances by deteriorating body tissues instead of protecting them.

Mastocytosis: causes and types 

Definition of mastocytosis

Mastocytosis is a rare haematological (blood), immune, and heterogeneous genetic disorder characterised by abnormal division and accumulation of mast cells in one or more organs. 

Causes of mastocytosis

Mastocytosis is a known genetic disorder which proceeds due to KIT mutation. The KIT receptor is encoded by a gene present at chromosome number 4. Stem cell factor (SCF) is the ligand that binds with the KIT receptor and undergoes hematopoiesis, the development and proliferation of different blood cells in bone marrow including mast cells which are mainly focused.

When the KIT mutation occurs it makes the KIT receptors sensitive to SCF which increases the uncontrolled abnormal development of Mast cells.¹ 

Types of mastocytosis

There are two types of mastocytosis:

Cutaneous mastocytosis

Cutaneous mastocytosis is a benign condition characterised by an accumulation of mast cells under the skin. It is usually more prominent in neonatal infants and children of up to 16 years. Symptoms arise from the release of mediators under the skin, which persist in the formation of lesions within the first year of their lives. Rubbing the affected area can worsen the condition, causing erythema, swelling and blister formation.²

Systemic mastocytosis

Systemic mastocytosis, an aggressive systemic disorder, commonly occurs in adults where there is an accumulation of mast cells in body tissues such as the skin, bones, and internal organs. Symptoms appear due to the release of vasoactive mediators from hyperactive mast cells, which include anaphylaxis, flushing, itching, diarrhoea, and nonspecific gastrointestinal as well as neuropsychiatric complaints.³

Indolent systemic mastocytosis 

This is a rare chronic and common type of systemic mastocytosis that accounts for 75%-90% of systemic mastocytosis cases, where the accumulation of neoplastic mast cells occurs in the bone marrow and in some other organs, such as the skin. It occurs in adults and is marked by the formation of lesions in most cases, however, a few cases have been reported where no lesion formation was seen. It is an indolent, non-progressive and benign form of systemic mastocytosis. Indolent systemic mastocytosis may appear with an array of symptoms, ranging in severity from frequently troublesome to potentially deadly. It is also frequently misdiagnosed as other internal illnesses, which can cause up to a 10-year wait to receive a diagnosis.⁴

Advanced systemic mastocytosis

Advanced systemic mastocytosis is a rare myeloid uncontrolled and abnormal growth of mast cells in different organs that ultimately leads to organ impairment, drug resistance and poor prognosis. It is a progressive and aggressive disease that could be more fatal than any other form of mastocytosis.

The major issue in this case is organ dysfunction. Advanced systemic mastocytosis causes symptoms such as an enlarged liver, spleen, or lymph nodes in which imaging studies can assist in identifying these indicators. Anaemia or bone damage are further indicators of advanced systemic mastocytosis.⁵

Mast cells and their role in allergic reactions 

The role of mast cells in the immune system

Mast cells are generated from myeloid progenitor cells that are prevalent in connective tissues and blood vessels. They have a prominent inflammatory role in response to foreign invasions and allergic reactions by releasing different mediators. They are activated by allergens, antigens, or psychological factors.

Activation of mast cells in allergic reactions

Mast cells are activated during the second exposure to the same allergen, antigens or pollen. This occurs when antibodies have already been produced and there was insufficient production of lgE during the initial exposure. In the initial exposure, B cells are activated and differentiated to produce plasma cells and IgE. These IgE binds at the surface of mast cells leaving their active site exposed to the antigens. 

Release of mediators (histamine, cytokines, etc.)

The sensitised mast cells and basophil cells when bound with the allergens, cross-linking of IgE takes place that leads to degranulation (release of mediators). These mediators include histamine, which increases vascular permeability (the ability of a blood vessel to allow small molecules or cells into or out of the vessel) and smooth muscle contraction. This also includes protease which causes tissue damage, and cytokines which promote T-Helper² differentiation and IgE production. 

Allergic reactions: mechanisms and symptoms

Definition of allergic reactions 

Allergic reactions are an overactive or exaggerated response of the immune system towards a usually harmless substance.

The immune system is responsible for identifying and attacking harmful substances that enter the body. However, in some cases, allergens can be mistaken for viruses or bacteria, triggering an immune response that can result in various symptoms such as itching, inflammation, tissue injury, sneezing, runny nose, and rash.

Types of allergic reactions 

There are four types of allergic reactions or hypersensitivity:

• Immediate hypersensitivity (Type I)
• Cytotoxic hypersensitivity (Type II)
• Immune complex hypersensitivity (Type III)
• Cell-mediated, or delayed hypersensitivity (Type IV)

Symptoms of allergic reactions

Symptoms of allergic reactions can include:

• Itching
• Inflammation
• Tissue injury
• Sneezing
• Runny nose
• Rash

More severe allergic reactions (anaphylaxis) can be potentially fatal and include additional symptoms such as:

• Hives
• Pale or flushed skin
• Difficulty breathing or wheezing, due to constriction of the airways or swollen tongue/throat
• Low blood pressure
• A weak and rapid pulse
• Nausea, vomiting or diarrhoea
• Dizziness or fainting

Relationship between mastocytosis and allergic reactions 

Increased susceptibility to allergic reactions in mastocytosis patients 

It is estimated that mast cells are the responsive cells that promote allergic responses in our body. According to various studies, patients with mastocytosis have been found to be significantly more prone to anaphylaxis, with a reported risk that is 1000 times higher than that of the general population. In addition, allergic reactions are more predominant by 22% to 49% in mastocytosis patients.⁶

Minor heat, cold, dust, drugs, venom, exercise and stress can provoke anaphylaxis in patients with mastocytosis.

Mechanisms linking mastocytosis to allergic reactions

Stem cell factor (SRF) induced altered and abnormal production of neoplastic mast cells is more common in the human body than in any other usual case. These increased mast cell numbers in the human body make the body more sensitive towards allergens. The increase in mast cells results in heightened sensitivity towards allergens. When the body is exposed to allergens, the excessive increase in cells triggers an uncontrolled immune response, leading to potentially fatal allergic reactions in the body.

Diagnosis of mastocytosis and allergic reactions

Diagnosis of mastocytosis

There are various tests that your general physician may perform:

Skin biopsy 

Dermatologists would take a minuscule segment of your skin, and with proper staining mast cells can be identified.

Bone marrow biopsy

An invasive surgical method in which a needle is inserted to withdraw a small amount of bone marrow, in order to trace the mastocytosis. 

Blood test 

In blood, measuring the tryptase level can help identify mastocytosis. Tryptase is an enzyme released by mast cells during the degranulation process.

Urine test 

Measurements of urinary N-methylimidazole, and urinary leukotriene E (LTE) can identify the root cause.

Diagnosis of allergic reactions 

Diagnostic techniques for allergies include:

Skin prick test (SPT)

The skin of the forearm is pricked with a needle containing potential allergens. When all possible allergens are injected, it takes 10-15 minutes for the reaction to occur if the patient is allergic to a specific allergen. This method allows us to assess allergic reactions. 

Patch test 

In this technique, possible allergens are placed on the skin that are then covered by patches. These patches remain intact for 48-72 hours, after 3-4 days dermatologists examine the skin if any redness, inflammation or hives have appeared. 

Blood tests

Blood tests are used to examine the level of IgE in blood against certain allergens. Common Blood Tests are RAST (radioallergosorbent test) and ELISA (enzyme-linked immunosorbent assay).

Treatment and management 

Treatment options for mastocytosis 

Medications (antihistamines, mast cell stabilisers, etc.) 

Topical corticosteroids

They help decrease the number of mast cells that cause inflammation, redness, and itchiness. 

Antihistamine

This class of medicine is helpful in the treatment of mastocytosis, especially those antihistamines that target H-receptors and stop histamine from producing its inflammatory effects.

Mast cell stabilisers

These medications stop the influx of calcium through the mast cell membrane, which in turn stops the degranulation process thus, the effects of mastocytosis are prevented.

Moreover, Alpha-Interferons, midostaurin and steroid tablets can also be used in the treatment process.⁷

Lifestyle modifications

• Reduce stress: Stress can trigger mastocytosis, so managing stress can lessen the symptoms 
• Dietary changes: A diet that doesn't promote histamine release in the body can help suppress the symptoms 
• Taking care of your skin: Using moisturisers and other skin care products can help decrease the symptoms 

Treatment options for allergic reactions 

Avoidance strategies 

• During the pollen season, keep your windows closed, especially during the day
• Find out which pollen you are sensitive to and then check the pollen counts
• After working or playing outside, take a shower, wash your hair, and change into new clothes
• Wear sunglasses or glasses to reduce the amount of pollen that may cling to towels and sheets⁸

Pharmacological interventions (epinephrine, corticosteroids, etc.)

• Nasal decongestant 
• Antihistamine
• Mast cell stabilisers
• Corticosteroids 
• Immunotherapy 

Summary 

Mastocytosis is a hereditary immunological illness that causes an excessive release of inflammatory mediators due to aberrant mast cell buildup in tissues. Mast cells, which derive from myeloid progenitors, are important players in allergic reactions because they activate through the release of histamines and other mediators, frequently as a result of IgE cross-linking.

There are two primary ways that mastocytosis presents itself: cutaneous, which affects children with skin lesions, and systemic, which affects adults with extensive organ involvement. Allergic reactions are categorised as hypersensitised immune responses to harmless chemicals, including Type I (immediate) and Type IV (delayed) hypersensitivities.

Patients with mastocytosis are markedly more likely to experience severe allergic reactions, suggesting a complicated interaction between increased allergy vulnerability and aberrant mast cell growth.

Many tests are used to make the diagnosis, including blood tests, skin prick tests, bone marrow and skin biopsies for mastocytosis. To reduce symptoms and enhance quality of life, the treatments focus on symptom management using drugs, lifestyle modifications, and allergy avoidance techniques.

FAQs

What is mastocytosis? 

Mastocytosis is a rare genetic disorder characterised by the abnormal accumulation of mast cells in various tissues of the body. These mast cells release inflammatory mediators, like histamine upon activation, leading to a range of symptoms from skin lesions to systemic complications.

What are the types of mastocytosis? 

There are two main types:

• Cutaneous mastocytosis: Primarily affects children, characterised by mast cell accumulation in the skin, leading to lesions and localised symptoms
• Systemic mastocytosis: Affects adults, involving mast cell accumulation in multiple organs such as skin, bones, and internal tissues, leading to systemic symptoms and potential organ damage

What role do mast cells play in allergic reactions? 

Mast cells are integral to allergic responses. Derived from myeloid progenitor cells, mast cells release histamines, cytokines, and other mediators upon activation by allergens. This triggers symptoms such as itching, inflammation, and respiratory distress in allergic individuals.

How are mastocytosis and allergic reactions related?

Mastocytosis patients are more susceptible to allergic reactions due to the excessive number of mast cells and their hypersensitivity to allergens. This heightened sensitivity can lead to severe allergic manifestations like anaphylaxis, and increased inflammatory responses.

How is mastocytosis diagnosed? 

Diagnosis involves various methods including:

• Skin biopsy to detect mast cell accumulation
• Bone marrow biopsy to confirm systemic involvement
• Blood tests to measure tryptase levels, a marker of mast cell activation
• Urine tests to detect specific metabolites associated with mastocytosis

What are the types of allergic reactions discussed?

Allergic reactions are categorised into several types, including immediate hypersensitivity (Type I), which involves rapid IgE-mediated responses, and delayed hypersensitivity (Type IV), mediated by T-cells,causing several reactions like contact dermatitis.

How are mastocytosis and allergic reactions treated? 

Treatment strategies include:

• Medications such as antihistamines, mast cell stabilisers, and corticosteroids to manage symptoms
• Lifestyle modifications to reduce triggers and manage stress
• Allergen avoidance strategies and, in severe cases, immunotherapy to desensitise the immune system

What are the challenges in managing mastocytosis and allergic reactions? 

Managing mastocytosis and allergic reactions can be challenging due to the variability in symptoms and individual responses to treatment. Additionally, the overlap between symptoms of mastocytosis and allergic reactions can complicate diagnosis and treatment planning.

Are there specific precautions mastocytosis patients should take? 

Yes, mastocytosis patients are advised to avoid known triggers such as certain foods, medications, and environmental factors that may induce mast cell activation and exacerbate symptoms. They should also carry emergency medications like epinephrine for severe allergic reactions.

What is the prognosis for mastocytosis patients? 

The prognosis varies depending on the type and severity of mastocytosis. Cutaneous mastocytosis generally has a better prognosis, while advanced systemic mastocytosis can be more challenging to manage, and may lead to organ dysfunction in severe cases.