Overview

Mastocytosis is a group of disorders resulting from an increased accumulation of mast cells in the body's tissues. Symptoms may vary widely depending on the organs involved and tend to be nonspecific, which makes diagnosis more challenging and subsequently affects the quality of life.

Introduction

Definition of mastocytosis 

Mastocytosis is defined by increased mast cell numbers in tissues, leading to several health problems. Mast cells are immune cells, acting as first-line guardians in our tissues, defending our body against invaders, including microorganisms, pathogens, and potentially harmful substances. However, when mast cells are abnormally accumulated and activated, they release mediators, enhancing inflammation and accumulation of other immune cells, damaging surrounding tissues. Common mast cell mediators are histamine and tryptase.¹

Importance of differential diagnosis 

Mastocytosis includes many different disorders and as a result, symptoms can vary. People frequently show several unspecific symptoms to clinicians that can easily fit into disorders unrelated to mastocytosis. A delay in the correct diagnosis can be stressful causing often more unpleasant symptoms and might lead to organ damage. It is important to examine each case individually, considering their medical history and performing appropriate diagnostic tests. 

Types of mastocytosis

Cutaneous mastocytosis 

Cutaneous mastocytosis usually presents in childhood and it improves in adulthood. However, it can also be present in adults. Common symptoms include typical skin lesions. According to clinical evaluation and disease course, cutaneous mastocytosis can be further classified into:^2,3 

• Urticaria pigmentosa (UP): also known as maculopapular cutaneous mastocytosis (MPCM). It is a skin condition characterised by the appearance of darker patches on the skin along with intense itching
• Localised mastocytoma
• Diffuse cutaneous mastocytosis (DCM): this is a more severe and rare form with a more generalised infiltration of mast cells in the skin, blisters and thickening, while other symptoms that accompany DCM can occur such as anaphylaxis 

Systemic mastocytosis

Systemic monocytosis can vary in severity among individuals. It commonly affects adults and at least two organs are affected by mast cells or their mediators. It is further classified into 5 subtypes:^4,5

• Indolent systemic mastocytosis (ISM): this is usually a mild form of systemic mastocytosis, with low progression and lower mast cell numbers in comparison to the other forms, however, some cases can be severe
• Smouldering systemic mastocytosis: can vary among individuals, involving a higher mast cell burden
• Aggressive systemic mastocytosis: the aggressive form is usually more severe and can progress faster, causing organ damage
• Mast cell leukemia (MCL): is also a severe and rare form, characterised by the accumulation of immature mast cells and organ damage
• Mast cell sarcoma (MCS): another rare form of mastocytosis which initially appears locally but has aggressive spreading properties

Symptoms of mastocytosis

Patients may exhibit symptoms related to the skin, cardiovascular system, gastrointestinal tract, or nervous system, depending on which organs are affected by abnormal mast cell counts and their secreted mediators. Symptoms vary among individuals and they can be cutaneous or extracutaneous systemic symptoms. Common symptoms are:^3,6

Skin lesions and rashes

Manifestations might include brown or red skin lesions, which may be palpable, while skin thickening might also occur. Redness, itchiness or blistering of the skin might be observed.

Gastrointestinal symptoms 

Gastrointestinal symptoms are frequent and often present as abdominal pain, bloating, gas, diarrhoea, nausea, and vomiting.

Cardiovascular symptoms 

Increased or irregular heartbeat low blood pressure and breathing issues might occur.

Neurological symptoms 

Neurological symptoms have also been observed and may include loss of concentration and aggressive or depressive behaviour.

Anaphylactic reactions and fatigue

Among the most life-threatening and often unpredictable manifestations is anaphylaxis. Certain substances might initiate an anaphylactic reaction, during which swelling of the skin or mouth might be observed. Breathing difficulties and low blood pressure might also rapidly present.³ 

It is important to note that although these are common symptoms of mastocytosis, the clinical course can vary according to the specific subtype, with some individuals presenting only a few of them. 

Differential diagnosis

Depending on the organ or groups of organs impacted by mastocytosis, vague symptoms may arise, which can complicate the differential diagnosis in certain situations.

Skin disorders

Several skin disorders present with similar skin lesions and can mislead the diagnostic process, especially when supplementary tests are not performed.⁷

• Chronic urticaria
• Flat warts
• Parapsoriasis
• Neurofibromatosis

Haematologic disorders

Several haematological disorders can present similar features and findings with mastocytosis.⁸

• Chronic myelogenous leukemia 
• Myelodysplastic syndromes 
• Polycythemia vera 

Gastrointestinal disorders 

Certain inflammatory gastrointestinal conditions can be similar to systemic mastocytosis with gut involvement as mast cells are important gatekeepers of the gastrointestinal system.³ 

• Irritable bowel syndrome (IBS)
• Inflammatory bowel disease (IBD)

Allergic conditions 

The activation of mast cells and the subsequent release of mediators play a crucial role in allergic reactions and certain types of mast cell syndromes that are not linked to mastocytosis.⁹

• Anaphylaxis
• Allergic rhinitis 
• Food Allergies - examples include nuts, dairy, shellfish, etc.

Diagnostic criteria for mastocytosis

Since mastocytosis disorders are similar to other unrelated conditions and are often misdiagnosed, the World Health Organisation (WHO) has proposed classifications and criteria to simplify and accelerate the diagnostic process. Cutaneous mastocytosis is based on the morphology and location of skin rashes, and the absence of fulfilled criteria for systemic mastocytosis. Diagnosing systemic mastocytosis is more challenging. A diagnosis of mastocytosis is established when at least one major criterion and one minor criterion, or three minor criteria, are met. 

The major criterion involves finding an accumulation of mast cells in the bone marrow and/or other organs outside the skin. Minor criteria pertain to the structure and location of mast cells, the identification of specific modified genes and proteins within mast cells, and the presence of their mediator tryptase in the serum of patients.¹⁰

Clinical evaluation and workup

Since differential diagnosis might occur in mastocytosis, a detailed medical history, including symptom onset, severity and possible triggers is important. Clinical evaluation and assessment by experts are also necessary. Specific diagnostic tests might be required to reach the correct diagnosis, including clinical evaluation, blood tests, biopsies, and genetic or imaging tests. 

Individuals are often affected by mild to severe symptoms, causing both physical and psychological. A fast and accurate diagnosis can relieve the patients and significantly improve their quality of life by providing a suitable treatment. 

FAQs

How long does a mastocytosis diagnosis usually require?

This might vary among individuals and depends on the type of mastocytosis and the clinical manifestations and findings. Typically, systemic mastocytosis is more difficult to diagnose compared to subcutaneous, especially in adults where the period of symptom onset and the official diagnosis can last even for years. Patients describe this period often as uncertain and stressful.¹¹

Is mastocytosis often serious?

Some cases of mastocytosis are mild, especially cutaneous mastocytosis, which is frequently limited to the skin. It is also the most frequent type presented in children and symptoms can improve, as individuals reach adulthood.²

The World Health Organization has set criteria for diagnosis, focusing on mast cell accumulation and other specific indicators. Accurate diagnosis and thorough evaluation are crucial for managing symptoms and improving patient quality of life through appropriate treatment.

Summary

Mastocytosis is a group of disorders caused by an increase in mast cells in the body. The symptoms can vary significantly based on the organs involved, making diagnosis challenging and impacting quality of life. Mastocytosis occurs when mast cells, which protect the body from harmful substances, accumulate and release mediators like histamine and tryptase, causing inflammation and tissue damage.

Diagnosis is important because symptoms of mastocytosis can overlap with other disorders, leading to delays and unnecessary complications. Each case must be evaluated individually, taking into account medical history and necessary diagnostic tests. There are different types of mastocytosis. Cutaneous mastocytosis often appears in childhood and may improve with age, while systemic mastocytosis typically affects adults and involves multiple organs. Cutaneous mastocytosis can be divided into subtypes such as urticaria pigmentosa, localised mastocytoma, and diffuse cutaneous mastocytosis, the latter being more severe.

Symptoms vary by individual, impacting skin, cardiovascular, gastrointestinal, and nervous systems. Common symptoms include skin lesions, gastrointestinal issues like abdominal pain, cardiovascular problems like irregular heartbeat, and neurological symptoms such as concentration loss. Anaphylaxis, a severe reaction, can also occur unpredictably, requiring urgent attention. Differential diagnosis can be complicated due to similar symptoms in skin disorders, haematological issues, gastrointestinal conditions, and allergic reactions.