Mastocytosis refers to a group of disorders characterized by an abnormal accumulation of mast cells in various tissues throughout the body. Mast cells are critical components of the immune system, involved in the body’s allergic responses and inflammation. These cells are particularly abundant in the skin and gastrointestinal tract but are also present in other tissues, such as the bone marrow, liver, and spleen. Mastocytosis can be classified into two primary forms: cutaneous and systemic. Cutaneous mastocytosis can be further categorized into urticaria pigmentosa (UP) and solitary mastocytomas, while systemic mastocytosis involves the infiltration of mast cells into internal organs, leading to a range of symptoms and complications.

Pathophysiology

Mast cells are responsible for releasing a variety of chemical mediators, including histamine, heparin, and tryptase, which play essential roles in immune responses. These chemicals help to attract white blood cells to areas of infection or injury, modulate vascular permeability, and facilitate wound healing. While mast cells are essential for normal immune function, their abnormal accumulation in mastocytosis leads to excessive release of these mediators, resulting in a variety of clinical manifestations such as itching, hives, gastrointestinal symptoms, and even anaphylaxis.

Classification of Mastocytosis

Mastocytosis can occur in two primary forms: cutaneous and systemic.

• Cutaneous Mastocytosis: This form is confined to the skin and is further subdivided into:
  • Urticaria Pigmentosa (UP): The most common cutaneous form, characterized by the infiltration of mast cells into the skin. Lesions typically present as erythematous, brown, or tan macules, papules, or plaques. 
  • Mastocytoma: A solitary lesion, typically less than 1 cm in size, presenting as a reddish-brown nodule or plaque.
• Systemic Mastocytosis: This form involves the infiltration of mast cells into various internal organs, such as the bone marrow, liver, spleen, and gastrointestinal tract. It can result in symptoms such as bone pain, nausea, vomiting, abdominal cramps, and in severe cases, anaphylaxis or hypotension.

Epidemiology

Mastocytosis is relatively rare, with an estimated incidence of 1 in 10,000 individuals. While it is most commonly diagnosed in children, the more severe forms, particularly systemic mastocytosis, often present in adulthood. Urticaria pigmentosa (UP) represents the most common form of cutaneous mastocytosis, and mastocytomas are more frequently observed in children. The exact incidence of mastocytosis remains uncertain, but it is generally considered an orphan disease, affecting fewer than 200,000 individuals in the United States.

Symptoms and Clinical Features

The clinical manifestations of mastocytosis are primarily due to the excessive release of mast cell mediators. Symptoms can range from mild to severe and may include:

• Cutaneous Symptoms: Itching, erythema, and the formation of hives or lesions, particularly following physical stimulation (e.g., rubbing or stroking the lesions).
• Gastrointestinal Symptoms: Abdominal pain, cramping, nausea, vomiting, diarrhea, and ulcers.
• Systemic Symptoms: Bone pain, fatigue, hypotension, flushing, and anaphylactic shock in severe cases.

Diagnosis

The diagnosis of mastocytosis is based on clinical evaluation, histologic examination, and biochemical markers.

• Cutaneous Mastocytosis: The diagnosis of urticaria pigmentosa (UP) is typically made by the presence of characteristic skin lesions and a high concentration of mast cells, confirmed through skin biopsy and special stains such as Giemsa or toluidine blue.
• Systemic Mastocytosis: This form is diagnosed by biopsy of affected organs, demonstrating an increased number of mast cells, often in the bone marrow. Elevated levels of serum tryptase (a mast cell-specific protease) and histamine metabolites in urine are considered biochemical hallmarks of the disease. In addition, tests such as a bone marrow biopsy and bone scan may be used to assess the extent of mast cell infiltration.

Course and Prognosis

In general, mastocytosis has a favorable prognosis, particularly in the pediatric population, where cutaneous forms such as UP and mastocytomas often resolve spontaneously by the age of 10. However, adult-onset UP with extensive cutaneous involvement carries a higher risk of progression to systemic mastocytosis. Systemic mastocytosis, particularly in its severe form, can lead to organ damage, anaphylactic reactions, and a reduced life expectancy. The course of the disease can be unpredictable, and treatment focuses on symptom management and preventing complications.

Treatment

Management of mastocytosis is primarily symptomatic and aims to reduce the effects of mast cell mediator release. The main treatment options include:

• Antihistamines: First-line therapy for managing symptoms such as itching and hives. Both H1 and H2 antihistamines may be used to block histamine receptors and prevent degranulation of mast cells.
• Corticosteroids: Topical or systemic corticosteroids may be used to reduce inflammation in cases of cutaneous involvement. Systemic corticosteroids are occasionally used for more severe cases, especially in systemic mastocytosis.
• Leukotriene Receptor Antagonists: These medications, such as montelukast, can help manage symptoms related to bronchoconstriction or gastrointestinal discomfort.
• Mast Cell Stabilizers: Agents like cromolyn sodium can help stabilize mast cells, preventing their degranulation and the subsequent release of mediators.
• Targeted Therapies: In more severe or refractory cases of systemic mastocytosis, tyrosine kinase inhibitors, such as midostaurin, may be used to target abnormal cellular signaling pathways involved in mast cell proliferation.

Conclusion

Mastocytosis is a rare disorder characterized by an abnormal accumulation of mast cells in the skin or internal organs. While cutaneous forms such as urticaria pigmentosa and mastocytomas typically have a good prognosis, systemic mastocytosis can lead to more severe complications, including organ damage and anaphylaxis. The management of mastocytosis focuses on symptom control, with antihistamines and mast cell stabilizers being the mainstay of treatment. Ongoing research into targeted therapies offers hope for more effective treatments, particularly for systemic forms of the disease.

References

1. Akin, C. (2015). Mastocytosis: Clinical findings and management. Journal of Allergy and Clinical Immunology, 135(5), 1096-1102. https://doi.org/10.1016/j.jaci.2015.03.010
2. Akin, C., Metcalfe, D. D., & Castells, M. (2020). Advances in the treatment of systemic mastocytosis. The Journal of Allergy and Clinical Immunology: In Practice, 8(6), 1860-1869. https://doi.org/10.1016/j.jaip.2020.06.012
3. Metcalfe, D. D., Baram, D., & Mekori, Y. A. (2016). Mast cells. Physiological Reviews, 96(4), 1157-1180. https://doi.org/10.1152/physrev.00011.2016