SM Basics

The diagnosis of systemic mastocytosisMastocytosis Rare disease caused by the buildup of mast cells. Cutaneous mastocytosis primarily affects the skin and is more common in children, while systemic mastocytosis affects internal organs and is more common in adults. (SM) includes a review of the patient’s symptoms and medical history, as well as blood tests, imaging tests, bone marrow biopsies and genetic testing.

Blood tests

During a blood test, levels of an enzyme called tryptaseTryptase A protein enzyme that is primarily produced by mast cells and stored in small pockets within the cells, known as granules. High levels of tryptase are a key indicator of SM. are checked if SM is suspected, based on the patient’s symptoms and medical history.

This enzyme is constitutively secreted by the mast cells, and its levels correlate with the number of mast cells. 

The normal median serum level of tryptase is around 5 ng/mL. The levels are often elevated in the case of SM, and a baseline serum tryptase level of more than 20 ng/mL is one of the diagnostic criteria for the disease.

Imaging tests

Imaging tests such as an ultrasound scan may be conducted to check whether the patient has an enlarged liver or spleen, which is associated with SM. 

A DEXA scan may also be conducted to measure the density of the bones. This technique uses low-dose X-rays to understand how dense, or strong the bones are.  

Bone marrow biopsyBone marrow biopsy A procedure to collect a sample of bone marrow using a needle. Often used to examine the characteristics of mast cells and diagnose SM.

A bone marrow biopsy involves taking a sample of the bone marrow using a needle while the patient is under local anesthesia. This sample is then analyzed under a microscope. The bone marrow biopsy is usually taken from the pelvis.

Genetic testing

In some cases, genetic testing may also be performed to look for mutations in the KIT, which are often associated with SM. 

Diagnostic criteria

For a definite diagnosis of SM, the World Health Organization (WHO) has established major and minor criteria. An SM diagnosis requires that at least one major and one minor or three minor criteria are fulfilled.

Major

The major criteria for a diagnosis of SM is the presence of multifocal dense infiltrates of at least 15 mast cells in bone marrow sections, or sections obtained from other organs like the gastrointestinal tract and stained with tryptase.

Minor

There are four minor criteria for the diagnosis of SM. These include: 

• More than a quarter of mast cells in the bone marrow or other organs apart from the skin having an abnormal shape like atypical mast cellMast cell A type of white blood cell produced in the bone marrow. They help defend against infections and play a key role in allergic reactions. In SM, mast cells become overactive and build up throughout the body. type 1 or spindle-shaped mast cells in multifocal lesions in histologic examination.
• A mutation in the KIT gene at codon 816 in the bone marrow or peripheral blood.
• Mast cells with a KIT mutation having an aberrant CD25, CD2 or CD30 expression. 
• Levels of total tryptase of more than 20 ng/mL in the serum except in patients with associated hematologic neoplasm-type disease.

Disorders with similar symptoms

There are other diseases that cause symptoms that may be similar to those of SM, and it may be useful to compare these symptoms on your way to diagnosis.

These diseases include inflammatory bowel disease, irritable bowel syndrome, malabsorption, myeloproliferative disease, urticaria, endocrine disorder, monoclonal mast cell activationMast cell activation Describes when mast cells release histamine and other mediators into the blood stream in response to an allergen or other trigger. This leads to symptoms like fatigue, rash and, in severe cases, anaphylaxis. syndrome, idiopathic mast cell activation syndrome, idiopathic anaphylaxisAnaphylaxis A severe allergic reaction that can turn fatal without treatment. Patients with SM are at a higher risk of developing anaphylaxis. and hereditary alpha tryptasemia.