I am KIT D816V. I hide behind a wide range of unexplained and persistent symptoms. If you know what to look for, you can find me.12,27,28

Skin lesions, anaphylaxis, diarrhea?
Suspect systemic mastocytosis

There are 20+ severe and unpredictable symptoms that may occur in patients with systemic mastocytosis. However, patients often experience hallmark symptoms of systemic mastocytosis that commonly appear with unexplained persistence or recurrence.1,3,6,7,19,28

Small monomorphic lesions often appear on the thighs or trunk of the body.

Wheal-and-flare reaction is elicited by stroking lesion with a tongue spatula.

Anaphylaxis is often coupled with hypotension and is potentially fatal.

Symptoms can be unpredictable and severe.
97% of patients presenting with adult-onset cutaneous mastocytosis actually have systemic mastocytosis30,a

In adults, rashes may frequently be diagnosed as cutaneous mastocytosis, although systemic mastocytosis criteria can reveal systemic mastocytosis when fully investigated.18

~50% of adult patients experience anaphylaxis6,b

Commonly triggered by hymenoptera stings (such as bees or wasps) or can be idiopathic. Clinical course of anaphylactic reactions in patients with systemic mastocytosis is often severe and presents with cardiovascular features including hypotensive syncope.31

64% of patients experience diarrhea3,28,c

While increased presence of gastrointestinal (GI) mucosal mast cells is seen in many common GI disorders such as irritable bowel disease, spindle-shaped mast cell aggregates and/or CD25 expression are unique to only systemic mastocytosis.32

  • Based on a study with 59 patients with the clinical diagnosis of adult-onset mastocytosis in the skin established between 2004 and 2008.
  • As described by an expert-panel review of adult-onset mastocytosis (predominantly indolent population).31
  • Data from a validation study of 2 patient-reported outcome measures of quality of life and symptom burden in 164 patients with indolent systemic mastocytosis.

Systemic mastocytosis may be missed in patients with suspected myeloid neoplasms33

  • Approximately 60%-70% of patients with advanced systemic mastocytosis have an associated neoplasm10
  • The hematologic neoplasm is often diagnosed by itself, and the systemic mastocytosis is overlooked33
  • In patients with a KIT mutation diagnosed with a chronic myeloid neoplasm, 91% (20/22) were confirmed to have an SM-AHN33,d
  • In 30% (9/30) of these cases, a systemic mast cell disorder was never suspected upon clinical and pathologic review33
  • 8-year retrospective review of 64 patients with suspected or confirmed myeloid malignancies with pathogenic KIT mutations.

Explore case studies of the types of patients you may see in your practice

The profiles below are examples of different patient types, which may help you recognize patients in your practice who may be at risk for systemic mastyocytosis. Patient profiles are fictionalized through review of published literature and are not actual patients.

Case 1: SM-AHN confirmed on second evaluation

Patient history and presentation:

  • Initial signs and symptoms and pathology work-up confirmed Gregory’s diagnosis of chronic myelomonocytic leukemia (CMML). At the time of CMML diagnosis, next-generation sequencing (NGS) on bone marrow detected TET2, SRSF2, RUNX1, and KIT D816V mutations
  • After initiating first-line therapy with a hypomethylating agent, patient returned for follow-up due to:
    • unresolved splenomegaly
    • recent onset of bone pain
    • worsening fatigue
    • unexplained weight loss
    • increased episodes of diarrhea

Full lab results:

  • Complete blood count and chemistry profile normal
  • Serum tryptase: persistently elevated, 110 ng/mL
  • KIT D816V in bone marrow with high-sensitivity assay: reconfirmed positive mutation status
  • IHC staining for CD25 and CD117 on bone marrow biopsy revealed CD25 spindle-shaped mast cells of >15 cells per cluster, >35% infiltration of cellularity by mast cells
Combined with the bone marrow mast cell aggregates, a confirmed KIT D816V mutation status allowed Gregory’s diagnosis to be revised to systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), where the -AHN component was CMML.

Case 2: Indolent systemic mastocytosis presenting with skin lesions

Patient history and presentation:

  • After presenting to her local dermatologist with bothersome maculopapular lesions on her torso and upper thigh, Katherine was diagnosed with cutaneous mastocytosis
  • She was prescribed topical steroids for a year with limited relief
  • Referred to allergist for second opinion after reporting recent onset of headaches, increasing fatigue, and diarrhea
  • Had constant trouble focusing; expressed inability to work. Reported increased frequency of “flare-ups” and inadequacy of over-the-counter medications, such as H1, H2 blockers in symptom management
  • Lab results came back showing elevated serum tryptase at >100 ng/mL

Full lab results:

  • Complete blood count, chemistry profile, and liver function tests normal: overall stable organ function
  • Follow-up serum tryptase: persistently elevated, 130 ng/mL
  • KIT D816V in peripheral blood with high-sensitivity assay: positive mutation status
  • Referred to hematologist/oncologist to conduct bone marrow biopsy. Pathology report revealed ~35% spindle-shaped bone marrow mast cells
With persistently elevated serum tryptase, >30% mast cell infiltration of bone marrow, and a positive KIT D816V mutation status, Katherine’s diagnosis was revised to indolent systemic mastocytosis.

Case 3: Indolent systemic mastocytosis presenting with anaphylaxis

Patient history and presentation:

  • Martha presented to ER after going into anaphylactic shock with hypotension from a bee sting
  • Past medical history of chronic urticaria, managed with high-dose antihistamines
  • Reported increased frequency of unexplained anaphylaxis (3 episodes in previous month)
  • Recent onset of diarrhea of daily occurrence
  • Blood work revealed heightened risk for future anaphylactic episodes with elevated IgE and baseline serum tryptase (106 ng/mL)
  • Referred to allergist on suspicion of underlying mast cell involvement

Full lab results:

  • From allergist:
    • Complete blood count and chemistry profile normal
    • Serum tryptase: persistently elevated, 110 ng/mL
    • KIT D816V in peripheral blood with high-sensitivity assay: positive mutation status
    • Referred to hematologist on suspicion of underlying systemic mastocytosis
  • From hematologist:
    • IHC staining for CD25 and CD117 on bone marrow biopsy revealed CD25 spindle-shaped mast cells of >15 cells per cluster, >35% infiltration of cellularity by mast cells
With a positive KIT D816V mutation status, >35% infiltration of cellularity by mast cells, aberrant expression of CD25 and irregular, spindle-shaped mast cells, the hematologist was able to diagnose Martha with indolent systemic mastocytosis.
Learn how to screen suspected patients with high-sensitivity KIT D816V diagnostic assays.

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