• Cutaneous Mastocytosis: Limited to involvement of the skin. Includes Urticaria
Pigmentosa (most common), Telangiectasia macularis eruptive perstans, diffuse cutaneous mastocytosis, solitary mastocytoma
• Systemic Mastocytosis: Infiltration of extracutaneous organs (may have skin involvement as well). Consists of indolent systemic mastocytosis (most common), smoldering systemic mastocytosis, systemic mastocytosis w/associated hematologic non-mast cell lineage disorder (may be MDS, MPN, or lymphoproliferative),
aggressive systemic mastocytosis (a/w organ dysfunction), & Mast cell leukemia.
Signs and Symptoms
• Sx: Largely result from release of mast cell mediators. Can produce variety of sx including: Flushing, nausea, diarrhea, HoTN, pruritus, syncope. And anaphylaxis. Other sx include: Pain syndrome & neuropsychiatric sx
• Signs: Darier Sign: Development of erythema & urticaria when rubbing skin infiltrated by mast cells.
Exam and Laboratory
• Physical findings: Splenomegaly, hepatomegaly, maculopapular skin lesions
• Lab findings: Anemia, eosinophilia, thrombocytopenia, elevated serum tryptase
• Must distinguish from other disorders w/↑ mast cells, including chronic eosinophilic leukemia & myeloproliferative variant of hypereosinophilic syndrome (distinguished by FIP1L1-PDGFRA or PRKG2-PDGFRB)
• Skin bx should be performed to diagnose cutaneous mastocytosis.
• BM bx should be pursued in all adult pts, & in those w/o cutaneous involvement but systems consistent w/systemic mastocytosis & elevated tryptase.
• Evaluation for D816V KIT Mt (most pts have) should be performed
• Evaluation of serum tryptase & urinary histamine should be performed (elevated)
• Evaluation for presence of “B” & “C” sx (Table 1)
• Pts should have epinephrine available for anaphylaxis
• Mgmt of sx related to mast cell mediator release
• Imatinib generally ineffective due to presence of KIT D816V Mt
• ASM: Tx options in clued Interferon alpha 2b, cladribine, hydrea, glucocorticoids, all w/variable response.
MYELOPROLIFERATIVE VARIANT OF HYPEREOSINOPHILIC SYNDROME
Diagnosis and Classification
• Blood eosinophilia ≥ 1500/μL w/no other etiology
• Myeloproliferative variant: A/w anemia, thrombocytopenia or thrombocytosis, organomegaly.
• Rearrangements of FIP1L1-PDGFRA & of PDGFRB found in subset of pts. (NEJM 2003;348:1201)
• Monitor for end organ damage: Particularly cardiac & pulm
• PDGFRA rearrangements: Imatinib is first-line Rx (FIP1L1-PDGFRA is particularly sensitive to Imatinib). Other TKI (such as Dasatinib, Nilotinib) may be used in second-line setting
• Therapies for non-FIP1L1-PDGFRA: Steroids, hydrea, Interferon-alpha
• Allogeneic SCT may be considered for refractory cases