How I treat patients with indolent and smoldering mastocytosis (rare conditions but difficult to manage)

Abstract

Indolent systemic mastocytosis (SM) patients have a varied clinical presentation, ranging from predominantly cutaneous symptoms to recurrent systemic symptoms (eg, flushing, palpitations, dyspepsia, diarrhea, bone pain) that can be severe and potentially life threatening (anaphylaxis). Mastocytosis patients without skin involvement pose a diagnostic challenge; a high index of suspicion is needed in those with mast cell–degranulation symptoms, including anaphylaxis following Hymenoptera stings or other triggers. Modern-era molecular and flow-cytometric diagnostic methods are very sensitive and can detect minimal involvement of bone marrow with atypical/clonal mast cells; in some cases, full diagnostic criteria for SM are not fulfilled. An important aspect of treatment is avoidance of known symptom triggers; other treatment principles include a stepwise escalation of antimediator therapies and consideration of cytoreductive therapies for those with treatment-refractory symptoms. The perioperative management of mastocytosis patients is nontrivial; a multidisciplinary preoperative assessment, adequate premedications, and close intra- and postoperative monitoring are critical. Smoldering mastocytosis is a variant with high systemic mast cell burden. While its clinical course can be variable, there is greater potential need for cytoreductive therapies (eg, interferon-alpha, cladribine) in this setting. A systematic approach to the diagnosis and treatment of indolent SM using a case-based approach of representative clinical scenarios is presented here.

Systemic mastocytosis in adults: 2015 update on diagnosis, risk stratification, and management

“…Biopsy of organs other than BM, such as liver or spleen, is infrequently pursued, either for diagnostic purposes or to demonstrate MC infiltration as the cause of impaired organ dysfunction. The diagnosis of SM in the absence of skin involvement is considerably more challenging, particularly in those patients with an indolent SM (ISM) variant with low mast cell burden, termed isolated BM mastocytosis (BMM) [53,54]; consequently, a high index of suspicion is required in the setting of recurrent unexplained anaphylaxis, flushing, osteoporosis, gastrointestinal ulcerative disease, or chronic abdominal cramping.…”

Sensitive KIT D816V mutation analysis of blood as a diagnostic test in mastocytosis

“…Detection of KIT mutation also represents a technical challenge because the fraction of cells carrying the mutation is often low in all tissues. It has therefore been repeatedly argued that mutation analysis should be performed on samples containing neoplastic MCs, such as BM aspirate, and that peripheral blood (PB) is not acceptable for mutation analysis in suspected SM [5,12]. However, we recently introduced a method for KIT D816V mutation analysis with unprecedented sensitivity that allows consistent detection of the mutation in unfractionated PB in SM patients, including patients with indolent SM (ISM) [2,13].…”

Um Novo Olhar sobre a Telangiectasia Macularis Eruptiva Perstans

“…5,19 Não existe, até ao momento, nenhuma terapia capaz de alterar o curso natural da MC, nomeadamente da TMEP. 20,21 Assim, a abordagem terapêutica passa pela evicção dos fatores desencadeantes da desgranulação mastocitária e tratamento sintomático. 21 Os desencadeantes mais comuns incluem calor, stress físico e emocional, álcool, veneno de himenópteros, anti-inflamatórios não esteroides, narcóticos, agentes de contraste iodado e alguns relaxantes musculares (succinilcolina, rocurónio, atracúrio).…”

“…20,21 Assim, a abordagem terapêutica passa pela evicção dos fatores desencadeantes da desgranulação mastocitária e tratamento sintomático. 21 Os desencadeantes mais comuns incluem calor, stress físico e emocional, álcool, veneno de himenópteros, anti-inflamatórios não esteroides, narcóticos, agentes de contraste iodado e alguns relaxantes musculares (succinilcolina, rocurónio, atracúrio). 2,20 Os antagonistas dos recetores H1 da histamina podem ser eficazes na redução do prurido, enquanto os anti-H2 podem melhorar simultaneamente as queixas digestivas.…”

“…20 A abordagem terapêutica à MS indolente inclui as medidas previamente referidas para tratamento da MC. 21 As terapias sistémicas citorredutoras para diminuir a infiltração mastocitária -interferão alfa-2b, cladribina, hidroxiureia, prednisolona -não estão geralmente indicadas, pela sua toxicidade. 22 A monitorização clínica e analítica regulares são importantes para deteção precoce de alterações compatíveis com progressão para formas avançadas de MS. 21 Em conclusão, consideramos que a TMEP, pelas suas caraterísticas clínicas e histológicas próprias deverá ser vista como uma entidade separadas das demais formas de MC.…”