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A rare manifestation of indolent systemic mastocytosis and its management during the coronavirus disease 2019 pandemic; educational lessons from Syria.

ABSTRACT: The diagnosis of indolent systemic mastocytosis can be quite a challenge due to its wide spectrum of clinical manifestations. We are reporting a case of misdiagnosed indolent systemic mastocytosis in a 41-year-old male that has been wrongly treated first as a Non-Hodgkin lymphoma. The patient had generalized lymphadenopathy and eosinophilia, which are rare manifestations of indolent systemic mastocytosis. The chronic neglected pruritus and elevated tryptase levels along with histological findings were the main clues that have led us to the final diagnosis of indolent systemic mastocytosis. Later during the coronavirus disease 2019 pandemic, the patient presented with symptoms that are common between coronavirus disease 2019 and mast cell activation syndrome. Coronavirus disease 2019 was confirmed with a polymerase chain reaction test. There were no clear guidelines for managing a case like ours, so our management plan was based on the latest recommendations published at that time.

SUBMITTER: Slaibi A

PROVIDER: S-EPMC7825900 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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A rare manifestation of indolent systemic mastocytosis and its management during the coronavirus disease 2019 pandemic; educational lessons from Syria.

Slaibi Anas A Alshehabi Zuheir Z Soltany Amjad A Isber Yasmin Y Eid Raghad R Al-Armani Azzam A Mohanna Farah F

Annals of medicine and surgery (2012) 20210121

The diagnosis of indolent systemic mastocytosis can be quite a challenge due to its wide spectrum of clinical manifestations. We are reporting a case of misdiagnosed indolent systemic mastocytosis in a 41-year-old male that has been wrongly treated first as a Non-Hodgkin lymphoma. The patient had generalized lymphadenopathy and eosinophilia, which are rare manifestations of indolent systemic mastocytosis. The chronic neglected pruritus and elevated tryptase levels along with histological finding ...[more]

PMID: 33520224

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Project description:BackgroundMastocytosis is a clinically heterogeneous, usually acquired disease of the mast cells with a survival time that depends on the onset of the disease and ranges from skin-limited to systemic disease, including indolent and more aggressive variants. The crucial element in pathogenesis is the presence of oncogenic KIT somatic mutation D816V. Further epigenetic alterations are responsible for regulating the expression of genes. It is essential to identify indicators of disease progression, and the specific clinical picture to establish an appropriate therapeutic strategy.ObjectiveThe aim of this study was to analyze the relation of mastocytosis symptoms and epigenetic changes, and to identify epigenetic predictors of the disease.MethodsGlobal DNA methylation profile analysis was performed in peripheral blood collected from 73 patients with indolent systemic mastocytosis (ISM) and 43 healthy adult volunteers. Levels of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) were determined using an ELISA-based method, while the methylation of the Alu and LINE-1 repeats were assayed with the quantitative methylation-specific PCR technique. A questionnaire interview was conducted among the study participants to collect data on possible epigenetic modifiers. Additionally, the methylation profile was compared between three human mast cell lines: ROSA KIT D816V, ROSA KIT WT, and HMC-1.1 KIT V560G, in order to assess the association between KIT mutations and methylation profile.ResultsA significantly lower level of DNA hydroxymethylation (5-hmC) in the blood was found in patients with ISM as compared to the controls (0.022% vs. 0.042%, p = 0.0001). Differences in the markers of global DNA methylation (5-mC, Alu, LINE-1) were not statistically significant, although they did indicate generally higher DNA methylation in patients with mastocytosis. The 5-hmC level was significantly associated with allergy (p = 0.011) in patients with ISM, showing a higher level of 5-hmC in patients with allergy as compared to patients without allergy. The in vitro study revealed significant differences between the studied cell lines at the level of 5-mC, Alu, and LINE-1.ConclusionsThis study confirms that epigenetic changes are involved in mastocytosis, and suggests that allergy may be an important epigenetic modifier of the disease. A possible association between KIT mutations and methylation status observed in human mast cell lines requires further investigation in human studies.Clinical implicationsEpigenetic alterations are involved in mastocytosis pathology. The possible role of allergy as an important epigenetic modifier suggests the more impaired function of mast cells in ISM patients without allergy.Capsule summaryDecreased DNA demethylation in the blood DNA of patients with ISM confirms that epigenetic alterations are involved in mastocytosis pathology. We observed a possible role of allergy as an important epigenetic modifier. There is a possible association between KIT mutations and the methylation status observed in human mast cell lines.

Project description:BackgroundIndolent systemic mastocytosis, including the subvariant of smouldering systemic mastocytosis, is a lifelong condition associated with reduced quality of life. Masitinib inhibits KIT and LYN kinases that are involved in indolent systemic mastocytosis pathogenesis. We aimed to assess safety and efficacy of masitinib versus placebo in severely symptomatic patients who were unresponsive to optimal symptomatic treatments.MethodsIn this randomised, double-blind, placebo-controlled, phase 3 study, we enrolled adults (aged 18-75 years) with indolent or smouldering systemic mastocytosis, according to WHO classification or documented mastocytosis based on histological criteria, at 50 centres in 15 countries. We excluded patients with cutaneous or non-severe systemic mastocytosis after a protocol amendment. Patients were centrally randomised (1:1) to receive either oral masitinib (6 mg/kg per day over 24 weeks with possible extension) or matched placebo with minimisation according to severe symptoms. The primary endpoint was cumulative response (≥75% improvement from baseline within weeks 8-24) in at least one severe baseline symptom from the following: pruritus score of 9 or more, eight or more flushes per week, Hamilton Rating Scale for Depression of 19 or more, or Fatigue Impact Scale of 75 or more. We assessed treatment effect using repeated measures methodology for rare diseases via the generalised estimating equation model in a modified intention-to-treat population, including all participants assigned to treatment minus those who withdrew due to a non-treatment-related cause. We assessed safety in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT00814073.FindingsBetween Feb 19, 2009, and July 15, 2015, 135 patients were randomly assigned to masitinib (n=71) or placebo (n=64). By 24 weeks, masitinib was associated with a cumulative response of 18·7% in the primary endpoint (122·6 responses of 656·5 possible responses [weighted generalised estimating equation]) compared with 7·4% for placebo (48·9 of 656·5; difference 11·3%; odds ratio 3·6; 95% CI 1·2-10·8; p=0·0076). Frequent severe adverse events (>4% difference from placebo) were diarrhoea (eight [11%] of 70 in the masitinib group vs one [2%] of 63 in the placebo group), rash (four [6%] vs none), and asthenia (four [6%] vs one [2%]). The most frequent serious adverse events were diarrhoea (three patients [4%] vs one [2%]) and urticaria (two [3%] vs none), and no life-threatening toxicities occurred. One patient in the placebo group died (unrelated to study treatment).InterpretationThese study findings indicate that masitinib is an effective and well tolerated agent for the treatment of severely symptomatic indolent or smouldering systemic mastocytosis.FundingAB Science (Paris, France).

Dataset Information

A rare manifestation of indolent systemic mastocytosis and its management during the coronavirus disease 2019 pandemic; educational lessons from Syria.

Publications

A rare manifestation of indolent systemic mastocytosis and its management during the coronavirus disease 2019 pandemic; educational lessons from Syria.

Similar Datasets

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