Neuropsychiatric, cognitive and sexual impairment in mastocytosis patients

Abstract

Background Mastocytosis is a rare disease characterised by the accumulation and/or proliferation of abnormal mast cells (MCs) in one or several organs. It may present with a number of different symptoms that involve various organ systems. The current study aims to assess the prevalence of MC mediator-related symptoms in a cohort of mastocytosis patients with a specific focus on neurological, psychiatric, cognitive and sexual symptoms. We also assessed the impact of the disease on patients’ professional lives. Patients were administered a validated multidimensional questionnaire to collect information on patients’ perception of the severity of their symptoms. From the questionnaires we extracted the neurological, cognitive, psychiatric and sexual symptoms and the impact of the disease on patients’ professional lives as well as their grading. The affective status was assessed using the 17-item version of the Hamilton Depression Rating Scale. Results We included 139 patients. Mastocytosis was classified as systemic in 113 patients and cutaneous in 26 patients. The prevalence of MC mediator-related systemic symptoms was as follows: cutaneous (71%), gastro-intestinal (48%), cardio-vascular (36%), musculoskeletal (26.6%), fatigue (24%), urinary (14.4%) and respiratory (10%). Headaches and vertigo were noted in respectively 55% and 32% of patients. Irritability, episodes of memory loss and difficulty concentrating were reported in 54%, 52% and 40% of cases, respectively. Sexual impairment was noted in 24% of patients. No associations were found between neuropsychiatric/cognitive impairment and age, gender, diagnostic delay, disease form, the presence of cutaneous lesions, the level of serum and bone marrow tryptase and the presence of KIT mutation in bone marrow and/or skin. Depression was noted in 49% of patients. One in four patients reported a negative impact of the disease on their professional lives. Conclusion This current study provides some insights regarding symptoms related to mastocytosis and their impact on patients’ professional lives.

Cognitive, neuropsychiatric and neurological alterations in mastocytosis: A systematic review

“…The frequency of CI in patients with mastocytosis has been reported in up to 39% in a study including a total of 57 patients, 24 where memory loss, difficulty concentrating, and attention span were the most frequent alterations 9,24 . In another study, the percentage of atypical mast cells and the bone pain degree, but not serum tryptase levels, were found to correlate with the Minimental score decrease 33…”

“…50 Headache severity seemed to increase with greater histaminergic symptoms 28 ; however, they were also noted to be associated with antihistaminic treatments. 9 Finally, the presence of KIT mutations negatively correlated with increased stress 14 ; in contrast, inhibitory treatment with masitinib showed improvement in depression. 15 Low serotonin levels have been reported in mastocytosis patients.…”

“…Emerging evidence suggests that brain mast cells may play a role in mood changes, cognition, behavior and stress responsiveness 14 . Therefore, neurological and psychocognitive impairments may result from the abnormal proliferation of mast cells and their deposition in the nervous system or from the effect of the inflammatory mediators they release 9,15 …”

“…In contrast, patients frequently experienced neurological, cognitive and psychiatric complaints, with symptoms including headaches (55%), vertigo (32%), irritability (54%), memory loss (52%) to difficulty concentrating in (40%). 9 Overall, all these symptoms often have a remarkable negative impact on the patients' quality of life. 10 Mast cell disease exhibits distinct behaviors in pediatric and adult populations.…”

“…14 Therefore, neurological and psychocognitive impairments may result from the abnormal proliferation of mast cells and their deposition in the nervous system or from the effect of the inflammatory mediators they release. 9,15 Various established and emerging therapies for mastocytosis, such as targeted drugs against KIT, flavonoids and oral cromolyn, have demonstrated effectiveness in reducing neurological and cognitive symptoms associated with the condition. For instance, the tyrosine-kinase inhibitor masitinib has not only displayed a high efficiency in vivo by reducing MC burden and tryptase levels, 16 but has also been shown to decrease depression by 43% compared to baseline.…”