Coping, social support, and anxiety in people with mast cell disorders.

BACKGROUND: Mast cell disorders (MCDs) are rare, chronic, debilitating diseases with a varied and complex clinical trajectory that creates challenges to physical and mental health. Reliable estimates of the prevalence of anxiety in this population are largely nonexistent. Furthermore, very little is known on how sufferers' coping efforts affect their emotions and adjustment. Because a person with an MCD cannot eliminate the stressors associated with their chronic illness, it is important to understand what helps them adjust. OBJECTIVE: To document the magnitude of anxiety in those with MCD, their physical symptoms, levels of social support, and ways of coping with the stress of the disease and to evaluate the extent to which symptoms, social support, and coping are associated with anxiety. METHODS: Individuals with MCDs completed an anonymous Internet-based survey (N = 157). RESULTS: More than half of individuals with MCDs in this study found their illness to be very stressful, and nearly a third were experiencing moderate levels of anxiety. Participants who had more frequent and severe physical symptoms reported higher levels of anxiety. Those who reported coping with their problems by using planning strategies and those who felt they had more social support available to them were less anxious; those who used more avoidant strategies to cope were more anxious. CONCLUSION: Based on the current results, and intervention work in other chronic illness groups, it seems likely that coping behaviors are a fruitful target of intervention for patients with MCD to reduce their emotional distress.

Mast Cell Activation Syndrome: A Primer for the Gastroenterologist.

Mast cell activation syndrome is thought to be a common, yet under-recognized, chronic multi-system disorder caused by inappropriate mast cell activation. Gastrointestinal symptoms are frequently reported by these patients and are often mistaken by physicians as functional gastrointestinal disorders. This syndrome can be diagnosed by the medical history and measurable biomarkers. Gastroenterologists manage diseases associated with active inflammatory cells including neutrophils, lymphocytes, macrophages, and eosinophils. The mast cell has only recently been recognized as a major player in our specialty. Gastrointestinal disorders from mast cell mediators often present with apparent irritable bowel syndrome, dyspepsia, chronic or cyclical nausea, and heartburn. Individuals with mast cell activation syndrome experience significant delays in diagnosis. The gastrointestinal symptoms are often refractory to symptom-targeted prescription medications. Beyond avoiding triggers, the best therapy is directed at modulating mast cell activation and the effects of the mediators. Many of these therapies are simple over-the-counter medications. In this article, we review mast cell function and dysfunction and the gastrointestinal symptoms, comorbid conditions, diagnosis, and management of mast cell activation syndrome. Gastroenterologists who become aware of this syndrome can dramatically improve the quality of life for their patients who previously have been labeled with a functional gastrointestinal disorder.

Psychological functioning and quality of life in patients with mastocytosis: A cross-sectional study.

BACKGROUND: Psychological symptoms appear to be frequent among patients with mastocytosis and can significantly affect patient quality of life. However, it remains unclear whether and to which extent this may be the case. OBJECTIVE: To investigate he presence and type of psychological symptoms and quality of life in patients with mastocytosis. METHODS: In this cross-sectional cohort study of adult patients with mastocytosis, all patients completed the 36-item Short Form Health Survey (SF-36) and the 90-item Symptom Checklist (SCL-90). Results were compared with those of a healthy groups of patients with other diseases (chronic pain and cancer) and healthy populations. RESULTS: Fifty patients were included in the study. Seventy percent had indolent systemic mastocytosis. Patients with mastocytosis scored significantly worse than a healthy norm group on the total SCL-90 and more specifically on the dimensions of depression, somatization, sleeping problems, and inadequacy of acting and thinking. Strikingly, patients with mastocytosis scored similarly to patients with cancer on the SF-36 subdomains of general health perception and vitality. However, no significant difference in the mental health subdomain of the SF-36 was found when compared with a healthy group. CONCLUSION: In addition to the presence of psychological symptoms, the physical symptoms that are associated with mastocytosis also have a significant impact on the quality of life of patients with this disease. Therefore, correct treatment through symptom control and psychological counseling is necessary. TRIAL REGISTRATION: EudraCT Identifier 2015-004604-37.

Patient Perceptions in Mast Cell Disorders.

Understanding experiences, perceptions, and perspectives of patients with a mast cell disorder (MCD), including cutaneous mastocytosis, systemic mastocytosis, mast cell activation syndromes, and hereditary α-tryptasemia, is an important aspect of successful care, treatment, and informed development of novel therapies. This article reviews existing studies and presents new data on MCD patient perceptions regarding medical care, symptoms, allergies/sensitivities, triggers, future health/disease progression, treatment, impact on daily living, quality of life, support needs, and concerns regarding possible familial disease. Discussion includes aspects affecting the MCD community that require further consideration and development.

Psychosocial impact of mast cell disorders: Pilot investigation of a rare and understudied disease.

Mast cell disorders are rare, chronic diseases involving unpredictable physical symptoms ranging in severity, duration, and frequency. Almost two-thirds of participants with these disorders ( n = 180) experienced clinically meaningful depressive symptoms. Depressed mood was associated with somatic symptomatology, poorer quality of life, lower resilience, and indirectly with ways of coping. Newly developed measures for this population performed psychometrically well. There was no gender difference in depression but women reported greater use of several ways of coping, greater disease-related distress, poorer quality of life, and more symptoms. Results underscore the need for further research and development of effective psychosocial interventions for this population.

Mastocytosis in adulthood and neuropsychiatric disorders.

Patients with mastocytosis can display various disabling general and neuropsychological symptoms among one third of them, including general signs such as fatigue and musculoskeletal pain, which can have a major impact on quality of life. Neurological symptoms are less frequent and mainly consist of acute or chronic headache (35%), rarely syncopes (5%), acute onset back pain (4%), and in a few cases, clinical and radiological symptoms resembling or allowing the diagnosis of multiple sclerosis (1.3%). Headaches are associated with symptoms related to mast cell activation syndrome (flushes, prurit, and so forth) and more frequently present as migraine (37.5%), with often aura (66%). Depression-anxiety like symptoms can occur in 40% to 60% of the patients and cognitive impairment is not rare (38.6%). The pathophysiology of these symptoms could be linked to tissular mast cell infiltration or to mast cell mediators release or both. The tryptophan metabolism could be involved in mast cell-induced neuroinflammation through indoleamine-2,3-dioxygenase activation. Treatments targeting mast cell may be useful to target neuropsychological features associated with mastocytosis, including tyrosine kinase inhibitors.

The Mastocytosis Society survey on mast cell disorders: patient experiences and perceptions.

BACKGROUND: Mast cell diseases include mastocytosis and mast cell activation syndromes, some of which have been shown to involve clonal defects in mast cells that result in abnormal cellular proliferation or activation. Numerous clinical studies of mastocytosis have been published, but no population-based comprehensive surveys of patients in the United States have been identified. Few mast cell disease specialty centers exist in the United States, and awareness of these mast cell disorders is limited among nonspecialists. Accordingly, information concerning the experiences of the overall estimated population of these patients has been lacking. OBJECTIVE: To identify the experiences and perceptions of patients with mastocytosis, mast cell activation syndromes, and related disorders, The Mastocytosis Society (TMS), a US based patient advocacy, research, and education organization, conducted a survey of its members and other people known or suspected to be part of this patient population. METHODS: A Web-based survey was publicized through clinics that treat these patients and through TMS's newsletter, Web site, and online blogs. Both online and paper copies of the questionnaire were provided, together with required statements of consent. RESULTS: The first results are presented for 420 patients. These results include demographics, diagnoses, symptoms, allergies, provoking factors of mast cell symptoms, and disease impact. CONCLUSION: Patients with mastocytosis and mast cell activation syndromes have provided clinical specialists, collaborators, and other patients with information to enable them to explore and deepen their understanding of the experiences and perceptions of people coping with these disorders.

Leukocyte telomere length in mastocytosis: correlations with depression and perceived stress.

BACKGROUND: Mastocytosisis a rare disease associated with chronic symptoms related to mast cell mediator release. Patients with mastocytosis display high level of negative emotionality such as depression and stress sensibility. Brain mast cells are mainly localized in the diencephalon, which is linked to emotion regulatory systems. Negative emotionality has been shown to be associated with telomere shortening. Taken together these observations led us to hypothesize that mast cells activity could be involved in both negative emotionality and telomere shortening in mastocytosis. OBJECTIVE: To demonstrate a possible relationship between negative emotionality in mastocytosis and leukocytes telomere length. METHODS: Leukocyte telomere length and telomerase activity were measured among mastocytosis patients and were correlated with perceived stress and depression assessed by the Beck Depression Inventory revised and the Perceived Stress Scale. RESULTS: Mild-severe depression scores were frequent (78.9%) as well as high perceived stress (42.11%). Telomere length was correlated to perceived stress (r=0.77; p=0.0001) but not to depression in our population. Patients displaying Wild-type KIT significantly presented higher perceived stress levels. Patients with the D816VC KIT mutation who had high perceived stress scores displayed significantly shorter telomere but not if they had high depression scores. CONCLUSION: These findings suggest that high perceived stress in mastocytosis could accelerate the rate of leukocytes telomere shortening. Since mastocytosis is, by definition, a mast cell mediated disease; these cells could be involved in this phenomenon. Mechanistic causal relationships between these parameters need to be investigated.

Depression in patients with mastocytosis: prevalence, features and effects of masitinib therapy.

Depression in patients with mastocytosis is often reported but its prevalence and characteristics are not precisely described. In addition, the impact of therapies targeting mast cells proliferation, differentiation and degranulation on psychic symptoms of depression have never been investigated. Our objective was to determine the prevalence and to describe features of depression in a large cohort of mastocytosis patients (n = 288) and to investigate the therapeutic impact of the protein kinase inhibitor masitinib in depression symptoms. The description of depression was based on the analysis of a database with Hamilton scores using Principal Component Analysis (PCA). Efficacy of masitinib therapy was evaluated using non parametric Wilcoxon test for paired data within a three months period (n = 35). Our results show that patients with indolent mastocytosis present an elevated prevalence of depression (64%). Depression was moderate in 56% but severe in 8% of cases. Core symptoms (such as psychic anxiety, depressed mood, work and interests) characterized depression in mastocytosis patients. Masitinib therapy was associated with significant improvement (67% of the cases) of overall depression, with 75% of recovery cases. Global Quality of Life slightly improved after masitinib therapy and did not predicted depression improvement. In conclusion, depression is very frequent in mastocytosis patients and masitinib therapy is associated with the reduction its psychic experiences. We conclude that depression in mastocytosis may originate from processes related to mast cells activation. Masitinib could therefore be a useful treatment for mastocytosis patients with depression and anxiety symptoms.

Brief report: "allergic symptoms" in children with Autism Spectrum Disorders. More than meets the eye?

Many children with Autism Spectrum Disorders (ASD) have either family and/or personal history of "allergic symptomatology", often in the absence of positive skin or RAST tests. These symptoms may suggest mast cell activation by non-allergic triggers. Moreover, children with mastocytosis or mast cell activation syndrome (MCAS), a spectrum of rare diseases characterized by increased number of activated mast cells in many organs, appear to have ASD at a rate tenfold higher (1/10 children) than that of the general population (1/100 children). Mast cell activation by allergic, infectious, environmental and stress-related triggers, especially perinatally, would release pro-inflammatory and neurotoxic molecules. We speculate these could disrupt the gut-blood-brain barriers, thus contributing to brain inflammation and ASD pathogenesis. Increased mast cell responsiveness may define at least a subgroup of ASD subjects, who could benefit from inhibition of mast cell activation.

Case-control cohort study of patients' perceptions of disability in mastocytosis.

BACKGROUND: Indolent forms of mastocytosis account for more than 90% of all cases, but the types and type and severity of symptoms and their impact on the quality of life have not been well studied. We therefore performed a case-control cohort study to examine self-reported disability and impact of symptoms on the quality of life in patients with mastocytosis. METHODOLOGY/PRINCIPAL FINDINGS: In 2004, 363 mastocytosis patients and 90 controls in France were asked to rate to their overall disability (OPA score) and the severity of 38 individual symptoms. The latter was used to calculate a composite score (AFIRMM score). Of the 363 respondents, 262 were part of an ongoing pathophysiological study so that the following data were available: World Health Organization classification, standard measures of physical and psychological disability, existence of the D816V KIT mutation, and serum tryptase level. The mean OPA and AFIRMM scores and the standard measures of disability indicated that most mastocytosis patients suffer from disabilities due to the disease. Surprisingly, the patient's measurable and perceived disabilities did not differ according to disease classification or presence or absence of the D816V KIT mutation or an elevated (> or = 20 ng/mL) serum tryptase level. Also, 32 of the 38 AFIRMM symptoms were more common in patients than controls, but there were not substantial differences according to disease classification, presence of the D816V mutation, or the serum tryptase level. CONCLUSIONS: On the basis of these results and for the purposes of treatment, we propose that mastocytosis be first classified as aggressive or indolent and that indolent mastocytosis then be categorized according to the severity of patients' perceived symptoms and their impact on the quality of life. In addition, it appears that mastocytosis patients suffer from more symptoms and greater disability than previously thought, that mastocytosis may therefore be under-diagnosed, and that the symptoms of the indolent forms of mastocytosis might be due more to systemic release of mediators than mast cell burden.

Pediatric mastocytosis.

The onset of mastocytosis occurs between birth and 2 years of age in approximately 55% of all cases; an additional 10% develop the disease before the age of 15 years. Mastocytosis in these age groups differs in many respects from mastocytosis that has its onset in adulthood. The typical presentation of pediatric-onset mastocytosis consists of cutaneous manifestations: either a solitary mastocytoma, urticaria pigmentosa, or, less commonly, diffuse cutaneous mastocytosis. Particularly in infants, bullous eruptions may occur. Mastocytosis in infants and children may involve internal organs, including the bone marrow and the gastrointestinal tract, although such manifestations appear to be less common in children than in adults. Plasma histamine levels may be elevated in pediatric-onset mastocytosis. Treatment usually involves the use of H1 and H2 antihistamines to control itching and to control the hypersecretion of gastric acid that may occur. The prognosis for children with mast cell disease is variable; approximately half of the children with urticaria pigmentosa may experience resolution of lesions and symptoms by adolescence.

Systemic mastocytosis: retrospective review of a decade's clinical experience at the Brigham and Women's Hospital.

The clinical experience with a group of 21 patients with systemic mastocytosis followed at our institution is summarized. Cutaneous and gastrointestinal symptoms and findings were the most prominent chronic manifestations; episodic vascular collapse was the most dramatic acute event. All patients had indolent mastocytosis. There was no mortality.

A preliminary assessment of behavioral problems in children with mastocytosis.

OBJECTIVE: The objectives of this study were to 1) review mastocytosis in terms of the behavioral pathology in adults, and 2) to assess a group of pediatric patients with mastocytosis to determine if similar behavioral pathology is evident. METHOD: Twelve children ages two to eleven referred to the NIH, a tertiary referral center for mastocytosis, were studied. Questionnaires were mailed for assessment of the child's behavior: parents completed the Childhood Behavior Checklist (CBCL) and children four years of age or more were evaluated by their teachers via the Child Behavior Checklist-Teacher Report form. Scores were compared to published normative data and to published data from other medically ill pediatric groups. Pathology was defined as present if the child scored greater than two standard deviations above published age and sex-matched norms. RESULTS: Mean factor scores on the CBCL for children with mastocytosis did not differ significantly from published norms, but individual ratings by parents were significantly elevated in four of ten subjects. Moreover, CBCL ratings by parents were similar to those seen in other medically ill pediatric groups. None of the teacher ratings were in the pathological range. CONCLUSIONS: The results of this study indicate that no clear excess of pathology exists in children with mastocytosis. Individual children treated with antihistamines for mastocytosis seem to have a nonspecific increase in behavioral difficulties at rates similar to other medically ill groups. No unique behavioral pattern implicating histamine overproduction was identified.