When following patients with mastocytosis – whether classical urticaria pigmentosa in children or adult mastocytosis – I usually ask a directed review of systems, focusing on flushing, palpitations, and gastrointestinal symptoms. I am always concerned about the possibility of systemic disease, including the remote possibility of mast cell leukemia or a non-mast cell clonal lymphoproliferative disorders (especially in adults); I will examine for hepatosplenomegaly and lymphadenopathy, and check a CBC, liver function studies, and serum tryptase.
Other than patients being displeased (or even depressed) by their clinical appearance, I have never given the neuropsychiatric aspects of mastocytosis much (if any) thought.
According to Moura et al, approximately one-third of mastocytosis patients can display various disabling general and neuropsychological symptom, which may have a profound impact on their quality of life. In a majority of cases, the pathophysiology of these symptoms is not known but could be linked to mast cell infiltration, mast cell mediator release, or both. Cognitive impairment is not linked to depression in these patients. Treatments aiming at reducing mast cell number and/or stabilizing mast cells may be useful. Preliminary results suggest that treatment with kinase inhibitors may improve symptoms of depression and cognitive impairment (1).
Neurological symptoms are less frequent and mainly consist of acute or chronic headache (35%), rarely syncope (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 (flushing and pruritus) 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%) (2).
According to Theoharides et al, “brain fog” is a constellation of symptoms that include reduced cognition, inability to concentrate and multitask, as well as loss of short and long term memory. Brain “fog” characterizes patients with autism spectrum disorders (ASDs), celiac disease, chronic fatigue syndrome, fibromyalgia, mastocytosis, and postural tachycardia syndrome (POTS), as well as “minimal cognitive impairment,” an early clinical presentation of Alzheimer’s disease (AD), and other neuropsychiatric disorders. Brain “fog” may be due to inflammatory molecules, including adipocytokines and histamine released from mast cells (MCs) further stimulating microglia activation, and causing focal brain inflammation (3).
What about children with mastocytosis? In a pilot study that surveyed the parents of 17 children with mastocytosis, including the Colorado Learning Difficulties Questionnaire (CLDQ), 1 child had attention deficit hyperactive disorder and 1 was autistic; 3 children required special services and 4 needed either physical, occupational, or speech therapy. Importantly, 76% were unlikely to have cognitive impairment based on the CLDQ (4). These observations warrant further investigation.
Soter et al were the first to recognize the neuropsychiatric manifestations of mastocytosis. Out of 8 patients, central-nervous-system dysfunction was reported in 5, in terms of the cognitive manifestations of depression with few affective components. “These patients reported a poor attention span, irritability, fatigue, difficulty in concentration, headache, inability to work effectively, problems in dealing with other people and poor motivation.” (5).
I feel as though I have experienced more than three decades of “brain fog” managing patients with mastocytosis by not being attuned to (or even aware of) these issues. It’s time I snap out of it!
- Moura DS, et al. Neuropsychological features of adult mastocytosis. Immunol Allergy Clin North Am 2014; 34: 407-22.
- Georgin-Lavialle S, et al. Mastocytosis in adulthood and neuropsychiatric disorders. Trans Res 2016; 174: 77-85.
- Theoharides TC, et al. Brain “fog” inflammation and obesity: Key aspects of neuropsychiatric disorders improved by luteolin. Front Neurosci 2015; 9: 225.
- Seamens A, et al. Exploring the prevalence of learning disabilities in children with cutaneous mastocytosis: A pilot cohort study. J Am Acad Dermatol 2016; 75: 1254-5.
- Soter NA, et al. Oral disodium cromoglycate in the treatment of systemic mastocytosis. N Engl J Med; 1979: 301: 465-9.