Disability in mastocytosis

Patients with indolent mastocytosis do not have a shortened life span or organ damage, but they do suffer from a wide range of symptoms that result in varying levels of disability.  In a French study, 363 patients were asked how they would rate their disability in general, with considerations for pain, overall health and impact of disease on their lives.  0 was considered no disability, while 4 was the most severe, intolerable disability.  They were also asked about the severity of 38 individual symptoms seen in mastocytosis.  

70% of patients said they suffered from some level of disability, compared with 9% of the control group, who did not have mast cell disease.  17% of mastocytosis patients considered their disabilities to be severe or intolerable, with none in the control group.  The finding of the paper was that CM and SM patients feel equally disabled by their disease.

The D816V mutation is often thought to correlate with disease progression in adult SM patients, and is sometimes used as a surrogate marker for severity.  There was no difference in perception of disability when comparing those with the mutation to those without.  Another marker for disease severity is serum tryptase.  Again, there was no correlation between tryptase level and disability.

The second part of the study focused on both the severity of individual symptoms and their impact on life.  Mastocytosis patients reported significantly more symptoms than the control group.  CM and SM patients  again had comparable reportings, and tryptase level and presence of D816V mutation did not affect the outcome. 

The ten symptoms that patients considered the most disabling were: psychological impact of cutaneous problems; fatigue; itching; food allergies/intolerances; severe flushing; muscle and joint pain/cramps; frequent urination; drug allergy; frequent swallowing of air and uncontrollable belching (aerophagia/eruction); and shortness of breath/respiratory difficulties.  Importantly, with the exception of frequent urination, these symptoms were all found disproportionately in patients with severe or intolerable disability, suggesting that they are the most disabling symptoms of mastocytosis. 

For many individual symptoms, there was no difference between CM and SM patients.  31% of SM patients had reduced eructions or ability to have intercourse, compared with only 3% of CM patients.  15% of SM patients also reported that this symptom was severe or intolerable.  57% of SM patients had disability stemming from bowel pseudoobstructions, while only 33% of CM had the same.  88% of SM patients suffered from muscle and joint pain/cramps compared to 70% of CM patients.

Some symptoms were more closely associated with the D816V mutation than others.  Severe flushing, psychological impact of disease, and bowel pseudoobstructions were found more frequently in people with the mutation than those without.  Inability to smell, GI pain, mobility difficulties, eye disorders and inflammation of the mouth/lips were more common in those without the mutation.  When considering only those with severe or intolerable disabilities, only the psychological impact of cutaneous problems was significantly more common in those with the mutation.  Tryptase level had no obvious correlation to symptomology.

This study also assessed mastocytosis patients using standard measures of disability, including the Hamilton scale for depression, QLQ-C30 (used to measure quality of life in cancer patients) and pruritis score.  It also used four quantifiable measures of disability: existence of life-threatening anaphylactoid episodes; number of flushes per week; number of stools per day; and number of urinations per day.  Patients were considered disabled if they had recurrent life-threatening anaphylactoid reactions, found in 19%; at least 7 episodes of flushing per week, 66%; at least 4 stools per day, 12% or at least 8 urinations per day, 32%; disability rating according to the pruritis scale, 77%; disability rating according to the Hamilton scale for depression, 75%; and disability rating according to the QLQ-C30 system, 32%.  61% of all mastocytosis patients in the study had at least one disability, with many have multiple.  Furthermore, the type of disease (CM vs SM), presence of D816V mutation and tryptase level had no effect on the type or severity of disability.

This study was the first to conclusively prove that a number of symptoms were associated with mastocytosis.  These include food and drug allergy/intolerance, muscle and joint pain/cramps, swallowing of air and uncontrolled belching, reduced sexual relations, eye pain, ringing in the ears, bowel pseudoobstructions, frequent infections (bronchitis, rhinitis, conjunctivitis), inability to smell, reduced mobility, hemorrhoidal inflammation, cough, ear/nose/throat inflammation and general pain.  It also confirmed the relationship to mastocytosis of many other symptoms previously reported.

Psychological and neurological symptoms contribute the most to disability in mastocytosis.  72% of patients felt that psychological impact of skin appearance was their worst symptom, with 23% feeling it was severe or intolerable.  General weakness (asthenia) was found in 82% of respondents, and was severe or intolerable in 28%.  52% felt they had reduced performance status (at work), 55% had social difficulties, 57% had depression, 66% had memory loss, 69% had headache and 20% had pain. 

The confirmation of psychological symptoms supports earlier findings that mastocytosis is associated with diminished attention and memory, anger, irritability and depression, referred to collectively as “mixed organic brain syndrome.”  Another study found in the mastocytosis population a prevalence of neuropsychiatric symptoms including poor attention span, irritability, fatigue, difficulty concentrating, headache, inability to work effectively, problems interacting with others, and poor motivation.  Furthermore, the study concluded that neurologic symptoms are far more common in mastocytosis patients than previously thought.  It also surmised that due to their nonspecific nature of their neuropsychiatric complaints, many people are likely to have been misdiagnosed with mental illness prior to being correctly diagnosed with mastocytosis. 

Cutaneous, gastrointestinal and skeletal symptoms are common in SM.  Pulmonary symptoms are also significantly associated with mastocytosis, with 26% of all patients saying they were severe or intolerable.  An unexpected finding was that reduced sexual relations was one of the most important symptoms, and one that patients felt most acutely.  18% described this symptom as being severe or intolerable. 

The extent of disability and symptom type and severity were largely the same for CM and SM patients.  This indicates that the presence of excessive mast cells in extracutaneous tissues was not helpful for understanding the disability and symptoms of mastocytosis patients.  Owing to these findings, the authors asserted that CM and SM are not, in fact, different diseases, but merely different manifestations of the same continuum. 

There was no significant difference in disability frequency depending on the presence of the D816V mutation or high serum tryptase levels.  Importantly, the authors concluded that the measure of serum tryptase was completely unrelated to the type and severity of symptoms.  They feel that the level of activated, mature tryptase, which is a measure of true mast cell activation, will be more useful for determining extent of disability than total serum tryptase, which is currently used. 

This study found that the symptoms of indolent mastocytosis are largely unrelated to cell proliferation or infiltration, and are instead the result of mediator release.  They also feel that indolent mastocytosis should be subdivided into groups that represent the extent of patient disability.  The number of symptoms associated with this disease is even higher than previously suspected, including many that had been previously overlooked, such as neuropsychiatric concerns.  They suspect many mastocytosis patients are misdiagnosed and that the disease may be more prevalent than previously thought.

Citation:

Hermine O, Lortholary O, Leventhal PS, Catteau A, Soppelsa F, et al. (2008) Case-Control Cohort Study of Patients' Perceptions of Disability in Mastocytosis. PLoS ONE 3(5): e2266.