Characterization Of Common Blood Test Abnormalities Potentially Aiding Diagnosis Of Mast Cell Activation Syndrome: A Preliminary Analysis

Recognized since roughly a century ago, mastocytosis (typically cutaneous (CM) or systemic (SM)) is a rare disease of constitutive mast cell (MC) activation and inappropriate MC accumulation.  A few specific, usually somatic mutations in the dominant MC control element KIT, most commonly KIT-D816V, drive most cases of mastocytosis.  Recently there has been new recognition of another class of suspected far more prevalent MC diseases, now termed MC activation syndrome (MCAS, J Hematol Oncol 2011;4:10), characterized by constitutive MC activation with little to no MC accumulation and leading to chronic multisystem polymorbidity of a generally inflammatory theme with variable, but potentially disabling, severity.  Evidence has been found in MCAS patients (pts) of a much wider array of KIT mutations than in SM (likely generally driving constitutive activation as in SM) (Immunogenetics 2010;62:721 et al.), but diagnosis of MCAS presently rests on identifying chronic/recurrent aberrant mediator release symptoms and elevated MC mediator levels, eliminating other diagnostic considerations, and, ideally but not necessarily, demonstrating response to therapies targeted at MC mediator production or action.  Following diagnosis, many pts improve with therapy, but diagnosis often is substantially delayed for many reasons including marked heterogeneity of clinical presentation (likely due to marked heterogeneity of driver mutations and their resulting patterns of aberrant mediator expression and MC reactivity).  We nevertheless noted in such pts’ common blood tests seemingly recurrent, longstanding patterns of (typically modest) abnormalities, and sought to better characterize these abnormalities as a step toward developing aids for earlier diagnosis.  With local institutional review board approval, we reviewed the charts of 298 pts at our center diagnosed with MCAS (per available diagnostic criteria at the time) dominantly between December 2008 and July 2012, compiling a database including complete blood counts, leukocyte differentials, common metabolic panels, and other MCAS diagnostic data.  Common blood test abnormalities found included decreases in hematocrit (Hct, 69% of pts) and albumin (48%) and increases in white blood cell count (WBC, 49%), mean corpuscular hemoglobin (MCH, 48%), red cell distribution width (RDW, 56%), reactive lymphocytes (RLs, 27%), monocytes (monos, 43%), eosinophils (eos, 38%), basophils (basos, 26%), glucose (glu, 73%), blood urea nitrogen (BUN, 60%), creatinine (Cr, 32%), total bilirubin (TB, 31%), aspartate aminotransaminase (AST, 60%), alanine aminotransferase (ALT, 60%), and alkaline phosphatase (AP, 38%).  Abnormality in these parameters generally was frequent: Hct, 86% of all determinations; MCH, 51%; RDW, 78%; WBC, 67%; monos, 28%; eos, 18%; basos, 5%; glucose, 42%; BUN, 76%; Cr, 43%; TB, 45%; AST, 59%; ALT, 54%; AP, 34%; and albumin 32%.  Magnitude of abnormality in most of these parameters generally was modest: on average an abnormal Hct, relative to the midpoint of its normal range (generally ±2.0 standard deviations (SDs) around the midpoint), was 3.0 SDs below the midpoint (i.e., -3.0); RDW, +3.5; WBC, +3.0; RLs, +0.3; monos +8.1; eos, +3.1; basos, +0.59; BUN, +3.0; Cr, +5.2; TB, +5.2; AST, +3.0.  Trend analyses showed that standardized magnitudes of abnormality in these parameters remained stable over time.  Median persistence of abnormality prior to diagnosis in pts with ≥2 determinations across ≥1 year was Hct, 8.3 years (y); MCH, 10.5 y; RDW, 8.0 y; WBC, 8.3 y; RLs, 10.5 y; monos, 12.6 y; eos, 12.0 y; basos, 13.1 y; glucose, 7.3 y; BUN, 10.4 y; Cr, 9.9 y; TB, 14.4 y; AST, 9.2 y; ALT, 9.5 y; AP, 6.7 y; and albumin, 8.1 y.  We preliminarily conclude that typically modest abnormalities in common blood tests, including several tests often accorded little attention when abnormalities are modest in magnitude (e.g., Hct, RDW, % RLs/monos/eos/basos, AST, ALT, AP), have been present for many years prior to diagnosis of MCAS.  In concert with general efforts to increase awareness of MCAS, it may be worthwhile developing and studying automation for alerting providers to these persistent abnormalities and their association with MCAS, possibly abetting earlier diagnosis and initiation of therapeutic efforts in at least some pts with chronic multisystem inflammatory polymorbidity of otherwise unapparent unifying explanation.