A Review of the Dermatologic Symptoms of Idiopathic Mast Cell Activation Syndrome

February 2019 | Volume 18 | Issue 2 | Original Article | 162 | Copyright © February 2019

Azam A. Qureshi BAa and Adam J. Friedman MDb,c

aUniversity of Maryland School of Medicine, Baltimore, MD bDepartment of Dermatology, George Washington Medical Faculty Associates, Washington, DC cGeorge Washington School of Medicine and Health Sciences, Washington, DC

Figure 1Figure 2hydrotic eczema, and Raynaud’s.34 More recently, Afrin et al reported two cases of iMCAS involving symptoms of flushing,diffuse migrating pruritus and edema, diaphoresis, alopecia, poor healing, longitudinal nail ridging, brittle nails, and loss of nail growth plates.35 One patient also experienced a diffusely migrating, patchy, macular, and erythematous rash.35 Molderingset al published a case report describing a iMCAS patient with symptoms including Raynaud’s syndrome, easy bruising and bleeding, alopecia, dermatographism, diffuse edema, and longitudinal nail ridging.36 Lastly, Simpson reports a suspected iMCAS patient with diaphoresis, pruritus, erythema, facial swelling, and pressure-induced urticaria, similar to symptoms seen in patients described in other recent case reports and smaller published samples of iMCAS patients.37–40Larger samples of iMCAS patients have also been characterized, including six studies with 10 or more iMCAS patients in which pruritus, flushing, urticaria, and bleeding tendency have all shown to be prominent features (Table 2).13,14,17,41,42 Seidel et al found bleeding diathesis to be prevalent (47%) in a cohort of 60 iMCAS patients.42 Flushing and pruritus were commonly noted by Alvarez-Twose in 32 patients with iMCAS (31 and 34%, respectively).41 In a sample of 12 patients, Schafer et al also noted symptoms of telangiectasia, rosacea-like folliculitis, angioedema, and urticaria pigmentosa.13

Cutaneous Manifestations of iMCAS: Bringing Together the Evidence

Notably, 413 of 562 patients included in cited reports were from a single study.14 Excluding this single large study, the mostcommon dermatologic sequelae described included flushing in 34.9% of patients (52/149), pruritus in 32.2% of patients (48/149),clotting dysfunction or bleeding disorder in 28.2% of patients (42/149), and urticaria or hives in 14.1% (21/149) patients. Recently, in the aforementioned largest study of iMCAS patients to date, Afrin et al reported pruritus and urticaria to affect asmany as 63% of the 413-patient sample.14 Results also conveyed that the other most common dermatologic findings in iMCAS include dermatographism (76% of patients), edema (up to 56%), unspecified rash (up to 49%), sweats (up to 47%), bruising (upto 39%), and flushing (up to 31%) (Table 2).14 Alopecia and onychodystrophy were symptoms in 15% and 13% of patients, respectively (Table 2).14


Familial hypertryptasemia and MCAD variants, including iMCAS, have been observed in association with CTDs.27,28,43–45 Lyons et al studied 33 atopic patients with persistently elevated serum tryptase and found an initially found a high prevalence of CT abnormalities (23 patients).45 Flushing and episodic urticaria, as shown in Figure 1, was noted in 26 patients.45 Further, 17 patients had history of itch, while 5 patients had history of angioedema.45 In a subsequent study investigating the genetic basis for CT abnormalities in patients with familial hypertryptasemia, Lyons et al discovered that increased copy number of TPSAB1, a gene encoding for α-tryptase, coincides with inherited increased basal serum tryptase levels.44 Although familial hypertryptasemia is likely a distinct entity from MCAD, these findings are highly relevant as they demonstrate a potential etiology of CTDs occurring in iMCAS and MCAD, which may also be mediated by products of MC degranulation.27,28,44 Indeed, in the author’s own experience, histopathological examination of an erythematous papule from a patient with MCAD and EDS symptoms demonstrates prominent staining with tryptase immunohistochemistry (Figure 2).MMPs are also released from MCs and are tryptase-activated enzymes directly involved in breaking down extracellular ma