Elevated mast cell numbers have been implicated in a wide range of clinical conditions, from allergic rhinitis and asthma to systemic mastocytosis. Familial etiologies for mast cell disease have been suggested including defects in c-kit regulation.
Purpose To evaluate a family with multiple presentations of probable mast cell disease.
Methods A case review of a family cohort is presented.
Summary The index case, a 26-year-old Caucasian male, was initially followed at our institution for reversible airway obstruction as a young child. He was lost to follow-up, returning to the allergy/immunology clinic at the age of 18 years with fixed airway obstruction and severe, steroid-dependent asthma, as well as allergic rhinitis, GER, dilated cardiomyopathy of unknown etiology, and sleep apnea. Due to the refractory nature of his disease,and his continued decline on aggressive medical therapy, he underwent extensive evaluation, ultimately including endobronchial and open lung biopsies. Prior to biopsy, findings included a normal high-resolution chest CT, normal plethysmography, normal sweat chloride, normal α1-antitrypsin, normal CBC (with no eosinophilia), and an elevated IgE (1295 IU/mL). Biopsy showed chronic airway inflammation (eosinophils and neutrophils) plus an abundance of mast cells. Based on his biopsy results, cyclosporin and a leukotriene receptor antagonist were added to his treatment regimen with little clinical improvement. Our index patient is now the father of two children: a 4-year-old daughter (patient 2) with mild asthma and a 3-year-old son (patient 3) who has been diagnosed with systemic mastocytosis (with urticaria pigmentosa and GI involvement), moderate asthma, and allergic rhinitis. Patient 3 is currently followed at our institution for his mast cell disease. He has had urticaria pigmentosa lesions and severe reflux since birth, and he developed a GI bleed at 21 months of age. EGD revealed gastritis with increased mast cells on biopsy. A bone marrow aspirate and biopsy, abdominal ultrasonography, and bone scan were performed and showed no evidence of mastocytosis. Skin biopsy showed mast cell infiltration. Urine histamine was elevated (614 nmol/g), though both N-methylhistamine and serum tryptase were within normal range. His mastocytosis and atopic disease are under good control currently.
Conclusions This case report suggests a familial defect leading to mast cell disease of varying clinical presentation. Further genetic evaluation is warranted and may prove valuable for future targeted therapy.