Mast Cell Burden in a Patient With Cutaneous Disease

A 31-year-old Caucasian male with history of asthma and anxiety presented to our institution with a pruritic eruption for 5 years. He reported a personal history of waking up with itchiness. He denied accompanying symptoms, including fatigue, diarrhea, nausea, vomiting, syncope, or anaphylaxis.Physical examination revealed scattered monomorphous, reddish brown macules and papules on the chest and back (Figure 1). Prior biopsy of the chest by an outside dermatologist showed histopathology significant for sparse to mild superficial perivascular chronic inflammatory infiltrate with scattered eosinophils and subtle spongiosis. Laboratory findings included a normal CBC and markedly elevated serum tryptase level of 41.4 μg/L. Given the clinical picture and histopathology, mast cell stain was requested and showed a slight increase in the number of perivascular and interstitial mast cells, supportive of cutaneous mast cell disease (Figure 2). Symptomatic treatment was started with antihistamines for pruritus and epinephrine auto-injector as needed for increased risk of anaphylaxis.In consultation with the oncology service, the patient underwent a bone marrow (BM) biopsy to investigate for systemic involvement. BM findings included a moderate patchy increase in reticulin fibers associated with mast cell lesions and 0.1% atypical mast cells with expression of CD117, CD2, and CD25, confirming a diagnosis of indolent systemic mastocytosis (ISM).

The majority of mastocytosis cases (80% or more) initially present with skin involvement.¹ The disorder is rare with a prevalence of under 5 cases per 10,000.² Mastocytosis is categorized by systemic involvement and cutaneous findings (Table 1). In most adults, CM presents as small red to brown monomorphic (maculopapular) lesions with histology showing mast cells infiltrating the dermis.1 CM may manifest with a flare and wheal response (Darier’s sign) after stroking of the lesions.¹In distinction from childhood onset mastocytosis, cutaneous lesions in adults are usually associated with systemic disease, often developing between ages 20 to 35.^1,3 Systemic mastocytosis (SM) is defined and classified by the WHO major and minor diagnostic criteria (Table 2). Features of systemic disease include abdominal cramping, diarrhea, headache, loss of memory, and bone pain. Physical exam findings may include enlarged lymph nodes and hepatosplenomegaly.⁴ISM is differentiated from other SM variants by its relatively benign course.^4,5 Our patient presented with no signs of systemic manifestations despite elevated serum tryptase level and involvement of the BM. In a study of 460 patients with mastocytosis, 225 (49%) of the patients had ISM with cutaneous findings (ISM+).⁴ The ISMs+ were found to have normal organ function, mean BM infiltration rate of 14.4% (SD ± 13.2%), and median tryptase level of 35 μg/L (range of 4.2 - 591 μg/L). The authors documented the lowest rates of neurologic (8.7%) and musculoskeletal (26.1%) symptoms in the ISM+ population. However, the 165 patients with ISM without cutaneous findings were found to have less gastrointestinal symptoms than the ISM+ patients (20.7% vs 39.8%). Reported rates of anaphylaxis vary widely from 20.7% to 63.3% in ISM in several studies.^4-6 Notably, evidence suggests ISM patients have a life expectancy comparable with the general population.⁶We present this case of ISM to remind clinicians of the need to investigate for systemic involvement in patients with evidence of CM who lack symptoms of systemic disease but have an elevated tryptase level.