There are no epidemiologic studies of pediatric cutaneous mastocytosis. Overall estimates of prevalence of mastocytosis in European populations are around 9–13 per 100,000 [6]. Pediatric mastocytosis is largely a benign condition, with about 75% of children reported in recent literature presenting with urticaria pigmentosa, 20% with solitary mastocytoma, 5% with diffuse cutaneous mastocytosis, and <1% with TMEP [3]. Systemic and malignancy-related forms are rarely encountered in pediatric populations.

Mastocytosis has a variety of clinical manifestations from limited skin involvement to systemic signs and symptoms. The rate of anaphylaxis in children with all types of mastocytosis is estimated to be 5–9% [3, 17]. Rates in urticaria pigmentosa are lower, around 1.5%, but greater cutaneous involvement is associated with higher risk of anaphylaxis [16, 17]. In one study, 13% of adults with cutaneous mastocytosis reported a history of anaphylaxis, whereas in adults with systemic mastocytosis rates of anaphylaxis have been reported to be as high as 56% [17].

Clinical manifestations may vary by mastocytosis subtypes. Pediatric cutaneous mastocytosis subtypes include solitary mastocytoma (SM) , maculopapular cutaneous mastocytosis or urticaria pigmentosa (UP) , diffuse cutaneous mastocytosis (DCM) , and telangiectasia macularis eruptiva perstans (TMEP), with UP representing the most common variant (see Table 4.1). Rare cases of localized xanthelasmoid mastocytosis have been reported, often favoring flexural areas, with appearance similar to pseudoxanthoma elasticum or juvenile xanthogranuloma [18–20].

About 20% of cases of pediatric mastocytosis present as a solitary mastocytoma [3]. Solitary mastocytomas typically present in early childhood as a single yellow-brown lesion. Induration of skin with associated dimpling resulting from cutaneous infiltration has been referred to as having a peau d’orange (or orange skin) appearance (Fig. 4.1). Systemic symptoms are rarely encountered in association with solitary mastocytomas, and >90% of lesions will spontaneously resolve [3].

Urticaria pigmentosa presents with multiple yellow-brown macules, papules, plaques, or blisters. Lesions range from a few millimeters to 1–2 cm, tend to first appear on the trunk, and generally spare acral regions. Blistering can be seen, most prominently in association with lesions on the head [21]. Blistering tends to appear and resolve in the first few years of life [22]. In patients with UP, both the number and severity of skin lesions predict systemic symptoms, most commonly gastrointestinal, respiratory, or neuropsychiatric disturbances [16].

Patients with DCM present with generalized hyperpigmentation and induration of skin, as opposed to the discrete lesions seen in UP or SM. Two cutaneous manifestations of DCM have been described, including indurated plaques or blisters with background generalized erythema and yellow/orange plaques mimicking xanthomatous skin lesions [23, 24]. Systemic symptoms such as flushing, GI distress, and bone pain are more common in DCM than other forms of cutaneous mastocytosis [3, 15].

Telangiectasia macularis eruptiva perstans (TMEP) is a form of cutaneous mastocytosis seen in <1% of childhood cutaneous mastocytosis, and in up to 14% of adult cases, with median age of onset at 50 years [5]. TMEP is characterized by small red-brown telangiectatic macules more commonly located on extremities. Up to 50% of adult patients with TMEP experience systemic symptoms [5], but there is a paucity of pediatric data due to the rarity of this presentation in children.

It is important to note the distinctions in clinical features between pediatric and adult-onset mastocytosis. Adult-onset mastocytosis is much more likely to be associated with systemic manifestations, is less likely to regress, and presents with smaller, monomorphic lesions on the trunk and thighs. Children typically have larger, polymorphic macules, papules, plaques, or blisters targeting the head and neck, trunk, and extremities [21]. Interestingly, children with small (<1 cm), monomorphic maculopapular lesions may have a later onset in disease and higher likelihood of disease persistence beyond childhood [9].

Though pediatric fatalities in the perioperative period have not been reported, the perioperative period represents a clinical situation that requires special attention. While 2–4% of children with cutaneous mastocytosis may experience moderate symptoms secondary to mast cell release and/or anaphylaxis from anesthesia, such complications may be avoided with prophylactic antihistamines [25]. Importantly, there are no reported cases of anesthesia-related complications in patients with solitary mastocytoma [26]. The incidence in pediatric systemic mastocytosis is unknown due to rarity of the diagnosis. The perioperative period may introduce numerous triggers, including stress, temperature change, mechanical stress, and medications. Therefore, anesthesiologists should be aware of the patient’s diagnosis and obtain a thorough history of past triggers. Most authors advocate for continued administration of maintenance mastocytosis-directed treatment, incremental administration of medications with potential for mast cell release, and substitution of fentanyl or sufentanil for known degranulators, including atracurium, mivacurium, meperidine, and morphine [26]. NSAIDs may be used, with caution, in children without known sensitivity. Regardless of procedure, medication list, or severity of cutaneous symptoms, medical providers should be prepared to respond to episodes of anaphylaxis in children with cutaneous mastocytosis undergoing anesthesia.

The diagnosis of cutaneous mastocytosis is established by identifying the highly characteristic clinical exam (see Fig. 4.1) and/or with skin biopsy. Lesions of cutaneous mastocytosis are hyperpigmented, fixed macules, papules or plaques that tend to exhibit a wheal and flare reaction when stroked, known as the Darier’s sign . Skin biopsy of suspected lesions demonstrates a mast cell infiltrate in the papillary dermis. Increase in mast cell number can be subtle, particularly in patients with TMEP . Giemsa, toluidine blue, or immunohistochemical stains with CD117/c-kit and tryptase can help to identify mast cells on skin biopsy.

Many experts suggest that evaluation for systemic mastocytosis is unnecessary for most children with mastocytosis, but for certain patients with severe disease, further workup may be warranted. Though controversial, some authors recommend consideration of systemic workup in the following scenarios: organomegaly, elevated tryptase, unexplained peripheral blood abnormalities, or persistence of cutaneous lesions after puberty. Differentiation of cutaneous mastocytosis from systemic mastocytosis generally requires a bone marrow biopsy and is supported by the criteria listed in Box 4.1 [27].

Recommendations for initial laboratory testing vary between authors and clinicians. Some suggest that CBC with differential and biochemistry should be obtained at diagnosis in addition to baseline tryptase in those with UP or DCM [28]. Frequency of repeat testing has not been established but likely should be based on the severity of systemic symptoms.

Monitoring of tryptase levels may be helpful in determining burden of cutaneous disease and risk for systemic involvement. Children with diffuse cutaneous mastocytosis display significantly higher levels than those with urticaria pigmentosa or solitary mastocytoma [15, 29]. Serum tryptase tends to decrease over time and correlate with improvement in symptoms. As such, increases in serum tryptase may indicate the need for further evaluation and consideration of bone marrow biopsy [30]. In a case series of 105 children evaluated for cutaneous mastocytosis, systemic mastocytosis was found only in children with both elevated tryptase (>20 ng/mL) and organomegaly, suggesting that these factors should be considered in the decision to pursue bone marrow biopsy in pediatric patients [30]. Importantly, there were no patients with elevated tryptase in the absence of organomegaly who were found to have systemic mastocytosis [30]. Plasma histamine, though elevated in most cases of CM, has not been found correlate with active disease in mastocytosis [31].

The SCORing MAstocytosis (SCORMA) index correlates with serum tryptase and has been proposed as a standardized method to grade severity of mastocytosis [32]. This index combines the anatomical area involved, intensity of cutaneous findings, and subjective symptoms reported by patients or families.

Treatment of mastocytosis is dependent on the severity of symptoms relating to mast cell degranulation and mast cell mediator release (Table 4.3). Treatment can successfully ameliorate symptoms but does not appear to hasten resolution of mastocytosis. A detailed protocol for management is proposed by Heide et al. 2008 [33]. For patients with severe disease, avoidance of triggers of mast cell degranulation (Table 4.4) can help prevent systemic symptoms.