A mother brings her healthy 6-month-old girl to the outpatient clinic with disseminated, asymptomatic, golden-brown bumps that occasionally become red and swollen. FOR MORE ON THIS CASE, TURN TO PAGE XX.
DERMCASE diagnosis: MASTOCYTOSIS—URTICARIA PIGMENTOSA
Mastocytosis is a condition characterized by the accumulation of mast cells and CD34+ mast cell precursors in the skin or other organs of the body. The cause of mastocytosis is unknown but it has been associated with a point mutation (D816V) in the c-KIT stem cell ligand on mast cells, leading to unregulated stimulation of mast cell receptors and mast cell degranulation.1 This mutation may result in release of mast cell mediators including histamine, prostaglandin D2, heparin, tryptase, chymase, leukotrienes, and others.
Potential triggers of mastocytosis can be physical and environmental, as well as reactions to medications and certain foods (Table).
Mastocytosis may occur in individuals from birth to middle age, but most commonly occurs before the age of 2 years.2 In pediatric patients, mastocytosis typically has an early onset before age 1 year and improves without treatment. Up to 25% of pediatric cases may be congenital. Mastocytosis in pediatric patients rarely infiltrates internal organs.
Cutaneous manifestations include solitary mastocytomas, urticaria pigmentosa (UP), diffuse cutaneous mastocytosis, and telangiectasia macularis eruptive perstans.2,3 Blistering and vesiculation may occur because of histamine-mediated or other chemically-mediated leakage resulting in detachment of the epidermis from the underlying dermis. Patients often present with a positive Darier sign, representing localized erythema and urticarial wheals after rubbing the papule.
Rarely, patients may develop systemic symptoms including flushing, blistering, itching, hives, nausea, abdominal pain, diarrhea, bone pain, hypotension, or anaphylaxis.2 The risk of anaphylaxis is comparable to the general population in patients with solitary mastocytomas or UP. It is seen in 9% of pediatric patients (slightly increased from the general population) with severe cutaneous manifestations.4
Mastocytomas are solitary fixed, flesh-colored to hyperpigmented papules or plaques often with a peau d’orange (orange peel-like) surface. Local edema may be severe enough to cause blistering, particularly in infants. These lesions are more often located on the neck, upper extremities, or trunk.
Urticaria pigmentosa appears as 2 or more well-demarcated, reddish-brown or golden-brown macules and papules located on any cutaneous surface, including mucous membranes, but often sparing the palms and soles. Clinical UP is the most common presentation of mastocytosis with improvement of lesions similar to the course of solitary lesions. These patients may be more prone to the development of itching and subtle systemic symptoms when multiple mastocytomas are irritated.
Diffuse cutaneous mastocytosis features diffuse thickened, erythematous reddish-brown to yellow plaques with a peau d’orange surface. This condition is rare and patients are more likely to have associated systemic manifestations, including gastrointestinal symptoms such as abdominal pain, nausea, vomiting, diarrhea, or gastrointestinal hemorrhage secondary to gastritis or peptic ulcer disease. Infants and young children are also at risk for mastocytosis syndrome, which includes bronchospasm, headache, flushing, diarrhea, pruritus, hypotension, and occasionally death.
Telangiectasia macularis eruptive perstans manifests as small, red-brown, telangiectatic macules on the trunk or extremities, most commonly seen in adults. These lesions have little tendency toward urtication. This condition is extremely rare and most patients are not symptomatic.
The differential for brown macules, papules, and plaques includes pigmented nevi, postinflammatory hyperpigmentation, lentigines, and café au lait macules. The golden-brown color and fuzzy borders as well as Darier sign help to distinguish mastocytomas from these pigmented lesions. The differential for bullous lesions includes bullous impetigo, herpes simplex infection, epidermolysis bullosa, contact dermatitis, or linear immunoglobulin A dermatosis. Patients with cutaneous and systemic manifestations may be misdiagnosed with carcinoid syndrome or amyloidosis.
Diagnosis of UP is primarily clinical with a positive Darier sign and occasionally positive dermatographism. Laboratory studies and skin biopsy are not routinely required.
Most patients with mastocytosis are asymptomatic and their condition improves by the time they reach puberty.2,5 Symptomatic patients may respond to antihistamines (eg, hydroxyzine, diphenhydramine, cyproheptadine, chlorpheniramine) daily, and they should avoid known triggers (such as hot baths or extreme exercise that may increase histamine release). Other possible treatments include doxepin, leukotriene antagonists, or cromolyn sodium (mast cell stabilizer). However, these treatments are usually reserved for patients with severe cutaneous symptoms or systemic manifestations. Photochemotherapy (PUVA) is rarely used to treat diffuse infiltrative mastocytosis or improve the cosmetic appearance of the rash.
Of note, practitioners should be aware of anesthesia-related adverse events associated in pediatric patients with mastocytosis.6 A baseline serum tryptase may be helpful in identifying systemic mastocytosis. Practitioners should avoid preoperative drug skin testing and minimize mechanical cutaneous pressure. Nonsteroidal anti-inflammatory drugs may be given with caution to help with flushing, but may also result in further degranulation.
The patient was growing and developing normally and did not require any treatment. The parents were reassured accordingly.
1. Méni C, Bruneau J, Georgin-Lavialle S, et al. Paediatric mastocytosis: a systematic review of 1747 cases. Br J Dermatol. 2015;172(3):642-651.
2. Paller AS, Mancini AJ. Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence. 5th ed. New York: Elsevier; 2016:215-218.
3. Metcalfe DD. Classification and diagnosis of mastocytosis: current status. J Invest Dermatol. 1991;96(3 suppl):2S-4S.
4. Brockow K, Jofer C, Behrendt H, Ring J. Anaphylaxis in patients with mastocytosis: a study on history, clinical features and risk factors in 120 patients. Allergy. 2008;6392):226-232.
5. Castells M, Metcalfe DD, Escribano L. Diagnosis and treatment of cutaneous mastocytosis in children: practical recommendations. Am J Clin Dermatol. 2011;12(4):259-270.
6. Ahmad N, Evans P, Lloyd-Thomas AR. Anesthesia in children with mastocytosis: a case based review. Paediatr Anaesth. 2009;19(2):97-107.