May 2015 Dermatology Clinic
A white male, aged 10 weeks, presented with a lesion on the left forearm. His mother reported that the lesion, initially suspected to be from trauma, had persisted for two weeks without resolution. It appeared asymptomatic throughout that time. Examination revealed a reddish-orange patch of approximately 2 cm on the patient’s dorsal left forearm with superimposed blistering. Stroking the skin resulted in rapid urtication and further blister development. The patient was noted to be fussy upon palpation and immediately after palpation. The infant had no other medical issues, and he had not received any medications for his symptoms. His social and family histories were noncontributory.
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Mastocytosis refers to a wide array of rare clinical entities characterized by an accumulation of mast cells within one or more tissues, most commonly the skin (cutaneous mastocytosis) or extracutaneous sites such as the bone marrow (systemic mastocytosis). These disorders may present at any age, but they tend to arise between birth and age 2 years with a slight male predominance1 preferentially involving the skin.2
The four forms of cutaneous mastocytosis include urticaria pigmentosa, solitary mastocytomas, diffuse cutaneous mastocytosis, and telangiectasia macularis eruptiva perstans. Studies have differed in determining the most prevalent pediatric cutaneous appearances, as both urticaria pigmentosa1,2 and mastocytomas3 have been recorded as most common.
Mastocytomas may present as either solitary or scattered lesions, most commonly yellow-brown or red-brown macules, plaques, or nodules on the trunk, buttocks, limbs, head, and neck that tend to have either an edematous peau d’orange or smooth texture.3 Symptoms tend to be localized manifestations of mast cell mediator release, although the eruptions may also be asymptomatic. Complaints may include pruritus or blistering about the lesion, as well as generalized flushing, restlessness, and urticaria. Classically, the presence of Darier’s sign, an urtication with stroking of the lesion, confirms the diagnosis of mastocytosis.2,3 This should be distinguished from the pseudo-Darier’s sign, seen in a smooth muscle hamartoma when stroking the lesion causes it to become firm and erythematous secondary to smooth muscle contraction.4
Histopathologically, mastocytomas will demonstrate a characteristic dermal mast cell infiltrate,5 although clinical diagnosis with Darier’s sign in combination with a typical yellow-orange blot morphology6 is usually sufficient. In rare cases, Darier’s sign has been shown to mask other disorders, including scabies7 and juvenile xanthogranuloma.8
Cutaneous mastocytomas should be differentiated from other similarly appearing disorders, including congenital melanocytic nevus, insect bite, and juvenile xanthogranuloma. Blistering mastocytomas must also be differentiated from bullous impetigo, epidermolysis bullosa, and burns. Insect bites may be differentiated clinically, as they typically present with a crusted punctum and also resolve faster than mastocytomas. Congenital melanocytic nevi display pigment networks on dermatoscopy and an abundance of melanocytes at the dermal-epidermal junction, in addition to a perivascular and adnexal pattern, upon histopathologic evaluation.9 Juvenile xanthogranulomas present as red to yellow nodules with nodular aggregations of histiocytes containing vacuolated, foamy cytoplasm.10 However, these should not urticate or change significantly, and they tend to be more red and dome-shaped in appearance. Blistering diseases such as bullous impetigo can look similar with yellow crusts and blisters, but bullous impetigo is secondary to Staphylococcus aureus. The lesions of bullous impetigo should not urticate on palpation, and the persistence of blisters should differentiate it. Other blistering diseases such as epidermolysis bullosa can be identified through a lack of consistent skin fragility elsewhere. Burns should be detected by geometric appearance and history.
Mast cells release vasoactive mediators, such as histamine, prostaglandins, leukotrienes, heparin, proteases, and cytokines, that protect the body from foreign invasion. The molecular pathogenesis for mastocytosis, however, has not been fully elucidated. Somatic gain-of-function mutations in the c-KIT gene with a D816 V mutation11 are suspected to play a key role in the pathogenesis of both cutaneous and systemic mastocytosis. This mutation is present in almost all cases of adult-onset systemic mastocytosis,12 whereas it is present in a lower but still significant percentage (36%) of cases of childhood-onset mastocytosis.13
Despite this mutation being seen in childhood cases, infantile cutaneous mastocytomas tend to regress spontaneously without scarring,3 commonly resolving by adolescence.5 Therefore, medical care should be conservative and symptomatic, focused on avoidance of triggers causing mast cell degranulation and providing relief of symptoms related to mast cell mediators. Triggers of degranulation include physical contact (e.g., pressure, friction, heat, cold), medications (e.g., aspirin, nonsteroidal anti-inflammatory drugs, opiates, anticholinergics, systemic anesthetics), insect venom, and radiocontrast mediums.14,15 For symptomatic therapy, H1 antihistamines such as hydroxyzine should be used for itching and flushing. H2 blockers may also be added to treat gastric hypersecretion. Although topical steroids have been shown to induce faster healing of cutaneous mastocytomas (16.4 months), a noninterventional approach has been found to be just as effective in reaching complete resolution, albeit in 34.7 months.16
Some symptoms, including abdominal complaints, neuropsychiatric symptoms, or fibromyalgia-like pain, could suggest systemic disease, prompting further evaluation. Blood work in systemic mastocytosis may demonstrate a mild-to-moderate anemia, eosinophilia, monocytosis, and increased liver function tests. Although systemic mastocytosis is exceedingly rare in children, failure of lesions to resolve or evidence of substantial systemic symptoms may prompt further testing. Testing for serum tryptase levels would be the best screening tool in childhood.17 If serum tryptase levels are normal, no further workup needs to be conducted.
Our patient was treated conservatively without use of topical steroids, as well as avoidance of friction. His lesion has been contained, and he is being followed yearly.
Grant F. McKinley, BA, is a medical student at the Philadelphia College of Osteopathic Medicine in Suwanee, Ga., and Benjamin H. Kaffenberger, MD, is an assistant professor of dermatology and director of the inpatient consultation service at the Ohio State University Wexner Medical Center and College of Medicine in Columbus.
- Ben-Amitai D, Metzker A, Cohen HA. Pediatric cutaneous mastocytosis: A review of 180 patients. Isr Med Assoc J. 2005;7(5):320-322. Available at ima.org.il/IMAJ/ViewArticle.aspx?year=2005&month=05&page=320
- Akoglu G, Erkin G, Cakir B, et al. Cutaneous mastocytosis: Demographic aspects and clinical features of 55 patients. J Eur Acad Dermatol Venereol. 2006;20(8):969-973.
- Hannaford R, Rogers M. Presentation of cutaneous mastocytosis in 173 children. Australas J Dermatol. 2001;42(1):15-21.
- Viglizzo G, Nemelka O, Nozza P, et al. Congenital smooth muscle hamartoma presenting with an unusual pseudo-Darier’s sign. Clin Exp Dermatol. 2006;31(1):148-149.
- Wolff K, Komar M, Petzelbauer P. Clinical and histopathological aspects of cutaneous mastocytosis. Leuk Res. 2001;25(7):519-528.
- Vano-Galvan S, Alvarez-Twose I, De las Heras E, et al. Dermoscopic features of skin lesions in patients with mastocytosis. Arch Dermatol. 2011;147(8):932-940. Available at archderm.jamanetwork.com/article.aspx?articleid=1105536
- Salces IG, Alfaro J, Sáenz de Santamaría MC, Sanchez M. Scabies presenting as solitary mastocytoma‐like eruption in an infant. Pediatr Dermatol. 2009;26(4):486-488.
- Nagayo K, Sakai M, Mizuno N. Juvenile xanthogranuloma with Darier’s sign. J Dermatol. 1983;10(3):283-285.
- Tannous ZS, Mihm MC Jr, Sober AJ, Duncan LM. Congenital melanocytic nevi: Clinical and histopathologic features, risk of melanoma, and clinical management. J Am Acad Dermatol. 2005;52(2):197-203.
- Sangüeza OP, Salmon JK, White CR Jr, Beckstead JH. Juvenile xanthogranuloma: A clinical, histopathologic, and immunohistochemical study. J Cutan Pathol. 1995;22(4):327-335.
- Cruse G, Metcalfe DD, Olivera A. Functional deregulation of KIT: Link to mast cell proliferative diseases and other neoplasms. Immunol Allergy Clin North Am. 2014;34(2):219-237.
- Longley BJ Jr, Metcalfe DD, Tharp M, et al. Activating and dominant inactivating c-KIT catalytic domain mutations in distinct clinical forms of human mastocytosis. Proc Natl Acad Sci USA . 1999;96(4):1609-1614. Available at pnas.org/content/96/4/1609.long
- Bodemer C, Hermine O, Palmérini F, et al. Pediatric mastocytosis is a clonal disease associated with D816 V and other activating c-KIT mutations. J Invest Dermatol. 2010;130(3):804-815. Available at nature.com/jid/journal/v130/n3/full/jid2009281a.html
- Bains SN, Hsieh FH. Current approaches to the diagnosis and treatment of systemic mastocytosis. Ann Allergy Asthma Immunol. 2010;104(1):1-10.
- Briley LD, Phillips CM. Cutaneous mastocytosis: A review focusing on the pediatric population. Clin Pediatr (Phila). 2008;47(8):757-761.
- Patrizi A, Tabanelli M, Neri I, Virdi A. Topical corticosteroids versus “wait and see” in the management of solitary mastocytoma in pediatric patients: A long‐term follow‐up. Dermatol Ther. 2015;28(2):57-61.
- Brockow K, Akin C, Huber M, Metcalfe DD. Assessment of the extent of cutaneous involvement in children and adults with mastocytosis: Relationship to symptomatology, tryptase levels, and bone marrow pathology. J Am Acad Dermatol. 2003;48(4):508-516.
All electronic documents accessed on May 4, 2015.