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Journal of the Dermatology Nurses' Association:
doi: 10.1097/JDN.0b013e31829cbef4
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Urticaria Pigmentosa

Garcia-Albea, Victoria

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Author Information

Victoria Garcia-Albea, CPNP, MSN, Lahey Clinic, Burlington, MA.

The author declares no conflict of interest.

Correspondence concerning this article should be addressed to Victoria Garcia-Albea, CPNP, MSN, Lahey Clinic, 41 Mall Road, Burlington, MA 01805. E-mail: toribeebe@gmail.com

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Abstract

Urticaria pigmentosa is one of a spectrum of diseases of the mast cell, termed mastocytosis. This is an uncommon disorder in which mast cells are overproduced and accumulate in various organs. In urticaria pigmentosa, mast cells accumulate in the skin, causing a rash. In this article, the diagnosis and management of urticaria pigmentosa will be reviewed by examining a case occurring in a 5-month-old boy. There is also a brief review of systemic mastocytosis and other mastocytosis variants.
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5-MONTH-OLD BOY WITH EDEMATOUS PAPULES AND PLAQUES

Patient History

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A 5-month old boy was referred to the dermatology clinic for a 1-week history of an asymptomatic rash. The patient’s mother initially thought he had bug bites; however, when he seemed to wake up with more lesions, she became concerned. The lesions did not seem to bother the patient; he was not scratching them. He had no history of systemic symptoms such as fever or weight loss, and there were no changes in sleep, bowel, or eating habits. His mother denied that he ever developed any blisters or facial flushing.

The patient’s past medical history was unremarkable. He was a healthy 5-month-old boy, who was born to a healthy 32-year-old woman, with no complications during pregnancy or delivery (Figure 1). His 2-year-old sister was healthy. There was no recent travel and no new pet exposures in the weeks preceding the rash. His medications included only a vitamin D supplement, which was not new. He was breastfed exclusively. His immunizations were all up to date. No one else at home had a rash. The patient’s mother reported no changes in soaps, detergents, lotions, or moisturizers.

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PHYSICAL FINDINGS

On presentation, the patient was a healthy-appearing 5-month-old White boy, who was awake and alert during the examination. He was playful and smiling, well-nourished and well-hydrated, moving all extremities, and was in no apparent distress. His mucous membranes were moist, and the anterior fontanel was open and soft. Located on his face and trunk, but with the highest concentration on the extremities, were numerous pinkish-brown edematous 3-mm to 1-cm smooth, dermal papules and plaques. There was no epidermal change. When two discrete pinkish-brown 3-mm macules on the lower abdomen were stroked with a pencil eraser, they developed into erythematous urticarial wheals, displaying a positive Darier’s sign (Paller & Mancini, 2006; Skrabs, 2002).

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Laboratory Findings

A complete blood count (CBC) was performed, which was normal. The patient did not have a skin biopsy. The Darier’s test was performed as described above, and it was positive. The Darier’s test or Darier’s sign refers to a localized urticarial wheal that is produced at the site when a lesion is rubbed or scratched with a tongue blade or pencil eraser (Avshalumov, Pichardo, Jorizzo, Sangueza, & Goldenberg, 2008; Skrabs, 2002). This will be discussed in greater detail below.

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Diagnosis

On the basis of the patient’s history of present illness, clinical presentation, and positive Darier’s sign, the diagnosis of urticaria pigmentosa (UP) was made (Almahroos & Kurban, 2003; Longley et al., 1993). UP is one of several forms of mastocytosis (Avshalumov et al., 2008). Mastocytosis refers to a heterogeneous group of clinical disorders characterized by increased mast cell accumulation in the skin or other organs (Longley et al., 1993; Paller & Mancini, 2006). UP can occur at any time from birth to middle age but is most often seen in children; 55% of cases present before 2 years old (Almahroos & Kurban, 2003; Paller & Mancini, 2006).

The diagnosis of pediatric mastocytosis is based on characteristic skin findings and a positive Darier’s sign (Paller & Mancini, 2006). This test is “notoriously positive” in 90% of patients with UP (Paller & Mancini, 2006, p. 226). The skin will develop localized erythema and urticarial wheals when rubbed with a tongue blade or pencil eraser (Avshalumov et al., 2008; Paller & Mancini, 2006). In children under 1 year old, rubbing can cause a blister to form (Avshalumov et al., 2008). A positive Darier’s sign aids in diagnosing all forms of cutaneous mastocytosis, although it can be negative in patients with mastocytosis, especially when lesions are macular at baseline (Paller & Mancini, 2006). One should use caution when performing the Darier’s test, because when positive, histamine is released and anaphylaxis has been reported.

When skin lesions are present, a skin biopsy can be performed to confirm the diagnosis. The biopsy should be performed on lesional skin and should be sent for hematoxylin and eosin staining; direct immunofluorescence is not needed. Local anesthetic without epinephrine should be used because epinephrine can cause mast cell degranulation, making them more difficult to identify (Alto & Clarcq, 1999). In UP, this would show accumulation of mast cells in the dermis. Special stains can help confirm the mast cell nature of the infiltrate. When systemic symptoms are present, such as nausea, abdominal pain, diarrhea, weight loss, headache, hypotension, bone pain, fatigue, syncope, tachycardia, or respiratory distress, a biopsy of the bone marrow or the gastrointestinal tract may be necessary (Paller & Mancini, 2006).

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Etiology

The etiology of UP is not well understood. Mast cell growth and regulation is dependent on stem cell factor, which is cytokine that binds to the c-kit gene (Paller & Mancini, 2006). Studies of adult patients with mastocytosis have shown c-kit mutations. However, these genetic mutations are not typically present in pediatric patients with UP. Mastocytosis is usually a sporadic disorder, but there have been reports of familial cases (Paller & Mancini, 2006).

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Disease Classification

Cutaneous mastocytosis includes mastocytomas, which can be single or multiple; UP; bullous mastocytosis; diffuse cutaneous mastocytosis; and telangiectasia macularis eruptiva perstans. Mastocytosis can be separated into a cutaneous form and a systemic form, with potential overlap. There are consistent differences between adult and pediatric mastocytosis. Adult disease is classified into indolent mastocytosis, mastocytosis with associated hematologic disorder, mast cell leukemia, and lymphadenopathic mastocytosis with eosinophilia. In pediatric patients, there tends to be an earlier onset, usually within the first year of life; more common spontaneous resolution, often before puberty; rare association with hematologic disorders; and rare extracutaneous involvement (Paller & Mancini, 2006).

The classification of mastocytosis can be confusing; however, categorization of pediatric disease can be simplified (Paller & Mancini, 2006). The most common pediatric presentations are mastocytomas (single or multiple), UP, and occasionally, diffuse cutaneous mastocytosis. Vesicular or bullous variants of each of these can occur.

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Associated Signs and Symptoms

In some patients, facial flushing is seen, along with blistering and itching (Almahroos & Kurban, 2003; Paller & Mancini, 2006). These symptoms are related to the release of histamine, prostaglandin, heparin, tryptase, leukotrienes, and other mast cell mediators (Paller & Mancini, 2006). Signs and symptoms of mast cell disease vary depending on where in the body the mast cells are located (Bains & Hsieh, 2010). The most common location for mast cell accumulation is in the skin; therefore, most patients with mastocytosis have cutaneous involvement (Bains & Hsieh, 2010). Other organs can be involved, most commonly the bones, bone marrow, gastrointestinal system, heart, lungs, and central nervous system (Avshalumov et al., 2008; Longley et al., 1993). Bone involvement can be lytic, sclerotic, or a mixed process (Barete et al., 2010). Diffuse involvement is more common, and in many adult patients with systemic mastocytosis, there is generalized osteoporosis (Barete et al., 2010). Sclerotic changes are seen in the axial skeleton and the ends of the long bones (Barete et al., 2010). When the disease is more severe, patients may experience systemic symptoms demonstrating accumulation of mast cells in other organs. Patient may experience nausea, abdominal pain, diarrhea, malabsorption with hypoalbuminemia, weight loss, headache, hypotension, bone pain, fatigue, syncope, tachycardia, and less commonly, pulmonary symptoms (Almahroos & Kurban, 2003; Avshalumov et al., 2008; Bains & Hsieh, 2010; Paller & Mancini, 2006). In adults, the extent of cutaneous disease can correlate with systemic symptoms (Paller & Mancini, 2006). In children, this correlation does not exist (Paller & Mancini, 2006).

Extensive laboratory or radiographic studies are generally not indicated in the pediatric population (Paller & Mancini, 2006). In diffuse cutaneous mastocytosis, a CBC, complete metabolic panel, and serum tryptase may be indicated (Paller & Mancini, 2006). Serum tryptase measures the level of mast cell activation (Sperr et al., 2002). A urine histamine level would be elevated (Paller & Mancini, 2006).

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Skin Findings

Mastocytomas, a common type of childhood mastocytosis, are skin-colored to yellow, orange, or tan papules or plaques. They can look like bruises or café au lait macules and can range in size from a few millimeters to several centimeters. Mastocytomas display a positive Darier’s sign. They can appear anywhere on the skin, but the most common locations are the arms, neck, and trunk (Paller & Mancini, 2006).

UP, the most common type of pediatric mastocytosis, presents with multiple mastocytomas. Lesions may be purpuric or may have a yellowish hue. Darier’s sign is positive, and dermatographism is present in 30%–50% of patients (Paller & Mancini, 2006).

Diffuse cutaneous mastocytosis is a more rare type of mastocytosis and is especially uncommon in children (Paller & Mancini, 2006). Skin appears thick and reddish-brown and may have a peau d’orange texture, which when translated from French means “orange peel-like texture” (Paller & Mancini, 2006, p. 227). These patients are more likely to have systemic disease and may experience pruritus, flushing, fever, vomiting, diarrhea, abdominal pain, gastric ulceration, or respiratory distress. Pediatric patients with diffuse cutaneous mastocytosis may be at risk for peptic ulcer disease (Paller & Mancini, 2006).

Telangiectasia macularis eruptiva perstans is a type of mastocytosis that occurs almost exclusively in adults. It has rarely been reported in children. These patients have minute, reddish-brown telangiectatic macules on the trunk and extremities (Paller & Mancini, 2006).

Mastocytosis with systemic involvement is significantly more common in adults than in children (Paller & Mancini, 2006). Organs most commonly involved are the gastrointestinal tract and skeletal system; however, lungs, kidneys, lymph nodes, myocardium, pericardium, liver, spleen, and bone marrow can be involved (Pardanani & Tefferi, 2010). In adults, there is an increased risk for hematologic malignancy. In pediatric patients with systemic mastocytosis, the hematologic system is rarely involved; therefore, their level of risk for hematologic malignancy is unclear (Paller & Mancini, 2006).

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Course and Prognosis

The course and prognosis of mastocytosis depends on the subtype, disease severity, and age of onset (Paller & Mancini, 2006). Usually, pediatric patients with mastocytosis have a favorable outcome, and at least 50% of patients have complete resolution by adolescence (Paller & Mancini, 2006). If mastocytosis persists into adulthood, patients have the same risk of systemic disease as patients with adult-onset mastocytosis (Paller & Mancini, 2006). However, adults with pediatric-onset mastocytosis generally have milder symptoms as adults (Jappe, Aumann, Mittler, & Gollnick, 2003). When adults develop UP, it is usually more severe, involvement in extracutaneous organs is more common, and the disease is termed systemic mastocytosis (Jappe et al., 2003).

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Treatment

Treatment is symptomatic as there is no cure for mastocytosis. There should be a focus on patient and parent education about the disease, its natural history, differences between adult and pediatric disease, and possible triggers. Antihistamines help reduce dermatographism, itch, facial flushing, and gastrointestinal symptoms. Oral nonsedating histamine type 1 receptor (H1) antagonists are the first-line treatment. These include cetirizine, loratadine, and fexofenadine. In more severe cases, oral sedating H1 antagonists may be useful. These include diphenhydramine and cyproheptadine. Adding an oral H2 antagonist may be helpful for persistent gastrointestinal symptoms. These include cimetidine, ranitidine, and famotidine (Paller & Mancini, 2006).

Another treatment of gastrointestinal symptoms is oral chromolyn sodium, although it has not been studied extensively in children. Psoralen plus UVA can be effective for UP, cutaneous mastocytosis, and systemic mastocytosis. Aspirin and nonsteroidal anti-inflammatory drugs can cause mast cell degranulation, but they also reduce flushing in some patients. Potent topical steroids applied with occlusion can ameliorate or clear mastocytomas. Short courses of oral prednisone can be used for temporary symptom relief. Cyclosporin and low-dose methotrexate have been used in adults with aggressive forms of systemic mastocytosis (Molderings, Brettner, Homann, & Afrin, 2011; Paller & Mancini, 2006). Finally, patients who experience intermittent hypotension should carry an epinephrine pen at all times for emergency use (Paller & Mancini, 2006).

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SUMMARY

One month after his initial presentation, the patient returned to the dermatology clinic for a follow-up examination. At that time, his mother stated that the rash was getting worse. She reported that the patient was developing a higher number of lesions, more frequently (Figures 2–6). He was still without itch, fever, diarrhea, weight loss, or pain and was otherwise healthy. The patient’s mother denied any other signs or symptoms of UP and stated that she was unaware of any triggers, such as heat, hot baths, or stress. She was visibly nervous about her son’s skin condition and was also concerned that his disease seemed to be worsening. After a lengthy discussion with the patient’s mother about the benign nature of UP, she was reassured. The patient was started on oral cetirizine at bedtime.

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FIGURE 5.
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FIGURE 6.
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Since the last visit, the patient has continued to have numerous mastocytomas. These lesions occasionally become inflamed and raised, primarily when the patient’s temperature is elevated. The patient is monitored every 6 months in the dermatology clinic to screen for systemic involvement. This screening includes a thorough review of systems and a physical examination. His pediatrician is aware of his diagnosis, and she monitors him as well, including checking his CBC regularly. He is expected to outgrow this condition sometime during adolescence.

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REFERENCES

Almahroos M., Kurban A. K.. (2003);. Management of mastocytosis. Clinics in Dermatology. , 21:(1), 274–277.

Alto W. A., Clarcq L.. (1999);. Cutaneous and systemic manifestations of mastocytosis. American Family Physician. , 59:(11), 3047–3054.

Avshalumov K., Pichardo R., Jorizzo J. L., Sangueza O. P., Goldenberg G.. (2008);. Bullous mastocytosis: Report of a patient and a brief review of the literature. American Journal of Dermatopathology. , 30:(5), 455–457.

Bains S. N., Hsieh F. H.. (2010);. Current approaches to the diagnosis and treatment of systemic mastocytosis. Annals of Allergy, Asthma and Immunology. , 104:(1), 1–10.

Barete S., Assous N., de Gennes C., Grandpeix C., Feger F., Palmerini F, Frances C.. (2010);. Systemic mastocytosis and bone involvement in a cohort of 75 patients. Annals of the Rheumatic Diseases. , 69:(10), 1838–1841.

doi: 10.1136/ard.2009.124511


Jappe U., Aumann V., Mittler U., Gollnick H.. (2003);. Familial urticaria pigmentosa associated with thrombocytosis as the initial symptom of systemic mastocytosis and Down’s syndrome. Journal of the European Academy of Dermatology and Venereology. , 17:(6), 718–722.

Longley B. J., Morganroth G. S., Tyrrell L., Gang-Ding T., Anderson D. M., Williams D. E., Halaban R.. (1993);. Altered metabolism of mast-cell growth factor (c-kit LIGAND) in cutaneous mastocytosis. The New England Journal of Medicine. , 328:(18), 1302–1307.

Molderings G. J., Brettner S., Homann J., Afrin L. B.. (2011);. Mast cell activation disease: A concise practical guide for diagnostic workup and therapeutic options. Journal of Hematology and Oncology. , 4:(10).

doi: 10.1186/1756-8722-4-10.


Paller A. S., Mancini A. J.. (2006); . Hurwitz clinical pediatric dermatology. ( 3rd ed.). Philadelphia, PA: Elsevier Saunders.

Pardanani A., Tefferi A.. (2010);. Systemic mastocytosis in adults: A review on prognosis and treatment based on 342 Mayo Clinic patients and current literature. Current Opinion in Hematology. , 17:(1), 125–132.

Skrabs C. C.. (2002);. Darier sign: A historical note. Archives of Dermatology. , 138:(9), 1253–1254. http://archderm.jamanetwork.com/article.aspx?articleid=478962

Retrieved from http://archderm.jamanetwork.com/article.aspx?articleid=478962


Sperr W. R., Jordan J. H., Fiegl M., Escribano L., Bellas C., Dirnhofer S., Valent P.. (2002);. Serum tryptase levels in patients with mastocytosis: Correlation with mast cell burden and implication for defining the category of disease. International Archives of Allergy and Immunology. , 128:(2), 136–141.

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Keywords:

Cutaneous Mastocytosis; Mast Cell; Mastocytoma; Mastocytosis; Systemic Mastocytosis; Urticaria Pigmentosa

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