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Urticaria Pigmentosa/ Mastocytosis

Overview

Mastocytosis results from systemic or localized mast cell proliferation. The natural history and pathogenesis of cases occurring in childhood (before age 2) and cases occurring in adults is distinctly different. Childhood cases are usually solitary mastocytomas, less commonly generalized papules, and rarely diffuse cutaneous mastocytosis. In virtually all cases the condition spontaneously involutes by puberty. In adults widespread papules is the most common presentation, Adults have the potential to develop systemic lesions, although most have indolent systemic mastocytosis which has a benign natural history. Therapy is determined by the symptoms caused by the mast cell proliferation, and the pattern of involvement (cutaneous versus systemic).

Localized mastocytosis (solitary mastocytoma)

Even though this is a solitary cutaneous lesion, flushing, diarrhea, pruritus, GI complaints, and headaches can result from circulating mast cell products released when the mastocytoma is rubbed or irritated. These symptoms may require treatment.

First steps

Children with localized mast cell tumors are best treated by parental reassurance. Most lesions slowly resolve spontaneously.

Alternative Steps

  1. If a solitary mastocytoma is causing generalized symptomatology as outlined above, treatment is appropriate. Occlusion with a semipermeable (hydrocolloid) dressing may result in improvement of symptoms without requiring systemic treatment.
  2. Apply a superpotent topical steroid with occlusion to the mastocytoma nightly. Response is usually noted at about 3 weeks. If this does not reduce the number of mast cells sufficiently, try intralesional triamcinolone 5 mg/cc to the lesion.
  3. In an occasional symptomatic case, excision of the lesion may be appropriate.
  4. If the child has symptoms of histamine excess, hydroxyzine, nonsedating antihistamines, H2 blockers, and nifedipine can be attempted.

Systemic mastocytosis

Adults usually harbor a mutation in c-KIT and often have systemic involvement. However it is frequently indolent and does not progress. This is termed indolent systemic mastocytosis. Children less commonly have systemic involvement. Symptoms caused by systemic mastocytosis are either related to released mediators–pruritus, flushing, whealing, episodic hypotension and flushing, GI symptoms (cramps and peptic ulcer disease), and headache. Mast cell lesions themselves may present a cosmetic problem, cutaneous hyperpigmentation. For these reasons, therapy is directed against symptoms caused by mediator release or may be intended to relieve the cosmetic alterations.

Treatment of Mediator release-related symptoms

First steps

  1. For patients with pruritus, flushing, whealing, and hypotension: Treat with oral H1 antihistamine to maintain pharmacologic action 24 h/day. Oral hydroxyzine 25-50 mg four times daily for adults and 1-2 tsp three times daily. in children is excellent, but frequently causes sedation. Non sedating antihistamines (fexofenadine 60 mg twice daily, loratadine 10 mg daily, or cetirizine 10 mg daily) may be efficacious and cause less sedation.
  2. Avoid drugs which cause mast cell release. These include aspirin, NSAIDs, morphine, iodine, d-tubocurarine, polymyxins, and decamethonium. Advise the patient to avoid alcohol if exacerbation of symptoms is observed.
  3. Have the patient carry EpiPen and wear a Medical Alert bracelet for emergency situations. Mastocytosis patients who have Hymenoptera stings can suffer anaphylaxis.

Subsequent Steps

  1. Reduce or maintain antihistamine at the dose necessary to control the patient’s symptoms, and maintain therapy indefinitely.
  2. If adequate control of symptoms is not possible, add an H2 antagonist (e.g., cimetidine 400 mg four times daily),
  3. Leukotriene antagonists such as Singulair 10 mg daily may be added
  4. Even though it is poorly absorbed, oral cromolyn sodium (see below) may at times help pruritus associated with mastocytosis.

Ancillary steps

  1. For GI symptoms of cramping, and diarrhea, consider oral sodium cromolyn (Gastrocrom Ampules 100 mg each). They are consumed by mixing the contents of the ampule(s) in a glass of water (adult dose: 200 mg or two ampules, four times daily, and for children age 3-13, 100 mg four times daily
  2. For peptic ulcer disease prescribe a proton pump inhibitor and/or H2 antihistamine

Subsequent Steps

  1. Phototherapy (PUVA or UVA1) may be useful. Treat patients 2-4 x/week until symptoms are relieved. Remission may last for several months.
  2. High potency topical steroids with nightly occlusion (at least 4-6 hours per day) for 6 weeks may improve symptoms and the appearance of the lesions.
  3. Short courses (several weeks) of systemic corticosteroids (25 mg-50 mg/d Prednisone) may be used for severe flares.
  4. Interferon alpha starting at 3 million units three times weekly may be used in patients with severe, refractory symptoms alone or in combination with systemic glucocorticoids. Osteopenia from mast cell heparin release may be managed with interferon alone.
  5. For patients with aggressive mastocytosis, Cladribine cytoreductive therapy may be considered.

Patients with Cosmetic Concerns

Mast cells release mediators which stimulate overlying melanocytes to produce more melanin, resulting in marked hyperpigmentation. This is most effectively treated with phototherapy with or without topical steroids as outlined above. Since both phototherapy and occlusive topical steroid treatments may produce sustained improvements, only intermittent cycles of treatment (every 6-12 months) may be required.