Knowledge on rare diseases and orphan drugs

DCM accounts for around 1-2% of all cases of CM and almost exclusively presents during infancy, mainly in the neonatal period. Less than 30 cases of neonatal onset DCM have been described in the literature so far.

The majority of patients present with generalized erythroderma with a reddish to brown-orange discoloration and extensive bullae. The blisters may become hemorrhagic, may be grouped or linear, and are usually located on the trunk, extremities or scalp. The bullous lesions typically resolve by 3-5 years of age. A small number of patients have been reported with yellow-orange infiltrated and xanthogranuloma-like abnormalities as the presenting feature of DCM (Pseudoxanthomatous DCM). Over time, the skin becomes thickened and has a doughy consistency. Other cutaneous manifestations may include pruritus, urticaria, a positive Darier's sign and marked dermographism. Systemic symptoms (including flushing, hypotension, severe anaphylaxis, hepatomegaly, diarrhea and gastrointestinal bleeding) appear to be more common in DCM than in other forms of CM with systemic symptoms.

DCM generally occurs sporadically but a few familial cases have been reported. Mutations in the KIT gene (4q11-q12) have been identified in patients with some forms of mastocytosis and mutations in this gene have been identified in a few patients with DCM.

Diagnosis may be suspected on the basis of the clinical findings and can be confirmed by histological examination using mast cell stains (Giemsa and toluidine blue) or immunohistochemical staining for tryptase or kit. Measurements of serum tryptase and urinary N-methylhistamine levels may also be useful for diagnosis and follow-up.

For patients presenting with widespread bullous lesions the differential diagnosis should include bullous congenital ichthyosiform erythroderma, early-onset forms of epidermolysis bullosa, Poikiloderma of Kindler and staphylococcal scalded skin syndrome.

Treatment is symptomatic with administration of antihistamines (H1 and H2 in cases with gastrointestinal symptoms), topical steroids and mast cell membrane stabilizers. Factors that trigger mast cell degradation (non-steroidal anti-inflammatory drugs, physical stimuli, emotional stress, insect venom and certain foods) should be avoided. Oral steroid treatment and photochemotherapy with UVA therapy may be of benefit but should only be used in infancy in severe cases that are refractory to alternative treatment options. Close follow-up is required for early detection and management of systemic symptoms.

Although spontaneous resolution of the bullous lesions occurs before 5 years of age in most DCM patients, the prognosis is variable: DCM is associated with an increased risk of systemic involvement with life-threatening manifestations (gastrointestinal bleeding, anaphylaxis etc.). The association of DCM with mast cell leukemia has been reported in a few patients and persistence of DCM into adult life with transformation to indolent systemic mastocytosis has been described.

Last update: June 2013 - Expert reviewer(s): Pr A.P. [Arnold] ORANJE