Cutaneous Mastocytosis Variants

An international consensus task force of mast cell disorder specialists has recently proposed updates to the diagnostic criteria and classification for cutaneous disease.¹ Typical skin lesions found in mastocytosis, along with a positive Darier’s sign (see below), is the major criterion for diagnosing skin involvement in patients with mastocytosis. The two minor criteria are identified via skin lesion biopsy: increased mast cell numbers and the presence of an (activating) KIT mutation.^{1, 2} Cutaneous mastocytosis (CM) includes maculopapular cutaneous mastocytosis (MPCM), also known as urticaria pigmentosa (UP), diffuse cutaneous mastocytosis (DCM), and cutaneous mastocytoma.¹ The taskforce recommends that telangiectasia macularis eruptiva perstans (TMEP) be removed as a separate category because, although some adult patients may have telangiectatic lesions on their chest, shoulders, neck and back, they may also demonstrate maculopapular lesions in other places, therefore fulfilling criteria for MPCM.

Most cases of pediatric mastocytosis fall into one of the above categories and may or may not include symptoms of systemic mast cell activation, including anaphylaxis, as a result of mediators released from the skin.^{3, 4} Pediatric CM encompasses a variety of clinical manifestations. In children, some forms of CM will spontaneously resolve, some will go on to be diagnosed as indolent systemic mastocytosis (ISM), with a smaller percentage identified as well-differentiated systemic mastocytosis (WDSM).⁵

In most adults with skin lesions typical for mastocytosis (in particular, the maculopapular type), systemic disease will ultimately be found, leading to a diagnosis of systemic mastocytosis, usually in an indolent form (indolent systemic mastocytosis).^{1, 6}

Definitions^{1, 7}

Darier’s sign is an important diagnostic finding of patients with mastocytosis. It can be elicited by stroking an existing CM lesion with a wooden tongue depressor, approximately 5 times with moderate pressure. Within a few minutes, a wheal and flare reaction of the lesion will be seen. A positive Darier’s sign is usually seen in pediatric patients, but not always in adults. It may be decreased by treatment with antihistamines. If the testing procedure for Darier’s sign is not done properly, false positives or false negatives may result. Darier’s sign is to be applied to the evaluation of fixed cutaneous lesions except in the case of a pediatric patient with cutaneous mastocytoma or nodular lesions. Testing for Darier’s sign may provoke a systemic reaction and should either be performed with the greatest of caution or avoided.

Dermatographism is a skin reaction characterized by a wheal and flare response when normal skin, not affected by skin lesions, is stroked with a tongue depressor, finger nails or other instrument. The nick-name for dermatographism is skin writing disease.

A macule is a lesion that is flat and even with the surrounding skin, identified by a change in color compared to the surrounding skin.

A papule is a small bump or elevated lesion, up to 1 cm in diameter, containing no visible fluid.

A nodule is a growth of abnormal tissue just below the skin.

A bulla is a large blister filled with fluid.

Telangiectasia is a vascular lesion formed by dilatation of a group of small blood vessels.

Variants of Cutaneous Mastocytosis

Maculopapular Cutaneous Mastocytosis (MPCM)/Urticaria Pigmentosa (UP)¹

• May be seen in infants, children or adults
• Adults presenting with maculopapular lesions have a very high likelihood of systemic disease, most frequently indolent systemic mastocytosis (ISM)
• Rarely, an adult presents with maculopapular lesions who does not have systemic disease, and has a diagnosis of MPCM
• Red maculopapular lesions tend to wheal when scratched (positive Darier’s sign)
• Blister formation can occur with rubbing or stroking of lesion and is associated with pruritis⁸
• Encompasses several clinical entities with different outcomes, including: pitted melanotic macules, reddish brown telangiectatic macules, lightly pigmented papules, brownish papules, and small nodules
• This group is divided into two sub-variants
  • Monomorphic variant
    • Mostly seen in adults and in a small subgroup of children
    • Small maculopapular lesions, similar in shape, size and color
    • Adults most typically express the KIT D816V mutation in exon 17 of the KIT gene
    • In adults, thigh, axilla, trunk, extremities and neck may be involved
    • 95% of adults diagnosed with ISM, 50% with advanced systemic mastocytosis [systemic mastocytosis with an associated clonal hematologic non-mast cell lineage disease (SM-AHNMD or SM-AHN) or aggressive systemic mastocytosis (ASM)] and less than 50 % of mast cell leukemia patients exhibit this variant
    • Children presenting with this form may have increased serum tryptase and a tendency toward systemic disease that persists into adulthood
    • The type of lesions can vary during the course of the disease, i.e., nodules during infancy may turn into plaques at age 6
  • Polymorphic variant
    • Mostly seen in children
    • Can be macular, plaque or nodular, with lesions of variable shape, color and size
    • Although, children typically express mutations in exon 8, 9, 11 or 17 of the KIT gene, KIT mutations may be negative
    • Usually involving head, neck and extremities
    • May involve blistering upon irritation until 3 years of age
    • Prognosis is favorable with regression of disease in adolescence or young adulthood

Diffuse Cutaneous Mastocytosis (DCM)¹

• Skin thickened, hyperpigmented and diffusely infiltrated
• Can involve up to 100% of the skin with the trunk, head and scalp heavily affected
• Can appear at birth or early infancy; may persist into adulthood, possibly as well differentiated systemic mastocytosis (WDSM)⁵
• Blisters, some of which are hemorrhagic, and bullae may be present and dermatographism may be prominent
• Flushing is a common symptom
• Tryptase may be elevated due to increased mast cell burden in the skin and can be indicative of WDSM⁵

Cutaneous Mastocytoma¹

• Usually present at birth
• Elevated lesion(s) (up to a total of three lesions) which usually resolves during childhood
• Four cutaneous mastocytomas or more become a diagnosis of MPCM
• Multiple mastocytomas may evolve into adult WDSM⁵