What is Responsible For This Young Woman’s Persistent Macules?

History

A 21-year-old female presented with a 4-year history of numerous reddish brown macules on her trunk and extremities. She stated that some lesions were raised and pruritic. Her history was significant for frequent tanning, both outside and in tanning booths. She denied systemic symptoms, including syncope, flushing, hypotension, bone pain, nausea, vomiting, abdominal pain, diarrhea, and weight loss. She was otherwise healthy with no significant past medical or surgical history. 

She was not taking any prescription or over the counter medications and was not allergic to any medications. She denied alcohol and tobacco use, as well as any significant family history. 

Physical Examination

On exam, the patient was noted to have numerous hyperpigmented macules, each measuring 6 mm or less, scattered diffusely on the trunk and extremities (Figures 1 and 2). There was no obvious Darier’s sign. The remainder of the exam was negative. Two punch biopsies were completed, one from the left flank and one from the left abdomen.

Laboratory Tests

Laboratory results showed a normal complete blood count, chemistry panel, and liver function tests. They also demonstrated a normal level of IL-6 level, 1.08 pg/mL, and a mildly elevated serum tryptase at 17 ng/mL. 

Pathology of both the biopsies revealed normal epidermis with slightly telangiectatic vessels in the superficial dermis, scattered eosinophils, and mildly increased perivascular mast cells. 

What’s Your Diagnosis? 

A. Secondary syphilis

B. Mastocytosis

C. Insect bites

D. Contact dermatitis

Answer: Mastocytosis

This patient’s presentation, laboratory test results, and pathology were consistent with the diagnosis of cutaneous mastocytosis, more specifically, telangiectasia macularis eruptive perstans (TMEP). For symptom management, 2-3 months of UVA-1 treatment was recommended. It was unlikely that this patient had systemic disease, but a bone marrow biopsy was considered as her symptoms began in adulthood. 

Discussion

Mastocytosis refers to a heterogenous group of rare disorders characterized by the presence of excessive mast cells in 1 or more tissues. Mast cells store histamine in granules, which is released by scratching the lesions or ingesting certain agents. Mast cell degranulation may cause episodic flushing, dyspepsia, diarrhea, abdominal pain, musculoskeletal pain, or hypotension. The most frequent site of organ involvement with all forms of mastocytosis is the skin. 

Children are more likely to have a benign course, with the majority having cutaneous manifestations only. Adults appear to have a more persistent course due to a higher likelihood of systemic disease. Cutaneous mastocytosis (CM) is the most common form and presents as mast cell hyperplasia limited to the skin. Systemic mastocytosis (SM) comprises multiple distinct entities in which mast cells infiltrate the skin and/or other organs.^1,2

The 4 clinical variants of CM are: 

• Urticaria pigmentosa. It is the most common form of skin manifestation in children and adults and may appear as yellow to reddish-brown macules, slightly raised papules or plaques. It is generally seen on the upper and lower extremities, but the chest and abdominal wall may also be affected. It is rare on the palms, soles, face, scalp, and other sun-exposed areas. Darier’s sign can be elicited.

• Diffuse cutaneous erythrodermic mastocytosis. It is a rare, generalized form of cutaneous disease. Diffuse erythrodermic cutaneous mastocytosis appears as thickened, reddish brown edematous skin with an orange peel texture. Bullae and blisters are common, and systemic symptoms can be severe.

• Isolated mastocytoma. Isolated mastocytoma is a larger solitary collection of mast cells. There may be 1 or multiple lesions that present as reddish brown nodules or plaques. Darier’s sign can be elicited. Most occur on the extremities and spare the palms and soles. These lesions may spontaneously involute.²

• Telangiectasis macularis eruptiva perstans. TMEP is the rarest cutaneous form. It is more frequent in adults with a clinical picture characterized by brownish erythematous macules, telangiectasia, and a diameter between 2 mm and 6 mm. The usual location of lesions is the chest and extremities. Darier’s sign is absent in most cases. 

Histologically, TMEP is characterized by a small mononuclear infiltrate, containing increased numbers of perivascular mast cells. Systemic involvement may be seen and bone marrow biopsy should be considered.³ High tryptase serum levels may be an indicator of systemic involvement. 

In a study with 52 patients, the prevalence of bone marrow biopsy samples compatible with SM increased, following the same proportion of tryptase level. The biopsy specimens were 100% positive when the tryptase level was greater than 75 ng/mL and 50% positive when the tryptase levels were 20 to 75 ng/mL.^4,5 

Treatment

Treatment is largely dependent on the presence of systemic involvement or clinical symptoms and is directed primarily at alleviating symptoms since there is no cure for the disorder. H1 antagonists are used to control pruritis and urticaria. Short-term glucocorticoids, oral cromolyn sodium, and proton pump inhibitors may be used depending on the presence and severity of clinical symptoms. It is essential to educate patients to identify and avoid triggers that induce mast cell degranulation, such as exposure to sunlight, extreme temperatures, alcohol, and drugs. Topical or intralesional injection of corticosteroids and psoralen + UVA treatment may also be considered.^3,6

Outcome of the Case

This patient was referred and evaluated by hematology and oncology. A bone marrow biopsy was not recommended at that time due to the fact that the patient did not have any signs of systemic disease other than a mildly elevated tryptase level. A bone marrow biopsy would be recommended if cytopenias or other signs of systemic disease developed. 

Imatinib and prednisone were not recommended, as there was no evidence of cytopenias to suggest a leukemic variant. Cetirizine and diphenhydramine were initiated for relief of pruritis. The patient declined treatment with UVA-1. The patient was scheduled for follow-up in 6 months.

References:

1. Habif T. Clinical Dermatology: A Color Guide to Diagnosis and Therapy. 5th ed. Maryland Heights, MO: Mosby Elsevier; 2010:211-216.

2.McNeill O, Katelaris CH. Mastocytosis—where are we now? World Allergy Organization. 2011.  www.worldallergy.org/professional/allergic_diseases_center/mastocytosis/. Accessed October 2014.

3.Costa, DL, Moura HH, Rodrigues R, et al. Telangiectasia macularis eruptiva perstans—a rare form of adult mastocytosis. J Clin Aesthet Dermatol. 2011;4(10):52-54.

4.Nguyen NQ. Telangiectasia macularis eruptiva perstans. Dermatol Online J. 2004;10(3):1.

5.Schwartz LB, Irani AM. Serum tryptase and the laboratory diagnosis of systemic mastocytosis. Hematol Oncol Clin North Am. 2000;14(3):641-657.

6.Alto WA, Clarcq L. Cutaneous and systemic manifestations of mastocytosis. Am Fam Physician. 1999;59(11):3047-3054.