CLINICAL HISTORY:

Signs and symptoms:  A 23-year-old female presents for evaluation of multiple hyperpigmented macules and papules on her thighs, arms, chest and abdomen. They have been present for approximately one year and are mildly pruritic. Review of systems reveals fatigue for two weeks. She has no significant past medical history and family history is non-contributory. She does report an allergy to bee stings.

Previous Treatment:  none

Other information: 

PHYSICAL EXAM:

Physical exam reveals scattered 2-5 mm orange to tan colored macules and papules on her bilateral thighs, upper extremities, abdomen and chest. These lesions show dermatographism with positive Darier’s sign. Hyperpigmentation of the lesions is persistent with diascopy. No hepatosplenomegally or lymphadenopathy are palpable.

LABORATORY TESTS:

Serum tryptase level was 70.3 ng/ml initially and 57.1 ng/ml on a repeat one week later (normal less than 11.5 ng/ml). CBC was within normal limits.

DERMATOHISTOPATHOLOGY:

3 mm punch biopsy demonstrated superficial perivascular infiltrate of lymphocytes around slightly ectatic vessels. A toluidine blue stain showed significantly increased mast cells within the papillary dermis (Figure 3). The above is consistent with urticaria pigmentosa, macular type.

Figure 3

DIFFERENTIAL DIAGNOSIS:

1.   Systemic mastocytosis
2.   Urticaria pigmentosa
3.   Amyloidosis, macular
4.   Amyloidosis,nodular localized cutaneous
5.   Carcinoid

SCROLL DOWN FOR ANSWER AND DISCUSSION.

CORRECT DIAGNOSIS:

Lymphocytoma

DISCUSSION:

Mastocytosis was originally described by Nettleship and Tay who reported a 2-year-old girl with hyperpigmented papules that spontaneously urticated. Paul Ehrlich discovered the mast cell in 1877, and a year later, Sangster described a patient with pruritus, urticaria, and pigmentation and labeled it uritcaria pigmentosa. It was later demonstrated by Unna that mast cells were responsible for this eruption and some 60 years later a first case of systemic mastocytosis was reported.

Mastocytosis can be present at birth or acquired any time during the adulthood. According to Bolognia approximately 55% of mastocytosis patients develop their disease by the time they are 2 years old, and another 10% have onset between the ages of 2 and 15 years. The disorder has equal distribution among all races and affect males and females equally.

The most common type of mastocytosis is cutaneous mastocytosis which predominately affects children and presents as a mast cell hyperplasia limited to the skin. Cutaneous mastocytosis is further divided into four types with urticaria pigmentosa being the most common. The other three types include solitary mastocytoma, diffuse cutaneous mastocytosis, and telangiectasia macularis eruptiva perstans (TMEP). Symptoms of cutaneous mastocytosis include pruritus, flushing, urticaria, and dermatographism.

In the systemic type of mastocytosis, the mast cells infiltrate the skin and other organs. The diagnosis of systemic mastocytosis is based on the presence of one major criterion and three minor criteria. Major criteria include the presence of multifocal dense infiltrates of >15 mast cells in bone marrow and/or other extracutaneous organs. Minor criteria include atypical mast cell morphology, the expression of CD2 and CD25 surface markers in c-kit-positive mast cells from bone marrow or other organs, elevated serum tryptase levels >20 ng/ml, and the presence of a c-kit mutations on bone marrow or lesional tissue. Most patient with systemic mastocytosis have indolent disease but minority may have more aggressive disease with poor prognosis. Systemic mastocytosis symptoms include cutaneous symptoms in association with abdominal pain, nausea, vomiting, diarrhea, bone pain, syncope, and neuropsychiatric symptoms. These symptoms can be exacerbated by exercise, heat, or local trauma to skin lesions as well as alcohol, salicylates, NSAIDs, narcotics, polymyxin B sulfate, and anticholinergic medications.

Treatment of patients with mastocytosis is geared towards alleviation of symptoms. Patients should be cautioned to avoid known mast cell degranulators including the above mentioned as well as excessive friction to the lesions and bug stings to which patient is allergic. Even though a number of systemic anesthetics are implicated as known mast cell degranulators, local injections of lidocaine can be used safely in these patients. Histamine receptor blockers, H1 and H2 are helpful in controlling many of the symptoms associated with mastocytosis. Psoralen plus UVA (PUVA) therapy has been used to control the pruritus but it does not alter other symptoms associated with the disorder. Potent topical corticosteroids under occlusion, as well as intralesional injections of triamcinolone acetonide have also been used and are successful at alleviating pruritus. Interferon-α2b has also been used in some patients. Certain patients with systemic mastocytosis may develop hypotension following a mast cell degranulator exposure and therefore should carry an EpiPen with them at all times. If patients have a more aggressive type of systemic mastocytosis, their prognosis is limited by associated hematologic malignancy and treatment is aimed at treating the associated malignancy.

TREATMENT:

Patient was referred to allergist for testing. She was found to be significantly atopic with positive reactions to ragweed, weeds, grass, dust mite and cats. Her elevated serum tryptase also indicated systemic involvement, which prompted a bone marrow biopsy. Patient’s bone marrow biopsy further confirmed the diagnosis of systemic mastocytosis. Patient has no GI symptoms, bone pain, diarrhea, etc. She is taking fexofenadine in the morning and cetirizine in the evening. She also has an epinephrine pen and was instructed to be cautious with alcohol, NSAIDs, aspirin, bee stings, local trauma to skin lesion, etc.

REFERENCES:

1. Soter NA. The Skin in Mastocytosis. J Invest Dermatol. 1991; 96 (3): 32S-39S.

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3. Johnson MR, Verstovsek S, Jorgensen JL, Manshouri T, Luthra R, et al. Utility of the World Health Organization Classification Criteria for the Diagnosis of Systemic Mastocytosis in Bone Marrow. Mod Pathol. 2009; 22: 50-57.

4. Metcalfe, D. D. The Mastocytosis Syndrome. Fitzpatrick’s Dermatology in General Medicine New York (NY) McGraw-Hill; 2003. p. 1603-1608.

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8. Lim K, Tefferi A, Lasho TL, Finke C, Patnaik M, et al. Systemic Mastocytosis in 342 Consecutive Adults: Survival Studies and Prognostic Factors. Blood. 2009; 113 (23): 5727- 5736.

9. Inamadar A, Palit A. Cutaneous Mastocytosis: Report of Six Cases. Indian J Dermatol Venereol Leprol. 2006; 72(1): 50-53.

10. Briley LD, Phillips CM. Cutaneous Mastocytosis: A Review Focusing on the Pediatric Population. Clin Pediatr (Phila). 2008; 47 (8):757-761.

11. Peterson AH. Systemic Mastocytosis: Case Report and Literature Review. J Natl Med Assoc. 1984; 76 (5): 469-473.
12. Metcalfe DD. Classification and Diagnosis of Mastocytosis: Current Status. J Invest Dermatol. 1991; 96(3): 2S-4S.

13. Bains SN, Hsieh FH. Current Approaches to the Diagnosis and Treatment of Systemic Mastocytosis. Ann Allergy Asthma Immunol. 2010; 104: 1-10.

14. Stevens EC, Rosenthal NS. Bone Marrow Mast Cell Morphologic Features and Hamatopoietic Dyspoiesis in Systemic Mast Cell Disease. Am J Clin Pathol. 2001; 116: 177-182.

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