AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Mastocytosis is a disorder characterized by mast cell proliferation and accumulation within various organs, most commonly the skin.

The World Health Organization (WHO) classification of mastocytosis includes the following^{1, 2}:

• Cutaneous mastocytosis
• • Urticaria pigmentosa 
  • Maculopapular cutaneous mastocytosis 
  • Diffuse cutaneous mastocytosis 
  • Mastocytoma of skin
• Indolent systemic mastocytosis
• Systemic mastocytosis with an associated (clonal) hematologic non–mast cell lineage disease
• Aggressive systemic mastocytosis
• Mast cell leukemia
• Mast cell sarcoma
• Extracutaneous mastocytoma^{1, 2}

When a UP or mastocytoma lesion is stroked, it typically urticates, becoming pruritic, edematous, and erythematous. This change is referred to as the Darier sign, which is explainable on the basis of mast cell degranulation induced by physical stimulation. Uncontrolled stroking of mastocytomas should be avoided in patients who have had a systemic reaction such as miosis and asthmalike symptoms in their past.³ The Darier sign usually is not positive in patients with TMEP because the lesions are paucicellular, and, therefore, mast cells may not be present in sufficient numbers for significant degranulation to occur.

Pathophysiology

Whether mastocytosis is a hyperplastic reaction to an unknown stimulus or whether it is a neoplastic condition is unknown. Increased local concentrations of soluble mast cell growth factor in lesions of CM are believed to stimulate mast cell proliferation, melanocyte proliferation, and melanin pigment production. The induction of melanocytes explains the hyperpigmentation that commonly is associated with cutaneous mast cell lesions. Impaired mast cell apoptosis has been postulated to be involved, as evidenced by up-regulation of the apoptosis-preventing protein BCL-2 demonstrated in patients with mastocytosis. Activating mutations of the proto-oncogene c-kit have been identified but do not explain the initiation of the disease.⁴ Interleukin 6 levels have been shown to be elevated and correlated with disease severity, indicating interleukin 6 is involved in the pathophysiology of mastocytosis.⁵

Associated systemic manifestations are believed to reflect the release of mast cell–derived mediators, such as histamine, prostaglandins, heparin, neutral proteases, and acid hydrolases. Symptoms and signs induced by mediators may include headache, flushing, dizziness, tachycardia, hypotension, syncope, anorexia, nausea, vomiting, abdominal pain, and diarrhea. The skeletal, hematopoietic, gastrointestinal (GI), cardiopulmonary, and central nervous systems may be involved either directly, via mast cell infiltration, or indirectly, via mast cell mediator release.

Frequency

United States

Of new patients visiting dermatology clinics, 0.1-0.8% have some form of mastocytosis.

International

The international incidence is not known to differ from the incidence observed in the United States.

Mortality/Morbidity

Most cases of UP in children resolve spontaneously, although acute extensive degranulation rarely can cause life-threatening episodes of shock. Patients with adult-  or adolescent-onset UP are more likely to have persistent disease and are at greater risk for systemic involvement. Juvenile-onset systemic mastocytosis has a malignant transformation rate as high as 7%, while adult-onset systemic mastocytosis has a malignant transformation rate as high as 30%.

Race

Most reported cases are in whites. The cutaneous lesions of most types of mastocytosis are less visible in persons with more heavily pigmented skin.

Sex

Mastocytosis affects males and females equally (no known sex predilection).

Age

Most patients with mastocytosis are children; 75% of cases occur during infancy or early childhood. Incidence peaks again in patients aged 30-49 years.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

Patients may present with cutaneous lesions, systemic symptoms of an acute nature, and/or chronic systemic symptoms.

• Most patients have pruritic cutaneous lesions.
• Some patients, especially those with extensive cutaneous disease, experience acute systemic symptoms exacerbated by certain activities or ingestion of certain drugs or foods. Possible systemic symptoms include flushing, headache, dyspnea, wheezing, rhinorrhea, nausea, vomiting, diarrhea, and syncope.
• Patients also may have chronic systemic symptoms involving various organ systems.
• • Involvement of the skeletal system may be manifested as bone pain or the new onset of a fracture.
  • Involvement of the central nervous system may produce neuropsychiatric symptoms, as well as nonspecific changes such as malaise and irritability.
  • GI involvement may yield weight loss, diarrhea, nausea/vomiting, and abdominal cramps.
  • Cardiovascular effects can include shock, syncope (resulting from vascular dilatation), or angina.
  • Anaphylactic reactions to hymenoptera stings may be the first sign of mastocytosis.

Physical

The most common physical findings in mastocytosis involve the skin, liver, spleen, and cardiovascular system.

• Skin - Lesion types
• • Macules, papules, nodules, and plaques (see Media File 4)
  • Blisters and bullae in children (see Media File 5)
  • Diffuse induration
  • Isolated nodule or tumor
• Skin - Distribution
• • Widespread symmetric distribution
  • Trunk involved more than extremities
  • Tendency to spare the face, scalp, palms, and soles; however, a patient with scarring alopecia has been reported⁶
• Skin - Lesion color, quantity, and size 
• • Yellow-tan to red-brown
  • From 1 to more than 1000
  • From 1 mm to several centimeters
• Skin - Special characteristics
• • Darier sign: Wheal and surrounding erythema develop in a lesion after rubbing it.
  • Dermatographism: In approximately half the patients, stroking macroscopically uninvolved skin produces dermographia.
  • Flushing: Flushing may occur spontaneously following skin stroke or after ingesting a mast cell degranulating agent.
• Liver - Possible hepatomegaly (present in 40% of adult patients with systemic mastocytosis)
• Spleen - Possible splenomegaly (present in 50% of patients with systemic mastocytosis)
• Cardiovascular - Hypotension and tachycardia

Causes

Mastocytosis probably is a hyperplastic response to an abnormal stimulus. Rare cases of familial UP have been recorded.⁷

DIFFERENTIALS

Section 4 of 11  

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• Clinical
• Differentials
• Workup
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• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Generalized eruptive histiocytoma
Histiocytosis X
Non-X histiocytosis of childhood
Secondary syphilis
Xanthogranuloma
Carcinoid⁸

WORKUP

Section 5 of 11  

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• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

In many patients, UP can be diagnosed when history and physical examination findings reveal the characteristic lesions that demonstrate the Darier sign. Usually, a skin biopsy is a necessary confirmatory test.

• CBC count: In systemic mastocytosis, CBC counts may reveal anemia, thrombocytopenia, thrombocytosis, leukocytosis, and eosinophilia.
• Plasma or urinary histamine level: Patients with extensive cutaneous lesions may have 24-hour urine histamine excretion at 2-3 times the normal level.
• Total tryptase level: Tryptase is a marker of mast cell degranulation released in parallel with histamine. Total tryptase levels in plasma correlate with the density of mast cells in UP lesions in adults with systemic mastocytosis. Patients with only CM typically have normal levels of total tryptase. Total tryptase values are recommended by the WHO as a minor criterion for use in the diagnostic evaluation of systemic mastocytosis.^{1, 2, 9} The total tryptase level in serum or plasma seems to be a more discriminating biomarker than urinary methylhistamine for the diagnosis of systemic mastocytosis.⁹ Most patients with systemic anaphylaxis of sufficient severity to result in hypotension have elevated serum or plasma beta-tryptase levels. During insect sting–induced anaphylactic hypotension, beta-tryptase levels in the circulation are maximal 15-120 minutes after the sting.⁹

WHO  criteria for diagnosis of systemic mast cell disease include the following:

• Major: Multifocal dense infiltrates of mast cells in bone marrow or other extracutaneous organs (>15 mast cells aggregating)
• Minor
• • Mast cells in bone marrow, or other extracutaneous organs show abnormal (spindling) morphology (>25%)
  • Codon 816 c-kit mutation D816V in extracutaneous organs
  • Mast cells in bone marrow express CD2, CD25, or both
  • Serum tryptase values greater than 20 ng/mL²

Imaging Studies

• Bone scan and radiologic survey: Obtain a bone scan and radiologic survey in nonpediatric patients or if the CBC count is abnormal in a young child. If a patient has skeletal system symptoms, perform a bone scan and radiologic survey to identify lytic bone lesions, osteoporosis, or osteosclerosis.
• GI workup (upper GI series, small bowel radiography, CT scanning, endoscopy): If a patient has GI symptoms, order a GI workup to identify peptic ulcers, abnormal mucosal patterns, or motility disturbances.

Other Tests

If a diagnosis of mastocytosis is uncertain, tests for elevated mast cell mediators and degradation products may help establish the diagnosis.

• Serum tryptase level
• • Tryptase levels are elevated in patients with mastocytosis.
  • Tryptase levels may be more useful than histamine levels, because histamine can be elevated in hypereosinophilic states.
• Urinary N-methylhistamine (NMH) and N-methylimidazoleacetic acid levels
• • These levels may be more specific and sensitive than urinary histamine levels.
  • NMH levels correlate directly with the extent of skin lesions.
  • NMH levels decrease with age; therefore, consider the patient's age when interpreting results.
• Urinary prostaglandin D₂ metabolite level
• • Even during asymptomatic periods, urinary prostaglandin D₂ metabolites levels may range from 1.5-150 times higher than normal levels.
  • This test is not widely available.

Procedures

• Bone marrow biopsy and aspirate: Perform bone marrow biopsy and aspirate in patients with UP if they have peripheral blood test abnormalities, hepatomegaly, splenomegaly, or lymphadenopathy to determine if they have an associated hematologic disorder.
• Biopsy: Inject an anesthetic agent without epinephrine adjacent to, not directly into, the lesion chosen as the biopsy specimen to avoid mast cell degranulation, which makes histologic examination difficult.

Histologic Findings

Examination reveals dermal mast cell infiltrates, especially in the papillary dermis around blood vessels (see Media File 6). Diagnosis of UP may require demonstration of mast cell granules using Giemsa stain (see Media File 7) or toluidine blue stain. The Leder stain is not dependent on intact mast cell granules.

Mast cell nuclei are round with surrounding ample cytoplasm producing a “fried egg” appearance. In TMEP, mast cells are brick shaped or spindle shaped. In nodular UP, mast cells are observed in dense aggregates and may extend through the entire dermis and into subcutaneous tissue. If the lesion from which the biopsy specimen was taken was traumatized during harvest, edema and eosinophil infiltrates may be present. The hyperpigmentation of CM is secondary to increased melanin in the basal cell layer and melanophages in the upper dermis.

Planar xanthoma has been described in association with mastocytomas.

TREATMENT

Section 6 of 11  

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• Follow-up
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Medical Care

Therapy is conservative and aimed at symptom relief because the prognosis for most patients with mastocytosis is excellent. None of the currently available therapeutic measures induces permanent involution of cutaneous or visceral lesions. Advise patients to avoid agents that precipitate mediator release, such as aspirin, nonsteroidal anti-inflammatory drugs, codeine, morphine, alcohol, thiamine, quinine, opiates, gallamine, decamethonium, procaine, radiographic dyes, dextran, polymyxin B, scopolamine, and D-tubocurarine. 

H1 and H2 antihistamines decrease pruritus, flushing, and GI symptoms. Oral disodium cromoglycate may ameliorate cutaneous symptoms, such as pruritus, whealing, and flushing, as well as systemic symptoms, such as diarrhea, abdominal pain, bone pain, and disorders of cognitive function. 

Cautious administration of aspirin to inhibit prostaglandin synthesis and maintain mast cell degranulation may be beneficial for patients with disease resistant to H1 and H2 antagonist therapy alone. The patient, premedicated with H1 and H2 antihistamines, may be started on small doses of aspirin, slowly titrated to reach a plasma level of 20-30 mg/100 mL. Initiate this treatment regimen in a controlled environment, because aspirin can induce mast cell mediator release and subsequent cardiovascular collapse.

Cutaneous lesions that involve a limited body area may be treated with a potent class 1 topical corticosteroid, with occlusion if required. Intralesional injections of small amounts of dilute corticosteroids may resolve skin lesions temporarily or indefinitely. The risk of skin atrophy and adrenocortical suppression resulting from the treatment is minimized by treating limited body areas during a single treatment session. Systemic corticosteroids are useful only in specific situations, such as ascites, malabsorption, and severe skin disease. Case reports have described complete remission of bullous mastocytosis with oral corticosteroids,¹⁰ but systemic therapy is often disappointing because the primary mode of action of corticosteroids is redistribution rather than death of mast cells.

Oral psoralen plus UV-A (PUVA) therapy results in general and cosmetic benefits in the treatment of CM, particularly TMEP; however, risks are involved, such as skin cancer if more than 200 treatments are required. PUVA rarely is required in children. Currently, PUVA is reserved for severe, unresponsive cases in adults. In a 2005 study, medium-dose UV-A1 therapy was shown to be as effective as high-dose UV-A1 in reducing symptoms and the number of mast cells in affected skin.¹¹

Medical alert bracelets should be made available, and an epinephrine self-injector demonstration should be performed and self-injector prescribed for patients with systemic mastocytosis. General anesthesia may be problematic in patients with systemic mastocytosis.¹² The treatment algorithm for systemic mastocytosis is complex, and the condition is primarily managed by a hematologist.^{12, 13}

Consultations

Consultation with a hematologist may be necessary for a bone marrow biopsy and staging. The WHO classification of systemic mastocytosis mandates a number of staging investigations to define the exact subtype of disease. Identification of ‘‘B’’ findings alone, such as the following, is indicative of a high systemic mastocytosis burden.

• Greater than 30% bone marrow mastocytosis  burden
• Serum tryptase level greater than 200 ng/mL 

The additional presence of ‘‘C’’ findings, such as the following, is diagnostic for the presence of aggressive disease.²

• Absolute neutrophil count less than 1000/µL
• Hemoglobin value less than 10 g/µL
• Platelet count less than 100 000/µL
• Hepatomegaly with ascites and impaired liver function
• Palpable splenomegaly with hypersplenism
• Malabsorption with hypoalbuminemia and weight loss
• Large-sized osteolysis or severe osteoporosis causing pathologic fractures or life-threatening organopathy in other organ systems definitively caused by an infiltration of the tissue by neoplastic mast cells

Diet

Traditionally, physicians have advised patients to avoid substances that induce mast cell mediator release, such as salicylates, crawfish, lobster, alcohol, spicy foods, hot beverages, and cheese. While evidence indicates that alcohol can cause adverse reactions, the role of the other foods mentioned above is hypothetical at this point and merits further investigation.

Activity

Advise patients to avoid certain physical stimuli, including emotional stress, temperature extremes, physical exertion, bacterial toxins, envenomation by insects to which the patient is allergic, and rubbing, scratching, or traumatizing the lesions of CM.

MEDICATION

Section 7 of 11  

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• Differentials
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• Follow-up
• Miscellaneous
• Multimedia
• References

Tailor therapy according to the patient's specific needs for symptomatic relief. Patients may be started on oral H1 antihistamine and/or oral disodium cromoglycate with or without the use of a potent topical steroid for selected cutaneous lesions. In patients with a limited number of lesions, intralesional corticosteroid injections are an additional therapeutic option. Oral histamine H2 antagonists may be administered in addition to an oral H1 antihistamine.

Drug Category: Antihistamines

Relieve pruritus and flushing.

Drug Category: Mast cell stabilizers

Cromolyn is a mast cell stabilizer that improves diarrhea, flushing, headaches, vomiting, urticaria, abdominal pain, nausea, and itching in some patients.

Drug Category: Histamine H2 antagonists

Addition of H2 antagonist to H1 antagonist helps control pruritus and whealing. In addition, GI symptoms associated with hyperchlorhydria, such as peptic ulcer disease and gastritis, respond well to this medication.

Drug Category: Vasopressors

For patients with systemic disease or extensive symptoms.

FOLLOW-UP

Section 8 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Inpatient Care

Emergency resuscitation or hospitalization may be required for severe syncope or hypotensive shock resulting from the sudden severe degranulation of many mast cells.

In/Out Patient Meds

Advise patients with systemic disease or extensive symptoms to wear a medical alert bracelet and carry injectable epinephrine in case of an acute event causing mast cell degranulation and subsequent shock. Adults have been reported with severe anaphylaxis after insect stings.

Complications

• Possible transformation into a hematologic malignancy
• Death secondary to mast cell degranulation
• Mast cell leukemia

Prognosis

The prognosis depends on the age of onset. Most patients with UP exhibit onset before age 2 years, which is associated with an excellent prognosis, often with resolution by puberty. The number of lesions diminishes by approximately 10% per year.

Disease onset after age 10 years portends a poorer prognosis, because late-onset disease tends to be persistent, is associated more often with systemic disease, and carries a higher risk of malignant transformation.

In patients with systemic mastocytosis, regression of UP is associated with a decreased frequency and severity of other symptoms. Bone marrow findings do not change with regression of UP.

Patient Education

Instruct patients about avoiding physical stimuli and substances that trigger the condition. Additionally, educate patients and/or parents about the signs and treatment of anaphylaxis, especially in patients with systemic disease or severe symptoms.

MISCELLANEOUS

Section 9 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
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• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

Cutaneous lesions in children have been mistaken for skin signs of child abuse.

MULTIMEDIA

Section 10 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Urticaria pigmentosa lesions on the face of a child. Courtesy of Lee H. Grafton, MD.
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Media file 2:  Urticaria pigmentosa lesions on the back of a child. Courtesy of Lee H. Grafton, MD.
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Media file 3:  Lesion on the scalp of an infant.
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Media file 4:  Lesion on the arm. Courtesy of Lee H. Grafton, MD.
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Media file 5:  Blistering lesion.
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Media file 6:  Hematoxylin and eosin stain revealing mast cells in the papillary dermis.
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Media file 7:  Giemsa stain revealing mast cells.
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REFERENCES

Section 11 of 11

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
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• Follow-up
• Miscellaneous
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• References

1. Valent P. Diagnostic evaluation and classification of mastocytosis. Immunol Allergy Clin North Am. Aug 2006;26(3):515-34. [Medline].
2. Patnaik MM, Rindos M, Kouides PA, Tefferi A, Pardanani A. Systemic mastocytosis: a concise clinical and laboratory review. Arch Pathol Lab Med. May 2007;131(5):784-91. [Medline].
3. Bussmann C, Hagemann T, Hanfland J, Haidl G, Bieber T, Novak N. Flushing and increase of serum typtase after mechanical irritation of a solitary mastocytoma. Eur J Dermatol. Jul-Aug 2007;17(4):332-4. [Medline].
4. Noack F, Escribano L, Sotlar K, Nunez R, Schuetze K, Valent P, et al. Evolution of urticaria pigmentosa into indolent systemic mastocytosis: abnormal immunophenotype of mast cells without evidence of c-kit mutation ASP-816-VAL. Leuk Lymphoma. Feb 2003;44(2):313-9. [Medline].
5. Brockow K, Akin C, Huber M, Metcalfe DD. IL-6 levels predict disease variant and extent of organ involvement in patients with mastocytosis. Clin Immunol. May 2005;115(2):216-23. [Medline].
6. Xu X, Solky B, Elenitsas R, Cotsarelis G. Scarring alopecia associated with mastocytosis. J Cutan Pathol. Oct 2003;30(9):561-5. [Medline].
7. Lappe U, Aumann V, Mittler U, Gollnick H. Familial urticaria pigmentosa associated with thrombocytosis as the initial symptom of systemic mastocytosis and Down's syndrome. J Eur Acad Dermatol Venereol. Nov 2003;17(6):718-22. [Medline].
8. Butterfield JH. Systemic mastocytosis: clinical manifestations and differential diagnosis. Immunol Allergy Clin North Am. Aug 2006;26(3):487-513. [Medline].
9. Schwartz LB. Diagnostic value of tryptase in anaphylaxis and mastocytosis. Immunol Allergy Clin North Am. Aug 2006;26(3):451-63. [Medline].
10. Verma KK, Bhat R, Singh MK. Bullous mastocytosis treated with oral betamethasone therapy. Indian J Pediatr. Mar 2004;71(3):261-3. [Medline].
11. Kinsler VA, Hawk JL, Atherton DJ. Diffuse cutaneous mastocytosis treated with psoralen photochemotherapy: case report and review of the literature. Br J Dermatol. Jan 2005;152(1):179-80. [Medline].
12. Wilson TM, Metcalfe DD, Robyn J. Treatment of systemic mastocytosis. Immunol Allergy Clin North Am. Aug 2006;26(3):549-73. [Medline].
13. Krishnan K, Ramu V, Krishnaswamy G, Vardhana H. Mastocytosis, Systemic. eMedicine from WebMD [serial online]. December 18, 2006;Accessed November 1, 2007. Available at http://www.emedicine.com/MED/topic1401.htm.
14. Allison MA, Schmidt CP. Reactivated urticaria pigmentosa. Cutis. Jul 1998;62(1):47-8. [Medline].
15. Braverman IM. Skin Signs of Systemic Disease. 3^rd ed. Philadelphia, Pa: WB Saunders; 1998:341-3.
16. Brockow K, Scott LM, Worobec AS, Kirshenbaum A, Akin C, Huber MM, et al. Regression of urticaria pigmentosa in adult patients with systemic mastocytosis: correlation with clinical patterns of disease. Arch Dermatol. Jun 2002;138(6):785-90. [Medline].
17. Eichenfield LF, Honig PJ. Blistering disorders in childhood. Pediatr Clin North Am. Aug 1991;38(4):959-76. [Medline].
18. Emanuel PD, Barton JC, Gualtieri RJ, Sams WM Jr. Urticaria pigmentosa and preleukemia: evidence for reactive mast cell proliferation. J Am Acad Dermatol. May 1991;24(5 Pt 2):893-7. [Medline].
19. Fitzpatrick TB, Johnson RA, Wolff K. Color Atlas and Synopsis of Clinical Dermatology. 3^rd ed. New York, NY: McGraw-Hill; 1997:562-5.
20. Freedberg IM, Eisen AZ, Wolff K, eds. Fitzpatrick's Dermatology in General Medicine. 5^th ed. New York, NY: McGraw-Hill; 1999:1902-8.
21. Gobello T, Mazzanti C, Sordi D, Annessi G, Abeni D, Chinni LM, et al. Medium- versus high-dose ultraviolet A1 therapy for urticaria pigmentosa: a pilot study. J Am Acad Dermatol. Oct 2003;49(4):679-84. [Medline].
22. Habif TP. Clinical Dermatology: A Color Guide to Diagnosis and Therapy. 3^rd ed. Philadelphia, Pa: Mosby; 1996:144-5.
23. Hartmann K, Artuc M, Baldus SE, Zirbes TK, Hermes B, Thiele J, et al. Expression of Bcl-2 and Bcl-xL in cutaneous and bone marrow lesions of mastocytosis. Am J Pathol. Sep 2003;163(3):819-26. [Medline].
24. Hartmann K, Henz BM. Mastocytosis: recent advances in defining the disease. Br J Dermatol. Apr 2001;144(4):682-95. [Medline].
25. Has C, Misery L, David L, Cambazard F. Recurring staphylococcal scalded skin syndrome-like bullous mastocytosis: the utility of cytodiagnosis and the rapid regression with steroids. Pediatr Dermatol. May-Jun 2002;19(3):220-3. [Medline].
26. Horny HP, Sotlar K, Valent P. Mastocytosis: state of the art. Pathobiology. 2007;74(2):121-32. [Medline].
27. Jordon RE. Immunologic Diseases of the Skin. East Norwalk, Conn: Appleton & Lange; 1991:245-8.
28. Kastrup EK. Drug Facts and Comparisons. St. Louis, Mo: Facts and Comparisons; 1998:1153-6, 1597-1600, 2057-67.
29. Leaf FA, Jaecks EP, Rodriguez DR. Bullous urticaria pigmentosa. Cutis. Nov 1996;58(5):358-60. [Medline].
30. Lever WF. Histopathology of the Skin. 8^th ed. Philadelphia, Pa: Lippincott-Raven; 1997:141-3.
31. Longley J, Duffy TP, Kohn S. The mast cell and mast cell disease. J Am Acad Dermatol. Apr 1995;32(4):545-61; quiz 562-4. [Medline].
32. Matsumoto M, Ikeda M, Takeya M, Kodama H. Plane xanthoma associated with multiple mastocytoma. Pediatr Dermatol. Sep-Oct 2007;24(5):E66-9. [Medline].
33. Roberts LJ 2nd, Sweetman BJ, Lewis RA, Austen KF, Oates JA. Increased production of prostaglandin D2 in patients with systemic mastocytosis. N Engl J Med. Dec 11 1980;303(24):1400-4. [Medline].
34. Schachner LA, Hansen RC. Pediatric Dermatology. 2^nd ed. New York, NY: Churchill Livingstone; 1995:852-8.
35. Soter NA. The skin in mastocytosis. J Invest Dermatol. Mar 1991;96(3):32S-38S; discussion 38S-39S. [Medline].
36. Van Gysel D, Oranje AP, Vermeiden I, de Lijster de Raadt J, Mulder PG, van Toorenenbergen AW. Value of urinary N-methylhistamine measurements in childhood mastocytosis. J Am Acad Dermatol. Oct 1996;35(4):556-8. [Medline].
37. van Toorenenbergen AW, Oranje AP. Comparison of serum tryptase and urine N-methylhistamine in patients with suspected mastocytosis. Clin Chim Acta. Sep 2005;359(1-2):72-7. [Medline].
38. Vlieg-Boerstra BJ, van der Heide S, Oude Elberink JN, Kluin-Nelemans JC, Dubois AE. Mastocytosis and adverse reactions to biogenic amines and histamine-releasing foods: what is the evidence?. Neth J Med. Jul-Aug 2005;63(7):244-9. [Medline].

Article Last Updated: Jan 8, 2008