Darier’s sign is a cutaneous reaction characterized by whealing and itching that occurs when pigmented macular lesions, typical of urticaria pigmentosa (cutaneous mastocytosis), are rubbed or irritated.

• The reaction results from histamine release from mast cells within the affected skin.

• A positive Darier’s sign presents as pruritic, erythematous, raised wheals surrounding the macules.

• This sign is considered pathognomonic for mastocytosis.

Pathophysiology

• Mast cells in the skin contain histamine, heparin, and other vasoactive mediators.

• Mechanical stimulation (rubbing or pressure) triggers mast cell degranulation, releasing histamine.

• Histamine causes:

  • Vasodilation → redness (erythema)

  • Increased vascular permeability → wheal formation

  • Nerve stimulation → pruritus

• The intensity of the reaction correlates with mast cell burden and activity.

Examination Technique

Patient Observation

• Identify pigmented macules or lesions typical of urticaria pigmentosa.

• Ensure patient is aware the test may provoke itching or temporary swelling.

Stimulation and Assessment

• Rub a lesion vigorously with the blunt end of a pen, tongue depressor, or similar object for 10–15 seconds.

• Observe for immediate development of erythematous, raised, pruritic wheals around the lesion.

• Record size, intensity, and duration of whealing.

Clinical Utility

• Diagnostic marker: Strongly supports the diagnosis of cutaneous mastocytosis.

• Assessment of disease activity: Wheal intensity may indicate mast cell reactivity.

• Monitoring: Can help in evaluating response to anti-histamine therapy.

Differential Diagnosis

Pediatric considerations

• Most cases of urticaria pigmentosa present in infancy or early childhood.

• Darier’s sign is commonly positive in children with mastocytosis.

• Rare systemic involvement should be evaluated if extensive lesions or flushing occurs.

Geriatric considerations

• Cutaneous mastocytosis is rare in older adults.

• Positive Darier’s sign in adults warrants investigation for systemic mastocytosis.

Limitations

• False negatives can occur in very lightly pigmented lesions or with chronic disease where mast cell activity is low.

• Test may provoke significant itching or discomfort; care should be taken in sensitive patients.

Patient counseling

• Explain that Darier’s sign is a diagnostic skin reaction and is not harmful, but may cause temporary itching or redness.

• Advise on avoiding trauma to lesions to reduce pruritus.

• Discuss potential management strategies, including antihistamines or mast cell stabilizers if symptomatic.

• Emphasize monitoring for systemic symptoms such as flushing, hypotension, or gastrointestinal complaints.

Conclusion

Darier’s sign is a pathognomonic dermatologic marker for mastocytosis, reflecting mast cell degranulation in response to mechanical stimulation. Recognition of this sign aids in diagnosis, disease monitoring, and management of cutaneous and systemic mast cell disorders.

References

1. Darier J. Ueber das Urticaria pigmentosa. Arch Dermatol Syph. 1886;17:77–86.

2. Carter MC, et al. Cutaneous mastocytosis: Clinical manifestations and diagnostic evaluation. J Am Acad Dermatol. 2002;46:458–465.

3. Valent P, et al. Mastocytosis: pathology, genetics, and current treatment options. Leuk Res. 2007;31:1507–1515.

4. Hartmann K, et al. Mastocytosis: a concise clinical review. Am J Clin Dermatol. 2005;6:105–116.

5. Bonadonna P, et al. Clinical and laboratory features of mastocytosis. Allergy. 2011;66:849–859.