|Year : 2018 | Volume
| Issue : 3 | Page : 277-279
Tarang Goyal, Sakshi Kohli
Department of Dermatology, Muzaffarnagar Medical College and Hospital, Muzaffarnagar, Uttar Pradesh, India
|Date of Web Publication||28-Jun-2018|
Dr. Tarang Goyal
Department of Dermatology, Muzaffarnagar Medical College and Hospital, Muzaffarnagar, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Goyal T, Kohli S. Darier's sign. Indian J Paediatr Dermatol 2018;19:277-9
| Introduction|| |
Darier's sign refers to whealing, erythema, and pruritus (urtication) which is elicited after mechanical stimulus to a lesion owing to an increase in the number of mast cells in the dermis.
| History|| |
Darier's sign was first described by Ferdinand Jean Darier (1856–1938) in 1905. Jean Darier, who was born in Budapest, Hungary in a French family, has many eminent contributions in the field of dermatology including the Darier white disease (Keratosis follicularis), Darier-Ferrand disease (dermatofibrosarcoma), and Darier-Roussy sarcoid More Details (subcutaneous sarcoidosis) to name a few.
| Conditions Showing Darier's Sign|| |
- Cutaneous mastocytosis
- Juvenile xanthogranuloma
- Histiocytosis X
- Leukemia cutis,
- Langerhans cell histiocytosis
- Cutaneous plasmacytosis,
- Scabies mimicking mastocytosis,
- Insect bite reactions
| Method of Elicitation|| |
Darier's sign can be elicited by stroking an existing lesion with a blunt object, for example, wooden tongue depressor, dull edge of a pen, fingernail, or a metallic key approximately 5 times with moderate pressure. Within 2–5 min, local wheal and erythema will be seen associated with pruritus which may persist from 30 min to several hours [Figure 1]. The lesion may blister or become hemorrhagic in neonates. Wheal and flare response have also been described in systemic mastocytosis after exercise, warm and hot baths, and sun exposure.
|Figure 1: Darier's sign: Erythema and whealing in a lesion of cutaneous mastocytosis on stroking|
Click here to view
| Variations in Eliciting Darier's Sign|| |
- Nonlesional Darier's sign: Classical Darier's sign is seen in lesional skin as whealing, erythema, and pruritus, but this sign may even be demonstrated on clinically normal skin in patients of mastocytosis. However, whether this phenomenon is a positive, nonlesional Darier sign, or dermatographism is not clear as yet
- Pseudoxanthomatous or xanthelesmoid mastocytosis, a variant of diffuse cutaneous mastocytosis, shows only erythema without wheals on rubbing as against a classic Darier's signss
- Local release of heparin from the sign mast cells may create a lesion with easy bruising by light contact as opposed to urtication due to the release of histamine.
| Points to Keep in Mind While Eliciting Darier's Sign|| |
- A positive Darier's sign is more commonly seen in pediatric patients as compared to adults
- It may be decreased by treatment with antihistamines
- If the testing procedure for Darier's sign is not done properly, false positive or false negative result may be seen
- Caution is advised while eliciting Darier's sign in pediatric patients with cutaneous mastocytocytosis as if there is enough histamine release; some patients may develop systemic symptoms including nausea, diarrhea, abdominal pain, flushing, hypotension, and bronchospasm. Hence, due to the risk of precipitation of a systemic reaction, it should either be performed with the greatest of caution or avoided
- Although considered pathognomonic for cutaneous mastocytosis, positive Darier's sign can be seen in the number of other disorders as listed above. Furthermore, not all cases of cutaneous mastocytosis show positivity, its positivity ranges from 88% to 92% of cases.
| Pathophysiology of Darier's Sign|| |
The basic pathophysiological mechanism underlying the elicitation of Darier's sign is the mechanical stimulation-induced degranulation of mast cells, which are increased in number in the dermis in a patient of mastocytosis. Gentle rubbing action causes exocytosis of granules from the mast cells while strong rubbing leads to mast cell rupture. Of all the inflammatory mediators released, histamine is primarily responsible for this response.
Kiorpelidou et al. have summarized how frictional forces lead to mast cell degranulation by three possible mechanisms:
- Minor tissue traumatization causing complement or plasminogen activation
- Mechanical nerve stimulation through either mechanoreceptor activation or local activation of nociceptive nerve endings resulting in mast cell degranulation
- Mechanical forces through tissue deformation may directly induce mast cell degranulation.
Anetoderma has been suggested as an atypical presentation of mastocytosis. Degranulation of mast cells with release of enzymes such as elastase, tryptase, and chymase can cause degeneration of elastic fibers. The elastin fragments thus formed attract phagocytes such as macrophage which aggravate dermal elastolysis and result in anetoderma.
Infiltration with few mast cells has been described in the superficial and mid dermis in patients with cutaneous plasmacytosis. Some direct or indirect factors from plasmacytes might promote degranulatory responses of mast cells infiltrating into the lesion of cutaneous plasmacytosis explaining the positive Darier's sign.
The role of mast cells in the pathogenesis of scabies has been evaluated. Mast cells' count was found elevated in biopsies of scabies nodules, predominantly during the night, with features of mast cell degranulation. The elevated level of mast cells in scabietic lesions could be postulated as the reason for positive Darier's sign; however, conclusive evidence is lacking.,
Mast cell infiltration has been described in the biopsy sections of juvenile xanthogranuloma showing positive Darier's sign. Furthermore, it has been suggested that lymphoid cells and histiocytes might release some vasodilatory substance which could be responsible for the urtication of lesion on stroking.
Skin lesions in acute lymphoblastic leukemia have shown an infiltrate of lymphoblasts as well as mast cells on skin biopsy confirmed by toluidine blue stain. Interleukin-13 produced by lymphocytes is known to stimulate mast cells. However, Darier's sign has also been reported in a neonate with acute lymphoblastic leukemia without the presence of mast cells on histopathology.
| Mimickers of Darier's Sign|| |
It is seen in congenital smooth muscle hamartoma where stroking, rubbing, or cooling of the lesion induces transient induration with piloerection, with erythema or whitening of the lesion seen at times. It has also been reported on exposure to warm air of a hair dryer. Although it may be seen in up to 80% of patients, its intensity diminishes with age. Pseudo-Darier's sign represents a functioning neural component of the hamartoma, rather than histamine release as seen in a true Darier's sign.
Dermatographism, also called as mechanical urticaria, is a type of physical urticaria where firm stroking of the skin produces an exaggerated triple response of Lewis. Initially, there is local erythema followed by edema and a surrounding flare reaction which assumes the shape of the stroke. Oral mucosal dermographism has also been reported.
Mechanco-immunological stimulation of mast cells with release of histamine due to hypersensitivity of the mast cells rather than an increase in the number of mast cells, as observed in mastocytosis underlies the pathogenesis of this phenomenon.
| Conclusion|| |
Darier's sign is considered a pathognomonic sign for cutaneous mastocytosis. It's elicitation being easy and noninvasive gives a clinical clue for the diagnosis of mastocytosis. However, a clinician should always keep in mind that a negative Darier's sign cannot rule out mastocytosis and neither is a positive Darier's sign confirmatory as it can be seen in a number of other conditions as discussed above.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Freiman A, Kalia S, O'Brien EA. Dermatologic signs. J Cutan Med Surg 2006;10:175-82.
Skrabs CC. Darier sign: A historical note. Arch Dermatol 2002;138:1253-4.
Kiszewski AE, Durán-Mckinster C, Orozco-Covarrubias L, Gutiérrez-Castrellón P, Ruiz-Maldonado R. Cutaneous mastocytosis in children: A clinical analysis of 71 cases. J Eur Acad Dermatol Venereol 2004;18:285-90.
Nagayo K, Sakai M, Mizuno N. Juvenile xanthogranuloma with Darier's sign. J Dermatol 1983;10:283-5.
Foucar E, Piette WW, Tse DT, Goeken J, Olmstead AD. Urticating histiocytosis: A mast cell-rich variant of histiocytosis X. J Am Acad Dermatol 1986;14:867-73.
Raj S, Khopkar U, Wadhwa SL, Kapasi A. Urticaria-pigmentosa-like lesions in acute lymphoblastic leukaemia (2 cases). Dermatology 1993;186:226-8.
Yen A, Sanchez R, Oblender M, Raimer S. Leukemia cutis: Darier's sign in a neonate with acute lymphoblastic leukemia. J Am Acad Dermatol 1996;34:375-8.
Lewis FM, Colver GB, Slater DN. Darier's sign associated with non-Hodgkin's lymphoma. Br J Dermatol 1994;130:126-7.
Ollivaud L, Cosnes A, Wechsler J, Gaulard P, Bagot M, Haioun C, et al.
Darier's sign in cutaneous large T-cell lymphoma. J Am Acad Dermatol 1996;34:506-7.
Madke B, Nayak C. Eponymous signs in dermatology. Indian Dermatol Online J 2012;3:159-65.
] [Full text]
Rafiei R, Hojat E, Daryakar A, Yusefkhani L, Rafiee B. Anetoderma with positive Darier's sign. Our Dermatol Online 2017;8:53-5.
Jin W, Jianzhong Z. Mast cell Infiltration in a patient with cutaneous plasmacytosis. Austin J Dermatol 2014;1:1012.
Nagai H, Nishigori C. Darier's sign in cutaneous plasmacytosis. Eur J Dermatol 2016;26:637-8.
Phan A, Dalle S, Balme B, Thomas L. Scabies with clinical features and positive Darier sign mimicking mastocytosis. Pediatr Dermatol 2009;26:363-4.
Cölgeçen-Özel E, Ertaş R, Utaş S, Kontaş O. Scabies mimicking mastocytosis in two infants. Turk J Pediatr 2013;55:533-5.
Cuervo-Pardo LB, Gonzalez-Estrada A, Ruiz SJ, Pien LC. Hyperpigmented cutaneous lesions that flare-up with scratching: Darier's sign. Oxf Med Case Reports 2015;2015:188-90.
Hartmann K, Escribano L, Grattan C, Brockow K, Carter MC, Alvarez-Twose I, et al.
Cutaneous manifestations in patients with mastocytosis: Consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma and Immunology; and the European Academy of Allergology and Clinical Immunology. J Allergy Clin Immunol 2016;137:35-45.
Surjushe A, Jindal S, Gote P, Saple DG. Darier's sign. Indian J Dermatol Venereol Leprol 2007;73:363-4.
] [Full text]
Püttgen KB, Cohen BA. Cutaneous congenital defects. In: Gleason CA, Devaskar SU, editors. Avery's Diseases of the Newborn. 9th
ed. Amsterdam: Elsevier; 2012. p. 1406-21.
Bhute D, Doshi B, Pande S, Mahajan S, Kharkar V. Dermatographism. Indian J Dermatol Venereol Leprol 2008;74:177-9.
] [Full text]
Srivastava N, Chand S, Singh S. Pseudoxanthomatous mastocytosis. Int J Dermatol 2008;47:50-1.
Tetzlaff JE, BenedettoPX. Skin and bone disorders. In: Fleisher LA, Dripps RD, editors. Anesthesia and Uncommon Diseases. 6th
ed. Amsterdam: Elsevier; 2012. p. 319-49.
Kiorpelidou D, Gaitanis G, Bassukas ID. Darier's sign: A model for studying dermographism. Indian J Dermatol Venereol Leprol 2008;74:271-2.
] [Full text]
Bilgiç Ö, Tunçez Akyürek F, Altınyazar HC. Pseudo Darier sign: A Distinctive finding for congenital smooth muscle hamartoma. J Pediatr 2016;169:318.
Viglizzo G, Nemelka O, Nozza P, Occella C, Rongioletti F. Congenital smooth muscle hamartoma presenting with an unusual pseudo-Darier's sign. Clin Exp Dermatol 2006;31:148-9.
Zarineh A, Kozovska ME, Brown WG, Elder DE, Rabkin MS. Smooth muscle hamartoma associated with a congenital pattern melanocytic nevus, a case report and review of the literature. J Cutan Pathol 2008;35 Suppl 1:83-6.
Sunil S, Deepak P. Oral manifestations of dermographism. J Oral Maxillofac Pathol 2006;10:36-9. [Full text]