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St John's Institute of Dermatology, King's College London, St Thomas Hospital, London, U.K.
Delayed pressure urticaria is a physical urticaria in®ltrate of neutrophils and eosinophils, without vas- where erythematous, often painful swellings occur at culitis. Treatment of delayed pressure is generally sites of sustained pressure on the skin, after a delay unsatisfactory, and is often resistant to antihistamine of several hours. If sought, it is present in up to 40% and a range of anti-in¯ammatory medication. Oral of patients with ordinary chronic ``idiopathic urti- steroids, although the most effective therapy, are caria'' to a varying degree. Compared with other unsuitable for long-term use. Delayed pressure urti- urticarias, the pressure-induced lesions impair the caria may persist for many years, and improved or quality of life of patients most severely. The patho- novel methods of management are under investiga- genesis is not well characterized, but whealing is tion. Journal of Investigative Dermatology Symposium dependent on mast cell activation, with the histology of lesions also showing a deep dermal in¯ammatory Delayedpressureurticaria(DPU)isimportantbecause urinary¯ow(PoonandKobzaBlack,1998).TheseverityofDPU it can interfere severely with the quality of life, the varies in individuals with time (Lawlor et al, 1989). Nearly all (94%) condition may be underdiagnosed, its pathogenesis is patients have associated ordinary idiopathic urticaria (Sussman et al, not de®ned, and its treatment is very dif®cult.
The incidence of DPU was previously stated to be approximately 2% of all urticarias (Champion, 1988). It is now recognized that DPU is more common, as 37% of patients with ordinary urticaria The severity of the impact of DPU on the quality of life has only attending hospital have associated DPU (Barlow, 1993). Other recently been documented in a specialist urticaria unit. When the types of urticaria may be associated with DPU (Dover et al, 1988), quality of life of patients with delayed pressure urticaria and chronic including angiedema, symptomatic immediate, and delayed urticaria was compared with patients with uncomplicated chronic ordinary urticaria, using a Nottingham health pro®le, a general health status measure, the patients with DPU were signi®cantly more restricted in mobility and types of clothing that they could wear, had a higher pain score, and had more problems related to The patient and physician may be unaware of the presence of DPU employment and hobbies (O'Donnell et al, 1997). Similar results unless direct questioning reveals the association of pressure and were obtained by using a skin disease speci®c questionnaire development of wheals after a delay. Lesions appear at pressure sites (Dermatology Life Quality Index; Poon et al, 1999). In addition, under tight clothes, on palms after using tools, and on soles of feet patients with DPU had the highest impairment of quality of life after prolonged walking or standing.
compared with the other types of urticaria questioned (Poon et al, Con®rmation of the diagnosis is made after application of a 1999). This impairment of quality of life of patients with DPU was standardized weight applied to a de®ned area of skin for a speci®ed comparable with that seen in atopic outpatients (Poon et al, 1999).
time results in a palpable wheal when inspected after 2±8 h (usually Patients may not reveal that DPU can cause sexual dif®culties 6 h). The presence of wheals resulting from rods of 1.5 cm diameter weighted with 2.5 or 3.5 kg applied for 20 min to the skin were designated as a gold standard for DPU. Using a pen-like instrument calibrated at 100 g per mm2 (dermographometer) pressed for various times against the back, the best combination DPU is characterized by the development of erythematous of speci®city and sensitivity of the diagnosis of DPU was at 70 s swellings at sites of sustained pressure application on the skin after a delay of 30 min to 12 h (Dover et al, 1988). The swellings are usually pruritic and/or painful, may persist for several days, and occasionally may blister (Mijailovic et al, 1997). Systemic features such as ¯u-like symptoms and arthralgia may be present and on a The pathogenesis of DPU is not well characterized, although a few occasions delayed pressure urticaria has led to obstruction of number of potential mechanisms and mediators have been It has been postulated that the pressure-induced wheals may be Manuscript received June 19, 2001; accepted for publication June 19, due to a late phase reaction (Sussman et al, 1982), but an antigen has Reprint requests to: Dr. A. Kobza-Black, St John's Institute of never been identi®ed. This reaction is dependent on mast cell Dermatology, King's College London, St Thomas Hospital, Lambeth activation and reduced stainable mast cells have been demonstrated in wheals of DPU (Barlow et al, 1995a) associated with a 1087-0024/01/$15.00 ´ Copyright # 2001 by The Society for Investigative Dermatology, Inc.
neutrophil- and eosinophil-rich in®ltrate present in some early and It is unclear whether immunotherapy including oral cyclosporine late wheals (Barlow et al, 1994). There is upregulation of E selectin and intravenous immunoglobulin, which have been used to treat (Barlow et al, 1994). These responses suggest the presence of the most resistant autoimmune chronic urticarias, may be bene®cial cytokines derived from mast or in¯ammatory cells. Increased interleukin 6 (Lawlor et al, 1993) and TNFa and IL3 expression related to the in¯ammatory cell in®ltrate were demonstrated in lesions of DPU (Hermes et al, 1999).
Barlow RJ, Warburton F, Watson K, Kobza-Black A, Greaves MW: Diagnosis and incidence of delayed pressure urticaria in patients with chronic urticaria. J Am Treatment is generally unsatisfactory and there are only a few Barlow RJ, Ross EL, MacDonald DM, Black AK, Greaves MW: Adhesion molecule expression and the in¯ammatory cell in®ltrate in delayed pressure urticaria. Br J controlled trials. Antihistamines are generally not effective (Sussman et al, 1982; Dover et al, 1988), though high doses of Barlow RJ, Ross EL, MacDonald DM, Kobza-Black A, Greaves MW: Mast cells and cetirizine (10 mg three times) reduced the areas of whealing in 14 T lymphocytes in chronic urticaria. Clin Exp Allergy 25:317±322, 1995a patients with DPU (Kontou-Fili et al, 1991), but in clinical practice Barlow RJ, MacDonald DM, Kobza-Black A, Greaves MW: The effects of topical steroids on delayed pressure urticaria. Arch Derm Res 287:285±288, 1995b the results have been generally disappointing.
Berkun Y, Shalit M: Successful treatment of delayed pressure urticaria with Nonsteroidal anti-in¯ammatory drugs (NSAID) have been used to treat DPU, with con¯icting results. Acetyl salicylic acid Champion RH: Urticaria then and now. Br J Dermatol 119:427±436, 1988 (3900 mg per d in divided doses) clinical suppressed experimentally Dover JS, Kobza-Black A, Milford Ward A, Greaves MW: Delayed pressure induced wheals in six of eight patients with DPU (Sussman et al, urticaria. Clinical features, laboratory investigations, and response to therapy of 44 patients. J Am Acad Dermatol 18:1289±1298, 1988 1982); however, in a double blind trial of indomethacin 25 mg Engler RJM, Squire E, Benson P: Chronic sulfasalazine therapy in the treatment of three times a day in 14 patients with DPU, there was no signi®cant delayed pressure urticaria and angioedema. Ann Allergy Asthma Immunol reduction of dermographometer-induced weal areas (Dover et al, 1988). It is important to note that NSAID may exacerbate ordinary Gould DJ, Campbell D, Dayani A: Delayed pressure urticaria. Successful treatment of 5 cases with dapsone. Br J Dermatol 125 (Suppl. 38):25, 1991 Hermes B, Prochazka A-K, Haas N, Jurgovsky K, Sticherling M, Henz BM: Colchicine at a dose of 0.5 mg and placebo twice a day in 13 Upregulation of TNF-a and IL-3 expression in lesional and uninvolved skin in patients with DPU in a double blind cross-over trial, did not different types of urticaria. J Allergy Clin Immunol 103:307±314, 1999 demonstrate a reduction of dermographometer-induced wheals Kontou-Fili K, Maniatakou G, Demaka P, Gonianakis M, Palaiologos G, Aroni K: Therapeutic effects of cetirizine in delayed pressure urticaria: clinicopathologic compared with placebo (Lawlor et al, 1989).
®ndings. J Am Acad Dermatol 24:1090±1093, 1991 There has been an isolated case report of the usefulness of Lawlor F, Kobza-Black A, Milford Ward A, Morris R, Greaves MW: Delayed dapsone 50 mg daily in ®ve patients (Gould et al, 1991), of pressure urticaria, objective evaluation of a variable disease using a sulfasalazine up to 4 g daily in two patients (Engler et al, 1995), and dermographometer and assessment of treatment using colchicine. Br J of montelukast, a leukotriene antagonist, in one patient (Berkun Lawlor F, Bird C, Camp RDR, et al: Increased interleukin 6, but reduced interleukin and Shalit, 2000) with DPU, but larger double blind, placebo- 1, in delayed pressure urticaria. Br J Dermatol 128:500±503, 1993 controlled studies are necessary to evaluate these treatments.
McFadden JP, Newton JA, Greaves MW: Dyspareunia as a complication of delayed In a study of 44 patients with DPU, one group was randomised pressure urticaria. Br J Sexual Med 15:61, 1998 to nimesulide 100 mg daily for 3 wk, ketotifen 1 mg b.d. was Mijailovic BB, Karadaglic DJM, Ninkovic MP, Mladenovic TM, Zecevic RD, Pavlovic MD: Bullous delayed pressure urticaria; pressure testing may produce added for 2 wk, and in the next 2 wk nimesulide was ceased but a systemic reaction. Br J Dermatol 136:434±436, 1997 ketotifen was continued. In another group prednisolone orally was O'Donnell BF, Lawlor F, Simpson J, Morgan M, Greaves MW: The impact of reduced from 40 mg daily for 3 wk, 30 mg daily for 2 wk, and chronic urticaria on the quality of life. Br J Dermatol 136:197±201, 1997 20 mg daily for 2 wk. There was a reduction of 93% of symptoms Poon E, Kobza-Black A: Delayed pressure urticaria causing obstruction of urinary in the ®rst group and 85% in the second, but longer follow-up Poon E, Seed PT, Greaves MW, Kobza-Black A: The extent and nature of diasability studies are necessary (Vena et al, 1998).
in different urticarial conditions. Br J Dermatol 140:667±671, 1999 Oral steroids are the most effective treatment, but doses above Sussman GL, Harvey RP, Schoket AL: Delayed pressure urticaria. J Allergy Clin 30 mg per day may be necessary, so it is unsuitable for long-term use (Dover et al, 1988). Topical steroids under occlusion may be Vena GA, D'Argento V, Cassano N, Mastrolonardo M: Sequential therapy with nimesulide and ketotifen in delayed pressure urticaria. Acta Derma Venereol helpful in pretreating small localized areas (Barlow et al, 1995b).

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