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Dermatographism and cold-induced urticaria
Volume 24 Number 6, Part 2 June 1991
Low-sedating HI antihistamines
21. Bernstein IL, Bernstein DI. Efficacy and safety of astemizole, a long-acting and non-sedating H1 antagonist for the treatment of chronic idiopathic urticaria. J Allergy Clin Immunol 1986;77:37-42. 22. Kailasam V, Mathews KP. Controlled clinical assessment of astemizole in the treatment of chronic idiopathic urticaria and angioedema. J AM ACAD DERMATOL 1987; 16:797-804. 23. Honsinger R, Thomsen R. Prolonged remission of chronic idiopathic urticari~ following astemizole treatment [Abstract]. J Allergy Clin ImmunoI 1986;77:187. 24. Juhlin L, Arendt C. Treatment of chronic urticaria with cetirizine dihydroehloride, a non-sedating antihistamine. Br J Derrnatol 1988;119:67-72. 25. Go MJT, Wuite J, Arendt C, et al. Double-blind, placebo controlled comparison of cetirizine and terfenadine in chronic idiopathic urticaria. Acta Therapeutic 1989;15:7786. 26. Monroe EW, Fox RW, Green AW, et al. Efficacy and safety of loratadine (10 mg once daily) in the management of idiopathic chronic urticaria. J AM ACAD DERMATOL 1988;19:138-9. 27. Newman Y. Antihistamine treatment of chronic urticaria: results of a multicenter trial with azatadine and terfenadine. Fortschr Med 1984;102:967-70. 28. Paul E, Bodecker RH. Comparison between astemizole and terfenadine in the treatment of chronic urticaria: a ran-
29. 30. 31. 32. 33. 34.
35.
36.
domized double-blind study in 40 patients. Z Hautkr 1985;60(suppl):50-5. Cainell T, Seidenari S, Valsecchi R, et al. Double-blind comparison of astemizole and terfenadine in the treatment of chronic urticaria. Pharmatherapeutica 1986;4:679-86. Mosbacken H, Faergeman J, Gisslen H, et al. Astemizole in chronic idiopathic urticaria: a comparison with chlorphenamine [Abstract]. Ann Allergy 1985;55:254. Sorer NA. Physical urticaria/angioedema as an experimental model of acute and chronic inflammation in human skin. Springer Semin Immunopathol 1981;4:73-8 I. Krause B, Shuster S. The effect of terfenadine on dermographic whealing. Br J Dermatol 1984;110:73-9. Krause LB, Shust~r S. A comparison of astemizole and chlorpheniramine in dermographic urticaria. Br J Dermatol 1985;112:447-53. Gendreau-Reid L, Simons KJ, Simons FER. Comparison of the suppressive effect of astemizole, terfenadine, and hydroxyzine on histamine-induced wheals and flares in humans. J Allergy Clin lmmunol 1986;77:335-40. Juhlin L, De Vos C, Rihoux J-P. Inhibiting effect of cetirizinc on histamine-induced and 48/80-induced wheals and flares, experimental dermographism, and cold-induced urticaria. J Allergy Clin Immunol 1987;80:599-602. Diffey BL, Farr PM. Treatment of solar urticaria with terfenadine. Photodermatology 1988;5:25-9.
P R E S E N T E D AT T H E S Y M P O S I U M , "TREATING DERMATOLOGIC H Y P E R S E N S I T I V I T Y DISORDERS: INVESTIGATIVE DEVELOPMEN'IS," S P O N S O R E D BY AN E D U C A T I O N A L GRANT F R O M P F I Z E R LABS I I
I I
l
I
Dermatographism and cold-induced urticaria Lennart Juhlin, MD, PhD Uppsala, Sweden Dermatographism and cold-induced urticaria are two common physical urticarias. Traditional treatment with antihistamines has been somewhat effective in alleviating symptoms; however, the sedative side effects of the agents pose problems. Results of treatment with the new low-sedating H1 antihistamines have been encouraging. (J AM ACAD DERMATOL 1991;24:1087-9.)
Physical urticarias make up a variety of disorders that as a group represent about 20% of all urticarias. They occur most frequently in persons between 17 and 40 years of age. Physical urticaria is frequently unrecognized, and its specific cause is often undetermined by either paFrom the Department of Dermatology,University Hospital. Reprint requests: Lennart Juhlin, MD, PhD, Department of Dermatology, University Hospital, S 751 85 Uppsala, Sweden.
16/0/~9o~
tient or physician. Such an oversight can, however, be readily corrected if assessment for physical urticaria is carried out as the initial step in the overall evaluation of a patient with urticaria. In our clinic the most commonly seen physical urticaria is dermatographism, which accounts for approximately 10% of all urticarias. The second most common type encountered at our facility is cold urticaria. 1 Traditionally these conditions have been treated with antihistamines, which, while effective in alleviating the symptoms of urticaria, have been associ1087
1088
Journal of the American Academy of Dermatology
Juhlin
Table I. Types of dermatographism Nonitching---simple Itching--pathologic Idiopathic Symptomatic, e.g., from penicillin, rubefacients, scabies, or acute urticaria Cholinergic (mainly with cholinergic urticaria) Follicular Red Delayed (4-20 hr)
ated with significant sedative effects that compromise their usefulness. In fact, until recently it was thought that such sedation was an integral component of the benefit imparted by these agents. However, good results have now been reported with the new, relatively nonsedating Hi-receptor blockers. DERMATOGRAPHISM The diagnosis of dermatographism, also known as urticaria factitia, can be made by stroking the skin firmly with a blunt object both on the volar surface of the forearm and on the back, where the familiar localized whealing is most commonly seen. The reaction is usually evident within a few minutes as an itching wheal and surrounding erythema. The patient is often unaware that it can result from scratching or pressure from clothes or from leaning against a chair. Why such a reaction suddenly develops is often unknown; in fact idiopathic dermatographism is most common (Table I). However, dermatographism has been seen after both bacterial and fungal infections, after treatment with penicillin, and as a concomitant of scabies. Once the scabies has been treated, the dermatographism often disappears within 2 months. In rare cases the reaction is follicular, 2 or it may appear as fine papules in patients with cholinergic or heat urticaria. 3 Another type, red dermatographism, an inflamed and swollen reaction that is easily evoked by rubbing, resembles vibratory urticaria or dermodistortive urticaria, which is often hereditary, a, s Delayed dermatographism, which is rare and resembles delayed pressure urticaria, is difficult to diagnose and treat. 6 Treatment of dermatographism. When the symptoms are mild, no treatment of dermatographism is required. However, the patient often has extremely dry, itching skin that provokes the scratching that produces dermatographism. For these patients, an emollient, such as an oil-in-water emulsion used af-
ter hydration, is helpful. Other patients have found that their dermatographism improves in the summer after sun exposure, and studies have confirmed that ultraviolet-B irradiation can be of value, particularly for chronic conditions] For reasons that are still unclear, treatment with psoralen plus ultraviolet light of the A wavelength (PUVA) has had no or very limited effect on simple dermatographism, s For patients with more severe itching, H1 antihistamines, especially hydroxyzine (10 to 25 mg), have been used with a good effect. 9, 10 The combination of H1 and H2 blockers has been found to improve the condition 11 but will not necessarily offer an advantage ever an effective Hi antihistaminic alone. 12 It is probable that hydroxyzine will be replaced by the less sedating antihistamines, la-16 In an uncontrolled investigation at our institution, we studied patients with severe idiopathic dermatographism. 16 After treatment with cetirizine, wheal-and-flare reactions to pressures of 100 to 500 grn/15 m m 2 were absent in 8 of 10 patients and reduced in the 2 with most serious disease. Itching was also inhibited. COLD URTICARIA Hives associated with cold urticaria most commonly appear during the warm-up period after exposure to cold. They tend to occur on skin that has been directly exposed, such as the face and hands, and usually disappear within an hour or less. Delayed cold urticaria is rare. Diagnosis and estimation of the degree of sensitivity can be achieved by testing with ice cubes for seconds to 20 minutes. In wet and windy weather the lesions can also appear at temperatures as high as 22 ~ C (72 ~ F). Patients should be warned of the risk of a reaction from swimming, even in a warm pool (18 ~ to 26 ~ C). Arctic clothing and a warm garage for the car are helpful in preventing the lesions. Treatment of cold urticaria. Treatment of cold urticaria is difficult. Desensitization with cold water has been used with some positive results, 17but it can induce shock or vasculitis and is quite unpleasant for the patient. Nevertheless, the treatment appears to render the mast ceils less responsive or cause a depletion of cold-induced antigen is and might have a place in some well-monitored patients. At 1-hour intervals, parts of the body are immersed in cold water. Tolerance is then maintained by a daily cold shower or bath. Intramuscular injection of penicillin two to three times per week has also been reported
Volume 24 Number 6, Part 2 June 1991
tO be effective, t7 although we have used the treatment in 15 patients without any effect. O f the "classic" antihistamines, dexchlorpheniramine maleate, clemastine fumarate, and cyproheptadine hydrochloride have been moderately successful.~7 However, their sedative effects and relatively slow onset of action reduce their practicality for everyday life. Patients tend to give up on them. Combinations with Ha blockers have been reported, but the advantage is doubtful. 11, 17 Antihistamines that also inhibit histamine release and are available on an experimental basis have been tried. 17 One, ketotifen, reportedly increased by twofold the minimum time to induce a whealing reaction to cold. These agents, however, have been of limited practical value because of their extreme sedative side effects. Good results with two less sedating antihistamines, cetirizine and acrivastine, have been reported.16, 19 Acrivastine has been reported by others 19 to be more effective than cyproheptadine in reducing the size of ice cube-induced wheals. The sedative side effects of acrivastine also seem to be less; drowsiness occurred in 4 of 18 subjects compared with 12 of 18 subjects receiving cyproheptadine.19 W e tested the effect of treatment with cetirizine on 12 patients with cold urticaria and positive ice cube tests. 16 After treatment, the whealing reaction to an ice cube disappeared in five patients and was markedly reduced in seven. In two patients whose baseline reaction time to cold was 30 seconds, urticaria was delayed until 6 minutes. REFERENCES 1. Juhlin L. Urticaria in the elderly. Semin Dermatol 1987;6:326-7. 2. Shelley WB, ShelleyED. Folliculardermographism.Cutis 1983;32:244-5. 3. Warin RP, Champion RH. The physical urticarias. In:
Dermatographism and cold-induced urticaria 1089 Warin RP, Champion RH, eels. Urticaria. Philadelphia: WB Saunders, 1974:131. 4. Wafin RP. Factitiousurticaria: red dermographism.Br J Dermatol 1981;104:285-8. 5. Epstein PA, Kidd KK. Dermo-distortive urticaria: an autosomal dominant dermatologicdisorder. Am J Med Genet 1981;9:307-15. 6. Sorer NA. Physicalurticaria/angioedema.SeminDermatel 1987;6:302-12. 7. JohnssonM, Falk ES, VoldenG. UV-B treatment of factitious urticaria. Photodermatol 1987;4:302-4. 8. Logan RA, O'Brien T J, Greaves M. The effect of photochemotherapy (PUVA) on symptomaticdermographism. Br J Dermatol 1984;111(suppl 26):41-2. 9. Matthews CNA, Kirby JD, James J, etal. Dermographism:reductionin whealsize by chlorpheniramineand hydroxyzine.Br J Dermatol 1973;88:279-82. 10. Breathnach SM, Allen R, Ward AM, etal. Symptomatic dermographism: natural history, clinicalfeatures,laboratory investigationsand responseto therapy.Clin Exp Dermatol 1983;8:463-76. 11. CzametzldBM. Therapy.In: CzarnetzldBM, ed. Urticaria. Berlin: Springer-Verlag, 1986:145. 12. CookJ, Shuster S.TheeffectofH1 and H2receptorantagonists on the dermographicresponse.Acta Derm Venereol (Stock.h) 1983;63:260-2. 13. BoyleJ, Marks P, Gibson JB. Acrivastineversus terfenadine in the treatment of symptomaticdermographism--a double blind, placebo-controlledstudy. J Int Meal Res 1989;17(suppl 2):9B-13B. 14. Krause LB, Shuster S. A comparison of astemizole and chlorpheniraminein dermographieurticaria. Br J Dermatel 1985;112:447-53. 15. Ormerod AD, Baker R, Watt J, et al. Terfenadine and brompheniramine maleate in urticaria and dermographism. Dermatologica1986;173:5-8. 16. Juhlin L, De Vos C, RihouxJ-P. Inhibitingeffectof cetirizine on histamine-inducedand 48/80-induced wheals and flares, experimentaldermographismand cold inducedurticaria. J AllergyClin Immunol 1987;80:599-602. 17. Black AK. Cold urticaria. Semin Dermatol 1987;6:292301. 18. KeaheyTM, IndrisanoJ, KalinerMA. A casestudyon the induction of clinical tolerance in cold urticaria. J Allergy Clin Immunol 1988;82:256-61. 19. Neittaanm~ikiH, Fr/ikiJE, GibsonJR. Comparisonof the new antihistamineacrivastine (BW 825 C) versus cyproheptadine in the treatment of idiopathic cold urticaria. Dermatologica 1988;177:98-103.
Low-sedating HI antihistamines
21. Bernstein IL, Bernstein DI. Efficacy and safety of astemizole, a long-acting and non-sedating H1 antagonist for the treatment of chronic idiopathic urticaria. J Allergy Clin Immunol 1986;77:37-42. 22. Kailasam V, Mathews KP. Controlled clinical assessment of astemizole in the treatment of chronic idiopathic urticaria and angioedema. J AM ACAD DERMATOL 1987; 16:797-804. 23. Honsinger R, Thomsen R. Prolonged remission of chronic idiopathic urticari~ following astemizole treatment [Abstract]. J Allergy Clin ImmunoI 1986;77:187. 24. Juhlin L, Arendt C. Treatment of chronic urticaria with cetirizine dihydroehloride, a non-sedating antihistamine. Br J Derrnatol 1988;119:67-72. 25. Go MJT, Wuite J, Arendt C, et al. Double-blind, placebo controlled comparison of cetirizine and terfenadine in chronic idiopathic urticaria. Acta Therapeutic 1989;15:7786. 26. Monroe EW, Fox RW, Green AW, et al. Efficacy and safety of loratadine (10 mg once daily) in the management of idiopathic chronic urticaria. J AM ACAD DERMATOL 1988;19:138-9. 27. Newman Y. Antihistamine treatment of chronic urticaria: results of a multicenter trial with azatadine and terfenadine. Fortschr Med 1984;102:967-70. 28. Paul E, Bodecker RH. Comparison between astemizole and terfenadine in the treatment of chronic urticaria: a ran-
29. 30. 31. 32. 33. 34.
35.
36.
domized double-blind study in 40 patients. Z Hautkr 1985;60(suppl):50-5. Cainell T, Seidenari S, Valsecchi R, et al. Double-blind comparison of astemizole and terfenadine in the treatment of chronic urticaria. Pharmatherapeutica 1986;4:679-86. Mosbacken H, Faergeman J, Gisslen H, et al. Astemizole in chronic idiopathic urticaria: a comparison with chlorphenamine [Abstract]. Ann Allergy 1985;55:254. Sorer NA. Physical urticaria/angioedema as an experimental model of acute and chronic inflammation in human skin. Springer Semin Immunopathol 1981;4:73-8 I. Krause B, Shuster S. The effect of terfenadine on dermographic whealing. Br J Dermatol 1984;110:73-9. Krause LB, Shust~r S. A comparison of astemizole and chlorpheniramine in dermographic urticaria. Br J Dermatol 1985;112:447-53. Gendreau-Reid L, Simons KJ, Simons FER. Comparison of the suppressive effect of astemizole, terfenadine, and hydroxyzine on histamine-induced wheals and flares in humans. J Allergy Clin lmmunol 1986;77:335-40. Juhlin L, De Vos C, Rihoux J-P. Inhibiting effect of cetirizinc on histamine-induced and 48/80-induced wheals and flares, experimental dermographism, and cold-induced urticaria. J Allergy Clin Immunol 1987;80:599-602. Diffey BL, Farr PM. Treatment of solar urticaria with terfenadine. Photodermatology 1988;5:25-9.
P R E S E N T E D AT T H E S Y M P O S I U M , "TREATING DERMATOLOGIC H Y P E R S E N S I T I V I T Y DISORDERS: INVESTIGATIVE DEVELOPMEN'IS," S P O N S O R E D BY AN E D U C A T I O N A L GRANT F R O M P F I Z E R LABS I I
I I
l
I
Dermatographism and cold-induced urticaria Lennart Juhlin, MD, PhD Uppsala, Sweden Dermatographism and cold-induced urticaria are two common physical urticarias. Traditional treatment with antihistamines has been somewhat effective in alleviating symptoms; however, the sedative side effects of the agents pose problems. Results of treatment with the new low-sedating H1 antihistamines have been encouraging. (J AM ACAD DERMATOL 1991;24:1087-9.)
Physical urticarias make up a variety of disorders that as a group represent about 20% of all urticarias. They occur most frequently in persons between 17 and 40 years of age. Physical urticaria is frequently unrecognized, and its specific cause is often undetermined by either paFrom the Department of Dermatology,University Hospital. Reprint requests: Lennart Juhlin, MD, PhD, Department of Dermatology, University Hospital, S 751 85 Uppsala, Sweden.
16/0/~9o~
tient or physician. Such an oversight can, however, be readily corrected if assessment for physical urticaria is carried out as the initial step in the overall evaluation of a patient with urticaria. In our clinic the most commonly seen physical urticaria is dermatographism, which accounts for approximately 10% of all urticarias. The second most common type encountered at our facility is cold urticaria. 1 Traditionally these conditions have been treated with antihistamines, which, while effective in alleviating the symptoms of urticaria, have been associ1087
1088
Journal of the American Academy of Dermatology
Juhlin
Table I. Types of dermatographism Nonitching---simple Itching--pathologic Idiopathic Symptomatic, e.g., from penicillin, rubefacients, scabies, or acute urticaria Cholinergic (mainly with cholinergic urticaria) Follicular Red Delayed (4-20 hr)
ated with significant sedative effects that compromise their usefulness. In fact, until recently it was thought that such sedation was an integral component of the benefit imparted by these agents. However, good results have now been reported with the new, relatively nonsedating Hi-receptor blockers. DERMATOGRAPHISM The diagnosis of dermatographism, also known as urticaria factitia, can be made by stroking the skin firmly with a blunt object both on the volar surface of the forearm and on the back, where the familiar localized whealing is most commonly seen. The reaction is usually evident within a few minutes as an itching wheal and surrounding erythema. The patient is often unaware that it can result from scratching or pressure from clothes or from leaning against a chair. Why such a reaction suddenly develops is often unknown; in fact idiopathic dermatographism is most common (Table I). However, dermatographism has been seen after both bacterial and fungal infections, after treatment with penicillin, and as a concomitant of scabies. Once the scabies has been treated, the dermatographism often disappears within 2 months. In rare cases the reaction is follicular, 2 or it may appear as fine papules in patients with cholinergic or heat urticaria. 3 Another type, red dermatographism, an inflamed and swollen reaction that is easily evoked by rubbing, resembles vibratory urticaria or dermodistortive urticaria, which is often hereditary, a, s Delayed dermatographism, which is rare and resembles delayed pressure urticaria, is difficult to diagnose and treat. 6 Treatment of dermatographism. When the symptoms are mild, no treatment of dermatographism is required. However, the patient often has extremely dry, itching skin that provokes the scratching that produces dermatographism. For these patients, an emollient, such as an oil-in-water emulsion used af-
ter hydration, is helpful. Other patients have found that their dermatographism improves in the summer after sun exposure, and studies have confirmed that ultraviolet-B irradiation can be of value, particularly for chronic conditions] For reasons that are still unclear, treatment with psoralen plus ultraviolet light of the A wavelength (PUVA) has had no or very limited effect on simple dermatographism, s For patients with more severe itching, H1 antihistamines, especially hydroxyzine (10 to 25 mg), have been used with a good effect. 9, 10 The combination of H1 and H2 blockers has been found to improve the condition 11 but will not necessarily offer an advantage ever an effective Hi antihistaminic alone. 12 It is probable that hydroxyzine will be replaced by the less sedating antihistamines, la-16 In an uncontrolled investigation at our institution, we studied patients with severe idiopathic dermatographism. 16 After treatment with cetirizine, wheal-and-flare reactions to pressures of 100 to 500 grn/15 m m 2 were absent in 8 of 10 patients and reduced in the 2 with most serious disease. Itching was also inhibited. COLD URTICARIA Hives associated with cold urticaria most commonly appear during the warm-up period after exposure to cold. They tend to occur on skin that has been directly exposed, such as the face and hands, and usually disappear within an hour or less. Delayed cold urticaria is rare. Diagnosis and estimation of the degree of sensitivity can be achieved by testing with ice cubes for seconds to 20 minutes. In wet and windy weather the lesions can also appear at temperatures as high as 22 ~ C (72 ~ F). Patients should be warned of the risk of a reaction from swimming, even in a warm pool (18 ~ to 26 ~ C). Arctic clothing and a warm garage for the car are helpful in preventing the lesions. Treatment of cold urticaria. Treatment of cold urticaria is difficult. Desensitization with cold water has been used with some positive results, 17but it can induce shock or vasculitis and is quite unpleasant for the patient. Nevertheless, the treatment appears to render the mast ceils less responsive or cause a depletion of cold-induced antigen is and might have a place in some well-monitored patients. At 1-hour intervals, parts of the body are immersed in cold water. Tolerance is then maintained by a daily cold shower or bath. Intramuscular injection of penicillin two to three times per week has also been reported
Volume 24 Number 6, Part 2 June 1991
tO be effective, t7 although we have used the treatment in 15 patients without any effect. O f the "classic" antihistamines, dexchlorpheniramine maleate, clemastine fumarate, and cyproheptadine hydrochloride have been moderately successful.~7 However, their sedative effects and relatively slow onset of action reduce their practicality for everyday life. Patients tend to give up on them. Combinations with Ha blockers have been reported, but the advantage is doubtful. 11, 17 Antihistamines that also inhibit histamine release and are available on an experimental basis have been tried. 17 One, ketotifen, reportedly increased by twofold the minimum time to induce a whealing reaction to cold. These agents, however, have been of limited practical value because of their extreme sedative side effects. Good results with two less sedating antihistamines, cetirizine and acrivastine, have been reported.16, 19 Acrivastine has been reported by others 19 to be more effective than cyproheptadine in reducing the size of ice cube-induced wheals. The sedative side effects of acrivastine also seem to be less; drowsiness occurred in 4 of 18 subjects compared with 12 of 18 subjects receiving cyproheptadine.19 W e tested the effect of treatment with cetirizine on 12 patients with cold urticaria and positive ice cube tests. 16 After treatment, the whealing reaction to an ice cube disappeared in five patients and was markedly reduced in seven. In two patients whose baseline reaction time to cold was 30 seconds, urticaria was delayed until 6 minutes. REFERENCES 1. Juhlin L. Urticaria in the elderly. Semin Dermatol 1987;6:326-7. 2. Shelley WB, ShelleyED. Folliculardermographism.Cutis 1983;32:244-5. 3. Warin RP, Champion RH. The physical urticarias. In:
Dermatographism and cold-induced urticaria 1089 Warin RP, Champion RH, eels. Urticaria. Philadelphia: WB Saunders, 1974:131. 4. Wafin RP. Factitiousurticaria: red dermographism.Br J Dermatol 1981;104:285-8. 5. Epstein PA, Kidd KK. Dermo-distortive urticaria: an autosomal dominant dermatologicdisorder. Am J Med Genet 1981;9:307-15. 6. Sorer NA. Physicalurticaria/angioedema.SeminDermatel 1987;6:302-12. 7. JohnssonM, Falk ES, VoldenG. UV-B treatment of factitious urticaria. Photodermatol 1987;4:302-4. 8. Logan RA, O'Brien T J, Greaves M. The effect of photochemotherapy (PUVA) on symptomaticdermographism. Br J Dermatol 1984;111(suppl 26):41-2. 9. Matthews CNA, Kirby JD, James J, etal. Dermographism:reductionin whealsize by chlorpheniramineand hydroxyzine.Br J Dermatol 1973;88:279-82. 10. Breathnach SM, Allen R, Ward AM, etal. Symptomatic dermographism: natural history, clinicalfeatures,laboratory investigationsand responseto therapy.Clin Exp Dermatol 1983;8:463-76. 11. CzametzldBM. Therapy.In: CzarnetzldBM, ed. Urticaria. Berlin: Springer-Verlag, 1986:145. 12. CookJ, Shuster S.TheeffectofH1 and H2receptorantagonists on the dermographicresponse.Acta Derm Venereol (Stock.h) 1983;63:260-2. 13. BoyleJ, Marks P, Gibson JB. Acrivastineversus terfenadine in the treatment of symptomaticdermographism--a double blind, placebo-controlledstudy. J Int Meal Res 1989;17(suppl 2):9B-13B. 14. Krause LB, Shuster S. A comparison of astemizole and chlorpheniraminein dermographieurticaria. Br J Dermatel 1985;112:447-53. 15. Ormerod AD, Baker R, Watt J, et al. Terfenadine and brompheniramine maleate in urticaria and dermographism. Dermatologica1986;173:5-8. 16. Juhlin L, De Vos C, RihouxJ-P. Inhibitingeffectof cetirizine on histamine-inducedand 48/80-induced wheals and flares, experimentaldermographismand cold inducedurticaria. J AllergyClin Immunol 1987;80:599-602. 17. Black AK. Cold urticaria. Semin Dermatol 1987;6:292301. 18. KeaheyTM, IndrisanoJ, KalinerMA. A casestudyon the induction of clinical tolerance in cold urticaria. J Allergy Clin Immunol 1988;82:256-61. 19. Neittaanm~ikiH, Fr/ikiJE, GibsonJR. Comparisonof the new antihistamineacrivastine (BW 825 C) versus cyproheptadine in the treatment of idiopathic cold urticaria. Dermatologica 1988;177:98-103.