Search

Delayed pressure urticaria is a mechanical urticaria in which pressure causes whealing. Delayed cutaneous erythema and edema occur in association with marked subcutaneous swelling after the application of a sustained pressure stimulus to the skin. The earliest reports and theories of the pathogenesis of delayed pressure urticaria are summarized. Detailed attention is given to making the diagnosis by taking a history and provoking the lesions. The clinical features and natural history are considered. The effects of the disorder on quality of life are delineated, and management strategies are suggested.

Urticaria is predominantly due to release of mast cell mediators, mainly histamine. Chronic idiopathic urticaria, in which disease activity continues on most days for more than 6 weeks and there is no evidence of a physical urticaria or urticarial vasculitis, is common. An external cause is rarely identified even if a thorough history and appropriate investigation based on this are undertaken. However, approximately 50% of patients with chronic idiopathic urticaria (CIU) have a serum histamine releasing factor present. In one-third of patients with CIU this is an IgG autoantibody directed against the high affinity IgE receptor (FceRI) or less frequently against IgE. Patients with autoinimune urticaria, are clinically more severe. Urticaria can affect the quality of life markedly, being comparable to that of patients awaiting triple coronary by-pass surgery. The rational management of urticaria takes account of likely causes and mediators involved. However explanation and attention to general measures such as minimizing stress, overheating and alcohol are important. Aspirin, nonsteroidal anti-inflammatory drugs and opiates should be avoided if possible. Exclusion diets such as of food colourings and additives may be of some value to a limited number of patients. Second- and third-generation low sedation H1 antagonists are the treatment of choice and improve many patients. Addition of an H2 antagonist or a mast cell stabilizing drug may provide additional benefit for a few. There are reports that leukotriene receptor antagonists improve some patients. Oral steroids are reserved if possible for severe exacerbation of chronic urticaria, and disabling pressure urticaria. Third-line therapies involving immunosuppressive agents are only appropriate for patients with chronic urticaria refractory to other measures, and usually autoimmune. The encouraging results using short courses of oral cyclosporin, high dose intravenous immunoglobulin and plasmapheresis need to be confirmed in placebo-controlled trials, in patients with or without demonstrable serum histamine releasing activity.

We report two cases of Schnitzler's syndrome in which anti-interleukin-1α autoantibodies and functional autoantibodies against the high affinity IgE receptor (FceRIα) or against IgE were absent. One patient responded well to TL-01 phototherapy, a treatment which may be considered in patients with Schnitzler's syndrome if, as is usually the case, they are unresponsive to antihistamine therapy.

Circulating functional autoantibodies to the high-affinity IgE receptor (Fc(epsilon)RI) or to IgE have been found in approximately one third of patients with chronic idiopathic urticaria (CIU).We sought to compare basophil histamine release and basophil numbers in patients with CIU with and without autoantibodies.Basophil histamine release to the anti-Fc(epsilon)RI mAb 22E7, anti-IgE, and formyl-methionyl-leucyl-phenylalanine (fMLP); basophil numbers; and total cellular histamine were measured in 26 patients with CIU and 18 healthy control subjects. Twelve patients were classified as having functional anti-Fc(epsilon)RI and/or anti-IgE autoantibodies on the basis of their serum-evoked histamine release from the basophils of 2 healthy donors.22E7 and anti-IgE, but not fMLP, released less histamine from basophils of patients with CIU than from those of control subjects. Mean+/-SEM maximum histamine release to 22E7 from basophils of control subjects and patients with CIU with and without autoantibodies was 38.5%+/-5.0%, 17.9%+/-6.0% (P =.01), and 1.0%+/-0.3% (P.0001), respectively. Similar results were obtained with anti-IgE, which is dependent on and cross-links cell bound IgE, and 22E7, which directly cross-links the IgE receptor. The mean+/-SEM basophil counts for control subjects and patients with CIU without and with autoantibodies were 52+/-7, 34+/-9 (P =.04), and 5+/-1 (P.0001) x 10(6) cells/L, respectively, and similar changes were found in measurements of total cellular histamine.Patients with autoantibodies have both markedly reduced basophil numbers and basophil histamine release to factors acting through Fc(epsilon)RI, which indicates either a residual pool of functionally distinct basophils or may be a consequence of desensitization of the Fc(epsilon)RI pathway.

Angiotensin-converting enzyme inhibitors (ACEIs) are used increasingly for the treatment of hypertension and chronic heart failure, and they reduce mortality when given after myocardial infarction. Of the patients prescribed these drugs 0.1-0.7% develop angio-oedema, but the association is not widely recognized. In 60% of cases the onset occurs during the first week of treatment; however, it may be considerably delayed. Angio-oedema nearly always occurs on the head and neck, frequently involving the mouth, tongue, pharynx and larynx. The course is unpredictable, and attacks vary in severity from mild to fatal from laryngeal obstruction. Severe ACEI-induced angio-oedema may require emergency treatment with adrenalin and early intubation. The drug should be withdrawn in any patient who presents with ACEI-induced angio-oedema, and treatment continued with an appropriate drug of a different class. Therapy with ACEIs is contraindicated in patients with a prior history of idiopathic angio-oedema, or in patients with hereditary or acquired C1 esterase inhibitor deficiency.

SUMMARY The role of locally released cytokines in inducing lymphocyte activation and infiltration in the skin lesions of mycosis fungoides has been investigated. The levels of selected cytokines were measured in chamber fluid samples from lesional and control skin. Biologically active interleukin 6 was significantly elevated in lesional samples and a recombinant form of this cytokine was shown to induce lymphocyte migration in an in vitro assay. Biologically active interleukin 1 was detected in all control chamber fluid samples. Significantly reduced levels of this cytokine were present in lesional samples, which may be the result of the release of preformed material. Interleukin 2 and tumour necrosis factor activity, and γ interferon and granulocyte macrophage colony-stimulating factor immunoreactivity, were not detectable in any of the samples. Interleukins 1 and 6 may play a role in the pathogenesis of the lesional lymphocyte infiltrates in mycosis fungoides.

The pharmacologic and clinical effects of the 5-lipoxygenase inhibitor, lonapalene, have been determined in a double-blind, placebo-controlled, topical study in ten volunteers with psoriasis. A statistically significant clinical improvement was seen in lesions treated with 2% lonapalene ointment as compared with vehicle-treated sites. Although there was a statistically significant reduction in the levels of material similar or identical to the chemoattractant arachidonate 5-lipoxygenase product, leukotriene B4>, in skin chamber fluid samples from lonapalene versus vehicle treated lesions, no significant reduction in arachidonic acid or 12-hydroxy-5,8,10,14-eicosatetraenoic acid was seen. The reduction in leukotriene B4 equivalents occurred before significant clinical improvement in lesions was seen. This and the selectivity of the pharmacologic response suggest that the therapeutic effect of topical lonapalene in psoriasis might be related to inhibition of leukotriene B4 synthesis. These results support the view that 5-lipoxygenase inhibitors may be useful in the treatment of psoriasis, and that leukotriene B4 is a relevant mediator of the pathology of this disease.

The underlying pathophysiology of chronic urticaria is mast cell activation, with release of histamine and other mast cell mediators. A weal producing factor has been identified in the serum of 60% of patients with chronic idiopathic urticaria. In half of these patients there is evidence for functional autoantibodies against the high affinity IgE receptor or IgE, or both. These autoantibodies release histamine from basophils and mast cells. It is therefore likely that there is an autoimmune basis for up to 30% of patients with idiopathic urticaria. In the other half of patients whose serum causes weals, the factor releases histamine from mast cells only and is as yet unidentified. So far no clinical difference has been associated with presence/absence or type of weal producing factor. Exacerbating factors in chronic urticaria such as aspirin, food additives, febrile illness and psychological stress should be identified and avoided. Treatment is symptomatic with the low sedation antihistamines. In the most severe cases not responding to conventional therapy and which may have the weal producing factor, treatments with non specific immune therapy such as cyclosporin, and intravenous gammaglobulin and also plasmapheresis have been promising.

This investigation was carried out to compare the therapeutic efficacy and cosmetic acceptability of prednicarbate 0.25% ointment in the treatment of atopic dermatitis, and to monitor any local side-effects. A group of 51 patients suffering from atopic dermatitis were randomized to twice daily treatment with prednicarbate 0.25% ointment (n = 24) or vehicle control (n = 27) in a parallel group design with a 4-week treatment period. Prior to treatment, the groups were comparable in all clinically relevant aspects. Prednicarbate was shown to be statistically significantly superior to vehicle control in terms of efficacy. The number of adverse events was observed to be higher in the control group than in the prednicarbate group (15 and 2, respectively).

Background : Circulating autoantibodies against FcϵRI, IgE, or both occur in approximately one third of patients with chronic idiopathic urticaria (CIU), but not all autoantibodies initiate histamine release. Objective : We sought to classify patients with CIU into subsets on the basis of serum bioactivity and immunoreactivity and to examine the relationship between newly defined subtype and disease severity. Methods : Sera from patients with CIU (n = 78), dermog-raphism (n = 15), and cholinergic urticaria (n = 10) and sera from healthy subjects (n = 39) were analyzed by means of Western blot analysis for anti-FcϵRI autoantibodies and for histamine release from basophils and dermal mast cells. In vivo reactivity of autologous serum was tested by means of intradermal injection, and CIU severity was determined on the basis of clinical interview. Results : We classified sera from patients with CIU into 5 subsets: immunoreactive histamine-releasing anti-FcϵRI autoantibodies (n = 20 [26%]); immunoreactive anti-FcϵRI autoantibodies without histamine-releasing activity (n = 12 [15%]); anti-IgE-like autoantibodies (n = 7 [9%]); serum containing a mast cell-specific histamine-releasing factor (n = 7 [9%]); and sera with no identifiable factor (n = 32 [41%]). Patients with serum histamine-releasing activity had more severe urticaria than patients without such activity. Positive skin test responses to autologous sera were associated with histamine-releasing anti-FcϵRI autoantibodies but not with non-histamine-releasing anti-FcϵRI autoantibodies. Neither healthy subjects nor patients with dermographism or cholinergic urticaria had his-tamine-releasing anti-FcϵRI autoantibodies. Conclusion : These data support the specificity of functional anti-FcϵRI autoantibodies to CIU. The identification of distinctive subsets of patients suggests that other pathogenic mechanisms occur in CIU in addition to direct ligation of FcϵRI by autoantibodies causing dermal mast cell degranulation. Elucidating these mechanisms might lead to new treatments for CIU. (J Allergy Clin Immunol 2002;110:492-9.)

H1-antihistamines are the cornerstone of symptomatic treatment in acute and chronic urticaria, in which they not only relieve itching, but also reduce the number, size, and duration of urticarial lesions. Relief of whealing, flaring, and erythema may be incomplete as the vascular effects of histamine are mediated to its action at H2-receptors as well as at H1-receptors, and other vasoactive substances may also be involved. In randomized, prospective, placebo-controlled, double-blind studies, the new low-sedating H1-antihistamines have been found to be effective and safe in urticaria. Sedating antihistamines, although effective, place patients at risk for adverse effects, including decreased psychomotor performance. The response to H1-antihistamines in some types of urticaria, for example, in urticarial vasculitis, is unsatisfactory. An H2-antihistamine administered concurrently with an H1-antihistamine may modestly enhance relief of itching and wheal formation in some patients with urticaria refractory to treatment with an H1-antihistamine alone. The available evidence does not justify the routine addition of H2-antihistamine treatment to H1-antihistamine treatment.

H1-antihistamines are the cornerstone of symptomatic treatment in acute and chronic urticaria, in which they not only relieve itching, but also reduce the number, size, and duration of urticarial lesions. Relief of whealing, flaring, and erythema may be incomplete as the vascular effects of histamine are mediated to its action at H2-receptors as well as at H1-receptors, and other vasoactive substances may also be involved. In randomized, prospective, placebo-controlled, double-blind studies, the new low-sedating H1-antihistamines have been found to be effective and safe in urticaria. Sedating antihistamines, although effective, place patients at risk for adverse effects, including decreased psychomotor performance. The response to H1-antihistamines in some types of urticaria, for example, in urticarial vasculitis, is unsatisfactory. An H2-antihistamine administered concurrently with an H1-antihistamine may modestly enhance relief of itching and wheal formation in some patients with urticaria refractory to treatment with an H1-antihistamine alone. The available evidence does not justify the routine addition of H2-antihistamine treatment to H1-antihistamine treatment.

Urticaria is a common skin condition. Although an episode may be mild and last only a few days, chronic urticaria can significantly affect the quality of life. The condition is frequently misunderstood by patients who believe the condition is always the result of an allergy and is dangerous.

Background: Previous studies defining the histopathologic features of patients with chronic idiopathic urticaria (CIU) were performed on wheals of uncertain duration and before the identification of functional autoantibodies against FcϵRI and/or IgE, now known to be present in approximately 30% of patients with CIU. Objective: We sought to determine the timing of the inflammatory infiltrate in the wheals of patients with CIU and to detect differences between patients with and without autoantibodies. Methods: Immunohistochemistry was used to identify neutrophils (neutrophil elastase), T lymphocytes (CD3), and activated eosinophils (EG2) in biopsy specimens from uninvolved skin and wheals present for less than 4 hours and greater than 12 hours in 22 patients with CIU, as well as in biopsy specimens from the skin of 12 healthy control subjects. Patients were identified as having functional autoantibodies on the basis of their serum-evoked histamine release in vitro from the basophils of 2 healthy donors. Results: EG2 + , neutrophil elastase + , and, to a lesser extent, CD3 + cells were found in greater numbers in wheals undergoing biopsy at less than 4 and greater than 12 hours than in uninvolved skin ( P + cells in wheals of greater than 12 hours' duration than patients with autoantibodies (n = 10; P = .02). There was no other difference between patients with and without autoantibodies in the cutaneous cellular infiltrate. Conclusion: Neutrophil and eosinophil accumulation occurs early in the evolution of a wheal in patients with CIU, but eosinophil activation may occur later or be more persistent in patients without autoantibodies. (J Allergy Clin Immunol 1999;103:484-93.)

Six patients with delayed pressure urticaria (DPU) applied clobetasol propionate (0.05%) ointment or its base to predetermined test sites on the right and left thigh as part of a randomized, double-blind study. A pressure challenge was administered to each test site at the initial visit and repeated after 3 days and 6 weeks of treatment and at between 4 and 8 weeks after treatment. The areas of pressure-induced weals were measured 6 h after each challenge. At the 6-week visit, a 4-mm punch biopsy was taken from pressure-challenged skin on each test site. Sections were stained for mast cells and immunohistochemical labelling was used to demonstrate neutrophils (neutrophil elastase), eosinophils (eosinophil cationic protein), monocytes/macrophages (EBM 11), cells expressing the beta-2 integrins (CD11/18) and the vascular adhesion molecules, E selectin and intercellular adhesion molecule-1 (ICAM-1). In the steroid-treated sites, there was a significant decrease (P0.05, Wilcoxon's matched-pairs test) in the size of the pressure weals compared with baseline at 3 days, 6 weeks and at follow-up. Demonstrable mast cells were significantly decreased (P = 0.059) in the pressure-challenged areas in the steroid-treated sites compared with the base-treated sites. The histological response to pressure was minimal in both sites perhaps demonstrating an active pharmacological effect of the ointment base. In conclusion, the application of potent topical steroids significantly reduced the clinical response to pressure in patients with DPU, possibly through a reduction in mast cells.

SUMMARY The naevoid basal cell carcinoma syndrome is described in a 43-year-old male. The response of dividing fibroblasts from this patient to the lethal effects of ionizing radiation was indistinguishable from that of a normal control: mean inactivation dose (D)=1.74 Gy and 1.68 Gy, respectively. However, these cells were defective in the repair of potentially lethal damage (D=2.36 Gy and 3.26 Gy, respectively). The response to radiation of Go T lymphocytes derived from the patient was similar to that of the control. The frequency of mutant circulating T lymphocytes resistant to 6-thioguanine was 17 × 10−6 which was elevated when compared with age-matched controls. These results suggest an abnormality in the response of the fibroblasts to ionizing radiation damage.

We studied 44 patients with delayed pressure urticaria. The mean age at onset of the disease was 33 years (range, 5 to 63 years) and the mean duration of disease was 9 years (range, 1 to 40 years). After pressure stimulus, the mean onset of whealing occurred in 3 1/2 hours, the mean peak swelling occurred after 10 hours, and the mean lesion duration was 36 hours. Two thirds of patients had generalized flulike symptoms. Sixty percent had disabling nonremitting delayed pressure urticaria. Sixty-two percent had coexistent chronic idiopathic urticaria, and 27% had angioedema. Delayed pressure urticaria was confirmed by pressure tests with either a calibrated dermographometer or suspended weights. More than 50% of patients tested also had delayed dermographism. A double-blind, controlled, crossover trial of indomethacin therapy in 14 patients revealed no Significant subjective improvement or reduction in area of induced wheals. We conclude: (1) The diagnosis of delayed pressure urticaria can be easily made by dermographometer testing. (2) Delayed dermographism may be the same entity as delayed pressure urticaria induced by a different method of pressure application. (3) Systemic corticosteroids remain the only known effective treatment for disabling delayed pressure urticaria.

The 5,12-dihydroxy metabolite of arachidonic acid, leukotriene B 4 , is a highly potent neutrophil chemoattractant. In view of the characteristic epidermal neutrophil infiltrate in psoriasis, the presence of leukotriene B 4 in samples from untreated lesional and uninvolved skin has been sought. Chambers were fixed to abraded skin and filled with phosphate-buffered saline (PBS). After 35 mm, the fluid was removed, and acidic lipids were extracted and subjected to high-performance liquid chromatography (HPLC). Extracts were purified by both straight- and reversed-phase HPLC, and assay of evaporated fractions by an agarose microdroplet chemokinesis technique indicated the presence of leukotriene B 4 -like material. No significant leukotriene B 4 - like activity was found in samples from uninvolved skin. Subsequent experiments using a modification of the initial skin chamber method indicated that leukotriene B 4 was being released from deeper layers of lesional skin and not only from superficial scale. Monohydroxy-ei- cosatetraenoic acid-like activity was also seen in lesional samples as determined by straight-phase HPLC and chemokinesis assay. These findings and the proinflammatory properties of these compounds in human skin suggest that they may play a role in the pathogenesis of the psoriatic neutrophil infiltrate.

A randomized double-blind placebo controlled trial of colchicine in the treatment of 13 patients with delayed pressure urticaria enabled us to assess some of the variables in this disorder. We have modified a previously described method of pressure testing using a calibrated dermographometer and shown a pressure induced papular dose response curve. Assessment of disease activity was based on the number of pressure weals which occurred, the size of delayed pressure induced papules using a dermographometer calibrated at 9.75 x 10(5) pascals for five separate time periods on the back and estimations of erythrocyte sedimentation rate and the acute phase protein levels. We have been unable to show a therapeutic effect using colchicine 0.5 mg bd for I week.

Summary Twenty-seven biopsy specimens from 11 patients with pressure urticaria were studied. Sixteen of the specimens were from spontaneous lesions, of which five were pairs of early and late lesions. Some early lesions showed neutrophilia and eosinophilia in the deep tissue, and late lesions showed significant perivascular lymphocytosis with eosinophilia. Eleven dermograph-ometer-induced lesions showed neutrophilia in the superficial localized dermal tissue and progressive eosinophilia in the superficial localized dermal tissue; the deep vascular and dermal tissues were occasionally involved. The level of Cl-esterase inhibitor was elevated in eight of the nine cases studied. We believe that pressure urticaria may be similar to other whealing diseases, with an early neutrophilic phase of inflammation and a late phase of lymphocytosis and eosinophilia.

Urticarial responses in skin may be elicited in different ways, viz, stroking (dermographism), after sustained pressure (delayed pressure urticaria), and after vibration (vibratory angio-oedema). Pressure may localise lesions of chronic idiopathic urticaria. Trauma may exacerbate hereditary angio-oedema. The extent of the morbidity caused by trauma-induced urticaria among workers is unknown.

Psoriasis is a common chronic inflammatory and proliferative skin disease characterised by epidermal neutrophil infiltration which may be induced by chemotactic substances in the involved epidermis. Superficial psoriatic scale was shown to contain biologically active amounts of leukotriene B4 and monohydroxy-eicosatetraenoic acid (HETE)- like material as determined by assay for chemokinetic activity in high performance liquid chromatography (HPLC) fractions of scale extracts. Extracts of scale and chamber fluid from abraded lesional and uninvolved psoriatic skin were purified by HPLC and appropriate fractions were analysed by gas chromatography - mass spectrometry (GC-MS). The following monohydroxy metabolites of arachidonic, linoleic and 11,14-eicosadienoic acids were identified : 15-HETE, 12-HETE, 11-HETE, 9-HETE, 8-HETE, 5-HETE, 13-hydroxy-octadecadienoic acid (13-HODD), 9-HODD and 15-hydroxy-eicosadienoic acid (15-HEDE). The results suggested that 12-HETE, 13-HODD and 9-HODD are the most abundant monohydroxy fatty acids in the psoriatic skin extracts described above. Assays of 13-HODD, 9-HODD and 15-HEDE for chemokinetic activity were negative with concentrations up to 10−4M. The biological significance of these three compounds in not known, but some of the hydroxylated metabolites of arachidonic acid may, by virtue of their chemotactic properties, be relevant to the pathogenesis of the psoriatic neutrophil infiltrate.

SUMMARY Clobetasol propionate 0.05% ointment and an otherwise identical steroid-free base were applied topically to a 10 cm2 area on the anterior thighs of six patients with symptomatic dermographism for 6 weeks. Four patients showed a significantly decreased wealing response to stroking of steroid pretreated skin compared to that of control sites. There was a parallel decrease in mast cell numbers and histamine levels in skin biopsies taken from the steroid treated areas. At 6 weeks two patients demonstrated a decrease in flare areas following the intradermal injection of compound 48/80 in steroid pretreated skin compared to base treated sites. Flare areas following intradermal injection of histamine in these two patients were equivalent in base and steroid treated skin.

The responses to 12-HETE in normal human skin have been investigated by means of intradermal and topical administration in 15 subjects. Intradermal infusion of 12-HETE produced a neutrophil polymorphonuclear and mononuclear infiltrate in the dermis. Topical administration resulted in a dose-related erythematous response to 200 ng-50 micrograms. This was accompanied by a neutrophil and mononuclear dermal infiltrate at 6 and 24 h after application. In addition, collections of neutrophils were present in the epidermis in 4 of 10 subjects biopsied at 6 h and in all patients biopsied 24 h after topical application. Intradermal and topical application of 9-hydroxyoctadecadienoic acid (9-HODD), a chemically similar but chemokinetically inactive substance, did not produce neutrophil infiltration of the epidermis, nor did the chemical irritant nonanoic acid. The results suggest that the cellular infiltrates produced in vivo in humans by 12-HETE are due to its chemoattractant properties and are not the result of a nonspecific inflammatory response.

Delayed pressure urticaria is a physical urticaria where erythematous, often painful swellings occur at sites of sustained pressure on the skin, after a delay of several hours. If sought, it is present in up to 40% of patients with ordinary chronic "idiopathic urticaria" to a varying degree. Compared with other urticarias, the pressure-induced lesions impair the quality of life of patients most severely. The pathogenesis is not well characterized, but whealing is dependent on mast cell activation, with the histology of lesions also showing a deep dermal inflammatory infiltrate of neutrophils and eosinophils, without vasculitis. Treatment of delayed pressure is generally unsatisfactory, and is often resistant to antihistamine and a range of anti-inflammatory medication. Oral steroids, although the most effective therapy, are unsuitable for long-term use. Delayed pressure urticaria may persist for many years, and improved or novel methods of management are under investigation.