Pressure Urticaria 

Updated: Jan 25, 2019
Author: Sarah Beggs, MD; Chief Editor: Dirk M Elston, MD 

Overview

Background

Pressure urticaria is an uncommon form of physical urticaria, a subset of chronic urticaria, which presents with erythematous swelling at sites of pressure. Chronic urticaria is termed when patients have ongoing urticaria for more than 6 weeks. An inciting event or etiology is usually not identified for patients with chronic urticaria—hence the term chronic idiopathic urticaria (CIU) is often used. A proportion of patients diagnosed with chronic urticaria have physical urticaria, also referred to as chronic inducible urticaria (CIndU),[1] which is urticaria incited by a physical stimulus, such as mechanical (friction, vibration, pressure) urticaria, thermal (heat or cold) urticaria, solar urticaria, and symptomatic dermatographism.[2, 3]

Pressure urticaria may occur immediately (within minutes) or, more commonly, 4-6 hours after a pressure stimulus.[3, 4] For this reason, the term delayed pressure urticaria (DPU) is typically used. It appears as an erythematous, cutaneous, and often subcutaneous edema. The reaction may last up to 72 hours and can be associated with pruritus, burning, and pain.[5] Pressure sites, including the hands, feet, trunk, buttocks, and legs, are most commonly affected. Lesions can be induced by a variety of stimuli, including standing, walking, wearing of tight clothes, and sitting or leaning on a hard surface.[6] See the image below.

Delayed pressure urticaria. Courtesy of DermNet Ne Delayed pressure urticaria. Courtesy of DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/reactions/pressure2.jpg).

Pathophysiology

The pathogenesis of delayed pressure urticaria (DPU) is relatively unknown. Although the trigger stimulus of pressure is identified, no allergen has been established. Urticaria (hives) is a type I hypersensitivity reaction, where autoantibodies against IgE molecules are involved. When an antibody or autoantibody binds to the IgE molecule, a bridge is formed between two or more IgE molecules. This induces mast cell degranulation, releasing multiple proinflammatory mediators, including histamine, leukotriene, and prostaglandin. In chronic idiopathic urticaria (CIU), the mast cells are inappropriately activated.[3, 7]

Histamine levels are increased in the lesional skin, while intracellular histamine levels are decreased in peripheral white blood cells.[8] There is also an increased stimulation of histamine release. Despite these findings, histamine is unlikely to be the sole mediator in pressure urticaria. This is further demonstrated in the inconsistent effectiveness of antihistamine treatment in pressure urticaria.

Other mediators are believed to be involved, and mast cells may be triggered by IgE-independent pathways. Patients with chronic inducible urticaria (CIndU) have increased serum levels of IgE.[3] This includes eosinophils (as suggested by the presence of eosinophilia), eosinophil cationic protein (ECP), and eosinophil cationic factor (ECF) found in biopsy specimens from select patients with DPU, particularly those with bullous DPU.[9, 10] In addition, elevated concentrations of interleukin (IL)–1a, IL-5, and IL-6; tumor necrosis factor (TNF)–alpha; and leukotrienes have also been found in lesional skin of pressure urticaria patients.[11, 12, 13] Vascular endothelial growth factor has also been found to be elevated in patients with DPU.[14] Abnormalities in platelets and fibrin or fibrinolysis have also been investigated.[15, 16] Systemic inflammation has also been suggested, with elevations seen in C-reactive protein (CRP) and sCD40L, a platelet activator.[17, 18]

Etiology

Pressure stimuli may include the following[3, 6] :

  • Standing, walking, leaning, or sitting

  • Using tools 

  • Carrying a handbag or backpack

  • Wearing tight-fitting clothes (eg, bra straps or watches)

Occasionally, delayed pressure urticaria (DPU) is aggravated by heat, aspirin, or menstruation. Exacerbation of the condition during medical procedures is a reasonable possibility; urticaria flares following endoscopy have been described.[19]

Epidemiology

Delayed pressure urticaria (DPU) is generally considered a rare entity; however, this may be because it is not consistently recognized.[1] Approximately 37% of patients with chronic spontaneous urticaria also have pressure urticaria.[1, 20]

The mean age of onset of DPU is in the 30s (range, 5-63 y).[21] DPU is slightly more common in men than in women.

Prognosis

Delayed pressure urticaria (DPU) is a chronic disease that can last for years (mean, 9 y; range, 1-40 y).[21] The morbidity of DPU varies, depending on the severity and the response to treatment. In some patients, this condition can be disabling, especially in patients who perform manual labor.

Quality-of-life (QOL) tools have demonstrated that patients with urticaria can show impairments in QOL scores similar to those seen in patients with chronic dermatoses such as psoriasis and atopic eczema. QOL scores were lowest for patients with chronic idiopathic urticaria (CIU) compared with psoriasis and atopic dermatitis for “self-perception,” “social functioning,” and “treatment-induced restrictions.”[22]

 

Presentation

History and Physical Examination

The clinical manifestations of delayed pressure urticaria (DPU) differ from those typical of most types of urticaria. Onset is typically delayed, most commonly occurring 4 hours after the pressure stimulus. Less commonly, wheals due to pressure develop within minutes, in which case they may be confused with dermatographism. The lesions of DPU can persist for several hours and sometimes for as long as 72 hours, unlike those in typical urticaria, which resolve within 24 hours.

The physical findings in DPU include wheals, typically involving the palms, soles, legs, and waist. DPU lesions may also involve the genitals. The wheals, which appear as deep dermal and subcutaneous swellings, often resemble angioedema more than they do typical urticaria. Typical urticaria may also be present as a result of coexisting chronic idiopathic urticaria (CIU) or some other chronic physical urticaria.

The lesions may be pruritic, painful, or burning. They can occur on any cutaneous surface and may mimic angioedema. With severe episodes, patients may experience fever, malaise, fatigue, chills, headache, and generalized arthralgias. Affected areas can be refractory to the development of new lesions for 1-2 days.

As many as 60% of individuals with DPU have concomitant chronic idiopathic urticaria (CIU), immediate or delayed dermographism (dermatographism), or angioedema. In some reports, the incidence of DPU in patients with CIU varies considerably, ranging from 2% to 40%; other reports estimate the rate to be 2-4%.[1, 23, 24]

See the image below.

Delayed pressure urticaria. Courtesy of DermNet Ne Delayed pressure urticaria. Courtesy of DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/reactions/pressure2.jpg).

 

 

DDx

Diagnostic Considerations

The development of systemic signs of angioedema or urticaria, such as severe swelling and shortness of breath, may coexist with delayed pressure urticaria (DPU).

In addition to the conditions listed in the differential diagnosis, other problems to be considered include delayed dermographism and vibratory urticaria

Differential Diagnoses

 

Workup

Laboratory Studies

An elevated white blood cell (WBC) count or neutrophilia may be present.[25, 26] Complement levels are normal.

Some patients with delayed pressure urticaria (DPU) also have concomitant chronic idiopathic urticaria (CIU). Basic testing for CIU includes CBC count with differential, erythrocyte sedimentation rate, and/or C-reactive protein. Extended diagnostic testing includes the following[20, 27] :

  • Thyroid function tests and antibody testing for autoimmune thyroid disease

  • Antibody testing for Helicobacter pylori 

  • Autoantibody to IgE 

  • Allergy testing (skin tests and/or allergen avoidance tests)

Pressure Challenge Testing

Pressure challenge testing (with the dermographometer or the suspended-weight method) may be performed for delayed pressure urticaria (DPU). Because therapy may influence test results, it is recommended that testing be performed at a time when therapy has been interrupted or stopped for at least 3 days; however, some patients may have more severe disease that does not allow this. Repetitive testing can be used to assess response to therapy.

Multiple methods of applying measured amounts of pressure can be used to test for the development of DPU. A consensus conference review suggests using the following approaches[20] :

  • A shoulder strap 3 cm wide with a 7-kg weight for 15 minutes

  • A rod 1.5 cm in diameter with a 2.5-kg weight for 15 minutes

  • A rod 6.5 cm in diameter with a 5-kg weight for 15 minutes

  • A dermographometer to a pressure of 100 g/mm2 for 70 seconds

The tests are most often applied to the shoulders, upper back, posterior thighs, or volar forearm. Pressure provocation tests should be read at 6 hours. Both the weight and the application time should be recorded. The duration of application is inversely related to the pressure applied; for example, wheals take longer to develop with a lower pressure than with a higher pressure.

Histologic Findings

The histologic features of delayed pressure urticaria (DPU) lesions are variable, often depending on the age of the lesion. Biopsy within hours demonstrates moderate-to-heavy infiltration of eosinophils with neutrophils and lymphocytes in a perivascular and interstitial pattern in the dermis and subcutaneous fat. Degranulated mast cells may be noted. Biopsy of an older DPU lesion (>24 h) demonstrates eosinophils and lymphocytes.

No vessel-related changes (eg, leukocytoclasia or fibrinoid necrosis), such as those noted in urticarial vasculitis, are seen. Direct immunofluorescence test results are negative.

Several reports of bullous pressure urticaria have been reported, and histologic findings show spongiosis and intraepidermal bullae associated with an eosinophil-rich inflammatory infiltrate in the superficial and deep dermis.[10]

 

Treatment

Approach Considerations

Patients should avoid triggers of urticaria and attempt to limit pressure stimuli. A simple intervention is to broaden the handles on heavy items or straps on clothing to disperse the pressure over a larger area. However, avoidance is not easy and may not be helpful in patients with moderate-to-severe disease.

Second-generation antihistamines are considered first-line treatment for delayed pressure urticaria (DPU); however, DPU is relatively refractory to antihistamines.[28, 29] Omalizumab has shown promise for chronic inducible urticaria (CIndU) in patients with disease refractory to antihistamines, with few adverse effects.[30, 31, 32, 33, 34, 35] Systemic corticosteroid treatment leads to improvement of DPU; however, its use is limited owing to its adverse effect profile. Second- and third-line agents used have included colchicine, dapsone, sulfasalazine, montelukast, chloroquine, cyclosporine, intravenous immunoglobulin (IVIg), and anakinra.[28, 36, 37, 38, 39, 40, 41, 42, 43, 44]

Restrictions in activity depend on the severity of the disease. Consult a dermatologist or allergist for evaluation for other causes of urticaria.

Pharmacologic Therapy

Antihistamines can reduce the severity of swelling and frequency of urticaria and are helpful in controlling associated chronic idiopathic urticaria (CIU). There are few adverse effects of antihistamines, mainly sedation, which is less potent in the second-generation antihistamines. Some authors have suggested up to 4 times the recommended dose of nonsedating antihistamines to achieve control. However, delayed pressure urticaria (DPU) has notoriously been known to be refractory to antihistamines and antihistamines may not control the symptoms completely.[28, 29]

Omalizumab, a recombinant DNA monoclonal antibody that binds to IgE, is showing promising results in CIU, with few adverse effects, owing to its ability to decrease mast cell degranulation. It is approved by the US Food and Drug Administration for CIU, but not necessarily for chronic inducible urticaria (CIndU). Studies published in early 2019 express hope there will soon be approval for CIndU.[34] Three phase 3 clinical trials, ASTERIA I, ASTERIA II, and GLACIA, involving over 900 patients with chronic spontaneous urticaria showed the benefits of omalizumab.[45] A phase 3, multicenter study has shown that omalizumab decreased itchiness and hives and increased quality of life (QOL) in patients with CIU or chronic spontaneous urticaria, whose disease had been refractory to antihistamine therapy.[30] Patients, including those with DPU, who initially had a positive response to omalizumab, and then relapsed after stopping treatment, achieved remission after restarting omalizumab.[31] Multiple case reports have reported the benefit of omalizumab treatment in patients with DPU.[30, 31, 32, 33, 35]

Steroids are best restricted for recalcitrant and severe DPU.[21] Prednisone has some clinical efficacy, but long-term therapy is problematic because of its many adverse effects. One study of a small group of patients found high-potency topical steroids to be efficacious for reducing edema, erythema, and pruritus associated with DPU lesions.[46] Patients who see improvement with systemic steroid therapy often relapse when these agents are discontinued. The adverse effects of steroids must also be considered and managed.[47] Methotrexate has been used successfully in steroid reduction in a few patients with steroid-dependent DPU.[45]

NSAIDs produce variable responses. As treatment, they may be suboptimal because they, along with aspirin, may worsen urticaria and angioedema. 

Other therapeutic agents that have been tried include colchicine, dapsone, sulfasalazine, and montelukast.[28, 36, 44, 48, 49, 50] Colchicine has been largely ineffective as a therapy.[50] Dapsone has demonstrated beneficial results persisting after treatment in a small study.[36] A 2015 case series showed that in 17 patient treated with sulfasalazine, 11 had complete or near complete resolution and four had a partial response.[37] Reports from small studies have found leukotriene antagonists, alone or in combination, to be efficacious for the treatment of DPU[8, 44] ; other forms of chronic urticaria have not demonstrated similar responses to this treatment. Case reports have demonstrated some success with chloroquine, cyclosporine, IVIg, tricyclic antidepressants, selective serotonin reuptake inhibitors, and anakinra.[38, 39, 40, 41, 42, 43]

Combination therapy may decrease disease activity. Adjunctive agents that reportedly have been successfully used in this context include leukotriene antagonists (eg, montelukast, zafirlukast) and H2-receptor antagonists (eg, famotidine, ranitidine).[44]

 

Medication

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications. The mainstay agents used in the management of pressure urticaria include antihistamines and corticosteroids. The benefit of omalizumab has been established in chronic idiopathic urticaria (CIU) and shows benefit for patients with delayed pressure urticaria (DPU). Other medications such as leukotriene antagonists, dapsone, sulfasalazine, methotrexate, cyclosporine, and intravenous immunoglobin (IVIg) have limited data, with only few case reports.

Antihistamines, 2nd Generation

Class Summary

Antihistamines may be useful in helping control symptoms of chronic urticaria, which frequently coexists with delayed pressure urticaria (DPU). Second-generation antihistamines, also known as less-sedating or low-sedation antihistamines, produce less sedation than traditional H1 blockers because they are less lipid-soluble and only cross the blood-brain barrier in small amounts. They also have longer half-lives, allowing less frequent dosing. Many H1 antagonists are metabolized through the cytochrome P-450 system. Important exceptions include cetirizine, levocetirizine, and fexofenadine.

Fexofenadine (Allegra, Allegra Allergy 12 Hour, Allegra Allergy 24 Hour)

Fexofenadine is a nonsedating second-generation medication that has fewer adverse effects than first-generation medications. It competes with histamine for H1 receptors in the gastrointestinal (GI) tract, blood vessels, and the respiratory tract, reducing hypersensitivity reactions. Fexofenadine does not sedate. It is available in once-daily and twice-daily preparations.

Cetirizine (Aller-Tec, Children's Zyrtec Allergy, Children's Zyrtec Hives Relief)

Cetirizine selectively inhibits H1 receptor sites in blood vessels, the GI tract, and the respiratory tract, thereby inhibiting the physiologic effects that histamine normally induces at H1 receptor sites. Once-daily dosing is convenient; bedtime dosing may be useful if sedation is a problem.

Loratadine (Claritin, Claritin RediTabs, QlearQuil All Day & All Night 24 Hour Allergy Relief)

Loratadine selectively inhibits peripheral histamine H1 receptors.

Levocetirizine (Xyzal)

Levocetirizine is an H1-receptor antagonist and an active enantiomer of cetirizine. Peak plasma levels are reached within 1 hour, and the half-life is approximately 8 hours. Levocetirizine is available as a 5-mg breakable (scored) tablet and a 0.5 mg/mL oral solution. It is indicated for uncomplicated skin manifestations of chronic idiopathic urticaria (CIU).

Desloratadine (Clarinex, Clarinex RediTabs)

Desloratadine is a long-acting tricyclic histamine antagonist that is selective for H1 receptors. It is a major metabolite of loratadine, which, after ingestion, is extensively metabolized to the active metabolite 3-hydroxydesloratadine.

Antihistamines, 1st Generation

Class Summary

First-generation antihistamines compete with histamine at the tissue-receptor level, preventing it from carrying out its mediator functions in urticaria.

Diphenhydramine (Alka-Seltzer Plus Allergy, Benadryl, Benadryl Allergy Dye-Free LiquiGels)

Diphenhydramine is a first-generation antihistamine with anticholinergic effects. It binds to H1 receptors in the central nervous system (CNS) and the body, competitively blocking histamine from binding to these receptors.

Diphenhydramine is employed for symptomatic relief of pruritus caused by release of histamine in inflammatory reactions. It has significant antimuscarinic activity and penetrates the CNS and thus has a pronounced tendency to induce sedation. Approximately half of those treated with conventional doses experience some degree of somnolence. A small percentage of children paradoxically respond to diphenhydramine with agitation.

Hydroxyzine (Vistaril)

Hydroxyzine antagonizes H1 receptors in the periphery. It may suppress histamine activity in the subcortical region of the CNS.

Monoclonal Antibodies

Class Summary

Monoclonal antibodies directed to immunoglobulin E (IgE) binding may reduce the release of mediators that provoke an allergic response. These agents may be considered when H 1 -receptor antagonists are ineffective.

Omalizumab (Xolair)

Omalizumab is a recombinant humanized monoclonal antibody administered by subcutaneous injection every 4 weeks. It selectively binds to IgE and inhibits binding to IgE receptors on the surface of mast cells and basophils. It is indicated for chronic idiopathic urticaria in adults and children aged 12 years or older who remain symptomatic despite anti-H1 antihistamine treatment.

Corticosteroids

Class Summary

Because of their anti-inflammatory properties, corticosteroids have been used in the management of pressure urticaria, with variable success.

Prednisone (Deltasone, Prednisone Intensol, Rayos)

Prednisone may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte (PMN) activity. It stabilizes lysosomal membranes and suppresses lymphocyte and antibody production.

Prednisolone (FloPred, Millipred, Millipred DP)

This glucosteroid occurs naturally and synthetically. It is used for both acute and chronic asthma. It may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte activity.

Antihistamines, H2 Blockers

Class Summary

H2 antagonist therapy can be used as an adjunct to H1 antagonist therapy.

Famotidine (Acid Controller, Act, Dyspep HB)

Famotidine is an H2 antagonist that, when combined with an H1 type, may be useful in treating allergic reactions that do not respond to H1 antagonists alone.

Ranitidine (Zantac, Zantac 150 Maximum Strength, Zantac 75)

Ranitidine is a second-generation agent that is effective for the treatment of urticaria. It is tolerated very well, with a rate of sedation that is not significantly different from that seen with placebo.

Nizatidine (Axid)

This agent competitively inhibits histamine at the H2 receptor of the gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and reduced hydrogen concentrations.

Cimetidine (Tagamet HB)

This agent inhibits histamine at H2 receptors of gastric parietal cells, which results in reduced gastric acid secretion, gastric volume, and hydrogen concentrations.

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

Class Summary

NSAIDs are the medications most commonly used to control mild to moderate pain and to decrease inflammation. Sulfasalazine, steroids, and immunosuppressive agents are sometimes used, with varying degrees of success. NSAIDs can also be a nonimmunologic trigger of mast cell degranulation and subsequent urticaria.

Ibuprofen (Advil, Motrin, PediaCare Children's Pain Reliever/Fever Reducer IB)

Ibuprofen is an NSAID with analgesic, anti-inflammatory, and antipyretic properties. It inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.

Naproxen (Aleve, Anaprox, Anaprox DS)

Naproxen inhibits inflammatory reactions and pain by decreasing the activity of cyclooxygenase, which results in a decrease of prostaglandin synthesis.

5-Aminosalicylic Acid Derivatives

Class Summary

These agents have anti-inflammatory effects.

Sulfasalazine

Sulfasalazine decreases the inflammatory response and systemically inhibits prostaglandin synthesis.

Antidepressants, TCAs

Class Summary

Agents in this class that antagonize the H1 receptor preventing histamine from causing urticaria. The tricyclic antidepressant doxepin is used in urticaria for its sedative and antihistaminic properties. Oral doxepin may be considered if oral antihistamines are not helpful.

Doxepin (Silenor)

Doxepin is a tricyclic antidepressant that has potent H1-blocking activity, which makes it quite useful for urticaria. However, doxepin has very potent sedative and anticholinergic effects. It can be quite effective if given at bedtime because its sedative effects can make it easier for patients with pruritus to sleep.

Corticosteroids, Topical

Class Summary

Some small studies have shown topical corticosteroids to be efficacious in reducing the size of pressure urticaria lesions, as well as the erythema and pruritus associated with them.

Clobetasol (Clarelux, Clobex, Clobex Spray)

Clobetasol propionate is a class I superpotent topical steroid; it suppresses mitosis and increases synthesis of proteins that decrease inflammation and cause vasoconstriction. Clobetasol decreases inflammation by stabilizing lysosomal membranes, inhibiting PMN leukocytes and mast cell degranulation.