When a patient presents to the office with symptoms and signs suggestive of CU, a good history and clinical examination aids in the accurate diagnosis of CU. 

Clinical history:

In addition to general history-taking, the clinician should focus particular attention on the history of exposure to potential causative agents in food, home/work environment, cosmetics, and personal care products. Temporal relationship from the time of exposure to the development of symptoms and time for resolution of symptoms is necessary information. Also include aggravating factors (i.e., temperature changes, physical pressure, etc.) and relieving factors like medications in history. Obtain details on the specific skin symptoms (Ex. wheals, tingling, burning, itching) and progression of symptoms. A personal and family history of atopy helps make the diagnosis of IgE-mediated ICU. Volatile proteins can cause signs and symptoms of conjunctivitis, rhinitis, or asthma when they come in contact with the mucosa of the conjunctiva or respiratory tract (Ex. flour). Other systemic symptoms like abdominal pain, itching in the mouth on oral ingestion (oral allergy syndrome), and diarrhea may develop in contact with the mucosa of the gastrointestinal tract. 

Physical examination:

Clinical presentation is commonly a wheal and flare response and urticarial swelling. Patients affected by CU can present with hives (urticaria) or dermatitis (eczema). The urticarial response appears as an erythematous swelling with surrounding pallor. In a NICU reaction, the typical wheal and flare response may be absent. The skin examination should focus on the site of involvement, the pattern of distribution, size, shape, and confluency of lesions, angioedema, erythema, pallor, dermographism, and urticarial vasculitis. CU wheals do not blister, and scaling is generally not seen. They remain transient without any residual skin changes or pigmentation.[21] The diagnostic signs are different during an active flare vs. a period of quiescence.

PCD presents as recurrent dermatitis with urticarial plaques or vesicles. The vesicles can develop rapidly and progress to erythematous-squamous or erythematous-vesicular lesions.[22] Paronychia with periungual edema and erythema can be a sign of PCD.[23]

In-vivo and in-vitro methods are useful in diagnostic evaluation, in addition to history and physical examination. Skin tests are quick to perform and considered relatively safe. 

In-vivo test

In-vivo tests are most common for the diagnosis of CU.  Clinical supervision with the provision to handle an impending anaphylactic shock is necessary. Both ICU and NICU reactions occur within 15 to 20 minutes or can be delayed. If testing on intact skin is negative, then previously affected skin sites are used. Positive test results require careful correlation with clinical symptoms. Medications like antihistamines, NSAIDs, and exposure to ultra-violet light can cause false-negative results. The patient should be off antihistamines for 48 hours before testing. See figure 1 for the diagnostic algorithm to test for immediate contact reactions.[6][24]

• Prick test: It is considered the test of choice for the diagnosis of ICU. The inner aspect of the forearm is the preferred site, and multiple allergens can undergo testing simultaneously, using positive control with histamine and negative control with normal saline with results interpreted in 30 minutes. False-positive results occur due to a positive reaction from one test site spreading to the neighboring site or irritant reaction. PCD is diagnosable with the prick test. If skin prick tests and serum allergen-specific IgE tests are negative, a provocation or direct challenge test may be needed.
• Open test/ skin provocation test: The open test is used for the diagnosis of NICU. The test consists of gently rubbing 0.1ml of the test substance over a 3 cm x 3 cm area of intact skin on the volar aspect of the forearm. The site requires an examination at 20, 40, and 60 minutes. The best vehicle for testing the agents is an alcohol-water or alcohol propylene glycol mixture.
• Use test: The test agent in the same vehicle of delivery is used to observe for the reaction. The serial incremental dosing of the agent is. The usual sites of skin testing are the upper back, flexor aspect of the upper arm, and forearm.
• Chamber/ patch test: The test substance is applied to small aluminum containers for 15 minutes and attached to the skin via porous tape. The results are recorded at 20, 40, and 60 minutes for an immediate reaction. A delayed-type response gets assessed at 48 to 96 hours after patch application to the back. The sensitivity of this test is higher due to increased absorption by the skin. A smaller area of skin is used than the open test. A false-positive response called 'angry back' due to active dermatitis is noted in some. A patch test is not routinely recommended because many common allergens may cause a false positive response (ex. balsam of Peru, paraben, sorbic acid, formaldehyde, cinnamaldehyde, etc.).
• Scratch test: A deep dermal scratch with the test substance is performed using the blunt bottom of a lancet after the allergen is applied to the skin; this is useful for diagnosing CU to non-standard allergens.[12] Due to the risk of anaphylaxis, it should always take place under medical supervision.
• Intradermal testing: The test uncommon due to the risk of anaphylaxis. When testing with non-standardized substances, the test controls should be assessed on at least 20 people to rule out false-positive results.
• Dimethylsulfoxide (DMSO) test: The test is fast, reliable, and used to test the integrity of the skin barrier function. A wheal response occurs on the application of DMSO to the skin in susceptible individuals. A clinical grading is available to quantify the response (0-no reaction, 1-follicular wheal, 2-slight elevated solid wheal, 3- elevated solid, tense wheal).                                                                                                                

In-vitro test

For the diagnosis of ICU, the presence of IgE-specific antibodies against the causative agent is used[10]. Based on the patient’s history, lab workup typically includes complete blood count (CBC), blood culture, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), basic metabolic panel (BMP), thyroid auto-antibodies, anti-nuclear antibody level (ANA) and complement levels (C3, C4) to rule out differential diagnosis like systemic illness, chronic idiopathic urticaria, autoimmune diseases, infection, etc[25].

Avoidance of the offending substance is the cornerstone of management. Patients should be educated on cross-reactive proteins and advised avoidance if they develop symptoms on exposure. 

Protective gear like gloves, skin conditioning creams or emollients, and cotton liners are necessary when the exposure at work is unavoidable.[26][27]

For patients with allergy to NRL, alternatives such as nitrile, neoprene, and polyvinyl chloride gloves are recommended. Some of the healthcare institutions around the world have banned powdered NRL gloves at work resulting in the decline of incidence of CU.[28][29] For patients with CU to NRL, avoidance of all latex-containing products is recommended.

Second-generation H1-receptor blockers (Ex. diphenhydramine, hydroxyzine, loratadine, desloratadine) are the first-line treatment in ICU. Leukotriene inhibitors like montelukast, zafirlukast, and zileuton inhibit the inflammatory component.[12]

Aspirin and NSAIDs are the first-line treatment options for the management of NICU.

Self-administered subcutaneous epinephrine pens should be available at all times to the patient.

Steroids are second-line treatment options and help to prevent the delayed phase of an anaphylactic reaction. 

Immunosuppressive drugs like cyclosporine and methotrexate are options in severe cases.

Ultraviolet A and B light inhibit NICU reaction, and the effect can last for up to 2 weeks after treatment. It has the advantage of inhibiting skin sites that are not directly irradiated.[30]

Subcutaneous immunotherapy in the management of CU is an object of research. A study on 41 bakers sensitized to wheat protein who received subcutaneous immunotherapy, has shown promise as an intervention in the management of CU.[31] Immunotherapy with standardized latex extract in workers sensitized to NRL has shown improvement in the skin reactivity.[32]

A rush (2 or 4-day) sublingual desensitization to NRL has shown significant improvement in symptom scores.[33][34]

• Urticaria and angioedema can be a part of systemic diseases like autoimmune disorders, endocrinopathies, malignancy, and hemolytic disease. Chronic idiopathic urticaria is usually associated with autoimmune disease.
• Anaphylaxis can present with generalized urticaria with other systemic symptoms.
• CU has overlapping features with allergic contact dermatitis, acquired angioedema, dermatographism, and irritant contact dermatitis.
• Glove related hand urticaria is a type of physical urticaria due to the shearing forces during the application and removal of gloves and requires differentiation from CU to NRL.
• Physical urticarial forms like aquagenic, cold, and solar urticaria can present similar to CU.
• Acute urticaria requires differentiation from erythema multiforme (with typical target lesions), toxic erythema (fixed and symmetric lesions), acute contact dermatitis, polymorphic eruption of pregnancy, and scombroid fish poisoning.[25]

Most of the patients affected by CU experience relief of symptoms with avoidance of triggers and medications. The disease duration is shorter for infants and children and prolonged when associated with other atopic diseases or with other systemic manifestations as seen in ICU.[25] Repeated exposure to the same agents may lead to a progressively severe response in ICU.

ICU has the potential to lead to life-threatening symptoms like anaphylaxis; hence, it is important to diagnose and manage these patients appropriately. Other complications include the risk of secondary bacterial infection from skin breakdown from repeated scratching.

Referral to allergist or dermatologist is necessary in severe cases.

• Avoidance of the offending agent is the key-stone to disease management. For patients with allergy to NRL, avoidance or use of alternative glove materials like bamboo viscose gloves, neoprene, nitrile, or polyvinyl chloride gloves is necessary.
• Primary prevention strategies like avoidance of triggers, pre-employment counseling, and the implementation of personal protective equipment are prudent measures.
• Organizational precautions at the workplace, early disease diagnosis, and screening are other measures.
• Patients with CU should carry subcutaneous epinephrine pens, anti-histamine, and NSAIDs for management.
• Avoid scratching the skin due to the risk of introduction of extraneous bacteria leading to the risk of cellulitis or skin abscess.

CU is widely un-recognized, and the provider's knowledge in diagnosing and management of CU will aid in the proper patient management. 

Contact urticaria is an often underdiagnosed dermatological condition that is recognized as occupational dermatoses by the World Health Organisation (WHO). It requires the efforts of an interprofessional healthcare team. The general physician is usually the first point of contact for patients seeking help and knowledge of disease presentation, testing, and management can help improve the quality of life of the patients and reduce disease burden. Due to the short time taken for symptom resolution, patients usually first present after the symptoms have disappeared, making diagnosis a challenge. Referral to allergist or dermatologist is integral while managing CU. Specialists can aid in the diagnosis of atypical presentations and management of poorly-controlled cases. Nursing plays a vital role during the diagnosis procedure due to the need to monitor patients closely for anaphylaxis. CU requires an inter-disciplinary approach for optimal results. The pharmacist should review all medications and discuss potential interactions with the prescribing/treating clinician, as well as verifying all dosing. The examples of interprofessional collaboration show how this approach can improve patient outcomes. [Level 5]