Of all the conditions presenting to the allergist, chronic urticaria or “hives” is the most difficult to control.
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Patients with Chronic Urticaria usually feel abandoned by their doctor and can become extremely depressed with constant itching and the unsightly rash which may persist or recur for many years.
Urticaria predominantly affects adult females and up to 20% of the population sometime in their life. It presents as a diffusely raised itchy wheal and flare reaction which migrates over the skin surface. All forms of Urticaria may occur in association with deeper skin swelling or angioedema and equally, angioedema may occur in isolation with no apparent urticaria (when Hereditary Angioedema (HAE) due to a deficiency of the C1 Esterase inhibitor enzyme should be suspected).
Causes
We classify Urticaria into Acute Urticaria when the rash duration is under 6 weeks and Chronic Urticaria when it persists for over 6 weeks. Physical Urticaria is due to an external physical trigger such as heat, cold, pressure or exercise (also called Inducible Urticaria). While Urticarial Vasculitis is a rare condition associated with underlying auto-immune connective tissue diseases which requires specialist referral.
The actual cause of Acute Urticaria is relatively easy to identify as the trigger is usually immediately apparent and is reproducible on re-exposure. Examples include: Shellfish, Peanut, Penicillin, Bee or Latex allergy. In children generalised Acute Urticaria is often triggered by a streptococcal or viral infection (hepatitis, herpes etc).
In Chronic Urticaria it is far more difficult to identify a specific cause and the actual trigger in over 50% of cases remains unknown (Spontaneous Urticaria). We call this urticaria due to unknown cause Chronic “Idiopathic” Urticaria (CIU) or Chronic Spontaneous Urticaria (CSU). Chronic Urticaria may be triggered by generalised illnesses such as autoimmune thyroid disease, collagen joint and vascular disease, chronic parasitic infections, chronic sinusitis, urinary infections, Helicobacter pylori and chronic dental infections. About one third of cases are due to auto-antibodies directed against IgE or the Mast Cell IgE receptor. Sometimes food additives and preservatives (Benzoate, Sulphites and Artificial dyes) can continuously trigger chronic urticaria, but true food allergy is unlikely to cause Chronic Urticaria.
Physical Urticaria (Inducible Urticaria) in its most simple form usually presents as linear scratches or Dermatographism. Physical Urticaria is triggered by common physical stimuli such as heat, cold, sun exposure, vibration, exercise, deep pressure and even occasionally from water exposure (Aquagenic). The weals occur within minutes of the stimulus and disappear rapidly within an hour or two. Just to complicate matters, Physical Urticaria may occur together with Chronic Idiopathic Urticaria. While Contact Urticaria an immediate allergy occuring after skin contact with fresh foods (potato, shellfish), pet saliva or latex and settles within a few hours.
Urticarial Vasculitis is a rare painful non-migratory wealing reaction which persist for more than 24 hours and is often associated with fever, bruising and joint pain. The associated with an underlying auto-immune diseases such as Serum Sickness, Systemic Lupus and Sjogren’s Syndrome should not be overlooked. Urticaria Pigmentosa is a diffuse dark freckle-like rash that weals on rubbing the skin (Dariers sign) and is due to excess mast cells in the skin (Cutaneous Mastocytosis). Children frequently develop discrete linear or grouped itchy Papular Urticaria from insect bite sensitivities.
If a specific urticarial trigger can be found, then avoiding that trigger is the most sensible course of action, but most often no underlying cause is ever found. The main focus of treatment is trying to alleviate symptoms while the urticaria slowly “burns” itself out and eventually clears – a process that may take many months or even some years.
Medical management of Urticaria
Antihistamines: The once-daily non-sedating antihistamines are the mainstay of current urticaria treatment, but quadrupling the normal recommended dose is often necessary to obtain symptom control (for example Cetirizine 10 to 30mg, Loratadine 10 to 30mg or Fexofenadine 180 to 540mg). Once the urticaria is controlled, the dose can slowly be reduced. Older sedating antihistamines such as Chlorpheniramine, Diphenhidramine or Hydroxyzine may help at night with sleep disturbance from itching. Tolerance to antihistamines can develop and it may help to periodically rotate through different antihistamines. Ketotifen may be effective in children with its antihistamine and mast cell stabilising properties. If it is necessary to use antihistamines in pregnancy, Chlorpheniraminealthough sedating, is safest. Stomach ulcer treating Histamine H2 blockers such as Ranitidine or Cimetidine offer additive antihistamine effective if used with conventional antihistamine medication.
Oral steroids: Although Prednisone (at least 30mg meticorten daily) is most effective in the short term for rapid symptom control, with long term use will it lead to undesirable side effects and problematic recurrent urticaria on withdrawal. Occasionally long term alternative-day regimens may be necessary to control chronic recalcitrant urticaria.
Steroid-sparing options: The older tricyclic antidepressant Doxepin (10 to 50mg daily) has histamine blocking properties and is useful as an adjunct especially if there is co-existent depression with the urticaria. Leukotriene Receptor antagonists, Singulair or Montelukast (10mg at night) has been used with variable success, and is most effective when used in combination with non-sedating anti-histamines. Montelukast is very useful in aspirin sensitive individuals (who are prone to urticaria, nasal polyps and asthma).
Other drugs such as Colchicine, Warfarin, Nifedipine, Dapsone, Methotrexate and Sulfasalazinehave been used with some success reported in chronic urticaria. Auto-immune thyroid disease with associated urticaria may respond to oral Thyroxine supplementation even if normal thyroid function. Immune suppressive therapy such as Cyclosporin is effective but can cause serious side effects such as kidney damage and uncontrolled hypertension. Oral Sodium Cromoglycate may benefit Food related Exercise induced Urticaria. Stress (public speaking, examinations, exercise and arguments) may trigger Cholinergic Urticaria and Propranolol will reduce symptoms.
A highly effective (but expensive) treatment now recommended by the American FDA and British NICE guidelines for use as the preferred third line add-on treatment of Chronic Urticaria unresponsive to high dose antihistamines, includes subcutaneous injections of 300mg Omalizumab (Xolair) once a month for 6 months. Recent studies on this monoclonal antibody (previously only used in asthma) show that once initial control is gained (after one month), the dose may be halved to maintain control for the 6 month induction period which can result in total remission of the Urticaria. However at least 40% will relapse after withdrawal of Omalizumab. (Zuberbier et al, EAACI Guidelines urticaria, Allergy 69(7) 2014)
Non-pharmacological interventions:
- Try not to rub the itchy and painful urticarial lesions.
- Try and keep as cool as possible at all times and wear loose fitting clothing.
- Avoid all wine and alcoholic drinks, which non-specifically trigger urticaria.
- Try to keep “Stress” under control with relaxation exercises and Yoga.
- Keep the skin well moisturised with non perfumed emollients.
- Avoid skin antihistamine creams (mepyramine, antazoline, diphenhydramine) and Lanolin, which can actually cause contact allergies.
- Topical steroid creams are of no benefit in Urticaria.
- Avoid all physical triggers such as excess heat, cold, exercise and rapid temp changes.
- Avoid junk foods and food colourings (Tartrazine), additives (Sodium Benzoate and Sulfites), and natural Salicylate (Berry fruit, Spices and strong Tea).
- Avoid all aspirin containing medication and flu-remedies and any other anti-inflammatory medication (NSAI) such as Ibuprofen, Mefenamic acid and Diclofenac as well as Codeine (opiate analgesics).
- Coloured multivitamin tablets which may also act as urticaria triggers.
- Paracetamol is the only painkiller or viral treatment that can safely be used in urticaria.
- Try Calamine, Aqueous cream with Menthol 1% or 10% Crotamiton (Eurax) lotions to soothe the skin.
Urticaria triggers in medication
If Aspirin & Salicylate intolerance is suspected then all forms of Salicylate including toothpaste, muscle rubs and peppermints should also be avoided. Aspirin sensitive individuals tolerate the newer Cyclo-oxygenase-2 selective inhibitors or COX-2 anti-inflammatory (NSAI) medications such as Celecoxib and Meloxicam.
Angiotensin converting enzyme inhibitors (ACE inhibitor) anti-hypertensives release Bradykinin and are a common trigger for angioedema and urticaria, especially Lisinopril, Perindopril and Enalapril. ACE inhibitors may trigger angioedema even after many years of use. The Angiotensin-II receptor anatagonists (ACE 2) such as Valsartan and Candesartan are less likely to induce angioedema and urticaria.
Many patients with chronic urticaria derive benefit from a Low Vaso-active Amine Diet. Histamine contained in foods such as dark fish, fermented cheese and cured meats may act non-specifically as a pseudo-allergen by perpetuating the urticaria. Avoidance of these foods will help reduce itch and flushing (Berlin Diet).
See Below: Foods with high Vaso-active amine (histamine) content:
| Dark Fish | Mackerel, Tuna, Smoked Salmon, Sardines, Snoek. |
| Strong Cheese | Emmenthal, Parmesan, Camembert, Cheddar, Roquefort. |
| Cured meat | Salami, Ham, Pork, Sausages, Spicy chicken, Biltong. |
| Fruit & Vegetable | Eggplant, Spinach, Red beans, Avocado, Tomato, Bananas and Dates, Green Tea. |
| Alcohol | Red wine, Cider and Homebrew beer. |
| Others | Marmite, Soy sauce, Chocolate and Tomato ketchup. |
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