What are the other Names for this Condition? (Also known as/Synonyms)

• Medication-Induced Urticaria
• Urticaria Medicamentosa

What is Drug-Induced Urticaria? (Definition/Background Information)

• Urticaria is a common inflammatory condition of skin that results in weals (reddish skin spots that are itchy) and/or angioedema (swelling due to fluid accumulation). It is seen in both children and adults and may arise from a variety of factors
• Drug-Induced Urticaria occurs secondary to the use of certain medication, as an adverse reaction of the body. Any of the acute, chronic, or contact types of urticaria may develop from the use of medications, which may be taken orally, administered intravenously, or applied topically. Urticaria is known to be the most common skin manifestation of a drug reaction
• The most common type of medications causing Drug-Induced Urticaria include non-steroidal anti-inflammatory drugs (NSAIDs), penicillin, and sulfa-containing drugs. The signs and symptoms may develop within a few hours or after a few days of using the medication. Discontinuing the use of such medications may decrease progression of Drug-Induced Urticaria and/or may result in resolution of the condition

Who gets Drug-Induced Urticaria? (Age and Sex Distribution)

• Drug-Induced Urticaria is a common form of urticaria. It is observed that nearly 9% of the individuals with urticaria develop the same following medication use
• Individuals of all ages (both children and adults) may be affected. The age range depends on the type of medication used, although chronic urticaria is not commonly seen in children
• Both males and females are affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Drug-Induced Urticaria? (Predisposing Factors)

The key risk factor for Drug-Induced Urticaria is the use of certain medications that cause the condition as a side effect.

The medications observed to strongly induce this abnormal skin condition (high-risk medications) include:

• Angiotensin-converting enzyme (ACE) inhibitors
• Antibiotics such as cephalosporin, penicillin (most commonly noted drug), and tetracycline
• Antifungal medication such as griseofulvin
• Non-steroidal anti-inflammatory drugs (NSAIDs) such as diclofenac, ibuprofen, and naproxen
• Opioids administered for pain, including codeine, fentanyl, and morphine
• Radiographic contrast agents used in certain imaging studies
• Salicylate medications such as aspirin

Other category of medicines that are associated with Drug-Induced Urticaria include:

• Alkylating antineoplastic agents, including methotrexate and taxane
• Antiarrhythmic agents such as quinidine
• Antibiotics including aminoglycoside, erythromycin, fluoroquinolone, sulphonamide, and vancomycin
• Anticoagulants such as heparin and protamine sulfate
• Anticonvulsant agents including hydantoin
• Betadine (povidone-iodine)
• Bisphosphonates
• Blood pressure medication such as hydralazine
• Corticosteroids
• Cough suppressants such as dextromethorphan
• Dextrans
• Enzymes that include chymopapain, streptokinase, and trypsin
• Muscle relaxants such as atracurium, curare, succinylcholine, and vecuronium
• Non-sugar sweetener such as mannitol
• Opioid drugs such as meperidine
• Oral antifungals including fluconazole and ketoconazole
• Polypeptide hormones such as corticotrophin, insulin, vasopressin
• Progesterone
• Sorbitol complexes
• Thrombolytics including alteplase and urokinase
• Vaccines

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Drug-Induced Urticaria? (Etiology)

Drug-Induced Urticaria develops from the use of certain medications/drugs that are administered for various health conditions.

• It is believed that the offending drug potentially causes an abnormal cell-mediated immune response (allergic reaction) on the skin and body
• In some cases, urticaria following medication use may develop from non-immunological factors, termed pseudo-allergic reactions
• Sometimes, the appearance of signs and symptoms due to the drug may not be observed immediately after starting the medication. The condition may arise after a period of time

What are the Signs and Symptoms of Drug-Induced Urticaria?

The signs and symptoms of Drug-Induced Urticaria may vary from one individual to another. It may be mild or severe and may be related to the type and usage of the drug. Generally, the condition is known to get better after stoppage of the offending medication.

The signs and symptoms of Drug-Induced Urticaria may include:

• Localized itching of skin that may appear swollen
• Formation of red skin rashes or weals that are associated with intense itching
• The weals may change in shape and size; weals may be spherical, arranged in a random form, or in a ring-like pattern
• In some individuals, there may be a burning sensation accompanying itching
• Pain or pain on touch
• Individual weals may vary in size from a few mm to few cm
• Urticaria can occur in any part of the body and can be focal (localized) or extensive
• In some cases, it can lead to hyperpigmentation (increased skin pigmentation) or hypopigmentation (decreased skin pigmentation)
• Scratching can result in worsening of the symptoms and lead to further skin complications such as ulceration and secondary infections
• Angioedema: It is the swelling observed in the mucus membranes or deep within the skin from fluid accumulation. This may last for a few days, can be itchy, and may involve any part of the body
• In contact urticaria, the rashes and associated symptoms are noted at the sites of application of topical creams and ointments

The itching may be worsened by substances or factors such as viral infections, tight clothing, food allergies, alcohol, stress, and exercises.

Acute forms of Drug-Induced Urticaria may present the urticarial rashes within a few hours to days after usage of the drug. In chronic forms, the rashes may appear from time to time, between periods of remission.

In some cases, there may be other systemic side effects of the administered medications.

How is Drug-Induced Urticaria Diagnosed?

The diagnosis of Drug-Induced Urticaria may involve the following tests and procedures:

• Complete physical examination with comprehensive evaluation of medical history (which includes the use of any drug/medication)
• Assessment of the signs and symptoms
• Blood and urine tests, as necessary, to detect various antibodies against allergens including:
  • Complete blood count (CBC) test
  • Antinuclear antibody (ANA) test
  • Erythrocyte sedimentation rate (ESR) test
  • Serum level of complement
  • Serum C-reactive protein blood test
• Skin prick (allergy) test
• Tests to assess immunoglobulin levels (IgE levels)
• Oral provocation test
• Tests to rule-out other underlying conditions (infections, autoimmune disorders, etc.), if required

A differential diagnosis is important to exclude other conditions presenting similar signs and symptoms. These include:

• Autoinflammatory syndrome(s)
• Erythema multiforme
• Inducible urticaria
• Maculopapular cutaneous mastocytosis
• Morbilliform drug eruption
• Serum sickness
• Spontaneous urticaria types
• Urticarial vasculitis
• Urticaria-like lesions

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Drug-Induced Urticaria?

In some cases, Drug-Induced Urticaria may present significant complications, which include:

• Intense scratching may result in skin scarring
• Itching can lead to ulceration of skin, causing superimposed bacterial and fungal skin infections
• Sleep disruption
• Cosmetic concerns
• Low blood pressure (hypotension)
• Involvement of the larynx due to angioedema - this may be life-threatening and a medical emergency from sudden breathing difficulties
• Severe urticaria can result in anaphylactic shock, which is a potentially life-threatening medical condition
• Recurrence of the condition - it is important to note that some recurrences may be more severe than the initial allergic attacks
• Reduced quality of life, especially from frequent episodes (recurrence) of the condition

How is Drug-Induced Urticaria Treated?

Discontinuing the medication responsible for the side effect may result in a cure, or in improvement of the condition. IgE-mediated type 1 drug allergy is known to resolve within 2 days of stopping the offending medication.

If treatment is needed for Drug-Induced Urticaria, then the following measures may be considered:

• Cooling the affected skin region using moist towels or ice packs
• Use of moisturizing skin creams and lotions
• Acute urticaria may be treated through antihistamine therapy
• Systemic (oral) corticosteroids may be recommended when antihistamines are ineffective
• In the case of anaphylaxis (severe allergic reaction), epinephrine or adrenaline is immediately administered
• Patient education in understanding the condition is beneficial
• Stress management for severe and chronic conditions
• Follow-up care with screening and check-ups are important at regular intervals

Note: If any of the prescribed treatment medication or methods cause new symptoms, then it is important to discontinue the medication and immediately inform the healthcare provider.

How can Drug-Induced Urticaria be Prevented?

Current medical research has not established a method of preventing Drug-Induced Urticaria. However, the following measures may be considered to help lower one’s risk for the condition:

• When possible, the causative medication may be discontinued and/or alternatives prescribed; nevertheless, this has to be decided by the concerned healthcare provider
• Inform your physician if you are allergic to any medication. In this context, wearing a suitable medical alert bracelet indicating the medication allergy is highly recommended
• Avoid self-medication
• Avoid bringing about any changes to one’s medications (substitution with medicines of the same class/type) without consulting the healthcare provider, since there is a risk for cross-reaction in individuals who have been sensitized to the drug
• Avoid known triggers which can aggravate the condition, where possible

What is the Prognosis of Drug-Induced Urticaria? (Outcomes/Resolutions)

• The prognosis for Drug-Induced Urticaria is usually good in many cases, upon discontinuation of the medication and adequate treatment of the condition, if necessary
• In a vast majority of individuals, the symptoms may last only for a short period of time, particularly in acute and contact urticaria cases; an immediate improvement is observed following discontinuation of the offending medication
• However, the prognosis may also depend upon the type of medication involved, the period of exposure to the offending medication, and severity of the symptoms

Additional and Relevant Useful Information for Drug-Induced Urticaria:

The following DoveMed website link is a useful resource for additional information:

https://www.dovemed.com/healthy-living/skin-disorders/