What Is Sulfa Allergy

Introduction

An allergic reaction to medications is known as a drug allergy. It occurs when certain medications cause your immune system to overreact. A drug allergy develops when a drug causes your body to become sensitive to it and your body "remembers" the drug as a harmful, foreign invader, like bacteria or viruses. When you take that drug again, your immune system will. An allergy to drugs can be fatal. There is a list of medications that are reported to trigger allergic responses in patients, such as penicillin, sulfa drugs, opiates, chemo-drugs etc.⁸

Definition of sulfa allergy

A sulfa sensitivity is a type of medicine sensitivity. Sulfa drugs (also called sulfur medications or sulfonamide-containing drugs) are drugs that contain a sulfonamide functional group in their compound structure. These drugs have different purposes and can be classified into anti-microbial agents and non-antimicrobial drugs.²

Prevalence of sulfa allergy

Roughly 3-8% of patients are estimated to encounter sulfonamide sensitivity. Sulfonamide sensitivity can manifest as different physical reactions. However, dermatological reactions to sulfonamide antimicrobial agents occur 10 to 20 times more frequently in HIV patients than in immunocompetent patients.¹

Understanding sulfa allergens

Sulfa drugs

These drugs come under a class of synthetic antimicrobials which are used for several bacterial infections. All sulfonamides contain a NH₂-SO₂ moiety, but the antimicrobial sulfonamide class comprises an aryl-amine group at the 4 position of a heterocyclic ring and another nitrogen group on the 1 position of the structure. These extra structures are known to be the essential determinant of sulfonamide sensitivity, as opposed to the base NH₂-SO₂ moiety contained in all sulfonamides. This means that other sulfonamide drugs that do not contain the aryl-amine group will not trigger sulfonamide sensitivity^1,3

Common examples and their medical uses:

Anti-microbial sulfonamides include

• Sulfadiazine and sulfisoxazole: used to treat infections in the brain, ear etc
• Sulfamethoxazole: used in combination with Trimethoprim to treat UTI, middle ear infection (otitis media) and other diarrheal conditions¹
• Sulfasalazine (Azulfidine): used to treat Crohn's disease, ulcerative colitis and rheumatoid arthritis.
• Dapsone: used to treat leprosy, dermatitis and Pneumocystis jirovecii pneumonia⁵

Non-antimicrobial sulfonamides include

• Hydrochlorothiazide and furosemide: act as a diuretic and help control blood pressure
• Glyburide: used to lower blood sugar levels
• Celecoxib: a non-steroidal anti-inflammatory drug (NSAID) used to reduce pain and inflammation⁴

Mechanism of sulfa drug

As competitive inhibitors of the dihydropteroate synthetase (DHPS) enzyme, antibacterial sulfonamides target the bacterial metabolic pathway. Folate, also known as vitamin B9, is synthesised by dihydropteroate synthetase. Bacterial cells cannot produce nucleic acids like DNA or RNA without folate. Without nucleic acid, bacterial cells cannot undergo cellular division, thus the number of bacterial cells will remain the same, achieving bacteriostasis.¹⁰

Hypersensitivity reactions

Type I (Immediate)

Type I reaction is referred to as an immediate hypersensitivity reaction that occur within 24 hours of exposure to the allergen. This immunoglobulin E (IgE) mediated response causes symptoms like hypersensitivity, angioedema, and urticaria (hives). This is because the N1 heterocyclic ring on the sulfa drug is mistaken for IgE by the immune system.^1,9

Type IV (Delayed)

Type IV reaction is referred to as a delayed hypersensitivity reaction because it typically occurs between 48 and 72 hours after exposure to the allergen.⁹ This life-threatening reaction can lead to Stevens-Johnson Syndrome, sometimes also known as toxic epidermal necrosis if not treated urgently.¹

Symptoms of sulfa allergy

The most common symptoms of sulfa allergy include:

• Skin conditions such as urticaria, and irritation
• GI disturbance symptoms such as vomitting and diarrhoeaalso
• Headache

Sulfa allergies can cause several less common but potentially serious symptoms, such as:

• rouble swallowing
• difficulty breathing
• muscle and joint pain
• sore throat
• fever and influenza-like symptoms
• blisters and peeling of the skin

Some individuals develop hypersensitivity, and the most severe adverse reactions include comatose, organ dysfunction, Stevens-Johnson syndrome and severe epidermal necrolysis.⁴

Diagnosis of sulfa allergy

The following diagnostic procedures are utilized to evaluate the cause of allergy:

Medical history

To determine whether your allergic reaction is the result of a sulfa allergy, your healthcare provider will inquire about the medications you take and examine your symptoms.⁴

Skin tests

An allergist or nurse performs a skin test by injecting, patching, or applying a small amount of a suspected drug to your skin. A red, itchy, and raised bump is typically the sign of a positive test result.⁶

Blood test

IgE antibodies to specific allergens are measured in the blood during allergy tests. The most common test is known as the radioallergosorbent test (RAST). Alternatively, an enzyme-linked immunosorbent assay (ELISA) can be used to diagnose non-immediate sulfa allergy by measuring the amount of cytokines produced when using a sulfonamide antibiotics. When skin tests are not possible, blood tests should be used instead.⁷

Oral challenge test

By taking a sulfa medication under the care of a doctor to see if it causes a reaction, you can test for sulfa sensitivity. This is called an oral medication challenge test. ⁴

Management and treatment

If the patient and the healthcare provider are aware of the sulfa allergy, the healthcare provider should avoid prescribing sulfonamides and opt for alternative medications.

If the patient develops an allergic reaction to sulfa drugs, they need to immediately discontinue the use of sulfa drugs and contact their healthcare practitioner. The healthcare practitioner might need to administer allergic medications depending on the severity of the allergic reaction. These include antihistamines, corticosteroids and epinephrine.

When the sulfa allergy is not confirmed, healthcare professionals should do a graded challenge procedure where the lowest dose of a sulfa drug is given to the patient to see if that concentration of the drug is tolerable.⁶

Living with sulfa allergy

The following measures should be taken to avoid the complications of sulfa allergy:⁶

• Lifestyle adjustments: Carefully read the composition of medication and products to prevent cross reactions
• Communication with healthcare providers: Inform healthcare professionals such as your GP or dentist to update your medical records. This ensures that your sulfa allergy is clearly documented
• Allergy bracelets or identifiers: Wear a medical alert bracelet that informs people of your sulfa allergys. In an emergency, this information will be useful in getting the appropriate treatment⁶

FAQ's

Are sulfa and sulfite allergies the same?

Sulfa allergy is caused by the nitrogen containing heterocyclic ring and aryl-amine moiety. In contrast, sulfites are found naturally in food products and do not cause allergic reactions. Sulfites can cause sensitivity reactions, which do not involve the immune system but can take on allergy-like symptoms.

Complications of sulfa allergy?

Sulfa drug allergy complications include anaphylaxis and Stevens-Johnson syndrome.

Organs are mostly affected by sulfa drug allergy?

Sulfa allergic reactions most commonly affect the skin and airway (in severe cases). 

Do all sulfa moiety-containing drugs cause allergic reactions?

No, medications that have sulfa moiety but not the aryl-amine and N heterocyclic ring will not trigger an allergic reaction. 

What's the use of sulfa drugs?

Sulfa drugs used in antimicrobial and non-antimicrobial treatments. For example, antimicrobial sulfa drugs are used in urinary tract infections, ear infections and to some extent in malaria as well. For non-antimicrobial means it is used as a diuretic and NSAID.

Summary

Drug allergies can manifest themselves in many ways but the most common form of manifestation is skin reactions or anaphylaxis. Allergic response to medication occurs when the immune system gets irritated and referred them as a harmful agent. Sulfa drugs, also known as sulfonamides, contain specific functional groups in their chemical structure which are responsible for the allergic responses.

Sulfa drugs are used as diuretics, NSAIDs and anti-diabetic medicine. Symptoms of sulfa drug allergic reaction include headache, emesis, diarrhea and skin conditions such as urticaria, erythema etc. If these symptoms worsen and, patient develops life-threatening reactions such as anaphylaxis, Stevens-Johnson syndrome and epidermal necrosis, emergency treatment is required.

There is no specific diagnostic test available for sulfa allergy, so healthcare providers need to follow the basic protocol of taking medical history, carrying out blood tests or skin tests, etc., to evaluate a patient's immune reaction to sulfa drugs. Sulfa allergy can be managed by stabilizing the patient’s symptoms using medications such as anti-histamines and corticosteroids.

Exposure to sulfa drugs can be prevented when the patient knows they have a sulfa allergy. It is also advised that patients inform their healthcare providers regarding their current allergies, check the composition of medication and wear an allergy identifier bracelet.