Sulfonamide hypersensitivity syndrome

Overview

Sulfonamide hypersensitivity syndrome (SHS) is a serious adverse drug reaction caused by an immune-mediated hypersensitivity to sulfonamide-containing medications. These drugs, commonly used as antibiotics (e.g., sulfamethoxazole), diuretics, and other therapeutic agents, can trigger a range of allergic reactions that vary from mild skin rashes to life-threatening systemic involvement.

SHS typically presents with fever, rash, and internal organ involvement, often occurring within days to weeks after starting sulfonamide therapy. It is an important clinical entity because early recognition and treatment can prevent severe complications.

Causes

Sulfonamide hypersensitivity syndrome results from an abnormal immune response to sulfonamide drugs. The reaction is believed to be mediated by T-cells recognizing drug metabolites as antigens, leading to widespread inflammation. Risk factors include:

• Genetic predisposition affecting drug metabolism

• High or prolonged exposure to sulfonamides

• Previous history of drug allergies

• Immunocompromised states or concurrent infections

Symptoms

Symptoms of SHS usually appear 1-3 weeks after drug initiation and may include:

• High fever

• Widespread maculopapular rash, which may progress to exfoliative dermatitis or Stevens-Johnson syndrome

• Lymphadenopathy (swollen lymph nodes)

• Hepatitis or liver dysfunction

• Eosinophilia (elevated eosinophils in blood)

• Possible involvement of kidneys, lungs, or other organs

• Malaise, fatigue, and other systemic symptoms

Diagnosis

Diagnosis is clinical, based on symptom onset following sulfonamide exposure and supportive laboratory findings. Steps include:

• Detailed drug history identifying recent sulfonamide use

• Physical examination noting characteristic rash and systemic signs

• Laboratory tests showing eosinophilia, elevated liver enzymes, and organ function abnormalities

• Exclusion of infections or other causes of symptoms

• Skin biopsy in some cases to confirm hypersensitivity reaction

Treatment

Treatment focuses on immediate discontinuation of the offending sulfonamide and supportive care:

• Withdrawal of sulfonamide medication

• Systemic corticosteroids to reduce inflammation and immune response

• Supportive care including hydration, nutritional support, and treatment of organ dysfunction

• Monitoring for complications such as secondary infections

• Hospitalization in severe cases

Prognosis

With prompt recognition and management, the prognosis of sulfonamide hypersensitivity syndrome is generally good. Most patients recover fully over weeks to months. However, delayed diagnosis or continued drug exposure can lead to severe, potentially fatal complications including extensive skin necrosis and multi-organ failure.

Patients with a history of SHS should avoid all sulfonamide-containing medications and inform healthcare providers to prevent recurrence.