Sulfonamide allergy label and the risk of opportunistic infections in solid organ transplant recipients - A retrospective matched cohort study.

BACKGROUND: While a penicillin allergy label has been linked to various negative clinical outcomes, limited studies have specifically characterized the implication of sulfonamide allergy labels (SAL) on clinical outcomes. We examined the impact of SAL on clinical outcomes of solid organ transplant recipients. METHODS: In this retrospective matched cohort study, we utilized the TriNetX US collaborative Network, a multicenter de-identified US database, and identified solid organ transplant recipients with and without SAL. The 1-year probability of developing Pneumocystis jirovecii pneumonia (PJP), toxoplasmosis, and nocardiosis was estimated and contrasted between the two study groups. The hazard ratio (HR) and the 95% confidence interval (CI) quantified the strength and direction of the association between SAL and these outcomes. RESULTS: When comparing 1571 solid organ transplant recipients with SAL to an equal number of matched controls, patients with SAL had a higher probability of developing nocardiosis (HR 3.85; 95% CI, 1.44-10.30; p = .004; corrected p = .04), and toxoplasmosis (HR, 1.87; 95% CI, 1.10-3.17; p = .019; corrected p = .19), but no difference in the risk of developing PJP (HR, 1.64; 95% CI, 0.68-3.95; p = .27). There was no mortality difference (HR, 1.31; 95% CI, 0.99-1.75; p = .061; corrected p = .6). SAL influenced antibiotic prescription with overutilization of dapsone, atovaquone, and pentamidine and underutilization of trimethoprim and sulfamethoxazole. CONCLUSION: SAL is associated with an increased risk of opportunistic infections following solid organ transplantation. Measures to evaluate and de-label sulfonamide allergy prior to transplantation or desensitizing shortly after transplantation are advisable.

Rituximab for linear immunoglobulin A bullous dermatosis.

Linear immunoglobulin A bullous dermatosis (LABD) is an idiopathic or drug-induced vesiculobullous disease typically managed with dapsone or colchicine. We report a case of LABD successfully treated with rituximab in a patient who was intolerant to first-line therapies and recalcitrant to typical immunosuppressants. The patient was initially started on prednisone and mycophenolate mofetil which resulted in minimal response and disease progression. Improvement was seen after two infusions of rituximab 1000 mg at 2 weeks apart with planned maintenance therapy.

Viral infections and drug hypersensitivity.

Virus infections and T-cell-mediated drug hypersensitivity reactions (DHR) can influence each other. In most instances, systemic virus infections appear first. They may prime the reactivity to drugs in two ways: First, by virus-induced second signals: certain drugs like ß-lactam antibiotics are haptens and covalently bind to various soluble and tissue proteins, thereby forming novel antigens. Under homeostatic conditions, these neo-antigens do not induce an immune reaction, probably because co-stimulation is missing. During a virus infection, the hapten-modified peptides are presented in an immune-stimulatory environment with co-stimulation. A drug-specific immune reaction may develop and manifest as exanthema. Second, by increased pharmacological interactions with immune receptors (p-i): drugs tend to bind to proteins and may even bind to immune receptors. Without viral infections, this low affine binding may be insufficient to elicit T-cell activation. During a viral infection, immune receptors are more abundantly expressed and allow more interactions to occur. This increases the overall avidity of p-i reactions and may even be sufficient for T-cell activation and symptoms. There is a situation where the virus-DHR sequence of events is inversed: in drug reaction with eosinophilia and systemic symptoms (DRESS), a severe DHR can precede reactivation and viremia of various herpes viruses. One could explain this phenomenon by the massive p-i mediated immune stimulation during acute DRESS, which coincidentally activates many herpes virus-specific T cells. Through p-i stimulation, they develop a cytotoxic activity by killing herpes peptide-expressing cells and releasing herpes viruses. These concepts could explain the often transient nature of DHR occurring during viral infections and the often asymptomatic herpes-virus viraemia after DRESS.

"Doctor, I have a Sulfa Allergy": Clarifying the Myths of Cross-Reactivity.

Our purpose is to present an evidence-based approach, directed primarily towards eye-care specialists, clarifying whether certain drugs should or should not be used in patients with sulfonamide allergy. We conducted a literature search using PubMed to identify the risk of ophthalmic-specific drugs in patients with a self-reported sulfonamide allergy. MeSH key words included "sulfonamide" and "hypersensitivity". Articles specifically geared towards ophthalmic diseases were sought. The evidence illustrates that individuals with sulfonamide allergy are intrinsically predisposed to higher rates of allergic reaction that is not specific towards sulfonamide non-antimicrobials or sulfur-based medications. We provide a simplified algorithm using the 2017 Clinical Guide to Ophthalmic Drugs to help busy eye care clinicians determine whether a certain common ophthalmic medication is safe or unsafe to prescribe in a patient with a "sulfa allergy".