T-cell-mediated drug hypersensitivity represents a significant proportion of immune mediated drug hypersensitivity reactions. In the recent years, there has been an increase in understanding the immune mechanisms behind T-cell-mediated drug hypersensitivity. According to hapten mechanism, drug specific T-cell response is stimulated by drug-protein conjugate presented on major histocompatibility complex (MHC) as it is presented as a new antigenic determinant. On the other hand, p-i concept suggests that a drug can stimulate T cells via noncovalent direct interaction with T-cell receptor and/or peptide-MHC. The drug binding site is quite variable and this leads to several different mechanisms within p-i concept. Altered peptide repertoire can be regarded as an 'atypical' subset of p-i concept since the mode of the drug binding and the binding site are essentially identical to p-i concept. However, the intracellular binding of abacavir to HLA-B*57:01 additionally results in alteration in peptide repertoire. Furthermore the T-cell response to altered peptide repertoire model is only shown for abacavir and HLA-B*57:01 and therefore it may not be generalised to other drug hypersensitivity. Danger hypothesis has been postulated to play an important role in drug hypersensitivity by providing signal 2 but its experimental data is lacking at this point in time. Furthermore, the recently described allo-immune response suggests that danger signal may be unnecessary. Finally, in view of these new understanding, the classification and the definition of type B adverse drug reaction should be revised.

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Case series Patients: Female, 31-year-old • Male, 43-year-old • Female, 64-year-old Final Diagnosis: IgA vasculitis Symptoms: Abdominal pain • haematuria • hemoptysis • joint pain • proteinuria • rash Medication: — Clinical Procedure: — Specialty: Immunology Objective: Rare disease Background: IgA vasculitis (IgAV) is a rare and potentially life-threatening small-vessel vasculitis in adults. The disease course is often more severe than its childhood counterpart. The disease is noted for its heterogeneous presentation with varying severity. There are no current treatment guidelines for severe multi-organ involvement of IgAV. The treatment approaches based on the clinical discretion of treating doctors remain controversial, especially regarding the role, duration, and type of immunosuppression. Case Reports: We present 3 cases of severe multi-organ IgAV encountered at our tertiary referral center between 2016 and 2021, which were treated with different immunosuppression regimens, including combination of systemic corticosteroids, oral immunosuppressants (azathioprine, mycophenolate, and sirolimus), rituximab, and cyclophosphamide. In these patients, IgAV presented differently but were all organ-threatening or life-threatening in nature. IgAV in all patients responded to therapies; however, infection complicating underlying comorbidities was the cause of death in 1 patient and the cause of comorbidities in the other 2. Other treatment-related complications included weight gain, adrenal insufficiency, and secondary hypogammaglobulinemia. Conclusions: IgAV can be a polyphasic and a potentially challenging severe organ-threatening disease to treat in adults. The outcomes presented here highlight the morbidity and substantial risks involved in treating complex IgAV patients. Early use of biologics may have a role in preventing treatment-related toxicity. Further studies on IgAV in adults are urgently needed.