If the p-i stimulation resulted in T cell expansion and activation (MPE, DRESS), some of the p-i-activated T cells might continue to react in the absence of drug: their TCR may be cross-reactive with unmodified, self HLA presenting exogenous peptides (mainly of herpes virus origin) or some self-peptides: this kind of cross-reactivity with exogenous or self peptides and self-HLA explain two late complications after severe DHR, mostly DRESS: one is viral reactivation: herpes viruses are permanently harboured in various cell types after infection (fibroblasts, endothelial cells, hematopoietic cells, brain cells, etc.) and are controlled by T cells. When these herpes-virus specific T cells are activated by p-i, they react with the herpes virus peptide expressing cells and damage them by their cytotoxic potential: a consequence is the release virus particles into the circulation  and symptoms of viral reactivation (high virus load, possibly increase of liver enzymes and of activated lymphocytes) appear.
A second wave of peptide reactivity may end up in autoimmunity: the abnormal stimulation by p-i includes T cells from the naïve and memory T cell pool. It may include self-peptide reactive T cells, which, if the corresponding self-peptides are presented and are encountered, release cytokines and exert cytotoxicity - autoimmunity may arise. As such self-peptide reactive T cells are present in relatively low amounts, they need >6–8 weeks to expand and appear after the virus-reactivations. Autoimmunity occurs in a minority of patients (<20%), and may is often manifested as autoimmune poly-endocrine syndrome.
Multiple drug hypersensitivity (MDH): a further consequence of p-i stimulations like DRESS or severe MPE is MDH; such patients develop an additional DHR to a structurally different drug, with the same or different clinical manifestations. MDH occurs in ca. 20% of patients with DRESS, and can occur any time, from the start of DRESS (often to a combination therapy), during the initial activation, and can even appear years after the first DHR