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Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disorder characterized by multiorgan failure due to uncontrolled activation of cytotoxic T-lymphocytes and natural killer (NK) cells. Here, we describe a rare and difficult case of Stevens-Johnson syndrome (SJS) complicated by HLH.

Individuals differ substantially in their response to pharmacological treatment. Personalized medicine aspires to embrace these inter-individual differences and customize therapy by taking a wealth of patient-specific data into account. Pharmacogenomic constitutes a cornerstone of personalized medicine that provides therapeutic guidance based on the genomic profile of a given patient. Pharmacogenomics already has applications in the clinics, particularly in oncology, whereas future development in this area is needed in order to establish pharmacogenomic biomarkers as useful clinical tools. In this review we present an updated overview of current and emerging pharmacogenomic biomarkers in different therapeutic areas and critically discuss their potential to transform clinical care. Furthermore, we discuss opportunities of technological, methodological and institutional advances to improve biomarker discovery. We also summarize recent progress in our understanding of epigenetic effects on drug disposition and response, including a discussion of the only few pharmacogenomic biomarkers implemented into routine care. We anticipate, in part due to exciting rapid developments in Next Generation Sequencing technologies, machine learning methods and national biobanks, that the field will make great advances in the upcoming years towards unlocking the full potential of genomic data.

Vemurafenib improves survival in advanced metastatic melanoma, but has rarely been associated with severe skin reactions including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).1, 2 Dabrafenib is a BRAF inhibitor that shares a sulfonamide moiety with vemurafenib, and only one prior report documents a switch to dabrafenib after the development of SJS/TEN with vemurafenib.2, 3 We report a case of vemurafenib-induced TEN followed by successful transition to full-dose therapy with dabrafenib in a patient with metastatic melanoma.

Fixed drug eruption (FDE) is a type IV hypersensitivity reaction characterized by recurrence of lesions at identical sites with each exposure to the offending medication. After morbilliform exanthems, FDE is the most common cutaneous drug reaction.1 Generalized bullous fixed drug eruption (GBFDE) is a variant of FDE that can present rarely with significant, life-threatening body surface involvement akin to Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).2 There are few reported cases of GBFDE occurring after the influenza vaccine, and all occurred after decades of receiving the vaccine.3, 4 Here we report a rare case of GBFDE occurring as a result of administration of the influenza vaccine.

Drug hypersensitivity reactions are an important clinical problem for both health care and industry. Recent advances in genetics have identified a number of HLA alleles associated with a range of these adverse reactions predominantly affecting the skin but also other organs, such as the liver. The associations between abacavir hypersensitivity and HLA-B*57:01 and carbamazepine-induced Stevens-Johnson syndrome and HLA-B*15:02 have been implemented in clinical practice. There are many different mechanisms proposed in the pathogenesis of drug hypersensitivity reactions, including the hapten hypothesis, direct binding to T-cell receptors (the pharmacologic interaction hypothesis), and peptide-binding displacement. A problem with all the hypotheses is that they are largely based on in vitro findings, with little direct in vivo evidence. Although most studies have focused on individual mechanisms, it is perhaps more important to consider them all as being complementary, potentially occurring at the same time with the same drug in the same patient. This might at least partly account for the heterogeneity of the immune response seen in different patients. There is a need to develop novel methodologies to evaluate how the in vitro mechanisms relate to the in vivo situation and how the highly consistent genetic findings with different HLA alleles can be more consistently used for both prediction and prevention of these serious adverse reactions.