PurposeThe once daily formulation of tacrolimus is an important immunosuppressive drug. Interpatient variability in metabolism has been related to genetic variation in CYP3A4 and CYP3A5. However, in liver transplantation, both donor and recipient genotypes may affect pharmacokinetics. The primary objective of this study was to investigate the effect of CYP3A4*22 and CYP3A5*3 of both donor and recipient on once daily tacrolimus pharmacokinetics. The secondary objective was to develop a limited sampling model able to accurately predict exposure.MethodsStable liver transplant patients receiving once daily tacrolimus (N = 66) were included. Population pharmacokinetic analysis was performed with patients of whom DNA was available (N = 49), and demographic factors, CYP3A4*22 and CYP3A5*3, were tested as covariates. Moreover, a limited sampling model was developed using data of 66 patients.ResultsPharmacokinetics was best described by a two-compartment model with delayed absorption. CYP3A5*1 carrying recipients engrafted with a CYP3A5*1 carrying liver had an average 1.7-fold higher clearance compared to non-carriers. CYP3A5*1 carrying recipients engrafted with a CYP3A5*1 non-carrying liver or vice versa showed an average 1.3-fold higher clearance compared with non-carriers. CYP3A4*22 was not significantly associated with once daily tacrolimus pharmacokinetics. Using 0, 2, and 3 h postdose as limited sampling model resulted in significantly improved prediction of tacrolimus exposure compared with trough concentration.ConclusionsBoth donor and recipient CYP3A5 genotype significantly influences tacrolimus once daily pharmacokinetics. In contrast, CYP3A4*22 appears not suitable as biomarker. The developed limited sampling model can be used to accurately estimate tacrolimus once daily exposure.Electronic supplementary materialThe online version of this article (doi:10.1007/s00228-015-1963-3) contains supplementary material, which is available to authorized users.

BackgroundDuring the last decade, the number of people with ≥1 tattoo has increased noticeably within the European population. Despite this, limited safety information is available for tattoo inks.ObjectivesTo test the skin sensitization potential of 5 tattoo inks in vitro by using reconstructed human skin (RHS) and the contact sensitization biomarker interleukin (IL)‐18.MethodsTwo red and 3 black tattoo inks, 1 additive (Hamamelis virginiana extract) and 1 irritant control (lactic acid) were tested. The culture medium of RHS (reconstructed epidermis on a fibroblast‐populated collagen hydrogel) was supplemented with test substances in a dose‐dependent manner for 24 hours, after which cytotoxicity (histology; thiazolyl blue tetrazolium bromide assay) and skin sensitization potential (IL‐18 secretion; enzyme‐linked immunosorbent assay) were assessed.ResultsAll but 1 ink showed cytotoxicity. Notably, 1 red ink and 1 black ink were able to cause an inflammatory response, indicated by substantial release of IL‐18, suggesting that these inks may be contact sensitizers.ConclusionsThe in vitro RHS model showed that 4 tattoo inks were cytotoxic and 2 were able to cause an inflammatory IL‐18 response, indicating that an individual may develop allergic contact dermatitis when exposed to these tattoo inks, as they contain contact sensitizers.

underserved areas. In the future, these patients could have the ability to scan their lesions so that a dermatologist can print it out at their respective location. However, even in combination with 3D printing, teledermatology does not allow for the assessment of certain portions of the clinical examination, such as induration and warmth. Although 3D technology is studied and utilized in the dermatologic setting, it is not currently being used for the purposes described herein. Skin cells are routinely 3D printed to treat burns and wounds, but not to create replicas of cutaneous disease for the purpose of medical education or teledermatology measures. This article aims to highlight the incredible potential of 3D scanning and 3D printing in an effort to identify gaps in the current application of this useful technology.

Background: Worldwide 10-20% of the population is tattooed. However, tattoo complications can occur, such as allergic tattoo reactions, infections, and manifestations of autoimmune dermatoses. Despite the growing popularity of tattoos and changes in tattoo ink composition over the last decades, little is known about these complications, its clinical aspects, pathomechanism, and relative occurrence.Objective: The aim of this article is to describe the types and clinical aspects of dermatological tattoo complications, its relative occurrence and underlying conditions. Methods:We performed a retrospective cohort study enrolling all patients with tattoo complications from the Tattoo Clinic. Tattoo complications were categorized into infections, inflammatory tattoo reactions, neoplasms, or miscellaneous reactions and correlated to clinical data.Results: Of the total of 326 patients, 301 patients were included with 308 complications. The majority of the complications were chronic: 91.9%. Allergic red tattoo reactions and chronic inflammatory black tattoo reactions (CIBTR) accounted for 50.2% and 18.2%, respectively, of all tattoo complications. Of these CIBTR reactions, extracutaneous involvement was found in 21.4%, including tattoo-associated uveitis (7.1%) and systemic sarcoidosis (14.2%). Of all black tattoo reactions, systemic sarcoidosis was found in 7.8%. Conclusion:Tattoos can cause a wide range in complications that may start years after getting the tattoo. The most frequent tattoo reactions are allergic red tattoo reactions and chronic inflammatory black tattoo reactions, making these the most relevant for the dermatologist. CIBTR have a high percentage of multi-organ involvement, and therefore, screening for sarcoidosis, including ocular involvement, is advised.