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Abstract Background In recent years inhibitors directed against the epidermal growth factor receptor (EGFR) have evolved as effective targeting cancer drugs. Characteristic papulopustular exanthemas, often described as acneiform rashes, are the most frequent adverse effect associated with this class of novel cancer drugs and develop in > 90% of patients. Notably, the rash may significantly compromise the patients' quality of life, thereby potentially leading to incompliance as well as dose reduction or even termination of the anti-EGFR therapy. Yet, an effective dermatologic management of cutaneous adverse effects can be achieved. Whereas various case reports, case series or expert opinions on the management of EGFR-inhibitor (EGFRI) induced rashes have been published, data on systematic management studies are sparse. Methods Here, we present a retrospective, uncontrolled, comparative study in 49 patients on three established regimens for the management of EGFRI-associated rashes. Results Strikingly, patients' rash severity improved significantly over three weeks of treatment with topical mometason furoate cream, topical prednicarbate cream plus nadifloxacin cream, as well as topical prednicarbate cream plus nadifloxacin cream plus systemic isotretinoin. Conclusions In summary our results demonstrate that EGFRI-associated rashes can be effectively managed by specific dermatologic interventions. Whereas mild to moderate rashes should be treated with basic measures in combination with topical glucocorticosteroids or combined regiments using glucocorticosteroids and antiseptics/antibiotics, more severe or therapy-resistant rashes are likely to respond with the addition of systemic retinoids.

Purpose: The purpose of this study was to analyse the factors that influence patients` choice of obstetric and gynaecological medical centre., Methods: Patients attending the gynaecological and obstetric outpatient department (gyn./obs.) at a large tertiary university hospital were asked to voluntarily complete an anonymous 34-item-questionnaire on factors influencing their choice of medical centre at a large tertiary university hospital. Apart from epidemiological factors the preferences were analysed using a Likert scale of 1-5 (1 least, 5 most). Between 10/2023 and 04/2024, 445 outpatients (170 gynaecological, 275 obstetric) were included., Results: In both outpatient departments (gynaecological/obstetric), the most important factors (4&5/5 possible points) were considered to be clear communication (90%/92%), sufficient time for consultation with the medical staff (90%/90%), friendly care (89%/92%), good professional qualifications (86%/89%), treatment according to the latest findings (85%/86%) and empathy (83%/91%). The following factors were considered less important: Doctor's degree was considered important by only 31%/28%, appearance by 32%/35%, internet rating by 41%/36% and professional background by 35%/38% of patients. Regarding organisational structures, medical care was most important (91%/93%), followed by availability by telephone or e-mail (88%/82%), clear communication of possible costs (79%/76%) and organisation of consultations (76%/69%). Less important were short waiting times (67%/63%), flexible opening hours (63%/56%), the facilities (46%/68%) and the location (43%/66%)., Conclusion: Patients often prioritise interpersonal factors when choosing a centre for medical treatment, external factors such as academic qualifications or organisational issues appear to be less important. While it is unsurprising that the best medical treatment is of paramount importance, the other findings can help to increase patients´ satisfaction and experience of the treatment., Competing Interests: Declarations. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Postpartum depression (PPD) is a severe complication in the postpartum period and equals a major depression occurring in the first weeks after delivery. During the COVID-19 pandemic, an increased incidence of PPD was observed. For this reason, we conducted an intervention study to test the effectiveness of the "7mind"-app, an app-based mindfulness training program, in the prevention of PPD., Methods: For this purpose, 145 women who gave birth between March and September 2021 were observed up to six months postpartum, with 80 women using the "7mind"-app. The BSF (Berlin Mood Questionnaire) and the EPDS (Edinburgh Postnatal Depression Scale) were used to measure depressive symptoms at different time points and were supplemented by questionnaires regarding COVID-related anxieties., Results: The BSF showed a significant improvement over time in the categories "anxiety" (p < .001) and "fatigue" (p < .001). Regarding the EPDS, there were no significant differences between the intervention and control groups. With a mean EPDS of 7.6 prepartum and 7.4 postpartum, our sample group can be classified as a low-risk collective. Furthermore, there were no significant differences between the control and intervention groups with regard to COVID-19-related anxiety. However, a comparison of the correlation analysis of COVID-19-related fears over time showed a clear advantage of the intervention. In particular, fear of the consequences of maternal COVID-19 infection increased significantly in the control group over time (r = 0.98, p = 0.040), while there was no significant change in the intervention group (r = -0.39, p = 0.218)., Conclusions: In conclusion, the intervention with the app "7mind" seems to lead to a clear benefit in the prevention of general anxiety and COVID-19-related anxieties, but needs further research to represent a valid intervention for the prevention of PPD., Competing Interests: Declarations. Conflict of interest: Sv.M.: Research support, advisory board, honoraria and travel expenses from AbbVie, AstraZeneca, Clovis, Eisai, GlaxoSmithKline, Medac, MSD, Novartis, Olympus, PharmaMar, Pfizer, Roche, Sensor Kinesis, Teva, Tesaro; T.K.: holds stock of Roche, Biontech, Valneva, BayerAG, relative employed at BayerAG; The other authors declare no conflicts of interest. Ethical approval and consent to participate: This study was performed in line with the principles of the Declaration of Helsinki and was approved by the local ethics committee of the Ludwig Maximilian University of Munich (reference number–Nr. 20–378). Consent to participate and to publish: Informed consent was obtained from all individual participants included in the study. A specific consent to publish was not necessary as no individuals can be identified in this publication., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Depending on the ambient pH, ionizable substances are present in varying proportions in their neutral or charged form. The extent to which these two chemical species contribute to the pH-dependant toxicity of ionizable chemicals and whether intracellular ion trapping has a decisive influence in this context is controversially discussed. Against this background, we determined the acute toxicity of 24 ionizable substances at up to 4 different pH values on the embryonic development of the zebrafish, Danio rerio, and supplemented this dataset with additional data from the literature. The LC 50 for some substances (diclofenac, propranolol, fluoxetine) differed by a factor of even >10 3 between pH5 and pH9. To simulate the toxicity of 12 acids and 12 bases, six models to calculate a pH-dependant logD value as a proxy for the uptake of potentially toxic molecules were created based on different premises for the trans-membrane passage and toxic action of neutral and ionic species, and their abilities to explain the real LC 50 data set were assessed. Using this approach, we were able to show that both neutral and charged species are almost certainly taken up into cells according to their logD-based distribution, and that both species exert toxicity. Since two of the models that assume all intracellular molecules to be neutral overestimated the real toxicity, it must be concluded, that the toxic effect of a single charged intracellularly present molecule is, on the average, lower than that of a single neutral molecule. Furthermore, it was possible to attribute differences in toxicity at different pH values for these 24 ionizable substances to the respective deltas in logD at these pH levels with high accuracy, enabling particularly a full logD-based model on the basis of logP ow as a membrane passage descriptor to be used for predicting potential toxicities in worst-case scenarios from existing experimental studies, as stipulated in the process of registration of chemicals and the definition of Environmental Quality Standards (EQS)., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare, (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Target-site concentrations obtained via the catheter-based minimally invasive microdialysis technique often exhibit high variability. Catheter calibration is commonly performed via retrodialysis, in which a transformation factor, termed relative recovery (RR), is determined. Leveraging RR values from a rich data set of a very large clinical microdialysis study, promised to contribute critical insight into the origin of the reportedly high target-site variability. The present work aimed (i) to quantify and explain variability in RR associated with the patient (including non-obese vs. obese) and the catheter, and (ii) to derive recommendations on the design of future clinical microdialysis studies., Methods: A prospective, age- and sex-matched parallel group, single-centre trial in non-obese and obese patients (BMI=18.7-86.9 kg/m 2 ) was performed. 1-3 RR values were obtained in the interstitial fluid of the subcutaneous fat tissue in one catheter per upper arm of 120 patients via the retrodialysis method (n RR =1008) for a panel of drugs (linezolid, meropenem, tigecycline, cefazolin, fosfomycin, piperacillin and acetaminophen). A linear mixed-effects model was developed to quantify the different types of variability in RR and to explore the association between RR and patient body size descriptors., Results: Estimated RR was highest for acetaminophen (69.7%, 95%CI=65.0% to 74.3%) and lowest for piperacillin (40.4%, 95%CI=34.6% to 46.0%). The linear mixed-effects modelling analysis showed that variability associated with the patient (σ=15.9%) was the largest contributor (46.7%) to overall variability, whereas the contribution of variability linked to the catheter (σ=5.55%) was ~1/6 (16.8%). The relative contribution of residual unexplained variability (σ=12.0%, including intracatheter variability) was ~1/3 (36.4%). The limits of agreement of repeated RR determinations in a single catheter ranged from 0.694-1.64-fold (linezolid) to 0.510-3.02-fold (cefazolin). Calculated fat mass affected RR, explaining the observed lower RR in obese (ΔRR mean = -29.7% relative reduction) versus non-obese patients (p<0.001); yet only 15.8% of interindividual variability was explained by this effect. No difference in RR was found between catheters implanted into the left or right arm (p=0.732)., Conclusions: Three recommendations for clinical microdialysis trial design were derived: 1) High interindividual variability underscored the necessity of measuring individual RR per patient. 2) The low relative contribution of intercatheter variability to overall variability indicated that measuring RR with a single catheter per patient is sufficient for reliable catheter calibration. 3) The wide limits of agreement from multiple RR in the same catheter implied an uncertainty of a factor of two in target-site drug concentration estimation necessitating to perform catheter calibration (retrodialysis sampling) multiple times per patient. To allow routine clinical use of microdialysis, research efforts should aim at further understanding and minimising the method-related variability. Optimised study designs in clinical trials will ultimately yield more informative microdialysis data and increase our understanding of this valuable sampling technique to derive target-site drug exposure., (Copyright © 2020. Published by Elsevier B.V.)

Background: Linezolid is used for the treatment of soft tissue infections in critically ill patients. However, data for characterizing the pharmacokinetics (PK) and assessing whether effective concentrations are reached at the target site are lacking. We hypothesized that current dosing regimens do not lead to effective concentrations in the plasma and interstitial fluid (ISF) of subcutaneous tissue in obese patients. Methods: As a controlled clinical model, critically ill obese and non-obese patients undergoing intra-abdominal surgery received 600 mg linezolid as a single infusion. Concentrations in the plasma and microdialysate from the ISF of subcutaneous tissue were determined up to 8 h after dosing. Pharmacokinetic analysis was performed by non-compartmental methods. As a therapeutic target, we used f AUC/MIC > 80. Results: Fifteen obese (BMI: 48.7 ± 11.2 kg/m 2 ) and 15 non-obese (23.9 ± 2.1 kg/m 2 ) patients were analyzed. AUC 0-8 in ISF decreased by -1.69 mg*h/L (95% CI: -2.59 to -0.79, p < 0.001) for every 10 kg increase in weight. PK in obese patients were characterized by lower maximal plasma concentrations (median 3.8 vs. 8.3 mg/L, p < 0.001) and a higher volume of distribution (41.0 vs. 30.8 L, p < 0.001), and the therapeutic target was not reached for MIC ≥ 1 mg/L in ISF and ≥ 2 mg/L in plasma. Conclusions: Increasing the weight led to a decrease of linezolid concentrations in the plasma and subcutaneous tissue. The current dosing regimen does not seem to produce sufficient concentrations to kill bacteria with MIC ≥ 2 mg/L, especially as empirical antimicrobial therapy in critically ill obese patients.

Effective antibiotic dosing is vital for therapeutic success in critically ill patients. This work aimed to develop an algorithm to identify appropriate meropenem dosing in critically ill patients. Population pharmacokinetic (PK) modelling was performed in NONMEM®7.3 based on densely sampled meropenem serum samples (n patients  = 48; n samples  = 1376) and included a systematic analysis of 27 pre-selected covariates to identify factors influencing meropenem exposure. Using Monte Carlo simulations newly considering the uncertainty of PK parameter estimates, standard meropenem dosing was evaluated with respect to attainment of the pharmacokinetic/pharmacodynamic (PK/PD) target and was compared with alternative infusion regimens (short-term, prolonged, continuous; daily dose, 2000-6000 mg). Subsequently, a dosing algorithm was developed to identify appropriate dosing regimens. The two-compartment population PK model included three factors influencing meropenem pharmacokinetics: the Cockcroft-Gault creatinine clearance (CLCR CG ) on meropenem clearance; and body weight and albumin on the central and peripheral volume of distribution, respectively; of these, only CLCR CG was identified as a vital influencing factor on PK/PD target attainment. A three-level dosing algorithm was developed (considering PK parameter uncertainty), suggesting dosing regimens depending on renal function and the level (L) of knowledge about the infecting pathogen (L1, pathogen unknown; L2, pathogen known; L3 (-MIC) , pathogen and susceptibility known; L3 (+MIC) , MIC known). Whereas patients with higher CLCR CG and lower pathogen susceptibility required mainly intensified dosing regimens, lower than standard doses appeared sufficient for highly susceptible pathogens. In conclusion, a versatile meropenem dosing algorithm for critically ill patients is proposed, indicating appropriate dosing regimens based on patient- and pathogen-specific information., (Copyright © 2019. Published by Elsevier B.V.)

The need for pharmacokinetic knowledge about antibiotics directly at the site of infection, typically the interstitial space fluid (ISF) of tissues, is gaining acceptance for effective and safe treatment. One option to acquire such data is the microdialysis technique employing a catheter with a semipermeable membrane inserted directly in the ISF. A prerequisite is catheter calibration, e.g. via retrodialysis, yielding a conversion factor from measured to true ISF concentrations, termed relative recovery. This value can be influenced by various factors. The present investigation assessed the impact of three of them on relative recovery using seven drugs: (I) drug combinations/order, (II) air in the microdialysis system, (III) flow rate changes inherent when using common in vivo microdialysis pumps. All experiments were performed in a standardised in vitro microdialysis system. (I) Relative recovery of single antibiotics (linezolid, meropenem, cefazolin, metronidazole, tigecycline) was determined in microdialysis and retrodialysis settings and compared with values using either antibiotic or antibiotic+analgesic (acetaminophen and metamizole) combinations or single drugs with reversed microdialysis order. For assessing these factors for lower relative recovery values (as in in vivo), these were mimicked by increasing the flow rate for linezolid. (II) For the impact of air, linezolid relative recovery of freshly carbonated solutions was compared to degassed ones in microdialysis and retrodialysis settings. For each condition in (I) and (II), summary statistics of relative recovery were calculated and for the impact of the factors a linear mixed-effect model developed. (III) From samples taken during an automatic flush sequence (15 μL/min) of an in vivo pump and afterwards switching to the flow rate of 1 and 2 μL/min for 120 min, the time necessary for relative recovery to reach equilibrium was determined. (I) High relative recovery values (flow rate 2 μL/min: ≥84%; flow rate 5 μL/min: ≥65%) were observed for all investigated single drugs. Intra- and intercatheter variability ranged from 0.3%-11% and 3%-25%, respectively. Based on these values and on the statistical model, the impact of drug combination versus single drug as well as of reversed order was small with changes in relative recovery of smaller equal 9%. (II) Compared to degassed solutions, relative recovery in carbonated solutions was 23% and 19% lower (relative reduction) in the microdialysis and retrodialysis setting, respectively, with increased intercatheter variability (up to 37%). (III) As expected, relative recovery increased after the flush sequence and was constant 10-15 min after the switch to the typical 1 and 2 μL/min flow rate. Given the intercatheter variability, combinations and the order of drugs showed minor but clinically negligible impact on relative recovery. In contrast, air in the microdialysis catheter/system caused falsely low and inconsistent relative recovery values and must be avoided when performing a trial. Also changes in flow rate at the end of pump flush sequence impacted relative recovery. Hence, a sufficient equilibration time of 10-15 min prior to sampling should be implemented in sampling protocols. In vitro microdialysis presents a highly valuable complementary platform to clinical microdialysis studies impacting the design, sampling schedule and data analysis of such trials to gain knowledge of target-site pharmacokinetics for contributing to better informed decisions in the individual patient/special populations in future., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Severe bacterial infections remain a major challenge in intensive care units because of their high prevalence and mortality. Adequate antibiotic exposure has been associated with clinical success in critically ill patients. The objective of this study was to investigate the target attainment of standard meropenem dosing in a heterogeneous critically ill population, to quantify the impact of the full renal function spectrum on meropenem exposure and target attainment, and ultimately to translate the findings into a tool for practical application., Methods: A prospective observational single-centre study was performed with critically ill patients with severe infections receiving standard dosing of meropenem. Serial blood samples were drawn over 4 study days to determine meropenem serum concentrations. Renal function was assessed by creatinine clearance according to the Cockcroft and Gault equation (CLCR CG ). Variability in meropenem serum concentrations was quantified at the middle and end of each monitored dosing interval. The attainment of two pharmacokinetic/pharmacodynamic targets (100%T >MIC , 50%T >4×MIC ) was evaluated for minimum inhibitory concentration (MIC) values of 2 mg/L and 8 mg/L and standard meropenem dosing (1000 mg, 30-minute infusion, every 8 h). Furthermore, we assessed the impact of CLCR CG on meropenem concentrations and target attainment and developed a tool for risk assessment of target non-attainment., Results: Large inter- and intra-patient variability in meropenem concentrations was observed in the critically ill population (n = 48). Attainment of the target 100%T >MIC was merely 48.4% and 20.6%, given MIC values of 2 mg/L and 8 mg/L, respectively, and similar for the target 50%T >4×MIC . A hyperbolic relationship between CLCR CG (25-255 ml/minute) and meropenem serum concentrations at the end of the dosing interval (C 8h ) was derived. For infections with pathogens of MIC 2 mg/L, mild renal impairment up to augmented renal function was identified as a risk factor for target non-attainment (for MIC 8 mg/L, additionally, moderate renal impairment)., Conclusions: The investigated standard meropenem dosing regimen appeared to result in insufficient meropenem exposure in a considerable fraction of critically ill patients. An easy- and free-to-use tool (the MeroRisk Calculator) for assessing the risk of target non-attainment for a given renal function and MIC value was developed., Trial Registration: Clinicaltrials.gov, NCT01793012 . Registered on 24 January 2013.

Background: Perioral dermatitis (POD) is a common inflammatory skin disease without standard therapy., Objective: We sought to evaluate the clinical value of a soothing fluid for the treatment of POD., Methods: We included 51 patients with POD in this 8-week clinical trial. The Toleriane Fluide Efficacy in Perioral Dermatitis (TOLPOD) study had an open-label design and involved twice-daily application of Toleriane Fluide, a soothing cosmetic fluid. Clinical assessment of POD was performed with a predefined questionnaire including the POD severity index (PODSI). Control visits were made after 4 and 8 weeks of treatment., Results: The results were compared with those of a historical control group treated with a vehicle cream. Patients treated with the soothing fluid showed a continuous and significant improvement of the PODSI over time. The improvement of PODSI observed with the soothing fluid was better, but not significantly better, than that observed in the historical controls. In addition, the subjective complaints of patients such as disease burden, itching, distension of the skin, and appearance improved during treatment., Conclusion: A soothing fluid could be a clinically useful treatment option for POD.

In recent years, several new classes of compounds have successfully been established in the treatment of cancer. They selectively inhibit disturbed signaling pathways or induce anti-tumor immune responses. These novel targeted cancer drugs show a favorable safety profile compared to conventional chemotherapeutic agents. The most important side effects of these anticancer agents include cutaneous reactions and occur in a time-dependant manner and show class-specific patterns. In this review article, we compare the cutaneous side effects of epidermal growth factor inhibitors (EGFRI), multikinase inhibitors (MKI), BRAF inhibitors (BRAFI), mTor inhibitors (mTorI) and immune checkpoint inhibitors and discuss severity-adapted management strategies.

Phacomatosis pigmentokeratotica (PPK) is a rare epidermal nevus syndrome characterized by the co-occurrence of a sebaceous nevus and a speckled lentiginous nevus. The coexistence of an epidermal and a melanocytic nevus has been explained by two homozygous recessive mutations, according to the twin spot hypothesis, of which PPK has become a putative paradigm in humans. However, the underlying gene mutations remained unknown. Multiple tissues of six patients with PPK were analyzed for the presence of RAS, FGFR3, PIK3CA, and BRAF mutations using SNaPshot assays and Sanger sequencing. We identified a heterozygous HRAS c.37G>C (p.Gly13Arg) mutation in four patients and a heterozygous HRAS c.182A>G (p.Gln61Arg) mutation in two patients. In each case, the mutations were present in both the sebaceous and the melanocytic nevus. In the latter lesion, melanocytes were identified to carry the HRAS mutation. Analysis of various nonlesional tissues showed a wild-type sequence of HRAS, consistent with mosaicism. Our data provide no genetic evidence for the previously proposed twin spot hypothesis. In contrast, PPK is best explained by a postzygotic-activating HRAS mutation in a multipotent progenitor cell that gives rise to both a sebaceous and a melanocytic nevus. Therefore, PPK is a mosaic RASopathy.

Granulomatous rosacea is an uncommon variant of rosacea. It is characterized by disseminated, red-brown papules and nodules especially in periocular and centrofacial locations. This form of rosacea causes considerable distress among patients because of the inflammatory facial lesions and represents a therapeutic challenge. A 62-year old man with granulomatous rosacea failed to improve with systemic doxycycline. Systemic isotretinoin and corticosteroids produced only a temporary reduction in cutaneous findings. Finally, systemic treatment with dapsone resulted in remission of the skin lesions and long-term stabilization.

Acrokeratosis paraneoplastica Bazex is a rare, obligate paraneoplasia initially presenting with palmoplantar hyperkeratosis. Later stages show acral psoriasiform lesions on other parts of the body. Common associated malignancies are laryngeal cancer and other tumors of the head or neck region or neck lymph node metastases. A 49-year-old woman presented with palmoplantar hyperkeratoses for 4 months; in addition she had a squamous cell carcinoma of the larynx. We diagnosed a minor form of acrokeratosis paraneoplastica Bazex. Some authors consider this as a separate entity, but the well- known course argues against this hypothesis. We report a case and review the literature.

Recently, inhibitors of the epidermal growth factor receptor (EGFR) and multikinase inhibitors have been successfully established in the therapy of various solid tumors. EGFR inhibitors and multikinase inhibitors are specific and selective agents that intervene with the dysfunctional regulatory processes of malignant cells. This results in a favorable safety profile and range of side effects, especially in comparison to conventional chemotherapy. The various cutaneous adverse drug reactions are considered substance class effects and are the most frequent side effects of these targeted therapies. Therapy with EGFR inhibitors is associated with acneiform rash, painful paronychia, xerosis cutis, acral fissures, hair changes, and pruritus. Treatment with tyrosin kinase inhibitors may cause hand-foot syndrome, various types of drug rash, hair loss, xerosis cutis, and pruritus. These side effects may be stigmatizing and place a huge burden on the patient's quality of life. Treatment is a challenge and best performed in interdisciplinary cooperation of dermatologists and oncologists.

History and Clinical Findings: A 52-year-old patient presented with a 6-months history of painful, progressive erythematous periumbilical papules and nodules. Seven months previously, an advanced stage of an adenocarcinoma of the stomach with peritoneal carcinosis and malignant ascites had been diagnosed., Investigations: Clinical examination showed ten firm, painful, umbilicated, erythematous, polygonal papules and nodules (size up to 7 mm), partly covered with central hemorrhagic crusts or scales. The histological examination revealed epithelial cell clusters infiltrating the dermis and forming tubular structures. The prominent nuclei varied in size, some were vacuolated. Signet ring structures were visible in the tumor. Immunohistochemical staining revealed MNF116 expressing tumor cells, consistent with a moderately differentiated adenocarcinoma., Diagnosis: Multiple Sister Mary Joseph's nodules - periumbilical skin metastases from gastric carcinoma., Treatment and Course: The previous palliative chemotherapy with capecitabine will be expanded by irinotecan after completion of local iradiation of an esophageal stenosis. The patient declined additional local therapeutic options such as excision or electric chemotherapy., Conclusion: Sister Mary Joseph's nodule is a rare, umbilical cutaneous metastatic tumor originating from advanced metastatic intraabdominal or intrapelvic malignancies. Our case is remarkable because of the number of the umbilical and periumbilical, but otherwise characteristic nodules. Sister Mary Joseph's nodules are associated with a dismal prognosis. As they may precede cancer diagnosis, histological investigation of suspect umbilical nodules should be performed., (© Georg Thieme Verlag KG Stuttgart · New York.)

Epidermal growth factor receptor (EGFR) inhibitors are an increasingly important treatment option for metastasized cancer in patients. In addition to the pivotal role of EGFR in the development and progression of malignant tumors, EGFR is also important for proliferation and differentiation of the human epidermis and hair follicles. As a consequence, cutaneous side-effects are frequently observed during cancer therapy with EGFR inhibitors. During the first few weeks of treatment, acneiform eruptions are the earliest common side-effect. Xerosis and fissures are complications appearing in later treatment phases. Paronychia and alterations in hair growth are less common and generally seen after a longer period of treatment. We present an overview of the various cutaneous side-effects associated with EGFR inhibition and discuss their respective therapeutic options.