Symmetrical Facial Giant Plaque-Type Juvenile Xanthogranuloma: Case Report and Review of the Literature.

Juvenile xanthogranuloma (JXG) is the most common type of non-Langerhans cell histiocytosis. JXG is a rare benign tumor, which may be present at birth or develop later. The classical form of JXG is characterized by a red-yellowish benign papule or nodule with predilection sites on the head, neck, and trunk, although lesions can appear on extremities or extracutaneous sites. In most cases there is only one lesion, whereas numerous papules or nodules may occur. Special forms of JXG such as mixed, giant, subcutaneous, eruptive, clustered, and plaque-like have been reported and associations between JXG and systemic diseases have been made. Diagnosis mainly relies on the clinical appearance, and histology usually can confirm the disease. Here we present a very rare case of symmetrical giant facial plaque-type juvenile xanthogranuloma (SGFP-JXG) and compare it with classical JXG, variations of JXG, and discuss the differential diagnosis. A 4-year-old Caucasian female presented with plaque-like lesions composed of yellowish confluent papules on both the cheeks. The histological evaluation revealed a histiocytic lesion with a formation of Touton giant cells and immunohistochemistry results confirmed the diagnosis of the SGFP-JXG. In comparison to classical JXG, the onset of SGFP-JXG sometimes occurs later and the spontaneous resolution period may be prolonged. No associated diseases and no systemic involvements were observed. Histopathology is required to differentiate this form of JXG from other histiocytosis. To the best of our knowledge, only four cases of SGFP-JXG have been reported in the literature so far.

Gene expression is stable in a complete CIB1 knockout keratinocyte model.

Epidermodysplasia verruciformis (EV) is a genodermatosis characterized by the inability of keratinocytes to control cutaneous ß-HPV infection and a high risk for non-melanoma skin cancer (NMSC). Bi-allelic loss of function variants in TMC6, TMC8, and CIB1 predispose to EV. The correlation between these proteins and ß-HPV infection is unclear. Its elucidation will advance the understanding of HPV control in human keratinocytes and development of NMSC. We generated a cell culture model by CRISPR/Cas9-mediated deletion of CIB1 to study the function of CIB1 in keratinocytes. Nine CIB1 knockout and nine mock control clones were generated originating from a human keratinocyte line. We observed small changes in gene expression as a result of CIB1 knockout, which is consistent with the clearly defined phenotype of EV patients. This suggests that the function of human CIB1 in keratinocytes is limited and involves the restriction of ß-HPV. The presented model is useful to investigate CIB1 interaction with ß-HPV in future studies.

When life is an itch: What harms, helps, and heals from the patients' perspective? Differences and similarities among skin diseases.

Itch is the commonest skin-related symptom, associated with a high psychosocial and economic burden. While the main focus of itch research lies on a few chronic skin diseases, only little is known about the perception of itch, itch-aggravating/-relieving factors and treatment preferences in patients with acute and chronic itch of various etiology. In this cross-sectional study, we assessed these aspects in 126 patients (mean age 61.7 ± 18.4 years, 67 females, median itch duration 3.9 years) using a 78-item questionnaire. The diseases were categorized into 11 diagnostic groups for descriptive analysis; the three most frequent groups ("atopic dermatitis," "nonatopic eczema," "inflammatory dermatoses") were statistically compared. Itch was most often perceived as localized 42.9%, burning (40.5%), and worrying (39.7%) with worsening in the evening (49.2%), due to warmth (42.1%) and sweating (26.2%). While itch perception, itch-aggravating factors and treatment preferences differed broadly among patients, the itch-relieving personal strategies were more uniform ("scratching by hand 70.6%, applying topicals 57.9%). Also, 69.8% of patients suffered from itch-related sleep disturbance, consequently affecting their relatives in 30.0%. Subgroup comparisons revealed significant differences regarding itch-aggravating factors (P = .0012) and itch duration (P = .0082). Patients rated the antipruritic effectiveness of phototherapy, "complementary and alternative medicine" and "other tablets" as high, but oral antihistamines, "cortisone tablets" and any topical as only moderately efficacious. The preferred administration of an ideal itch treatment was "creams/ointments" (51.6%) or "tablets" (35.7%), only few patients preferred "injections" or "patches." Consideration of such differences and similarities in itch characteristics and treatment preferences could help to better tailor treatment in itch patients.

Pain reduction by dehydrated human amnion/chorion membrane allograft in nondiabetic leg ulcers might be an early indicator of good response: A case series.

Dehydrated human amnion/chorion membrane allograft (dHACM) derived from placenta is increasingly used for skin and soft tissue repair in several medical specialties. Promising effects of dHACM were also reported in chronic venous and diabetic leg ulcers. However, dHACM is cost-intensive and its effect on chronic leg ulcers of other etiologies and pain reduction is unknown. Clinical predictors of a favorable response to dHACM during the early treatment period could help to limit unnecessary costs. In our case series with six patients suffering from chronic lower leg ulcers of various etiology, the effect of dHACM once per week on reduction of pain and wound size during a 5-week period was examined. dHACM resulted in effective pain reduction and improved wound healing in three patients with chronic leg ulcers due to calciphylaxis, chronic venous disease and reactive angioendotheliomatosis. Pain reduction after 1 to 2 applications of dHACM predicted a favorable healing response. Hence, our observation indicates that assessment of pain 3 weeks after initiation of dHACM may be a clinical predictor to justify dis-/continuation of dHACM and thereby may help to limit costs.

Pruritic and antipruritic colors: An exploratory pilot study.

Itch is the commonest skin-related symptom and can be influenced by visual cues as exemplified by the phenomenon of "contagious itch." Colors are visual cues able to modify somatosensory inputs. We explored the relationship of colors and itch and the impact of color viewing on itch intensity. In this cross-sectional study, patients suffering from itch with a mean intensity of ≥2 on a Numerical Rating Scale during the last 7 days were evaluated. The study consisted of a questionnaire-based part using The Manchester Color Wheel and the ItchyQoL, followed by an interventional part. All 72 itch patients were able to match their itchy sensation with a color: In 68 patients (94.4%) this "pruritic" basic color was red. Likewise, all patients were able to define a subjective "antipruritic" color: The leading basic color choice was blue (31/72, 43.0%) followed by green (21/72, 29.1%), yellow (7/72,9.7%) and others. The impairment of the itch-related quality of life (as measured by the ItchyQoL) correlated with the brightness and saturation of the pruritic and antipruritic colors. Ten patients were visually exposed to their subjective antipruritic and pruritic color during 10 minutes resulting in a significant decrease and increase of itch intensity compared to baseline (5.1 ± 1.52 vs. 2.8 ± 1.47 [0-10 Numerical Rating Scale, NRS], p=0.0004 and 4.9 ± 1.66 vs. 6.8± 2.09 NRS, p=0.0009). These results indicate that itch can be modified by color viewing and colors matter when treating itch patients. However, further investigations are required to elucidate the therapeutic potential of colors in itch patients.

Sexually transmitted coinfections in patients with anogenital warts - a retrospective analysis of 196 patients.

BACKGROUND AND OBJECTIVES: Anogenital warts (AGWs) are most commonly caused by low-risk human papillomavirus (HPV) types, and although they are the most frequent viral sexually transmitted infections (STIs), little is known about STI coinfections in affected patients. We therefore sought to assess STI coinfection rates in patients with AGW, specify STI coinfections and calculate the number needed to screen (NNS) for each STI. METHODS: A retrospective cross-sectional study analyzing data sets from AGW patients treated in our clinic between 2008-2016. RESULTS: 142/196 (72 %) patients had been variably screened for infections with HIV, HBV and HCV, Treponema pallidum, Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium and HSV. The STI coinfection rate in all tested patients was 24.6 %, yielding an NNS of 4.1 to detect any STI. Of note, the coinfection rate did not differ significantly between heterosexual men, homosexual men and women, respectively. The NNS for syphilis was 8.4, for HIV 14.0, for HCV 28.5 and for HBV 39.0. The NNS for asymptomatic patients tested for HSV, Chlamydia trachomatis and Mycoplasma genitalium were 1.4, 5.3 and 12.0, respectively. CONCLUSION: Due to the high prevalence of STI coinfections, AGW patients should be screened for other STIs.

Arginine- but not alanine-rich carboxy-termini trigger nuclear translocation of mutant keratin 10 in ichthyosis with confetti.

Ichthyosis with confetti (IWC) is a genodermatosis associated with dominant-negative variants in keratin 10 (KRT10) or keratin 1 (KRT1). These frameshift variants result in extended aberrant proteins, localized to the nucleus rather than the cytoplasm. This mislocalization is thought to occur as a result of the altered carboxy (C)-terminus, from poly-glycine to either a poly-arginine or -alanine tail. Previous studies on the type of C-terminus and subcellular localization of the respective mutant protein are divergent. In order to fully elucidate the pathomechanism of IWC, a greater understanding is critical. This study aimed to establish the consequences for localization and intermediate filament formation of altered keratin 10 (K10) C-termini. To achieve this, plasmids expressing distinct KRT10 variants were generated. Sequences encoded all possible reading frames of the K10 C-terminus as well as a nonsense variant. A keratinocyte line was transfected with these plasmids. Additionally, gene editing was utilized to introduce frameshift variants in exon 6 and exon 7 at the endogenous KRT10 locus. Cellular localization of aberrant K10 was observed via immunofluorescence using various antibodies. In each setting, immunofluorescence analysis demonstrated aberrant nuclear localization of K10 featuring an arginine-rich C-terminus. However, this was not observed with K10 featuring an alanine-rich C-terminus. Instead, the protein displayed cytoplasmic localization, consistent with wild-type and truncated forms of K10. This study demonstrates that, of the various 3' frameshift variants of KRT10, exclusively arginine-rich C-termini lead to nuclear localization of K10.

[The Interdisciplinary Stomatology Service at the Department of Oral Surgery and Dental Imaging, University Center for Dental Medicine and the University Hospital Basel, Switzerland - Results from 2003 - 2013]. / Rückschau auf 10 Jahre interdisziplinäre Stomatologie-Sprechstunde an den Universitätszahnkliniken in Basel.

The Interdisciplinary Stomatology Service at the Department of Oral Surgery and Dental Imaging, University Center for Dental Medicine and the University Hospital Basel, Switzerland - Results from 2003 - 2013 Abstract. Stomatological problems are common, but rarely diagnosed in private dental practice. Even for oral surgeon's diagnosis and therapy of these disorders could be challenging. Stomatological problems can indicate general health problems. Hence, the oral cavity is also known as the «mirror of systemic diseases¼. To tackle this problem, an interdisciplinary stomatological service in a specialized dental clinic was established in 1999 at the Center for Dental Medicine, University of Basel, Switzerland. A board of specialists (Dermatologists, Otorhinolaryngologists, Oral- and Maxillofacial surgeons) was summoned monthly to perform interdisciplinary consultations of selected patients with complex oral and medical disorders. The specific knowledge of each specialist helped to ensure a diagnosis, even of rare systemic disorders and symptoms. Networking with a variety of specialists built the foundation for synoptic therapy approaches. Thus, the center was able to provide appropriate care for patients suffering from severe, chronic and complex stomatological findings. The results presented in this article are part of a dissertation based on the analysis of 154 patients who were seen in the interdisciplinary consultations in 2003 - 2013.

Assessment of the impact of sex in intensity, skin flares and central processing of histaminergic itch-A pilot study.

Itch is the commonest skin-related symptom, and sex differences are increasingly recognised as important determinants in stratified medicine, but only little is known about sex differences in itch. Questionnaire-based studies indicated that women perceive itch as more intensive and bothersome in comparison with men. However, data of studies using standardised itch models to objectify sex differences are scarce and inconsistent. To determine sex differences in intensity, skin flares and central processing of histaminergic itch, we compared 15 female and 15 male healthy subjects in a double-blinded, within-subject, placebo-controlled study using a histamine skin prick itch model (histamine 1% applied onto the volar forearm) and functional MRI. We found trends in higher mean itch intensity (0.58 VAS, CI 95% 0.004-1.19, P = .056) and maximum itch intensity (men 3.93 VAS ± 0.39 SD at 3 minutes, women 4.73 VAS ± 0.31 SD at 4 minutes, P = .073) in women paralleled by a trend in a stronger positive correlation between itch intensity and blood oxygen level-dependent (BOLD) activity in brain structures identified during itch in comparison with men (rs in women: .46, P = .08, rs in men: .07, P = .79). The erythema and wheal following histamine skin pricking were (non-significantly) larger in men, indicating that higher mean itch intensities on the right volar forearm in women may not be explained by more intense flares. The comparison of the activation patterns between the sexes revealed increased activity in men compared to women in the left middle temporal gyrus (temporooccipital part)/lateral occipital cortex. Thus, our findings indicate that histaminergic itch perception and central itch processing differ between the sexes under standardised conditions.

Assessment of the risk and characterization of non-melanoma skin cancer in Kindler syndrome: study of a series of 91 patients.

BACKGROUND: Kindler Syndrome (KS) is a rare genodermatosis characterized by skin fragility, skin atrophy, premature aging and poikiloderma. It is caused by mutations in the FERMT1 gene, which encodes kindlin-1, a protein involved in integrin signalling and the formation of focal adhesions. Several reports have shown the presence of non-melanoma skin cancers in KS patients but a systematic study evaluating the risk of these tumors at different ages and their potential outcome has not yet been published. We have here addressed this condition in a retrospective study of 91 adult KS patients, characterizing frequency, metastatic potential and body distribution of squamous cell carcinoma (SCC) in these patients. SCC developed in 13 of the 91 patients. RESULTS: The youngest case arose in a 29-year-old patient; however, the cumulative risk of SCC increased to 66.7% in patients over 60 years of age. The highly aggressive nature of SCCs in KS was confirmed showing that 53.8% of the patients bearing SCCs develop metastatic disease. Our data also showed there are no specific mutations that correlate directly with the development of SCC; however, the mutational distribution along the gene appears to be different in patients bearing SCC from SCC-free patients. The body distribution of the tumor appearance was also unique and different from other bullous diseases, being concentrated in the hands and around the oral cavity, which are areas of high inflammation in this disease. CONCLUSIONS: This study characterizes SCCs in the largest series of KS patients reported so far, showing the high frequency and aggressiveness of these tumors. It also describes their particular body distribution and their relationship with mutations in the FERMT-1 gene. These data reinforce the need for close monitoring of premalignant or malignant lesions in KS patients.

Smoking does not Alter the Therapy Response to Systemic Anti-psoriatic Therapies: A Two-country, Multi-centre, Prospective, Non-interventional Study.

Psoriasis can involve the skin, joints, nails and cardiovascular system and result in a significant impairment in quality of life. Studies have shown a lower response rate to systemic anti-psoriatic therapies in smokers, and smoking is a trigger factor for psoriasis. The aim of this study was therefore to analyse the response to systemic therapies for psoriasis, with a focus on smoking. Prospectively collected data from patients with moderate to severe psoriasis included in the national psoriasis registries for Germany and Switzerland (PsoBest and SDNTT) were analysed. Therapy response was defined as reaching a Psoriasis Area and Severity Index (PASI) reduction of 75%, PASI ≤ 3 or Dermatology Life Quality Index (DLQI) ≤ 1. Out of 5,346 patients included in these registries, 1,264 met the inclusion criteria for this study. In the smoking group, 715 (60.6%) reached therapy response at month 3, compared with 358 (63.7%) in the non-smoking group (p ≤ 0.269), 659 (74.1%) vs. 330 (77%) reached therapy response at month 6 (p ≤ 0.097), and 504 (76.6%) vs. 272 (79.0%) at month 12 (p ≤ 0.611). Therefore, these data do not show that smoking affects the response rate of anti-psoriatic therapy after 3, 6 and 12 months.

Implementation and evaluation of an algorithm for the management of scabies outbreaks.

BACKGROUND: Infestations with scabies mites are a global burden affecting individuals of all ages, classes and ethnicities. As poor sanitation and overcrowding favor the transmission of this highly contagious disease, epidemic outbreaks are frequently observed among displaced persons and asylum seekers. Due to the growing influx of refugees during the last years, public health authorities in host countries are frequently confronted with the challenge to treat individuals with diagnosed or suspected scabies promptly and effectively to avoid further spreading of the infestation. This study aimed to establish a straightforward and efficient algorithm for rapid screening and treatment of large numbers of patients with confirmed or suspected scabies infestations. METHODS: Forty-eight individuals (58% males, mean age 22.4 yrs.) from Syria with suspected scabies infestation were allocated to 3 colour-coded groups: (1) no signs or symptoms of infestation, (2) itch only, and (3) itch and typical skin lesions. Patients were treated with a single (group 1) or two doses of oral ivermectin at an interval of 7 days (group 2), or with a combination of 2 doses of ivermectin plus 2 applications of permethrin ointment at an interval of 7 days (group 3). Follow-ups were performed 4 weeks after initial treatments. RESULTS: All individuals with signs and/or symptoms of infestation had improved skin lesion; in 10/11 (90.9%) lesion had completely resolved. All individuals with initial itch only (n = 32) reported improvement of its intensity or complete resolution. None of the patients of group 1 developed itch or skin lesions. The algorithm was reapplied in 4 individuals (8.3%) after 4 weeks and the outbreak was completely controlled after 8 weeks. Colour-coding ensured fast flow of information between health-care providers at the interfaces of the algorithm. CONCLUSIONS: Our algorithm proved to be both highly efficient for treatment of large numbers of patients with suspected or diagnosed scabies infestation as well as for prevention of spreading of the disease. Hence, this algorithm is well suited for the management of scabies mass outbreaks.

The Absence of Evidence is Evidence of Non-Sense: Cross-Sectional Study on the Quality of Psoriasis-Related Videos on YouTube and Their Reception by Health Seekers.

BACKGROUND: Approximately 80% of internet users access health information online and patients with chronic illnesses especially rely on internet-based resources. YouTube ranks second among the most accessed websites worldwide and hosts an increasing number of videos with medical information. However, their quality is sometimes unscientific, misleading, or even harmful. OBJECTIVE: As little is known about YouTube as a source of information on psoriasis, we aimed to investigate the quality of psoriasis-related videos and, if necessary, point out strategies for their improvement. METHODS: The quality of the 100 most viewed psoriasis-related videos was assessed using the DISCERN instrument and the Global Quality Scale (GQS) by categorizing the videos into useful, misleading, and dangerous and by evaluating the reception of the videos by users. RESULTS: Evaluation of the videos exhibited a total of 117,221,391 views and a total duration of 10:28 hour. The majority of clips contained anecdotal personal experiences with complementary and alternative psoriasis treatments, topical treatments, and nutrition and diets being the most frequently addressed topics. While advertisements accounted for 26.0% (26/100) of the videos, evidence-based health information amounted to only 20.0% (20/100); 32.0% (32/100) of the videos were classified as useful, 52.0% (52/100) as misleading, and 11.0% (11/100) as even dangerous. The quality of the videos evaluated by DISCERN and GQS was generally low (1.87 and 1.95, respectively, on a 1 to 5 scale with 5 being the maximum). Moreover, we found that viewers rated poor-quality videos better than higher quality videos. CONCLUSIONS: Our in-depth study demonstrates that nearly two-thirds of the psoriasis-related videos we analyzed disseminate misleading or even dangerous content. Subjective anecdotal and unscientific content is disproportionately overrepresented and poor-quality videos are predominantly rated positively by users, while higher quality video clips receive less positive ratings. Strategies by professional dermatological organizations are urgently needed to improve the quality of information on psoriasis on YouTube and other social media.

Good vibrations: Itch induction by whole body vibration exercise without the need of a pruritogen.

Mechanically induced itch is an important cofactor in many patients with chronic itch. However, studying mechanical itch in a controlled environment is challenging because it is difficult to evoke. We investigated the use of whole body vibration (WBV) exercise, a training method used for musculoskeletal rehabilitation, to experimentally evoke mechanical itch. Mild to severe itch ascending from the soles to the groins was evoked in 16 of 20 healthy participants. We observed a characteristic on/off itch crescendo pattern reflecting the alternating intervals of vibration and no vibration. Wheals or an angioedema was absent, and serum mast cell tryptase was not increased by the exercise. Participants described the evoked sensation primarily as "itching" with some nociceptive components. Itch intensity correlated with the intensity of a concomitant erythema (R = 0.45, P = 0.043) and with the rise in skin temperature (R = 0.54, P = 0.017). Hence, WBV can be used as an easily applicable, noninvasive, investigator- and user-friendly framework for studying mechanical itch. Moreover, WBV allows to "switch itch on and off" rapidly and to simultaneously study interactions between itch, skin blood flow and skin temperature.