Bi-allelic Alterations in AEBP1 Lead to Defective Collagen Assembly and Connective Tissue Structure Resulting in a Variant of Ehlers-Danlos Syndrome.

AEBP1 encodes the aortic carboxypeptidase-like protein (ACLP) that associates with collagens in the extracellular matrix (ECM) and has several roles in development, tissue repair, and fibrosis. ACLP is expressed in bone, the vasculature, and dermal tissues and is involved in fibroblast proliferation and mesenchymal stem cell differentiation into collagen-producing cells. Aebp1-/- mice have abnormal, delayed wound repair correlating with defects in fibroblast proliferation. In this study, we describe four individuals from three unrelated families that presented with a unique constellation of clinical findings including joint laxity, redundant and hyperextensible skin, poor wound healing with abnormal scarring, osteoporosis, and other features reminiscent of Ehlers-Danlos syndrome (EDS). Analysis of skin biopsies revealed decreased dermal collagen with abnormal collagen fibrils that were ragged in appearance. Exome sequencing revealed compound heterozygous variants in AEBP1 (c.1470delC [p.Asn490_Met495delins(40)] and c.1743C>A [p.Cys581∗]) in the first individual, a homozygous variant (c.1320_1326del [p.Arg440Serfs∗3]) in the second individual, and a homozygous splice site variant (c.1630+1G>A) in two siblings from the third family. We show that ACLP enhances collagen polymerization and binds to several fibrillar collagens via its discoidin domain. These studies support the conclusion that bi-allelic pathogenic variants in AEBP1 are the cause of this autosomal-recessive EDS subtype.

Simulation: An Effective Method of Teaching Cosmetic Botulinum Toxin Injection Technique.

BACKGROUND: Learning to inject botulinum toxin for cosmetic purposes is difficult for beginners, given the nature of the procedure and patient population. Simulation training is an effective modality for medical professionals to acquire skills in an environment that provides low stress and ample opportunity for questions and correction of mistakes. OBJECTIVES: Compare posttraining comfort, knowledge, and practical botulinum toxin injection scores among trainees who underwent simulation vs video training only. METHODS: A total of 20 nurse practitioners, physician assistants, and resident physicians underwent cosmetic botulinum toxin injection training either through lecture and video, or lecture and hands-on simulation training. Comfort, knowledge, and practical test scores were recorded and compared between the groups. RESULTS: There was no evidence of a statistically significant difference in comfort or knowledge scores between simulation and video groups. The median (range) practical score was significantly higher in the simulation group compared to the video group (59.0 [31-60] vs 44.5 [27-57]; P < 0.01). CONCLUSIONS: Despite feeling similarly comfortable and having similar written knowledge test scores, the trainees who underwent simulation training had significantly higher hands-on practical test scores compared to trainees who underwent video training only for cosmetic botulinum toxin injections.

Reducing unnecessary testing: an intervention to improve resident ordering practices.

PURPOSE OF THE STUDY: To reduce the number of unnecessary laboratory tests ordered through a measurement of effects of education and cost awareness on laboratory ordering behaviour by internal medicine residents for common tests, including complete blood cell count (CBC) and renal profile (RP), and to evaluate effects of cost awareness on hospitalisation, 30-day readmission rate and mortality rate. STUDY DESIGN: 567 patients admitted during February, March and April 2014 were reviewed as the control group. Total CBC, CBC with differential and RP tests were counted, along with readmission and mortality rates. Interventions were education and visual cost reminders. The same tests were reassessed for 629 patients treated during 12 months after intervention in 2015. RESULTS: Data showed a significant increase in CBCs ordered after the intervention (mean number per hospitalisation changed from 1.7 to 2.3 (p<0.001)), a decrease in CBCs with differential (mean number changed from 1.7 to 1.2 (p<0.001)) and no change in RPs ordered (mean number, 3.7 both before and after intervention (p=0.23)). No change was found in mortality rate, but the decrease in the readmission rate was significant (p=0.008). CONCLUSIONS: Education in the form of cost reminders did not significantly reduce the overall ordering of the most common daily laboratory testing in our academic teaching service. We believe further research is needed to fully evaluate the effectiveness of other education forms on the redundant ordering of tests in the hospital setting.

Vitamin D receptor and CD86 expression in the skin of vitamin D-deficient swine.

The immunomodulatory role of vitamin D in many diseases is well established. However, the relationship between vitamin D status and skin cancers is unclear. In this study, we examined the effect of vitamin D deficiency and sufficiency on VDR, NF-κB, and CD86 in the epidermis of Yucatan microswine tragi. All of these proteins have known roles in the pathogenesis of cutaneous malignancies such as melanoma and non-melanoma skin cancer. There was weaker and less discrete nuclear staining for VDR and weaker CD86 immunoreactivity with patchy membranous expression in the epidermis of vitamin D-deficient compared to vitamin D-sufficient swine. There was no difference in the immunostaining for NF-κB. Since VDR and CD86 expression are decreased in the setting of melanoma and non-melanoma skin cancers, our findings suggest a potential role of vitamin D-deficiency in the progression of skin malignancies.

Dermatologic side effects of psychotropic medications.

BACKGROUND: Although relatively uncommon, cutaneous reactions to psychotropic medications may thwart treatment of psychiatric illness and confuse diagnostic efforts especially when they occur in the context of comorbid medical conditions. Psychiatrists may be asked to comment on whether a particular cutaneous condition is due to a psychotropic medication or to recommend a replacement psychotropic agent. OBJECTIVE: To review the available literature describing cutaneous adverse effects prompted by psychotropic medications. METHOD: A search of the literature using PubMed was undertaken using the terms "psychotropic," "psychiatric," "antidepressant," "anxiolytic," "mood stabilizer," "antipsychotic," and "neuroleptic" in combination with either of the terms "dermatologic," "cutaneous" or "skin." RESULTS: Psychotropic medications from all classes have been associated with a broad variety of dermatologic reactions with variable rates of incidence. Psychiatrists should be aware of the potential cutaneous adverse effects of the medications they prescribe. Psychiatrists practicing in the general hospital, where cutaneous symptoms may present for any number of reasons, should be aware of the typical presentations and relative likelihood of these reactions to forestall unnecessary "blaming" of psychotropics for cutaneous reactions.

Clinical features of shiitake dermatitis: a systematic review.

Shiitake dermatitis is a rare cutaneous reaction to lentinan, a polysaccharide component in the cell walls of shiitake mushrooms (Lentinula edodes). Herein, we systematically review the case report and case series English-language literature on shiitake dermatitis, which refers to a total of 50 patients (38 males, 12 females; mean age: 44.58 years). The majority of cases occurred after the consumption of raw mushrooms, whereas 22% of cases were caused by the eating of lightly or undercooked mushrooms. The most common clinical presentations, localized symptoms, and systemic findings include linear flagellated dermatitis (98%), pruritus (78%), and fever, diarrhea, and mucosal ulcers, respectively. The diagnosis of this entity continues to be based on clinical findings as laboratory abnormalities, and the findings of skin biopsies and patch/prick tests are nonspecific and inconsistent. The condition is self-limiting, resolving in approximately 12.5 d without treatment. Based on the included case reports, it appears that medical treatment may slightly shorten the course of disease (to 9-11 d, varying by therapy) but should be considered on an individual patient basis. However, the treatment of symptoms, reassurance, and the avoidance of re-exposure are sufficient treatment recommendations for this condition.

Triggering Receptor Expressed on Myeloid Cells in Cutaneous Melanoma.

The tumor microenvironment plays an important role in the progression of melanoma, the prototypical immunologic cutaneous malignancy. The triggering receptor expressed on myeloid cells (TREM) family of innate immune receptors modulates inflammatory and innate immune signaling. It has been investigated in various neoplastic diseases, but not in melanoma. This study examines the expression of TREM-1 (a proinflammatory amplifier) and TREM-2 (an anti-inflammatory modulator and phagocytic promoter) in human cutaneous melanoma and surrounding tissue. Indirect immunofluorescence staining was performed on skin biopsies from 10 melanoma patients and staining intensity was semiquantitatively scored. Expression of TREM-1 and TREM-2 was higher in keratinocytes than melanoma tissue (TREM-1: p < 0.01; TREM-2: p < 0.01). Whereas TREM-2 was the dominant isoform expressed in normal keratinocytes, TREM-1 expression predominated in melanoma tissue (TREM-1 to TREM-2 ratio: keratinocytes = 0.78; melanoma = 2.08; p < 0.01). The increased TREM ratio in melanoma tissue could give rise to a proinflammatory and protumor state of the microenvironment. This evidence may be suggestive of a TREM-1/TREM-2 paradigm in which relative levels dictate inflammatory and immune states, rather than absolute expression of one or the other. Further investigation regarding this paradigm is warranted and could carry prognostic or therapeutic value in treatment for melanoma.

Immunomodulation of malignant melanoma by contact sensitizing agents.

The importance of host defense against malignant melanoma is underlined by the use of immunomodulating agents as effective therapies. Diphencyprone and 2,4-dinitrochlorobenzene (DNCB) have been used successfully as contact sensitizing agents in this regard. Through haptenation of cell surface and cytoplasmic proteins, these agents trigger a CD8(+) T-lymphocyte predominant allergic contact hypersensitivity response. Th17 cells may also play a critical role. The effectiveness of these agents at stimulating tumor defense may be limited to melanoma of the skin. Response to immunotherapy using diphencyprone and DNCB is governed by the immune status of the host, which is affected by tumor burden, UV light and age. Additionally, diphencyprone and DNCB elicit synergy with other methods of treatment and thus may be used as adjuncts. Two current prospective trials may aid in elucidating the impact that this treatment modality has on the prognosis and quality of life of patients with melanoma.