A severe presentation of acute generalized exanthematous pustulosis with non-infectious circulatory shock in an adolescent.

We present a severe case of acute generalized exanthematous pustulosis (AGEP) secondary to trimethoprim-sulfamethoxazole complicated by non-infectious circulatory shock in a 16-year-old boy. Hemodynamic instability has been reported as a complication of AGEP in adults, but is rarely observed in pediatric patients. The patient we present demonstrated characteristic cutaneous findings of AGEP including isolated non-follicular, sterile pustules on a background of erythema with involvement at intertriginous areas and subsequently developed non-infectious circulatory shock. This case expands the spectrum of possible clinical presentations for AGEP in pediatric patients.

Pyoderma gangrenosum (PG) associated with levamisole-adulterated cocaine: Clinical, serologic, and histopathologic findings in a cohort of patients.

BACKGROUND: Recently, isolated reports of pyoderma gangrenosum (PG) secondary to levamisole-contaminated cocaine have been described, with similar serologic findings to the vasculopathic presentation. OBJECTIVE: We sought to describe clinical, histopathological, and serologic findings in 8 patients with PG associated with levamisole-contaminated cocaine. METHODS: Eight consecutive patients presenting with this disease spanning the period from 2011 to 2015 were included for the cohort. Observed variables included: lesion distribution, morphology, serologic titers, and histopathologic evaluation for vasculitis and vasculopathy. RESULTS: All patients reported cocaine exposure prior to the onset of lesions resembling PG. Lesions appeared primarily on the upper (6 of 8 patients) and lower (all 8 patients) extremities. Most patients demonstrated elevated titers for p-ANCA and antiphospholipid antibodies, and a diffuse dermal infiltrate dominated by neutrophils was seen in all biopsy specimens. Lesions improved or remained stable with conservative management or short courses of steroids, and recurrence was only noted on re-exposure to adulterated cocaine. LIMITATIONS: The study is limited by sample size. CONCLUSIONS: PG may occur after exposure to levamisole-adulterated cocaine. Clinical and histopathological findings resemble those seen in conventional forms of PG, whereas serologic findings mirror those seen in other levamisole-associated vasculopathic or vasculitic eruptions. Cocaine avoidance represents a cornerstone of management in these patients.

Human rod photoreceptor outer segments are supported by accessory inner segment structures.

The first steps in vision take place in photoreceptor cells, which are highly compartmentalized neurons exhibiting significant structural variation across species. The light-sensitive ciliary compartment, called the outer segment, is located atop of the cell soma, called the inner segment. In this study, we present an ultrastructural analysis of human photoreceptors, which reveals that, in contrast to this classic arrangement, the inner segment of human rods extends alongside the outer segment to form a structure hereby termed the "accessory inner segment". While reminiscent of the actin-based microvilli known as "calyceal processes" observed in other species, the accessory inner segment is a unique structure: (1) it contains an extensive microtubule-based cytoskeleton, (2) it extends far alongside the outer segment, (3) its diameter is comparable to that of the outer segment, (4) it contains numerous mitochondria, and (5) it forms electron-dense structures that likely mediate adhesion to the outer segment. Given that the spacing of extrafoveal human photoreceptors is more sparse than in non-primate species, with vast amounts of interphotoreceptor matrix present between cells, the closely apposed accessory inner segment likely provides structural support to the outer segment. This discovery expands our understanding of the human retina and directs future studies of human photoreceptor function in health and disease.

Single administration of lesion-limited high-dose (TURBO) ultraviolet B using the excimer laser: clinical clearing in association with apoptosis of epidermal and dermal T cell subsets in psoriasis.

BACKGROUND/PURPOSE: Development of effective therapy for psoriasis is confounded by numerous factors contributing to disease pathogenesis, including pathogenic immunocytes which appear to drive epidermal keratinocyte hyperproliferation. Our objective was to study clinical and biomarker effects of a single dose of TURBO laser UVB (308 nm) applied directly to psoriatic plaques. METHODS: Eighteen patients with chronic plaque psoriasis received a single dose of 10 minimal erythema dose (MED) UVB and were followed for 8 weeks. Keratome and punch biopsies were assessed for T cell depletion and apoptosis following a single 308-nm dose of UVB. RESULTS: Patients demonstrated clinical improvement as indicated by decreased global Psoriasis Area and Severity Index scores and reduced numbers of pathogenic memory/effector T cells infiltrating lesional epidermis and dermis. Consistent with apoptosis induction, caspase activation increased in lesional T cells after treatment. CONCLUSION: We conclude that a single 10 MED dose of TURBO UVB is effective at reducing the severity and extent of psoriatic lesions. We hypothesize that the reason a single treatment is sufficient to clear a psoriatic plaque is that the 10 MED dose is able to deliver sufficient photons to a microanatomic area of the lesion where susceptible pathogenic T cell mechanisms are operative.

Patient safety in dermatology: a review of the literature.

OBJECTIVE: We performed a literature review of patient safety topics pertinent to dermatology and related to outpatient settings for situations in which data from dermatology are lacking. METHODS: Searches in MEDLINE via PubMed interface, OVID and Google Scholar were carried out from October, 2008 through May, 2009 for English-language articles published between 1948 and 2009. Each search combined 2 or 3 of the following terms: patient safety, medical error, human error, preventable adverse event, dermatology, outpatient, ambulatory care, medication error, diagnostic error, laboratory error, pathology error, office-based surgery, wrong-site procedure, infections, falls, laser safety, scope of practice. Personal communications, websites, books, dermatology newsletters and major textbooks were also scrutinized. Potentially relevant articles and communications were critically evaluated by the authors. References from these articles were searched for "other relevant articles." SUMMARY: Patient safety studies in dermatology and outpatient settings are lagging behind those in inpatient settings. Systems changes are needed to reduce medical errors rather than penalize individual healthcare workers. Although technology may improve patient safety in numerous aspects, it introduces new sources of errors. CONCLUSION: Our review reveals few studies on dermatologic patient safety, supporting the pressing need for such studies and reports in the future.

Myeloid-Derived Suppressor Cells in Psoriasis Are an Expanded Population Exhibiting Diverse T-Cell-Suppressor Mechanisms.

Psoriasis vulgaris is an inflammatory skin disease caused by hyperactivated T cells regulated by positive and negative mechanisms; although the former have been much studied, the latter have not. We studied the regulatory mechanism mediated by myeloid-derived suppressor cells (MDSCs) and showed that MDSCs expanded in melanoma patients express dendritic cell-associated heparan sulfate proteoglycan-dependent integrin ligand, a critical mediator of T-cell suppressor function. We examined expansion of DC-HIL(+) MDSCs in psoriasis and characterized their functional properties. Frequency of DC-HIL(+) monocytic MDSCs (CD14(+)HLA-DR(no/low)) in blood and skin was markedly increased in psoriatic patients versus healthy control subjects, but there was no statistically significant relationship with disease severity (based on Psoriasis Area and Severity Index score). Blood DC-HIL(+) MDSC levels in untreated patients were significantly higher than in treated patients. Compared with melanoma-derived MDSCs, psoriatic MDSCs exhibited significantly reduced suppressor function and were less dependent on DC-HIL, but they were capable of inhibiting proliferation and IFN-γ and IL-17 responses of autologous T cells. Psoriatic MDSCs were functionally diverse among patients in their ability to suppress allogeneic T cells and in the use of either IL-17/arginase I or IFN-γ/inducible nitric oxide synthase axis as suppressor mechanisms. Thus, DC-HIL(+) MDSCs are expanded in psoriasis patients, and their mechanistic heterogeneity and relative functional deficiency may contribute to the development of psoriasis.

Psoriasis and cardiovascular risk factors: increased serum myeloperoxidase and corresponding immunocellular overexpression by Cd11b(+) CD68(+) macrophages in skin lesions.

BACKGROUND: Recent studies report independent associations between psoriasis, cardiovascular (CV) events and risk factors. Blood Myeloperoxidase (MPO) from activated myeloid cells is associated with CV risk mainly through lipid oxidation, induction of endothelial dysfunction and release of IL-12 from macrophages. OBJECTIVES: To elucidate associations between psoriasis and conventional CV risk factors. METHODS: We performed a cross-sectional study of 100 psoriasis patients and 53 controls, group matched on age, gender and body mass index, to assess levels of MPO in serum, as well as immunohistochemical staining from psoriasis skin lesions, psoriasis uninvolved skin, and normal skin. RESULTS: Although the groups did not differ on waist circumference, glucose, cholesterol, triglycerides, creatinine or personal history of CV events, psoriasis patients had significantly higher waist-to-hip ratios, blood pressures, proportion of current smokers, and lower high density lipoprotein level than controls. Serum MPO level was elevated 2.5 fold (P<0.001) in psoriasis patients, even after adjusting for the CV risk factors on which the groups differed. MPO did correlate with coronary artery calcification, carotid plaque, carotid intima media thickness and flow mediated dilation, but did not correlate with psoriasis severity. However, MPO was highly expressed in lesional psoriatic skin and colocalized predominantly with CD45(+) CD11b(+) leukocytes. CD11b(+) cell density correlated with circulation MPO levels. CONCLUSION: Lesional skin CD11b(+) leukocytes activated to generate MPO may contribute to serum levels of MPO. Lesional CD11b(+) cell activity may be an alternative measure of disease burden to PASI that underlies the MPO biomarker for systemic inflammation related to Cardiovascular Disease.

Physical and mental impact of psoriasis severity as measured by the compact Short Form-12 Health Survey (SF-12) quality of life tool.

The Short Form-12 Health Survey (SF-12) is used to assess the patient's quality of life (QoL) using the physical component score (PCS) and the mental component score (MCS). The purpose of this study was to determine whether the SF-12 PCS and MCS are associated with psoriasis severity and to compare QoL between Murdough Family Center for Psoriasis (MFCP) patients and patients with other major chronic diseases included in the National Survey of Functional Health Status data. We used data from 429 adult patients enrolled in MFCP. Psoriasis Area Severity Index (PASI) was used to assess psoriasis severity at the time of completion of the SF-12 questionnaire. Other variables included age, sex, body mass index, psoriatic arthritis, psychiatric disorders, and comorbidities. Linear regression models were used to estimate effect sizes ± 95% confidence intervals. For every 10-point increase in PASI, there was a 1.1 ± 1.3 unit decrease in MCS (P=0.100) and a 2.4 ± 1.3 unit decrease in PCS (P<0.001). Psoriasis severity was associated with PCS and MCS after adjusting for variables, although the strength of the relationship was attenuated in some models. Psoriasis severity is associated with decreased QoL. SF-12 may be a useful tool for assessing QoL among psoriasis patients.

Psoriasis treatment patterns of dermatologists in northeast Ohio.

AIM: To describe the psoriasis treatment patterns of community-based dermatologists in northeast Ohio. MATERIALS AND METHODS: A prospective cross-sectional survey was performed among dermatologists in northeast Ohio. The survey was initiated by the Murdough Family Center for Psoriasis and members of LIFEDERMNET (Leaders Initiative For Excellence In Dermatology Network). A questionnaire was sent to all community-based dermatologists in northeast Ohio. RESULTS: Forty-seven of 145 questionnaires were returned and analyzed. The annual mean number of psoriasis patients seen in the community-based dermatology practices was 250, representing approximately 4% of the total patients seen. Among the systemic treatment options for psoriasis, each of the following was used at least once to treat a patient with psoriasis in the previous year by the following percentage of community-based dermatology practices: methotrexate, 72%; acitretin, 68%; biologics, 66%; phototherapy, 55%; cyclosporine, 36%; and the excimer laser, 28%. CONCLUSION: Our findings demonstrate that dermatologists in northeast Ohio use both systemic and biologic agents for the treatment of patients with psoriasis.

Allergic contact dermatitis to synthetic rubber gloves: changing trends in patch test reactions to accelerators.

BACKGROUND: Rubber gloves are one of the most frequent causes of occupational allergic contact dermatitis, especially in health care workers. OBSERVATIONS: We describe 23 patients with allergic contact dermatitis due to rubber accelerators in rubber gloves, some with disseminated dermatitis, treated during a 2-year period. Three had IgE-mediated latex allergies. Sixteen were health care workers from a single institution whose dermatitis was temporally related to the switch to latex-safe gloves. Each had positive patch test reactions to 1 or more rubber accelerators, including carbamates, thiurams, 2-mercaptobenzothiazole, and 1,3-diphenylguanidine. Chemical analysis of 6 glove samples identified 2-mercaptobenzothiazole in 4 and zinc diethyldithiocarbamate in 1. There were discordances between patch test results for glove chemicals and glove swatches and between available information on chemicals used during glove production and chemicals detected during glove analysis. Although these factors may complicate the search for culprit and alternative gloves, dermatitis cleared in each of 9 patients with follow-up data and for whom alternative gloves were provided based on published information of glove composition. CONCLUSIONS: Allergic contact dermatitis due to synthetic rubber gloves occurs even with the use of latex-safe products. More knowledge about chemicals present in these gloves, to which the skin is exposed during use, is necessary to prevent and treat allergic contact dermatitis.

Hand/face/neck localized pattern: sticky problems--resins.

Plastic resin systems have an increasingly diverse array of applications but also induce health hazards, the most common of which are allergic and irritant contact dermatitis. Contact urticaria, pigmentary changes, and photoallergic contact dermatitis may occasionally occur. Other health effects, especially respiratory and neurologic signs and symptoms, have also been reported. These resin systems include epoxies, the most frequent synthetic resin systems to cause contact dermatitis, (meth)acrylics, polyurethanes, phenol-formaldehydes, polyesters, amino resins (melamine-formaldehydes, urea-formaldehydes), polyvinyls, polystyrenes, polyolefins, polyamides and polycarbonates. Contact dermatitis usually occurs as a result of exposure to the monomers and additives in the occupational setting, although reports from consumers, using the raw materials or end products periodically surface. Resin- and additive-induced direct contact dermatitis usually presents on the hands, fingers, and forearms, while facial, eyelid, and neck involvement may occur through indirect contact, eg, via the hands, or from airborne exposure. Patch testing with commercially available materials, and in some cases the patient's own resins, is important for diagnosis. Industrial hygiene prevention techniques are essential to reduce contact dermatitis when handling these resin systems.

Biologics in the management of psoriasis.

Psoriasis is a chronic inflammatory systemic disease for which there exist topical, ultraviolet, systemic, and biologic treatments. Biologic agents selectively interfere with the immune mechanisms responsible for psoriasis. Etanercept, infliximab, and adalimumab target tumor necrosis factor-alpha and have demonstrated efficacy in the treatment of psoriasis and psoriatic arthritis. Alefacept and efalizumab target T lymphocytes, are effective in the treatment of psoriasis, but are not approved for psoriatic arthritis. Finally, ustekinumab and ABT-874 target interleukin-12 and interleukin-23, and they have demonstrated efficacy in the treatment of psoriasis. The objective of this review is to present efficacy and safety data from randomized controlled trials of the biologic agents in the treatment of psoriasis.