Epidermolytic ichthyosis complicated by staphylococcal scalded skin syndrome in the newborn.

Epidermolytic ichthyosis is characterized by erythema and blistering at birth. We present a neonate with epidermolytic ichthyosis who had a subtle change in clinical findings while hospitalized, including increased fussiness, erythema, and a change in her skin odor, which represented superimposed staphylococcal scalded skin syndrome. This case highlights the unique challenge of recognizing cutaneous infections in neonates with blistering skin disorders and emphasizes the importance of having a high suspicion for superinfection in this population.

Examining the prior authorization process, patient outcomes, and the impact of a pharmacy intervention: A single-center review.

BACKGROUND: Dermatology experiences a disproportionately high burden of prior authorizations (PAs). OBJECTIVE: To examine the effect of a centralized pharmacy intervention on the PA process and the impact of PAs on patient outcomes. METHODS: A retrospective review of PAs submitted for medications before and after implementation of pharmacy intervention was conducted. RESULTS: PA was required for 8.1% of all prescriptions. PAs were most frequently submitted for topical steroids, topical antibiotics and antifungals, and topical retinoids. Most common indications included acne, psoriasis, and dermatitis. Biologic agents (55.2%) and brand-name only medications (42.8%) required PA at higher rates. Pharmacy intervention resulted in shorter time to PA submission (4 days vs 1 day, P < .001) and decision (6 days vs 1 day, P < .001) and higher approval rates (63.9% vs 80.6%, P < .001) but did not decrease the total number of PAs. Patients with approved PAs had higher likelihood of disease improvement vs those with denied PAs (71.1% vs 58.0%, P = .013). LIMITATIONS: Data were collected from a single academic institution. Patient medication compliance was not assessed. CONCLUSIONS: The current PA process may result in delays in care and a negative impact on patients. A centralized pharmacy intervention is an effective measure but does not eliminate the overall burden of PAs.

Paraneoplastic pemphigus without antibodies to desmoglein 1 and 3.

Paraneoplastic pemphigus is a severe autoimmune blistering disease presenting in the setting of underlying malignancy. Paraneoplastic pemphigus is associated with diffuse painful stomatitis throughout the oral cavity with extension to the lips. The cutaneous findings are varied and have been described as lichenoid, pemphigoid, and targetoid lesions. Herein, we report a patient with paraneoplastic pemphigus whose routine testing led to a diagnosis of pemphigus vulgaris. However, further testing was pursued revealing an antibody profile consistent with paraneoplastic pemphigus. Subsequent neoplastic workup revealed an intra-abdominal mass. Our case represents a subtle, non-classic presentation of paraneoplastic pemphigus and suggests the importance of a comprehensive investigative work-up in atypical cases of pemphigus.

Ganglioside GM3 synthase depletion reverses neuropathic pain and small fiber neuropathy in diet-induced diabetic mice.

BACKGROUND: Small fiber neuropathy is a well-recognized complication of type 2 diabetes and has been shown to be responsible for both neuropathic pain and impaired wound healing. In previous studies, we have demonstrated that ganglioside GM3 depletion by knockdown of GM3 synthase fully reverses impaired wound healing in diabetic mice. However, the role of GM3 in neuropathic pain and small fiber neuropathy in diabetes is unknown. PURPOSE: Determine whether GM3 depletion is able to reverse neuropathic pain and small fibers neuropathy and the mechanism of the reversal. RESULTS: We demonstrate that GM3 synthase knockout and the resultant GM3 depletion rescues the denervation in mouse footpad skin and fully reverses the neuropathic pain in diet-induced obese diabetic mice. In cultured dorsal root ganglia from diet-induced diabetic mice, GM3 depletion protects against increased intracellular calcium influx in vitro. CONCLUSIONS: These studies establish ganglioside GM3 as a new candidate responsible for neuropathic pain and small fiber neuropathy in diabetes. Moreover, these observations indicate that systemic or topically applied interventions aimed at depleting GM3 may improve both the painful neuropathy and the wound healing impairment in diabetes by protecting against nerve end terminal degeneration, providing a disease-modifying approach to this common, currently intractable medical issue.

An assessment of current practices in the treatment of hidradenitis suppurativa: the rise of biologic therapy.

INTRODUCTION: Treatments for hidradenitis suppurativa (HS) have changed in the last decade. In this context, we studied how management practices have shifted. METHODS: We analyzed the National Ambulatory Medical Care Survey (NAMCS) from 2010 to 2016 to assess current treatment practices for HS. RESULTS: There were 1.78 (95% confidence interval 1.35, 2.22) million visits. Antibiotics were observed at 55.7% of visits and observations remained stable over time (p = .9, odds ratio 0.99 [0.73, 1.3]). Pain medications were observed at 15.5% of visits and observations remained stable over time (p = .4, odds ratio [0.87 [0.61, 1.2]). Biologic agents were observed at 0.9% of visits and observations remained stable over time (p = .4, odds ratio 0.61 [0.21, 1.7]). Systemic immunomodulators were observed at 2.6% of visits and observations remained stable over time (p = .08, odds ratio 0.42 [0.12, 1.1]). 100% of biologic agents and 88% of systemic immunomodulators were prescribed by dermatologists. DISCUSSION: The use of biologic agents did not increase in this interval, but it is higher than in an earlier assessment of the NAMCS. Nearly all systemic immunomodulators are prescribed by dermatologists. The ambulatory uptake of these agents did not alter the use of other treatment modalities within this timeframe.

Treatment of psoriasis in pregnancy.

Many women report improvement in psoriasis during pregnancy; others report that psoriasis becomes worse during pregnancy. Balancing effective management of psoriasis against potential risk in pregnancy is important, especially because the severity of psoriasis can have an impact on the pregnancy experience and possibly the outcome. This article discusses current understanding of pregnancy risk profiles of medications used to treat psoriasis.

Methotrexate shows benefit in a subset of patients with severe hidradenitis suppurativa.

BACKGROUND: Methotrexate is an immunomodulatory therapy that may offer benefit to patients with hidradenitis suppurativa (HS). Despite its theoretical advantages, there is a paucity of available data regarding long-term methotrexate use in patients with HS. OBJECTIVE: This study aimed to assess whether methotrexate treatment leads to improvement in HS disease severity. METHODS: We conducted an institutional review board-approved, single-center, retrospective chart review of patients with HS who were treated with methotrexate between 2000 and 2018. Primary outcome measurements included the HS Physician's Global Assessment (HS PGA), Hurley staging, abscess count, fistula count, and inflammatory nodule count. RESULTS: A total of 29 patients were identified; 14 were excluded for reasons including never starting methotrexate and missing follow-up data. For remaining patients (n = 15), the average cumulative dose of methotrexate was 520.1 mg (range, 30-1665 mg) and the average length of treatment was 11.7 months (range, 1-38 months). Patients taking methotrexate as a primary therapy had a higher cumulative dose and length of treatment (520.13 mg; 14.6 months) compared with those taking biologics concomitantly (468.44 mg; 9.1 months). Patients using methotrexate as primary therapy demonstrated nonsignificant reductions in HS PGA, inflammatory nodule count, and abscess count. Patients on concomitant biologic therapy failed to demonstrate any change in HS PGA, inflammatory nodule count, and abscess count. LIMITATIONS: Limitations of the study include its retrospective nature, small sample size, length of time on methotrexate between groups, and homogeneity of the patient population. CONCLUSION: Methotrexate may represent an effective treatment option in older patients with lower body mass indices but fails to offer benefit in patients taking concurrent biologic therapy.

Biologic Treatment for Hidradenitis Suppurativa.

Patients with hidradenitis suppurativa (HS) are often undertreated and there are limited efficacious therapies available for treating this population. Biologics are an emerging therapeutic modality used in the management of many inflammatory conditions including HS. Implementation of biologics is typically reserved for moderate-to-severe cases or in those cases that are refractory to treatment. Though many biologics have been trialed for use in HS, only one biologic, adalimumab, is currently US FDA (Food and Drug Administration) approved for the treatment of moderate-to-severe HS. Limitations in the use of biologics for HS include the many scoring systems utilized in research studies and the relatively few well-designed, adequately powered clinical trials.

Hidradenitis suppurativa for the dermatologic hospitalist.

Patients with hidradenitis suppurativa (HS) often experience disease flares, which can culminate in a visit to the emergency department (ED) and inpatient admission. Appropriate management of HS patients in the acute setting is integral to controlling disease activity, limiting further sequelae, and preventing readmission. The pathophysiology of HS is poorly understood but likely involves a host of hormonal, microbial, and immunological factors. Laboratory abnormalities, including leukocytosis, thrombophilia, an elevated erythrocyte sedimentation rate, as well as an elevated C-reactive protein level, are common in HS patients and generally represent a chronic inflammatory state rather than overt infection. The Hurley staging system is an appropriate way to triage patient severity and guide treatment, as reviewed in this article. In all cases, expedited outpatient follow-up with dermatology and primary care is imperative to limiting disease morbidity.

TNF-α inhibitors in the treatment of hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a complex disease with a dramatic impact on the quality of life of patients that it afflicts. Despite this, there are few treatment options offering long-term relief. The exact pathophysiology of HS is unclear, although the current theory involves follicular obstruction, rupture, and subsequent inflammation leading to fistula and abscess development in intertriginous skin. Several inflammatory modulators have been implicated in the development of HS, including tumor necrosis factor (TNF)-α as well as interleukin (IL)-1ß, IL-10, and IL-17. Initial evidence for the use of TNF-α inhibitors in HS stemmed from recognition that inflammatory bowel disease patients treated with these medications saw a concurrent improvement in their HS symptoms. Early case reports and case series illustrated TNF-α inhibitors' value in the treatment of HS. Later, two phase III clinical trials, PIONEER I and PIONEER II, demonstrated that adalimumab is an efficacious treatment for HS. Infliximab represents another effective HS treatment option with its main advantage being dosing flexibility. In contrast, clinical trials have failed to show evidence for application of etanercept in HS. There is limited data on other TNF-α inhibitors such as certolizumab-pegol and golimumab. This review outlines the history, dosing, response, and adverse effects of TNF-α inhibitors in the treatment of HS.

Genetic basis for skin youthfulness.

Aging skin is a consequence of both intrinsic factors, including genetics, and extrinsic factors, including environmental exposures such as ultraviolet (UV) radiation and smoking. This contribution focuses on intrinsic factors that promote aging skin. Specifically, in this contribution we review the literature describing how single nucleotide polymorphisms, epigenetic changes, variable gene expression, microRNA, and mitochondrial depletion relate to skin aging. Investigations studying intrinsic factors associated with skin aging are important as they promote a better understanding of the underlying pathophysiology of aging skin. This contribution also describes potential avenues for future genetic research in skin aging. Molecular mechanisms that may be therapeutically intervened upon are of particular interest given the cultural value placed on youthful appearing skin. Future research efforts will hopefully reveal a means upon which to intercede on the skin aging process.

A review on SLE and malignancy.

Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease characterized by autoantibody production, complement activation, and immune complex deposition. It predominantly affects young and middle-aged women. While improvements in the diagnosis and treatment of SLE have altered prognosis, morbidity and mortality rates remain higher than the general population. In addition to renal injury, cardiovascular disease, and infection, malignancy is known to be a significant cause of death in this population. There is increasing evidence to suggest that patients with SLE have a slightly higher overall risk of malignancy. The risk of malignancy in SLE is of considerable interest because the immune and genetic pathways underlying the pathogenesis of SLE and the immunosuppressant drugs (ISDs) used in its management may mediate this altered risk. Our current understanding of these and other risk factors and the implications for treating SLE and screening for malignancy is still evolving. This review summarizes the association between SLE and malignancy. The first section discusses the risk of overall and site-specific malignancies in both adult- and pediatric-onset SLE. Next, we evaluate the risk factors and possible mechanisms underlying the link between malignancy and SLE, including the use of ISDs, presence of certain SLE-related autoantibodies, chronic immune dysregulation, environmental factors, and shared genetic susceptibility. Finally, we review guidelines regarding cancer screening and vaccination for human papilloma virus.

Preferential secretion of inducible HSP70 by vitiligo melanocytes under stress.

Inducible HSP70 (HSP70i) chaperones peptides from stressed cells, protecting them from apoptosis. Upon extracellular release, HSP70i serves an adjuvant function, enhancing immune responses to bound peptides. We questioned whether HSP70i differentially protects control and vitiligo melanocytes from stress and subsequent immune responses. We compared expression of HSP70i in skin samples, evaluated the viability of primary vitiligo and control melanocytes exposed to bleaching phenols, and measured secreted HSP70i. We determined whether HSP70i traffics to melanosomes to contact immunogenic proteins by cell fractionation, western blotting, electron microscopy, and confocal microscopy. Viability of vitiligo and control melanocytes was equally affected under stress. However, vitiligo melanocytes secreted increased amounts of HSP70i in response to MBEH, corroborating with aberrant HSP70i expression in patient skin. Intracellular HSP70i colocalized with melanosomes, and more so in response to MBEH in vitiligo melanocytes. Thus, whereas either agent is cytotoxic to melanocytes, MBEH preferentially induces immune responses to melanocytes.