Kristina Lee

The role of IL-17 in vitiligo: A review

IL-17 is involved in the pathogenesis of several autoimmune diseases; however its role in vitiligo has not been well defined. Emerging human and mouse studies have demonstrated that systemic, tissue, and cellular levels of IL-17 are elevated in vitiligo. Many studies have also shown significant positive correlations between these levels and disease activity, extent, and severity. Treatments that improve vitiligo, such as ultraviolet B phototherapy, also modulate IL-17 levels. This review synthesizes our current understanding of how IL-17 may influence the pathogenesis of autoimmune vitiligo at the molecular level. This has implications for defining new vitiligo biomarkers and treatments.

The Patient’s Guide to Psoriasis Treatment. Part 1: UVB Phototherapy

BackgroundPsoriasis is a chronic immune-mediated disease that affects 2–3% of the world population. Ultraviolet B (UVB) phototherapy is an effective treatment for psoriasis compared to other systemic treatments. Currently there is a lack of easily accessible online patient educational material regarding this form of treatment.ObjectiveTo present a freely available online guide and video on UVB treatment that is informative to patients and increases the success and compliance of patients starting this therapy.MethodsThe UVB treatment protocol used at the University of California—San Francisco Psoriasis and Skin Treatment Center as well as available information from the literature was reviewed to design a comprehensive guide for patients receiving UVB treatment.ResultsWe created a printable guide and video resource that reviews the fundamentals of UV light, UVB safety considerations, flow of treatment, side effects, and post-phototherapy skin care.ConclusionThis guide serves as a valuable resource for patients preparing for UVB phototherapy, the clinicians who treat them, and trainees wishing to learn more about this form of therapy.

The Role of the Nervous System in the Pathophysiology of Psoriasis: A Review of Cases of Psoriasis Remission or Improvement Following Denervation Injury

As most efforts in the last decade have focused on the immunologic basis of inflammatory skin disease, there has been less emphasis on the role of the nervous system in the disease process of psoriasis. Evidence in support of the neurocutaneous pathway has come from observations of patients experiencing unilateral improvement and even complete remission following nerve damage in the affected dermatomal region. The aim of this review was to investigate the role of neuropeptides in the intricate pathophysiology of psoriasis. The PubMed database was searched for individual case reports or case series that reported clearance or significant improvement in psoriatic disease in patients following documented nerve injury. A total of 11 cases were found that reported improvement of psoriatic lesions in areas afflicted by central or peripheral nerve injury. The most common causes of denervation were inadvertent surgical interruption, cerebrovascular accident, and poliomyelitis. In four cases the patients eventually regained neurologic function, which was associated with a recurrence of skin lesions. In cases of permanent nerve damage, there was remission of psoriasis. The cases reported in the literature to date provide clinical evidence that absence of neural input leads to psoriasis improvement, suggesting a crucial role of the nervous system in the pathophysiology of psoriatic disease. In fact, neuropeptides such as nerve growth factor, substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide may be important contributors of psoriatic disease and potential targets for future therapies.

Outcomes of Melanoma In Situ Treated With Mohs Micrographic Surgery Compared With Wide Local Excision

Importance Melanoma in situ (MIS) is increasing in incidence, and expert consensus opinion recommends surgical excision for therapeutic management. Currently, wide local excision (WLE) is the standard of care. However, Mohs micrographic surgery (MMS) is now used to treat a growing subset of individuals with MIS. During MMS, unlike WLE, the entire cutaneous surgical margin is evaluated intraoperatively for tumor cells. Objective To assess the outcomes of patients with MIS treated with MMS compared with those treated with WLE. Design, Setting, and Participants Retrospective review of a prospective database. The study cohort consisted of 662 patients with MIS treated with MMS or WLE per standard of care in dermatology and surgery (general surgery, otolaryngology, plastics, oculoplastics, surgical oncology) at an academic tertiary care referral center from January 1, 1978, to December 31, 2013, with follow-up through 2015. Exposure Mohs micrographic surgery or WLE. Main Outcomes and Measures Recurrence, overall survival, and melanoma-specific survival. Results There were 277 patients treated with MMS (mean [SD] age, 64.0 [13.1] years; 62.1% male) and 385 treated with WLE (mean [SD] age, 58.5 [15.6] years; P < .001 for age; 54.8% male). Median follow-up was 8.6 (range, 0.2-37) years. Compared with WLE, MMS was used more frequently on the face (222 [80.2%] vs 141 [36.7%]) and scalp and neck (23 [8.3%] vs 26 [6.8%]; P < .001). The median (range) year of diagnosis was 2008 (1986-2013) for the MMS group vs 2003 (1978-2013) for the WLE group (P < .001). Overall recurrence rates were 5 (1.8%) in the MMS group and 22 (5.7%) in the WLE group (P = .07). Mean (SD) time to recurrence after MMS was 3.91 (4.4) years, and after WLE, 4.45 (2.7) years (P = .73). The 5-year recurrence rate was 1.1% in the MMS group and 4.1% in the WLE group (P = .07). For WLE-treated tumors, the surgical margin taken was greater for tumors that recurred compared with tumors that did not recur (P = .003). Five-year overall survival for MMS was 92% and for WLE was 94% (P = .28). Melanoma-specific mortality for the MMS group was 2 vs 13 patients for the WLE group, with mean (SD) survival of 6.5 (4.8) and 6.1 (0.8) years, respectively (P = .77). Conclusions and Relevance No significant differences were found in the recurrence rate, overall survival, or melanoma-specific survival of patients with MIS treated with MMS compared with WLE.

Eczema as an adverse effect of anti-TNFα therapy in psoriasis and other Th1-mediated diseases: a review

Abstract Introduction: There have been rare reports of eczema occurring as an adverse effect of anti-tumor necrosis factor-alpha (TNFα) therapy. Methods: A literature search was conducted on PubMed for articles describing new onset or worsening of preexisting eczema during anti-TNFα therapy for the treatment of various inflammatory diseases. Results: Eczema as an adverse effect of anti-TNFα therapy may occur in approximately 5–20% of patients with various Th1-mediated inflammatory diseases such as psoriasis, inflammatory arthritis and inflammatory bowel disease. Personal history of atopy appears to increase this risk. Out of the anti-TNFα agents indicated for the treatment of moderate-to-severe psoriasis, infliximab may be more strongly associated with development or exacerbation of preexisting eczema. Discussion: Inhibitors of key mediators in the Th1 pathway such as TNFα are successful therapeutic targets for the treatment of various inflammatory conditions such as psoriasis, psoriatic arthritis, rheumatoid arthritis and inflammatory bowel disease. Blocking the Th1 pathway may create an imbalance favoring increased activity of the opposing Th2 pathway implicated in inflammatory conditions such as eczema. Further research is needed to better understand the role of the Th1/Th2 balance in various inflammatory diseases and how the immunologic environment is affected by immunotherapies.

Transcriptional landscape of epithelial and immune cell populations revealed through FACS-seq of healthy human skin

Human skin consists of multiple cell types, including epithelial, immune, and stromal cells. Transcriptomic analyses have previously been performed from bulk skin samples or from epithelial and immune cells expanded in cell culture. However, transcriptomic analysis of bulk skin tends to drown out expression signals from relatively rare cells while cell culture methods may significantly alter cellular phenotypes and gene expression profiles. To identify distinct transcriptomic profiles of multiple cell populations without substantially altering cell phenotypes, we employed a fluorescence activated cell sorting method to isolate keratinocytes, dendritic cells, CD4+ T effector cells, and CD8+ T effector cells from healthy skin samples, followed by RNA-seq of each cell population. Principal components analysis revealed distinct clustering of cell types across samples, while differential expression and coexpression network analyses revealed transcriptional profiles of individual cell populations distinct from bulk skin, most strikingly in the least abundant CD8+ T effector population. Our work provides a high resolution view of cutaneous cellular gene expression and suggests that transcriptomic profiling of bulk skin may inadequately capture the contribution of less abundant cell types.

The metabolomics of psoriatic disease

Metabolomics is an emerging new “omics” field involving the systematic analysis of the metabolites in a biologic system. These metabolites provide a molecular snapshot of cellular activity and are thus important for understanding the functional changes in metabolic pathways that drive disease. Recently, metabolomics has been used to study the local and systemic metabolic changes in psoriasis and its cardiometabolic comorbidities. Such studies have revealed novel insights into disease pathogenesis and suggest new biochemical signatures that may be used as a marker of psoriatic disease. This review will discuss common strategies in metabolomics analysis, current findings in the metabolomics of psoriasis, and emerging trends in psoriatic metabolomics.

Ethnicity affects the presenting severity of psoriasis

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The Patient’s Guide to Psoriasis Treatment. Part 4: Goeckerman Therapy

BackgroundThe Goeckerman regimen remains one of the oldest, most reliable treatment options for patients with moderate to severe psoriasis. Goeckerman therapy currently consists of exposure to ultraviolet B light and application of crude coal tar. The details of the procedure can be confusing and challenging to understand for the first-time patient or provider.ObjectiveTo present a freely available online guide and video on Goeckerman treatment that explains the regimen in a patient-oriented manner.MethodsThe Goeckerman protocol used at the University of California—San Francisco Psoriasis and Skin Treatment Center as well as available information from the literature were reviewed to design a comprehensive guide for patients receiving Goeckerman treatment.ResultsWe created a printable guide and video resource that covers the supplies needed for Goeckerman regimen, the treatment procedure, expected results, how to monitor for adverse events, and discharge planning.ConclusionThis new resource is beneficial for prospective patients planning to undergo Goeckerman treatment, healthcare providers, and trainees who want to learn more about this procedure. Online media and video delivers material in a way that is flexible and often familiar to patients.

Combining biologic and phototherapy treatments for psoriasis: safety, efficacy, and patient acceptability

Background The efficacy and safety of biologic and phototherapy in treating moderate-to-severe psoriasis is well known. However, some patients may not respond well to biologic agents or phototherapy on their own and may require combination therapy. Skillfully combining a biologic agent and phototherapy may provide an additive improvement without much increase in risks. Objective To summarize the current state of evidence for the efficacy and safety of combining biologics with phototherapy in the treatment of moderate-to-severe plaque psoriasis. Methods We conducted an extensive search on Pubmed database for English language literature that evaluated the use of a combination of biologic and phototherapy for the treatment of moderate-to-severe psoriasis through January 2016. The search included the following key-words: psoriasis, etanercept, adalimumab, infliximab, ustekinumab, biologics, phototherapy, and combination therapy. Results The primary literature included randomized controlled trials, a head-to-head study, open-label controlled and uncontrolled trials, case series, and case reports. Etanercept was used in over half of the reported cases, but other biologic agents used included ustekinumab, adalimumab, and infliximab. The vast majority of phototherapy was narrowband ultraviolet B (NBUVB) radiation. Most cases reported enhanced improvement with combination therapy. Serious adverse events throughout the study duration were reported in <3% of the patients. Long-term adverse events cannot be excluded. Conclusion Combination of biologic and phototherapy appears to be a viable clinical strategy in the treatment of moderate-to-severe psoriasis not responsive to monotherapy, despite limitations in the data available. NBUVB in combination with biologics appears to be especially effective. However, the long-term impact of these combinations is yet to be determined.