Paediatric-onset lymphomatoid papulosis: results of a multicentre retrospective cohort study on behalf of the EORTC Cutaneous Lymphoma Tumours Group (CLTG).

BACKGROUND: Lymphomatoid papulosis (LyP) is a rare cutaneous T-cell lymphoproliferative disorder. Comprehensive data on LyP in the paediatric population are scarce. OBJECTIVES: To characterize the epidemiological, clinical, histopathological and prognostic features of paediatric LyP. METHODS: This was a retrospective multicentre international cohort study that included 87 children and adolescents with LyP diagnosed between 1998 and 2022. Patients aged ≤ 18 years at disease onset were included. LyP diagnosis was made in each centre, based on clinicopathological correlation. RESULTS: Eighty-seven patients from 12 centres were included. Mean age at disease onset was 7.0 years (range 3 months-18 years) with a male to female ratio of 2 : 1. Mean time between the onset of the first cutaneous lesions and diagnosis was 1.3 years (range 0-14). Initial misdiagnosis concerned 26% of patients. LyP was most often misdiagnosed as pityriasis lichenoides et varioliformis acuta, insect bites or mollusca contagiosa. Erythematous papules or papulonodules were the most frequent clinical presentation. Pruritus was specifically mentioned in 21% of patients. The main histological subtype was type A in 55% of cases. When analysed, monoclonal T-cell receptor rearrangement was found in 77% of skin biopsies. The overall survival rate was 100%, with follow-up at 5 years available for 33 patients and at 15 years for 8 patients. Associated haematological malignancy (HM) occurred in 10% of cases (n = 7/73), including four patients with mycosis fungoides, one with primary cutaneous anaplastic large cell lymphoma (ALCL), one with systemic ALCL and one with acute myeloid leukaemia. If we compared incidence rates of cancer with the world population aged 0-19 years from 2001 to 2010, we estimated a significantly higher risk of associated malignancy in general, occurring before the age of 19 years (incidence rate ratio 87.49, 95% confidence interval 86.01-88.99). CONCLUSIONS: We report epidemiological data from a large international cohort of children and adolescents with LyP. Overall, the disease prognosis is good, with excellent survival rates for all patients. Owing to an increased risk of associated HM, long-term follow-up should be recommended for patients with LyP.

Lymphomatoid papulosis is a very rare skin condition caused by an abnormal increase in white blood cells (called 'lymphocytes') in the skin. The condition rarely affects children, so most of the scientific data published about this disease focuses on adults. This study involved 12 academic dermatology centres in Europe, the Middle East and North America, and gathered data from about 87 children who presented with symptoms of lymphomatoid papulosis before the age of 19 years. The aim of this study was to better describe this disease in the paediatric population and discuss its treatment options and evolution. We found that the presentation of the disease in children is roughly the same as in adults. Safe and effective treatment options exist. The disease is not life threatening, but it requires investigation by a dermatologist, both to make a careful diagnosis and to monitor it as sometimes associated cancers that originate from blood cells can occur, mostly on the skin.

Negative impact of comorbidities on all-cause mortality of patients with psoriasis is partially alleviated by biologic treatment: A real-world case-control study.

BACKGROUND: Cardiovascular comorbidities are believed to cause higher mortality in psoriasis patients. Conversely, systemic therapy may improve overall survival. OBJECTIVE: To evaluate the impact of different comorbidities and therapy on mortality risk of psoriasis patients in the entire population of Alberta, Canada (population 4.37 million). METHODS: Cohorts of psoriasis cases (n = 18,618) and controls (ambulatory patients matched 1:3 by age and sex) were retrieved from Alberta Health Services Data Repository of Reporting database within the period 2012 to 2019. Cases were stratified according to Charlson Comorbidity Index, and the type of therapy. RESULTS: Mortality in psoriasis cohort was significantly higher than in the controls (median age of death 72.0 years vs 74.4 years, respectively). Charlson Comorbidity Index and comorbidities were strong predictors of mortality, in particular drug induced liver injury (hazard ratio 1.8, affective bipolar disease, hazard ratio 1.6, and major cardiovascular diseases. Mortality was lower in patients treated with biologics (hazard ratio 0.54). LIMITATIONS: Some factors (psoriasis type and severity, response to treatment, smoking, alcohol intake) could not be measured. CONCLUSIONS: Hepatic injury, psychiatric affective disorders and cardiovascular disease were major determinants of overall survival in psoriasis. Biologic therapy was associated with a reduced mortality risk.

Early Organ Metastasis in Granulomatous Mycosis Fungoides: A Systematic Review.

BACKGROUND: Granulomatous mycosis fungoides (GMF) is a rare form of cutaneous T-cell lymphoma characterized by a granulomatous inflammatory infiltrate. OBJECTIVE: The impact of granulomatous inflammation on the prognosis of the disease remains controversial as there have been both favorable and unfavorable outcomes documented. METHODS: We performed a systematic review of 116 GMF cases previously described in the literature. RESULTS: In contrast to the classic Alibert-Bazin type of mycosis fungoides (MF), cutaneous lesions in GMF tend to involve distal extremities (lower legs, feet, hands) early in the disease course. In the literature, 30% of GMF patients developed organ metastasis, most frequently to the lung. The median time to stage progression was 25 months. CONCLUSION: GMF is an aggressive form of MF. Therefore, screening for distant metastases should be considered at presentation and repeated during follow-up.

Architecture of skin inflammation in psoriasis revealed by spatial transcriptomics.

Psoriasis is a chronic inflammatory skin disease, thought to be predominantly mediated by TH17 cells. Significance of other inflammatory pathways and the innate immune system is not well understood and the spatial heterogeneity of inflammation in the skin has largely been overlooked. Our aim was to create a comprehensive map of skin inflammation in psoriasis, exploring the tissue patterning of inflammation. In situ whole transcriptome sequencing (spatial sequencing) was performed on lesional psoriatic skin in four patients with moderate-to-severe disease to quantify all expressed genes within a tissue section. Transcriptional analysis revealed three major inflammatory niches in psoriasis skin, each with distinct cytokine circuits and chemokines: the hyperplastic epidermis, upper (papillary) dermis, and reticular dermis. Interestingly, key cytokines such as IL-23, IL-17 s, and TNFα were not notably present in the skin's transcriptomic signature. Unexpectedly, IL-32 showed strong expression in the dermis. Our findings underscore the complexity of psoriatic inflammation, highlighting its architectural heterogeneity and the roles of innate cytokines. Both IL-32 and IL-1 family cytokines appear to play critical roles in the dermal and epidermal inflammation, respectively, and may provide pharmacological targets to improve the control of the inflammatory process.

The cancer-associated glycan polysialic acid is dysregulated in systemic sclerosis and is associated with fibrosis.

OBJECTIVE: Systemic sclerosis (SSc) is a rare but deadly disease characterized by autoimmunity, vasculopathy, and fibrosis. Fibrotic complications associated with SSc correlate with severe morbidity and mortality. Previous studies in SSc have identified fibroblasts as the primary drivers of fibrosis; however, the mechanism(s) promoting this are not well understood. Aberrant glycosylation, particularly polysialylation (polySia), has been described as a prominent feature of aggressive cancers. Inspired by this observation, we aimed to determine if polySia is dysregulated in various forms of SSc. METHODS: All patients with SSc met the 2013 ACR/EULAR. Patients were sub-classified into limited cutaneous (lSSc, N = 5 or 46 patients for polySia quantification in the dermis or serum; respectively), diffuse cutaneous (dSSc, N = 11 or 18 patients for polySia quantification in the dermis or serum; respectively), or patients with dSSc treated with an autologous stem cell transplantation (post-ASCT, N = 4 patients for quantification in the dermis). Dermal polySia levels were measured via immunofluorescence microscopy in 10 µm dermal sections, quantified in each group (healthy volunteers (HC), lSSc, dSSc, and post-ASCT) and correlated with skin fibrosis (via the modified Rodnan skin score (mRSS)). Similarly, serum polySia was quantified in each group, and correlated with the mRSS. RESULTS: Dermal polySia levels were highest in patients with dSSc (compared to HC < 0.001), and correlated with the degree of fibrosis in all of the groups (P = 0.008). Serum polySia was higher in all SSc groups (p < 0.001) and correlated with the severity of mRSS (p < 0.0001). CONCLUSION: Polysia is more abundant in the skin and sera from patients with SSc and correlates with the degree of skin fibrosis. The aberrant expression of polySia highlights its potential use as a biomarker in patients with progressive forms of SSc. Dysregulated polySia levels in SSc further emphasizes the cancer-like phenotype present in SSc, which may promote fibrosis and immune dysregulation.

Subcutaneous immunoglobulin for patients with idiopathic inflammatory myopathies: a real-world single centre experience.

OBJECTIVES: Idiopathic inflammatory myopathies (IIMs) are heterogeneous diseases characterized by skeletal muscle inflammation associated with cutaneous, pulmonary, and/or other visceral organ involvement. Intravenous immunoglobulin (IVIG) has been recommended as an adjunct therapy for IIM patients refractory to conventional therapy. However, IVIG has high resource needs and increased risk of adverse reactions. Subcutaneous immunoglobulin (SCIG) therapy has been used as an alternative to IVIG in primary immunodeficiencies and neuroinflammatory disorders. We assessed the satisfaction, patient preference and effectiveness in IIM patients transitioned from IVIG to SCIG. METHODS: We retrospectively reviewed consecutive 20 patients with IIM who were transitioned from IVIG to SCIG therapy for >12 months. Patient preference between IVIG vs SCIG was surveyed using a questionnaire previously used in studies with neuroinflammatory conditions. In addition, disease flares, changes in immunosuppression, cumulative prednisone doses and global disease activity were evaluated using the Myositis Intention to Treat Index (MITAX) 12-months prior to- and post-SCIG initiation. RESULTS: Most patients (78.9%) preferred SCIG over IVIG and preferred home-based therapies to hospital-based therapies. There was no significant difference in global disease activity (MITAX 3.31 vs 3.02) nor in cumulative steroid doses 12-months prior to- or post-SCIG initiation. Three patients experienced disease flares, 5 escalated in immunosuppression, while 4 patients deescalated in immunosuppressive medications. CONCLUSIONS: SCIG is preferred by most patients over IVIG without a substantial increased disease activity or need for additional corticosteroids. Future cost effectiveness studies may provide an additional rationale for utilizing SCIG over IVIG for maintenance therapy for IIM.

Skin disorders and interstitial lung disease: Part I-Screening, diagnosis, and therapeutic principles.

Numerous inflammatory, neoplastic, and genetic skin disorders are associated with interstitial lung disease (ILD), the fibrosing inflammation of lung parenchyma that has significant morbidity and mortality. Therefore, the dermatologist plays a major role in the early detection and appropriate referral of patients at risk for ILD. Part 1 of this 2-part CME outlines the pathophysiology of ILD and focuses on clinical screening and therapeutic principles applicable to dermatological patients who are at risk for ILD. Patients with clinical symptoms of ILD should be screened with pulmonary function tests and high-resolution chest computed tomography. Screening for pulmonary hypertension should be considered in high-risk patients. Early identification and elimination of pulmonary risk factors, including smoking and gastroesophageal reflux disease, are essential in improving respiratory outcomes. First-line treatment interventions for ILD in a dermatological setting include mycophenolate mofetil, but the choice of therapeutic agents depends on the nature of the primary disease, the severity of ILD, and comorbidities and should be the result of a multidisciplinary assessment. Better awareness of ILD among medical dermatologists and close interdisciplinary collaborations are likely to prevent treatment delays improving long-term outcomes.

Skin disorders and interstitial lung disease: Part II-The spectrum of cutaneous diseases with lung disease association.

Part 2 of this 2-part CME introduces dermatologists to noninfectious inflammatory skin diseases associated with pulmonary involvement. In many cases, dermatologists may be the first physicians recognizing respiratory complications associated with these diagnoses. Because pulmonary involvement is often the leading cause of morbidity and mortality, dermatologists should be comfortable screening and monitoring for lung disease in high-risk patients, recognizing cutaneous stigmata of lung disease in these patients and referring to pulmonary specialists, when appropriate, for prompt treatment initiation. Some treatments used for skin disease may not be appropriate in the context of lung disease and hence, choosing a holistic approach is important. Interstitial lung disease and pulmonary hypertension are the most common pulmonary complications and a significant cause of mortality in autoimmune connective tissue diseases, especially systemic sclerosis, dermatomyositis, and mixed connective tissue disease. Pulmonary complications, notably interstitial lung disease, are also common and life-threatening in sarcoidosis and vasculitis, while they are variable in neutrophilic and autoimmune blistering diseases.

Baseline Characteristics of Canadian Patients in the Psoriasis Longitudinal Assessment and Registry (PSOLAR).

BACKGROUND: The Psoriasis Longitudinal Assessment and Registry (PSOLAR) is a global, prospective, longitudinal, disease-based registry. It serves as a post-marketing safety commitment with a focus on patients with moderate to severe plaque psoriasis who are candidates for systemic therapy. OBJECTIVES: To describe the baseline disease demographics and clinical characteristics of a Canadian subgroup of participants enrolled in PSOLAR. METHODS: Baseline demographic/disease characteristics, medical histories, and previous psoriasis treatments for Canadian patients in PSOLAR were summarized using descriptive statistics. RESULTS: There were 1896 patients analyzed in the Canadian subgroup at 37 clinical sites, accounting for 15.7% of the global PSOLAR population. Baseline disease and clinical characteristics were as expected for a moderate to severe psoriasis population and were generally similar to the global PSOLAR population. Two distinctions were noted in the Canadian subgroup versus those enrolled globally: a higher proportion of patients were overweight/obese (84.7% vs. 80.4%) and male (61.4% vs. 54.7%). In addition, the Canadian subgroup had numerically higher historical peak disease activity (PGA score 3.35 vs. 3.1) and longer disease duration (22.3 years vs. 17.5 years). Canadian PSOLAR patients reported a variety of comorbidities, including psoriatic arthritis (31.5%), hypertension (34.6%), hyperlipidemia (24.3%), mental illness (24.1%), and inflammatory bowel disease (1.6%). CONCLUSION: The Canadian subgroup of PSOLAR patients was generally similar to those enrolled globally with respect to baseline disease demographics and clinical characteristics. Multiple comorbidities are noted in the Canadian subgroup, underscoring the need for a holistic approach to the treatment of psoriatic patients.

Top Ten Research Priorities for Psoriasis, Atopic Dermatitis and Hidradenitis Suppurativa: The SkIN Canada Priority Setting Initiative.

BACKGROUND: The Skin Investigation Network of Canada (SkIN Canada) is a new national skin research network. To shape the research landscape and ensure its value to patient care, research priorities that are important to patients, caregivers, and health care providers must be identified. OBJECTIVES: To identify the Top Ten research priorities for 9 key skin conditions. METHODS: We first surveyed health care providers and researchers to select the top skin conditions for future research within the categories of inflammatory skin disease, skin cancers (other than melanoma), and wound healing. For those selected skin conditions, we conducted scoping reviews to identify previous priority setting exercises. We combined the results of those scoping reviews with a survey of patients, health care providers, and researchers to generate lists of knowledge gaps for each condition. We then surveyed patients and health care providers to create preliminary rankings to prioritize those knowledge gaps. Finally, we conducted workshops of patients and health care providers to create the final Top Ten lists of research priorities for each condition. RESULTS: Overall, 538 patients, health care providers, and researchers participated in at least one survey or workshop. Psoriasis, atopic dermatitis and hidradenitis suppurativa (inflammatory skin disease); chronic wounds, burns and scars (wound healing); and basal cell, squamous cell and Merkel cell carcinoma (skin cancer) were selected as priority skin conditions. Top Ten lists of knowledge gaps for inflammatory skin conditions encompassed a range of issues relevant to patient care, including questions on pathogenesis, prevention, non-pharmacologic and pharmacologic management. CONCLUSIONS: Research priorities derived from patients and health care providers should be used to guide multidisciplinary research networks, funders, and policymakers in Canada and internationally.

Chlormethine Gel for the Treatment of Mycosis Fungoides (Cutaneous T-cell Lymphoma) in Canada.

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL), representing almost 50% of all lymphomas arising in the skin. There is an unmet need in the treatment of MF in Canada, as current available therapies for early-stage MF are limited, without topical agents previously indicated. Chlormethine gel is a topical antineoplastic agent with phase II clinical trial and real-world data demonstrating safety and efficacy as a treatment option for adults with MF. Skin-related side effects such as dermatitis can be managed through appropriate strategies. The use of chlormethine gel can be considered for patients with stage IA and IB MF-CTCL as it provides an easily administered, skin-directed treatment option that fills an unmet need in Canada.

Genomic instability in early systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) is associated with secondary malignancies. Previous studies have suggested that mutated cancer proteins, such as RNA polymerase III, are autoantigens promoting an inflammatory response in SSc. However, it has never been previously investigated whether non-neoplastic tissue in SSc harbors mutations which may play a role in SSc pathogenesis. METHODS: Skin biopsies were obtained from 8 sequential patients with a progressive form of early stage SSc (with severe skin and/or lung involvement). Areas of dermal fibrosis were microdissected and analyzed with deep, whole exome sequencing. Gene mutation patterns were compared to autologous buccal mucosal cells as a control. RESULTS: SSc skin biopsies were hypermutated with an average of 58 mutations/106 base pairs. The mutational pattern in all samples exhibited a clock-like signature, which is ubiquitous in cancers and in senescent cells. Of the 1997 genes we identified which were mutated in at least two SSc patients, 39 genes represented cancer drivers (i.e. tumor suppressor genes or oncogenes) which are commonly found in gynecological, squamous and gastrointestinal cancer signatures. Of all the mutations, the most common mutated genes were important in regulating pathways related to epigenetic histone modifications, DNA repair and genome integrity. CONCLUSIONS: Somatic hypermutation occurs in fibrotic skin in patients with early progressive SSc. Cancer driver gene mutations may potentially play a fundamental role in the pathogenesis of SSc.

Analysis of Geographic and Environmental Factors and Their Association with Cutaneous Melanoma Incidence in Canada.

BACKGROUND: Over 90% of skin cancers including cutaneous melanoma (CM) are related directly to sun exposure. Despite extensive knowledge on ultraviolet radiation's (UVR) detrimental impact, many still fail to implement sun protection/sun avoidance. Human behavior, attitudes, and cultural norms of individuals and communities heavily depend on the surrounding climate/environment. In many instances, the climate shapes the culture/norms of the society. Canada has vast geographic/environmental differences. METHODS: In the current ecological study, we sought to examine the relationship between various geographic and environmental factors and the distribution of CM incidence by Forward Sortation Area (FSA) postal code across Canada. CM incidence data were extracted from the Canadian Cancer Registry, while environmental data were extracted from the Canadian Urban Environmental Health Research Consortium (greenspace, as measured by the normalized difference vegetation index; annual highest temperature; absolute number and average length of yearly heat events; annual total precipitation [rain and snow]; absolute number and average length of events with precipitation [rain and snow]; and summer UVR index). The above geographic/environmental data by FSA were correlated with the respective CM incidence employing negative binomial regression model. RESULTS: Our analysis highlights that increases in annual average temperature, summer UVR, and greenspace were associated with higher expected incidence of CM cases, while higher number of annual heat events together with highest annual temperature and higher average number of annual rain events were associated with a decrease in CM incidence rate. This study also highlights regional variation in environmental CM risk factors in Canada. CONCLUSIONS: This national population-based study presents clinically relevant conclusions on weather/geographic variations associated with CM incidence in Canada and will help refine targeted CM prevention campaigns by understanding unique weather/geographic variations in high-risk regions.

Extracorporeal Photopheresis and Its Use in Clinical Dermatology in Canada

Extracorporeal photopheresis (ECP) is an immunomodulatory therapy that has been used for over 35 years to treat numerous conditions. ECP was initially approved by the US FDA in 1988 for the treatment of Sézary syndrome, a leukemic form of cutaneous T-cell lymphoma (CTCL). Although CTCL remains the only FDA-approved indication, ECP has since been used off-label for numerous other conditions, including graft-versus-host disease (GvHD), systemic sclerosis, autoimmune bullous dermatoses, Crohn's disease, and prevention of solid organ transplant rejection. In Canada, ECP is mainly used to treat CTCL, acute and chronic GvHD, and in some instances systemic sclerosis. Herein, we review the current concepts regarding ECP mechanism of action, treatment considerations and protocols, and efficacy.

Skin colonization by circulating neoplastic clones in cutaneous T-cell lymphoma.

Mycosis fungoides (MF) is a mature T-cell lymphoma currently thought to develop primarily in the skin by a clonal expansion of a transformed, resident memory T cell. However, this concept does not explain the key characteristics of MF, such as the debut with multiple, widespread skin lesions or inability of skin-directed therapies to provide cure. The testable inference of the mature T-cell theory is the clonality of MF with respect to all rearranged T-cell receptor (TCR) genes. Here, we used a whole-exome sequencing approach to detect and quantify TCR-α, ß, and γ clonotypes in tumor cell clusters microdissected from MF lesions. This method allowed us to calculate the tumor cell fraction of the sample and therefore an unequivocal identification of the TCR clonotypes as neoplastic. Analysis of TCR sequences from 29 patients with MF stage I to IV proved the existence of multiple T-cell clones within the tumor cell fraction, with a considerable variation between patients and between lesions from the same patient (median, 11 clones; range, 2-80 clones/sample). We have also detected multiple neoplastic clones in the peripheral blood in all examined patients. Based on these findings, we propose that circulating neoplastic T-cell clones continuously replenish the lesions of MF, thus increasing their heterogeneity by a mechanism analogous to the consecutive tumor seeding. We hypothesize that circulating neoplastic clones might be a promising target for therapy and could be exploited as a potential biomarker in MF.

The Clinical Spectrum of Primary Cutaneous CD4+ Small/Medium-Sized Pleomorphic T-Cell Lymphoproliferative Disorder: An Updated Systematic Literature Review and Case Series.

BACKGROUND: Primary cutaneous CD4+ small/medium pleomorphic T-cell lymphoproliferative disorder (SMPLPD) is a provisional entity within the 2016 World Health Organization classification of primary cutaneous lymphomas. The condition is currently classified as a lymphoproliferative disorder to emphasize its benign course and discourage aggressive, systemic treatment modalities. OBJECTIVE: To provide a relevant synthesis for the dermatological practitioner on the prevalence, presentation, and treatment of SMPLPD. METHODS: We conducted an updated systematic literature review and a retrospective chart review of diagnosed cases of SMPLPD from 2 Canadian academic cutaneous lymphoma centers. RESULTS: A total of 23 studies with 136 cases were extracted from the systematic review and 24 patients from our retrospective chart review. SMPLPD proved relatively common accounting for 12.5% of all cutaneous T-cell lymphomas encountered in our cutaneous lymphoma clinics, second in frequency only to mycosis fungoides. The typical clinical presentation was that of an older individual (median age 59 years) with an asymptomatic solitary lesion on their upper extremity. The most common clinical differentials were cutaneous lymphoid hyperplasia, basal cell carcinoma, and lymphoma unspecified. T follicular helper markers were reliably detected. The main treatment modalities were surgical excision, local radiation therapy, and topical or intralesional steroids. Cure was achieved in the vast majority of cases. CONCLUSIONS: SMPLPD is an underdiagnosed T-cell lymphoma with an overtly benign clinical course. The condition has an excellent prognosis and responds well to skin-directed therapies. Practitioners should be aware of this condition to avoid aggressive systemic treatments.

Evaluation of Alitretinoin for the Treatment of Mycosis Fungoides and Sézary Syndrome.

BACKGROUND: Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma (CTCL). There is currently no cure for CTCL, and treatment is aimed at limiting disease progression. This study evaluated the efficacy and tolerability of alitretinoin in CTCL management. METHODS: A retrospective, multicenter study was conducted on CTCL patients treated with alitretinoin as a primary agent or in combination with standard therapies. RESULTS: Forty-eight patients with MF (n = 40) and SS (n = 8) with a median age of 59.7 years (±14.3) were eligible for study inclusion. Treatment response data were evaluated in 40 patients and safety in 42 patients. 40.0% of the patients had early-stage, 43.8% had advanced-stage CTCL, and in 16.7% of patients there was insufficient information for staging. 40.0% (16/40) of the patients achieved a complete or partial response, whereas 47.5% (19/40) achieved stable disease, 12.5% (5/40) had progressive disease, and there were no cases of disease relapses in responders. Both early and advanced stages of CTCL were responsive to alitretinoin as a primary or combined modality. Alitretinoin was well tolerated, and 64.3% (27/42) of patients did not report any side effects. The most commonly observed side effect was hypertriglyceridemia. CONCLUSIONS: This retrospective analysis supports the efficacy and safety of alitretinoin in clearing skin disease and preventing disease progression in CTCL as a monotherapy or in combination with standard therapies.

Clinical Outcomes Among Bullous Pemphigoid Patients-A Comparison of Urban and Rural Populations.

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering disease. It can be challenging to manage and is associated with an increased risk of mortality. Access to dermatologic care is essential for patients with BP. However, the influence of geographic residence and distance to specialty care on patient outcomes or treatment regimens is unknown. OBJECTIVE: Assess whether the rural-dwelling or urban-dwelling geographic status of our patients impacts the treatment duration of systemic corticosteroids (CS) in the management of BP. Numerous secondary outcomes were evaluated including the cumulative systemic corticosteroid dose received, steroid-sparing agent utilized, and duration and number of follow-up appointments. METHODS: Retrospective analysis of patient records from January 2013 to May 2019 seen at the university-associated clinic in Edmonton, Alberta. Patients were stratified based on their rural-dwelling or urban-dwelling status via their Forward Sortation Area. RESULTS: There were 59 patients with BP. Of these, 37 completed their systemic corticosteroid course. The time required for 51.0% of the urban group to complete their steroid course was 543 days, and for 51.5% of the rural group it was 507 days. Methotrexate and azathioprine were the most common steroid-sparing agents utilized in both groups. Rural patients were seen in follow-up significantly less often than urban patients. CONCLUSION: Our findings demonstrate that the location of a patient's geographic residence does not influence the systemic corticosteroid or steroid-sparing agent use at our center. Interestingly, rural patients are able to receive similar treatment to urban patients despite having significantly fewer follow-up appointments.

Cutaneous Immune-Related Adverse Events (irAEs) to Immune Checkpoint Inhibitors: A Dermatology Perspective on Management [Formula: see text].

Immune checkpoint inhibitors have proven to be efficacious for a broad spectrum of solid organ malignancies. These monoclonal antibodies lead to cytotoxic T-cell activation and subsequent elimination of cancer cells. However, they can also lead to immune intolerance and immune-related adverse event (irAEs) that are new and specific to these therapies. Cutaneous irAEs are the most common, arising in up to 34% of patients on PD-1 inhibitors and 43% to 45% on CTLA-4 inhibitors. The most common skin manifestations include maculopapular eruption, pruritus, and vitiligo-like lesions. A grading system has been proposed, which guides management of cutaneous manifestations based on the percent body surface area (BSA) involved. Cutaneous irAEs may prompt clinicians to reduce drug doses, add systemic steroids to the regiment, and/or discontinue lifesaving immunotherapy. Thus, the goal is for early identification and concurrent management to minimize treatment interruptions. We emphasize here that the severity of the reaction should not be graded based on BSA involvement alone, but rather on the nature of the primary cutaneous pathology. For instance, maculopapular eruptions rarely affect <30% BSA and can often be managed conservatively with skin-directed therapies, while Stevens-Johnson syndrome (SJS) affecting even 5% BSA should be managed aggressively and the immunotherapy should be discontinued at once. There is limited literature available on the management of the cutaneous irAEs and most studies present anecdotal evidence. We review the management strategies and provide recommendations for psoriatic, immunobullous, maculopapular, lichenoid, acantholytic eruptions, vitiligo, alopecias, vasculitides, SJS/toxic epidermal necrolysis, and other related skin toxicities.

Use of Extracorporeal Photopheresis in Scleroderma: A Review.

BACKGROUND: Scleroderma is a heterogeneous group of diseases that can be localized or systemic. Localized scleroderma is a fibrosis of the skin characterized by inflammation and thickening due to excessive collagen deposition, and systemic sclerosis (SSc) is characterized by vasculopathy, immune dysregulation and skin fibrosis. In general, the prognosis of scleroderma highly depends on the degree of visceral involvement and relates to the degree of skin fibrosis. Despite the numerous therapies used for patients with scleroderma, the disease-related morbidity and mortality are high. Studies have explored the effects of extracorporeal photopheresis (ECP) in scleroderma treatment. Originally used in the treatment of cutaneous T-cell lymphoma, ECP is an immunomodulatory procedure in which a patient's white blood cells are treated with 8-methoxypsoralen and exposed to UVA radiation to inhibit cell proliferation and induce immunosuppression. SUMMARY: Multiple lines of evidence suggest that ECP may be a safe and possibly effective therapy for patients with scleroderma, specifically demonstrating improvement in patients with cutaneous manifestations of the disease. However, future studies assessing its role in managing visceral involvement are needed. Our review aims to examine and consolidate the results of clinical studies and propose a possible role for ECP in the management of scleroderma. KEY POINTS: ECP may be an effective and safe procedure for the treatment of SSc.