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175 Development of neutrophilic dermatoses in profoundly neutropenic patients
Clinical Research I: Epidemiology and Patient Outcomes Research | ABSTRACTS 172
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New keratinocyte carcinomas worsen skin-related quality of life JA Siegel1, M Chren2 and MA Weinstock1,3 1 VA Med Ctr, Providence, RI, 2 University of CA, San Francisco, CA and 3 Brown Univ, Providence, RI The incidence of keratinocyte carcinoma (KC), the most common malignancy in the U.S., continues to rise. Because KC impacts a significant portion of the population but has a low mortality rate, it is important to quantify skin-related quality of life (QoL) in those affected. We aim to determine if KC, actinic keratoses (AK), and several demographic and health-related factors are associated with skin-related QoL in those at high risk for KC. We used data from a double-blind, placebo-controlled trial in which 930 veterans with a history of multiple KCs were randomized to apply a single course of topical 5-fluorouracil (5-FU) or vehicle control cream to the face and ears. Skin-related QoL was measured at baseline, 12, 24, and 36 months using Skindex-29 and Skin Cancer Index and participants received complete skin examinations semiannually. At baseline, worse skin-related QoL was strongly associated (p0.01) with younger age and greater functional impairments (e.g. inability to bathe, walk). It was also associated with higher comorbidities, increased sun-sensitivity and history of 5-FU use, but almost entirely unrelated to number of AKs and prior KCs. However, participants who developed new KCs during the trial had a greater worsening of skin-related QoL, or a lesser degree of improvement, compared to those who did not develop new KCs, particularly in year 1. Similar results were seen in participants who developed increased AKs. Our ability to detect these relationships in longitudinal analyses but not in baseline cross-sectional analyses may indicate the importance of the more precise control of potential confounding factors that is inherent in comparing each individual to their own prior state. These findings suggest that in addition to chronic conditions of sun damage, additional KCs and increased AKs may worsen skin-related QoL in individuals with a history of multiple KCs. Also, as skin-related QoL is particularly diminished in those with greater functional impairments, it is especially important to address their dermatologic needs.
Teledermatology as a tool to improve access to care for medically underserved populations: A retrospective descriptive study S Kessler1, E Leavitt1, S Pun1, T Gill1, L Escobedo2, M Cockburn3, A Sutton1 and A Crew1 1 Department of Dermatology, Keck School of Medicine of University of Southern California, Los Angeles, CA, 2 Spatial Sciences Institute and Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA and 3 Department of Preventative Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA In medically underserved populations, teledermatology (TD) can be utilized to broaden access to care via “tele-triage”. Our group evaluated the capacity of the Los Angeles County Department of Health Services (LAC DHS) TD platform to “tele-triage” consults, with a goal of increasing access to urgent dermatologic care in a health care system where the wait for a non-urgent visit often exceeds six months. This was a retrospective descriptive study involving manual review of 9,499 TD consults placed by primary care physicians (PCPs) in the LAC DHS TD system between July 2012 and May 2014. The primary outcome variable was percentage of consults referred for an in-person appointment with a dermatologist versus those in which the patient’s needs were addressed remotely. 68% of all consults were referred face-toface, while 29% of consults were managed exclusively via TD, and 3% were closed pending additional diagnostics, typically a photograph. Consults were managed solely via TD more frequently if they were for rashes rather than lesions (38% vs. 25%), included adequate photographs (31% vs. 23%), or included greater than 1000 characters of dialogue exchange (46% vs 19%). With adequate photographs, in-person visits were deemed unnecessary in 21% of consults where the PCP suspected any malignancy and in 29% of consults where the PCP suspected melanoma. By avoiding in-person visits for conditions that can be managed by a PCP under remote guidance from a dermatologist, more clinic appointments are made available for those with urgent conditions. We found that the LAC DHS TD system was effective in “tele-triaging” both benign rashes and suspicious lesions, thus increasing access to urgent dermatologic care.
Predictors of dermatologic medication primary nonadherence in an urban hospital population: Are electronic prescriptions superior? A Adamson1,2 and A Gorman3 1 Dermatology, UNC - Chapel Hill, Chapel Hill, NC, 2 Dermatology, UTSW, Dallas, TX and 3 Biostatistics, UTSW, Dallas, TX Electronic prescribing increases co-ordination between pharmacist and physician and decreases errors; however, it is less certain if electronic prescribing affects medication primary nonadherence. A retrospective chart review of medical records from January 2011 to December 2013 at a single urban safety-net hospital outpatient dermatology clinic identified new patients prescribed paper or electronic prescriptions. Patients were excluded if they were not prescribed medication, were seeking follow up care, or did not receive medication through a countysubsidized health plan. Patients with this health plan had access to a pharmaceutical benefit, which provided medications within a closed pharmacy system. Using the electronic medical record, medication primary nonadherence rates and patient characteristics were tracked. The primary outcome was the overall rate of primary nonadherence, allowing for a 1-year prescription fill period. Our study cohort (n¼2,579) was prescribed 4,635 medications. The average age of the patients was 48 years old with 66% women, 49% Hispanic, 26% AfricanAmerican, and 18% Caucasian; 37% identified Spanish as their primary language. Of the prescriptions, 67% were paper versus 33% electronically routed to the pharmacy. The overall primary nonadherence rate was 41%. Primary nonadherence was 16% (p<0.0001) higher in the paper prescription group compared to the electronic prescription group. Patients younger than 30 years old had a 14% (p<0.0001) higher primary nonadherence rate and patients with English as their primary language had 5% (p<0.008) higher primary nonadherence rate. Primary nonadherence increased with increasing number of medications prescribed per patient. This study is the largest report directly measuring primary nonadherence to dermatologic medications. Efforts must be made to ensure that we understand why primary nonadherence occurs, identify patients prone to primary nonadherence, and simplify medication regimens to maximize adherence and quality of care.
Development of neutrophilic dermatoses in profoundly neutropenic patients GA Romar, L Compton, TS Kupper and S Divito Dermatology, Harvard Medical School, Boston, MA Anecdotally, inflammatory skin diseases are not infrequently observed in patients with profound leukopenia, though literature is limited to case reports/studies. The development of inflammatory dermatoses despite profound leukopenia suggests that either the few cells remaining in circulation preferentially home to skin, or leukocytes in skin survive chemotherapy. To begin to investigate this, we performed a retrospective cohort study to determine the effect of profound neutropenia on development of neutrophilic dermatoses. Patients 18 years old seen by the inpatient dermatology consult service at Brigham and Women’s Hospital who underwent skin biopsy and had a peripheral white blood cell (WBC) count with differential drawn on the day of biopsy were included. Patients were categorized as profoundly neutropenic if their absolute neutrophil count (ANC) was < 1 K/ml, or as not if their ANC was 1 K/ml. Total number of cases was 234, of which 48 were profoundly neutropenic. Of these, 5 had a neutrophilic dermatosis (incidence proportion 10.4%). Comparatively, 16 of 186 non-profoundly neutropenic patients developed a neutrophilic dermatosis (incidence proportion 8.6%). Relative difference was 1.8% and relative risk 1.21 (95% CI 0.464-3.158, 1 sided Fisher’s exact test p ¼ 0.439, power 72%). Though slightly underpowered, these data suggest that there is no significant difference in development of neutrophilic dermatoses despite profound neutropenia. Within the profound neutropenia non-neutrophilic dermatoses group, cases with robust neutrophilic infiltrate in skin were noted such infections and leukocytoclastic vasculitis, further indicating that large numbers of neutrophils can be found in skin despite low numbers in blood. Finally, development of neutrophilic dermatoses in profoundly neutropenic patients was independent of G(M)-CSF treatment, and there was no correlation between disease development and trend in peripheral WBC, counter to previous hypotheses.
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Epidemiology and treatment of refractory cutaneous lupus erythematosus R Fruchter2, D Kurtzman1, J Lin1, AN Femia2 and R Vleugels1 1 Department of Dermatology, Brigham and Women’s Hospital, Boston, MA and 2 The Ronald O. Perelman Department of Dermatology, NYU School of Medicine, NY, NY Cutaneous lupus erythematosus (CLE) is an autoimmune skin disease that can result in severe morbidity. Although antimalarial therapy is considered first line systemic therapy for CLE, up to 55% of patients are refractory to hydroxychloroquine. Several systemic agents have been studied individually for recalcitrant CLE; however, no study examines the overall treatment experience of refractory CLE. Using the NYU and Partners Healthcare electronic medical records, we conducted a retrospective review to identify patients with refractory CLE (695.4, ICD-9) seen at 3 tertiary care centers from 2005 to 2015. We identified 46 patients with CLE refractory to at least one antimalarial medication. Treatment outcomes were based on review of clinical examination, patient symptoms, and photographs when available. Mean age at diagnosis was 36.1 years; 87% were female. 27% (n¼12) had disease limited to the head and neck, and 73% (n¼32) had generalized disease. Systemic agents used for refractory CLE included methotrexate, mycophenolate mofetil, thalidomide, lenalidomide, belimumab, prednisone, rituximab, and dapsone. Thalidomide demonstrated the greatest efficacy with 4 out of 5 patients experiencing >50% improvement. Five out of 11 patients on methotrexate, 4 out of 11 on dapsone, and 3 out of 9 on belimumab experienced >50% improvement. Other medications had lower rates of success. Overall, cutaneous disease not responsive to antimalarial agents was recalcitrant to subsequent immunomodulatory therapy. This pilot study represents the largest to date describing treatment alternatives in aggregate for antimalarialresistant CLE. Additional study is needed to delineate an appropriate therapeutic algorithm for antimalarial-refractory CLE.
Trends of skin cancer incidence following transplantation in the United States GL Garrett and ST Arron UCSF, San Francisco, CA Population-based data on skin cancer incidence post-transplantation is limited. The Transplant Skin Cancer Network (TSCN) was created in 2014 with seed funding by the American Academy of Dermatology. The TSCN Incidence Study is the first US population-based study investigating post-transplant skin cancer outcomes. Our aim was to assemble a 25-center population-based cohort based on the OPTN database, which lists all US transplants, and dermatologic data from chart review. We included all primary solid organ transplants in the US received between January 1st 2003 and December 31st 2003 or January 1st 2008 and December 31st 2008 at participating sites. We analyzed patient demographics and calculated the incidence rate (IR) and the crude incidence of overall skin cancer, squamous cell carcinoma (SCC), melanoma, and Merkel cell carcinoma (MCC). 25 transplant centers participated in the study. Of 10,411 primary transplants identified, 46% occurred in 2003 and 53% occurred in 2008. The majority of patients were 50 years of age or older (56%), males (64%), white (68%), and kidney transplant recipients (48%). We had complete skin cancer outcome data on 70% of patients. 909 skin cancer cases occurred over a total person time of 5.9x104 years, for an incidence rate (IR) of 1518.0 per 100,000 person years (95% CI 1421.4 1621.1). Of these, 839 (8.1%) were SCC, 115 (1.1%) were melanoma, and 4 (0.1%) were MCC. The predictors of post-transplant skin cancer were male sex (HR 1.64, 95% CI 1.40 1.92), age of 50 or older (HR 2.93, 95% CI 2.45 e 3.51), thoracic transplant (HR 1.38, 95% CI 1.18 - 1.60), and white race (HR 7.38, 95% CI 5.28 - 10.31). The predictors of missing outcome data were white race, being transplanted in 2008 vs. 2003, and transplant center. Methods to investigate missing data are in progress. Complete analysis of these data will be able to investigate more detailed race- and organ-specific risk factors, define the stratified IR of SCC, MM, and MCC, determine the mortality rate of skin cancer, and highlight the predictors of skin cancer incidence and mortality.
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New keratinocyte carcinomas worsen skin-related quality of life JA Siegel1, M Chren2 and MA Weinstock1,3 1 VA Med Ctr, Providence, RI, 2 University of CA, San Francisco, CA and 3 Brown Univ, Providence, RI The incidence of keratinocyte carcinoma (KC), the most common malignancy in the U.S., continues to rise. Because KC impacts a significant portion of the population but has a low mortality rate, it is important to quantify skin-related quality of life (QoL) in those affected. We aim to determine if KC, actinic keratoses (AK), and several demographic and health-related factors are associated with skin-related QoL in those at high risk for KC. We used data from a double-blind, placebo-controlled trial in which 930 veterans with a history of multiple KCs were randomized to apply a single course of topical 5-fluorouracil (5-FU) or vehicle control cream to the face and ears. Skin-related QoL was measured at baseline, 12, 24, and 36 months using Skindex-29 and Skin Cancer Index and participants received complete skin examinations semiannually. At baseline, worse skin-related QoL was strongly associated (p0.01) with younger age and greater functional impairments (e.g. inability to bathe, walk). It was also associated with higher comorbidities, increased sun-sensitivity and history of 5-FU use, but almost entirely unrelated to number of AKs and prior KCs. However, participants who developed new KCs during the trial had a greater worsening of skin-related QoL, or a lesser degree of improvement, compared to those who did not develop new KCs, particularly in year 1. Similar results were seen in participants who developed increased AKs. Our ability to detect these relationships in longitudinal analyses but not in baseline cross-sectional analyses may indicate the importance of the more precise control of potential confounding factors that is inherent in comparing each individual to their own prior state. These findings suggest that in addition to chronic conditions of sun damage, additional KCs and increased AKs may worsen skin-related QoL in individuals with a history of multiple KCs. Also, as skin-related QoL is particularly diminished in those with greater functional impairments, it is especially important to address their dermatologic needs.
Teledermatology as a tool to improve access to care for medically underserved populations: A retrospective descriptive study S Kessler1, E Leavitt1, S Pun1, T Gill1, L Escobedo2, M Cockburn3, A Sutton1 and A Crew1 1 Department of Dermatology, Keck School of Medicine of University of Southern California, Los Angeles, CA, 2 Spatial Sciences Institute and Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA and 3 Department of Preventative Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA In medically underserved populations, teledermatology (TD) can be utilized to broaden access to care via “tele-triage”. Our group evaluated the capacity of the Los Angeles County Department of Health Services (LAC DHS) TD platform to “tele-triage” consults, with a goal of increasing access to urgent dermatologic care in a health care system where the wait for a non-urgent visit often exceeds six months. This was a retrospective descriptive study involving manual review of 9,499 TD consults placed by primary care physicians (PCPs) in the LAC DHS TD system between July 2012 and May 2014. The primary outcome variable was percentage of consults referred for an in-person appointment with a dermatologist versus those in which the patient’s needs were addressed remotely. 68% of all consults were referred face-toface, while 29% of consults were managed exclusively via TD, and 3% were closed pending additional diagnostics, typically a photograph. Consults were managed solely via TD more frequently if they were for rashes rather than lesions (38% vs. 25%), included adequate photographs (31% vs. 23%), or included greater than 1000 characters of dialogue exchange (46% vs 19%). With adequate photographs, in-person visits were deemed unnecessary in 21% of consults where the PCP suspected any malignancy and in 29% of consults where the PCP suspected melanoma. By avoiding in-person visits for conditions that can be managed by a PCP under remote guidance from a dermatologist, more clinic appointments are made available for those with urgent conditions. We found that the LAC DHS TD system was effective in “tele-triaging” both benign rashes and suspicious lesions, thus increasing access to urgent dermatologic care.
Predictors of dermatologic medication primary nonadherence in an urban hospital population: Are electronic prescriptions superior? A Adamson1,2 and A Gorman3 1 Dermatology, UNC - Chapel Hill, Chapel Hill, NC, 2 Dermatology, UTSW, Dallas, TX and 3 Biostatistics, UTSW, Dallas, TX Electronic prescribing increases co-ordination between pharmacist and physician and decreases errors; however, it is less certain if electronic prescribing affects medication primary nonadherence. A retrospective chart review of medical records from January 2011 to December 2013 at a single urban safety-net hospital outpatient dermatology clinic identified new patients prescribed paper or electronic prescriptions. Patients were excluded if they were not prescribed medication, were seeking follow up care, or did not receive medication through a countysubsidized health plan. Patients with this health plan had access to a pharmaceutical benefit, which provided medications within a closed pharmacy system. Using the electronic medical record, medication primary nonadherence rates and patient characteristics were tracked. The primary outcome was the overall rate of primary nonadherence, allowing for a 1-year prescription fill period. Our study cohort (n¼2,579) was prescribed 4,635 medications. The average age of the patients was 48 years old with 66% women, 49% Hispanic, 26% AfricanAmerican, and 18% Caucasian; 37% identified Spanish as their primary language. Of the prescriptions, 67% were paper versus 33% electronically routed to the pharmacy. The overall primary nonadherence rate was 41%. Primary nonadherence was 16% (p<0.0001) higher in the paper prescription group compared to the electronic prescription group. Patients younger than 30 years old had a 14% (p<0.0001) higher primary nonadherence rate and patients with English as their primary language had 5% (p<0.008) higher primary nonadherence rate. Primary nonadherence increased with increasing number of medications prescribed per patient. This study is the largest report directly measuring primary nonadherence to dermatologic medications. Efforts must be made to ensure that we understand why primary nonadherence occurs, identify patients prone to primary nonadherence, and simplify medication regimens to maximize adherence and quality of care.
Development of neutrophilic dermatoses in profoundly neutropenic patients GA Romar, L Compton, TS Kupper and S Divito Dermatology, Harvard Medical School, Boston, MA Anecdotally, inflammatory skin diseases are not infrequently observed in patients with profound leukopenia, though literature is limited to case reports/studies. The development of inflammatory dermatoses despite profound leukopenia suggests that either the few cells remaining in circulation preferentially home to skin, or leukocytes in skin survive chemotherapy. To begin to investigate this, we performed a retrospective cohort study to determine the effect of profound neutropenia on development of neutrophilic dermatoses. Patients 18 years old seen by the inpatient dermatology consult service at Brigham and Women’s Hospital who underwent skin biopsy and had a peripheral white blood cell (WBC) count with differential drawn on the day of biopsy were included. Patients were categorized as profoundly neutropenic if their absolute neutrophil count (ANC) was < 1 K/ml, or as not if their ANC was 1 K/ml. Total number of cases was 234, of which 48 were profoundly neutropenic. Of these, 5 had a neutrophilic dermatosis (incidence proportion 10.4%). Comparatively, 16 of 186 non-profoundly neutropenic patients developed a neutrophilic dermatosis (incidence proportion 8.6%). Relative difference was 1.8% and relative risk 1.21 (95% CI 0.464-3.158, 1 sided Fisher’s exact test p ¼ 0.439, power 72%). Though slightly underpowered, these data suggest that there is no significant difference in development of neutrophilic dermatoses despite profound neutropenia. Within the profound neutropenia non-neutrophilic dermatoses group, cases with robust neutrophilic infiltrate in skin were noted such infections and leukocytoclastic vasculitis, further indicating that large numbers of neutrophils can be found in skin despite low numbers in blood. Finally, development of neutrophilic dermatoses in profoundly neutropenic patients was independent of G(M)-CSF treatment, and there was no correlation between disease development and trend in peripheral WBC, counter to previous hypotheses.
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Epidemiology and treatment of refractory cutaneous lupus erythematosus R Fruchter2, D Kurtzman1, J Lin1, AN Femia2 and R Vleugels1 1 Department of Dermatology, Brigham and Women’s Hospital, Boston, MA and 2 The Ronald O. Perelman Department of Dermatology, NYU School of Medicine, NY, NY Cutaneous lupus erythematosus (CLE) is an autoimmune skin disease that can result in severe morbidity. Although antimalarial therapy is considered first line systemic therapy for CLE, up to 55% of patients are refractory to hydroxychloroquine. Several systemic agents have been studied individually for recalcitrant CLE; however, no study examines the overall treatment experience of refractory CLE. Using the NYU and Partners Healthcare electronic medical records, we conducted a retrospective review to identify patients with refractory CLE (695.4, ICD-9) seen at 3 tertiary care centers from 2005 to 2015. We identified 46 patients with CLE refractory to at least one antimalarial medication. Treatment outcomes were based on review of clinical examination, patient symptoms, and photographs when available. Mean age at diagnosis was 36.1 years; 87% were female. 27% (n¼12) had disease limited to the head and neck, and 73% (n¼32) had generalized disease. Systemic agents used for refractory CLE included methotrexate, mycophenolate mofetil, thalidomide, lenalidomide, belimumab, prednisone, rituximab, and dapsone. Thalidomide demonstrated the greatest efficacy with 4 out of 5 patients experiencing >50% improvement. Five out of 11 patients on methotrexate, 4 out of 11 on dapsone, and 3 out of 9 on belimumab experienced >50% improvement. Other medications had lower rates of success. Overall, cutaneous disease not responsive to antimalarial agents was recalcitrant to subsequent immunomodulatory therapy. This pilot study represents the largest to date describing treatment alternatives in aggregate for antimalarialresistant CLE. Additional study is needed to delineate an appropriate therapeutic algorithm for antimalarial-refractory CLE.
Trends of skin cancer incidence following transplantation in the United States GL Garrett and ST Arron UCSF, San Francisco, CA Population-based data on skin cancer incidence post-transplantation is limited. The Transplant Skin Cancer Network (TSCN) was created in 2014 with seed funding by the American Academy of Dermatology. The TSCN Incidence Study is the first US population-based study investigating post-transplant skin cancer outcomes. Our aim was to assemble a 25-center population-based cohort based on the OPTN database, which lists all US transplants, and dermatologic data from chart review. We included all primary solid organ transplants in the US received between January 1st 2003 and December 31st 2003 or January 1st 2008 and December 31st 2008 at participating sites. We analyzed patient demographics and calculated the incidence rate (IR) and the crude incidence of overall skin cancer, squamous cell carcinoma (SCC), melanoma, and Merkel cell carcinoma (MCC). 25 transplant centers participated in the study. Of 10,411 primary transplants identified, 46% occurred in 2003 and 53% occurred in 2008. The majority of patients were 50 years of age or older (56%), males (64%), white (68%), and kidney transplant recipients (48%). We had complete skin cancer outcome data on 70% of patients. 909 skin cancer cases occurred over a total person time of 5.9x104 years, for an incidence rate (IR) of 1518.0 per 100,000 person years (95% CI 1421.4 1621.1). Of these, 839 (8.1%) were SCC, 115 (1.1%) were melanoma, and 4 (0.1%) were MCC. The predictors of post-transplant skin cancer were male sex (HR 1.64, 95% CI 1.40 1.92), age of 50 or older (HR 2.93, 95% CI 2.45 e 3.51), thoracic transplant (HR 1.38, 95% CI 1.18 - 1.60), and white race (HR 7.38, 95% CI 5.28 - 10.31). The predictors of missing outcome data were white race, being transplanted in 2008 vs. 2003, and transplant center. Methods to investigate missing data are in progress. Complete analysis of these data will be able to investigate more detailed race- and organ-specific risk factors, define the stratified IR of SCC, MM, and MCC, determine the mortality rate of skin cancer, and highlight the predictors of skin cancer incidence and mortality.
www.jidonline.org S31