- Email: [email protected]
To compare the sensitivity pattern of direct immunofluorescence of perilesional skin and plucked hair in pemphigus vulgaris
4586
5797
Time to rebound in joint symptoms following discontinuation of TNFi therapy after achieving low disease activity in psoriatic arthritis patients enrolled in the US Corrona Registry Leslie R. Harrold, MD, University of Massachusetts; Brad Stolshek, PharmD, Amgen; Sabrina Rebello, MPH, Corrona, LLC; David Collier, MD, Amgen; Alex Mutebi, PhD, Amgen; Sally W. Wade, MPH, Wade Outcomes Research and Consulting; Jeffery D. Greenberg, MD, Corrona. LLC; Carol J. Etzel, PhD, Corrona, LLC Background: The treatment goal for patients (pts) with psoriatic arthritis (PsA) is to suppress disease activity. Little is known about clinical outcomes in pts who stop TNFi therapy after achieving low disease activity (LDA) during routine care. Objectives: We evaluated time to rebound (ie, increase in joint symptoms after therapy discontinuation) in pts with PsA who achieved LDA prior to stopping TNFi therapy as well as changes in measures of disease activity at the first visit following TNFi discontinuation. Methods: In the Corrona registry, we identified pts with PsA who initiated a TNFi (adalimumab, etanercept, infliximab, golimumab), achieved LDA based on Clinical Disease Activity Index (CDAI) # 10 on TNFi therapy, discontinued TNFi altogether while still in LDA (persistence on conventional disease modifying medication was allowed) and had at least 1 follow-up visit while off TNFi. Demographic and clinical characteristics were assessed at discontinuation date (index date). To assess time to rebound, pts were followed until earliest of the following events: rebound of symptoms (CDAI [ 10), initiation of another biologic/small molecule or last followup visit. Kaplan-Meier curves were generated for time to rebound (CDAI [ 10). To assess impact of TNFi discontinuation, change in disease activity measures including CDAI, modified Health Assessment Questionnaire (mHAQ), pt and physician global assessments of disease activity or severity, and pt pain were assessed between discontinuation and first post-index visit. Results: There were 94 pts (57% female, 51% biologic-experienced at TNFi initiation) who met study criteria. At TNFi discontinuation, mean (standard deviation [SD]) age and disease duration were 52.6 (12.7) and 9.8 (7.4) years, respectively. Over time, 67 (73%) pts had a rebound in symptoms, with median time to rebound of 8 months (95% CI 6-12). At first post-index visit, there was a significant (p # 0.01) mean [SD] increase (worsening) in CDAI (3.2 [6.9]), physician (4.8 [15.4]) and pt (6.5 [23.7]) global assessments and pt pain (5.6 [20.7]) but not mHAQ (0.03 [0.26]). Conclusions: Rebound of symptoms in PsA patients occurred frequently with the majority of patients having worsening of disease activity by the next visit after TNFi discontinuation. These results suggest careful consideration before stopping these agents after achievement of low disease activity.
To compare the sensitivity pattern of direct immunofluorescence of perilesional skin and plucked hair in pemphigus vulgaris Ghazala Butt, King Edward Medical University Mayo Hospital Lahore
Commercial support: This study is sponsored by Corrona, LLC. The Corrona RA registry has been supported through contracted subscriptions in the last two years by AbbVie, Amgen, BMS, Crescendo, Genentech, Horizon Pharma USA, Janssen, Eli Lilly, Novartis, Pfizer, and UCB.
Pemphigus vulgaris is an autoimmune intraepidermal blistering disease of skin and mucous membranes in which autoantibodies are formed against desmoglein 3 and 1. The major histopathological features is acantholysis, disruption of normal cell-cell adhesion, which leads to intraepidermal blister formation. Blisters are thin walled, flaccid which rupture easily leaving slow healing erosions. Most patients with pemphigus vulgaris demonstrate IgG autoantibodies directed against antigens located on surface of keratinocytes which is demonstrated through direct immunofluorescence of plucked hair. Because the outer root sheath (ORS) of anagen hair is structurally analogous to epidermal keratinocytes, pemphigus vulgaris specific patter of IF may be seen in plucked hair too. Direct immunofluorescence is a histochemical staining lab technique for demonstrating presence of antibodies bound to antigens in tissue & ORS of plucked hair. The principle of this technique is that when fluorochrome dyes are exposed to UV light, they emit fluorescent radiation, color of these dyes depend upon the fluorochrome used. These dyes are then conjugated to protein and subsequently added to tissue sections. The position of proteins can be observed microscopically by the fluorescence they emit under illumination with UV light. The fluorochrome used widely is FITC which emits a yellow green fluorescence. The study was conducted at Dermatology Department, Mayo Hospital, Lahore. It was an experimental study with purposive sampling technique. 20 patients belonging to either sex, of age 12 to 65 years and histopathologically diagnosed as pemphigus vulgaris were enrolled. Patients of pemphigus vulgaris on long term treatment or in remission were excluded from the study. skin biopsy specimen were taken from the perilesional skin, wrapped in saline moistened gauze and then placed in a cryostat. Sections were made and applied to the glass slide, rinsed in the phosphate buffered saline and overlaid in moist chamber with FITC conjugate for 30 minutes for 378C, then washed in PBS 3 times, 10 minutes each. Sections were air-dried and then after putting a drop of buffered glycerin, were examined under fluorescence microscope. Hairs were plucked in a similar fashion to that of trichogram. Approximately 5 anagen hairs per patient were selected, processed and stained with fluorescein isothiocyanate (FITC) conjugates for DIF in order to detect immunoglobulin G and C3. Interpretation of immunofluorescence was done depending upon the site of deposition, type of immunoreactants and the number of immunoreactants. Data were recorded in a proforma. Statistical analysis was done using SPSS version14. Among 20 patients included in study, 15 were male and rest of them were females. IgG autoantibodies were seen against the cell surface of keratinocytes in all he 20 patients(100%).This autoantibody was also seen in the outer root sheath of the hair.50% of the patients showed C3 autoantibodies and 30%IgA and IgM autoantibodies both on the surface of keratinocytes as well as on the outer root sheath of hair follicles. We conclude that diagnosis of pemphigus vulgaris patients can be done using plucked hair as specific autoantibodies are seen on the outer root sheath of the hairs on direct immunofluorescence. So early diagnosis can be made and further treatment of the patients of pemphigus vulgaris can be started, thereby benefitting the patient both in treatment response and improving the prognosis of the patient. Commercial support: None identified.
4840 Time-lapse total body photography followed by dermoscopy improves melanoma outcomes in a private practice setting Rebecca Sarac, BS, Tulane University School of Medicine; Elizabeth Drugge Hobbs, PhD, New York Medical College Introduction: The persistent increase in the incidence and mortality of cutaneous melanoma in the US drives the search for early detection strategies. Total body photography (TBP) and dermoscopy are techniques that increase the diagnostic accuracy of secondary screening measures. However, integration of combined approaches remains a challenge. To our knowledge, no general dermatology clinics routinely use TBP with dermoscopy or, more specifically, sequential time-lapse TBP image-to-image comparison plus dermoscopy when evaluating lesions. We hypothesize that melanomas detected using this technique will yield thinner (Breslow thickness) lesions than those detected without time-lapse image comparison. Methods: A retrospective chart review was performed to determine the quantity of pathology-confirmed melanoma diagnoses and the utilization of TBP in patients over a two-year period (July, 2014 - June, 2016). Re-excisions and recurrent lesions were excluded. Patients were determined to have undergone TBP at least twice or not at all prior to the biopsy date. After successive TBP image capture, a semi-automated animation technology was used to register and scale sequential images. New or changed lesions were identified by flickering between the image sets. Digital dermoscopy was used for all cases. Results: 96 primary melanomas were identified in 81 patients. The melanoma in situ (MIS):invasive melanoma (INV) ratio was 1.29 (54 MIS, 42 INV), and the median thickness of INV was 0.33 mm (range, 0.11, 3.5). 77 melanomas were diagnosed in patients who underwent time-lapse TBP, and 19 melanomas were detected without the use of TBP. The MIS:INV ratios were 1.66 (48 MIS, 29 INV) and 0.46 (6 MIS, 13 INV), respectively (P ¼ .015). Melanomas detected in the TBP group were more likely to result in MIS than INV (OR 3.55, P ¼ .021, 95% CI: 1.207, 10.461) after adjusting for age and gender. The median thicknesses of INV were 0.29 mm (range, 0.12, 1.15) for the TBP group and 0.65 mm (range, 0.11, 3.5) for the group without TBP (P ¼ .0005). Conclusions: TBP with time-lapse image comparison followed by dermoscopy resulted in an increased MIS:INV ratio and a decreased Breslow thickness compared to melanomas identified without TBP and dermoscopy. This technique enhances melanoma screening and may detect melanoma at the earliest and most treatable stage. Commercial support: None identified.
AB260
J AM ACAD DERMATOL
JUNE 2017
5797
Time to rebound in joint symptoms following discontinuation of TNFi therapy after achieving low disease activity in psoriatic arthritis patients enrolled in the US Corrona Registry Leslie R. Harrold, MD, University of Massachusetts; Brad Stolshek, PharmD, Amgen; Sabrina Rebello, MPH, Corrona, LLC; David Collier, MD, Amgen; Alex Mutebi, PhD, Amgen; Sally W. Wade, MPH, Wade Outcomes Research and Consulting; Jeffery D. Greenberg, MD, Corrona. LLC; Carol J. Etzel, PhD, Corrona, LLC Background: The treatment goal for patients (pts) with psoriatic arthritis (PsA) is to suppress disease activity. Little is known about clinical outcomes in pts who stop TNFi therapy after achieving low disease activity (LDA) during routine care. Objectives: We evaluated time to rebound (ie, increase in joint symptoms after therapy discontinuation) in pts with PsA who achieved LDA prior to stopping TNFi therapy as well as changes in measures of disease activity at the first visit following TNFi discontinuation. Methods: In the Corrona registry, we identified pts with PsA who initiated a TNFi (adalimumab, etanercept, infliximab, golimumab), achieved LDA based on Clinical Disease Activity Index (CDAI) # 10 on TNFi therapy, discontinued TNFi altogether while still in LDA (persistence on conventional disease modifying medication was allowed) and had at least 1 follow-up visit while off TNFi. Demographic and clinical characteristics were assessed at discontinuation date (index date). To assess time to rebound, pts were followed until earliest of the following events: rebound of symptoms (CDAI [ 10), initiation of another biologic/small molecule or last followup visit. Kaplan-Meier curves were generated for time to rebound (CDAI [ 10). To assess impact of TNFi discontinuation, change in disease activity measures including CDAI, modified Health Assessment Questionnaire (mHAQ), pt and physician global assessments of disease activity or severity, and pt pain were assessed between discontinuation and first post-index visit. Results: There were 94 pts (57% female, 51% biologic-experienced at TNFi initiation) who met study criteria. At TNFi discontinuation, mean (standard deviation [SD]) age and disease duration were 52.6 (12.7) and 9.8 (7.4) years, respectively. Over time, 67 (73%) pts had a rebound in symptoms, with median time to rebound of 8 months (95% CI 6-12). At first post-index visit, there was a significant (p # 0.01) mean [SD] increase (worsening) in CDAI (3.2 [6.9]), physician (4.8 [15.4]) and pt (6.5 [23.7]) global assessments and pt pain (5.6 [20.7]) but not mHAQ (0.03 [0.26]). Conclusions: Rebound of symptoms in PsA patients occurred frequently with the majority of patients having worsening of disease activity by the next visit after TNFi discontinuation. These results suggest careful consideration before stopping these agents after achievement of low disease activity.
To compare the sensitivity pattern of direct immunofluorescence of perilesional skin and plucked hair in pemphigus vulgaris Ghazala Butt, King Edward Medical University Mayo Hospital Lahore
Commercial support: This study is sponsored by Corrona, LLC. The Corrona RA registry has been supported through contracted subscriptions in the last two years by AbbVie, Amgen, BMS, Crescendo, Genentech, Horizon Pharma USA, Janssen, Eli Lilly, Novartis, Pfizer, and UCB.
Pemphigus vulgaris is an autoimmune intraepidermal blistering disease of skin and mucous membranes in which autoantibodies are formed against desmoglein 3 and 1. The major histopathological features is acantholysis, disruption of normal cell-cell adhesion, which leads to intraepidermal blister formation. Blisters are thin walled, flaccid which rupture easily leaving slow healing erosions. Most patients with pemphigus vulgaris demonstrate IgG autoantibodies directed against antigens located on surface of keratinocytes which is demonstrated through direct immunofluorescence of plucked hair. Because the outer root sheath (ORS) of anagen hair is structurally analogous to epidermal keratinocytes, pemphigus vulgaris specific patter of IF may be seen in plucked hair too. Direct immunofluorescence is a histochemical staining lab technique for demonstrating presence of antibodies bound to antigens in tissue & ORS of plucked hair. The principle of this technique is that when fluorochrome dyes are exposed to UV light, they emit fluorescent radiation, color of these dyes depend upon the fluorochrome used. These dyes are then conjugated to protein and subsequently added to tissue sections. The position of proteins can be observed microscopically by the fluorescence they emit under illumination with UV light. The fluorochrome used widely is FITC which emits a yellow green fluorescence. The study was conducted at Dermatology Department, Mayo Hospital, Lahore. It was an experimental study with purposive sampling technique. 20 patients belonging to either sex, of age 12 to 65 years and histopathologically diagnosed as pemphigus vulgaris were enrolled. Patients of pemphigus vulgaris on long term treatment or in remission were excluded from the study. skin biopsy specimen were taken from the perilesional skin, wrapped in saline moistened gauze and then placed in a cryostat. Sections were made and applied to the glass slide, rinsed in the phosphate buffered saline and overlaid in moist chamber with FITC conjugate for 30 minutes for 378C, then washed in PBS 3 times, 10 minutes each. Sections were air-dried and then after putting a drop of buffered glycerin, were examined under fluorescence microscope. Hairs were plucked in a similar fashion to that of trichogram. Approximately 5 anagen hairs per patient were selected, processed and stained with fluorescein isothiocyanate (FITC) conjugates for DIF in order to detect immunoglobulin G and C3. Interpretation of immunofluorescence was done depending upon the site of deposition, type of immunoreactants and the number of immunoreactants. Data were recorded in a proforma. Statistical analysis was done using SPSS version14. Among 20 patients included in study, 15 were male and rest of them were females. IgG autoantibodies were seen against the cell surface of keratinocytes in all he 20 patients(100%).This autoantibody was also seen in the outer root sheath of the hair.50% of the patients showed C3 autoantibodies and 30%IgA and IgM autoantibodies both on the surface of keratinocytes as well as on the outer root sheath of hair follicles. We conclude that diagnosis of pemphigus vulgaris patients can be done using plucked hair as specific autoantibodies are seen on the outer root sheath of the hairs on direct immunofluorescence. So early diagnosis can be made and further treatment of the patients of pemphigus vulgaris can be started, thereby benefitting the patient both in treatment response and improving the prognosis of the patient. Commercial support: None identified.
4840 Time-lapse total body photography followed by dermoscopy improves melanoma outcomes in a private practice setting Rebecca Sarac, BS, Tulane University School of Medicine; Elizabeth Drugge Hobbs, PhD, New York Medical College Introduction: The persistent increase in the incidence and mortality of cutaneous melanoma in the US drives the search for early detection strategies. Total body photography (TBP) and dermoscopy are techniques that increase the diagnostic accuracy of secondary screening measures. However, integration of combined approaches remains a challenge. To our knowledge, no general dermatology clinics routinely use TBP with dermoscopy or, more specifically, sequential time-lapse TBP image-to-image comparison plus dermoscopy when evaluating lesions. We hypothesize that melanomas detected using this technique will yield thinner (Breslow thickness) lesions than those detected without time-lapse image comparison. Methods: A retrospective chart review was performed to determine the quantity of pathology-confirmed melanoma diagnoses and the utilization of TBP in patients over a two-year period (July, 2014 - June, 2016). Re-excisions and recurrent lesions were excluded. Patients were determined to have undergone TBP at least twice or not at all prior to the biopsy date. After successive TBP image capture, a semi-automated animation technology was used to register and scale sequential images. New or changed lesions were identified by flickering between the image sets. Digital dermoscopy was used for all cases. Results: 96 primary melanomas were identified in 81 patients. The melanoma in situ (MIS):invasive melanoma (INV) ratio was 1.29 (54 MIS, 42 INV), and the median thickness of INV was 0.33 mm (range, 0.11, 3.5). 77 melanomas were diagnosed in patients who underwent time-lapse TBP, and 19 melanomas were detected without the use of TBP. The MIS:INV ratios were 1.66 (48 MIS, 29 INV) and 0.46 (6 MIS, 13 INV), respectively (P ¼ .015). Melanomas detected in the TBP group were more likely to result in MIS than INV (OR 3.55, P ¼ .021, 95% CI: 1.207, 10.461) after adjusting for age and gender. The median thicknesses of INV were 0.29 mm (range, 0.12, 1.15) for the TBP group and 0.65 mm (range, 0.11, 3.5) for the group without TBP (P ¼ .0005). Conclusions: TBP with time-lapse image comparison followed by dermoscopy resulted in an increased MIS:INV ratio and a decreased Breslow thickness compared to melanomas identified without TBP and dermoscopy. This technique enhances melanoma screening and may detect melanoma at the earliest and most treatable stage. Commercial support: None identified.
AB260
J AM ACAD DERMATOL
JUNE 2017