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Overview of adverse cardiovascular events in the brodalumab psoriasis studies
5524
5600 Orbital and epidural extension of a locally advanced basal cell carcinoma Michael Abrouk, BS, UC Irvine School of Medicine; Suchismita Paul, MD, University of Miami Department of Dermatology & Cutaneous Surgery; Jennifer Abrahams, MD, University of Miami Department of Dermatology & Cutaneous Surgery; Scott Lindsey, MD, University of Miami Department of Dermatology & Cutaneous Surgery; Antonella Tosti, MD, University of Miami Department of Dermatology & Cutaneous Surgery Article: Advanced basal cell carcinomas (BCC) are a subset of BCCs that can be difficult to treat given their location, extent of involvement, and proximity to vital structures. We report a case of advanced BCC with local advancement into the orbit, sinuses and anterior cranial fossa resulting in unilateral blindness. We believe this case demonstrates the difficulty in management and treatment consideration for patients with advanced BCC. Report of Case: A cachectic 92-year-old female with a prior history of BCC presented with her caretaker to the dermatology clinic for a skin check, and was found to have a 7-year history of an ulcerated lesion on her left scalp which she had been shaving down with a nail file. The patient and her caretaker reported vision loss in the right eye for an unspecified duration. Physical exam revealed large blue cribriform plaque of the left scalp, large draining nodule of right eyelid, and blue to black papule of the dorsum of the nose. The telangiectatic nodule of the right eyelid drained yellow exudate. Shave biopsies were performed, and the patient was immediately referred to the ophthalmology emergency room for further evaluation. An MRI revealed a 5.7 cm 3 3.3 cm 3 3.7 cm mass involving the entire nasal cavity with extension into the ethmoid, sphenoid, frontal and maxillary sinuses. Further extension into cribriform plate, invasion of bilateral orbits, and epidural extension along the anterior cranial fossa was also visualized. Biopsy results revealed a pigmented BCC of the left scalp, nodular BCC of the right eyelid, and pigmented and nodular BCC of the nose. Figures Figure 1. Clinical Presentation Figure 2. MRI orbits and CT sinuses. Discussion: Orbital invasion of locally advanced BCC can permanently compromise vision and is potentially life threatening, often requiring multidisciplinary management. The management of these patients can be difficult when considering the extent of involvement, patient age, and quality of life. There are few treatments available for the locally advanced case presented in this clinical vignette, given that she is a poor surgical candidate. Vismodegib and sonodegib are recently approved oral medications targeting the hedgehog signaling pathway for the treatment of locally advanced and metastatic BCC. Furthermore, vismodegib has demonstrated efficacy in the treatment BCCs with orbital involvement. However, in managing these patients it is important to consider the overall clinical picture and treatment goals. While the side effect profile of vismodegib is relatively well tolerated, dysgeusia and nausea in an already cachectic nonagenarian may not provide the best quality of life. It is important to consider patient wishes in determining the treatment plan of patients with advanced BCC, including palliative care. While therapy targeting the hedgehog signaling pathway is promising for patients with advanced BCC, it is not always an option for certain patients.
Pachydermatous eosinophilic dermatitis Miguel Villacorta, DO, Broward Health Medical Center & Nova Southeastern University; June Kunapareddy, DO, Broward Health Medical Center & Nova Southeastern University; Trevor Batty, DO, Broward Health Medical Center & Nova Southeastern University; Carlos Cohen, MD, Adult & Pediatric Dermatology of South Florida Pachydermatous eosinophilic dermatitis was first described in 1996 by Jacyk et al. Only two case reports with 4 patients have been described in the medical literature. It is an extremely rare eosinophilic dermatitis which clinically presents with pruritic papules and nodules on rough and thick pachydermatous skin. Lesions are typically seen on distal extremities and on the genitalia. Eosinophilic rich dermal superficial infiltrate with lichenification and small vessel proliferation, ectasia, and dermal fibrosis is seen on histology. Patients show elevated levels of peripheral eosinophilia, leukocytosis, and IgE levels. We report a case of 55-year-old Hispanic female with a past skin history significant for sensitive skin and asthma as a child now presents with a pruritic rash that has been present for about one year. Upon presentation to our clinic she was using topical steroids and oral antihistamines. A prior biopsy showed lichen simplex chronicus. On examination the patient presented with mostly acral flat topped confluent papules and plaques resembling pachydermatous skin on her bilateral upper and lower extremities with palmoplantar hyperkeratosis. Laboratory workup showed eosinophilia and elevated IgE. Initially the patient was continued on prior treatments with the addition of narrow band UVB. After several phototherapy treatments mild improvement was noted, which prompted an additional biopsy showing an eosinophilic infiltrate in the superficial dermis with lichenification. Subsequently, the patient was started on prednisone in conjunction with phototherapy with marked clinical improvement of plaque thickness and pruritus. Although some of the features displayed by our patient may represent a peculiar form of adult-onset atopic dermatitis, we do believe the patient presented herein displays enough distinctive clinical and pathological features that meet the original description of pachydermatous eosinophilic dermatitis. This case highlights the need to differentiate pachydermatous eosinophilic dermatitis from other hypereosinophilic disorders and chronic atopic dermatitis. Commercial support: None identified.
Commercial support: None identified.
4758 Overview of adverse cardiovascular events in the brodalumab psoriasis studies Bruce Strober, MD, University of Connecticut Health Center; Lawrence F. Eichenfield, MD, University of California; April Armstrong, MD, University of Southern California; Alice Gottlieb, MD, New York Medical College; Kenneth B. Gordon, MD, Northwestern University Feinberg School of Medicine; Tina Lin, Valeant Pharmaceuticals North America LLC; Robert Israel, MD, Valeant Pharmaceuticals North America LLC Background: Psoriasis is associated with increased cardiovascular (CV) risk factors and events. The efficacy and safety of brodalumab (140 or 210 mg q2w), an IL-17RA antagonist, were studied in a phase 2 trial and 3 phase 3 large, multicenter, randomized trials of patients with moderate-to-severe plaque psoriasis (AMAGINE-1/-2/-3). Cardiovascular events, including major adverse cardiac events (MACE), were analyzed in these studies. Methods: Cardiovascular events were grouped as ischemic cerebrovascular disease (ICVD) and ischemic heart disease (ISHD) Standardised MedDRA Queries (SMQ). Occurrence of MACE (CV death, myocardial infarction [MI], or stroke) was prospectively evaluated and adjudicated in the phase 3 studies. The 12-week data (summarized as patient incidence) allowed direct randomized comparisons of brodalumab with placebo and ustekinumab. Data from the 52-week and long-term pools were summarized as exposureadjusted rates (events per 100 patient-years [py] and 95% confidence intervals [CIs]). Results: In the psoriasis studies, 4464 patients had a total of 8655 py of brodalumab exposure, 92% of whom received $1 dose of brodalumab 210 mg. Approximately 88% of patients were on brodalumab 210 mg by week 52. Eighty-three percent of brodalumabexposed patients had $1 CV risk factor at baseline. In the 12-week placebo-controlled period, low numbers of CV events were reported and there were no imbalances among the placebo, ustekinumab, and brodalumab groups in either SMQ. There was no indication of a dose dependency in the brodalumab groups. At week 52, exposureadjusted rates of ICVD (brodalumab, 0.2; 7 events vs ustekinumab, 0.2; 1 event) and ISHD (brodalumab, 1.2; 40 events vs ustekinumab, 1.0; 5 events) were comparable between treatment groups. There were 3 occurrences of MACE in the brodalumab 140 mg group at 12 weeks (2 MIs, 1 stroke). Exposure-adjusted rates of MACE in the brodalumab and ustekinumab groups at 52 weeks were similar with overlapping CIs (0.6 [0.37, 0.94]; 20 events vs 0.4 [0.05, 1.46]; 2 events) and remained stable with brodalumab (0.5 [0.36, 0.69]; 40 events) in the long-term analysis. No notable temporal trends were observed; a time-to-event analysis showed that rates of MACE over time were constant. Most patients with reported MACE had $1 CV risk factor and additional comorbidities. Conclusions: The results suggest no increased CV risk associated with brodalumab treatment beyond the potential underlying risk with psoriasis. Commercial support: This study was sponsored by Amgen Inc. Medical writing support was provided by MedThink SciCom and funded by Valeant Pharmaceuticals North America LLC.
AB186
J AM ACAD DERMATOL
5100 Pancreatic panniculitis mimicking necrotizing fasciitis Kyle Kaltwasser, MD, University of Texas Medical Branch; Cedar H. Malone, MD, University of Texas Medical Branch; Brent Kelly, MD, University of Texas Medical Branch Pancreatic panniculitis is an uncommon entity that occurs in the setting of pancreatic disease. Classically pancreatic panniculitis presents as painful erythematous nodules on the lower extremities, but a rare plaque form has been described in a few case reports. Plaque type pancreatic panniculitis can mimic infectious processes such as cellulitis and necrotizing fasciitis leading to potentially devastating surgical intervention. Thus, knowledge of this unusual clinical manifestation of pancreatic disease is essential. We present a rare case of a 45-year-old Hispanic lady with biopsy proven pancreatic panniculitis with 35% total body surface area involvement that was initially concerning for necrotizing fasciitis. Commercial support: None identified.
JUNE 2017
5600 Orbital and epidural extension of a locally advanced basal cell carcinoma Michael Abrouk, BS, UC Irvine School of Medicine; Suchismita Paul, MD, University of Miami Department of Dermatology & Cutaneous Surgery; Jennifer Abrahams, MD, University of Miami Department of Dermatology & Cutaneous Surgery; Scott Lindsey, MD, University of Miami Department of Dermatology & Cutaneous Surgery; Antonella Tosti, MD, University of Miami Department of Dermatology & Cutaneous Surgery Article: Advanced basal cell carcinomas (BCC) are a subset of BCCs that can be difficult to treat given their location, extent of involvement, and proximity to vital structures. We report a case of advanced BCC with local advancement into the orbit, sinuses and anterior cranial fossa resulting in unilateral blindness. We believe this case demonstrates the difficulty in management and treatment consideration for patients with advanced BCC. Report of Case: A cachectic 92-year-old female with a prior history of BCC presented with her caretaker to the dermatology clinic for a skin check, and was found to have a 7-year history of an ulcerated lesion on her left scalp which she had been shaving down with a nail file. The patient and her caretaker reported vision loss in the right eye for an unspecified duration. Physical exam revealed large blue cribriform plaque of the left scalp, large draining nodule of right eyelid, and blue to black papule of the dorsum of the nose. The telangiectatic nodule of the right eyelid drained yellow exudate. Shave biopsies were performed, and the patient was immediately referred to the ophthalmology emergency room for further evaluation. An MRI revealed a 5.7 cm 3 3.3 cm 3 3.7 cm mass involving the entire nasal cavity with extension into the ethmoid, sphenoid, frontal and maxillary sinuses. Further extension into cribriform plate, invasion of bilateral orbits, and epidural extension along the anterior cranial fossa was also visualized. Biopsy results revealed a pigmented BCC of the left scalp, nodular BCC of the right eyelid, and pigmented and nodular BCC of the nose. Figures Figure 1. Clinical Presentation Figure 2. MRI orbits and CT sinuses. Discussion: Orbital invasion of locally advanced BCC can permanently compromise vision and is potentially life threatening, often requiring multidisciplinary management. The management of these patients can be difficult when considering the extent of involvement, patient age, and quality of life. There are few treatments available for the locally advanced case presented in this clinical vignette, given that she is a poor surgical candidate. Vismodegib and sonodegib are recently approved oral medications targeting the hedgehog signaling pathway for the treatment of locally advanced and metastatic BCC. Furthermore, vismodegib has demonstrated efficacy in the treatment BCCs with orbital involvement. However, in managing these patients it is important to consider the overall clinical picture and treatment goals. While the side effect profile of vismodegib is relatively well tolerated, dysgeusia and nausea in an already cachectic nonagenarian may not provide the best quality of life. It is important to consider patient wishes in determining the treatment plan of patients with advanced BCC, including palliative care. While therapy targeting the hedgehog signaling pathway is promising for patients with advanced BCC, it is not always an option for certain patients.
Pachydermatous eosinophilic dermatitis Miguel Villacorta, DO, Broward Health Medical Center & Nova Southeastern University; June Kunapareddy, DO, Broward Health Medical Center & Nova Southeastern University; Trevor Batty, DO, Broward Health Medical Center & Nova Southeastern University; Carlos Cohen, MD, Adult & Pediatric Dermatology of South Florida Pachydermatous eosinophilic dermatitis was first described in 1996 by Jacyk et al. Only two case reports with 4 patients have been described in the medical literature. It is an extremely rare eosinophilic dermatitis which clinically presents with pruritic papules and nodules on rough and thick pachydermatous skin. Lesions are typically seen on distal extremities and on the genitalia. Eosinophilic rich dermal superficial infiltrate with lichenification and small vessel proliferation, ectasia, and dermal fibrosis is seen on histology. Patients show elevated levels of peripheral eosinophilia, leukocytosis, and IgE levels. We report a case of 55-year-old Hispanic female with a past skin history significant for sensitive skin and asthma as a child now presents with a pruritic rash that has been present for about one year. Upon presentation to our clinic she was using topical steroids and oral antihistamines. A prior biopsy showed lichen simplex chronicus. On examination the patient presented with mostly acral flat topped confluent papules and plaques resembling pachydermatous skin on her bilateral upper and lower extremities with palmoplantar hyperkeratosis. Laboratory workup showed eosinophilia and elevated IgE. Initially the patient was continued on prior treatments with the addition of narrow band UVB. After several phototherapy treatments mild improvement was noted, which prompted an additional biopsy showing an eosinophilic infiltrate in the superficial dermis with lichenification. Subsequently, the patient was started on prednisone in conjunction with phototherapy with marked clinical improvement of plaque thickness and pruritus. Although some of the features displayed by our patient may represent a peculiar form of adult-onset atopic dermatitis, we do believe the patient presented herein displays enough distinctive clinical and pathological features that meet the original description of pachydermatous eosinophilic dermatitis. This case highlights the need to differentiate pachydermatous eosinophilic dermatitis from other hypereosinophilic disorders and chronic atopic dermatitis. Commercial support: None identified.
Commercial support: None identified.
4758 Overview of adverse cardiovascular events in the brodalumab psoriasis studies Bruce Strober, MD, University of Connecticut Health Center; Lawrence F. Eichenfield, MD, University of California; April Armstrong, MD, University of Southern California; Alice Gottlieb, MD, New York Medical College; Kenneth B. Gordon, MD, Northwestern University Feinberg School of Medicine; Tina Lin, Valeant Pharmaceuticals North America LLC; Robert Israel, MD, Valeant Pharmaceuticals North America LLC Background: Psoriasis is associated with increased cardiovascular (CV) risk factors and events. The efficacy and safety of brodalumab (140 or 210 mg q2w), an IL-17RA antagonist, were studied in a phase 2 trial and 3 phase 3 large, multicenter, randomized trials of patients with moderate-to-severe plaque psoriasis (AMAGINE-1/-2/-3). Cardiovascular events, including major adverse cardiac events (MACE), were analyzed in these studies. Methods: Cardiovascular events were grouped as ischemic cerebrovascular disease (ICVD) and ischemic heart disease (ISHD) Standardised MedDRA Queries (SMQ). Occurrence of MACE (CV death, myocardial infarction [MI], or stroke) was prospectively evaluated and adjudicated in the phase 3 studies. The 12-week data (summarized as patient incidence) allowed direct randomized comparisons of brodalumab with placebo and ustekinumab. Data from the 52-week and long-term pools were summarized as exposureadjusted rates (events per 100 patient-years [py] and 95% confidence intervals [CIs]). Results: In the psoriasis studies, 4464 patients had a total of 8655 py of brodalumab exposure, 92% of whom received $1 dose of brodalumab 210 mg. Approximately 88% of patients were on brodalumab 210 mg by week 52. Eighty-three percent of brodalumabexposed patients had $1 CV risk factor at baseline. In the 12-week placebo-controlled period, low numbers of CV events were reported and there were no imbalances among the placebo, ustekinumab, and brodalumab groups in either SMQ. There was no indication of a dose dependency in the brodalumab groups. At week 52, exposureadjusted rates of ICVD (brodalumab, 0.2; 7 events vs ustekinumab, 0.2; 1 event) and ISHD (brodalumab, 1.2; 40 events vs ustekinumab, 1.0; 5 events) were comparable between treatment groups. There were 3 occurrences of MACE in the brodalumab 140 mg group at 12 weeks (2 MIs, 1 stroke). Exposure-adjusted rates of MACE in the brodalumab and ustekinumab groups at 52 weeks were similar with overlapping CIs (0.6 [0.37, 0.94]; 20 events vs 0.4 [0.05, 1.46]; 2 events) and remained stable with brodalumab (0.5 [0.36, 0.69]; 40 events) in the long-term analysis. No notable temporal trends were observed; a time-to-event analysis showed that rates of MACE over time were constant. Most patients with reported MACE had $1 CV risk factor and additional comorbidities. Conclusions: The results suggest no increased CV risk associated with brodalumab treatment beyond the potential underlying risk with psoriasis. Commercial support: This study was sponsored by Amgen Inc. Medical writing support was provided by MedThink SciCom and funded by Valeant Pharmaceuticals North America LLC.
AB186
J AM ACAD DERMATOL
5100 Pancreatic panniculitis mimicking necrotizing fasciitis Kyle Kaltwasser, MD, University of Texas Medical Branch; Cedar H. Malone, MD, University of Texas Medical Branch; Brent Kelly, MD, University of Texas Medical Branch Pancreatic panniculitis is an uncommon entity that occurs in the setting of pancreatic disease. Classically pancreatic panniculitis presents as painful erythematous nodules on the lower extremities, but a rare plaque form has been described in a few case reports. Plaque type pancreatic panniculitis can mimic infectious processes such as cellulitis and necrotizing fasciitis leading to potentially devastating surgical intervention. Thus, knowledge of this unusual clinical manifestation of pancreatic disease is essential. We present a rare case of a 45-year-old Hispanic lady with biopsy proven pancreatic panniculitis with 35% total body surface area involvement that was initially concerning for necrotizing fasciitis. Commercial support: None identified.
JUNE 2017