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Skin-limited GVHD after pancreatic transplantation
4537
4911
Skin-limited GVHD after pancreatic transplantation Elika Hoss, MD, Mayo Clinic; David DiCaudo, MD, Mayo Clinic; PIttelkow Mark, MD, Mayo Clinic; Hasan Khamash, MD, Mayo Clinic; Amit Sharma, MD, Mayo Clinic Graft versus host disease (GVHD) is a common complication after bone marrow transplantation; GVHD, however, is rare after solid organ transplant (SOT), where it carries a very poor prognosis. We report a unique case of skin-limited GVHD after pancreatic transplantation. We report a case of a 40-year-old woman with trisomy 21 who developed an acute eruption on the hands, legs, and face 57 days after her second pancreas transplant for type 1 diabetes. Initial pancreas transplant was 12 years prior, complicated by antibody-mediated rejection. Patient received her second pancreas from a deceased male donor. She had induction with thymoglobulin and oral corticosteroids. On physical examination, there were scaly pink plaques in the periocular area, dorsum of the hands, and the lower legs. In addition, she had punctate firm hemorrhagic papules of the fingertips and palms. Two skin biopsies were performed on the different morphologies on the hands. Histopathologic evaluation of both specimens revealed scattered apoptotic keratinocytes within the epidermis, with vacuolization at the dermal-epidermal junction. There was a dense superficial to mid dermal lymphocytic infiltrate, with some scattered eosinophils. Additional finding of hemorrhage was seen in specimen from the fingertip. Findings were consistent with lichenoid tissue reaction, and thus raised concern for lichenoid GVHD. Fluorescence in situ hybridization (FISH) testing for chromosomes X and Y found the lymphocytes as XY, while the surrounding normal tissue was XX, indicating that the inflammatory infiltrate was primarily of male (donor) origin, confirming the diagnosis of GVHD. Chimerism analysis on the peripheral blood showed approximately 100% of CD3-positive T-cells and CD33positive myeloid cells to be recipient DNA, and approximately 0% donor DNA. Patient was diagnosed with cutaneous GVHD and improved with use of topical corticosteroids. Routine laboratory analysis, as well as EGD and colonoscopy revealed no other organ involvement with GVHD. Unfortunately, patient subsequently developed recalcitrant post-transplant lymphoproliferative disease of the CNS and passed away. To our knowledge, this is the first case of skin-limited GVHD after SOT. GVHD is a rare, but devastating complication of SOT. Given the poor prognosis, it is important for dermatologists to be suspicious for this rare, but devastating complication of SOT, when evaluating patients in the early posttransplant period for a rash.
SNA-001-mediated selective thermolysis of the pilosebaceous unit: An innovative approach to the treatment of common dermatologic conditions Paul F. Lizzul, MD, Sienna Biopharmaceuticals; Edward T. Castellana, PhD, Sienna Biopharmaceuticals; Todd J. Harris, PhD, Sienna Biopharmaceuticals
Commercial support: None identified.
SNA-001, a suspension of ultra-efficient light absorbing silver particles, is in clinical development as a topical accessory to laser therapy for acne and permanent reduction of unwanted light-pigmented hair (LPH). Laser therapy is increasingly used for common dermatologic conditions, including acne and permanent hair reduction; however, effectiveness is limited by lack of an efficient targeted endogenous chromophore or pigment for facilitating thermal injury to the pilosebaceous unit (PSU). We describe SNA-001, its physical properties, proposed mechanism of action, and clinical implications for treatment of acne and unwanted LPH. SNA-001 silver particles are non-cytotoxic to human skin and do not penetrate the epithelial barrier, making them a safe and efficient exogenous pigment. Particles (ie, nanoplates) are tuned (size, shape) to precisely match the wavelength (WL) of commonly used lasers (755 nm, 810 nm, 1064 nm). Data from weight-normalized absorbance studies, show that SNA-001 absorbs near-infrared light energy more efficiently than gold nanoshells and melanin. Highly selective localized rapid heating is facilitated through the plasmonic resonance-based absorbance and photothermal conversion of laser energy by SNA-001. Studies using porcine skin found that SNA001 can be delivered into the PSU (including the sebaceous gland) up to 1 mm in depth using mechanical vibration. Our research has shown that SNA-001 is an ultraefficient near-infrared light absorber with tunable absorption based on silver particles that resonate at these near-infrared WLs, producing photothermal heat. Delivery of silver particles into PSUs enable targeted local destruction of sebaceous glands and hair follicles. This has implications for the treatment of acne and permanent reduction of LPH. Currently, laser therapy alone targets iron/hemoglobin present in inflammatory acne lesions rather than specifically the sebaceous gland. Therefore, laser therapy has minimal effect on normal, non-inflamed follicles, which can develop into new acne lesions. SNA-001 plus laser may reduce future acne lesions. For permanent hair reduction, the target of laser therapy is melanin; therefore, it is ineffective for LPH. Feasibility studies using SNA-001-mediated selective thermolysis for moderate to severe acne and permanent reduction of LPH suggest it may be efficacious; results of large controlled trials are awaited. Commercial support: This study was sponsored by Sienna Biopharmaceuticals.
5400 SLNB in cutaneous SCC: A review of the current state of literature and the direction for the future Omeed Ahadiat, BS, Keck Medicine of USC; Ashley Wysong, MD, Keck Medicine at USC; Shauna Higgins, MD, Keck Medicine at USC; Alexandre Ly, RN, Keck Medicine at USC The concept of the sentinel lymph node biopsy (SLNB) has been universally accepted for melanoma skin cancer, however, remains relatively controversial for other types of skin cancer, including squamous cell carcinoma (SCC). The cases that have gathered the most attention are SCCs that contain particular features deemed to place the tumor at a higher risk of metastasis. These features have been debated in literature and include clinical, histologic, and patient-specific factors. No clear criteria for the use of SLNB in high risk SCC has been defined to date. We performed a quantitative systematic review of all cases of SLNB in cutaneous SCC using PubMed and keywords ‘‘SLNB’’ and ‘‘SCC’’. A total of 364 cases of high risk SCC that had a SLNB were found. The positivity rate was calculated to be approximately 13.4 %, a number within very close range of the positivity rate in sentinel lymph nodes of melanoma in literature. In addition, the literature was qualitatively reviewed to determine whether a positive SLNB has any bearing on prognosis in high risk SCC cases. All cases were followed to compare SLNB negative to SLNB positive cases. The conclusion of these studies revealed a statistically significant relationship between a poor prognosis and a positive SLN in comparison to a negative SLN (P ¼ .0082). Given the recent developments in literature we point out recommendations for future studies on the topic. We conclude that SLNB is likely underutilized in high risk SCC and is definitely a management option to consider with every case of high risk SCC. Commercial support: None identified.
AB238
J AM ACAD DERMATOL
5266 Sneddon’s syndrome—A diagnostic and therapeutic challenge Olivia Lai, MD, Eisenhower Medical Center; Detlef Zillikens, MD, University of L€ ubeck; Iakov Shimanovich, MD, University of L€ ubeck A 49-year-old female presented with a four-hour history of ataxia and left-sided hemidysesthesia. A generalized, irregular, violaceous, net-like skin pattern was noted. The young patient had suffered five strokes over the last six years. In the past, despite extensive workup, no diagnosis had been made. Antinuclear and antiphospholipid antibodies were negative, and no evidence of thrombophilia was found. Magnetic resonance imaging showed acute dot-like diffusion anomalies in the medial and posterior cerebral artery-supplied areas as well as old stroke residues. Skin biopsy revealed occlusion of arteries at the dermal-subcutaneous tissue interface by subintimal proliferation of smooth muscle actin-positive cells. We diagnosed the patient with Sneddon’s syndrome (SS), a rare vasculopathy characterized by the combination of cerebrovascular disease with livedo racemosa. Controversy exists over whether anticoagulation or immunosuppression is the optimal therapy for SS. Our patient was put on a therapeutic dose of enoxaparin, but suffered a new left-sided stroke one week later. Subsequently, pulsed cyclophosphamide was added to the treatment regimen. She has not had any new strokes since. Our case demonstrates that a combination of generalized livedo racemosa and stroke should always prompt a consideration of SS, as its early diagnosis is essential to prevent further neurologic damage. Commercial support: None identified.
JUNE 2017
4911
Skin-limited GVHD after pancreatic transplantation Elika Hoss, MD, Mayo Clinic; David DiCaudo, MD, Mayo Clinic; PIttelkow Mark, MD, Mayo Clinic; Hasan Khamash, MD, Mayo Clinic; Amit Sharma, MD, Mayo Clinic Graft versus host disease (GVHD) is a common complication after bone marrow transplantation; GVHD, however, is rare after solid organ transplant (SOT), where it carries a very poor prognosis. We report a unique case of skin-limited GVHD after pancreatic transplantation. We report a case of a 40-year-old woman with trisomy 21 who developed an acute eruption on the hands, legs, and face 57 days after her second pancreas transplant for type 1 diabetes. Initial pancreas transplant was 12 years prior, complicated by antibody-mediated rejection. Patient received her second pancreas from a deceased male donor. She had induction with thymoglobulin and oral corticosteroids. On physical examination, there were scaly pink plaques in the periocular area, dorsum of the hands, and the lower legs. In addition, she had punctate firm hemorrhagic papules of the fingertips and palms. Two skin biopsies were performed on the different morphologies on the hands. Histopathologic evaluation of both specimens revealed scattered apoptotic keratinocytes within the epidermis, with vacuolization at the dermal-epidermal junction. There was a dense superficial to mid dermal lymphocytic infiltrate, with some scattered eosinophils. Additional finding of hemorrhage was seen in specimen from the fingertip. Findings were consistent with lichenoid tissue reaction, and thus raised concern for lichenoid GVHD. Fluorescence in situ hybridization (FISH) testing for chromosomes X and Y found the lymphocytes as XY, while the surrounding normal tissue was XX, indicating that the inflammatory infiltrate was primarily of male (donor) origin, confirming the diagnosis of GVHD. Chimerism analysis on the peripheral blood showed approximately 100% of CD3-positive T-cells and CD33positive myeloid cells to be recipient DNA, and approximately 0% donor DNA. Patient was diagnosed with cutaneous GVHD and improved with use of topical corticosteroids. Routine laboratory analysis, as well as EGD and colonoscopy revealed no other organ involvement with GVHD. Unfortunately, patient subsequently developed recalcitrant post-transplant lymphoproliferative disease of the CNS and passed away. To our knowledge, this is the first case of skin-limited GVHD after SOT. GVHD is a rare, but devastating complication of SOT. Given the poor prognosis, it is important for dermatologists to be suspicious for this rare, but devastating complication of SOT, when evaluating patients in the early posttransplant period for a rash.
SNA-001-mediated selective thermolysis of the pilosebaceous unit: An innovative approach to the treatment of common dermatologic conditions Paul F. Lizzul, MD, Sienna Biopharmaceuticals; Edward T. Castellana, PhD, Sienna Biopharmaceuticals; Todd J. Harris, PhD, Sienna Biopharmaceuticals
Commercial support: None identified.
SNA-001, a suspension of ultra-efficient light absorbing silver particles, is in clinical development as a topical accessory to laser therapy for acne and permanent reduction of unwanted light-pigmented hair (LPH). Laser therapy is increasingly used for common dermatologic conditions, including acne and permanent hair reduction; however, effectiveness is limited by lack of an efficient targeted endogenous chromophore or pigment for facilitating thermal injury to the pilosebaceous unit (PSU). We describe SNA-001, its physical properties, proposed mechanism of action, and clinical implications for treatment of acne and unwanted LPH. SNA-001 silver particles are non-cytotoxic to human skin and do not penetrate the epithelial barrier, making them a safe and efficient exogenous pigment. Particles (ie, nanoplates) are tuned (size, shape) to precisely match the wavelength (WL) of commonly used lasers (755 nm, 810 nm, 1064 nm). Data from weight-normalized absorbance studies, show that SNA-001 absorbs near-infrared light energy more efficiently than gold nanoshells and melanin. Highly selective localized rapid heating is facilitated through the plasmonic resonance-based absorbance and photothermal conversion of laser energy by SNA-001. Studies using porcine skin found that SNA001 can be delivered into the PSU (including the sebaceous gland) up to 1 mm in depth using mechanical vibration. Our research has shown that SNA-001 is an ultraefficient near-infrared light absorber with tunable absorption based on silver particles that resonate at these near-infrared WLs, producing photothermal heat. Delivery of silver particles into PSUs enable targeted local destruction of sebaceous glands and hair follicles. This has implications for the treatment of acne and permanent reduction of LPH. Currently, laser therapy alone targets iron/hemoglobin present in inflammatory acne lesions rather than specifically the sebaceous gland. Therefore, laser therapy has minimal effect on normal, non-inflamed follicles, which can develop into new acne lesions. SNA-001 plus laser may reduce future acne lesions. For permanent hair reduction, the target of laser therapy is melanin; therefore, it is ineffective for LPH. Feasibility studies using SNA-001-mediated selective thermolysis for moderate to severe acne and permanent reduction of LPH suggest it may be efficacious; results of large controlled trials are awaited. Commercial support: This study was sponsored by Sienna Biopharmaceuticals.
5400 SLNB in cutaneous SCC: A review of the current state of literature and the direction for the future Omeed Ahadiat, BS, Keck Medicine of USC; Ashley Wysong, MD, Keck Medicine at USC; Shauna Higgins, MD, Keck Medicine at USC; Alexandre Ly, RN, Keck Medicine at USC The concept of the sentinel lymph node biopsy (SLNB) has been universally accepted for melanoma skin cancer, however, remains relatively controversial for other types of skin cancer, including squamous cell carcinoma (SCC). The cases that have gathered the most attention are SCCs that contain particular features deemed to place the tumor at a higher risk of metastasis. These features have been debated in literature and include clinical, histologic, and patient-specific factors. No clear criteria for the use of SLNB in high risk SCC has been defined to date. We performed a quantitative systematic review of all cases of SLNB in cutaneous SCC using PubMed and keywords ‘‘SLNB’’ and ‘‘SCC’’. A total of 364 cases of high risk SCC that had a SLNB were found. The positivity rate was calculated to be approximately 13.4 %, a number within very close range of the positivity rate in sentinel lymph nodes of melanoma in literature. In addition, the literature was qualitatively reviewed to determine whether a positive SLNB has any bearing on prognosis in high risk SCC cases. All cases were followed to compare SLNB negative to SLNB positive cases. The conclusion of these studies revealed a statistically significant relationship between a poor prognosis and a positive SLN in comparison to a negative SLN (P ¼ .0082). Given the recent developments in literature we point out recommendations for future studies on the topic. We conclude that SLNB is likely underutilized in high risk SCC and is definitely a management option to consider with every case of high risk SCC. Commercial support: None identified.
AB238
J AM ACAD DERMATOL
5266 Sneddon’s syndrome—A diagnostic and therapeutic challenge Olivia Lai, MD, Eisenhower Medical Center; Detlef Zillikens, MD, University of L€ ubeck; Iakov Shimanovich, MD, University of L€ ubeck A 49-year-old female presented with a four-hour history of ataxia and left-sided hemidysesthesia. A generalized, irregular, violaceous, net-like skin pattern was noted. The young patient had suffered five strokes over the last six years. In the past, despite extensive workup, no diagnosis had been made. Antinuclear and antiphospholipid antibodies were negative, and no evidence of thrombophilia was found. Magnetic resonance imaging showed acute dot-like diffusion anomalies in the medial and posterior cerebral artery-supplied areas as well as old stroke residues. Skin biopsy revealed occlusion of arteries at the dermal-subcutaneous tissue interface by subintimal proliferation of smooth muscle actin-positive cells. We diagnosed the patient with Sneddon’s syndrome (SS), a rare vasculopathy characterized by the combination of cerebrovascular disease with livedo racemosa. Controversy exists over whether anticoagulation or immunosuppression is the optimal therapy for SS. Our patient was put on a therapeutic dose of enoxaparin, but suffered a new left-sided stroke one week later. Subsequently, pulsed cyclophosphamide was added to the treatment regimen. She has not had any new strokes since. Our case demonstrates that a combination of generalized livedo racemosa and stroke should always prompt a consideration of SS, as its early diagnosis is essential to prevent further neurologic damage. Commercial support: None identified.
JUNE 2017