- Email: [email protected]
Neoadjuvant, intralesional methotrexate treatment of cutaneous squamous cell carcinoma
5181
5212
Neoadjuvant, intralesional methotrexate treatment of cutaneous squamous cell carcinoma Brian Lee, MD, LSU Department of Dermatology; Rawaa Almukhtar, MD, LSU Department of Dermatology; Aaron Coulon, BS, LSU Department of Dermatology Background: Methotrexate (MTX) is a folic acid analog that irreversibly inhibits dihydrofolate reductase and prevents thymidine synthesis. It, therefore, hinders cellular proliferation and is used to treat numerous neoplastic diseases. Direct placement of methotrexate into a neoplasm allows for higher local concentration with less systemic toxicity. Cutaneous squamous cell carcinomas (cSCC) are typically treated with surgery, but removal of large lesions can be difficult due to complex reconstructions and its impact on functionality and cosmesis. Intralesional MTX (il-MTX) has been used successfully as monotherapy and neoadjuvant therapy for keratoacanthomas, which has prompted researchers to explore its efficacy for neoadjuvant treatment of cSCC.
Neoscytalidium dimidiatumespecific PCR-based identification with DNA sequences of nuclear ribosomal internal transcribed spacer 1 region primers Charussri Leeyaphan, MD, Department of Dermatology Faculty of Medicine Siriraj Hospital Mahidol University; Koichi Makimura, PhD, Laboratory of Space and Environmental Medicine, Graduate School of Medicine Teikyo University; Sumanas Bunyaratavej, MD, Department of Dermatology Faculty of Medicine Siriraj Hospital, Ma; Wichit Suthammarak, PhD, Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University; Supannee Kaewsutthi, Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University; Sutasinee Phaitoonwattanakij, Department of Dermatology Faculty of Medicine Siriraj Hospital, Mahidol University Background: Neoscytalidium dimidiatum is an important causative organism for nondermatophytes (NDMs) skin and nail infection in worldwide. Difficulties in treatment and drug resistance had been reported in N dimidiatum infection. Objectives: This study aims to develop of N dimidiatum-specific primers to use in PCR identification method that provide rapid and accuracy identification and lead to proper management. Materials and Methods: N dimidiatum-specific PCR primers were designed based on the nuclear ribosomal internal transcribed spacer 1 region, located between 18S and 5.8S rDNA. Fungal DNAs extracted from dermatophytes (DMPs) and NDMs colonies grown on culture plates and clinical specimens were used for primer sensitivity and specificity analysis. Results: Using N dimidiatum-specific PCR primers, the specific PCR product was amplified from two standard strain of N dimidiatum but there was no expression from other DMPs and NDMs species. Sensitivity of this N dimidiatum-specific PCR method was able to detect 10 pg of N dimidiatum DNA with ethidium bromide staining. Moreover, this specific PCR method could detect N dimidiatum from clinical samples.
Objective: To review and explore the efficacy of il-MTX as a neoadjuvant treatment for cSCC. Methods: A MEDLINE search (1970 to present) was performed to identify articles investigating il-MTX for the treatment of cSCC. Articles were screened for relevance by title and abstract. References from identified articles were used to expand the search results. Results: Only one retrospective cohort study investigated the use of il-MTX to treat cSCC. An average amount of 0.74 mL of MTX (25 mg/mL) was used for 43 subjects via a one-time injection. Tumors shrunk by an average of 42.6 percent. Further, complex surgical reconstruction was needed significantly less often after il-MTX. Three case reports of neoadjuvant il-MTX have been identified. The first was a cSCC on the lower lip treated with three weekly doses of il-MTX (25 mg/mL) for a total of 2.5 mL. The second was also a cSCC on the lower lip treated with three weekly 1 mL doses of il-MTX (25 mg/mL). The most recent case was a patient taking vemurafenib for metastatic melanoma who had multiple cSCCs. One was treated with four injections of MTX at 3-4-week interval (25 mg/mL) for a total of 1.45 mL; the other was treated with three injections for a total of 0.95 mL. All four lesions significantly decreased in size. No systemic side effects were reported in any of these studies. Conclusion: These data suggest that il-MTX could be a safe, and cheap neoadjuvant prior to surgery in the treatment in cSCC. It may achieve decreased tumor size, which results in smaller surgical defects, and improved functional and cosmetic outcomes. However, data is limited, and larger studies with long-term follow up are needed to determine safety, efficacy, and optimal treatment regimens.
Conclusions: A PCR identification system specific for N dimidiatum is rapid, sensitive, and specific. This method will be beneficial in making early diagnosis and indicating appropriate treatment for patients. Commercial support: None identified.
Commercial support: None identified.
5732 Neonatal purpura fulminans due to protein C deficiency: A case report Francisco-Jos e Navarro-Trivi~ no, MD, Francisco Jose Navarro Trivi~ no; Lucıa Gonzalez-Ruız, MD, Lucıa Gonzalez Ruız; Paula Aguayo-Carreras, Paula Aguayo Carreras; Antonio Martınez-Martınez, MD, Antonio Martınez Martınez; Israel Perez-P erez, Israel Perez Perez; Javier Pacheco-SanchezLafuente, Javier Pacheco-Sanchez-Lafuente; Ricardo Ruız-Villaverde, Ricardo Ruız Villaverde Introduction: Family protein C and S deficit, autosomal dominant inheritance, leads to prothrombotic state. Clinically, it can lead to coagulopathic purple picture, whose severity even lead to death if not treated early. We report the case of neonatal purpura fulminans with asymmetric back involvement in the forearm and left hand side protein C deficiency and S. Case Presentation: Male infant born at 36 + 3 weeks’ gestation, CIR type 1, which featured at birth the bruise on forearm and back of the hand, which quickly evolved into a hemorrhagic bulla with subsequent transformation into necrotic slough. Patient was admitted to neonatal ICU to study purpura fulminans. The possibility of neonatal sepsis was discarded, while it confirmed thrombopathy deficit of protein C and S. Began with ceprotin treatment according to protocol, associated with escharotomy and local priests, with a satisfactory evolution. Discussion: Neonatal purpura fulminans is a rare clinical condition. Sepsis, drugs and hereditary disorders of coagulation factors are the main causes of purpura fulminans. Within thrombopathies deficit protein C and S is one of the pictures described, with a prevalence of 1/40,000 to 250,000 individuals. Microvascular thrombosis affects not only the skin, but other organs, mainly the cerebral veins (thrombosis of the cavernous sinus with secondary intracerebral bleeding, hydrocephalus, seizures and mental retardation) or retinal veins (vitreous hemorrhage or retinal detachment). The diagnosis of fulminant purpura is clinical, and does not usually require skin biopsy for study, however, it is essential to make the relevant additional tests to rule out sepsis and study thrombopathies since early specific treatment improves the prognosis of these patients. Thrombopathies family study is part of this clinical study. The prognosis is reserved, as many patients will have longterm sequelae. A multidisciplinary management with the pediatric ward, hematology, pediatric surgery and radiology, for proper patient management is necessary.
4930 Neurogenic rosacea successfully treated with pulsed dye laser following failed medical management Laurel Wessman, BS, University of North Dakota; Daniel D. Miller, MD, University of Minnesota; Noah I. Goldfarb, MD, University of Minnesota; Ronda S. Farah, MD, University of Minnesota Introduction: Neurogenic rosacea is a newly described clinical subtype of rosacea with relatively little known about its pathogenesis and effective treatment modalities. Classically, this disease is difficult to treat, as antibiotics, neuroleptic agents, and surgical therapies, which target the autonomic nervous system, are only variably effective. Herein, we report a patient with neurogenic rosacea who was successfully managed with pulsed day laser (PDL) following multiple failed medical therapies. Because reports of laser and light based therapy for the treatment of neurogenic rosacea are scarce, and the positive response that our patient had with this therapy, we hope to promote awareness and provide viable treatment options for patients with this disease. Methods: Our patient was treated with the 595-nm PDL. A test spot of the cheek was initially performed with the following settings: 7-mm spot size, 6-ms pulse duration, at 7 J/cm2, with cryogen cooling for patient comfort. He tolerated the procedure well and was subsequently treated with similar settings and a 10-mm spot size. He has completed two treatments to date, spaced at least 3 weeks apart. Results: Our patient reported that his symptoms improved by 50% and his redness had improved by 30%. Conclusion: PDL has been reported to be effective for other types of rosacea, and has been found to decrease the amounts of substance P and calcitonin geneerelated peptide (CGRP), pain-modulating neuropeptides, in the skin. Therefore, it would be reasonable to surmise that PDL would be successful for the treatment of neurogenic rosacea. Other than aberrancy of pain modulation pathways, other proposed mechanisms of disease for patients with neurogenic rosacea include neurovascular instability and immune system dysregulation. Because of the novelty of this treatment for a difficult to manage disorder, we hope that this report will positively affect the management of future neurogenic rosacea patients. Commercial support: None identified.
Commercial support: None identified.
JUNE 2017
J AM ACAD DERMATOL
AB177
5212
Neoadjuvant, intralesional methotrexate treatment of cutaneous squamous cell carcinoma Brian Lee, MD, LSU Department of Dermatology; Rawaa Almukhtar, MD, LSU Department of Dermatology; Aaron Coulon, BS, LSU Department of Dermatology Background: Methotrexate (MTX) is a folic acid analog that irreversibly inhibits dihydrofolate reductase and prevents thymidine synthesis. It, therefore, hinders cellular proliferation and is used to treat numerous neoplastic diseases. Direct placement of methotrexate into a neoplasm allows for higher local concentration with less systemic toxicity. Cutaneous squamous cell carcinomas (cSCC) are typically treated with surgery, but removal of large lesions can be difficult due to complex reconstructions and its impact on functionality and cosmesis. Intralesional MTX (il-MTX) has been used successfully as monotherapy and neoadjuvant therapy for keratoacanthomas, which has prompted researchers to explore its efficacy for neoadjuvant treatment of cSCC.
Neoscytalidium dimidiatumespecific PCR-based identification with DNA sequences of nuclear ribosomal internal transcribed spacer 1 region primers Charussri Leeyaphan, MD, Department of Dermatology Faculty of Medicine Siriraj Hospital Mahidol University; Koichi Makimura, PhD, Laboratory of Space and Environmental Medicine, Graduate School of Medicine Teikyo University; Sumanas Bunyaratavej, MD, Department of Dermatology Faculty of Medicine Siriraj Hospital, Ma; Wichit Suthammarak, PhD, Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University; Supannee Kaewsutthi, Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University; Sutasinee Phaitoonwattanakij, Department of Dermatology Faculty of Medicine Siriraj Hospital, Mahidol University Background: Neoscytalidium dimidiatum is an important causative organism for nondermatophytes (NDMs) skin and nail infection in worldwide. Difficulties in treatment and drug resistance had been reported in N dimidiatum infection. Objectives: This study aims to develop of N dimidiatum-specific primers to use in PCR identification method that provide rapid and accuracy identification and lead to proper management. Materials and Methods: N dimidiatum-specific PCR primers were designed based on the nuclear ribosomal internal transcribed spacer 1 region, located between 18S and 5.8S rDNA. Fungal DNAs extracted from dermatophytes (DMPs) and NDMs colonies grown on culture plates and clinical specimens were used for primer sensitivity and specificity analysis. Results: Using N dimidiatum-specific PCR primers, the specific PCR product was amplified from two standard strain of N dimidiatum but there was no expression from other DMPs and NDMs species. Sensitivity of this N dimidiatum-specific PCR method was able to detect 10 pg of N dimidiatum DNA with ethidium bromide staining. Moreover, this specific PCR method could detect N dimidiatum from clinical samples.
Objective: To review and explore the efficacy of il-MTX as a neoadjuvant treatment for cSCC. Methods: A MEDLINE search (1970 to present) was performed to identify articles investigating il-MTX for the treatment of cSCC. Articles were screened for relevance by title and abstract. References from identified articles were used to expand the search results. Results: Only one retrospective cohort study investigated the use of il-MTX to treat cSCC. An average amount of 0.74 mL of MTX (25 mg/mL) was used for 43 subjects via a one-time injection. Tumors shrunk by an average of 42.6 percent. Further, complex surgical reconstruction was needed significantly less often after il-MTX. Three case reports of neoadjuvant il-MTX have been identified. The first was a cSCC on the lower lip treated with three weekly doses of il-MTX (25 mg/mL) for a total of 2.5 mL. The second was also a cSCC on the lower lip treated with three weekly 1 mL doses of il-MTX (25 mg/mL). The most recent case was a patient taking vemurafenib for metastatic melanoma who had multiple cSCCs. One was treated with four injections of MTX at 3-4-week interval (25 mg/mL) for a total of 1.45 mL; the other was treated with three injections for a total of 0.95 mL. All four lesions significantly decreased in size. No systemic side effects were reported in any of these studies. Conclusion: These data suggest that il-MTX could be a safe, and cheap neoadjuvant prior to surgery in the treatment in cSCC. It may achieve decreased tumor size, which results in smaller surgical defects, and improved functional and cosmetic outcomes. However, data is limited, and larger studies with long-term follow up are needed to determine safety, efficacy, and optimal treatment regimens.
Conclusions: A PCR identification system specific for N dimidiatum is rapid, sensitive, and specific. This method will be beneficial in making early diagnosis and indicating appropriate treatment for patients. Commercial support: None identified.
Commercial support: None identified.
5732 Neonatal purpura fulminans due to protein C deficiency: A case report Francisco-Jos e Navarro-Trivi~ no, MD, Francisco Jose Navarro Trivi~ no; Lucıa Gonzalez-Ruız, MD, Lucıa Gonzalez Ruız; Paula Aguayo-Carreras, Paula Aguayo Carreras; Antonio Martınez-Martınez, MD, Antonio Martınez Martınez; Israel Perez-P erez, Israel Perez Perez; Javier Pacheco-SanchezLafuente, Javier Pacheco-Sanchez-Lafuente; Ricardo Ruız-Villaverde, Ricardo Ruız Villaverde Introduction: Family protein C and S deficit, autosomal dominant inheritance, leads to prothrombotic state. Clinically, it can lead to coagulopathic purple picture, whose severity even lead to death if not treated early. We report the case of neonatal purpura fulminans with asymmetric back involvement in the forearm and left hand side protein C deficiency and S. Case Presentation: Male infant born at 36 + 3 weeks’ gestation, CIR type 1, which featured at birth the bruise on forearm and back of the hand, which quickly evolved into a hemorrhagic bulla with subsequent transformation into necrotic slough. Patient was admitted to neonatal ICU to study purpura fulminans. The possibility of neonatal sepsis was discarded, while it confirmed thrombopathy deficit of protein C and S. Began with ceprotin treatment according to protocol, associated with escharotomy and local priests, with a satisfactory evolution. Discussion: Neonatal purpura fulminans is a rare clinical condition. Sepsis, drugs and hereditary disorders of coagulation factors are the main causes of purpura fulminans. Within thrombopathies deficit protein C and S is one of the pictures described, with a prevalence of 1/40,000 to 250,000 individuals. Microvascular thrombosis affects not only the skin, but other organs, mainly the cerebral veins (thrombosis of the cavernous sinus with secondary intracerebral bleeding, hydrocephalus, seizures and mental retardation) or retinal veins (vitreous hemorrhage or retinal detachment). The diagnosis of fulminant purpura is clinical, and does not usually require skin biopsy for study, however, it is essential to make the relevant additional tests to rule out sepsis and study thrombopathies since early specific treatment improves the prognosis of these patients. Thrombopathies family study is part of this clinical study. The prognosis is reserved, as many patients will have longterm sequelae. A multidisciplinary management with the pediatric ward, hematology, pediatric surgery and radiology, for proper patient management is necessary.
4930 Neurogenic rosacea successfully treated with pulsed dye laser following failed medical management Laurel Wessman, BS, University of North Dakota; Daniel D. Miller, MD, University of Minnesota; Noah I. Goldfarb, MD, University of Minnesota; Ronda S. Farah, MD, University of Minnesota Introduction: Neurogenic rosacea is a newly described clinical subtype of rosacea with relatively little known about its pathogenesis and effective treatment modalities. Classically, this disease is difficult to treat, as antibiotics, neuroleptic agents, and surgical therapies, which target the autonomic nervous system, are only variably effective. Herein, we report a patient with neurogenic rosacea who was successfully managed with pulsed day laser (PDL) following multiple failed medical therapies. Because reports of laser and light based therapy for the treatment of neurogenic rosacea are scarce, and the positive response that our patient had with this therapy, we hope to promote awareness and provide viable treatment options for patients with this disease. Methods: Our patient was treated with the 595-nm PDL. A test spot of the cheek was initially performed with the following settings: 7-mm spot size, 6-ms pulse duration, at 7 J/cm2, with cryogen cooling for patient comfort. He tolerated the procedure well and was subsequently treated with similar settings and a 10-mm spot size. He has completed two treatments to date, spaced at least 3 weeks apart. Results: Our patient reported that his symptoms improved by 50% and his redness had improved by 30%. Conclusion: PDL has been reported to be effective for other types of rosacea, and has been found to decrease the amounts of substance P and calcitonin geneerelated peptide (CGRP), pain-modulating neuropeptides, in the skin. Therefore, it would be reasonable to surmise that PDL would be successful for the treatment of neurogenic rosacea. Other than aberrancy of pain modulation pathways, other proposed mechanisms of disease for patients with neurogenic rosacea include neurovascular instability and immune system dysregulation. Because of the novelty of this treatment for a difficult to manage disorder, we hope that this report will positively affect the management of future neurogenic rosacea patients. Commercial support: None identified.
Commercial support: None identified.
JUNE 2017
J AM ACAD DERMATOL
AB177