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Recalcitrant Cutaneous Mastocytosis Treated With Genetically Informed Targeted Therapy:A Case Report

International Journal of Dermatology and Venereology 2023年第2期6卷 107-109页

作者： Laura Gleason Volkan Tekmen Alexa Cohen Safiyyah Bhatti Burcu Beksac Jisun Cha Pierluigi Porcu Neda Nikbakht department of Dermatology and Cutaneous Biology Thomas Jefferson UniversityPhiladelphiaPA 19107USA Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplant Department of Medical OncologySidney Kimmel Cancer CenterThomas Jefferson UniversityPhiladelphiaPA 19107USA department of dermatopathology Schweiger Dermatology GroupNew YorkNY 10006USA

Introduction:Mastocytosis,a clonal proliferation of mast cells commonly involving the skin and bone marrow,has a varied clinical presentation ranging from cutaneous lesions to systemic disease.Cutaneous mastocytosis is managed symptomatically,but systemic mastocytosis is treated with targeted therapy against the mutated receptor tyrosine kinase c-KIT,the pathogenic driver of mastocytosis.However,there are no guidelines for the treatment of cutaneous mastocytosis refractory to symptomatic management.We herein report a method to select genetically informed therapy for symptomatic and recalcitrant cutaneous mastocytosis.Case presentation:We performed a mutational analysis of dermal mast cells after enrichment by laser capture in a 23-year-old woman with recalcitrant cutaneous mastocytosis.The analysis revealed a aspartic acid to valine substitution at codon 816(D816V)mutation in the protein c-KIT.Based on these results,we initiated treatment with the multi-kinase/KIT inhibitor midostaurin,a treatment effective against the D816V c-KIT mutation.After 3 months of treatment,the patient exhibited a reduction in the number and size of cutaneous lesions and reported resolution of pruritus and decreased severity of other mast cell-related symptoms.Discussion:The treatment of mastocytosis relies heavily on whether the disease is limited to the skin or systemic.However,there are no guidelines for cutaneous mastocytosis that does not respond to symptomatic management.In the present report describing a patient with recalcitrant cutaneous mastocytosis,we describe a strategy in which skin mutational analysis is used to guide the selection of targeted therapy.Conclusion:Performing mast cell mutational analyses in the skin provides a means to select targeted therapy for symptomatic and refractory cutaneous mastocytosis.

关键词： mastocytosis c-KIT molecular genetics targeted therapy midostaurin

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Cutaneous allergic reaction to subcutaneous vitamin K_(1):A case report and review of literature

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World Journal of Clinical Cases 2022年第29期10卷 10742-10754页

作者： Miao Zhang Jia Chen Chun-Xiao Wang Nai-Xuan Lin Xin Li department of Dermatology Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai 200437China Institute of Dermatology Shanghai Academy of Traditional Chinese MedicineShanghai 201203China department of dermatopathology Shanghai Skin Disease HospitalTongji UniversityShanghai 200443China

BACKGROUND Vitamin K1(phytomenadione)is a fat-soluble naturally occurring vitamin that is widely used to treat certain coagulation disorders.Adverse cutaneous reactions to vitamin K1 can occur;however,owing to its low incidence and considerable variability in presentation and morphology,its diagnosis can be easily overlooked.Managing these reactions may be challenging for patients and clinicians.Therefore,reviewing the adverse cutaneous reactions to vitamin K1 is important.CASE SUMMARY Here we report the case of a 50-year-old woman with no pre-existing hepatic disease who developed a cutaneous allergic reaction to subcutaneous vitamin K1 that presented as localized eczematous plaques at the vitamin K1 injection site.The eruption developed within 5 d of the injection and persisted for 32 mo despite treatment with topical and intralesional steroids.Eczema was diagnosed based on the results of the pathological examination,immunohistochemical staining,and a skin biopsy.The patient was advised to take herbal medicines orally twice daily.After treatment and follow-up,the patient’s eczematous urticarial plaques improved and her condition stabilized.CONCLUSION Here we present the first case of a cutaneous allergic reaction to subcutaneous vitamin K1 that was successfully treated with Chinese medicine.

关键词： Vitamin K1 Subcutaneous injection Adverse reactions Herbal medicine Polyoxyethylated castor oil Case report guidelines Case report

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Tale of Two Alopecias: Alopecia Areata and Central Centrifugal Cicatricial Alopecia Occurring in the Same Patient

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International Journal of Dermatology and Venereology 2022年第1期5卷 45-49页

作者： Sharlene Helene C.See Timothy L.Tan Oyinade Aderibigbe Pedram Yazdan department of Pathology Northwestern University Feinberg School of MedicineChicagoIL 60611USA Consolidated Pathology Consultants LibertyvilleIL 60048USA department of Dermatology Division of DermatopathologyNorthwestern University Feinberg School of MedicineChicagoIL 60611USA

Introduction:Scarring and non-scarring alopecias have rarely been described to occur together in the same patient.Distinguishing these two different types of alopecia is important as treatment and prognosis can be different.Case presentation:Here,we report the first case of simultaneous alopecia areata(AA)and central centrifugal cicatricial alopecia(CCCA)in a 35-year-old woman.New alopecic patches were noted on her frontal and vertex scalp.Biopsy of the frontal scalp revealed miniaturized hair follicles and dense lymphocytic infiltrate surrounding the hair bulbs,consistent with AA;while biopsy of the vertex scalp revealed decreased hair follicles,perifollicular fibroplasia with eccentric atrophy of the follicular epithelium,and premature desquamation of the inner root sheath at the level of the lower isthmus,consistent with CCCA.Discussion:Proposed mechanisms of these two alopecia types occurring together include loss of immune privilege,genetic predisposition,as well as unknown external factors that trigger an autoimmune lymphocytic response.Most recently,the peptidylarginine deiminase type III gene has been implicated in both diseases.Although treatment options can overlap between thetwo diseases,treatment response can differ and CCCA tendsto have a worse prognosis.Conclusion:Awareness of this concomitant presentation of two alopecic types is important for appropriate treatment and prognostication.

关键词： alopecia areata central centrifugal cicatricial alopecia non-scarring alopecia scarring alopecia peptidylarginine deiminase type III gene

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Acquired Syphilis in a Chinese Family among Three Generations

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Chinese Medical Journal 2018年第14期131卷 1761-1762页

作者： Fu-Quan Long Li-Shi Zhao Jia Chen department of Sexually Transmitted Diseases Shanghai Dermatology Hospital Shanghai 200443 China department of dermatopathology Shanghai Dermatology Hospital Shanghai 200443 China

To the Editor： Syphilis is primarily a sexually transmitted disease caused by Treponema pallidum, which can be present in various body fluids such as blood, saliva, sperm, cerebrospinal fluid, and also in active skin lesions,i^i Acquired syphilis contracted by Children is highly attributed to sexual abuse; however, infection can also occur by nonsexual contact： for example, prechewing feeding, kissing, fondling, or by contaminated utensils, particularly when family members or caregivers have active syphilis.

关键词： CHILDREN

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Cutaneous Metastases Arising from Synovial Sarcoma： A Case Report

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Chinese Medical Journal 2017年第24期130卷 3019-3020页

作者： Xue Zeng Li Li Wa-Li Liu department of Dermatology Guang'anmen Hospital China Academy of Chinese Medical Sciences Beijing 100053 China department of dermatopathology Guang'anmen Hospital China Academy of Chinese Medical Sciences Beijing 100053 China

To the Editor：Synovial sarcoma （SS） is a relatively rare type of soft tissue sarcoma that constitutes approximately 8% of all soft tissue sarcomas.SS frequently occurs in the para-articular structures of the limbs and is predominantly found in the lower limbs.The other involved locations of invasion are lung,lymph nodes,and bone.However,the skin is rarely involved.[1-3] Here,we reported an extremely rare case ofbiphasic SS presenting with disseminated cutaneous metastases.

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Chromoblastomycosis:a tropical-subtropical fungal disease with pathognomonic features not to be neglected in a global health scenario

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Clinical Research Communications 2023年第1期6卷 1-4页

作者： Larissa de Andrade Defendi Giuliano Ferreira Morgantetti Guilherme Alencar de Medeiros Marcelo Balancin department of Radiology Escola Paulista de MedicinaSão Paulo/SP 04024-002Brazil department of dermatopathology NORDD PathologyFortaleza/CE 60140-110Brazil department of Pathology FOSPOncocentro FoundationSão Paulo/SP 04024-002Brazil

Chromoblastomycosis(CBM)is a fungal disease,distributed in tropical and subtropical regions,affecting mainly rural workers.It is characterized by chronic skin lesions that may vary from nodular,tumorous,verrucous or plaque type.Associated constitutional symptoms are rarely found.The histological presentation may yield a pathognomonic feature,the Medlar(sclerotic)bodies,in which a typical brown to black pigment is depicted,explaining“copper pennies”as its alias.In this article,the case of a 56-year-old woman in the countryside of Brazil is reported,whose main complaint was a chronic leg ulcer for the past 8 years.The left leg had a large,partially ulcerated plaque lesion was found.Microbiological cultures were positive for the pathogen.Histological analysis demonstrated pseudoepitheliomatous hyperplasia,lymphohistiocytic infiltrate and sclerotic bodies(“copper pennies”).CBM’s epidemiological panorama,once established uniquely by geographical distribution,is transitioning to a global health issue,influenced by immunosuppressive conditions,global warming and migration.This scenario demands CBM to be widely considered as a differential diagnosis and may represent a clinical challenge in regions whose professionals have little expertise in infectious tropical diseases.

关键词： chromoblastomycosis fungal infection histopathology global health

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Cutaneous perivascular epithelioid cell tumors:A review on an infrequent neoplasm

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World Journal of Methodology 2016年第1期6卷 87-92页

作者： Mar Llamas-Velasco Luis Requena Thomas Mentzel department of Dermatology Hospital Universitario de La Princesa department of Dermatology Fundación Jiménez Díaz department of dermatopathology Dermatohis- topathologisches Gemeinschaftslabor

"Perivascular epithelioid cutaneous" cell tumors(PEComa) are a family of mesenchymal tumors with shared microscopic and immunohistochemical properties: They exhibit both smooth muscle cell and melanocytic differentiation. Non-neoplastic counterpart of PEComa's cells are unknown, as well as the relationship between extracutaneous PEComa and primary cutaneous ones. We will review the clinical setting, histopathologic features, chromosomal abnormalities, differential diagnosis and treatment options for cutaneous PEComa.

关键词： Perivascular epithelioid cell tumor Skin Cutaneous perivascular epithelioid cell tumors Clear cell myomelanocytic tumor

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Inhibitory Effects of Berberine on the Activation and Cell Cycle Progression of Human Peripheral Lymphocytes

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Cellular & Molecular Immunology 2005年第4期2卷 295-300页

作者： Lihui Xu Yi Liu Xianhui He Key Laboratory of Ministry of Education for Tissue Transplantation and Immunology College of Life Science and Technology Jinan University Guangzhou 510632 China Institute of Bioengineering Jinan University Guangzhou 510632 China department of dermatopathology Institute of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College Nanjing 210042 China

The immunosuppressive property of berberine, an isoquinoline alkaloid, has been well documented, but the mechanism of its action on lymphocytes has not been completely elucidated. The present study is to investigate the effect of berberine on the activation and proliferation of lymphocytes, in particular T lymphocytes. Whole peripheral blood from healthy donors was stimulated with phytohemagglutinin （PHA） alone or phorbol dibutyrate （PDB） plus ionomycin, and the expression of CD69 and CD25 on T lymphocytes was evaluated with flow cytometry. The distribution of cell cycles and cell viability were analyzed by staining with propidium iodide （PI） and 7-aminoactinomycin D （7-AAD）, respectively. The results showed that 100 μmol/L and 50 μmol/L of berberine significantly inhibited CD69 expression on T cells stimulated with PDB plus ionomycin or PHA, whereas the effect of 25 μmol/L berberine was not significant. As the incubation time increased, the extent of inhibition decreased. Similarly, the expression of CD25 was also reduced by berberine in a dose-dependent manner over the concentration range of 25-100 μmol/L. Besides, this alkaloid could block lymphocyte cell cycle progression from G0/G1 phase to S and G2/M phase without phase specificity. Moreover, analysis following 7-AAD staining revealed that berberine had no significant cytotoxicity on lymphocytes. Taken together, berberine significantly inhibits the expression of activation antigens on T lymphocytes and also blocks the progression of cell cycles of lymphocytes, suggesting that berberine may exert immunosuppressive effect through inhibiting the activation and proliferation of T cells.

关键词： berberine lymphocyte activation antigen cell cycle

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Expression and Purification of Soluble Human Programmed Death-1 in Escherichia coli

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Cellular & Molecular Immunology 2006年第2期3卷 139-143页

作者： Lihui Xu Yi Liu Xianhui He Institute of Bioengineering College ot Life Science and lecnnology Jinan University Guangzhou 510632 China Institute of Tissue Transplantation and Immunology College of Life Science and Technology Jinan University Guangzhou 510632 China department of dermatopathology Institute of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College Nanjing 210042 China

Programmed death-1 （PD-1）, a member of CD28 family, is able to negatively regulate the TCR complex-initiated signaling by interacting with its cognate ligands （PD-L1 and/or PD-L2）. PD-1/PD-L1 pathway plays an important role in down-regulating the effective phase of adaptive immune responses and the blockade of this pathway has been proved to enhance antiviral and antitumoral immunity, suggesting that it might be a potential target for the development of therapies to improve T cell responses in patients with virus infections or malignancies. In present study, the extracellular domain of human PD-1 with a carboxyl terminal His-tag （designated as sPD-1） was expressed as inclusion bodies in Escherichia coll. The product was on-column refolded, purified by immobilized metal affinity chromatography, and characterized by Western blotting. Furthermore, the soluble PD-1 with high purity possessed specific binding activity with its cognate ligand PD-L1, and the dissociation constant was 0.43 nmol/L as determined by Scatchard plot analysis. These results suggest that refolded sPD-1 from prokaryotic cells may be of therapeutic interest in enhancing antivirus and antitumoral immune responses.

关键词： PD-1 extracellular domain prokaryotic expression inclusion body binding activity

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Treatment of Wrinkles and Acne Scars Using the TriFractional, a Novel Fractional Radiofrequency Technology—Clinical and Histological Results

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Journal of Cosmetics, Dermatological Sciences and Applications 2012年第3期2卷 117-125页

作者： Alex Levenberg Andrea Gat Marie Christine Branchet Sylvie Boisnic dermatopathology Unit Sourasky Medical Center Tel Aviv Israel GREDECO Research Group Paris France Physicians Center Plastic Surgery Department Tel Aviv Israel

Introduction: The need for cosmetic facial enhancement procedures with minimal down time and low risk has led to the development of methods for non-surgical skin rejuvenation. Various ablative lasers were developed, which remove the full skin surface in a controlled manner. However, the prolonged recovery and the significant risks prompted the development of fractional lasers which ablate the skin in a fractional manner, leaving untreated areas to improve healing process. In the past few years, fractional radiofrequency (RF) systems have been introduced that enable controlled skin resurfacing accompanied with dermal collagen remodeling. The new TriFractional technology from Pollogen? is designed to enable skin resurfacing and treatment of wrinkles using RF energy. The objective of the current research was to evaluate the safety and effectiveness of the novel TriFractional technology using the TriFractional applicator (A3F) for micro-ablative skin resurfacing and the treatment of wrinkles and acne scars. Methods: Healthy volunteers consented to undergo TriFractional treatments for various aesthetic indications. In addition, in-vivo and ex-vivo histologycal results showing immediate and long term effects of the TriFractional technology were obtained. A portion of the subjects underwent the complete TriLipo MedTM Procedure which includes 2 TriFractional treatments spaced one month apart, with 2 TriLipo RF + Dynamic Muscle Activation (DMA) face treatments two weeks after each TriFractional treatment. Results: Subjects experienced an improvement of wrinkles, skin texture and acne scars along with facial contouring. No significant adverse effects were detected post-treatment. Histology findings demonstrated immediate and long term TriFractional effects on both epidermal and dermal skin layers. Conclusions: TriFractional is a promising technology for skin resurfacing, treatment of wrinkles and improvement of additional aesthetic indications such as acne scars. The TriLipo MEDTM procedure is a unique combination approach

关键词： Radiofrequency Trifractional Wrinkles Acne Scars Collagen

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