Jamie MacKelfresh

Fulvene-5 potently inhibits NADPH oxidase 4 and blocks the growth of endothelial tumors in mice

Hemangiomas are the most common type of tumor in infants. As they are endothelial cell-derived neoplasias, their growth can be regulated by the autocrine-acting Tie2 ligand angiopoietin 2 (Ang2). Using an experimental model of human hemangiomas, in which polyoma middle T-transformed brain endothelial (bEnd) cells are grafted subcutaneously into nude mice, we compared hemangioma growth originating from bEnd cells derived from wild-type, Ang2+/-, and Ang2-/- mice. Surprisingly, Ang2-deficient bEnd cells formed endothelial tumors that grew rapidly and were devoid of the typical cavernous architecture of slow-growing Ang2-expressing hemangiomas, while Ang2+/- cells were greatly impaired in their in vivo growth. Gene array analysis identified a strong downregulation of NADPH oxidase 4 (Nox4) in Ang2+/- cells. Correspondingly, lentiviral silencing of Nox4 in an Ang2-sufficient bEnd cell line decreased Ang2 mRNA levels and greatly impaired hemangioma growth in vivo. Using a structure-based approach, we identified fulvenes as what we believe to be a novel class of Nox inhibitors. We therefore produced and began the initial characterization of fulvenes as potential Nox inhibitors, finding that fulvene-5 efficiently inhibited Nox activity in vitro and potently inhibited hemangioma growth in vivo. In conclusion, the present study establishes Nox4 as a critical regulator of hemangioma growth and identifies fulvenes as a potential class of candidate inhibitor to therapeutically interfere with Nox function.

Autoimmune blistering diseases in the elderly

Autoimmune blistering diseases are a significant cause of morbidity and mortality in the elderly population. Given the advancing age of the population, the incidence of these disorders, particularly bullous pemphigoid, is expected to rise. This contribution reviews autoimmune immunobullous disorders of particular relevance in the elderly population. These include bullous pemphigoid, cicatricial pemphigoid, epidermolysis bullosa acquisita, pemphigus, paraneoplastic pemphigus, and linear immunoglobulin A bullous dermatosis. Because therapy and management of individual immunobullous dermatoses differ, establishing the diagnosis is often critically important. An overall approach to bullous diseases in the elderly, as well as key clinical features, appropriate diagnostic tests, microscopic findings, immunofluorescence microscopy patterns, and molecular targets for select disorders are reviewed. Elucidation of antigenic targets at the molecular level has allowed for development of serum enzyme-linked immunofluorescence assays, which have enhanced diagnostic accuracy for several autoimmune blistering disorders. Given the relative rarity of these diseases, large randomized trials evaluating efficacy of various treatments are few, and therapy for most immunobullous disorders in the elderly has not been standardized. Despite this, appropriate therapeutic considerations for each condition are presented and the evidence for them is reviewed.

Targeted therapy of oral hairy leukoplakia with gentian violet

Oral hairy leukoplakia (OHL) is a common oral manifestation of HIV infection. Clinically, these lesions appear as white plaques on the edges of the tongue. Pathophysiologically, these lesions occur because of infection of oral epithelium with Epstein-Barr virus (EBV). No universally effective therapy exists for OHL. We have previously shown that EBV infection and EBV viral products induce the generation of reactive oxygen. We have also demonstrated that the Food and Drug Administration-approved over-the-counter medication gentian violet is a potent inhibitor of reactive oxygen species. We thus chose to treat a patient with biopsy-proven OHL with topical gentian violet. Gentian violet solution was applied topically to the tongue of a patient with OHL. Complete clinical resolution was noted after three treatments. Treatment with topical gentian violet resulted in resolution of the lesions. Further studies with larger numbers of patients are required. The application of gentian violet can be used as a method to OHL treatment. Gentian violet is an inexpensive and safe therapy and, given that it inhibits reactive oxygen, this old therapy is now a targeted novel therapy.

A nonsteroidal alternative to impetiginized eczema in the emergency room

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Utility of additional tissue sections in dermatopathology: diagnostic, clinical and financial implications

As histopathologic assessment is subject to sampling error, some institutions ‘preorder’ deeper sections on some or all cases (hereafter referred to as prospective deeper sections), while others order additional sections only when needed (hereafter referred to as retrospective deeper sections). We investigated how often additional sections changed a diagnosis and/or clinical management. Given the recent decrease in reimbursement for CPT‐code 88305, we also considered the financial implications of ordering additional sections.

Disseminated pyoderma gangrenosum: Role for vascular endothelial growth factor and hypoxia inducible factor-2

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Pregnancy and changes in melanocytic nevi.

A 36-year-old primigravida at 36 weeks gestation presented to the dermatology clinic for her semi-annual check of multiple melanocytic nevi. Her medical history was significant for 2 in situ melanomas removed from her abdomen 2 years earlier. The remainder of her history was unremarkable. The patient thought that some of her nevi had gotten darker since her last visit, but she had not noticed any changes in size or shape. An examination of the patients skin was performed, and her present nevi were compared with those in photographs taken 6 months before at an earlier visit (Fig. 1). Examination revealed no new nevi and no change in size of nevi, but a universal darkening (from light brown to dark brown) of all nevi was noted compared with those in photographs taken 6 months earlier. Should the patient and physicians worry? We sought dermatologic advice to sort this out.

Tuberculosis verrucosa cutis lesions exhibit a greater microvessel count than lupus vulgaris lesions

Tuberculosis verrucosa cutis lesions exhibit a greater microvessel count than lupus vulgaris lesions Sulochana S. Bhandarkar, Padmavathy Lanka, Lakshmana Rao Lanka, Emir Veledar, Michael Y. Bonner, Jamie MacKelfresh and Jack L. Arbiser Department of Dermatology, Emory University School of Medicine, Atlanta, GA, USA; Department of Dermatology, Veterans Administration Medical Center, Atlanta, GA, USA; Department of Pathology, Vinayaka Mission’s Medical College, Karaikal, Pondicherry UT, India; Baptist Health South Flordia, Jacksonville, FL, USA; Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA Correspondence: Jack L. Arbiser, Department of Dermatology, Emory University School of Medicine, WMB 5309, 101 Woodruff Circle, Atlanta, GA 30322, USA, Tel.: (404) 727-5063, Fax: (404) 727-0923, e-mail: jarbise@emory.edu

Dermato-Neuro Syndrome in a Patient Treated With Autologous Stem Cell Transplant for Scleromyxedema

Scleromyxedema is a chronic and unpredictable disease associated with a monoclonal gammopathy. It can have severe systemic manifestations including neurologic, hematologic, and cardiologic involvement. Scleromyxedema can be treated using autologous bone marrow transplant. Dermato-neuro syndrome is a rare and potentially fatal neurological manifestation of scleromyxedema characterized by fever, confusion, dysarthria, lethargy, convulsions, and even coma. Dermato-neuro syndrome can be treated successfully with immunoglobulins and steroids.

Comparison of elliptical excision versus punch incision for the treatment of epidermal inclusion cysts: A prospective, randomized study

To the Editor: Epidermal inclusion cysts (EICs) are commonly encountered neoplasms in dermatology. Elliptical excision with or without cyst content expulsion and manual, blunt dissection of the cyst wall are the most common means for extirpating such lesions. Complete excision has been beleaguered, however, by a longer scar than certain less invasive techniques. To date, there have been few prospective, randomized controlled trials comparing the expediency, incision and scar length, complication rate, and recurrence rate of the different surgical techniques for EIC removal. Lee et al performed the first and only prospective, randomized trial comparing punch incision with removal of cyst contents with elliptical excision of noninflamed, nonruptured EICs. The group found that punch incision operative time and scar length were significantly shorter than elliptical excision, without a statistical difference in recurrence rates or complications. We compared elliptical excision and punch incision of truncal, 1-3 cm, noninflamed, noninfected, nonruptured EICs on the basis of recurrence longitudinally over 16-months’ time in 40 subjects [18 years of age. The secondary objectives were to compare elliptical excision and punch incision on the basis of scar length, procedure time, postoperative complications, patient satisfaction, and skin-specific quality of life (QOL).