Timothy C. Flynn

Neutrophilic eccrine hidradenitis: A distinctive rash associated with cytarabine therapy and acute leukemia

Neutrophilic eccrine hidradenitis (NEH) is a recently described neutrophilic dermatosis associated with acute myelogenous leukemia (AML) and chemotherapy. This disorder is a distinct clinicopathologic entity separate from leukemid reactions and other neutrophilic dermatoses. We describe two cases in which plaques or nodules developed in the second week after initiation of induction chemotherapy for AML. The lesions regressed in 1 week and recurred in one case when induction chemotherapy was given a second time. Histologically, the findings were similar in each case. Neutrophils palisaded about and infiltrated the eccrine coil in which necrosis of secretory epithelium was present. Focal mucinous degeneration of the eccrine adipose tissue cuff was the only other significant alteration. No vasculitis was observed. Cultures and histologic preparations for pathogenic organisms were negative. Cytarabine was the chemotherapeutic agent used in all three cases. NEH most likely represents either an unusual response caused by cytarabine or a manifestation of AML. Recognition of NEH is important in order to exclude other neutrophilic dermatoses associated with AML, such as sepsis and leukemia cutis, which may appear clinically similar.

Erythema nodosum leprosum: Nature and extent of the cutaneous microvascular alterations

Skin biopsy specimens from four patients with erythema nodosum leprosum, when examined as Epon-embedded, 1-micron sections, exhibited a necrotizing vasculitis involving capillaries, venules, and small-to-medium arteries and veins. In the superficial dermis, affected venules and capillaries showed endothelial cell enlargement and focal necrosis associated with perivascular infiltrates of lymphocytes. In the deep dermis and subcutaneous tissue, affected venules, arterioles, and arteries exhibited endothelial cell necrosis and matted fibrin in the vessel walls associated with perivascular infiltrates of neutrophils. Throughout the dermis, mononuclear phagocytes with vacuoles containing numerous fragmented organisms were observed. By electron microscopy, electron-dense material resembling immune complexes was observed in the walls of these vessels. These observations support the concept that erythema nodosum leprosum is an immune complex-mediated necrotizing vasculitis involving capillaries, arterioles, arteries, venules, and veins.

Multicenter, Randomized, Phase III Study of a Single Dose of IncobotulinumtoxinA, Free from Complexing Proteins, in the Treatment of Glabellar Frown Lines

BACKGROUND Botulinum toxin type A is a proven, effective aesthetic treatment for glabellar frown lines. IncobotulinumtoxinA (NT 201, Xeomin/Xeomeen/Bocouture, Merz Pharmaceuticals GmbH, Frankfurt, Germany) is a 150‐kDa botulinum toxin type A free of complexing proteins. OBJECTIVE To assess the efficacy and safety of incobotulinumtoxinA in a randomized, double‐blind, placebo‐controlled, Phase III study in patients with moderate to severe glabellar frown lines. MATERIALS AND METHODS Two hundred seventy‐six patients were randomized 2:1 to receive a single injection of 20 U of incobotulinumtoxinA or placebo, respectively. Efficacy was assessed at day 30 using a Food and Drug Administration–mandated composite endpoint; a responder was defined as a patient with a 2‐point or greater improvement in glabellar frown lines on a 4‐point scale as assessed by investigator and patient. Safety was assessed periodically through Day 120. RESULTS Treatment with a single dose of incobotulinumtoxinA was significantly superior to placebo in the treatment of glabellar frown lines at Day 30 using the composite endpoint (p < .001), with investigators and patients assessing glabellar frown lines as significantly more improved after incobotulinumtoxinA injection than with placebo (p < .001). IncobotulinumtoxinA was well tolerated. CONCLUSION A single dose of 20 U of incobotulinumtoxinA demonstrated efficacy and safety in the treatment of glabellar frown lines using new Food and Drug Administration efficacy variables.

Antigen and receptor-driven regulatory mechanisms: IX. T cell-T cell interaction in the generation of first-order idiotype-bearing suppressor T cells☆

Abstract We have studied the influence of allogeneic effects directed at specific intra-I region gene products on the stimulation of suppressor cells. Intravenous administration of low doses (1.26 m M ) of azobenzenearsonate (ABA)-derivatized spleen cells, but not ABA-protein conjugates, induces a population of thymus-derived suppressor cells (pre-Ts) which can be activated by an I-J-specific allogeneic effect. After the allogeneic effect such Ts express their antigen-specific suppressive capacity. These cells were found to be Lyt 1 + 2− and I-J+ by antiserum plus complement treatment. In A/J mice, which express a major cross-reactive idiotype to ABA, these pre-Ts also bear idiotypic determinants on the cell surface. Evidence is presented which shows that the pre-Ts are allotype but not H-2 restricted in their ability to transfer suppression to other strains. The pre-Ts are also able to suppress the afferent (sensitization) but not the efferent (elicitation) limb of the immune response. The cell(s) which induce the allogeneic effect were found to be radioresistant (1500 R), Lyt 1 + 2− T cells. These results indicate that a population of Lyt 1 I-J+ cells unable to suppress Lyt 1 DTH reactions can be induced to do so by specific allogeneic effects mediated by an Lyt 1 population.

The convergence of medicine and neurotoxins: a focus on botulinum toxin type A and its application in aesthetic medicine--a global, evidence-based botulinum toxin consensus education initiative: part I: botulinum toxin in clinical and cosmetic practice.

Background The U.S. Food and Drug Administration has approved four distinct formulations of botulinum toxin (BoNT) serotypes A and B (BoNTA and BoNTB) for medical use. These four products are indicated for many medical applications, but the three BoNTA formulations are the most widely used worldwide and are the only products approved for aesthetic use. The latest approval of a BoNTA with no complexing proteins (incobotulinumtoxinA) necessitates a review and discussion of differences between available formulations and the effect that these differences may have on clinical practice. Objectives To review the history, science, safety information, and current and emerging applications of BoNT in clinical and cosmetic practice and to compare commercially available BoNTA formulations. Methods and Materials Publications, clinical trials, and author experience were used as a basis for an up‐to‐date review of BoNT and its use in human medicine. The similarities and differences between formulations are presented, and diffusion, spread, equivalency ratios, stability, and storage are discussed. Results Each commercial formulation has unique characteristics that may influence its use in aesthetic medicine. Familiarity with the similarities and differences between products will aid physicians in making patient care decisions. Conclusion New formulations, emerging uses, and continued research into the science and uses of BoNTA will lead to increasingly refined therapeutic approaches and applications. Continued education is important for physicians to optimize use of the agent according to the most current evidence and approaches.

Ultrastructural analysis of 3 hyaluronic acid soft-tissue fillers using scanning electron microscopy.

BACKGROUND Although hyaluronic acid (HA) specifications such as molecular weight and particle size are fairly well characterized, little information about HA ultrastructural and morphologic characteristics has been reported in clinical literature. OBJECTIVE To examine uniformity of HA structure, the effects of extrusion, and lidocaine dilution of 3 commercially available HA soft-tissue fillers. MATERIALS AND METHODS Using scanning electron microscopy and energy-dispersive x-ray analysis, investigators examined the soft-tissue fillers at various magnifications for ultrastructural detail and elemental distributions. RESULTS All HAs contained oxygen, carbon, and sodium, but with uneven distributions. Irregular particulate matter was present in RES but BEL and JUV were largely particle free. Spacing was more uniform in BEL than JUV and JUV was more uniform than RES. Lidocaine had no apparent effect on morphology; extrusion through a 30-G needle had no effect on ultrastructure. CONCLUSION Descriptions of the ultrastructural compositions and nature of BEL, JUV, and RES are helpful for matching the areas to be treated with the HA soft-tissue filler architecture. Lidocaine and extrusion through a 30-G needle exerted no influence on HA structure. Belotero Balance shows consistency throughout the syringe and across manufactured lots.

Cytotoxic T lymphocytes and phenotypically abnormal epidermal dendritic cells in fixed cutaneous eruptions

Fixed cutaneous eruptions are erythematous plaques or bullae that recur, often after drug ingestion, at precisely the same cutaneous sites. The study of this condition may provide insight into the mechanisms responsible for regionally localized, immunologically mediated dermatoses. Biopsy specimens from both advancing borders and established centers of fixed eruptions were studied by immunofluorescence microscopy, light microscopy (1-micron sections), and transmission electron microscopy, and with a panel of monoclonal antibodies to Langerhans cells and subsets of T lymphocytes. The dermal inflammatory infiltrates of the advancing edges of the lesions were composed predominantly of OKT4/Leu-3a-positive lymphoid cells in perivascular array. In more established regions (the centers of the lesions), the majority of mononuclear cells were OKT8-positive lymphocytes disposed along the dermal-epidermal junction and migrating into the epidermis through focal defects in the basement membrane. In these areas, keratinocyte reactivity for anti-HLA-DR antibody and the apposition of intraepidermal lymphocytes to degenerating keratinocytes were observed. T6-positive epidermal dendritic cells were observed in normal numbers in the epidermis, although extensive study failed to reveal characteristic Langerhans cell granules within these cells. It is concluded that fixed cutaneous eruptions are characterized by an early vascular phase involving lymphocytes with helper/inducer phenotypes, and a later epidermal phase involving cytotoxic/suppressor cells. Potential effector cells with the phenotypic characteristics of cytotoxic T cells appear to represent important mediators of the epidermal damage characteristic of fixed cutaneous eruptions. Morphologically abnormal epidermal dendritic cells may contribute to regionally altered antigen presentation and may thus be relevant to the recurrence of lesions at identical cutaneous sites.