Andrew D. Montemarano

Transcutaneous immunization: A human vaccine delivery strategy using a patch

Transcutaneous immunization, a topical vaccine application, combines the advantages of needle-free delivery while targeting the immunologically rich milieu of the skin. In animal studies, this simple technique induces robust systemic and mucosal antibodies against vaccine antigens. Here, we demonstrate safe application of a patch containing heat-labile enterotoxin (LT, derived from Escherichia coli) to humans, resulting in robust LT-antibody responses. These findings indicate that TCI is feasible for human immunization, and suggest that TCI may enhance efficacy as well as improve vaccine delivery.

Safety and immunogenicity of a proteosome-Shigella flexneri 2a lipopolysaccharide vaccine administered intranasally to healthy adults.

ABSTRACT We studied the safety and immunogenicity of a Shigella flexneri 2a vaccine comprising native S. flexneri 2a lipopolysaccharide (LPS) complexed to meningococcal outer membrane proteins—proteosomes—in normal, healthy adults. A two-dose series of immunizations was given by intranasal spray, and doses of 0.1, 0.4, 1.0, and 1.5 mg (based on protein) were studied in a dose-escalating design. The vaccine was generally well tolerated. The most common reactions included rhinorrhea and nasal stuffiness, which were clearly dose related (P ≤ 0.05). These reactions were self-limited and generally mild. The vaccine elicitedS. flexneri 2a LPS-specific immunoglobulin A (IgA), IgG, and IgM antibody-secreting cells (ASCs) in a dose-responsive manner. At doses of 1.0 or 1.5 mg, highly significant (P < 0.001) increases in ASCs of all antibody isotypes occurred and 95% of subjects had an ASC response in at least one antibody isotype. Dose-related serum antibody responses were observed, with geometric mean two- to fivefold rises in specific serum IgA and IgG titers and two- to threefold rises in IgM in the 1.0- and 1.5-mg-dose groups (P < 0.0001 for each isotype). Elevated serum antibody levels persisted through day 70. Increases in fecal IgG and IgA and also in urinary IgA specific for S. flexneri 2a LPS were demonstrated. These were most consistent and approached statistical significance (P = 0.02 to 0.12 for various measures) on day 70 after the first dose. The magnitude of immune responses to intranasally administered proteosome-S. flexneri 2a LPS vaccine is similar to those reported for live vaccine candidates associated with protective efficacy in human challenge models, and further evaluation of this product is warranted.

Confluent and reticulated papillomatosis: Response to minocycline

BACKGROUND Confluent and reticulated papillomatosis (CRP) of Gougerot and Carteaud is an uncommon disorder of unknown cause for which a variety of treatments have been proposed. OBJECTIVE We attempted to evaluate the effectiveness of oral minocycline. METHODS Nine patients with CRP were treated with oral minocycline, 50 mg twice a day, for 6 weeks. The average follow-up period was 11 months. Recurrence rate, side effects, and effectiveness of therapy were assessed. RESULTS All patients except two had a 90% to 100% response to therapy. Recurrences were noted in three patients, all of whom responded to re-treatment with minocycline. None of the nine patients had an adverse reaction. CONCLUSION Minocycline, 50 mg twice a day, is safe and effective for CRP.

Staphylococcus aureus as a Cause of Perianal Dermatitis

Abstract: Perianal dermatitis has been reported to be caused by group A ß‐hemolytic Streptococcus. We present a case caused by Staphylococcus aureus. A clinical clue pointing to this organism was the presence of satellite pustules, identifying the pathogen in perianal dermatitis is therapeutically Important, as oral penicillin VK will not be effective If 5. aureus is the true cause. Other streptococcal and staphylococcal cutaneous infections may exhibit overlapping clinical features, including scarlet fever, Impetigo, toxic shock syndrome, and cellulitis.

Hypersensitivity to paclitaxel manifested as a bullous fixed drugeruption

Paclitaxel is the first of a new class of microtubule-stabilizing antitumor agents, with demonstrated activity against advanced and refractory ovarian, breast, lung, and head and neck cancers. It was first isolated from the bark of the endangered Pacific yew Taxus brevifolia. 1 Neutropenia is the dose-limiting toxicity of paclitaxel. A high incidence of major hypersensitivity reactions (HSRs) (including those with cutaneous manifestations) occurred in phase I studies, but they were minimized by premedication schemes and prolonged administration times. 2 We describe a previously unrecognized hypersensitivity to paclitaxel that we classified as a bullous fixed drug eruption.

Skin cancers, blindness, and anterior tongue mass in African brothers

HistoryTwo Northern African brothers presented to theNational Institutes of Health for evaluation of severedamage to sun-exposed areas of the skin, eyes, andmucosae; multiple skin cancers; a tongue mass; andphotophobia with loss of vision.The patients were born full term after uncompli-cated pregnancies and achieved age-appropriatedevelopmental milestones. Patient XP393BE (Fig 1,A), 23 years old, was noted to have freckle-likepigmented lesions on his face at 2.5 years andphotophobia by age 3 (Table I). A squamous cellcarcinoma(SCC)hadbeenremovedfromhisnoseatage 13 and the site was grafted with sun-shieldedskin from his thigh. His brother, patient XP394BE(Fig 1, D), 17 years old, developed freckle-likelesions on his face by 8 years of age. At age 13, anSCCwasexcisedfromhisrightcheek.Bothboyshadbilateral progressive loss of vision with unilateralblindness since the age of 12 to 14 years (Fig 1, B).PatientXP393BEhada10-year history ofaslowlyenlarging, painful, bleeding mass on the tip of histongue (Fig 2, A). He denied weight loss, excessiveconsumption of alcohol, or chewing of tobacco orbetel quid.LivinginKuwait,Sudan,Libya,andEgypt,neitherpatient had a history of sunburns or use of sunprotection. The patients have a 21-year-old unaf-fected brother. Their parents were second cousinsand members of the same tribe in the Sudan. Therewas no family history of cancer.Physical examinationSkin examination of both patients revealed nu-merous 1- to 5-mm hyperpigmented macules on thecheeksandscalp(seeFigs1and2)andsun-exposedportions of the chest and extremities with sparing ofsun-protected sites. Patient XP393BE had a 1.3- 31.7-cm stellate, indurated, black, brown and grayplaque on his left cheek (Fig 1, A). Dermatoscopyrevealed characteristic leaf-like structures and blue-gray ovoid nests that distinguish pigmented basalcell carcinoma from melanoma (Fig 1, C). A 1-cmnodular, ulcerated mass was present on the base ofhis nose, and there were multiple translucent blacklesions on his face. Patient XP394BE had a crusted,darklypigmentedplaqueontheleftalaandtipofthe

Surgical Pearl: Purse string suture in the management of poorly delineated melanomas

The purse string suture technique has received little attention in the surgical literature. Its application in dermatologic surgery has been mainly to reduce the size of a surgical defect to allow placement of a smaller, full-thickness skin graft.1-4 We have found the purse string suture to be effective in the management of poorly demarcated melanoma. We have used the purse string technique in 10 patients with biopsy-confirmed melanoma. For most of them, the clinical margin of the neoplasm was poorly defined. All underwent excision of the clinically detectable lesion, using recommended guidelines of 5 mm for in situ melanoma, 1 cm for invasive melanoma with Breslows depth less than 1 mm, and 2 cm for intermediate-thickness melanomas.5,6 The oval surgical defects were then managed with an intradermal circumferential purse string suture, with 3-0 or 4-0 nonabsorbable polypropylene.4 The purse string was tied, thereby either reducing the size of or in some cases completely closing the defect. The pathology reports were received in 48 to 72 hours. If a positive margin was present, the patient returned for additional surgery. The original oval defect was re-created after the removal of the purse string suture. This greatly facilitated a more precise measurement for additional margins and excision of the residual tumor. The newly created larger defect was often managed again with a purse string suture. If clear surgical margins were achieved, the purse string suture was removed after 21 days. The type of final reconstruction and its timing were primarily dependent on size and location of the lesion, as well as the degree of confidence in obtaining clear margins. We used fullthickness skin grafts, flaps, primary closure, and second-intention healing as final reconstructive options. No significant complications were observed. A biopsy-confirmed lentigo maligna on the right cheek (Fig. 1) with poorly definable clinical margins was outlined with the aid of a Woods lamp and excised with a 5 mm margin. The oval From the Dermatology Service, Walter Reed Army Medical Center. The opinions and assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the Department of Defense or the United States Army. Reprints not available from the authors. J Am Acad Dermatol 1998;38:99-101. 16/74/85559 Surgical Pearl: Purse string suture in the management of poorly delineated melanomas