Understanding visual search patterns of dermatologists assessing pigmented skin lesions before and after online training.

The goal of this investigation was to explore the feasibility of characterizing the visual search characteristics of dermatologists evaluating images corresponding to single pigmented skin lesions (PSLs) (close-ups and dermoscopy) as a venue to improve training programs for dermoscopy. Two Board-certified dermatologists and two dermatology residents participated in a phased study. In phase I, they viewed a series of 20 PSL cases ranging from benign nevi to melanoma. The close-up and dermoscopy images of the PSL were evaluated sequentially and rated individually as benign or malignant, while eye position was recorded. Subsequently, the participating subjects completed an online dermoscopy training module that included a pre- and post-test assessing their dermoscopy skills (phase 2). Three months later, the subjects repeated their assessment on the 20 PSLs presented during phase I of the study. Significant differences in viewing time and eye-position parameters were observed as a function of level of expertise. Dermatologists overall have more efficient search than residents generating fewer fixations with shorter dwells. Fixations and dwells associated with decisions changing from benign to malignant or vice versa from photo to dermatoscopic viewing were longer than any other decision, indicating increased visual processing for those decisions. These differences in visual search may have implications for developing tools to teach dermatologists and residents about how to better utilize dermoscopy in clinical practice.

Interleukin-16 as a marker of Sézary syndrome onset and stage.

INTRODUCTION: Sézary syndrome is one of the most common forms of cutaneous T cell lymphoma (CTCL). It is characterized by skin infiltration of malignant T cells. We examined interleukin-16, a potent T cell chemoattractant and cell-cycle regulator, as a prospective marker of disease onset and stage. METHODS: The correlation of total intracellular interleukin-16 and surface CD26 was studied by flow cytometry. Confocal microscopy was performed to determine localization of interleukin-16 at different stages of the disease. The levels of interleukin-16 in plasma and culture supernatants were examined by enzyme-linked immunoassay. Additionally, lymphocytes from stage IB patients were cultured in the presence of interleukin-16 alone and in combination with interleukin-15, and their ability to survive and proliferate was determined by cell counts and [3H]TdR incorporation. RESULTS: The data indicate that loss of both nuclear and intracellular pro-interleukin-16 highly correspond to disease stage, with a concomitant increase in secreted mature interleukin-16 in both culture supernatants and patients' plasma that peaks at stage IB. Loss of intracellular interleukin-16 strongly corresponded to loss of surface CD26, which has been shown to occur with more advanced stage of CTCL. Nuclear translocation of pro-interleukin-16 was not observed in late stages of Sézary syndrome, indicating this loss is not reversible. CONCLUSIONS: We propose that it is feasible to use plasma levels of IL-16 as a potential diagnostic marker of Sézary syndrome and to use loss of intracellular IL-16 as a prognostic indicator of disease severity and stage.

Dermatology in the Diagnosis of Noncutaneous Malignancy: Paraneoplastic Diseases.

It is important to recognize paraneoplastic dermatoses because they allow the practitioner to begin an early, directed workup to detect an underlying malignant neoplasm. In this review, several paraneoplastic dermatoses are outlined using existing data to detail each one's association with underlying malignancy, demographics, prognosis, and treatment considerations.

Orf-induced immunobullous disease: A distinct autoimmune blistering disorder.

BACKGROUND: Many complications have been reported after orf infection, including lymphadenopathy, secondary bacterial infection, and erythema multiforme. Rare associations with papulovesicular eruptions, including a bullous pemphigoid-like eruption, have also been described. OBJECTIVES: Our purpose was to clinically, histologically, and immunologically characterize two cases of orf-induced blistering disease, and to determine whether this condition represented a novel disease entity distinct from known immunobullous diseases. METHODS: Two patients were clinically described and skin biopsy specimens were collected for routine histology, direct immunofluorescence studies, and polymerase chain reaction analysis to detect orf viral DNA. Patients' sera were assessed for autoantibodies by indirect immunofluorescence studies using normal-appearing human salt-split skin, by Western blot analysis using keratinocyte extracts, dermal extracts, and recombinant type VII collagen, and immunoprecipitation studies of extracts from biosynthetically radiolabeled human keratinocytes. RESULTS: Two distinctive cases of severe, diffuse blistering eruptions after orf infection are described. In one patient, orf virus DNA was detected in the inciting orf lesion, but not in blistered skin, ruling out disseminated orf infection as a cause of the blisters. In both cases, histology revealed subepidermal blisters with mixed inflammatory cell infiltrates containing neutrophils and eosinophils, direct immunofluorescence microscopy studies demonstrated IgG and C3 deposited at the dermoepidermal junctions of perilesional skin, and indirect immunofluorescence studies demonstrated circulating antibasement membrane IgG that bound the dermal side of salt-split skin. Extensive immunoblot and immunoprecipitation studies failed to reveal a consistent, identifiable autoantigen. LIMITATIONS: We describe only two cases. The autoantigen recognized by circulating autoantibodies was not identified. CONCLUSIONS: Orf-induced immunobullous disease is a unique disease entity that is clinically and immunologically distinct from bullous pemphigoid, epidermolysis bullosa acquisita, and other known immunobullous conditions.

Red Rashes of the Vulva.

Red patches and plaques of the vulva may be manifestations of neoplasms, infections, or inflammatory skin diseases. These diseases can mimic one another clinically; features that generally allow the diseases to be identified on most cutaneous surfaces can be altered in the moist, occluded vulvar environment, making clinical diagnosis difficult. A detailed history and thorough physical examination can point to the likely diagnosis, but biopsy and culture may be needed for diagnosis especially in refractory disease. It is not uncommon for several of these processes to be present concomitantly or complicating other vulvar diseases.

Palisaded neutrophilic and granulomatous dermatitis: an unusual cutaneous manifestation of immune-mediated disorders.

OBJECTIVE: Palisaded neutrophilic and granulomatous dermatitis (PNGD) is an uncommon skin eruption most often associated with rheumatoid arthritis and other immune-mediated diseases. We present 4 cases to familiarize rheumatologists with the clinical presentation and histopathology of PNGD. METHODS: We report 4 cases to illustrate the clinical and histologic spectrum of this rare skin disease found in rheumatologic patients. The disease pathogenesis and treatment options are discussed. RESULTS: All 4 patients presented with symmetric erythematous-to-violaceous papules and plaques that, upon biopsy, revealed a dermatitis composed of variable numbers of histiocytes and neutrophils. Some cases responded to topical corticosteroid treatment or to dapsone, whereas others resolved spontaneously. CONCLUSIONS: PNGD is a rare cutaneous finding in patients with a variety of immune-mediated systemic diseases, most often rheumatoid arthritis. It is a benign condition that may spontaneously remit or may respond favorably to topical corticosteroids or dapsone.

Therapy of refractory pemphigus vulgaris with monoclonal anti-CD20 antibody (rituximab).

Three patients with refractory pemphigus vulgaris improved after rituximab, an anti-CD20 monoclonal antibody directed against B cells. Treatment was well tolerated immediately, but one patient developed fatal pneumocystis carinii pneumonia. Serious infections have occurred in several pemphigus patients treated with rituximab and immunosuppressive medications, warranting further evaluation of risk-benefit ratio.

Cycle therapy of actinic keratoses of the face and scalp with 5% topical imiquimod cream: An open-label trial.

BACKGROUND: Preliminary studies indicate that topically applied immune response modifiers may be an effective and safe method of treating actinic keratoses (AKs). OBJECTIVE: Our aim was to study the potential efficacy of topical 5% imiquimod cream in the treatment of facial or scalp AKs and improve the safety profile by using a novel "cycle" dosing regimen. METHODS: This pilot study is an open-label trial that included 25 patients who had between 5 and 20 discrete AKs within a cosmetic unit of the forehead, scalp, or cheek. Treatment consisted of once-daily application of 5% imiquimod cream, 3 times a week for 4 weeks. to the entire cosmetic unit, followed by a rest period of 4 weeks. The cycle was repeated if any AKs remained after a complete 8-week cycle. A maximum of 3 cycles was permitted (24 weeks). Thirty-three sites in 25 patients were evaluated. RESULTS: Compliance was excellent with a very tolerable safety profile. Complete clearing of all AKs was noted in 82% (27/33) of anatomic sites in 25 study subjects. Almost half the sites (15/33) were clear at the end of the first cycle. A "therapeutic interval" was noted during the rest period wherein clinical inflammation subsided but AKs continued to clear. An added effect was the uncovering and clinical appearance and subsequent eradication of incipient (subclinical) AKs in the treatment area. CONCLUSION: There was excellent compliance with the cycle therapy regimen. The observations and hypotheses made in this pilot study will be tested in controlled, randomized trials with larger study populations. The identification of a therapeutic interval may prove to be beneficial in formulating individualized dosing regimens.

An open trial of topical tacrolimus for erosive oral lichen planus.

Erosive oral lichen planus is a chronic, painful disease that is frequently refractory to treatment. We describe 6 patients with erosive oral lichen planus, not responsive to topical steroids, who showed substantial improvement with the use of topical tacrolimus ointment 0.1%. This medication was well tolerated and appears to be effective in controlling erosive oral lichen planus.