Holly B. Faust

Administration of DAB389IL-2 to patients with recalcitrant psoriasis: A double-blind, phase II multicenter trial

BACKGROUND Current therapies for recalcitrant psoriasis focus on immunoregulation and targeting of activated T-lymphocytes rather than keratinocytes. Previous studies with low doses of the lymphocyte-selective fusion protein DAB389IL-2 have shown benefit to patients with psoriasis. OBJECTIVE We examined the safety and efficacy of DAB389IL-2 in 41 volunteers receiving more frequent and higher doses than in a previous trial. METHODS Patients were randomized to receive either placebo or 5, 10, or 15 microg/kg daily of DAB389IL-2 intravenously for 3 consecutive days each week for 4 consecutive weeks with a subsequent 4-week observation period. RESULTS Of the placebo group, 17% (2 of 12) exhibited at least 50% improvement from baseline Psoriasis Area and Severity Index scores at the end of the study, whereas 24% of all treated patients (7 of 29) showed the same improvement. Overall, 3 of 12 (25%) patients given placebo as opposed to 12 of 29 (41%) patients treated with DAB389IL-2 improved to this same extent at some point during the study. The rate of improvement for treated patients was significantly greater than for placebo patients (p = 0.04; repeated measures ANOVA). Among treated patients, decreases in Psoriasis Area and Severity Index scores were paralleled by changes in the Physicians Global Assessment and the Dermatology Life Quality Index. Treatment in ten patients was discontinued because of adverse events. Flu-like symptoms were the most common with severity increasing at the two higher doses. Only one serious adverse event was reported. This occurred in a patient receiving 5 microg/kg daily who experienced vasospasm and a coagulopathy resulting in arterial thrombosis. CONCLUSION Our findings are consistent with the potential antipsoriatic activity of DAB389IL-2 demonstrated in an earlier study. However, DAB389IL-2 was less well tolerated at this dosing regimen, particularly at the highest dose, and it was too toxic at these doses and schedules to be considered in the routine treatment of psoriasis.

The diagnostic yield in submitting nevi for histologic examination.

BACKGROUND Dermatologists have expertise in the clinical diagnosis of benign melanocytic nevi. However, there are no data to confirm the accuracy of diagnosis. Differences in the diagnostic accuracy between dermatologists and nondermatologists with regard to cutaneous tumors has been infrequently studied. OBJECTIVE We examined the rate of malignant tumors occurring in lesions submitted for routine microscopic examination that were clinically diagnosed as benign melanocytic nevi. METHODS We conducted a study at a regional, non-hospital-based dermatopathology laboratory using specimens submitted by physicians of various specialties who were practicing in a 5-state Midwest region of the United States. The preoperative and postoperative diagnoses were examined on the basis of information provided by the clinician and of the subsequent histopathologic diagnosis. A total of 7734 cutaneous pathology reports were reviewed. Specimens submitted with a preoperative clinical diagnosis of mole or nevus, with or without a modifier, were examined and compared with postoperative microscopic diagnoses. RESULTS Of 1946 specimens clinically diagnosed and submitted as benign nevi, 45 (2.3%) were histologically diagnosed as malignant tumors. This included 12 melanomas, 30 basal cell carcinomas, and 3 squamous cell carcinomas. For specimens submitted by dermatologists, the rate of malignant tumors increased when clinical information suggested findings beyond the classic benign clinical presentation with the addition of modifiers such as irritated or atypical, or if a malignancy was considered in the differential diagnosis (trend for increasing clinical suspicion: P = .00002). Fewer dermatologists than nondermatologists mistook a malignant tumor for a benign nevus (1.3% vs 3.8%, P = .003). CONCLUSION Our data document that 2.3% of clinically diagnosed benign nevi were microscopically diagnosed as malignant tumors. Whether this malignancy rate in clinically diagnosed, benign, melanocytic nevi is above or below the threshold to establish a policy for submission for histopathologic examination remains to be determined as a collective societal and medical professional responsibility.

Outcomes research: An overview

During the past few years there has been significant interest in studying methods that document outcomes of medical care. Outcomes management should result in higher quality health care at lower cost. However, what does outcomes research mean and how does it apply to dermatology and specifically to the individual dermatologist? This article reviews the evolution of medical outcomes research and presents the status of the current instruments, indices, and methods.

Cutaneous Histoplasma capsulatum in a nonimmunocompromised patient with previously treated cutaneous Mycobacterium kansasii

This report describes a black woman with a history of cutaneous Mycobacterium kansasii responsive to antituberculous drugs. A culture several years later of cutaneous lesions was also positive for Histoplasma capsulatum. Both cutaneous diseases are rare and most often occur in immunocompromised hosts. There is no known association between these two diseases. This patient may have an as-yet unidentified immunodeficiency that predisposes her to these rare infections. Her case emphasizes the importance of repeat biopsy for atypical skin lesions.

Outcomes research in your office

This article reviews the definition of outcomes research. It explores the reasons that outcomes research should be conducted by practicing physicians in both university and private practice settings. Methods for outcomes research with examples relevant to dermatologists are detailed.