Biomedical subjects
Publications and source records attributed to D P Fivenson.
Lower extremity ulcers can be challenging diagnostically and therapeutically. This article, provides an overview of the different kinds of lower extremity wounds typically seen by the medical dermatologist. It also reviews new treatment modalities, including topical growth factors and bioengineered skin. A team approach is emphasized.
Lupus profundus is an unusual clinical variant of cutaneous lupus erythematosus that has previously been described as a benign disease that follows a mild course. This report describes the extent of disease and associated comorbidities in patients with severe lupus profundus and systemic lupus erythematosus. Four cases of lupus profundus are reviewed and their associated systemic disease complications are highlighted. All four patients fulfilled at least four of the 11 criteria for systemic lupus erythematosus. One patient suffered from severe facial disfigurement and Parry-Romberg syndrome. Two patients developed nonhealing ulcers on the scalp. All four patients had scarring alopecia as well as depressed areas over large areas of their body surfaces. All patients were resistant to conservative therapy, and required long-term aggressive therapy. Clinical depression secondary to disfigurement was a major problem in three patients. Extensive lupus profundus may be associated with more serious systemic disease and warrants aggressive treatment early on to prevent permanent disfigurement and its resultant psychological consequences.
This report highlights the finding of ulcerative plantar keratoderma in two patients with systemic lupus erythematosus (SLE). Both patients suffered from painful plantar ulcerations and fissures; in one patient there was diffuse desquamation over the entire plantar surface, while the other patient's lesions were focal and accentuated over weight-bearing surfaces. Other etiologies for keratoderma including papulosquamoua disease, contact dermatitis, tinea and primary keratodermas were excluded. Both patients were resistant to multiple topical therapies including super-potent topical corticosteroids, vitamin D analogues and retinoids, but did report moderate relief with hydrocolloid dressings applied over super-potent topical corticosteroids and pressure off-loading measures. Lupus-associated keratoderma can be recurrent and recalcitrant to treatment, often necessitating aggressive therapy and particular attention to advanced wound care methodologies. While not a specific cutaneous sign of lupus, it should be recognized as a cause for considerable morbidity.
Tazarotene 0.1% gel and tretinoin 0.025% gel are both effective in the treatment of acne vulgaris. Results of a multicenter, double-blind, randomized, parallel-group study that compared the efficacy and tolerability of these drugs are presented here. A total of 143 patients with mild-to-moderate facial acne vulgaris were randomized to receive tazarotene 0.1% gel or tretinoin 0.025% gel once daily for 12 weeks. Tazarotene 0.1% gel was more effective than tretinoin 0.025% gel in reducing the open comedo count (P < or = .05), the total noninflammatory lesion count (P < or = .05), and the total inflammatory lesion count (not statistically significant). At some time points, tazarotene was associated with increased irritation, but peeling, erythema, dryness, burning, and itching never exceeded trace levels. We conclude that tazarotene 0.1% gel is more effective than tretinoin 0.025% gel in reducing noninflammatory lesions and similarly effective in reducing inflammatory lesions.
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BACKGROUND: In select cases, lichen planus has been observed to be a paraneoplastic condition sometimes associated with paraneoplastic pemphigus, a disease featuring autoantibodies directed against plakin proteins, desmogleins 3 and 1, and a still uncharacterized 170-kd antigen. Epitope spreading describes the phenomenon where underlying chronic inflammation leads to the sequential recognition of new epitopes on self-proteins over time. OBSERVATIONS: Five of 6 patients diagnosed as having paraneoplastic pemphigus had concomitant clinical and histological features of lichen planus. In 1 patient, results of the initial indirect immunofluorescence on rat bladder were negative and only 2 of the 5 antigens were identified by immunoprecipitation. After 1 year of worsening disease, repeated testing confirmed the presence of antibodies directed against all 6 of the implicated antigens, supportive of our hypothesis that epitope spreading may occur in paraneoplastic pemphigus. CONCLUSIONS: Lichenoid eruptions may predispose to an early evolutionary stage of paraneoplastic pemphigus. Cell-mediated autoimmunity at the dermoepidermal junction may promote the exposure of self-antigens and the development of subsequent and progressive humoral autoimmunity. As such, paraneoplastic pemphigus may demonstrate epitope spreading in a human, humoral-mediated autoimmune disease.
Thirty patients completed this open-label, multicenter prospective study performed to evaluate the efficacy and safety of terbinafine treatment of onychomycosis of the feet in elderly patients. Inclusion criteria included an age of 60 years or older, a diagnosis of onychomycosis confirmed by positive potassium hydroxide (KOH) preparation at baseline, and toenails capable of regrowth. Patients were excluded from the study if they had received any systemic antifungal therapy within the previous 3 months or topical antifungal therapy within 1 week prior to the start of the study; had psoriasis; had toenail abnormalities interfering with normal toenail appearance; were immunosuppressed or immunodeficient; or had serum hepatic enzyme (serum glutamic-oxaloacetic transaminase, SGOT; serum glutamic-pyruvic transaminase, SGPT) values greater than 1.5 times the upper limit of normal at baseline. Following baseline evaluations, eligible patients received a 12-week supply of oral terbinafine (250 mg/day) for self-administration. Compliance was assessed by tablet counts at each visit and defined as the use of at least 80% of the medication prescribed at the first two visits. Follow-up evaluations were conducted for the next 60 weeks, for a total study period of 72 weeks. These visits occurred at weeks 6, 12, 24, 36, 48, and 72. All follow-up visits included: (i) the reporting of adverse effects; (ii) assessment of efficacy by KOH preparation, mycologic culture, and investigator evaluation; and (iii) physician and patient global assessments of various quality of life parameters (except for the visit at week 36). Safety and tolerance were assessed by physical examination at baseline and week 12, by laboratory evaluations (hematology, blood chemistry, and urinalysis) at baseline, week 6 and week 12, and by reporting and evaluation of adverse events throughout the entire study. Investigators assessed the extent of involvement of the target toenail and recorded global assessments of therapeutic efficacy at all visits. Mycologic evaluation was conducted by KOH preparation and a mycologic culture of the target toenail. Because of discrepancies in KOH results between the investigator sites and the central laboratory in early analyses, we chose to use the mycologic culture results to evaluate efficacy. Because all 30 subjects were treated with terbinafine, the entire group was considered for safety evaluation.
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OBJECTIVE: To determine the efficacy of the 585-nm flashlamp-pumped pulsed-dye laser and silicone gel sheeting in the treatment of hypertrophic scars in lighter- and darker-skinned patients. DESIGN: Prospective, single-blind, randomized, internally controlled, comparison investigation. SETTING: Large academic dermatology department. PATIENTS: Twenty patients with hypertrophic scars (19 completed the laser treatments and 18 completed the silicone gel sheeting treatments). MAIN OUTCOME MEASURES: Clinical measurements included hypertrophic scar blood flow, elasticity, and volume. Patients' subjective complaints of pruritus, pain, and burning were also monitored. Histological assessment of fibrosis, number of telangiectasias, and number of mast cells was performed. Statistically significant improvements in clinical measurements and patients' subjective complaints determined treatment success. RESULTS: Mean scar duration was 32 months (range, 4 months to 20 years). There was an overall reduction in blood flow, volume, and pruritus over time (P = .001, .02, and .005, respectively). However, no differences were detected among treatment and control groups. There was no reduction in pain or burning (0-40 weeks), elasticity (8-40 weeks), or fibrosis (0-40 weeks, n = 5 biopsies) in the treated or control sections of the scars. Unlike in a previous study, the number of mast cells in the scars was similar to the number of mast cells in healthy skin. CONCLUSION: Clinical results demonstrate that the improvements in scar sections treated with silicone gel sheeting and pulsed-dye laser were no different than in control sections.
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BACKGROUND: A variety of immunologic abnormalities have been described in systemic and experimental lupus erythematosus (LE). Several T-cell defects, especially in helper T (Th) cell cytokines, have been reported. OBJECTIVE: Our purpose was to identify the Th cytokine profile in cutaneous LE. METHOD: Total RNA was extracted from punch biopsy specimens from 19 patients with cutaneous LE (nine, discoid LE; two, subacute cutaneous LE; and eight, systemic LE) and from four healthy control subjects. RNA was reverse transcribed into complementary DNA and amplified with polymerase chain reaction (PCR) primers specific for interleukin-2 (IL-2), IL-4, IL-5, IL-10, interferon gamma (IFN-gamma), and beta actin. PCR products were detected by agarose gel electrophoresis and Southern blot with 32P-labeled, nested probes. RESULTS: Sixteen of 19 cutaneous LE specimens lacked IL-2, all were negative for IL-4, and 10 of 19 had detectable IL-10, whereas IFN-gamma and IL-5 messenger RNAs were present in the majority of LE specimens. IFN-gamma and IL-10 mRNAs were found in all normal skin controls, whereas IL-2, IL-4, and IL-5 mRNAs were undetectable. Functional IFN-gamma protein was evidenced by intercellular adhesion molecule-1 and HLA-DR staining of keratinocytes in nine of nine LE specimens but not in normal skin. The pattern of cytokine mRNAs, intercellular adhesion molecule-1, and/or HLA-DR expression in cutaneous LE specimens did not vary with different subtypes of LE, antinuclear antibody titer, or the magnitude of inflammation. CONCLUSION: The presence of IL-5 mRNA in cutaneous LE specimens suggests that Th type 2 cells combine with local IFN-gamma production to augment disease and may be related to the pathophysiology of cutaneous LE.
This brief survey has, it is hoped, helped to ease some of the anxiety associated with the management of complex autoimmune skin disorders. The main points to remember are that there are numerous therapeutic options for each disease. I like to think of this method of therapeutics as 'informed trial and error.' One does not need to master the monitoring, side-effect profile, or dosing regimen for each of the drugs in Table 1; only a working knowledge of a few is sufficient. I hope that the readers take advantage of the many tables and caveats I have included so this article can be a ready reference for many future uses.
BACKGROUND: Treatment of postinflammatory hyperpigmentation in patients of Fitzpatrick skin types IV, V, and VI is difficult. Glycolic acid peels are useful for pigment dyschromias in caucasians; however, there are no controlled studies examining their safety and efficacy in dark-complexioned individuals. OBJECTIVE: To determine if serial glycolic acid peels provide additional improvement when compared with a topical regimen of hydroquinone and tretinoin. METHODS: Nineteen patients with Fitzpatrick skin type IV, V, or VI were randomized to a control or peel group. The control group applied 2% hydroquinone/10% glycolic acid gel twice daily and 0.05% tretinoin cream at night. The peel patients used the same topical regimen and, in addition, received six serial glycolic acid peels (68% maximum concentration). Patients were evaluated with photography, colorimetry, and subjectively. RESULTS: Sixteen patients completed the study. Both treatment groups demonstrated improvement, but the patients receiving the glycolic acid peels showed a trend toward more rapid and greater improvement. The peel group also experienced increased lightening of the normal skin. CONCLUSIONS: This pilot study demonstrates that serial glycolic acid peels provide an additional benefit, with minimal adverse effects, for the treatment of postinflammatory hyperpigmentation in dark-complexioned individuals.
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We used a standard polymerase chain reaction (PCR)/Southern blot assay (sensitivity > 10(-5)) to detect human T-cell lymphotrophic virus type I (HTLV-I) proviral pX, pol, and env genes in the lesional skin of 42 American patients with cutaneous T-cell lymphoma (CTCL). As in some prior reports using similar methods, a variable proportion of PCR tests were positive (seven of 42 for pX, three of 42 for pol, and two of 37 for env), resulting in an overall positive test rate of 12 of 121 (10%). To determine the significance of these positive test results, we performed several additional studies. D1S80 polymorphism analysis of CTCL cases and HTLV-I PCR analysis of non-CTCL dermatosis controls showed no evidence that positive PCR tests resulted from sample mislabeling, gross HTLV-I contamination, or human endogenous retroviruses. We then modified the standard PCR assay to incorporate ultraviolet (UV) light to destroy low-level PCR contamination. With this modified assay (sensitivity > 10(-5)), only three of 12 previously positive cases were still positive, suggesting that the earlier positives were due to trace contamination of PCR reagents or trace contamination of sample DNA. This interpretation was also supported by: (i) a match between pX and pol sequences cloned from one PCR-positive specimen and the MT4-positive control, (ii) our inability to confirm HTLV-I in any PCR-positive case using genomic dot blotting (sensitivity > 10(-2)), and (iii) negative PCR results when new samples from two of the remaining positive cases were analyzed. Finally, we used our modified UV/ PCR/Southern blot assay to test an additional 28 cases of American CTCL for pX. All of them were negative. Although these studies of 70 cases of American CTCL do not exclude the possibility that another virus is involved in the pathogenesis of this disease, they provide strong evidence against a role for HTLV-I. Furthermore, they emphasize the need for special strategies to control for false-positive PCR tests that can result from even trace levels of contamination with viral DNA. As a consequence, associations between diseases and viruses should be viewed skeptically if they are based primarily on conventional PCR data.
BACKGROUND: Treatment of hypertrophic scars can be difficult for both patients and physicians. Silicone-containing gel dressings have been reported to be an effective alternative treatment for hypertrophic scars, yet the mechanism of action of these dressings is unknown. OBJECTIVE: To determine whether silicone is an essential factor in the treatment of hypertrophic scars and investigate the effects of occlusive dressing therapy on the expression of key wound healing mediators. METHODS: A pilot paired comparison, nonrandomized study was conducted comparing a silicone gel sheeting (Silastic [SGS]) with a hydrogel dressing (ClearSite). The effects of the dressings were compared side by side in the treatment of 15 hypertrophic scars at both the clinical and molecular levels through the use of reverse transcriptase/polymerase chain reaction to evaluate effects on the expression of interleukin 8 (IL-8), basic fibroblast growth factor (bFGF), granulocyte-macrophage colony-stimulating factor (GMCSF), epidermal growth factor (EGF), transforming growth factor beta (TGF-beta), and fibronectin. RESULTS: Comparable clinical improvement of the hypertrophic scars was obtained with both dressings. Treatment of hypertrophic scars resulted in increased mean levels of IL-8, bFGF, and GMCSF mRNA; while mean TGF beta and fibronectin mRNAs decreased after treatment with both dressings. Comparison between the two dressings revealed significant changes in IL-8 and fibronectin mRNA levels after treatment with ClearSite, while only fibronectin changes were significant after treatment with SGS with respect to normal skin. Only ClearSite induced significant changes in IL-8 and bFGF levels when untreated scars were compared with posttreatment lesions, suggesting that the hydrogel augments collagenolysis via promotion of inflammation. CONCLUSIONS: This study demonstrates that silicone is not a necessary component of occlusive dressings in the treatment of hypertrophic scars. The pathogenesis of hypertrophic scars is further elucidated by demonstrating that there is molecular evidence for extensive connective tissue remodeling occurring during occlusive dressing therapy.
BACKGROUND: Borrelia burgdorferi has been linked to the pathogenesis of morphea and lichen sclerosus et atrophicus (LSA). However, considerable controversy still exists as to the actual role, if any, that this spirochete plays in the development of these diseases. Antibody titer determinations have been inconclusive and polymerase chain reaction (PCR) studies have yielded conflicting results. OBJECTIVE: We sought to show whether PCR analysis detected B. burgdorferi in archival tissue specimens from the involved skin of 20 North American patients with morphea, 10 patients with LSA, and four patients with scleroderma. METHODS: We used two different sets of PCR primers for the B. burgdorferi flagellin gene, one specific for European strains of B. burgdorferi, and another common to both European and American strains. A subset of these samples were further amplified with nested PCR primers. RESULTS: None of the samples showed PCR products with either primer sets, whereas purified B. burgdorferi DNA and lesional erythema chronicum migrans tissues, which were used as positive controls, yielded easily detectable products with all primer sets. CONCLUSION: These data suggest that B. burgdorferi infection plays no role in the development of morphea, LSA, or scleroderma in North American patients; these findings further support the recent observations that B. burgdorferi strain variability is associated with differential spectra of disease in North America compared with that found in various parts of Europe.