Karen S McGinnis

Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, United States

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Publications (13)51.24 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Eccrine poromas are benign, adnexal tumors that most often occur as a solitary lesion on the palm or sole. The occurrence of multiple eccrine poromas is extremely rare. In this report, we describe the development of several eccrine poromas in an acral distribution in a 42-year-old man. Before the appearance of these tumors, the patient had received total body irradiation and allogeneic bone marrow transplantation for treatment of acute lymphocytic leukemia. As a complication of the bone marrow transplant, the patient developed chronic graft-versus-host disease, which was treated with immunosuppressive therapy. We discuss this patient and review the available literature regarding multiple eccrine poromas.
    Journal of the American Academy of Dermatology 09/2006; 55(2 Suppl):S46-9. · 4.91 Impact Factor
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    ABSTRACT: We developed and validated a measurement instrument (CLASI—Cutaneous Lupus Erythematosus Disease Area and Severity Index) for lupus erythematosus that could be used in clinical trials. The instrument has separate scores for damage and activity. A group of seven American Dermato-Rheumatologists and the "American College of Rheumatology Response Criteria Committee on SLE (systemic lupus erythematosus)" assessed content validity. After a preliminary session, we conducted standardized interviews with the raters and made slight changes to the instrument. The final instrument was evaluated by five dermatologists and six residents who scored nine patients to estimate inter- and intra-rater reliability in two sessions. Consultation with experts has established content validity of the instrument. Reliability studies demonstrated an intra-class correlation coefficient (ICC) for inter-rater reliability of 0.86 for the activity score (95% confidence interval (CI)=0.73–0.99) and of 0.92 for the damage score (95% CI=0.85–1.00). The Spearman's (Sp) for intra-rater reliability for the activity score was 0.96 (95% CI=0.89 to 1.00) and for the damage score Sp was 0.99 (95% CI=0.97–1.00). Clinical responsiveness needs to be evaluated in a prospective clinical trial, which is ongoing.Keywords: clinical trial, cutaneous lupus erythematosus, discoid lupus erythematosus, outcome instrument, subacute lupus erythematosus
    Journal of Investigative Dermatology 10/2005; 125(5):889-894. · 6.19 Impact Factor
  • Archives of Dermatology 10/2005; 141(9):1176-8. · 4.79 Impact Factor
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    ABSTRACT: For nearly 2 decades clinicians have been treating cutaneous T-cell lymphoma (CTCL) with regimens that combine interferon alfa with retinoid compounds. In December 1999 a new retinoid, bexarotene, was approved by the US Food and Drug Administration for the treatment of CTCL. At the manufacturer's recommended dose of bexarotene (300 mg/m(2) of body surface area), it has proven to be a highly effective therapy for all stages of CTCL. Nevertheless, this dose is typically associated with adverse effects including severe hyperlipidemia. Furthermore, there appears to be no standardization of dosing among physicians who treat CTCL. We present 3 representative patients, 2 with erythrodermic CTCL and 1 with follicular mycosis fungoides, who experienced the rapid clearing of skin disease while being treated with a combination of low-dose bexarotene and low-dose recombinant interferon alfa. Combining low-dose bexarotene with low-dose interferon alfa was well tolerated and led to rapid improvement in our patients. We review the clinical and biologic basis for this approach.
    Journal of the American Academy of Dermatology 04/2004; 50(3):375-9. · 4.91 Impact Factor
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    ABSTRACT: The use of photochemotherapy for the treatment of cutaneous T-cell lymphoma (CTCL) was first reported by Gilchrest et al. in 1976. 1 Oral 8-methoxypsoralen (8MOP) was administered to patients with early-stage disease, followed by photoactivation with ultraviolet-A irradiation to the skin. This technique, referred to as PUVA, has since become a mainstay of therapy for CTCL and other inflammatory skin conditions. In the early 1980s PUVA was modified for the treatment of CTCL patients with more advanced disease. Subsequent to oral 8MOP administration, whole blood was collected and enriched for white blood cells. The leukocyte-enriched population was then irradiated with UVA and returned to the patient intravenously. This technique was referred to as extracorporeal photopheresis (ECP) and represented the first ‘‘systemic’’ form of PUVA therapy. In 1987 Edelson published the first report documenting the use of ECP in the treatment of patients with erythrodermic CTCL. 2 A 73% overall clinical response rate was reported, with a median survival time of 62 months from the onset of erythroderma. 3 In comparison to historical controls, ECP was associated with improved survival and decreased morbidity among patients with similar clinical characteristics. In 1988, ECP was approved by the U.S. Food and Drug Administration (FDA) for the treatment of CTCL. Aside from its proven effectiveness in the management of CTCL, ECP has been shown to be of clinical benefit in the treatment of systemic sclerosis, cutaneous graft-versus-host disease, systemic lupus erythromatosis (SLE), allograft rejection, and potentially other autoimmune conditions. 4-7
    Journal of Cutaneous Maedicine and Surgery 08/2003; 7(4 Suppl):8-12. · 0.78 Impact Factor
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    ABSTRACT: Multimodality biological response-modifier therapy that includes photopheresis, interferon, and bexarotene is the standard of care in our institution for advanced cutaneous T-cell lymphoma with peripheral blood involvement. We added psoralen plus long-wave UV-A (PUVA) to this regimen in 5 patients with Sézary syndrome. All patients responded with decreased Sézary counts, resolution of lymphadenopathy, and clearing of skin disease after the addition of PUVA. Adverse effects were well tolerated and managed via close clinical and laboratory follow-up. The addition of PUVA to a multimodality immunomodulatory regimen in patients with Sézary syndrome can result in rapid and sustained remission of both skin and blood-borne disease. Further in vitro and in vivo studies are needed.
    Archives of Dermatology 07/2003; 139(6):771-5. · 4.79 Impact Factor
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    ABSTRACT: It has long been known that certain immune augmenting therapeutics, particularly interferon alpha, can exert profound salutary effects on the clinical progress of patients with cutaneous T-cell lymphoma. Emerging evidence that the host immune response may play an important role in the control of this disorder has led to the clinical application of other cytokines including interleukin-12 and interferon gamma. In this review, the authors will summarize current knowledge regarding the use of cytokines, fusion proteins and antibodies for the treatment of cutaneous T-cell lymphoma.
    Dermatologic Therapy 02/2003; 16(4):331-6. · 1.96 Impact Factor
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    ABSTRACT: Sézary syndrome (SzS) is an advanced form of cutaneous T-cell lymphoma associated with involvement of the peripheral blood by malignant T cells. The disease is defined by impaired cell-mediated immunity and the production of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2), possibly as a result of deficient IL-12 production. To understand the mechanism of this impairment, we examined the composition and function of dendritic cells and monocytes in the blood of SzS patients with different levels of peripheral blood tumor burden. Consistent with our previous observations, numbers of monocytes in SzS patients were comparable to numbers observed in healthy donors. In contrast, decreased IL-12 production correlated with a decrease in the numbers of CD11c(+) dendritic cells, which was particularly profound among patients with medium (20%-50% circulating malignant T cells) and high (more than 50% circulating malignant T cells) tumor burden. Furthermore, CD123(+) dendritic cells, major producers of IFN-alpha, were significantly diminished in SzS patients, regardless of the level of tumor burden. Granulocyte macrophage-colony-stimulating factor-treated patients experienced an increase in the number of dendritic cells but not in IFN-alpha or IL-12 production. However, in vitro stimulation of peripheral blood mononuclear cells from SzS patients with rCD40L and IFN-gamma significantly increased the production of IL-12. Thus, our results demonstrate a profound defect in circulating dendritic cells in SzS patients that may contribute to the pathogenesis of the cytokine disorders and to the depressed cellular immunity. Importantly, the ability of rCD40L to potently induce IL-12 production from monocytes and residual dendritic cells of SzS patients could potentially serve as an immune-restorative therapeutic agent.
    Blood 12/2002; 100(9):3287-94. · 9.78 Impact Factor
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    ABSTRACT: Chronic graft-versus-host disease (cGVHD) is a multiorgan disorder with skin manifestations resembling scleroderma. Since photopheresis, a treatment that induces an anticlonotypic immune response, has proven to be effective in both cutaneous T cell lymphomas with circulating clonal T cells and in cGVHD, we have searched for circulating clonal T cell populations in patients with cGVHD, and determined whether T cell clonality in the blood is associated with therapeutic response. We screened blood samples from 27 patients after HLA-matched allogeneic bone marrow transplantation (allo-BMT), 10 without cGVHD and 17 with extensive cGVHD, for clonal T cell receptor gamma (TCR gamma) gene rearrangements using fluorescent-based polymerase chain reaction (PCR) and automated high-resolution capillary electrophoresis. Amplified populations of clonal T cells with unique TCR gamma gene rearrangements were found in six of 10 (60%) allo-BMT patients without cGVHD and 13 of 17 (76.5%) allo-BMT patients with cGVHD (P = 0.41), as compared to none of 10 (0%) healthy controls. Twelve patients with cGVHD were treated by photopheresis, and the presence of amplified populations of clonal T cells was found to be associated with a cutaneous response to photopheresis, as eight of eight (100%) clone-positive vs none of four (0%) clone-negative patients experienced a clinically significant cutaneous response to treatment (P = 0.001). Our findings suggest that patients with cGVHD that have detectable expanded clonal T cell populations in their peripheral blood, may be more likely to respond to treatment by photopheresis.
    Bone Marrow Transplantation 11/2002; 30(8):509-15. · 3.54 Impact Factor
  • Archives of Dermatology 07/2002; 138(6):740-2. · 4.79 Impact Factor
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    ABSTRACT: To determine if pathology review, within the context of a multidisciplinary pigmented lesion clinic, results in changes in diagnosis of melanocytic lesions and to ascertain if the change in diagnosis altered clinical management and outcome. Retrospective review of pathology reports, progress notes, and diagnoses entered in the University of Pennsylvania (Philadelphia) Pigmented Lesion Clinic database. A total of 5136 primary melanocytic lesions from patients referred to the pigmented lesion clinic between 1991 and 1999 were reviewed by a single pathologist. Of these, 559 (11%) had diagnoses that were changed significantly from the submitting diagnosis, with 120 (2.3%) undergoing a "critical" revision, 63 (1.2%) defined as a change from malignant to benign, and 57 (1.1%) from benign to malignant; 171 (3.3%) remained within the same category (benign or malignant) but had a downgrade in diagnosis (less severe) that would have a significant impact on treatment, prognosis, and research. Likewise, 268 (5.2%) remained within the same category but had an upgrade in diagnosis (more severe) that would have a significant impact on the same parameters. In addition, 257 reexcisions of melanocytic lesions were reviewed, of which 15 (5.8%) were changed from clear to involved margins, while another 16 (6.2%) were changed from involved to clear margins, for a total of 12%. Of the lesions with a critical revision, follow-up was obtained in 98 (83%). The patients in the malignant-to-benign category were followed up for an average of 2.6 years while those in the benign-to-malignant category were followed up for an average of 4.2 years. The change of diagnosis from malignant to benign resulted in 9 patients (17%) being spared a reexcision while 12 patients (23%) were downgraded from a radical to moderate reexcision. The change in diagnosis from benign to malignant resulted in 45 patients (98%) requiring a reexcision after review. Twenty-five of these patients were found to have residual disease in their reexcision specimens or had already had recurrence at the excision site. Furthermore, 7 patients (15%) underwent lymph node dissection or sentinel lymph node biopsy after review. However, none of the nodes were positive for metastatic disease. During this time, 8 patients (17%) in the benign-to-malignant category, and 1 patient (1.9%) in the malignant-to-benign category (who had previously had 4 primary melanomas) developed metastatic disease. Pathology review of primary melanocytic lesions, within the context of a multidisciplinary pigmented lesion clinic, results in changes in diagnosis in a significant proportion of cases. These changes have important implications for clinical decision making, patient outcome, and research data collection.
    Archives of Dermatology 06/2002; 138(5):617-21. · 4.79 Impact Factor
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    ABSTRACT: Cutaneous T-cell lymphomas (CTCLs) are a group of skin-invasive malignancies of clonally derived T lymphocytes. Mycosis fungoides and Sézary syndrome, characterized by the proliferation of CD4+ T cells, are the most common forms of CTCL. Among these latter disorders, the host antitumor response appears to play an important role in disease control. Thus, systemic therapeutic agents are used in an effort to augment the host antitumor response while selectively targeting the malignant cells. Both new and old biologic response-modifying treatment options currently used to treat CTCL are reviewed.
    Advances in Dermatology 02/2002; 18:29-43.
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    ABSTRACT: Cutaneous T-cell lymphoma (CTCL) is typically a skin-infiltrating malignancy of clonally derived CD4+ T lymphocytes. Because the host antitumor response appears to play an important role in disease control, systemic therapeutic agents are used in such a manner as to preserve the integrity of the host antitumor response while selectively targeting the malignant cells. The new biologic response-modifying treatment options currently used to treat CTCL are reviewed.
    Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer 02/2002; 160:321-8.

Publication Stats

237 Citations
51.24 Total Impact Points

Institutions

  • 2004
    • Hospital of the University of Pennsylvania
      • Department of Dermatology
      Philadelphia, Pennsylvania, United States
  • 2002–2004
    • University of Pennsylvania
      • Department of Dermatology
      Philadelphia, Pennsylvania, United States