Pseudocarcinomatous hyperplasia involving the ear from gout: a diagnostic pitfall.

The ear is a characteristic location for deposition of uric acid in patients with gout. Pseudocarcinomatous hyperplasia has not been described in this location. We report three patients with tophaceous gout on the ear whose biopsies exhibited epidermal hyperplasia mimicking squamous cell carcinoma, in order to call attention to this potential diagnostic pitfall.

Granulomatous changes associated with pigmented purpuric dermatosis.

Granulomatous pigmented purpuric dermatosis (GPPD) is a rare entity with few cases reported in the literature. We report 3 cases of pigmented purpuric dermatosis (PPD) with granulomatous features in a 9-year-old boy, a 49-year-old woman, and a 75-year-old woman. We also review the literature on PPDs with granulomatous features, including histopathologic features and disease associations. Most of the cases we reviewed described granulomas superimposed on classic changes of PPD. We also identify a new variant of GPPD in 2 of our patients who presented with granulomatous infiltrates in the mid to deep dermis. Granulomatous PPD does not appear to have a consistent association with underlying disease; notably, hyperlipidemia was seen in 7 cases we reviewed.

Improvement in peripheral blood disease burden in patients with Sézary syndrome and leukemic mycosis fungoides after total skin electron beam therapy.

BACKGROUND: There is a paucity of effective therapies for patients with Sézary syndrome and advanced mycosis fungoides with peripheral blood involvement. Total skin electron beam (TSEB) radiation therapy is an extremely effective skin-directed therapy for these patients, but, until recently, it was thought not to signifcantly affect the peripheral blood malignant T-cell population. OBJECTIVE: We conducted this study to determine if TSEB has therapeutic effect on the peripheral blood in patients with advanced mycosis fungoides and Sézary syndrome. METHODS: All patients on stable medication regimens seen in our photopheresis facility who received TSEB therapy between January 2008 and October 2011 at Temple University Hospital, Philadelphia, PA, were analyzed retrospectively for improvement in the peripheral blood, as documented by flow cytometry. RESULTS: Six of 11 patients achieved 50% or greater decrease in their peripheral blood malignant T-cell population after TSEB therapy, for an overall response rate of 55%. Within the group of patients who had a response in the skin, 67% also had a response in the peripheral blood. LIMITATIONS: This analysis is limited in 3 ways. First, the sample described is small. Second, the results may be confounded by the fact that each patient was on other systemic therapies in addition to TSEB, albeit stable pre-existing regimens. The time interval between completion of TSEB therapy and repetition of flow cytometry was not standardized among patients, which may result in an underestimation of the overall response to TSEB therapy. CONCLUSION: In patients with advanced mycosis fungoides and Sézary syndrome, the peripheral blood tumor burden may improve after treatment with TSEB.

Histopathology of the red lunula: new histologic features and clinical correlations of a rare type of erythronychia.

The lunula is the semi-lunar shaped area seen at the proximal aspect of the nail unit. It is the most distal aspect of the nail matrix that can be visualized through the transparent nail plate. The term red lunula describes erythema that partially or completely replaces the normal white color of the lunula. Red lunulae have been associated with a number of dermatologic and systemic conditions. However, the etiology and histopathology of the red lunula have not been characterized. We report a case of red lunulae of the fingernails in an adult male. Histopathologic examination revealed an increased density of benign-appearing and mildly dilated vascular channels present in the superficial papillary dermis of the nail matrix. To our knowledge, this is the first report of distinct pathologic findings seen on histologic examination of a red lunula. The increased vascularity of the lunula seen microscopically correlates with the clinically observed red color. These findings raise the possibility that systemic or local factors are responsible for angiogenesis within the nail unit in disorders associated with the red lunula.

Inhibition of cell-mediated immunity by the histone deacetylase inhibitor vorinostat: implications for therapy of cutaneous T-cell lymphoma.

Several histone deacetylase inhibitors (HDACi), including vorinostat, have been approved for the therapy of cutaneous T-cell lymphoma (CTCL). Emerging data suggest that HDACi may exert immune suppressive effects which would be disadvantageous for therapy of CTCL. We describe a patient with Sezary syndrome who was monitored for drug-induced immunosuppression while undergoing treatment with vorinostat. Analysis of the patient's natural killer cell function before and after initiation of treatment confirmed inhibition of this important cell-mediated immune function. In addition, the in vitro effects of vorinostat on the immunity of healthy volunteers confirmed that this class of drug can profoundly suppress multiple arms of the cellular immune response. These findings raise concerns of increased susceptibility to infection in this high-risk population.

Dysmenorrhea after bilateral tubal ligation: a case of retrograde menstruation.

BACKGROUND: Endometriosis, arising de novo, is believed to be uncommon in women who have undergone bilateral tubal ligation because the occluded tube prevents outflow of blood and menses. CASE: A woman 10-year status-post bilateral tubal ligation suffered from dysmenorrhea and menorrhagia that began within 1 year after sterilization. At the time of bilateral tubal ligation, no endometriosis was observed. A recent magnetic resonance imaging scan showed no pelvic abnormalities, and the patient underwent a diagnostic laparoscopy in anticipation of finding endometriosis, yet none was found. At laparoscopy performed on day 3 of her menstrual cycle, the proximal segments of her occluded fallopian tubes were dilated with blood. As this was the only abnormality found, we postulated that her dysmenorrhea might be related to the dilated proximal tubal stumps. We evacuated the bloody fluid and occluded the proximal tube at the cornua with Filshie clips. One year after surgery, the patient remains asymptomatic. CONCLUSION: This case is unique because bilateral tubal ligation combined with retrograde menstrual flow appears to have caused dysmenorrhea. Women who have undergone tubal ligation and who have dysmenorrhea may benefit from a diagnostic laparoscopy during menstruation to evaluate the possibility of retrograde menstruation dilating the proximal tubal stumps.

Lysine deacetylase inhibition promotes relaxation of arterial tone and C-terminal acetylation of HSPB6 (Hsp20) in vascular smooth muscle cells.

There is increasing interest in establishing the roles that lysine acetylation of non nuclear proteins may exert in modulating cell function. Lysine deacetylase 8 (KDAC8), for example, has been suggested to interact with α-actin and control the differentiation of smooth muscle cells. However, a direct role of smooth muscle non nuclear protein acetylation in regulating tone is unresolved. We sought to define the actions of two separate KDAC inhibitors on arterial tone and identify filament-interacting protein targets of acetylation and association with KDAC8. Compound 2 (a specific KDAC8 inhibitor) or Trichostatin A (TSA, a broad-spectrum KDAC inhibitor) inhibited rat arterial contractions induced by phenylephrine (PE) or high potassium solution. In contrast to the predominantly nuclear localization of KDAC1 and KDAC2, KDAC8 was positioned in extranuclear areas of native vascular smooth muscle cells. Several filament-associated proteins identified as putative acetylation targets colocalized with KDAC8 by immunoprecipitation (IP): cortactin, α-actin, tropomyosin, HSPB1 (Hsp27) and HSPB6 (Hsp20). Use of anti-acetylated lysine antibodies showed that KDAC inhibition increased acetylation of each protein. A custom-made antibody targeting the C-terminal acetylated lysine of human HSPB6 identified this as a novel target of acetylation that was increased by KDAC inhibition. HSPB6 phosphorylation, a known vasodilatory modification, was concomitantly increased. Interrogation of publicly available mass spectrometry data identified 50 other proteins with an acetylated C-terminal lysine. These novel data, in alliance with other recent studies, alert us to the importance of elucidating the mechanistic links between changes in myofilament-associated protein acetylation, in conjunction with other posttranslational modifications, and the regulation of arterial tone.

High clinical response rate of Sezary syndrome to immunomodulatory therapies: prognostic markers of response.

OBJECTIVES: To quantify response rates of Sézary syndrome (SS) to multimodality immunomodulatory therapy and to identify the important prognostic parameters that affect overall response to treatment. DESIGN: Retrospective cohort study. SETTING: Cutaneous T-cell lymphoma clinic at The Hospital at the University of Pennsylvania. PARTICIPANTS: Ninety-eight patients who met the revised International Society for Cutaneous Lymphomas (ISCL) and the European Organization of Research and Treatment of Cancer (EORTC) criteria for the diagnosis of SS and were seen over a 25-year period at the University of Pennsylvania. Intervention Patients were treated with at least 3 months of extracorporeal photopheresis and 1 or more systemic immunostimulatory agents. MAIN OUTCOME MEASURES: Overall response to treatment was the main measurement of outcome. RESULTS: A total of 73 patients had significant improvement with multimodality therapy: 30% had complete response, with clearing of all disease (n = 29), and 45% had partial response (n = 44). At baseline, the complete response group had a lower CD4/CD8 ratio than the nonresponse group (13.2 vs 44.2) (P = .04) and a lower median percentage of CD4(+)/CD26(-) cells (27.4% vs 57.2%) (P = .01) and CD4(+)/CD7(-) cells (20.0% vs 41.3%) (P < .01). Median monocyte percentage at baseline was higher for patients who had a complete response than for nonresponders (9.5% vs 7.3%) (P = .02). The partial response group did not have any statistically significant variables compared with the nonresponse group. CONCLUSIONS: In this large cohort study of patients with SS, a high clinical response rate was achieved using multiple immunomodulatory therapies. A lower CD4/CD8 ratio, a higher percentage of monocytes, and lower numbers of circulating abnormal T cells at baseline were the strongest predictive factors for complete response compared with nonresponse and warrant further examination in a larger cohort.

Photodynamic therapy with the silicon phthalocyanine pc 4 induces apoptosis in mycosis fungoides and sezary syndrome.

Our current focus on the effects of Photodynamic Therapy (PDT) using silicon phthalocyanine Pc 4 photosensitizer on malignant T lymphocytes arose due to preclinical observations that Jurkat cells, common surrogate for human T cell lymphoma, were more sensitive to Pc 4-PDT-induced killing than epidermoid carcinoma A431 cells. Mycosis fungoides (MF) as well as Sezary syndrome (SS) are variants of cutaneous T-cell lymphoma (CTCL) in which malignant T-cells invade the epidermis. In this study, we investigated the cytotoxicity of Pc 4-PDT in peripheral blood cells obtained from patients with SS and in skin biopsies of patients with MF. Our data suggest that Pc 4-PDT preferentially induces apoptosis of CD4(+)CD7(-) malignant T-lymphocytes in the blood relative to CD11b(+) monocytes and nonmalignant T-cells. In vivo Pc 4-PDT of MF skin also photodamages the antiapoptotic protein Bcl-2.

Age and gender effects on contact sensitization and photoimmune suppression in young and middle-aged adults.

BACKGROUND/PURPOSE: The contact hypersensitivity (CHS) response has been used to assess ultraviolet radiation (UVR)-induced immunosuppression and to evaluate the photoimmune protection of different sunscreen preparations in vivo. Earlier reports of the effect of age and gender on CHS response have led to variations in inclusion criteria for participants in regards to age and gender in the study of sunscreen immune protection factor (IPF). METHODS: This study is a retrospective analysis of data from 73 volunteers from prior CHS studies with the goal of determining the effect of age and gender in young and middle-aged adults on CHS response to dinitrochlorobenzene (DNCB) in unirradiated and UV-irradiated skin. RESULTS: In patients aged 18-63 years, the effect of age on CHS response as well as on UV suppression of CHS response was not statistically significant. In the unirradiated (n=45) and UV-irradiated (n=28) groups, the CHS response between men and women was similar when the timing of DNCB application avoided the period within 5 days before or after the first day of the menstrual cycle. CONCLUSION: Within a certain range, 18-63 years, age does not significantly affect the normal CHS response and the suppression of CHS response by UV. This study also demonstrated that as long as certain days of the menstrual cycle are avoided when sensitizing women of reproductive age, gender does not significantly affect CHS response. Thus, within these parameters, CHS can be appropriately evaluated in healthy individuals without much concern regarding independent effects of age and gender.

Struma ovarii coincident with Hashimoto's thyroiditis: an unusual cause of hyperthyroidism.

OBJECTIVE: To report the identification of struma ovarii in a patient with a history of struma ovarii and new hyperthyroidism. DESIGN: Case report. SETTING: Academic research hospital. PATIENT(S): A woman with hyperthyroidism who has struma ovarii coincident with Hashimoto's thyroiditis. INTERVENTION(S): Laparoscopic salpingo-oophorectomy. MAIN OUTCOME MEASURE(S): Measurement of thyroid hormone parameters before and after surgery. RESULT(S): After removal of the second struma ovarii, hyperthyroidism resolved. CONCLUSION(S): In a patient with two different causes of abnormal thyroid function, it is important to seek an encompassing clinical scenario.