Zoonotic Majocchi's Granuloma of the Vulva.

A healthy 32-year-old woman presented to clinic with tender pruritic lesions of 2-month duration at the vulva and lesions for weeks on the shins. She was treated with topical corticosteroids and intravenous vancomycin without significant improvement. On examination, dozens of follicular hemorrhagic papulopustules were detected at the suprapubic area and vulva (Figure 1). Similar but less prominent lesions were observed on the shins as well. Biopsies of the vulva and shin revealed a follicular inflammatory infiltrate of neutrophils, histiocytes, and lymphocytes as well as fungal hyphae within the follicular infundibulum and hair shafts, consistent with Majocchi's granuloma (MG). Gram and Fite-Faraco staining, direct immunofluorescence, and bacterial culture were negative. Tissue culture grew Trichophyton mentagrophytes, which was identified using sequence analysis of the D1/D2 region of the 28s rDNA. Minimum inhibitory concentrations for terbinafine, ketoconazole, and itraconazole were determined, with terbinafine having the lowest concentration. Additional history revealed that shortly prior to commencement of her clinical manifestations, the patient had acquired a pet guinea pig with eruptions and hair loss (Figure 2). The patient was prescribed ketoconazole cream and terbinafine, 250 mg daily, with almost immediate improvement. Based on clinical response, the patient remained on terbinafine and ketoconazole cream for 6 months. Her skin remained clear 4 months after discontinuing all antifungals. Based on the results of patient's culture, a veterinarian treated her guinea pig successfully with systemic terbinafine and miconazole lotion.

Acquired Lymphangiectasia in the Setting of a Gastrointestinal Stromal Tumor.

A 53-year-old woman presented for a skin cancer screening and was found to have scattered violaceous papulovesicles on the right buttock and right lower aspect of the abdomen. These lesions had been increasing in number for 3 years. The patient denied pain or pruritis at the site of lesions and denied any systemic fi ndings.

Prevaccine era human papillomavirus types 6, 11, 16 and 18 seropositivity in the U.S.A., National Health and Nutrition Examination Surveys, 2003-2006.

BACKGROUND: A vaccine is available to prevent human papillomavirus (HPV) 6, 11, 16 and 18; in the prevaccine era, seropositivity to vaccine types is a measure of natural exposure. METHODS: We describe HPV seropositivity in the USA among 14-59-year-olds using the 2003-2006 National Health and Nutrition Examination Surveys. RESULTS: Seropositivity to HPV 6, 11, 16 and 18 was 17.5%, 6.8%, 15.1% and 5.9%, respectively, among women, and 7.0%, 2.4%, 5.2% and 1.5%, respectively, among men. Overall in both sexes, seropositivity was 22.5% for any vaccine type (31.8% in women and 12.9% in men), but substantially lower for three or more types (1.7% overall, 2.8% in women and 0.6% in men). CONCLUSIONS: Almost a quarter of the participants were seropositive to any HPV vaccine type but few were seropositive to at least three vaccine HPV types in the prevaccine era. Further study is needed to assess if seropositivity would be useful as a biological marker of vaccination.

Hospitalization cost of congenital syphilis diagnosis from insurance claims data in the United States.

We analyzed medical insurance claims data (2005-2009) to determine the hospitalization costs of newborns with congenital syphilis (CS) diagnoses. We found 44 admission claims with CS diagnosis. The excess cost per case of CS (in 2009 US dollars) was estimated at $9969 (95% confidence interval, $5702-$16,769).

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.

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.

Donor-derived Strongyloides stercoralis infections in renal transplant recipients.

BACKGROUND: Donor-derived Strongyloides stercoralis infection occurs rarely after transplantation, and the risk factors are not well understood. We present cases of two renal allograft recipients who developed Strongyloides hyperinfection syndrome after receipt of organs from a common deceased donor who received high-dose steroids as part of a preconditioning regimen. METHODS: The two renal transplant patients who developed Strongyloides hyperinfection syndrome are reported in case study format with review of the literature. RESULTS: Microscopic examination of stool from one renal transplant patient and of tracheal and gastric aspirates from the other transplant patient revealed evidence of S. stercoralis larvae. Retrospective testing of serum from the deceased donor for Strongyloides antibodies by enzyme-linked immunosorbent assay was positive at 11.7 U/mL (Centers for Disease Control reference >1.7 U/mL positive). One patient was treated successfully with oral ivermectin. The other patient also had complete resolution of strongyloidiasis, but required a course of parenteral ivermectin because of malabsorption from severe gastrointestinal strongyloidiasis. CONCLUSIONS: These case studies provide some of the best evidence of transmission of S. stercoralis by renal transplantation. Because of the high risk of hyperinfection syndrome and its associated morbidity and mortality, high-risk donors and recipients should be screened for Strongyloides infection, so that appropriate treatment can be initiated before the development of disease. This study indicates that parenteral ivermectin can be used safely and effectively in patients in whom severe malabsorption would preclude the effective use of oral formulation. These cases also suggest that reconsideration should be given for the safety of steroids in donor-preconditioning regimens.

Validity assessment of the cutaneous T-cell lymphoma severity index to predict prognosis in advanced mycosis fungoides/Sézary syndrome.

BACKGROUND: There is a need for standardized quantitative disease assessment measures in mycosis fungoides/Sézary syndrome. In 2005, a cutaneous T-cell lymphoma (CTCL)-severity index (SI) that not only measures disease extent (on a scale of 0-75) independent of the classic TNM(B) staging system but can also be used to estimate individual 5-year survival (SR5) was reported. OBJECTIVE: We sought to assess the generalizability of the CTCL-SI/SR5 equation (SR5 equation) to predict prognosis in our cohort of patients with advanced mycosis fungoides/Sézary syndrome (n = 50, photopheresis service, 1984-2001). METHODS: TNM(B) staging, CTCL-SI score (based on skin involvement, presence of tumors, lymph node/visceral/blood involvement), and SR5 (SR5 equation = 124 - 2 × [CTCL-SI]%) at initial diagnosis were calculated retrospectively and compared with overall survival by the Kaplan-Meier method. The prognostic significance of TNM(B) staging versus the CTCL-SI was determined by Cox proportional hazards models and Brier scores. RESULTS: Patients had stage IIA to IVA disease with a median actuarial overall survival of 58 months. By disease stage, the overall 5-year survival was 70% (stage IIA), 48% (stage IIB-IIIB), and 36% (stage IVA). In our cohort, the CTCL-SI itself was predictive of overall survival (P = .028) but the SR5 equation was not predictive of survival (Brier score of 0.29). LIMITATIONS: Small sample size, single academic center population, and retrospective design are limitations. CONCLUSIONS: The CTCL-SI is a relatively simple-to-use quantitative tool that measures disease activity in all compartments (skin, nodes, blood, viscera) and has prognostic significance in multivariate analysis. The CTCL-SI may be a useful adjunct to the TNM(B) staging for tracking disease activity quantitatively in all disease compartments (skin, nodes, blood, viscera) in clinical practice and trials, but the predictive ability of the SR5 equation needs further validation at other centers in larger groups of patients.

A novel regimen of vorinostat with interferon gamma for refractory Sézary syndrome.

Long-term prognosis for advanced stages of cutaneous T-cell lymphoma may be beneficially altered with the use of multimodality therapy. However, refractory disease exists in which current therapeutic options fail to halt the progression of disease. We present 3 cases of refractory Sézary syndrome in which the combination of vorinostat and interferon gamma was well tolerated and produced significant clinical improvement. The potential immunologic basis for this is discussed.

CD8+ epidermotropic cytotoxic T-cell lymphoma with peripheral blood and central nervous system involvement.

BACKGROUND: Most cutaneous T-cell lymphomas demonstrate a malignant population with a CD4(+) phenotype. In rare cases, CD8(+) phenotypes have been described based on immunostaining of skin specimens. Although some CD8(+) lymphomas have an indolent course, others, such as CD8(+) epidermotropic cytotoxic T-cell lymphomas, are typically more aggressive. To our knowledge, involvement of peripheral blood or cerebrospinal fluid with a malignant population of CD8(+) cells demonstrated by flow cytometry and T-cell receptor gene rearrangement has not been previously described. OBSERVATIONS: We describe a patient with a CD8(+) cutaneous T-cell lymphoma with an initially indolent course and early stage diagnosed on the basis of a skin biopsy specimen. However, when flow cytometry was performed looking specifically at CD8(+)/CD4(-) cells in the peripheral blood and cerebrospinal fluid, a malignant population of CD8(+)/CD4(-)/CD26(-)/CD7(-) cells was discovered. CONCLUSIONS: It is important for prognosis and treatment to be able to identify CD8(+) epidermotropic cytotoxic T-cell lymphoma and separate it from other relatively indolent CD8(+) lymphomas. Furthermore, detection of an abnormal CD8(+)/CD26(-)/CD7(-) T-cell population within the peripheral blood has important prognostic and therapeutic implications. The use of flow cytometry looking for abnormal CD8(+) populations in the peripheral blood or cerebrospinal fluid can assist with this critical information.

Total skin electron beam therapy may be associated with improvement of peripheral blood disease in Sézary syndrome.

Total skin electron beam radiation is an effective therapy for palliation of the cutaneous symptoms of the most common types of cutaneous T-cell lymphomas, mycosis fungoides and Sézary syndrome. We report 4 cases of patients with Sézary syndrome who had significant improvement in their blood burden of malignant cells in addition to complete cutaneous responses to total skin electron beam therapy. The data from these 4 patients illustrate the potential for total skin electron beam to be used as both a skin and blood tumor debulking agent, and not merely as a palliation for skin symptoms.

Stem cell transplantation in advanced cutaneous T-cell lymphoma.

Cutaneous T-cell lymphomas are a type of indolent non-Hodgkin's lymphoma where patients with limited skin disease can be successfully treated with a variety of skin-directed, systemic, and immunomodulating therapies, whereas durable remissions are difficult to achieve in patients with tumor, erythrodermic, or systemic disease. We describe a patient with cutaneous T-cell lymphoma and malignant cells constituting 99% of her peripheral blood lymphocytes who had a sustained complete response after an HLA-matched sibling allogeneic stem cell transplantation. We also review the current literature regarding both autologous and allogeneic stem cell transplantations for advanced stages of cutaneous T-cell lymphoma, discuss the importance of the graft-versus-tumor immunomodulatory effect in successful transplantations, and suggest that allogeneic stem cell transplantation deserves further consideration and study as a potential treatment for selected patients who are younger and at high risk.

Cutaneous Hodgkin's disease.

Cutaneous Hodgkin's disease is a rare condition that usually occurs late in the course of Hodgkin's lymphoma. This rare condition is thought to have decreased in incidence in recent decades, likely owing to improved treatment of patients with Hodgkin's disease, who are receiving improved chemotherapy and radiation therapy, and the advent of peripheral blood stem cell transplantation. We present the case of a man who developed specific cutaneous Hodgkin's lymphoma 6 months after nonmyeloablative allogenic stem cell transplantation for his recurrent systemic disease. The patient's manifestation of relapse was cutaneous dissemination of the tumor, manifested by erythematous papules and ulcerated nodules. At the time of the cutaneous relapse he had minimal systemic disease. This case illustrates an example of this complication of Hodgkin's disease and stresses the importance of a timely diagnosis to direct appropriate therapy. A review of the literature demonstrates that the patient's lesion morphology and distribution are typical of specific manifestations of cutaneous Hodgkin's disease.

Association of change in clinical status and change in the percentage of the CD4+CD26- lymphocyte population in patients with Sézary syndrome.

BACKGROUND: Because there are currently many effective therapies available for Sézary syndrome, close monitoring of disease progression is required in order for a clinician to know when to institute or change an intervention. It has been our clinical experience that changes in patients' CD4+CD26- T-cell populations of peripheral blood lymphocytes herald changes in their clinical status. OBJECTIVE: Our purpose was to evaluate whether a change in patients' CD4+CD26- population of T cells presages a change in their clinical status. We also sought to investigate the association between a change in T-cell populations that are CD4+CD7-, CD8+, CD56+, and the CD4+/CD8+ T-cell ratio and a change in the patient's clinical status. METHODS: We conducted a retrospective chart review analysis of 21 patients with Sézary syndrome who had flow cytometry, usually including levels of CD4+CD26-, CD4+CD7-, CD8+, CD56+, and CD4+/CD8+ ratios measured at two time periods, 12 weeks apart. RESULTS: We report two cases in which changes in patients' clinical status were preceded by several weeks by a change in their CD4+CD26- level. We report weak associations between a decreasing CD4+CD26- T-cell population, a decreasing CD4+CD7- population, an increasing CD56+ population, and an improving clinical status. We also report stronger associations between both a decreasing CD8+ population and an increasing CD4+/CD8+ ratio and a worsening clinical status. LIMITATIONS: The study was limited by the number of patients and the time period over which the study was conducted. In addition, varying configurations of CD4+CD26- T-cell populations were observed that may have limited the utility of this measurement. CONCLUSIONS: Flow cytometry assays of patients' blood and, in particular, measurement of the CD4+CD26- population of lymphocytes over time may be a valuable tool for monitoring patients with Sézary syndrome. There exist varying configurations of CD26 T lymphocytes that may cause differences in standards for what is considered positive and negative between observers. Further prospective analysis involving larger groups of patients is recommended.