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Mycobacterium kansasii infections of the skin have been described in 31 previously published cases. The median age of these patients is 43 years, and male patients are more frequently affected than female patients. Most patients (72%) with this infection have some alteration of their immune status, but disseminated infection is relatively uncommon (22%). We present the first reported case of cutaneous M. kansasii infection in a patient with previously diagnosed systemic lupus erythematosus. The clinical presentation is similar to that expected in lupus profundus. While the duration of treatment is long (18 months), this case demonstrates that rifampin combined with at least 2 other antibiotics can provide excellent results. Clarithromycin has demonstrated encouraging in vitro results against M. kansasii but has not yet been reported for treatment of cutaneous infections.

Genital herpes, an incurable viral disease that can have a devastating impact on affected patients, is a serious public health concern affecting one in four Americans. Episodic treatment with nucleoside analogs for 3-5 days is the most common method of treatment; however, since maximum viral replication occurs within 24 hours after the onset of symptoms, single-day patient-initiated episodic treatment may be a better option. A recent study evaluated the effectiveness of patient-initiated single-day famciclovir versus placebo in the treatment of genital herpes and found that single-day famciclovir decreased healing time and the duration of pain and other symptoms, and increased the proportion of patients who did not progress to a full outbreak. Compared with previous studies, the results of single-day therapy are similar to or better than the results of conventional therapies of 2-5 days' duration. In addition, the convenience of single-day treatment may lead to greater patient adherence and improved overall management of recurrent herpes outbreaks.

The incidence of human papillomavirus (HPV) and HPV-related anal cancer has been increasing at an alarming rate. Human immunodeficiency virus-positive patients are at a particularly high risk, with prevalence increasing rapidly in this population as life expectancies have increased. Screening has been very effective in reducing the morbidity and mortality of HPV-related cervical cancer, which suggests its role in reducing the burden of HPV-related anal cancer as well. With appropriate screening, patient education and treatment, the incidence of HPV-related anal cancer may be greatly reduced.

Topical 5-fluorouracil (5-FU) has been used for the treatment of dermatological conditions for nearly half a century. Although the indications for 5-FU approved by the US Food and Drug Administration include actinic keratosis and superficial basal cell carcinoma, studies also have demonstrated therapeutic efficacy for 5-FU in the treatment of many other dermatological conditions, including squamous cell carcinoma in situ, warts, psoriasis of the nail, keratoacanthoma, and vitiligo. This review discusses clinical data which support the use of 5-FU for these disease states.

background. The histopathologic effects of curative doses of radiation therapy on cutaneous squamous cell carcinoma (SCC) have not been well described in the dermatologic literature. objective. To understand the histopathologic process of cutaneous SCC involution following radiation treatment. methods. Hematoxylin-eosin stain and immunoperoxidase stains for keratin were performed on tissue from the site of a primary cutaneous SCC 2 months after completion of fractionated radiation therapy (7000 cGy total) but prior to clinical involution. results. Histopathological examination of the irradiated SCC revealed dermal keratin pearls and keratinocytic necrosis resembling apoptosis as well as inflammation and foreign body giant cell reaction. Immunoperoxidase staining for keratin revealed cellular remnants of cutaneous SCC without intact keratinocytic nuclei within giant cells. conclusion. Complete clinical resolution of the SCC over the next several weeks without recurrence after 15 months confirmed the histopathologic findings of tumor destruction by primary radiation therapy.

Although etanercept is used as a continuous therapy for moderate to severe plaque psoriasis, intermittent use may be necessary in some instances.In this randomized, open-label study, we evaluated the effectiveness and safety of continuous versus interrupted etanercept therapy.All patients received uninterrupted etanercept 50 mg twice weekly during the first 12 weeks, followed by either continuous (n = 1272) or interrupted (n = 1274) etanercept 50 mg once weekly in the next 12 weeks. The primary effectiveness end point was the proportion of responders (those who achieved a Physician's Global Assessment [PGA] scoreor=2 and improvement from baseline) at week 24. Secondary end points included the PGA "clear/almost clear" status, the PGA Scalp Psoriasis score, and the Dermatology Life Quality Index. A modified intent-to-treat analysis was performed.At week 12, comparable high proportions of responders were reported in the continuous (71.3%) and interrupted (72.0%) arms. However, the proportion of responders at week 24 was greater in the continuous group than in the interrupted group (71.0% vs 59.5%; P.0001). Similar results were observed in secondary end points. The mean number of etanercept doses (1 dose = 50 mg) received by patients in the continuous group was 33.4, compared with 28.0 in the interrupted group. Etanercept was well tolerated in both treatment arms.We examined one round of discontinuation and re-treatment; interrupted therapy provided less total medication to responding patients.Continuous and interrupted etanercept therapy was effective and generally well tolerated in patients with psoriasis, with greater improvements observed in the continuous arm at week 24. Most patients regained their response after reinitiation of etanercept.

We investigated the aberrant promoter methylation status of 12 genes in skin lesions, both malignant (basal cell carcinomas (BCCs), n=68 and squamous cell carcinomas (SCCs), n=35) and non-malignant (tags, n=58) skin lesions and compared the results of lesions from sun exposed (SE) and sun protected (SP) regions. Methylation was studied using a methylation specific PCR (MSP) and methylation of CDH1 was also measured using a semi-quantitative fluorescence based real-time MSP method. The methylation index (MI) was calculated as the methylated fraction of the genes examined. In this report, we found high frequencies of methylation of several known or suspected tumor suppressor genes in tags and skin cancers. Among the 12 genes, for the cadherin genes CDH1 and CDH3 and for two of the laminin 5 encoding genes LAMA3 and LAMC2 methylation frequencies greater than 30% were noted in one or more specimen types. We investigated whether methylation was tumor related. Surprisingly, the differences in the methylation profile of genes among the three specimen types were modest, and the MI, indicators of overall methylation frequencies, was nearly identical. However, significant differences were noted in the frequencies of methylation among the three specimen types for the genes RASSF1A (P=0.002), CDH1 (P=0.007) and one or more of three CAD genes (P=0.02). Methylation was highly significantly related to sun exposure, and sun protected specimens had little or no methylation. As methylation of CDH1 was completely SE specific we analyzed all the skin samples using a semi-quantitative real-time PCR assay for the CDH1 gene. The concordance between standard MSP and real-time MSP for all the samples (n=161) was 75% (P0.0001). While weak signals were detected in the SP samples by real time PCR, the differences between SE and SP specimens were 148 fold for tags and 390 fold for BCCs. These differences were highly significant (P0.0001). These findings suggest that methylation commences in UV exposed skin at a relatively early age and occurs in skin prior to the onset of recognizable preneoplastic changes.

background. The incidence of nonmelanoma skin cancer, the most common form of cancer in the United States, continues to increase. It is important that physicians know what treatment modalities will be the most efficacious. objective. The purpose of this study was to compare recurrence rates by treatment modality for primary basal and squamous cell carcinomas in a private dermatological practice. methods. Between June 1993 and December 1994, 268 consecutive primary nonmelanomic tumors were treated by surgical excision or electrodesiccation and curettage in our practice. The charts of the 191 patients treated were retrospectively reviewed, and recurrence data were compared by treatment modality. results. The recurrence rates between the two types of treatment were not found to be significantly different. conclusion. In contrast to other studies reported from academic centers in which surgical excision has been found to have lower recurrence rates than tumors treated with curettage and electrodesiccation, this study found recurrence rates for two treatments to be approximately the same.

The molecular pathology of the common nevocellular nevus (NCN) and its relationship to the genetic model of malignant melanoma (MM) progression has not been fully characterized. We used laser capture microdissection of archival formalin-fixed material to study 34 melanocytic lesions (19 MM and 15 NCN). Twelve of the 15 NCN were acquired, 3 of which were congenital; none had dysplastic features. Ten polymorphic markers on five chromosomal regions (1p36, 6q22-23.3, 8p22-24, 10q23, and 11q23) were selected for loss of heterozygosity (LOH) analysis, based on previous studies demonstrating involvement in MM pathogenesis and progression. Loss of heterozygosity at any allelic locus was observed in 18 of 19 (95%) MM and in 9 of 15 (60%) NCN. Of the three congenital nevi analyzed, none showed LOH at any informative locus. The frequency of allelic loss was highest in the MM at 6q22-23.3 (64%), followed by 10q23 (62%), 8p22-24 (43%), 11q23 (43%), and 1p36 (13%). In the 15 NCN, the most frequent allelic losses were detected at 6q22-23.3 (29%), 1p36 (27%), and 10q23 (25%), with lower frequencies of LOH at 11q23 (10%) and 8p22-24 (7%). LOH at a single polymorphic marker, D6S1038, was detected in 70% of the MM and in 36% of the NCN, suggesting the presence of putative tumor-suppressor genes (TSGs) critical in melanocytic neoplasia at 6q22-23.3. The presence of clonal genetic alterations in acquired NCN justifies their classification as a benign neoplasm. The pattern of LOH in NCN is not random; rather, the relative frequencies of LOH at the chromosomal regions examined are consistent with a multistep model of MM progression that begins with NCN. Molecular analysis of NCN reiterates established epidemiologic and morphologic notions that NCN are precursor lesions for MM. H UM P ATHOL 33:191-197. Copyright 2002, Elsevier Science (USA). All rights reserved.

(Background) We have demonstrated that down-regulation of hMSH3 results in low levels of microsatellite instability (MSI-L) and elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) in tissue cultured cell lines. Primary tumor tissues exhibiting MSIL and/or EMAST from stage II/III CRC show intra-tumor depression of hMSH3 and upregulation of GLUT1 that is a marker for hypoxia. In vitro, hypoxia induces down-regulation of hMSH3 and the development of EMAST in CRC cell lines. Finally, Stage II/III primary CRC exhibitingMSI-L/EMAST has a shorter recurrence-free survival than that of microsatellite stable counterparts not exhibiting MSI-L/EMAST. These results support the concept that intra-tumor hypoxia may induce MSI-L/EMAST through down-regulation of hMSH3 and enhance the aggressiveness of primary CRC, leading to recurrence and/or distant metastasis. Thus, MSI-L/EMAST could be a marker for identifying genetic and/or epigenetic changes that control recurrence and/or distant metastasis from primary CRC. We previously reported that LOH at the SMARCA2 locus on 9p24.3 is significantly high in liver metastasis (LM) exhibiting MSI-L/EMAST (termed moderate MSI: MSI-M) from primary CRC. (Aim) The purpose of this study is to determine the pathobiological significance of MSI-L/EMAST and LOH at SMARCA2 region in CRC. (Methods) Eighty three LMs and 186 primary CRC with known clinicopathological factors and disease outcome were analyzed for MSI/EMAST and LOH at the 9p24.2 region. Significant associations between factors were determined by various statistical analyses. (Results) We proposed that a locus affected by 9p24.2 LOH might promote metastasis from primary CRC; such a locus was mapped to an 80 kb region at the 3' boundary of the SMARCA2 gene. Stage II and III primary CRCs exhibiting MSIM and 9p24.2 LOH were significantly more likely to give rise to a solitary LM suitable for hepatectomy, whereas MSI-M-positive counterparts without 9p24.2 LOH, or highly microsatellite stable (HMSS) tissues were more likely to give rise to simultaneous metastases to multiple organs, and therefore, not suitable for surgical management. Multivariate analysis showed that MSI-M with 9p24.2 LOH in the primary CRC is an independent positive prognostic factor following recurrence (HR = .1981, P=.0007). (Conclusions) The presence or absence of 9p24.2 LOH in Stage II/III primary CRCwithMSI-M is an important determinant of the aggressiveness of the recurrent metastasis.

The HIV epidemic has dramatically altered the field of sexually transmitted diseases (STDs). HIV infection is unique among sexually transmitted diseases because it can modify the clinical presentation and features of other STDs. Conversely, other STDs can affect the transmission of HIV. This review is the third part of a series that has provided a general overview of STDs. In this article, genital ulcer diseases (genital herpes, syphilis, chancroid, lymphogranuloma venereum, and granuloma inguinale), human papillomavirus infection (anogenital warts and subclinical infections), molluscum contagiosum, human herpesvirus 8 infection, viral hepatitis, and ectoparasitic infestations (scabies and pediculosis pubis) are discussed as they occur in HIV-infected hosts. Additional features as they relate to HIV-infected patients, such as epidemiology and transmission, are discussed when applicable. Learning objective: At the conclusion of this learning activity, participants should improve their understanding of sexually transmitted diseases in the HIV-infected host. (J Am Acad Dermatol 2000;43:409–32.)

Human herpesvirus 8 (HHV-8) has been causally linked to Kaposi's sarcoma (KS). There is significant homology between some HHV-8 genes and cellular genes including D-type cyclin (vCYC), G protein coupled receptor (vGCR), macrophage inflammatory proteins (vMIP-I, vMIP-II), bcl-2 (vBCL2), interferon regulatory factor-1 (vIRF1), interleukin-6 (vIL6), and complement-binding protein (vCBP). In this study, we analyzed expression of these viral homologs and HIV-1 Tat by reverse-transcriptase polymerase chain reaction (RT-PCR) coupled with Southern blot hybridization in AIDS-KS (AKS) tissue, classic KS tissue(CKS), and peripheral blood mononuclear cells, and phorbol ester (TPA)-treated and untreated HHV-8 positive lymphoma cells (BCBL1). While vCYC (AKS 6 of 6; CKS 3 of 3), vMIP-I (AKS 5 of 6, CKS 3 of 3), vBCL2 (AKS 6 of 6; CKS 3 of 3), and vIRF1 (AKS 5 of 6, CKS 3 of 3) transcripts were detected in both AKS and CKS, vGCR and HIV-1 Tat were expressed only in AKS samples (vGCR: AKS 3 of 6, CKS 0 of 3; Tat: AKS 4 of 6, CKS 0 of 3). vMIPII, vCBP, and vIL6 expression were not detected in any KS samples. Since vGCR expression is limited to AKS, it is possible that vGCR is activated by HIV-1 Tat. These results suggest that HIV-1 Tat may contribute to AKS pathogenesis through the tumorigenic and angiogenic effects of vGCR.