Rachel H. Gormley

Human papillomavirus–related genital disease in the immunocompromised host: Part I

Human papillomavirus (HPV) is responsible for common condyloma acuminata and a number of premalignant and malignant anogenital lesions. These conditions are of particular concern in immunocompromised individuals who have higher risk of malignant transformation and are more difficult to treat. This is part I of a two-part review that will highlight the cutaneous features of condyloma acuminata and vaginal, vulvar, penile, and anal intraepithelial neoplasias, with an emphasis on presentation of these HPV-mediated diseases in the immunocompromised host. Counseling patients about these conditions requires a thorough understanding of the epidemiology, natural history of HPV, transmission and infectivity, risk of malignancy, and the role of the host immune response in clearing HPV lesions. Part II will provide an updated review of available treatments, with a focus on recent advances and the challenges faced in successfully treating HPV lesions in immunocompromised patients.

Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma

Cutaneous T-cell lymphomas most commonly have a CD4(+) memory T-cell phenotype with relatively indolent course, but may in rare cases present with a CD8(+) cytotoxic phenotype exhibiting strikingly more aggressive clinical behavior. We present two cases of the clinically aggressive subtype of primary cutaneous epidermotropic CD8(+) cutaneous T-cell lymphoma and review the current literature, clinical behavior, and recommendations for treatment distinct from that of more common CD4(+) variants of cutaneous T-cell lymphoma.

Ipilimumab-associated Sweet syndrome in a melanoma patient

the buttocks, axillae, and groins and evolved in crops. Besides these nodules, physical examination revealed bridged scars, but no interconnecting tracts. Histologic examination of a skin biopsy and cultures ruled out Crohn disease and an opportunistic infection, respectively. The diagnosis was HS grade II according to the Hurley classification. A 6-month course of oxacillin (2 g/day), followed by a combination of rifampicin (600 mg/day) with clindamycin (600 mg/day) for 9 months were ineffective (Fig 1). In February 2012, Cs was replaced with tacrolimus (2 mg/day) based on the hypothesis of a deleterious effect of Cs on pilosebaceous apparatus and of a potential efficacy of tacrolimus as suggested in another report. In November 2012, all inflammatory lesions had disappeared (Fig 2). To our knowledge, this patient is the first case of HS appearing in the setting of organ transplantation. Although a fortuitous association cannot be excluded, considering the patient’s age, the clinical scenario speaks in favor of an iatrogenic origin of HS. Indeed, rare cases of iatrogenic HS have been reported. Even if several Cs-responsive cases of HS exist, Cs is known to induce hyperplasia of the pilosebaceous apparatus. Isotretinoin may also have played an aggravating role. This patient is similar to one suffering from HS for more than 20 years, in whom treatment with Cs had been ineffective. He was cured at the age of 40 years, a few months after kidney transplantation, while receiving tacrolimus and mycophenolate mofetil as immunosuppressive treatment. We recently observed another case of HS that appeared within 2 years after transplantation, for which we suggested a switch from Cs to tacrolimus. Although tacrolimus and Cs exert very similar immunosuppressive effects, the former proved more effective than the latter against HS in these cases. This may be due to the fact that tacrolimus exerts fewer effects on the pilosebaceous apparatus. This observation suggests that patients in whom HS develops while on Cs should be switched to tacrolimus.

Melanocytic tumors express connexin 43 but not 26: immunohistochemical analysis with potential significance in melanocytic oncogenesis.

Abstract:Connexins (Cx) are structural proteins that form gap junctions, which are vital to cell–cell communication and help to regulate cell division. The purpose of this study was to evaluate if there are diagnostically important differences in immunostaining for connexins 43 (Cx43) and 26 (Cx26) in melanoma compared with nevi. Formalin-fixed paraffin-embedded sections of 34 histologically well-characterized melanocytic lesions, 17 primary malignant melanomas (MM), and 17 nevi were stained with a polyclonal antibody to Cx43 and a polyclonal antibody to Cx26. Immunoreactivity in tumor cells was evaluated semiquantitatively based on extent (1%–100%) and intensity (0–3) of reactivity. A score of 0–300 was generated by the product of the extent and intensity readings in each case. Significantly higher Cx43 immunoreactivity was detected in MM (mean intensity score = 253.5; 95% confidence interval, 227.9–279.2; P = 0.002) compared with nevi (mean intensity score = 152.4; 95% confidence interval, 104.9–199.8). In contrast, Cx26 immunoreactivity was less than 5% or entirely absent in all melanocytic tumors (n = 34). The significantly higher Cx43 staining in MM when compared with nevi suggests an oncogenic role for this protein in melanocytic tumor progression. Consequently, the evaluation of immunohistochemical staining for Cx43 in conjunction with other ancillary stains and tumor histology may be helpful in distinguishing MM from nevi, although positive Cx26 reactivity suggests that a cutaneous neoplasm is of nonmelanocytic origin.

Intralesional Cidofovir for Treating Extensive Genital Verrucous Herpes Simplex Virus Infection

Verrucous herpes simplex viral infections in immunocompromised patients can be a therapeutic challenge, and we present a case of successful treatment with intralesional cidofovir.

Genitogluteal porokeratosis involving the scrotum: an unusual presentation of an uncommon disease.

Porokeratosis represents a heterogeneous group of keratinization disorders typified by the presence of annular plaques with distinct, raised borders that include cornoid lamellae. Histopathologically, a cornoid lamella is a column of parakeratotic scale overlying an epidermal invagination that displays nearby dyskeratotic keratinocytes and loss of the granular layer. Porokeratosis ptychotropica constitutes a rare variant that classically presents as a plaque in the gluteal cleft that mimics a dermatitis and microscopically contains numerous cornoid lamellae. We report a 28 year‐old man with a two‐month history of scrotal burning and itching associated with the development of multiple thin red plaques with distinct elevated borders and a pebbled appearance. Histopathological examination revealed psoriasiform acanthosis and multiple cornoid lamellae, which is consistent with a diagnosis of porokeratosis ptychotropica. Our patients presentation may represent a distinct variant with clinical features of verrucous porokeratosis and histopathological features of porokeratosis ptychotropica which may suggest that the finding of multiple cornoid lamellae is not unique to porokeratosis ptychotropica.

The diagnostic challenge of vulvar squamous cell carcinoma: Clinical manifestations and unusual human papillomavirus types

History of organ transplant 2 9% History of other cancer 4 17% History of autoimmune disease 0 0% History of eczema 1 4% History of prior systemic treatments (n, %) Yes 3 14% None/unknown 20 86% History of topical treatments to vulvar area (n, %) Yes 8 35% None/unknown 15 65% History of abnormal Paps (n, %) Yes 8 35% None/unknown 15 65% History of concurrent or previous vulvar dermatoses diagnosed clinically (n, %) Yes 4 83% None/unknown 19 17% Previous vulvar symptoms (n, %) Yes 17 74% None/unknown 6 26% Lesion size in cm (median, IQR)* Type of provider who first evaluated patient (N) Ob/gyn 18 78% J AM ACAD DERMATOL MARCH 2014 586 Letters

Use of mobile telemedicine for cervical cancer screening of HIV-positive women in Gaborone, Botswana

Throughout the developing world, delivery of women’s health care, specifically cervical cancer screening, is limited by cost and access to trained personnel. Visual inspection with application of 4% acetic acid (VIA) is a practical, inexpensive alternative to cytology-based screening in areas where resources are limited. Mobile telemedicine using a cellular phone to photograph the cervix after VIA allows clinicians in “see and treat” cervical cancer screening clinics to capture high-quality images of the cervix, which can then be transmitted through the cellular network to a gynecology specialist located remotely. We present results of a prospective case-control study evaluating the accuracy of offsite (remote) expert diagnosis using mobile telemedicine photographic images of the cervix with VIA (PIA) in HIV-positive women in Gaborone, Botswana.

Merkel cell polyomavirus in low levels in folliculotropic mycosis fungoides represents a passenger, not a driver

mycosis fungoides represents a passenger, not a driver There is currently no known causative agent for cutaneous T cell lymphoma (CTCL), although a possible infectious cause has long been suggested. The recent discovery of the etiologic role of Merkel cell polyomavirus (MCPyV) in Merkel cell carcinoma has led to numerous investigations into the role of MCPyV in other tumors. In general these studies have failed to demonstrate a role for MCPyV. A recent study by Kreuter et al. argued against a pathogenic role for polyomaviruses (PyVs) in primary cutaneous lymphoma overall; however, the authors found that six of eight folliculotropic mycosis fungoides (FT-MF) samples harbored MCPyV DNA. The present study was conducted to further investigate a role for MCPyV in FT-MF. We identified cases of FT-MF through a database search of biopsy specimens at the University of Pennsylvania. Controls were selected from cases read as folliculitis. Slides were reviewed to confirm the presence of follicular epithelium. Samples were then analyzed by real-time polymerase chain reaction (PCR) for the presence of MCPyV, with DNA quality assessment by b-globin reference gene PCR. DNA sufficient for analysis was present in all nine cases of FT-MF and in four of six controls. We performed PCR utilizing a primer set designed within the small T viral region with MCPyV copy number determination using the Quantification of MCPyV, Small T Region Kit (PrimerDesign Ltd, Southampton, UK), and the StepOne Plus instrument (Applied Biosystems, Foster City, CA, USA). Overall, MCPyV was detected in 77% of specimens (eight of nine cases of FT-MF and two of four controls). Levels of MCPyV were assessed using DNA copy number determination by real-time PCR and did not differ statistically between cases of FT-MF and controls. In all cases, levels of MCPyV (as measured by DNA copy number/ng DNA) were very low (range: 0.03–1.06/ng DNA). MCPyV was detected in 89% of FT-MF cases. However, it is important to note that 50% of control samples were also positive for MCPyV, which is similar to the 40% prevalence of MCPyV reported previously in studies of skin swab specimens from healthy adults. Although our results are suggestive of a higher prevalence of MCPyV in FT-MF compared with controls, this study was insufficiently powered to detect a statistically significant difference (P = 0.203, Fisher’s exact test) because of its small sample size. Moreover, although we confirmed that FT-MF frequently harbors MCPyV DNA, the presence of MCPyV in control follicles and the overall low level of viral copy numbers suggests that MCPyV is widespread and probably represents a passenger rather than a driver in FT-MF. As we seek to better understand viral oncogenesis in CTCL, it is critical to recognize that most viruses detected in tumor samples may not be etiologically relevant. In FT-MF, MCPyV is likely to represent a routine inhabitant of the human hair follicle rather than a true causative agent. Experimental findings are further confounded by the altered immune milieu of FT-MF, which may contribute to greater variety in the types and amounts of bystander viral DNA detected. To better understand and elucidate the roles of various viruses in oncogenesis, further studies must establish a more complete understanding of the human viral microbiome.

The Computer Will See You Now: Ethics of Teledermatology

Teledermatology is the use of telecommunication for dermatology diagnosis and care. This technology can provide diagnostic services to underserved and rural regions that lack access to higher-level specialty medical expertise. Accumulating data shows that teledermatology is diagnostically accurate, safe, cost-effective, and well received by patients. While the potential of teledermatology to increase access to care is exciting, it is critical to recognize that the nature of the doctor–patient relationship is drastically altered when the doctor is located remotely, never having face-to-face contact with the patient. This is a new type of therapeutic relationship, one in which the principles of respect for autonomy, beneficence, non-maleficence, and justice must be emphasized, and at the same time recontextualized. Case scenarios will be used to examine some of the ethical issues that may arise with the use of teledermatology. As a framework for our analysis, we will use the generally accepted ethical principles to which physicians are expected to adhere and will discuss how these principles apply specifically to challenging scenarios with which practitioners of teledermatology may be faced.