A Nonspecific Penile Ulcer Leading to the Diagnosis of Wegener's Granulomatosis.

The presented case describes a 53-year-old male who had been treated for non-specific cutaneous lesions for two months without any improvement. He was referred to our department after developing an erosive penile ulcer. Investigation for sexually transmitted diseases and Mycobacterium tuberculosis ended with negative results. Penile ulcer biopsy suggested the diagnosis of Wegener's granulomatosis (WG). The patient presented with upper respiratory tract symptoms during this period. Measuring antineutrophil cytoplasmic antibodies (c-ANCA), confirmed the diagnosis. Immunosuppressive therapy was initiated and resulted in a favorable response.

Association of HIV Infection With Anal and Penile Low-Risk Human Papillomavirus Infections Among Men Who Have Sex With Men in Amsterdam: The HIV & HPV in MSM Study.

BACKGROUND: This study among men who have sex with men (MSM) aimed to (1) assess prevalence of anogenital low-risk human papillomavirus (lrHPV) infections, (2) evaluate associations with HIV infection, and (3) investigate lrHPV concordance. METHODS: In 2010 to 2011, MSM 18 years or older were recruited in Amsterdam, the Netherlands, and provided anal and penile self-swabs (HIV & HPV in MSM study). Using the HPV SPF10-PCR/DEIA/LiPA25 system, the presence of lrHPV types 6, 11, 34, 40, 42, 43, 44, 53, 54, 66, 68/73, 70, and 74 could be detected. Logistic regression with generalized estimating equations was used to assess the independent effect of HIV on lrHPV infections. The model was repeated for lrHPV subcategories (nononcogenic and weakly oncogenic infections separately). Concordance was defined as detection of the same lrHPV type in both self-swabs of one individual. RESULTS: A total of 778 MSM were included, of whom 317 (41%) were HIV positive (median CD4 count at enrollment, 530 cells/mm). Prevalence of anal lrHPV was 45% (95% confidence interval [CI], 41%-50%) in HIV-negative MSM and 69% (95% CI, 64%-74%) in HIV-positive MSM. Prevalence of penile lrHPV was 20% (95% CI, 16%-24%) and 37% (95% CI, 31%-42%), respectively. In multivariable analysis, HIV infection was independently associated with anal (adjusted odds ratio [aOR], 1.9; 95% CI, 1.5-2.3) and penile lrHPV (aOR, 2.0; 95% CI, 1.4-2.7). Nononcogenic and weakly oncogenic lrHPV subcategories showed a similar pattern of association. Anal lrHPV infections were strongly associated with the presence of a type-concordant penile infection (aOR, 5.8; 95% CI, 4.4-7.5) and vice versa (aOR, 5.7; 95% CI, 4.4-7.5). CONCLUSIONS: Anal and penile infections with lrHPV are common in MSM. HIV infection was an independent determinant for lrHPV infections.

Primary cutaneous histoplasmosis developed in the penis of an immunocompetent patient.

A 70-year-old male presenting a 3-month history of genital painless erythematous nodules in the balanopreputial sulcus was referred to our service. Histopathological exam presented a chronic dermatitis with epithelioid granulomas and Grocott staining revealed numerous fungal structures with a suggestive morphology of Histoplasma sp. Cultures evidenced Histoplasma capsulatum var. capsulatum. Treatment with oral itraconazole led to complete remission of lesions.

Primary cutaneous histoplasmosis developed in the penis of an immunocompetent patient

A 70-year-old male presenting a 3-month history of genital painless erythematous nodules in the balanopreputial sulcus was referred to our service. Histopathological exam presented a chronic dermatitis with epithelioid granulomas and Grocott staining revealed numerous fungal structures with a suggestive morphology of Histoplasma sp. Cultures evidenced Histoplasma capsulatum var. capsulatum. Treatment with oral itraconazole led to complete remission of lesions.

No evidence for a protective effect of naturally induced HPV antibodies on subsequent anogenital HPV infection in HIV-negative and HIV-infected MSM.

OBJECTIVES: To assess whether HPV serum antibodies detected after natural infection protect against subsequent anal or penile infection with the same HPV type in HIV-negative and HIV-infected men who have sex with men (MSM). METHODS: MSM aged ≥18 years were recruited in Amsterdam, the Netherlands (2010-2011), and followed-up semi-annually. Antibodies against 7 high-risk HPV types in baseline serum samples were tested using a multiplex immunoassay; baseline, 6-, and 12-month anal and penile samples were tested for HPV DNA and genotyped using the SPF10-PCR DEIA/LiPA25 system (version 1). Statistical analyses were performed using the Wei-Lin-Weissfeld method. RESULTS: 719 MSM (median age 40 years; IQR 35-48) with baseline and follow-up data were included in these analyses; 287 (40%) were HIV-infected. HPV seropositivity at baseline was not significantly associated with subsequent type-specific HPV infection at 6 or 12 months in multivariable analyses (for anal infection adjusted hazard ratio (aHR) 1.2; 95% CI 0.9-1.6; for penile infection aHR 0.8; 95% CI 0.6-1.2). High antibody concentrations showed no protective effect against subsequent infection either. CONCLUSIONS: In a population of highly sexually active, adult MSM, naturally induced HPV antibodies may not protect MSM against subsequent anal or penile HPV infection within one year.

Benign mast cell hyperplasia and atypical mast cell infiltrates in penile lichen planus in adult men.

Introduction. Lichen planus (LP) is a chronic cytokine-mediated disease of possible auto-immune etiology. 25% of men have anogenital manifestations. Erosive penile LP causes a scarring phimosis of the foreskin in uncircumcised men. Mast cells as potent immune modulators have been implicated in a number of autoimmune and chronic inflammatory diseases, but have not been investigated in LP. Material and Methods. Formalin-fixed tissues of 117 circumcision specimens of adult men affected by LP were evaluated for the extent of mast cell and lymphocyte infiltrates, characterized immunohistochemically with antibodies to CD 3, 4, 8, 20, 21, 25, 30, 117c and human mast cell tryptase. Specimens with dense mast cell infiltrates were analyzed for point mutations of the c-kit gene (D816V). Results. Unaffected skin and modified mucosa of foreskins contained ⟨5 mast cells/mm². The inflammatory infiltrate of LP-lesions displayed ⟨15 mast cells/mm² in 33/117 foreskins, 16-40 mast cells/mm² in 22/117 and ⟩40 mast cells/mm² (average 70, range 40-100) in 62/117 foreskins. Lesional mast cells of 29/117 (24%) foreskins showed aberrant CD25-expression and/or spindled morphology, with 11/29 men having erosive LP, 13/29 a lymphocytic vasculitis and 1/28 a systemic mastocytosis. Neither CD30-expression nor c-kit mutations were identified. Atypical mast cell infiltrates in LP correlated with high disease activity, erosive LP and presence of lymphocytic vasculitis Conclusions. Increased mast cells in penile LP, mostly representing a benign hyperplasia/activation syndrome, suggests them as targets for innovative therapy options for symptomatic LP-patients not responding to corticosteroid therapy. Presently, the biological implications of atypical mast cell infiltrates in penile LP are unknown.

Immunological activity of photodynamic therapy for genital warts.

BACKGROUND: An increasing body of evidence supports the usefulness of photodynamic therapy (PDT) in the treatment of non-neoplastic pathological conditions, including genital warts. In particular, PDT has demonstrated good clinical cure rates and low recurrence, and is now suggested as a safe alternative means of treating condylomata. OBJECTIVE: To confirm the suitability of aminolaevulinic acid (ALA)-PDT for the treatment of this condition and to investigate the recruitment and significance of immune cells in lesional areas by immunohistochemical analysis at different time intervals after treatment. METHODS: Fifteen subjects with histologically proven, recalcitrant condylomata acuminata of the penis, urethra, vulva or perianal area underwent several cycles of PDT following ALA application. Biopsies were taken at baseline and at different intervals during the trial, and infiltrating immune cells, CD3, CD4, CD8, CD1a and CD68, were evaluated by double immunocytochemical alkaline phosphatase antialkaline phosphatase (APAAP) staining. RESULTS: Our trial provided a complete cure rate of nine of 15 subjects after five PDT sessions. Perianal lesions showed a particularly rapid remission. While progressing towards total lesion clearance, the immunohistochemical pattern was dominated by dense CD4+ T lymphocytes infiltrating the superficial dermis, accompanied by an accumulation of Langerhans cells. Simultaneously, CD8 began to increase in the lesions of responding patients, and Langerhans cells seemed to migrate towards the dermis. CD68+ macrophages apparently did not participate in the immune inflammatory response. CONCLUSIONS: This study, to the best of our knowledge, represents the first attempt to clarify the effect of ALA-PDT on infiltrating immune cells in condylomata acuminata. Our results appear to confirm previously reported clinical data, suggesting that rapid activation of specific immunity in lesional skin, CD4+ T lymphocytes and dendritic cells could be responsible for healing.

Condyloma overgrowth caused by immune reconstitution inflammatory syndrome.

A 46-year-old man with human immunodeficiency virus presented with a condyloma that formed during 6 months and encased his penis, scrotum, and perineum. Visible condyloma growth began when this immunocompromised patient started highly active antiretroviral therapy, and it grew rapidly as his viral load plummeted. The patient underwent resection and reconstruction with skin grafting. Pathology findings revealed benign condyloma acuminatum. This rapid progression of condyloma growth is a cutaneous manifestation of immune reconstitution inflammatory syndrome.

Detailed analysis of the T-cell lymphocytic infiltrate in penile lichen sclerosus: an immunohistochemical and molecular investigation.

AIM: To determine the extent of clonal outgrowth in the lymphocytic tissue infiltrate of lichen sclerosus (LS). The presence of T cells with a monoclonally rearranged T-cell receptor gamma-gene (TCRgamma) has been described in up to 50% of biopsies of vulvar and penile LS. MATERIAL AND RESULTS: We analysed 33 foreskin specimens with LS for the presence of clonal T cells by conventional polymerase chain reaction (PCR) analysis and with TCRgamma-PCR-based fluorescent fragment analysis. Eighteen of 33 patients revealed a band indicating a monoclonally rearranged TCRgamma on conventional PCR analysis. Subsequent TCRgamma-PCR-based fluorescent fragment analysis identified 8/18 patients with monoclonal T-cell DNA ranging from 1.4% to 23.1% of total T-cell DNA analysed and a size range from 56 to 72 base pairs. Four of 18 patients had an oligoclonal and 6/18 patients revealed a polyclonal banding pattern. The lymphocytic infiltrate contained low numbers of gammadelta T cells and cytotoxic T cells in comparable numbers to the low percentage of clonal TCRgamma DNA. CONCLUSIONS: The low percentage of clonal TCRgamma DNA argues against a systemic neoplastic disease, but rather for a local immune disorder. The target antigen of the clonal outgrowth is unknown, but an exaggerated antigen-dependent proliferation of T cells due to chronic local antigen exposure, probably an infectious antigen, is the most likely explanation.

Genital lichen sclerosus associated with morphoea or systemic sclerosis: clinical and HLA characteristics.

Although patients with both morphoea and lichen sclerosus have been reported previously, in the majority of these reports the lichen sclerosus has been extragenital. We report nine patients in whom genital lichen sclerosus coexisted with scleroderma spectrum disorders including seven with morphoea, one with morphoea and lichen planus, and one with systemic sclerosis. The clinical features, associated autoimmune disease, autoantibodies and HLA type are reported. Antibodies to Borrelia burgdorferi were not detected in any of the patients. The coexistence of these diseases raises a number of intriguing questions about the relationship between them.

Systemic immunosuppression by HIV infection influences HPV transcription and thus local immune responses in condyloma acuminatum.

Human immunodeficiency virus (HIV) infection is considered to influence the pathogenesis of human papillomavirus (HPV)-associated diseases. It is not clear whether this occurs directly through molecular interactions between viral genes and/or indirectly through effects on the immune functions. In the present study we compared molecular characteristics of penile condylomas from immunocompetent and HIV-positive individuals. Using polymerase chain reaction (PCR) and reverse transcriptase (RT)-PCR techniques we determined some characteristics of local immune responses and transcriptional activity of both viruses. Our findings revealed that HIV-seropositivity was accompanied by multiple HPV infection and a CD4-count-dependent appearance of oncogenic HPV-types. HIV infection also changed the patterns of HPV transcription favouring transcription of early genes such as E7. Apparently, HIV infection influences local immunity by altering HPV transcription and by systemic immunodeficiency.

The summer penile syndrome: seasonal acute hypersensitivity reaction caused by chigger bites on the penis.

OBJECTIVE: To describe the seasonal acute hypersensitivity reaction of the penis due to chigger bites, known as the summer penile syndrome. DESIGN: A consecutive series of patients. SETTING: The emergency department of an urban academic children's hospital in the midwestern United States. PARTICIPANTS: Male pediatric patients with an acute hypersensitivity reaction of the penis. RESULTS: Ninety-four patients were treated for summer penile syndrome during the four-month period from June through September. Patients ranged in age from seven months to 11 years (mean = 5.1, SD = 2.5). Twenty-one percent of patients had also experienced a similar prior episode of penile swelling. Symptoms included pruritus in 84% of cases, dysuria in 33%, and decreased strength of urine stream in 8% of patients. Eighty-four percent of patients had recent exposure to the woods, park, lawn, or poison ivy. In addition to edema, findings on physical examination included a papule or bite puncture mark in 50% of patients, erythema in 32%, and excoriation in 6% of patients. Fifty-six percent of patients had bites on other areas of the body. The emergency physician attributed the penile edema to an insect or chigger bite in 98% of cases. Treatment consisted of an oral antihistamine and cold compresses in most cases. The reported duration of penile swelling ranged from one to 18 days with a mean of 4.1 days (SD = 3.5), and the reported duration of pruritus ranged from 0 to 14 days with a mean of 3.0 days (SD = 2.6). CONCLUSION: This study provides an understanding of the summer penile syndrome for pediatric care providers. To our knowledge, this study is the first to describe this seasonal syndrome in the medical literature.

Tissue specific HPV expression and downregulation of local immune responses in condylomas from HIV seropositive individuals.

OBJECTIVE: To study the effect of tissue specific human papillomavirus (HPV) expression and its effect on local immunity in condylomas from HIV positive individuals. METHODS: Biopsy specimens of eight penile and eight perianal condylomas from HIV seropositive individuals were analysed. Expression of viral genes (HIV-tat and HPV E7 and L1) was determined by RT-PCR. The status of local immunity also was determined by RT-PCR by measuring CD4, CD8, CD16, CD1a, HLA-DR, and HLA-B7 mRNA levels in the tissues. Differentiation was determined by measuring involucrin, keratinocyte transglutaminase, as well as cytokeratins 10, 16, and 17. Proliferation markers such as PCNA and c-myc were also determined. RESULTS: The transcription pattern of HPV in perianal condylomas, which preferentially expressed the early (E7) gene, was different from that of penile condylomas, which primarily expressed the late (L1) gene. This transcription pattern is in good correlation with the keratinisation and differentiation patterns of the two epithelia: perianal biopsies preferentially expressed K16 and K17 while penile warts mainly expressed K10, markers of parakeratotic and orthokeratotic epithelia, respectively. Perianal biopsies also showed a higher degree of proliferation (PCNA and c-myc). Interestingly, transcription of HIV-tat was also higher in perianal than in penile biopsies. A high degree of local immunodeficiency was observed in perianal biopsies--that is, levels of CD4, CD16, and CD1a mRNAs were significantly lower. A negative correlation between CD1a (Langerhans cells) levels and HPV E7 levels was established. HPV E7 levels positively correlated with HIV-tat levels. Perianal tissues demonstrated more CD1a depression and tat associated HPV upregulation. CONCLUSION: HIV influences the expression of HPV genes resulting in local immunosuppression that might lead to an inappropriate immune surveillance of viral infection. Also, tissue type is an important factor in controlling viral transcription in a differentiation dependent manner. These findings may explain the higher rate of dysplasia and neoplasia in the perianal area.