Meatal Intraurethral Warts Successfully Treated with 5-fluorouracil Cream.

Condyloma acuminatum relatively rarely involves the urethra, and when it does it is usually only in the most distal portion of the urethra. A number of treatments have been described for urethral condylomas. These treatments are extensive and variable, comprising laser treatment, electrosurgery, cryotherapy, and topical application of cytotoxic agents such as 80% trichloroacetic acid, 5-fluorouracil cream (5-FU), podophyllin, podophyllotoxin, and imiquimod. Laser is still considered to be therapy of choice for treatment of intrauretral condylomata. We present the case of a 25-year-old male patient with meatal intraurethral warts who was successfully treated with 5-FU, after many unsuccessful treatment attempts with laser treatment, electrosurgery, cryotherapy, imiquimod, and 80% trichloroacetic acid.

Coexistence of Anogenital Psoriasis and Genital Warts - Is There an Optimal Treatment?

The prevalence of psoriasis is 2% of the world's population (1). Inverse psoriasis is characterized by the development of erythematous shiny plaques at intertriginous areas of the body. The prevalence of only anogenital involvement appears to be low, but involvement of the anogenital area together with other areas is found in up to 45% of patients with psoriasis (2). A 21-year-old female student with a 3-month history of mild psoriasis (erythematosquamous plaque on the elbows and nail pitting on the nails of the hand) was referred to our Department. One month earlier, suddenly appearance of erythematous, smooth, clearly demarcated plaques was observed on the labia majora, the mons pubis, the perineal and perianal region together with a brownish hyperkeratotic papule on the pubic region (Figure 1, a-b). The patient underwent excisional biopsy at the Department of Surgery, and the pathohistological finding was unavailable to us. The elbows were treated with corticosteroid-keratolytic preparation, whereas the anogenital lesions were treated with moderately potent topical corticosteroids. In addition to anogenital erythema, on clinical examination we noticed an erythematosquamous plaque on the site of excision with a hyperkeratotic verrucous papule on the edge of the lesion (the Koebner phenomenon on the site of skin injury). In the pubic region, we noticed two hyperkeratotic papules and a few verrucous papules on labia majora. Localized dermatophyte or candida infection were excluded with a KOH test and scrapings culture. Serology for syphilis, HIV, and hepatitis were negative. Cervical Pap smear was normal. Biopsy of erythematosus lesion from the mons pubis was conclusive for psoriasis, and of the keratotic papule with the genital wart with positive HPV 6 and 11. The patient's older sister had chronic plaque psoriasis. We employed physically ablative methods like liquid nitrogen cryosurgery, electrocauterization, and curettage, applied topical agents like 0.5% podophyllotoxin solution, 20% podophyllin, and 80% trichloroacetic acid, and treated the psoriatic lesions with a short course of moderate-potency corticosteroids and tacrolimus ointment. All therapeutic attempts were ineffective for curing both diseases. Our patient either had psoriasis with sparse genital warts or exacerbation of multiple anogenital warts (Figure 2, a-b). Anogenital psoriasis is a skin disease that causes great discomfort. The disease-related quality of life is significantly reduced, especially regarding sexual behavior. Therapy for either anogenital psoriasis or genital warts is not entirely satisfactory. Many topical agents suitable for use on the psoriatic lesions on the body, such as coal tar, anthralin, vitamin D derivatives or retinoids, may be too irritating in the anogenital region. The most useful therapy for treatment of anogenital psoriasis are moderately potent topical corticosteroids and topical tacrolimus or pimecrolimus (1). However, corticosteroid-induced atrophy is possible in intertriginous sites. The Koebner phenomenon isomorphic response is the appearance of new skin lesions on areas of cutaneous injury in otherwise healthy skin (3). About 25% of patients with psoriasis have elicitation of psoriatic lesions by injury to the skin (4). Other than in patients with psoriasis, the Koebner phenomenon can be found in other skin diseases like vitiligo, lichen planus, lichen nitidus, pityriasis rubra pilaris, flat warts, and keratosis follicularis (Darier disease) (5). According to Eyre at al., about 67% patients with psoriasis (4) present with clearing of psoriatic lesions following skin injury (positive "reverse" Koebner reaction) (4). There is no single treatment for genital warts that is 100% effective, and different types of treatment are very often combined. Accepted methods of treatment involve chemical and physical destruction or removal (6). Since psoriasis koebnerizes, any destructive technique may exacerbate the psoriasis. Coexistence of anogenital psoriasis and HPV presents a huge therapeutic problem because a therapy for psoriasis such as corticosteroids can provoke appearance and/or reappearance of HPV infection, while some therapies for anogenital warts, like cryotherapy, curettage, laser ablation, electrosurgery, or surgery can provoke the appearance and/or reappearance of psoriatic infection due to the Koebner phenomenon.

Coexistence of genital lichen sclerosus and genital warts.

Lichen sclerosus (LS) is a chronic, inflammatory, mucocutaneous disorder of the genital and extragenital skin. Anogenital warts are benign proliferative lesions caused by human papillomavirus (HPV), which is found in > 95% of lesions. We present two cases of the coexistence of LS and genital warts: one patient with and one without a previous history of genital warts. According to our knowledge and a literature search, only a few cases of the coexistence of LS and genital warts have been reported.

Genital Herpes Zoster as Possible Indicator of HIV Infection.

Herpes zoster (HZ) is an acute, cutaneous viral infection caused by the reactivation of varicella-zoster virus (VZV) (1). It is a frequent medical condition with an incidence rate of 2-3 cases per 1000 person/years in the general population and 7-10 cases per 1000 person/years after the age of 50 (1,2). Risk factors and triggers for reactivation of HZV have not yet been determined precisely, but are likely to include malignancies, immune deficiencies, solid organ and bone marrow transplant recipients, autoimmune diseases, psychological conditions, emotional stress, human immunodeficiency virus (HIV) infection, and other patients receiving immunosuppressive therapies (1,3). A 24-year-old IV drug user presented with grouped clusters of vesicles and erosions on an erythematous, edematous base distributed on the left side of the penile shaft and the left infraumbilical region (Figure 1, a and b), with regional lymphadenopathy. He had prodromal symptoms of pain, dysesthesia and burning a few days prior to the appearance of the skin lesion. The patient reported unprotected sexual contacts a few months before the eruptions. The unilateral distribution was highly suggestive of herpes zoster. A Tzanck smear was performed by obtaining scrapings from the base of a fresh vesicular lesion after it had been unroofed; it showed the characteristic presence of multinucleated giant cells that suggested herpes infection. Polymerase chain reaction (PCR) analysis of vesicular fluid yielded positive results for VZV. A 7-day course of acyclovir (800 mg 5 times a day) was initiated. The patient reported marked improvement on the second day of antiviral therapy. The course was uncomplicated, and the lesions healed without postherpetic neuralgia. Serologic tests for syphilis (VDRL/RPR and TPHA) and hepatitis C and B serologic tests were negative, but HIV test (enzyme immunoassays (EIA) for HIV-1 and HIV-2 antibodies were positive, which was later confirmed with Western blot (WB) tests. Because of the positive HIV test, the patient was referred to the Clinic for Infectious Diseases for further treatment. Herpes zoster is painful vesicular skin eruption with unilateral dermatomal involvement, usually with a severe impact on the quality of life in affected patients (1). The risk for developing HZ during a lifetime in patients exposed to VZV infection is 10-30% (4). However, the risk is higher in immunocompromised patients, particularly in cancer patients and HIV-positive patients (1,5,6). HZ is seen approximately 7 times more frequent in patients with HIV infection (5). Reactivated VZV infection may occur at any stage of HIV infection and may be the first clinical evidence of HIV infection. The development of HZ in immunocompromised individuals can be explain by decline in cell-mediated immunity and CD4 count (6). HZ predominantly affects the thoracic region, followed by the head, cervical, and lumbar regions (1). Sacral dermatomes are involved in only up to 2% of cases (1). HZ involving the penis is rarely reported, with only few case reports in the literature (3,7-9). Birch et al. compared VZV and herpes simplex virus (HSV) in specimens obtained from the genital lesions of adults presenting with presumed genital herpes infection (10). They found VZV in nearly 3% of virus-positive genital specimens, which demonstrates that this virus needs to be considered in the differential diagnosis of genital herpetic lesions (10) and that it is possible that genital HZ infection is underdiagnosed. Tzanck smear is a rapid and inexpensive method, but it cannot differentiate VZV from HSV. Genital HZ could be mistaken for zosteriform HSV infection, so a PCR test should be performed to confirm the underlying diagnosis (1). Genital forms of HZ are rare and sometimes clinically difficult to diagnose, especially when the typical zosteriform distribution is lacking; PCR testing is therefore suggested. HZ is considered a possible HIV indicator; an HIV test should therefore be performed. According to our knowledge and literature search, this is the first case report of penile HZ in an HIV-positive patient.

Sinecatechins and imiquimod as proactive sequential therapy of external genital and perianal warts in adults.

This review about the proactive sequential therapy (PST) of external genital and perianal warts (EGW) is based on the most current available clinical literature and on the broad clinical experience of a group of international experts, physicians who are well versed in the treatment of human papillomavirus-associated diseases. It provides a practical guide for the treatment of EGW, including epidemiology, etiology, clinical appearance, and diagnostic procedures for these viral infections. Furthermore, the treatment goals and current treatment options, elucidating provider- and patient-applied therapies, and the parameters driving treatment decisions are summarized. Specifically, the mode of action of the topical treatments sinecatechins and imiquimod, as well as the PST for EGW to achieve rapid and sustained clearance is discussed. The group of experts has developed a treatment algorithm giving healthcare providers a practical tool for the treatment of EGW which is very valuable in the presence of many different treatment options.

Human papillomavirus-related diseases of the female lower genital tract: oncogenic aspects and molecular interaction.

The causal role of human papillomavirus (HPV) in all cancers of the uterine cervix has been firmly established biologically and epidemiologically. Most cancers of both the vulva and the vagina are also induced by HPV. Papillomaviruses are perfectly adapted to their natural host tissue, the differentiating epithelial cell of skin or mucosae, and exploit the cellular machinery for their own purposes. The infectious cycle is initiated once the infectious particles reach the basal layer of the epithelium, where they bind to and enter the cells. The critical molecules in the process of virus replication are the viral proteins E6 and E7, which interact with a number of cellular proteins. In experimental system these interactions have been shown to induce proliferation and eventually immortalization and malignant transformation of cells. Binding of E7 to pRb activates the E2F transcription factor, which then triggers the expression of proteins necessary for DNA replication. Unscheduled S-phase would normally lead to apoptosis by the action of p53. However, in HPV-infected cells, this process is counteracted by the viral E6 protein, which targets p53 for proteolytic degradation. Besides blocking p53 function in regulation of apoptosis, high-risk HPV proteins interact with both extrinsic and intrinsic apoptotic pathways. As an aberration of virus infection, constant activity of the viral proteins E6 and E7 leads to increasing genomic instability, accumulation of oncogene mutations, further loss of cell-growth control and ultimately cancer. The immune system uses innate and adaptive immunity to recognize and combat foreign agents that invade the body, but these methods are sometimes ineffective against human papillomavirus. HPV has several mechanisms for avoiding the immune system. Furthermore, HPV infections disrupt cytokine expression with the E6 and E7 oncoproteins, particularly targeting the expression of interferon genes. Approximately 10% of individuals develop a persistent infection, and it is this cohort who is at risk of cancer progression, with the development of high-grade precursor lesions and eventually invasive carcinoma.

HPV-associated diseases.

Nearly 200 distinct human papilloma viruses (HPVs) have now been recognized, and each is associated with a specific set of clinical lesions. They are associated with a spectrum of diseases, from benign verrucae vulgares and condylomata acuminata to the malignancies of the cervix, vulva, anus, and penis. Disease associated with HPV can be divided into skin and mucosal lesion of the genital and extragenital regions. The relationship between HPV and nonmelanoma skin cancer (NMSC) is important clinically, because NMSC is the most common form of malignancy among fair-skinned populations. HPVs have also been detected in skin tags, lichen sclerosus, seborrheic keratoses, actinic keratoses, epidermal cysts, psoriatic plaques, and plucked hairs, but cutaneous HPV can be found on healthy skin.

Inherited epidermolysis bullosa - the spectrum of complications.

Epidermolysis bullosa is a group of inherited diseases that are characterized by skin and mucosal fragility and blister formation. A wide variety of extracutaneous manifestations can develop as well as various complications of the disease such as severe anemia, growth retardation, esophageal stenosis, mutilating deformities of hands and feet, glomerulonephritis leading to chronic renal failure, and many others. One of the most important and often occurring complications is the development of cutaneous squamous cell carcinomas that grow and metastasize quickly. The objective of this paper is to give dermatologists a review of major complications encountered in patients with epidermolysis bullosa. Since these complications occur so often and can be considered to be part of the clinical picture, it is mandatory to develop a multidisciplinary well-educated team involved in follow-up and treatment of these patients.

Molecular variants of human papilloma viruses type 16 and 6 in women with different cytological results detected by RFLP analysis.

HPV infections are common and the presence of the same high-risk type in cervical specimens can be due to reinfection or persistence. Persistent infection is the most important predictor for development of cervical carcinoma. The aim of this study was to validate PCR-RFLP with two sets of primers: MY09/MY11 that amplify a fragment of L1 and P1/P2 that amplify a fragment of E1 ORF. PCR product of MY09/MY11 was digested with a set of 6 restriction enzymes (RE) and PCR product of P1/P2 with a set of 12 RE. Cervical samples from 110 women patients of the University Gynecologic Clinic CHC Zagreb were analyzed. There were 98 (89.1%) PCR positive samples detected with P1/P2 primers, and 94 (85.5%) PCR positive samples detected with MY09/MY11 primers. Seven HPV types were detected with P1/P2-RFLP technique and 17 with MY09/MY11-RFLP PCR positive samples amplified with both primer pairs agreed with each other in 82 samples; 16 samples were only positive with P1/P2 and 12 samples were only positive by MY09/MY11. HPV 16 was detected in 39 samples with MY09/11-RFLP, out of these two variants (two different patterns) were found with P1/P2 using Dde I, Hae III and Eco I. HPV 6 was detected in 9 samples with MY09/11-RFLP, out of these two variants were found with P1/P2 using HinfI. Combining these two PCR-RFLP methods subtypes of HPV 16 and HPV 6 were detected.

[The specifities of the HPV-genital infections in males]. / Posebnosti genitalnih infekcija humanim papiloma virusom u muskaraca.

Anogenital infections caused by Human papillomavirus (HPV) are the most frequently diagnosed sexually transmitted infections of viral origin and up to 150 HPV DNA types have been recognized so far. Anogenital warts (condylomata acuminata) are the most common lesions presented in men, however, during the last decade the other HPV-associated exaggerated lesions such as condylomata plana, penile, scrotal, and anal intraepithelial neoplasias, as well as the penile, urine bladder and prostate cancer have been studied somewhat more extensively. The clinical variations might range from clinically invisible, asymptomatic lesions to the bizarre forms of giant condyloma of Buschke-Löwenstein type, including Bowenoid papulosis, Mb. Bowen, different kinds of eryhtroplasia both in men and women and a large spectrum of HPV-induced dermatovenereological entities in genital region including high-grade intraepithelial genital neoplasias, such as penile, anal, scrotal, vulvar, vaginal etc. (thus not only cervical), and, last but not least - the anogenital warts. A prophylactic vaccine that targets these types should thus substantially reduce the burden of HPV-associated clinical diseases. Ultimately, within the spectrum of therapeutic options for condylomata, no method is really superior to others; recurrences occurred in 30-70% of cases. We definitely need the HPV vaccination programme to eliminate one of the oldest and up to now unsolved problems of the mankind. Since HPV is transmitted by sexual intercourse, treatment of both partners is necessary in order to eliminate the virus from the population. Approaches to this include prophylactic vaccines such as quadrivalent HPV vaccine for both men and women.

[Diagnostic-therapeutic guidelines for men whose partners have HPV genital infection]. / Dijagnosticko-terapijski postupnik za muskarce kojih partnerice imaju HPV-genitalnu infekciju.

Human papilloma virus infection is the most frequent sexually transmitted disease. HPV infections are connected with different diseases such as benign warts, condylomata acuminata, malignant cervical, vulvar, vaginal, penile and anal carcinoma. Peniscopy with HPV detection is a specific diagnostic method for diagnosis of subclinical HPV genital infection in asymptomatic men. Taking the samples for HPV detection from asymptomatic men with curette is more qualitative way of getting enough samples then taking swab with wooden stick or (tongue) depressor. Early diagnosis and treatment of HPV infections in men is of potential benefit because their eradication can reduce the viral reservoir and as the result of that the incidence of CIN, carcinoma in situ and invasive cervical carcinoma can be reduced. For the correct diagnosis and for choosing the adequate therapeutical technique, we suggest diagnostic-therapeutic guidelines for HPV genital infection in men.

Zoon plasma cell balanitis: an overview and role of histopathology.

Balanitis circumscripta plasmacellularis or Zoon's balanitis is an idiopathic, benign condition of the genitalia that mostly presents as a solitary, persistent plaque on the glans of primarily uncircumcised, middle-aged to older men. Its etiology and pathogenesis remains speculative. This article provides an overview of the clinical morphology, microscopic features, differential diagnosis and therapy. Particular attention is paid to histopathologic features. Besides, a case is presented of an uncircumcised man with clinical and histologic features of balanitis circumscripta plasmacellularis who was successfully cured by circumcision. The distinction of this lesion from similar lesions is rather important, and a large group of disorders such as premalignant, infective and other inflammatory penile diseases should be definitely taken into consideration on the differential diagnosis. It seems that circumcision might be the current 'gold standard' for treatment of this disorder.