Comorbidities in Male Patients With Lichen Sclerosus: A Case-Control Study.

OBJECTIVE: Lichen sclerosus (LS) is a chronic inflammatory skin disease. In male patients, it usually involves the glans penis and foreskin and can cause phimosis or meatal stenosis. The aim of this cross-sectional case-control study was to identify clinically important comorbidities in male patients with LS. MATERIALS AND METHODS: By searching Turku University Hospital electronic health records, the authors identified 630 male patients diagnosed with LS between 2004 and 2020. To investigate possible comorbidities, the authors compared this patient group to a 10-fold larger control group. RESULTS: The incidence of LS increased during the study period, from 5 to 27.5 per 100,000 men. Patients were most often diagnosed at 21 to 25 years of age. Patients with LS exhibited markedly increased risks of penile carcinoma (odds ratio [OR], 81.0; 95% CI = 10.82-3516.7; p < .001) and carcinoma in situ of the penis (OR = 60.5; 95% CI = 7.32-2738.9; p < .001). Patients also more commonly exhibited lichen planus (OR = 16.8; 95% CI = 8.97-32.39; p < .001), psoriasis (OR = 3.3; 95% CI = 1.80-5.70; p = .004), angina pectoris (OR = 1.8; 95% CI = 1.10-2.81; p = .013), obesity (OR = 2.6; 95% CI = 1.72-3.77; p < .001), type 2 diabetes (OR = 2.3; 95% CI = 1.74-3.09; p < .001), and hypertension (OR = 1.9; 95% CI = 1.53-2.37; p < .001). The most commonly performed urological procedures were operation for phimosis, uroflowmetry, and ultrasound measurement of residual urine. CONCLUSIONS: Genital malignancies, other dermatological conditions, and diseases related to metabolic syndrome should be considered when treating patients with LS.

Balanitis Xerotica Obliterans:an underestimated cause of secondary phimosis.

Balanitis Xerotica Obliterans is a chronic, progressive, sclerosing inflammation of unclear etiology. It involves the external genitalia of males and more specifically the prepuce and its frenulum, the glans, and the external urethral meatus while it may extend to the peripheral part of the urethra. Recent studies have noted an increasing incidence in the paediatric population. It is the most common cause of secondary (pathologic) phimosis. Even more, in boys with physiologic phimosis that does not respond to conservative treatment, Balanitis Xerotica Obliterans should be considered as the underlying condition. In this study, we present all the latest data and attempt to create a diagnostic and curative algorithm regarding this condition.

Underestimation of genital lichen sclerosus incidence in boys with phimosis: results from a systematic review.

PURPOSE: Previous histological studies have shown a variable incidence of genital lichen sclerosus (LS). However, the results of these studies were inconsistent. To overcome the limitation of individual studies, we performed this systematic review to explore the true incidence of LS. METHODS: A comprehensive search of Pubmed, Embase, Web of Science and Cochrane Library was performed including cross-referencing independently by two assessors. RESULTS: A total of 22 articles published from 1980 to 2017 were included in our study. The proportion of LS in those with phimosis had been described in many literature studies, ranging from 2 to 95%. The actual incidence of LS is thought to be clinically underestimated by as much as 50%. CONCLUSIONS: The true incidence of LS in boys is more common than previously realized. LS may be observed in foreskin with or without phimosis. The presence of acquired phimosis may be an aggravating factor in the incidence of LS. The diagnosis LS must be based on biopsy for acquired phimosis because clinical findings underestimated the incidence of LS.

Outcomes of circumcision in children with single ventricle physiology.

PURPOSE: Children with single ventricle physiology (SVP) have been shown to have a high morbidity and mortality after non-cardiac surgical procedures. Elective circumcision is one of the most common pediatric operations with low morbidity and mortality. The purpose of our study was to review our institutional experience with SVP children undergoing circumcisions to determine peri-operative course and outcomes. METHODS: We performed a retrospective review of children with SVP who underwent an elective circumcision from 2000 to 2017. Children with non-single ventricle physiology or children undergoing circumcision in combination with another case were excluded. Demographics, surgical characteristics, and outcomes were analyzed. Descriptive statistics were performed, all medians were reported with interquartile range. RESULTS: 15 males underwent elective circumcision with a median age at the time of surgery of 1.13 (1.03, 1.38) years. Eighty-four percent underwent their circumcision after their 2nd stage cardiac operation. Most common operative indication was uncomplicated phimosis. Median operative time was 20 (16, 27) mins. Median total length of stay was 229 (185, 242) mins with no admissions. Post-operative complications included two (16%) hematomas with one requiring surgical intervention. There were no deaths. CONCLUSION: Children with SVP who undergo elective circumcision may have a higher risk of bleeding.

High Risk Human Papillomavirus Infection of the Foreskin in Asymptomatic Men and Patients with Phimosis.

PURPOSE: There has been increasing interest in understanding the natural history of HPV and the diseases that it causes in men. HPV infection is strongly associated with penile cancer, lack of neonatal circumcision and phimosis. We investigated the incidence of HPV infection in asymptomatic men and patients with phimosis. MATERIALS AND METHODS: We assessed 110 asymptomatic men and 30 patients who underwent circumcision due to phimosis. DNA was extracted from swabbed samples collected from asymptomatic men and from foreskin samples collected at circumcision. Polymerase chain reaction using consensus primers for detecting HPV-MY09/11 was performed to detect generic HPV DNA. HPV genotyping was done by polymerase chain reaction amplification with primers for the E6 gene DNA sequences HPV6, HPV11, HPV16, HPV18, HPV31, HPV33, HPV35, HPV45 and HPV58. RESULTS: HPV was present in 46.66% of patients with phimosis, of whom 50% had high risk HPV genotypes. Of asymptomatic cases 16.36% were HPV positive but only 1 sample showed high risk HPV. We detected a significantly high rate of HPV genital infection in patients presenting with phimosis compared with asymptomatic men (p = 0.00167). The prevalence of high risk HPV genotypes in patients with phimosis was also statistically significant (p = 0.0004). CONCLUSIONS: We found a robust association between phimosis and the genital HPV prevalence in men and a significant frequency of high risk HPV. Other studies are needed to investigate the occurrence of factors that can increase the incidence of penile carcinoma and determine its impact on female genital infection in cervical cancer.

Genital Graft-versus-Host Disease in Children: An Underdiagnosed and Undertreated Entity.

Genital graft-versus-host disease (GVHD) is an underdiagnosed and poorly recognized complication, especially in the pediatric population. We report our data on children with genital manifestations of GVHD and their unique clinical features. The study included children up to age 18 years who underwent hematopoietic stem cell transplantation (HSCT) over a 20-year period from February 2002 to February 2022. A total of 1035 children underwent HSCT during the study period. Genital GVHD was documented in 164 children (15.8%). Among these 164 children, 23 (14%) were age <2 years, 98 (59.8%) were age 2 to 10 years, and 43 (26.2%) were age ≥10 years. The conditioning regimen was myeloablative in 122 children (74.4%) and reduced intensity in 42 children (25.6%). Donor type was matched related donor in 62 (37.8%), matched unrelated donor in 44 (26.8%), and haploidentical in 34 (20.7%). Peripheral blood stem cells (PBSCs) were used in 78.7% of the children (n = 129), and sex mismatch was noted in 31.1% of genital GVHD cases (51 of 164). The overall incidence of chronic oral GVHD was 33% (342 of 1035), and of these, 47.9% (164 of 342) also had genital GVHD. Patients with genital GVHD ultimately may require surgical management; 21.5% (22 of 103) of boys with genital GVHD ultimately required circumcision for phimosis, and 1 female patient developed hematocolpos necessitating surgical management. Our case series highlights the significant association between chronic oral GVHD and genital GVHD. Given the strong association between oral GVHD and genital GVHD in children, it is imperative to examine the genital area in all children on follow-up for chronic GVHD. Donor-recipient sex mismatch and use of PBSC grafts predispose to chronic genital GVHD. Early identification and treatment of genital GVHD may help prevent complications, including scarring and phimosis.

Congenital phimosis in patients with and without lichen sclerosus: distinct expression patterns of tissue remodeling associated genes.

PURPOSE: Lichen sclerosus is a potentially important factor in the ongoing debate concerning the pathology of persistent congenital phimosis. We assessed the molecular differences of congenital phimosis in boys with and without lichen sclerosus compared to age matched boys with fully retractable foreskins to gain more insight into the pathogenesis of fibrotic remodeling of the prepuce. MATERIALS AND METHODS: A total of 150 boys were circumcised in a prospective study between 2007 and 2009. Using target gene specific preamplification and quantitative real-time polymerase chain reaction based low density arrays, we measured the mRNA expression of 45 tissue remodeling associated genes in foreskins of boys with absolute phimosis and lichen sclerosus (8 patients) and those of an age matched group of boys with phimosis but no lichen sclerosus (8), as well as a control group with foreskins without delimitable changes (6). Complementary protein expression and inflammatory infiltrates were assessed by immunohistochemical analysis. RESULTS: Cellular composition, inflammatory infiltrate and microenvironment as seen in histologically proven lichen sclerosis differed significantly from the other groups. In particular, lichen sclerosis was characterized by over expression of bone morphogenetic protein 2 and its corresponding receptor, matrix metalloproteinases 1 and 9 and tissue inhibitor of metalloproteinases 1, cytokine chemokine ligands 5 (RANTES) and interleukin 4, and transforming growth factor-ß2 and its corresponding receptor. There were no major molecular differences between specimens from boys with congenital phimosis without signs of lichen sclerosis and controls. CONCLUSIONS: Distinct expression patterns of tissue remodeling associated genes are evident in boys with congenital phimosis and lichen sclerosis, while congenital phimosis without lichen sclerosis represents a physiological condition.

[Balanitis xerotica obliterans with phimosis in elderly patients presenting with difficulty in urination].

Eight elderly patients (average age 76.1±4.3 years) with balanitis xerotica obliterans (BXO) accompanied by phimosis presented with difficulty in urination. Preoperative average international prostate symptom score, average maximum urinary flow rate, and average volume of residual urine were 20.7±6.3 points (n＝8), 5.1±3.6 ml/s (n＝5), and 85.4±77.3 ml (n＝8), respectively. Some of the patient's complaints, such as severe dribbling of urine, urinary stream division, and ballooning of the foreskin, were not included in the items of the major questionnaire on urination. Dorsal incision and circumcision was performed in all patients, and all were pathologically diagnosed with BXO. Meatoplasty was performed in one patient with a meatal stenosis. No coexistence of penile cancer was observed. Statistically significant improvements were observed in subjective and objective findings after treatment. In conclusion, BXO with phimosis in elderly patients should be considered as a cause of lower urinary tract symptoms.

Severe phimosis leading to obstructive uropathy in a boy with lichen sclerosus.

Lichen sclerosus (LS) is a chronic, inflammatory condition which commonly involves the anogenital skin. This condition may affect the foreskin, glans, frenulum, meatus and urethra in males. It manifests itself with voiding symptoms. Obstructive uropathy is an extremely rare clinical presentation in childhood. This study reports the case of a 13-year-old boy presenting with obstructive uropathy due to LS and reviews the published data on the diagnosis, management and follow-up of this condition.

[Penile squamous cell carcinoma]. / Carcinoma escamoso de pene.

Penile squamous cell carcinoma (SCC) is uncommon in Europe, where it accounts for approximately 0.7% of all malignant tumors in men. The main risk factors are poor hygiene, lack of circumcision, human papillomavirus (HPV) infection, and certain chronic inflammatory skin diseases. HPV infection is detected in 70% to 100% of all penile in situ SCCs and in 30% to 50% of invasive forms of the disease, mainly basaloid and warty SCCs. In situ tumors can be treated conservatively, but close monitoring is essential as they become invasive in between 1% and 30% of cases. The treatment of choice for penile SCC is surgery. Inguinal lymph node irradiation is no longer recommended as a prophylactic measure, and it appears that selective lymph node biopsy might be useful for reducing the morbidity associated with prophylactic inguinal lymph node dissection. Survival is directly related to lymph node involvement. Improving our knowledge of underlying molecular changes and their associated genotypes will open up new therapeutic pathways.

The role of occlusion and micro-incontinence in the pathogenesis of penile lichen sclerosus: an observational study of pro-inflammatory cytokines' gene expression.

PURPOSE: To assess the expression of selected cytokines in penile lichen sclerosus (PLS) and associate them with the occurrence of micro-incontinence (MI) in different stages of PLS. METHODS: The skin biopsies from 49 PLS affected, and 13 from nonlesional foreskins (healthy control adult males undergoing circumcision due to phimosis caused by short frenulum) were obtained. All specimens were used for RNA extraction and RT-qPCR. Quantitative assessment of the gene expression of interleukin 1-A (IL-1A), interleukin 1-B (IL-1B), interleukin 1 receptor antagonist (IL-1RN), interleukin 6 (IL-6), transforming growth factor ß1 (TGF-ß1), and interferon-gamma (INF-γ) was performed. To determinate the presence of MI, the patients were asked about voiding patterns, especially leaking tiny drops of urine from the urethral meatus after urination. RESULTS: IL-1A, IL-6, and INF-γ mRNA levels were approximately 150, 16, and 59 times higher in PLS than in control samples, respectively. The highest IL-1A mRNA levels were observed in early PLS (n = 13), INF-γ in moderate PLS (n = 32), while IL-6 in severe PLS (n = 4). MI was noted in 45 PLS patients vs. 0 in control (p < 0.0001). IL-1A and IL-6 vs control ratios were concentration (ca.) 400 and 30 times higher, respectively, in MI PLS samples than in PLS without MI. CONCLUSION: Occlusion and irritating urine effect are associated with the clinical progression of penile LS with increased mRNA expression of IL-1A, INF-γ, and IL-6 pro-inflammatory cytokines in the foreskin.

Lichen sclerosus in pediatric age: A new disease or unknown pathology? Experience of single centre and state of art in literature.

Lichen Sclerosus (LS) is a chronic inflammatory skin disease with unknown etiology. In pediatric age the main disease "lichenlinked" is the phimosis in male. This is a retrospective study that reports the experience of our clinic and review of the literature. We included all patients affected by pathological phimosis, treated by circumcision between January 2015 and May 2020, older than 6 years old and with an histopathological diagnosis of lichen sclerosus. The aim was to identify prognostic factors based on histological report to plan the clinical management of patients. Statistical analysis was done. We included 207 patients. The mean age of children was 9,78 years (5-18 years, DS±3.29). Based on the histological features we divided patients in 2 groups: early lesions (70/207, 34%) and advanced (137/207, 66%). In term of complications lichen linked we considered meatal stenosis that needed of urethral dilatations. We included 7 patients (7/207, 3,4%). We report P value Statistical Significance in many aspects. An early diagnosis of LS and surgical treatment of foreskin are essential to prevent early and late complications in children. The size of sample is a limit of the study but results encourage our management.

Lichen Sclerosus and Phimosis - Discrepancies Between Clinical and Pathological Diagnosis and Its Consequences.

OBJECTIVE: To assess the accuracy of clinical diagnoses and the true incidence of lichen sclerosus (LS) in patients with phimosis. MATERIALS AND METHODS: The 92 adult male patients who were qualified for circumcision due to phimosis, were included in the study. The patients were diagnosed clinically by a urologist and dermatologist before the surgical procedure. After the circumcision, the resected foreskins were examined by 2 independent uropathologists. RESULTS: Preoperative clinical diagnosis of LS was established in 54 patients (58.7%); healthy-looking skin in 26 (28.3%) and other penile diseases in 12 (13.1%) patients. After histopathological examination, the diagnosis of LS was established in 62 patients (67.4%), but only in 44 patients with previous LS clinical diagnosis. LS was histopathologically confirmed in 18 other patients with clinically diagnosed healthy skin (n = 17) or lichen planus (n = 1). Healthy skin was histopathologically confirmed in 10 cases in patients diagnosed clinically before as LS. Other 15 histopathological diagnoses were Zoon balanitis (n = 3), nonspecific balanitis (n = 5), lichen planus (n = 1), psoriasis (n = 1), invasive penile cancer (n = 3), Bowen's disease (n = 1), penile intraepithelial neoplasia 2 usual type (n = 1). CONCLUSION: LS has been revealed as the most common histopathological diagnosis in patients undergoing circumcision in our study. Histopathological examination seems to be necessary to exclude this disease.

Concomitant Hidradenitis Suppurativa and Eruptive Xanthomas Presenting with Phimosis - The Importance of Timely Diagnosis.

A 49-year-old man diagnosed with metabolic syndrome (MetS) was referred to us for treatment of xanthoma elements. Physical examination revealed widespread confluent yellow firm papules on his fingers, toes, arms, legs, and back. The diagnosis of eruptive xanthoma (EX) was clinically confirmed. During the examination of scar tissues, tombstone comedones and an inflammatory nodule was noted on his abdominal folds and right groin. These are diagnostic signs of hidradenitis suppurativa (HS), a condition the patient had reportedly suffered for 15 years without being diagnosed. The patient's HS nodule was treated with intralesional triamcinolone injection, and prophylactic resorcinol was initiated, and he was referred to endocrinologists for xanthoma management. Three weeks later he returned due to newly developed lesions on his preputium, which caused a painful phimosis. Both HS and EX are correlated with MetS and causes increased all-cause cardiovascular mortality. As the average diagnostic delay of HS is 7.2 years, it is likely that timely diagnosis of HS would have identified the patient as being at risk of developing MetS. With proper preventive measures, the resulting EX lesions and increase in cardiac mortality could have been avoided.

Phimosis and scrotal lesions in leprosy: two case reports.

We report two cases of borderline leprosy patients, one with scrotal lesions, the other presenting with leprosy on the prepuce with phimosis.

The use of steroid cream for physiologic phimosis in male infants with a history of UTI and normal renal ultrasound is associated with decreased risk of recurrent UTI.

BACKGROUND: An uncircumcised male infant with a history of urinary tract infection (UTI), physiologic phimosis, and a normal renal ultrasound is a common patient referred to pediatric urology clinics. Topical steroid creams have been shown to effectively release physiologic phimosis. OBJECTIVE: The objective of this study was to test the hypothesis that use of steroid cream for physiologic phimosis is associated with a lower UTI recurrence in uncircumcised male infants with normal renal ultrasounds. STUDY DESIGN: Uncircumcised males younger than 12 months referred for a UTI with a normal renal ultrasound were included. A longitudinal data set was created, and recurrent UTIs were identified. The proportion with a recurrent UTI was compared between those who received a prescription for a steroid cream for phimosis and those who did not. The morbidity of the initial and recurrent UTIs was also described. The association of recurrent UTI with vesicoureteral reflux (VUR) was also evaluated. RESULTS: A total of 192 uncircumcised males with a median age of 5.8 months (interquartile range [IQR]: 3.5-7.9 months) were included. Twenty-seven patients were treated with a course of betamethasone valerate 0.1% cream, and 165 were not (Summary Table). There were no significant differences between groups in the frequency of voiding cystourethrogram (VCUG), diagnosis of VUR, or use of continuous prophylactic antibiotics (CAP). During a median follow-up of 8.7 months (IQR: 3.1-17.5 months), none of the patients treated with steroid cream had a recurrent UTI compared with 27 of 165 (16%) patients not treated (P = 0.02). Among the 173 patients whose initial UTI was febrile, recurrent febrile UTIs occurred in no treated patients and 23 of 150 (15%) untreated patients (P = 0.047). DISCUSSION: The results of this study are consistent with those of a previous randomized trial of steroid cream for physiologic phimosis which found lower recurrent UTI in those whose foreskins became retractable. In addition, the results are consistent with the declining incidence of UTIs in uncircumcised males mirroring the natural history of physiologic phimosis resolving. This study is limited by its retrospective nature and non-standardized follow-up. CONCLUSION: The use of steroid cream for physiologic phimosis is associated with a decreased risk of recurrent UTIs in uncircumcised male infants with a normal renal ultrasound. In this group, steroid cream for physiologic phimosis is a well-tolerated and simple alternative to circumcision to potentially decrease risk of recurrent UTI.

Phimosis as a presenting feature of diabetes.

OBJECTIVE: To determine the prevalence of diabetes in men presenting with phimosis, and to establish the incidence of undiagnosed diabetes in men presenting with acquired or life-long phimosis. PATIENTS AND METHODS: We prospectively collected data on 100 men (mean age 38.5 years, range 17-82) who presented to our department with phimosis during 2006. Urinary glucose levels and random serum glucose levels were analysed, and if abnormal, the patient had further diagnostic tests for diabetes. RESULTS: In all, 31 men presented with a life-long history of phimosis and 69 with a history of acquired phimosis. There was no history of diabetes and no abnormal serum glucose levels in those with life-long phimosis. Eighteen of 69 (26%) of those with acquired phimosis had a history of type 2 diabetes. Type 2 diabetes was newly diagnosed in four of 50 (8%) men presenting with acquired phimosis and no history of a glycaemic disorder. A further two (4%) were diagnosed with impaired fasting glycaemia and impaired glucose tolerance. Urine analysis was positive for glucose in all new diagnoses of glycaemic disorders, except in one man. CONCLUSION: Diabetes can be associated with acquired phimosis in almost a third of cases, and 12% of men presenting with acquired phimosis and no history of diabetes were diagnosed with a disorder of glycaemic control. Therefore it is important that serum glucose levels are analysed when assessing men with acquired phimosis.

Lichen sclerosus et atrophicus in pediatric and adult male patients with congenital and acquired phimosis.

Lichen sclerosus et atrophicus is a chronic inflammatory sclerotic and atrophic disease of unknown cause that predominantly affects male and female genital skin. This study was designed to evaluate histological characteristics of congenital and acquired phimoses among pediatric (n=60) and adult (n=60) male patients who were admitted for circumcision to the Clinics of Urology and Pediatric Surgery of Kaunas University of Medicine Hospital between 2000 and 2003 and to determine the rate of lichen sclerosus et atrophicus and other histological diagnoses among them. This study demonstrates that 45.1% of congenital and 62.3% of acquired phimoses show histological signs of lichen sclerosus et atrophicus. The rate of lichen sclerosus et atrophicus was statistically significantly higher among patients with acquired than congenital phimosis. Boys with acquired narrowing of prepuce were statistically significantly 3.9 times more likely to develop lichen sclerosus et atrophicus than those with congenital phimosis. There were no statistically significant differences between rates of lichen sclerosus et atrophicus and other dermatological diagnoses among pediatric and adult male patients if the type of phimosis (acquired or congenital) was considered. Histological features of lichen sclerosus et atrophicus and other histological diagnoses in boys and men with phimosis were detected with equal frequency irrespective the age of the subjects. The rate of lichen sclerosus et atrophicus was similar among all boys (56.7%) and men (53.3%) treated for phimosis. Only the type of phimosis had a statistically significant influence on the rate of lichen sclerosus et atrophicus and other histological diagnoses.

[A case of urinary retention caused by true phimosis].

We report a case of urinary retention caused by true phimosis in a 67-year-old man with untreated diabetes mellitus. The patient could not void in a stream, and urine dropped out of the external urethral orifice with manual compression of the penis. Subsequently, he visited our hospital due to urinary retention. Ultrasonography revealed right hydronephrosis and ballooning of the foreskin. An emergency dorsal slit was performed, and hydronephrosis showed immediate improvement. Histopathologically, fibrosis and inflammation of the foreskin were observed. The mechanisms responsible for urinary retention in this case are discussed.