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.

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.

Rapid Anterior Capsular Phimosis in a Patient Without Risk Factors for Anterior Capsule Contraction Syndrome.

This case report discusses anterior capsular phimosis in a patient without the typical risk factors for anterior capsule contraction syndrome.

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.

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.

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.

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.

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.

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.

[Penile cancer: diagnosis and staging]. / Peniskarzinom: Diagnose und Staging.

Penile cancer is often an obvious visual diagnosis but histologic verification should be obtained prior to treatment. The clinical examination should determine the tumor stage and whether it has infiltrated the cavernous bodies and/or the urethra and it should adequately assess the inguinal lymph nodes. Preoperative imaging of the lesion is only indicated in equivocal cases. Curative treatment requires the complete removal of the primary tumor and all metastatic lymph nodes. Lymph node management is the key prognostic factor in the treatment of penile cancer. No imagining technique such as the ultrasound, CT, MRI or PET/CT is able to adequately detect micrometastatic lymph nodes. Therefore, invasive (inguinal) lymph node diagnosis is indicated for all tumour stages from pT1G2. Over 90% of penile cancer cases can be cured with early diagnosis and adequate treatment if routine self-examination and physical examinations are regularly performed.

[Human papillomavirus and penile cancer : Thinking about measures for prevention]. / Humane Papillomaviren und Peniskarzinom : Überlegungen zu Präventionsmaßnahmen.

Two major pathways of penile carcinogenesis are known: human papillomavirus (HPV)-induced penile cancer and HPV-negative cancers associated with chronic dermatoses. Therefore, modern measures for prevention of penile cancer may for example include prophylactic HPV vaccination. The resulting B­cell-mediated immunity to HPV capsid proteins is effective protection against future HPV infections. Contrarily when treating existing HPV infections or HPV-associated cancers an antigen-specific T­cell immunity is necessary. To date, screening and treatment of precancerous lesions to prevent penile cancer are not established in the German health care program and the highly expected therapeutic HPV vaccines are still on the horizon. In this article, we focus on possible strategies to prevent HPV-related penile cancer on different levels of carcinogenesis.

[Epidemiology of penile cancer]. / Epidemiologie des Peniskarzinoms.

BACKGROUND: Penile cancer represents a rarity in daily clinical practice. OBJECTIVES: The aim is to identify global differences concerning the incidence, social and risk factors. METHODS: The past and current epidemiologic literature is analyzed concerning incidence rates and risk factors. The latter are discussed concerning their potential with regard to disease prevention. RESULTS: Globally, incidence rates of penile cancer range from low to nonexistent. Distinct differences are found when comparing industrialized countries with emerging and developing countries. Phimosis seems to be a crucial risk factor in the formation of penile cancer. Additionally, chronic inflammatory diseases of the penis were found to be associated with a higher risk. CONCLUSIONS: Preventive measures should be considered in relation to the rarity of the disease, especially in the valuation of circumcision during early childhood. Regular clinical examination of the penis is a sensible measure of early detection.

HPV prevalence in the foreskins of asymptomatic healthy infants and children: Systematic review and meta-analysis.

The true HPV prevalence in the foreskins of infants and children has been little documented, but reporting on this prevalence is of great importance given its impact on the rationale for treating asymptomatic boys. We searched multiple databases from 1960 to 2016 for observational or prospective studies that reported on HPV prevalence in foreskins. We conducted a meta-analysis using a random-effects model to pool for HPV prevalence in the foreskins of infants and children. Eight studies, with a total of 556 infants and children with phimosis, were eligible for the meta-analysis. The pooled overall prevalence of general HPV, high-risk HPV, low-risk HPV, HPV 16/18, HPV 16, and HPV 18 were 17.3 (95%CI: 0.8-46.3), 12.1 (95% CI: 0.9-31.5), 2.4 (95% CI: 0.0-11.2), 4.8 (95% CI: 0.0-16.8), 1.7 (95% CI: 0.0-5.1), and 0 (95% CI: 0-0.5), respectively. The estimated HPV prevalence in foreskins was not zero among infants and children, which implies HPV transmission other than by sexual contact. Considering that high-risk HPV is detected in asymptomatic infants and children, future studies are warranted to determine whether preventive treatments in asymptomatic infants and children could be effective in preventing persistence or transmission of high-risk HPV.

Phimosis in a 10-yr-old Boy Without Urinary Infection-How to Inform Parents: For Circumcision.

Circumcision can be a viable option for phimosis in a 10-yr-old boy, also if asymptomatic, in the presence of skin alterations or if the parents prefer avoid observation. Morbidity is minimal if the procedure is performed in a hospital setting.

Phimosis in a 10-yr-old Boy Without Urinary Infection-How to Inform Parents: Against Circumcision.

In a 10-yr-old boy with no abnormalities or symptoms other than nonretractability of the foreskin, the foreskin should be preserved. If treatment is needed, local corticoid application should be used as first-line therapy, as it gives excellent results in up to 90% of cases, before removing this sensitive part of the body.

Autologous platelet-rich plasma (PRP) in chronic penile lichen sclerosus: the impact on tissue repair and patient quality of life.

PURPOSE: Lichen sclerosus (LS) is a chronic inflammatory skin condition that frequently involves the anogenital region. Ongoing research is focused on finding more effective treatments for tissue repair and reducing symptoms. The aim of this study is to evaluate the effectiveness of platelet-rich plasma (PRP) local injections in penile LS. METHODS: Forty-five male patients affected by penile LS underwent injections of autologous PRP in the affected skin areas. Age at diagnosis and at first treatment, number of treatments, clinical conditions (phimosis, splitting, inflammation, synechiae, meatus stenosis), symptoms (pain, burning, itching), and functional impairment were considered. Treatment efficacy was also evaluated through the Investigator's Global Assessment (IGA) on a six-point Likert scale and the Dermatology Life Quality Index (DLQI). RESULTS: The patient age at LS diagnosis was 36.20 ± 9.19 years, while the mean age at the first PRP treatment was 42.96 ± 11.32 years (p < 0.001). The number of treatments/patient ranged from 2 to 10. The follow-up was 17.60 ± 5.63 months. After PRP injections, it was observed in all patients a significant improvement in clinical conditions, with reduction/disappearance of symptoms. Topical steroid therapy, interrupted before PRP treatment, was not restarted by any patient. Only one patient underwent a later circumcision procedure. Both IGA scale and DLQI score showed a significant difference (p < 0.001) before and after PRP treatment. CONCLUSIONS: PRP treatment in penile LS seems to be helpful to regenerate scarring, reduce symptoms, and improve patient quality of life. Further studies are necessary to evaluate long-term results.