Intraurethral Steroid and Clean Intermittent Self-Dilatation for Lichen Sclerosus Proven Urethral Stricture Disease—A Retrospective Cohort Study

Abstract

Background/Objectives: Lichen sclerosus is a chronic lymphocyte-mediated inflammatory disorder with a predilection for the anogenital region. It is a common cause of urethral stricture disease in males. The gold standard treatment is considered to be surgical reconstruction; however, there are many patients who are not suitable or not willing to undergo surgery. Cutaneous lichen sclerosus restricted to the foreskin, prepuce or glans is often response to topical corticosteroids; however, the use of intraurethral corticosteroids for urethral involvement has limited research. Methods: We conducted a retrospective cohort study on 18 patients with histologically confirmed lichen sclerosus and associated urethral stricture disease. They were treated with clean intermittent self catheterisation using a hydrophilic catheter coated with 0.05% betamethasone ointment. International Prostate Symptom Score with Quality of Life scores were measured prior to treatment and at follow-up intervals. Results: There was significant improvement in International Prostate Symptom Score and Quality of Life scores at 3 months, 12 months and 24 months, with only 1 patient ceasing treatment due to intolerance. One patient required a single repeat endoscopic dilatation following a period of non-compliance with treatment. Conclusions: Intraurethral corticosteroids with clean-intermittent self-catheterisation is effective and well tolerated for treating lichen sclerosus-associated urethral stricture disease in the short to intermediate term for patients not willing to undergo urethroplasty.

1. Introduction

Lichen sclerosus (LS) is a chronic lymphocyte-mediated dermatosis with a predilection for involvement of the skin and mucosal surfaces of the anogenital region in both men and women [1]. The aetiology of lichen sclerosus is not completely understood; the currently proposed pathological mechanisms include autoimmunity, genetic factors, trauma/chronic irritation, infections and hormonal influences [2].

Its true prevalence in the community is difficult to establish as it is often unrecognised by various clinical specialties. Many patients may be reluctant to report symptoms due to embarrassment, and many patients are asymptomatic. Estimates of prevalence in various studies range from as low as 0.0014% to as high as 0.3% [3]. Nearly all cases involve the anogenital region, with only 6% of cases being reported as isolated extragenital lesions [4].

The urogenital manifestations in men are variable. The typical appearance of lesions are white plaques that may become fissured and irritated [5]. These lesions typically appear on the glans of the penis, prepuce of the foreskin and the frenulum. Prepucial involvement can lead to phimosis, and in cases of isolated prepucial involvement, circumcision can be curative [5]. In cases in which the glans is involved, progression to involvement of the meatus and urethra can occur [5]. In urethral involvement, most commonly only the distal urethra is involved, but in severe cases, it can progress to panurethral stricture disease [5].

Urethral stricture disease can present with voiding lower urinary tract symptoms (LUTS), urinary retention, dysuria and painful ejaculation [6,7]. In severe cases if outflow obstruction is not managed in the long term, complications can occur such as detrusor failure or high pressure bladder outlet obstruction manifesting as obstructive renal failure [8].

Management of patients with urethral stricture disease from lichen sclerosus has typically involved surgery with either recurrent endoscopic dilatations/direct vision optical urethrotomy [6], meatoplasty, urethroplasty, and in severe cases diversion with perineal urethrostomy [7]. The rates of recurrence following surgery have been reported to be as high as 71% in some studies [9].

In patients without meatal or urethral involvement, patients have been successfully managed with topical corticosteroid alone for many years. In a number of series, very few patients needed to progress to circumcision to treat lichen sclerosus isolated to the foreskin and prepuce [10,11]. The success of corticosteroids in treated lichen sclerosus has also been proven in female patients with vulval involvement. The responsiveness of lichen sclerosus to corticosteroid treatment has led to some small case series trialling intra-urethral steroids with clean intermittent self-dilatation for those patients with meatal/distal urethral involvement. Other intraurethral immune modulating agents have also been trialled such as Mitomycin C and Tacrolimus [12,13]. Potts et al. [7], published a study in 2016 describing the use of intraurethral steroids in patients with urethral stricture disease and biopsy proven lichen sclerosus. 89% of patients has successful disease control and did not need to proceed to surgical management.

Following the success of Potts et al. trial, and other similar studies [14], our institution implemented a similar treatment strategy for patients with biopsy proven lichen sclerosus with urethral involvement. The aim of this study is to determine if intraurethral steroids with clean intermittent self catheterisation will eliminate the need for invasive surgical treatment and improve patients quality of life from symptomatic improvement of their stricture disease.

2. Materials and Methods

A retrospective review of our Urology units audit database was undertaken, identifying all patients with histologically proven lichen sclerosus and concurrent urethral stricture disease at our tertiary level hospital. Patients were first treated for their stricture between September 2018 and September 2021. Histological specimens included foreskin specimens in patients treated with a circumcision for phimosis with concurrent stricture disease, and urethral biopsies. All patients were under the care of a single fellowship trained reconstructive Urologist. Patients were offered surgical management for their stricture disease and were included if they declined surgical treatment, and they were agreeable to performing clean intermittent self catheterisation with intraurethral steroids. All patients were males aged over eighteen.

Treatment was performed under the guidance of our units Urology nurse practitioner. Patients were taught the technique of clean intermittent self dilation (CISD) with a hydrophilic catheter, coated with 0.05% betamethasone cream or ointment. The treatment protocol consisted of once daily CISD with intraurethral steroids for two weeks, every second day for the next two weeks, twice weekly for two weeks and then weekly. Clinical review was performed at three months to titrate ongoing frequency of administration, which varied from weekly to monthly. CISD was recommended to continue indefinitely for disease maintenance. Catheter size was calibrated to the patient’s stricture.

Prior to commencing treatment, patients had an international prostate symptom score (IPSS) including Quality of Life (QoL) component recorded by the units nurse practitioner at the time of teaching CISD. Patients were followed up in the Urology outpatient clinic and IPSS was due to be performed again at 3 months after initiation of treatment, then 12 months, then annually thereafter. Improvement in IPSS was the primary outcome.

The main secondary outcomes was failure of treatment, which was defined as intolerance, requirement to have repeat endoscopical dilatation or progression to surgical management which was determined by review of medical records. Other metrics recorded included location of stricture, follow-up time and basic demographic data. Uroflowmetry was not routinely performed at the discretion of the treating Urologist.

Statistics were calculated using Prism 10. To compare baseline IPSS scores to the follow-up time points, we used the unpaired t-test due to the random loss of data from unrecorded or undocumented IPSS scores in patient notes.

3. Results

In total eighteen patients in our institution were included in this study and were first commenced on CISD with intraurethral steroid treatment between September 2018 and September 2021. Follow-up data has been recorded up until December 2023. The median follow-up time was 24.5 months, and mean follow-up time of 24.83 months (

Table 1. Demographic data.

Characteristic
Number of Patients	18
Mean age at diagnosis (Years)	52.27 (26–73)
Median Follow-up Time in Months (Range)	24.5 (5–50)

). The details of the patients strictures is available in

Table 2. Location of strictures.

Disease Location	Number of Patients (n)
Meatal/Submeatal	4
Meatal/Submeatal + Bulbar Urethra	2
Meatal//Submeatal + Penile Urethra	1
Bulbar Urethra	1
Penile + Bulbar Urethra	2
Panurethral	5
Data Missing	3

.

Twelve patients had pre-treatment IPSS scores recorded in their medical records with an average of 16.42 (range 6–27), and average quality of life score of 4.25 (range 2–6) (Figure 1 and Figure 2). Fourteen patients had IPSS scores recorded at three months after initiation of treatment with an average of 4.93 (range 1 to 11, p < 0.0001 compared to pre-treatment scores) and quality of life score average of 1.21 (range 0–3, p < 0.0001 compared to pre-treatment scores, Figure 1 and Figure 2). Twelve patient had scores recorded at twelve months, with average score of 3.41 (range 0–6, p < 0.0001) and a quality of life score average of 1.22 (range 0–2, p < 0.0001). (Table 2 and

Table 3. Complications with detailed description.

Complication	Total (n)	Description
Haematuria	1	Developed significant haematuria following self-catheterisation which prompted an admission for bladder washout at the bedside. Able to continue treatment following resolution.
Balanitis	1	Recurrent flares of balanitis with steroids and CISD, unable to tolerate despite multiple attempts leading to cessation of treatment.

CISD: clean intermittent self dilation.

). Six patients had scores recorded at 24 months, with an average of 2.5 (range 1–4, p < 0.0001) and quality of life score average of 0.83 (range 0–2, p < 0.0001, Figure 1 and Figure 2).

Thirty-six and forty-eight-month post treatment data is limited. Two patients have IPSS scores recorded at thirty-six months after initiation of treatment, both had symptom scores of 3, and QoL scores of 1. Only one patient has an IPSS score recorded at forty-eight months post treatment, his symptom score was 1, with a QoL score of 2.

Unfortunately, a number of patients were seen in our clinics at these longer time intervals but did not have IPSS scores recorded. One patient was seen at 48 months with clinic documentation reporting the patient was tolerating intraurethral steroids with self-dilatation well, with no bothersome lower urinary tract symptoms. Similarly, a further three patients were seen in clinic at 36 months post treatment and were discharged from clinic due to stable non-bothersome LUTS with their regimen.

There was only one complication recorded in this cohort. A single patient required admission to hospital and insertion of a three-way indwelling catheter (IDC) due to the development of haematuria after a traumatic insertion of his dilating catheter. Treatment was generally very well tolerated, with only 1 patient ceasing treatment due to pain and recurrent flares of balanitis (Table 3). He has not had a recurrent clinically significant stricture.

One patient required repeat endoscopic dilatation (

Table 4. Further endoscopic/surgical treatment episodes.

Treatment Required	Total (n)	Description
Repeat endoscopic dilatation	N = 1	After their initial 3-month review, the patient chose to discharge from the clinic due to stable symptoms. He was re-referred 27 months after initial dilatation with deterioration of symptoms requiring repeat dilatation—he informed our staff that he was non-compliant with treatment in the intervening period. He is now compliant with stable lower urinary tract symptoms.

) in the follow-up period following self discharge from clinic, and non-compliance in the community with his recommended treatment. He was again offered definitive surgical management but chose to reengage with this treatment. No patients have required definitive surgical treatment of their stricture disease at the time of writing. Other than the single patient who ceased CISD due to poor tolerance, all other patients continue to be compliant and perform CISD regularly with frequencies varying between once per week and once per month for maintenance treatment of their stricture.

4. Discussion

The pharmacological basis for using intraurethral steroids for lichen sclerosus-associated urethral strictures comes from the body of evidence that supports the use of topical corticosteroids for both vulval and penile lichen sclerosus [10]. International dermatological societies recommend topical corticosteroids as the first line treatment for the cutaneous conditions [11], and so the follow on logic is that applying corticosteroids to the strictures themselves should also have therapeutic benefit.

The evidence that guides treatment for lichen sclerosus-associated urethral stricture disease is quite limited and there are no randomised control trials comparing different treatment strategies [6].

A systematic review conducted by the EAU (European Association of Urology) Urethral Strictures Guidelines Panel investigated the use of single stage oral mucosal graft urethroplasty specifically for lichen sclerosus related penile urethral strictures, compared to other options [15]. 15 studies were included, of which none were randomised control trials, and the most common comparator was staged oral mucosal graft urethroplasty. It reported successful treatment between 65 and 100% with a median follow-up time of 67 months, The overall quality of evidence was deemed to be a poor and a clear answer to whether single stage urethroplasty was superior could not be provided.

Research on the use of intraurethral steroids for urethral stricture disease also mostly comprises small populations sizes. There have been 3 randomised control trials performed looking at intermittent self dilatation with and without intraurethral steroids, but they were not specific to the treatment of lichen sclerosus related strictures [16]. The pooled sample size across the three studies were 67 and 68, respectively, with results favouring the use of intraurethral steroids (fewer recurrences and longer time to recurrence) [16].

Two randomised control trials have been published investigating direct vision internal urethrotomy versus intermittent self dilatation for urethral stricture disease not specific to lichen sclerosus (and in both these studies, the CISD group was further randomised to include intra-urethral steroids or no intraurethral steroids) [17,18]. These studies had conflicting results, with one finding no difference between the CISD groups, and one finding similar results to the above three studies—fewer recurrences and longer time to recurrence.

The previously mentioned study by Potts et al. [7]., of a very similar nature to ours included 28 patients. Their paper was dedicated to biopsy proven lichen sclerosus patients and used CISD with intraurethral Clobetasol cream. They had a longer median follow-up time and similarly had no patients who progressed to requiring definitive surgical management. They also had very few complications and only three patients who were deemed to have failed (one patient having an episode of acute urinary retention, and two patients having worsening of symptoms despite treatment). Hayden et al. [19], followed Potts in 2020 reviewing their lichen sclerosus urethral stricture patients. 42 patients had histologically proven LS and 36 patients were treated with intraurethral steroids with CISD alone. None of their patients progressed to requiring surgical intervention, and had improvement in their LUTS symptoms score and quality of life scores. Their median follow-up was also short with only 8.4 months.

There is some data comparing different types of intraurethral agents in treating lichen sclerosus urethral stricture disease. Choudhury et al. [20], divided 80 patients into groups of 40, and treated one group with intraurethral clobetasol and CISD and the other to intraurethral tacrolimus (a calcineurin inhibitor). Both treatments were effective, but overall improvement in IPSS, number of patients progressing to surgical treatment, and side effects favoured the steroid group. Their follow-up period was only 12 weeks.

Other available data on the topic has found that patency rates for staged oral mucosal graft urethroplasty in patients with lichen sclerosus was lower than in single stage oral mucosal grafts, and compared to non-LS urethral stricture patients [21]. Genital skin for augmentation penile urethroplasties should also not be used in patients with LS due to the high rate of stricture recurrence from the diseased skin [22].

One of the concerns that has been discussed regarding intermittent self-dilatation with or without intraurethral steroids is the potential for stricture complexity to increase making definitive surgical management more difficult if conservative management fails. Two studies were identified examining this link [23,24]. The first study was specifically to bulbar urethral strictures and both studies excluded lichen sclerosus, making extrapolation of the data to lichen sclerosus patients difficult.

It is clear from the above literature search that the best treatment for LS urethral stricture disease is not yet clear in the evidence, although single stage oral mucosal graft urethroplasty might appear to be the most favourable option for long term cure overall. The main advantage of our study is that it helps to fill a gap in the literature, in demonstrating that there is a suitable alternative option in those patients not willing to undergo urethroplasty, or those not suitable. Although CISD with intraurethral steroids can not be considered a cure, the short to intermediate term data suggests it provides good disease control. One of the key disadvantages of this treatment is the need to continue to perform clean intermittent self-catheterisation (CISC) intermittently on an indefinite basis. One of the other unknowns is the what the quality of life outcomes for CISD patients are like compared to patients who undergo surgical management. An interesting follow-up study would be to see if cessation of CISC led to stricture recurrence, or whether a certain duration of treatment allowed for long term stabilisation of the disease.

Our study has some significant limitations. The short follow-up period means that we can not make any conclusions about long term efficacy. The retrospective design of the study means that there is bias associated with loss of data. This was evident in our study with a number IPSS scores either not recorded in notes, lost from paper records, or not performed because patients missed a follow-up appointment. This in particular affected pre-treatment scores, and the 36 and 48 month post-treatment scores. This can reduce the validity of our conclusions. Subjectively, the clinic letters of patients who reached these longer follow-up time points suggested they had stable non-bothersome LUTS, and were tolerating treatment without complication, and without need for repeat endoscopic dilatation treatment or surgical intervention. We did not control for confounders such as medications used to treat other causes of LUTS (e.g., benign prostatic hyperplasia [BPH]) and previous urological interventions. Uroflowmetry was not performed as an objective method of measuring control of stricture disease which may be considered a limitation. Quality of life outcomes were not reported in this study, this would be interesting to include in future studies, especially in comparison to patients undergoing surgical management of stricture disease. Finally, the small sample size limits the generalizability of the results, an issue often encountered in rare diseases.

5. Conclusions

The data from our patient cohort suggests that intraurethral steroids with clean-intermittent self dilatation are well tolerated, appear to be safe, and are an effective strategy to treat urethral strictures caused by lichen sclerosus in the short to medium intermediate term, for patients not willing to undergo urethroplasty, and for patients willing to continue CISC indefinitely. We suggest that it is a suitable alternative to urethroplasty in those unwilling or unable to have surgery. Longer term data to determine the longevity of disease control would be a useful follow-up study.