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Urogenital Manifestations in Wegener Granulomatosis: A Study of 11 Cases and Review of the Literature

Dufour, Jean-François MD*; Le Gallou, Thomas MD*; Cordier, Jean-François MD, PhD; Aumaître, Olivier MD, PhD; Pinède, Laurent MD, PhD; Aslangul, Elisabeth MD, PhD; Pagnoux, Christian MD, MPH; Marie, Isabelle MD, PhD; Puéchal, Xavier MD, PhD; Decaux, Olivier MD; Dubois, Alain MD; Agard, Christian MD, PhD; Mahr, Alfred MD, PhD; Comoz, François MD; Boutemy, Jonathan MD; Broussolle, Christiane MD; Guillevin, Loïc MD; Sève, Pascal MD, PhD; Bienvenu, Boris MD, PhD

doi: 10.1097/MD.0b013e318239add6
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We describe the main characteristics and treatment of urogenital manifestations in patients with Wegener granulomatosis (WG). We conducted a retrospective review of the charts of 11 patients with WG. All patients were men, and their median age at WG diagnosis was 53 years (range, 21–70 yr). Urogenital involvement was present at onset of WG in 9 cases (81%), it was the first clinical evidence of WG in 2 cases (18%), and was a symptom of WG relapse in 6 cases (54%). Symptomatic urogenital involvement included prostatitis (n = 4) (with suspicion of an abscess in 1 case), orchitis (n = 4), epididymitis (n = 1), a renal pseudotumor (n = 2), ureteral stenosis (n = 1), and penile ulceration (n = 1). Urogenital symptoms rapidly resolved after therapy with glucocorticoids and immunosuppressive agents. Several patients underwent a surgical procedure, either at the time of diagnosis (n = 3) (consisting of an open nephrectomy and radical prostatectomy for suspicion of carcinoma, suprapubic cystostomy for acute urinary retention), or during follow-up (n = 3) (consisting of ureteral double J stents for ureteral stenosis, and prostate transurethral resection because of dysuria). After a mean follow-up of 56 months, urogenital relapse occurred in 4 patients (36%).

Urogenital involvement can be the first clinical evidence of WG. Some presentations, such as a renal or prostate mass that mimics cancer or an abscess, should be assessed to avoid unnecessary radical surgery. Urogenital symptoms can be promptly resolved with glucocorticoids and immunosuppressive agents. However, surgical procedures, such as prostatic transurethral resection, may be mandatory in patients with persistent symptoms.

Abbreviations ANCA = antineutrophilic cytoplasmic antibodies

CRP = C-reactive protein

CT = computed tomography

FVSG = French Vasculitis Study Group

IVIg = intravenous immunoglobulins

MTX = methotrexate

PR3 = proteinase 3

WG = Wegener granulomatosis

Supplemental digital content is available in the text.

From Hospices Civils de Lyon (JFD, CB, PS), Hôpital de la Croix-Rousse, Department of Internal Medicine, Lyon, and Université Claude Bernard Lyon 1, Lyon; CHU de Caen (TLG, JB, BB), Department of Internal Medicine, Caen, and Université de Caen Basse-Normandie, UFR de Médecine, Caen; Hospices Civils de Lyon (JFC), Department of Pneumology, Hôpital Louis Pradel, Lyon,and Université Claude Bernard Lyon 1, Lyon; CHU de Clermont-Ferrand (OA), Hôpital Gabriel-Montpied, Department of Internal Medicine, Clermont-Ferrand; Clinique Protestante (LP), Department of Internal Medicine, Lyon; Hôtel-Dieu (EA), Assistance publique-Hôpitaux de Paris, Department of Internal Medicine, Paris; Descartes University Medical School (EA), Paris; Hôpital Cochin (CP, AM, LG), Assistance publique-Hôpitaux de Paris, Department of Internal Medicine, Paris, and Université Paris V, Paris; CHU de Rouen (IM), Department of Internal Medicine, Rouen; CH Le Mans (XP), Centre de compétences Maladies systémiques et auto-immunes rares, LeMans; CHU de Rennes (OD), Hôpital Sud, Department of Internal Medicine, Rennes; Clinique Beau Soleil (AD), Montpellier; CHU de Nantes (CA), Hôtel-Dieu, Department of Internal Medicine, Nantes; and CHU de Caen (FC), Department of Pathology, Caen; France.

*Dr. Dufour and Dr. Le Gallou contributed equally to this study.

†Pr. Sève and Pr. Bienvenu contributed equally to this study.

‡The members of the French Center-East Internists Group are Pascal Cathébras, Isabelle Durieu, Christian Massot, Jacques Ninet, Pierre Philippe, Marc Ruivard, and Denis Vital-Durand.

The authors have no funding or conflicts of interest to disclose.

Reprints: Boris Bienvenu, MD, PhD, Department of Internal Medicine, CHU de Caen, avenue de la côte de nacre, Boîte Postale 95182, 14033 Caen cedex 9, France (e-mail: bienvenu-b@chu-caen.fr).

Figure 2 can be viewed online in color at http://www.md-journal.com.

Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (www.md-journal.com).

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INTRODUCTION

Wegener granulomatosis (WG) is a necrotizing vasculitis of unknown origin. Its classic triad consists of necrotizing granulomatous vasculitis of the upper and lower respiratory tract in association with focal segmental glomerulonephritis.30 It is frequently associated with antineutrophilic cytoplasmic antibodies (ANCA) against serine proteinase 3 (PR3). Although any organ can be affected, urogenital WG manifestation including involvement of the prostate, seminal vesicles, testis, epididymis, bladder ureters, urethra, retroperitoneum, cervix, vagina, perineum, and penis have rarely been reported.9,13,27,28 Lê Thi Huong et al28 reported that, out of 80 patients seen between 1973 and 1993 at their institution, 8 patients with WG had symptomatic urogenital involvement. In 1996, Davenport et al12 reported 8 cases of limited WG that affected the urogenital tract, but did not detail the patients’ response to treatment.

We performed a retrospective analysis of 11 patients with urogenital WG: 4 were treated by physicians belonging to the French Center-East Internists Group and 7 were included from the French Vasculitis Study Group (FVSG) database. We conducted the study to 1) describe the clinical and laboratory characteristics of patients with urogenital manifestations of WG, and 2) assess the responses to medical treatment and the outcomes for these patients.

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PATIENTS AND METHODS

Study Design

Physicians belonging to the FVSG and French Center-East Internists Group were queried by e-mail if they had encountered WG patients with urogenital manifestations, and were then contacted again 6 months later. The design of the study was presented at the annual meeting of the FVSG in April 2009, and a call for observations was launched in June 2009 on the FVSG website.

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Inclusion Criteria

Cases of urogenital manifestations of WG were selected according to the following criteria: 1) a diagnosis of WG established on the basis of American College of Rheumatology (ACR) and/or Chapel Hill Consensus Conference (CHCC) criteria;30,34 2) urogenital manifestations that included involvement of the prostate, seminal vesicles, testis, epididymis, bladder, ureters, urethra, structural abnormalities of the kidney, cervix, vagina, or penis; 3) exclusion of alternative diagnoses, such as urogenital infection processes. The medical charts of all patients were retrospectively reviewed for their clinical, laboratory, radiologic, and pathologic data. The time of occurrence of the first symptoms attributable to WG was recorded, and also the organs or tissues involved at diagnosis. Patient outcomes were evaluated with regard to response to treatment, occurrence of a relapse, occurrence of severe infectious complications or other adverse events, and death. Complete remission was defined as the absence of any sign of disease activity; partial remission was defined as stabilization of disease activity.

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CASE REPORTS

We describe 5 of the 11 cases before reporting the results of the global analysis (for the other 6 case descriptions, see Supplemental Digital Content 1, http://links.lww.com/MD/A7).

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Case 1

A 52-year-old man presented with a 2-year history of recurrent genital ulcerations. Pathologic examination of the lesions revealed granuloma with multinucleated giant cells and vasculitis, which indicated WG. The patient reported a recent history of nasal pain with rhinitis, arthralgia, and myalgia. A diagnosis was supported by positive c-ANCA (against anti-PR3). A nasal biopsy was performed and revealed granulomatous and necrotizing vasculitis. Treatment was started with prednisone (50 mg daily) and methotrexate (MTX). MTX was replaced with cyclophosphamide (CYC) intravenous pulse therapy because of recurrence of genital ulceration and the presence of proteinuria (1 g/d), glomerular hematuria, and mononeuritis multiplex. CYC was then stopped 1 year later and azathioprine was started, but the renal and genital symptoms persisted. Finally, intravenous immunoglobulins (IVIg) associated with MTX and prednisone allowed control of disease activity. The patient was in remission under low-dose prednisone, MTX, and IVIg at more than 2 years postdiagnosis.

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Case 2

In June 1991, a 70-year-old man presented with weakness, sinusitis, cough, dyspnea, and mononeuritis multiplex. Chest and abdomen computed tomography (CT) scans showed bilateral pulmonary nodules and a solid, enhancing mass, 6.5 cm at its widest diameter, in the lower pole of the right kidney. Serum creatinine was 142 μmol/L, while urinalysis was normal. ANCA testing was positive with a perinuclear fluorescence pattern and specificity for antimyeloperoxidase. Because a renal carcinoma was suspected, the patient underwent a total right nephrectomy. Pathologic examination of the renal mass revealed necrotizing vasculitis with fibrinoid necrosis and granuloma, whereas the renal tissue surrounding the mass disclosed mild focal and segmental glomerulonephritis. The patient received glucocorticoids and CYC intravenous pulses, which resulted in the rapid resolution of symptoms within 15 days.

Two relapses involving the upper airway occurred in July 1992 and August 1993 after discontinuation of CYC. The patient committed suicide in 2004 while in remission and receiving prednisone at 13 years postdiagnosis.

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Case 3

In October 2004, a 43-year-old man presented with weight loss, fever, headache, subcutaneous nodules on the lower limbs, and right-sided epididymitis. His medical history was remarkable for acute cholangitis in May 2003 and recurrent sinusitis since January 2004. Sinus and chest CT scans revealed right-sided sinusitis, bilateral pulmonary nodules, and pleural effusion. ANCA testing was negative. A biopsy of the cutaneous tissue disclosed granulomatous and necrotizing angiitis. Based on these results, the patient was started on a combination of prednisone (70 mg/d) and CYC intravenous pulses. As the patient gained complete remission by April 2005, CYC was discontinued and maintenance therapy with azathioprine was started. A first relapse occurred in January 2006. The patient experienced weakness, myalgia, joint pain, and right-sided epididymitis. Azathioprine was stopped and he was given MTX. Three months later, hepatitis occurred, leading to discontinuation of MTX. Another relapse occurred in March 2009 after the patient stopped glucocorticoids therapy. The patient developed weight loss, fever, night sweats, joint pain, peripheral neuropathy, and right-sided epididymitis. Ultrasonography showed a mass, 2 cm in diameter, at the head of the right epididymis. The patient was successfully treated with prednisone (70 mg/d) and intravenous CYC.

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Case 4

A 53-year-old man was admitted to hospital in February 2000 for crusting rhinitis, sinusitis, chest pain, dyspnea, arthralgia, purpura, digital necrosis, and episcleritis. A chest CT scan revealed pleuropericarditis and splenic infarction. Laboratory evaluation showed high C-reactive protein (CRP) (341 mg/L). His creatinine was 105 μmol/L and urinary protein level was 0.67 g/day. An immunologic investigation showed ANCA with anti-PR3 activity (590 U/mL). A kidney biopsy showed no evidence of glomerulonephritis. Histologic examination of a purpuric lesion showed vasculitis with fibrinoid necrosis and giant cells. Prednisone and CYC intravenous pulses were started. The patient entered remission, and CYC was switched to MTX in July 2000.

In July 2005, right-sided hydronephrosis with ureteral stenosis was incidentally discovered during an investigation of hypertension. Creatinine level was 120 μmol/L. His immunosuppressive regimen was not changed and a ureteral catheter was inserted. By 6 months later, persistence of the ureteral obstruction led to resection of the stricture with end-to-end anastomosis. A histologic analysis of the ureteral tissue showed inflammatory fibrosis, defined by a cellular infiltrate composed of lymphocytes, plasma cells, and neutrophil granulocytes without granuloma, which was consistent with advanced lesions caused by WG. The patient died from metastatic carcinoma of the upper airway in December 2008 while still in remission from WG.

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Case 5

A 51-year-old man was admitted to the department of urology in December 2007 with fever and acute urinary retention. His medical history was remarkable for a right-sided sensorineural hearing loss in 2002 and right maxillary sinusitis in October 2007. On examination, the prostate was enlarged. Laboratory data revealed a leukocyte count of 12,000/mL and a raised CRP level (350 mg/L). Serum creatinine was 99 μmol/L, and prostate-specific antigen was normal. A transrectal ultrasound showed an enlarged prostate and a hypoechoic lesion that was consistent with a prostatic abscess (Figure 1). Urinalysis, including a urine culture, was normal. A suprapubic cystostomy was performed and the patient was given ciprofloxacin. During the next 2 weeks, the patient’s condition worsened: he developed chest pain and dyspnea. A chest CT scan revealed pleural and pericardial effusion with pulmonary infiltrates. On the 10th day after admission, a colonic perforation complicated by septic shock occurred. The patient had undergone a right colectomy and was transferred to the intensive care unit. Orchitis occurred on the 30th day, and subungual hemorrhages were noted. A histologic examination of the prostate and testis tissue revealed granulomatous and necrotizing vasculitis consistent with WG (Figure 2). ANCA testing was positive with specificity for anti-PR3. The patient was given prednisone and 7 pulses of CYC: most of the symptoms quickly resolved, except dysuria, weakness, and persistently elevated CRP. He then underwent transurethral resection of the prostate in May 2008. Pathologic examination of the prostatic tissue showed active vasculitis, confirming that the patient was in partial remission, and oral CYC was given for 3 months. He achieved complete remission, and maintenance therapy with azathioprine was started. Since March 2008, the patient has experienced recurrent urinary tract infections. Another transurethral prostatic resection was performed in November 2009 because of dysuria. Histologic examination revealed in situ prostatic adenocarcinoma with no evidence of active vasculitis.

FIGURE 1

FIGURE 1

FIGURE 2

FIGURE 2

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RESULTS

Eleven men were identified as having urogenital involvement related to WG. Their mean age at diagnosis was 53 years (range, 21–70 yr). Upper respiratory tract manifestations were present in all patients but 1 (90%), pulmonary opacities were present in 9 (81%), glomerulonephritis in 5 (45%), ocular manifestations in 3 (27%), mono- or polyneuropathy in 3 (27%), cutaneous involvement in 5 (45%), articular manifestations in 7 (63%), and involvement of the central nervous system in 2 (18%) patients. The main urogenital and extra-urogenital features are listed in Table 1. The median follow-up from the onset of urogenital manifestations was 56 months (range, 2–156 mo).

TABLE 1

TABLE 1

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Urogenital Manifestations

Urogenital involvement was present at the onset of WG in 9 cases, it was the first clinical evidence of WG in 2 (Patients 1, 10), and it was a symptom of WG relapse in 6 cases (Patients 1, 3, 4, 6, 9, 11).

Prostatitis and orchitis were the most common manifestations, and were observed in 4 patients, occurring simultaneously in 2 of these cases (Patients 5, 11). Prostatitis was revealed by dysuria, urinary frequency, and occasionally gross hematuria. Two patients presented with acute urinary retention (Patients 5, 9). Their prostates were enlarged and tender, with a hypoechoic lesion that mimicked an abscess in 1 patient (Patient 5; see Figure 1). Orchitis caused unilateral testicular pain with enlargement and redness of the testis in 4 patients (Patients 5, 6, 8, 11). Two patients presented with an asymptomatic renal pseudotumor (Patients 2, 7) (Figure 3). One patient developed penile ulceration at initial presentation (Patient 1), 1 patient presented with epididymitis at the time of WG diagnosis (Patient 3), and 1 patient had ureteral stenosis as the sole manifestation of relapse (Patient 4).

FIGURE 3

FIGURE 3

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Therapy and Outcome

All patients but 1 received glucocorticoid therapy and an intravenous CYC regimen as their initial treatment (Table 2). A complete response to the systemic manifestations was observed in 10 patients, and 1 died 2 months after treatment initiation. Two patients (20%) had a partial urogenital response. Patient 1 was treated with MTX and prednisone without success. He was then given intravenous CYC and glucocorticoids, which resulted in a rapid and complete response.

TABLE 2

TABLE 2

Three patients underwent surgical procedures at the time of diagnosis: suprapubic cystostomy for acute urinary retention (Patient 5), radical prostatectomy because of symptomatic prostatic involvement and suspicion of prostatic cancer (Patient 10), and nephrectomy for suspected carcinoma (Patient 2). Patient 5 underwent suprapubic catheterization; the catheter was removed after 6 months.

Three patients had surgical procedures during follow-up: a ureteral double J stent for unilateral ureteral stenosis, then resection of the stricture with end-to-end anastomosis (Patient 4), and transurethral resection of the prostate because of persistent dysuria (Patients 5, 9).

Seven patients (63%) experienced 13 recurrences of WG under maintenance therapy. Four patients experienced urogenital relapse (36%) that was isolated (n = 2) or was associated (n = 2) with other lesions caused by WG. All but 1 urogenital relapse occurred in patients receiving immunosuppressive agents. Patient 1 had recurrence of penile ulceration while receiving azathioprine. A change of treatment to IVIg, MTX, and prednisone resulted in marked clinical improvement, with resolution of the genital ulcerations. Patient 3 had 2 recurrences of epididymitis: 1 while receiving azathioprine and the other while treatment free. Among the 4 patients with prostatitis, 2 experienced recurrence of urogenital symptoms related to WG while receiving mycophenolate mofetil (Patients 9, 11), 2 patients underwent transurethral prostatic resection because of persistent dysuria despite immunosuppressive therapy (Patients 5, 9), and 3 suffered recurrent infections of the urinary tract (Patients 5, 9, 11).

Within the median follow-up of 56 months, 3 patients died. However, death was not related to urogenital factors. One patient died rapidly during the initial flare-up of WG from severe neurologic involvement (Patient 7). The second patient died from metastatic carcinoma of the upper airway while in remission from WG (Patient 4). The third patient committed suicide while in stable remission at 13 years postdiagnosis (Patient 2). At the end of follow-up, all other 8 patients were free of urogenital manifestations related to WG. However, Patient 5 had undergone a second transurethral resection of the prostate because of persistent dysuria: a prostate histologic examination showed adenocarcinoma.

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DISCUSSION

Involvement of the urogenital system in WG is considered uncommon and has been the subject of only a few reports. We report 11 patients with urogenital manifestation of WG identified among the approximately 1700 patients in the FVSG database. Given the study design, our series cannot pretend to be exhaustive and does not allow us to deduce the incidence of urogenital tract involvement in WG. Nevertheless, the small number of patients found in the current study confirms the infrequency of this condition reported in previous series. For example, no urogenital manifestation was reported in a series of 85 patients with WG followed at the National Institutes of Health (NIH, Bethesda, MD) for 21 years.17 In another study of 158 patients, biopsy-proven WG in the urethra, cervix, and vagina was noted in less than 1% of the cases.27

Authors from 2 tertiary centers (Lê Thi Huong et al28 and Davenport et al12) reported, more than 10 years ago, that the clinical features and treatment of patients with WG affects the urogenital tract. Unlike what is usually observed in “classic” WG, which affects women and men equally in large cohorts,27 in the present series, as in those earlier reports, almost all the patients were male.

It is noteworthy that in most of the cases from the present series, regardless of the patients’ age, urogenital involvement was an initial manifestation or was the first clinical evidence of WG. In previous series,12,28 it preceded the diagnosis of WG in 5 of 16 cases (31%) and occurred at the time of diagnosis in 8 patients (50%). Based on their results, Davenport et al12 advocate ANCA testing for patients who present with chronic or recurrent urogenital manifestations, especially if the patient’s past or present history suggests the presence of vasculitis. In the present series, ANCA testing was positive in 9 of 11 cases. However, in the particular setting of urogenital manifestations, physicians should be aware that patients with tuberculosis could be falsely diagnosed as having WG on the basis of an ANCA test alone.20 Indeed, although ANCA test results can be used by clinicians as adjunct evidence for the diagnosis of WG in patients with limited urogenital manifestations, these results should be viewed in the context of the patient’s complete clinical picture and the prevalence of WG in the clinical setting in which the patient is seen.

Prostatitis is considered the most common urogenital manifestation of WG, and was observed in 3 of the 8 patients in the study by Lê Thi Huong et al28 and in 4 of our patients. In previous series of WG patients, prostatic involvement has been reported in 2.3%–7.4% of cases.55,64 However, when considering granulomatous prostatitis, Stillwell et al56 reported that only 4 cases in a series of 200 cases appeared to be manifestations of WG. In this setting, infectious agents, such as mycobacteria, fungi and spirochetes, the Brucellaceae family, Schistosoma species, and Echinococci species; and noninfectious causes of granulomatous prostatitis, including transurethral resection, allergic and simple granulomatous prostatitis, as well as sarcoidosis, should be excluded.56

As noted in the current series, the clinical course of WG in the prostate includes urinary frequency, dysuria, gross hematuria, and, as in 2 of our cases, acute urinary retention.28,55 On physical examination, the prostate appeared firm, enlarged, and indurated, and sometimes had an indurated area mimicking carcinoma,28,55,60,66 or a necrotic area mimicking an abscess,28,29 as in Case 5. Prostate serum antigen may be slightly elevated.41 Although obstructive urinary symptoms are considered to improve rapidly with medical therapy, 2 of our patients underwent prostate resection during follow-up because of persistent dysuria.

Unilateral orchitis was observed in 4, and epididymitis in 1 of our patients. In previous series, only 3 cases had testicular involvement;12,28 these 3 patients were not reported as having typical granulomatous inflammation of the testes. To our knowledge only 1 other diagnosis of WG made from testicular pathology has been reported,2 as in our Case 5. Other testicular involvement in WG includes embolic testicular infarction secondary to nonbacterial thrombotic endocarditis45 and testicular infarction.6 WG limited to the epididymitis is very rare, with only 2 cases previously reported.3,42

A renal mass was observed in 2 of our 11 patients. The presence of a solitary or multiple renal masses resembling carcinoma in patients suffering from WG is rare: to our knowledge, only 13 cases have been reported.10,16,33,36,37,50–54,59,62,63 The inflammatory nature of these tumors has always been confirmed by histology and necrotizing vasculitis. Such a presentation should be investigated, as a case-control study58 found a link between WG and renal carcinoma, with an odds ratio of 8.7 compared to a control group of patients with rheumatoid arthritis. Although a more recent (2009) case-control study18 did not find clear evidence of an increased prevalence of preceding cancer in their WG cohort, the simultaneous occurrence of these 2 diseases has been reported in several other cases.57 These data emphasize, in such setting, the importance of confirming the diagnosis of suspected WG that presents with a renal mass after histologic examination and/or repeating imaging studies, so that appropriate treatment of mass lesions can be undertaken. However, a fine-needle biopsy during an abdominal CT scan should be avoided in patients with a strong suspicion of renal carcinoma. In doubtful cases, nephron-sparing surgery should be considered rather than total nephrectomy.

Ureteral stenosis was observed in 1 of our patients. This complication is rare: 17 cases (including ours) are reported in the literature.1,5,8,12,22,23,26,28,32,35,40,41,47–49 In most cases, ureteral involvement is an initial manifestation of WG. Ureteral stenosis is rarely reported as a recurrent feature of WG.48 This feature is usually revealed by urinary infection or hematuria.28 In 2 cases,35 a retroperitoneal pseudotumor encompassed both ureters and caused anuria. In most of these cases, stenosis was excised by surgery, and a pathologic examination revealed the histopathologic features of WG.

We report 1 patient who had penile ulceration due to angiitis, which revealed WG. To our knowledge, 17 cases of severe ureteral or urethropenile involvement have been previously described.4,12,14,15,21,24,28,31,39,43,46,55,61,65 As in the patient reported here, penile ulceration due to WG generally occurs as the presenting symptom, but may also be a sign of relapse. Urethropenile ulceration may mimic neoplasia and can be complicated by severe necrosis, which may require amputation.14,61

It is noteworthy that 2 urogenital localizations were observed either simultaneously or successively in 2 of our patients. Other urogenital manifestations of WG, not described in the current study, include uterine cervical involvement,7,38 bladder necrotic pseudotumor,19,24,28 and bladder neuropathy.25 It can be difficult to distinguish CYC toxicity from specific WG bladder involvement in patients with known WG. Cystoscopy is required for any durable urinary symptom in a WG patient who is or has been treated with CYC, to distinguish toxic from specific cystitis, and to exclude transitional carcinoma caused by this cytotoxicity.

Combined glucocorticoid and CYC therapy is the basic treatment for WG.11 A decisive step toward treating WG has been to develop a staged induction-maintenance strategy that reduces cumulative exposure to CYC. This strategy uses CYC to induce remission, followed by a less toxic immunosuppressant, such as azathioprine or MTX.44 This therapeutic regimen has been found to achieve either partial or complete remission in 91% and 75% of patients, respectively.27 However, induction relapses occur in approximately half of WG patients.9,27 But, as shown in the current study and in the study by Lê Thi Huong et al,28 urogenital manifestations respond rapidly to treatment with CYC and glucocorticoids. One patient who failed to respond to MTX and prednisone improved under CYC. Seven of our 11 patients (63%) experienced relapses under maintenance therapy, and 4 had urogenital recurrence (36%). Most urogenital manifestations can be resolved promptly with pharmaceutical therapy, although some patients need surgical procedures (for example, prostatic transurethral resection) because of persistent symptoms after receiving immunosuppressants.

In conclusion, symptomatic urogenital involvement is a rare feature of WG, but is probably underestimated because it is difficult to diagnose in some cases (such as ureteral stenosis and uterine cervical or testicular involvement). Because urogenital manifestations can be the first clinical symptom of WG, physicians should be aware of these presentations. Some presentations, such as the presence of a renal or prostate mass that mimics cancer, should be assessed to avoid unnecessary radical surgery.

Urogenital symptoms seem to be highly sensitive to CYC and glucocorticoid therapy. One-third of patients had urogenital relapse while on maintenance treatment. In this setting, CYC urothelial toxicity and urinary infection may occur in the course of WG and may mimic other manifestations, which should be excluded. However, most relapses rapidly resolve with medical treatment. Surgical procedures, such as a prostatic transurethral resection, can be useful in patients with persistent symptoms.

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