CASE REPORTS Ref: Ro J Rheumatol. 2019;28(2) DOI: 10.37897/RJR.2019.2.6 RARE CASE OF female Behçet’s disease WITH UROLOGICAL INVOLVEMENT Claudia Cobilinschi1,2, Catalin Belinski3, Daniela Opris-Belinski1,2 1„Carol Davila“ University of Medicine and Pharmacy, Bucharest, Romania 2„St. Maria“ Clinical Hospital, Bucharest, Romania 3„Prof. Dr. Dimitrie Gerota“ Emergency Hospital, Bucharest, Romania Abstract Behçet’s disease is a systemic vasculitis with several well-defined organ manifestations, including various mu- cocutaneous features. Among them, the urinary tract involvement is rarely cited, most data focusing on bladder dysfunction due to neuroBehçet. This article presents a rare case of a young female patient with urological complaints that was diagnosed with right ureteral ulceration, later confirmed as vasculitis at the histopathological examination. Urological intervention together with adequate immunosuppression let to the healing of the ulcer- ative lesion. The unusual vasculitic lesion site indicates the complexity of Behçet’s disease that requires careful investigation and treatment. Keywords: Behçet’s disease, ureteral ulceration, ureteral stent, immunosuppressant INTRODUCTION The onset of the disease was in 2013 when the patient presented to her general practitioner (GP) for Behçet’s disease (BD) is a variable size vasculitis repeated febrile episodes that were essentially ves- that can affect both arteries and veins characterized peral, occurring in the afternoon followed by odyno- by recurrent episodes of orogenital ulcers, eye and phagia and painful aphthae on her oral mucosa. Due skin involvement, neurologic manifestations accom- to her prominent ENT symptoms, her GP referred panied by a positive patergy test (1). The genetic the patient to a specialist who prescribed multiple background is best described by HLA B51 positivity antibiotic schemes because of the high suspicion of which associates with a more extensive clinical ex- streptococcal infection. Lack of patient response to pression of the disease (2). antibiotherapy, recurrent fever and negative throat While the above-mentioned organ involvement cultures led the patient further to search for an infec- are well described in the disease related literature, tionist’s opinion. The latter pointed out the presence including disease revised criteria and management of multiple aphthous lesions on the patient’s hard guidelines, urological suffering related to the urinary and soft palate, jugal mucosa and tonsils. Several eti- tract is rarely mentioned as possible in BD or re- ologies were excluded on this occasion, including ceived any specific indications for treatment (3). hepatitis B, C, HIV, herpes infections, vitamin defi- Considering ureteral lesions as an exquisitely ciencies or inflammatory bowel diseases. rare manifestation in BD, we present the case of a The patient was further transferred to a territorial female patient with this type of involvement. Rheumatology Department where multiple diagno- ses were investigated. Meanwhile, the patient com- CASE REPORT plained of inflammatory arthralgias in her small We present the rare case of a 34-year old female joints of the hands and alopecia which might have patient diagnosed with Behçet’s disease since Au- suggested the diagnosis of systemic lupus erythema- gust 2015 who was admitted in the Rheumatology tosus. However, complement levels were normal Department for her regular follow-up while com- and antibodies (anti-nuclear antibodies, dou- plaining of dysuria and right lumbar pain. ble-strandedDNA) were negative. Rheumatoid ar- Correspondence address: Catalin Belinski, „Prof. Dr. Dimitrie Gerota“ Emergency Hospital, Bucharest, Romania E-mail: [email protected] 80 ROMANIAN JOURNAL OF RHEUMATOLOGY – VOLUME XXVIII, NO. 2, 2019 ROMANIAN JOURNAL OF RHEUMATOLOGY – VOLUME XXVIII, NO. 2, 2019 81 thritis was ruled out based on the ultrasound aspect pressive tumor that might have led to these stenotic of the joints that showed no typical erosions, both changes. rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) were negative. The patient only exhibited a moderate inflammatory syndrome. Patient’s history added subsequent essential de- tails such as an episode of genital aphthous lesions, acneea and positive patergy test that together with the presence of the HLA-B51 gene concurred to the diagnosis of Behçet’s disease, two years after symp- tom onset. Treatment with colchicine, azathioprine and glucocorticoids (GC) was promptly initiated. The patient was later on regularly monitored in our University Clinic with episodes of disease flare that manifested with recurrent extensive ulcerative lesions on her tonsils that required a therapeutic FIGURE 1. Collected urine with hematuric aspect switch on cyclosporine and careful adjustment of GC dose. In June 2018 the patient was admitted for dysuria The patient’s renal function deteriorated and it and slight pain in her right lumbar area. Abdominal was accompanied by fever, leukocytosis and posi- ultrasound at the time highlighted a stage 2 hydrone- tive urine cultures that required prompt sanction of phrosis that inquired repeated ureteroscopic exami- the stent. A following ureteroscopic investigation nations and finally the placement of a Cook ureteral was conducted in another Urology Department stent, with no obvious lesion at the time. Persistent where the stent was replaced but surprisingly notic- pain, hematuria (Figure 1) and aggravation to a stage ing a ulcerative lesion on the right ureter (Figure 2). 5 hydronephrosis appeared after the stent was initial- The team questioned if the ulcer was due to repeated ly removed. Patient deterioration required a tomo- ureteroscopic interventions that might have injured graphic imaging that mentioned a severe stenosis of the mucosa on site or if it was a consequence of her the right pelvic ureter. This finding was followed by yet uncontrolled vasculitis. Thus, a biopsy was a pelvic MRI that ruled out the presence of a com- made. FIGURE 2. Ureteroscopic aspect of the mucosal ulcerative lesion 82 ROMANIAN JOURNAL OF RHEUMATOLOGY – VOLUME XXVIII, NO. 2, 2019 The histopathological finding showed urothelium genital area together with normalization of the renal fragments with reactive changes, intraepithelial ede- function and ultrasound aspect. ma, the connective tissue had a lymphocytic inflam- matory infiltrate as well as polymorphonuclear cells DISCUSSIONS in the interstitial and perivascular structures. These Behçet’s disease is a multisystemic vasculitis af- changes confirmed signs of vasculitis compatible fecting any size and type of vessels. Classical organ with the patient’s formerly established diagnosis. involvement include mucocutaneous, cardiovascu- At the time of the ureteral intervention, the pa- lar, neurological and ocular features. Apart from tient was on methotrexate at a dose of 10 milligrams per week due to incomplete response to previous im- genital aphthous lesions and epididymitis (4), other munosuppressants. Taking into account the severe urological manifestations are rarely cited. For exam- and unusual site of disease activity, the past lack of ple, the incidence of bladder manifestations, mostly response to azathioprine, she was put again on cy- urodynamic changes, were identified by Cetinel at closporine 100mg daily together with 1mg of colchi- al. to be at around 0.07% in BD patients. He suggest- cine and a descending dose of GC. ed that urological involvement can be present 1 to 10 Figure 3 depicts the ureteroscopic findings after 6 years after the onset of the disease. months of treatment, showing a significant improve- Bladder involvement was reviewed in 2011 by ment of the ureteral lesion. Its persistence led to the Alizadeh et al. based on case reports and case series decision to maintain the ureteral stent for a longer (5). Authors included in their online data search neu- interval in order to ensure the complete healing of ropathic bladder issues, voiding dysfunctions and the ulceration. urologic symptoms. They found out that most pa- Periodic urological reevaluations showed a slow tients with this system manifestations were mid- healing of the ureteral ulcer and the integrity of the dle-aged males with storage problems because of a ureteral mucosa that allowed the stent removal in deficient sphincter. They also found reasons for dy- March 2019 with no further discomfort in the uro- suria in BD patients such as meatal ulceration, sterile FIGURE 3. Ureteroscopic control reevaluation after 6 months of treatment ROMANIAN JOURNAL OF RHEUMATOLOGY – VOLUME XXVIII, NO. 2, 2019 83 urethritis or cystitis. Cyclophosphamide treatment that recurrent lesions that are reluctant to colchicine was the cause for most bladder located cancers in alone should be accompanied by immunomodulato- this patient category, but the rate was not higher than ry or immunosuppressive drugs (azathioprine, tha- in other patients (6). Rare urethrovaginal fistulas lidomide, interferon-alpha, anti-TNFs or apremilast) were identified. (10). Other biologics targeting interleukin-1 (IL-1), Bladder ulcers were cited as possible after being such as anakinra or canakinumab can be used in mu- confirmed by cystoscopic examination and were cocutaneous BD providing some benefits to the suf- suggested to be self-limited (7). fering (10). A cumulative analysis on renal Behçet’s pub- lished in 2012 estimated a rate up to 55% for this CONCLUSIONS organ involvement, the male gender representing a The present article