CASO CLÍNICO Lupus cystitis and repercussions of delayed diagnosis Abelha-Aleixo J 1, Moura M 2, Bernardo A 1, Almeida J 2, Brito I 1 ACTA REUMATOL PORT. 2015;40:294-298 AbstrAct tation symptoms with few abnormal urinalysis results, hydroureteronephrosis and reduced bladder capacity, We describe a case of a young female with lupus that associated with gastrointestinal involvement 2,3 . The de - complained about suprapubic pain, dysuria, fever and lay on diagnosis and prompt corticosteroid therapy can vomits, symptoms first interpreted as pyelonephritis, lead to irreversible damage, such as progressive blad - despite negative cultures and imaging studies showing der fibrosis and obstructive uropathy resulting in renal hydroureteronephrosis with inflammatory changes. failure 1. When she developed malar rash, anasarca and nephro - Thrombotic microangiopathy (TMA) is also a rare, tic syndrome, the diagnosis of lupus cystitis with stage life-threatening disease, rarely reported in SLE 5 . Accor - IV nephropathy was made, and she started immuno - ding to a cohort study by Ming-Han et al, there are only suppressive induction treatment with three pulses of 129 cases in the English literature, most of them being methylprednisolone followed by oral prednisolone (60 sporadic case reports 5. Kwok et al estimated and inci - mg/d) and mycophenolate (1.5 g/d). One month later dence rate of approximately 2.2% 5. Microangiopathic she was admitted again with blood exams compatible haemolytic anaemia (MAHA), thrombocytopenia, re - with thrombotic microangiopathy, requiring aggressive nal impairment, fever and neurologic manifestations immunosuppression and plasma exchange. After over - are the main features of this condition. SLE complicat - coming multiple complications, the patient gradually ed by two rare disorders, and the exhaustive immuno - improved, and was discharged with close surveillance. suppressive treatment used based on case reports led to This case poses the question: if the urogenital involve - a favorable outcome. ment had been recognized and treated in time, would it prevent the onset of lupus nephritis and other com - plications? cAse report Keywords: Systemic lupus erythematosus; We describe a 27-year-old female diagnosed with SLE in 2007, with malar rash, photosensitivity and arthri - tis, responsive to prednisolone (PDN) 10 mg/day (d) IntroductIon and hydroxycloroquine (HCQ) 400 mg/d. In 2010 she had a disease flare during pregnancy, resolved by a tran - Lupus cystitis is a manifestation of systemic lupus sitory increase of corticosteroid therapy and pre-term erythe matosus (SLE) mainly reported in the Asian li - birth. In October 2011 she developed malar rash and terature and in Asian patients living in Western coun - presented low complement, so azathioprine was start - tries 1-3 . It was first described by Nitze in 1907, and the ed in increasing doses up to 2 mg/Kg/d. concept of “lupus cystitis”, defining interstitial cystitis In December/2011 the patient went three times to complicated with SLE, was first used by Orth et al 4.The the hospital emergency room (ER) with dysuria, lum - incidence has been estimated as 0.01% with female pre - bar and suprapubic pain interpreted as a renal colic. dominance of 92% 1. It is characterized by bladder irri - During the assessments an ultrasonography and sub - sequently a pelvic tomography were done, both show - 1. Reumatologia, Centro Hospitalar S. João, Porto ing right hydroureteronephrosis and ureteral wall 2. Medicina interna, Centro Hospitalar S. João, Porto thickening with inflammatory changes without obs - ÓRgÃO OfICIAL dA SOCIEdAdE PORTUgUESA dE REUMATOLOgIA 294 AbelhA-Aleixo J et Al FIGure 1. Bilateral hydroureteronephrosis in the pelvic FIGure 2. Malar rash tomography truction. The blood tests had no leukocytosis, the C of the gastrointestinal mucosa (Figure 3) in the upper reac tive protein (CRP) was of 9.9 mg/L (NR 5.0 mg/L) endoscopy, unfortunately biopsy couldn’t be per - and the urinalysis was normal. She was treated with formed because the mucosa was very fragile. analgesics and antibiotics. She was diagnosed with lupus cystitis with stage IV In the following three months she was admitted se - nephropathy and started induction treatment with veral times with the same complaints associated with three intravenous pulses of methylprednisolone (MTP) fever (38ºC) and persistent vomits, diagnosed as 500mg and mycophenolate mofetil (MMF) 1.5 g/d. pyelonephritis, but always with negative cultures. By She was discharged also with HCQ 400mg/d, pre - this time she presented bilateral hydroureteronephro - dnisolone 60 mg/d, furosemide 160 mg/d, lisinopril sis (15.5 mm left; 8.8 mm right), and persisting in - 2.5 mg/d, calcium and vitamin D supplementation, flammatory changes, in the pelvic tomography (Figu - tansulosine 0.4 mg/d, omeprazol 20 mg/d, cotrimo - re 1). Renal function and urinalysis were normal. Per - xazole (CTX) prophylaxis, nystatine (for oral candidi - manent urinary catheterization was needed as a result asis) and urinary permcath. of an hypotonic bladder. One month later, the patient presented anasarca as - She returned to the ER with anasarca and malar rash sociated with pancytopenia: normocytic nor - (Figure 2). Laboratory tests showed worsening of re - mochromic anemia (hemoglobin 6.8 g/dL), leucopenia nal function and nephrotic range proteinuria, with (3.81x10 9/L) and thrombocytopenia (99x109/mL). casts and erythrocytes. She was hospitalized in the Her renal function had improved, but maintained hy - Rheumatology department (RhD). Blood tests con - poalbuminemia (24.4 g/L), nephrotic range proteinu - firmed: hemoglobin (Hb) 8.9 g/dl, ESR 129 mm/1st ria (4.0 g/L). MMF and CTX were suspended for the hour, CRP 1.2 mg/L, creatinine 2.5 mg/dl, hypocom - possibility of bone marrow toxicity and three intra - plementemia and elevated anti-dsDNA antibodies (Ab) venous pulses of MTP 500mg were given without (498UL/ml). Renal biopsy was consistent with lupus hematologic response. Further laboratory tests were nephropathy class IV (WHO), with an activity index of compatible with microangiopathic hemolytic anemia 9 and a chronicity index of 2. It also showed some hya - (blood smear with schistocytes, elevated lactate dehy - line thrombi. drogenase (LDH) and low haptoglobin). Coombs’test, Diagnosis of Lupus enteritis was assumed because anticardiolipin antibodies and lupus anticoagulant the patient presented persistent vomiting, nausea and were negative. Blood cultures were negative and urine marked weight loss associated with generalized edema culture was positive for multisensible E. coli, treated ÓRgÃO OfICIAL dA SOCIEdAdE PORTUgUESA dE REUMATOLOgIA 295 lupus cystitis And repercussions of delAyed diAgnosis training for intermittent urinary catheterization and was finally discharged two weeks later with close surveillance, medicated with HCQ 400 mg/d, PDN 20 mg/d, losartan 50 mg/d, prophylatic CTX, aspirin 100 mg/d, rosuvastatin 10 mg/d, pantoprazole 40 mg/d, calcium and vitamin D supplementation with weekly alendronic acid and sertraline. Her analytical parameters stabilized and she went on remission with resolution of the ureteropelvic di - latation. She evolved from urinary catheterization each six hours to spontaneous voiding without residual urine. MMF 1 g/d was restarted with PDN 15 mg/d two weeks after discharge. One year later she is on remission and regained au - tonomous bladder function, with MMF 1g/d and HCQ 400 mg/d, without PDN and no need to repeat RTX. FIGure 3. Uper endoscopy showing generalized edema of the gastrointestinal mucosa dIscussIon Interstitial cystitis should be suspected in the presence with ceftriaxone. Her SLE Disease Activity Index was of bladder irritation symptoms with few abnormal uri - 10. nalysis results, associated with gastrointestinal mani - The case was discussed in a multidisciplinary mee - festations, like enteritis. The diagnosis is reinforced by ting. Assuming the diagnosis of TMA the patient was the observation of hydroureteronephrosis or gastroin - admitted in an intermediate care unit. She began daily testinal wall edema in ultrasonography or tomography, sessions of plasmapheresis and immunosuppressive by the presence of reduced bladder capacity or by ede - treatment, based on a similar case report 6: intravenous ma and inflammatory infiltration on bladder biopsy 2. cyclophosphamide (CYC) 750 mg once per month, ri - Our patient exhibited dysuria, suprapubic pain, bilate - tuximab (RTX) 375 mg/m 2 weekly for a total of 4 admi - ral hydroureteronephrosis, normal urinalysis, bladder nistrations and PDN 80 mg/d with progressive dose ta - dysfunction, weight loss, persistent nausea and vomi - pering. Analytic stability was achieved but multiple ting with gastric wall edema, supporting the diagnosis complications arose that hampered the prognosis: neu - of lupus cystitis with associated lupus enteritis. tropenic fever needing granulocyte colony stimulating Interstitial cystitis is associated not only with SLE, factors treatment; opportunistic infections (celulitis, but also with other connective tissue diseases as Sjo - catheter associated infections, oral candidiasis and can - gren’s syndrome and Rheumatoid arthritis 4. Its physio - diduria); serous chorioretinitis associated to corticos - pathology remains unclear, but immune complex me - teroids (with improvement after dose reduction); acute diated vasculitis, anti-bladder and anti-intermediate pulmonary edema and electrolyte imbalance, which fila ment Abs and elevation