Saudi Journal of Kidney Diseases and Transplantation

: 2018  |  Volume : 29  |  Issue : 1  |  Page : 185--188

A case of renal granulomatosis with polyangiitis following intravesical bacillus Calmette-Guérin therapy

Yosra Selmi, Rania Kheder-Elfekih, Hela Jebali, Lilia Ben Fatma, Wided Smaoui, Madiha Krid, Soumaya Beji, Lamia Rais, Mohamed Karim Zouaghi 
 Department of Nephrology, La Rabta Hospital, Jebbari, Tunis, Tunisia

Correspondence Address:
Dr. Rania Kheder-Elfekih
Department of Nephrology, La Rabta Hospital, Jebbari 1007, Tunis


Various adverse reactions may occur after intravesical bacillus Calmette-Guérin (BCG) therapy. Although the virulence of attenuated BCG is low, serious complications such as bacterial cystitis, bladder contractures, granulomatous prostatitis, epididymitis, orchitis, and systemic reactions such as fever and malaise have been described. Disseminated granulomatosis such as hepatitis and pneumonitis have also been described, but are rare. We report here the case of a 67-year-old patient who presented with renal granulomatosis with polyangiitis following intravesical BCG therapy for superficial bladder tumor. The biological evaluation revealed the presence of perinuclear anti-neutrophil cytoplasmic antibodies with specificity for antimyeloperoxidase. Renal biopsy specimen revealed pauci-immune crescentic glomerulonephritis with segmental glomerular necrosis, presence of granulomas and no evidence of any caseating necrosis. He received antituberculosis drugs in addition to corticosteroids and cyclophosphamide without any improvement of the renal function.

How to cite this article:
Selmi Y, Kheder-Elfekih R, Jebali H, Fatma LB, Smaoui W, Krid M, Beji S, Rais L, Zouaghi MK. A case of renal granulomatosis with polyangiitis following intravesical bacillus Calmette-Guérin therapy.Saudi J Kidney Dis Transpl 2018;29:185-188

How to cite this URL:
Selmi Y, Kheder-Elfekih R, Jebali H, Fatma LB, Smaoui W, Krid M, Beji S, Rais L, Zouaghi MK. A case of renal granulomatosis with polyangiitis following intravesical bacillus Calmette-Guérin therapy. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2021 Mar 4 ];29:185-188
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Full Text


Bacillus Calmette-Guérin (BCG) is an alive, attenuated strain of the bovine tuberculosis bacillus, Mycobacterium bovis. In 1976, Morales et al were the first to use intravesical BCG instillation to treat superficial bladder cancer, and now, it is the standard treatment for bladder tumors not infiltrating the muscle at high risk of recurrence and progression.[1] Complications of BCG therapy are for the most part minor. Short-term symptoms of cystitis are almost expected. Mild hematuria, low-grade fever, and myalgias are common and usually of limited duration. Granulomatous complications (including prostatitis, epididymitis, orchitis, and granuloma formation in the liver and lungs) are rare; life-threatening BCG sepsis has been reported in only 0.4% of patients.[2] These effects are explained by cytotoxic action of BCG which stimulates the immune system leading to allergic and autoimmune reactions. The incidence of significant renal toxicity varies from 0.2% to 2%. We report for the first time, the case of a non-caseous granulomatosis with polyangiitis (GPA) following intravesical BCG therapy. Since it is a life-threatening disease, our observation aims to insist on detecting symptoms of vasculitis after BCG therapy.

 Case Report

A 67-year-old man with a history of superficial bladder tumor surgically removed 18 months before was treated with intravesical BCG therapy. He was referred to us to investigate urticarial eruption, joint pains, fever, a recent onset of microscopic hematuria, and acute renal failure occurred three days after the 9th course of intravesical BCG instillation. Routine blood tests revealed: hyperleukocytis (22,600), eosinophilia, an increase in the rate of C-reactive protein (185 mg/dL), serum creatinine (4.5 mg/dL) and a normal level of complement. Mantoux test was positive (10 mm). Sputum and urine cultures were all negative for Mycobacterium tuberculosis as was screening for fungi or atypical mycobacteria. The differential diagnosis was between a rapidly progressive glomerulonephritis, an acute immuno-allergic interstitial nephritis or renal tuberculosis. Investigations for antinuclear antibodies and anti glomerular basement membrane antibodies were negative.

Perinuclear anti-neutrophil cytoplasmic antibodies (ANCA) were positive with specificity for anti-myeloperoxidase (MPO) level 170 U/mL. Renal biopsy specimens revealed pauciimmune segmental and focal crescentic glomerulonephritis [Figure 1] and [Figure 2], presence of granulomas with giant cells [Figure 3] and [Figure 4] and no evidence of any caseating necrosis [Figure 5]. Tubules were normal. Some vessel walls were infiltrated with inflammatory cells, with the presence of a fibrotic endarteritis. Anti-IgA, anti-IgG staining were performed on the renal biopsy, and both were negative. There was no linear anti-IgG staining on the glomerular basement membrane. Negative stains for acid-fast bacillus were reported after Ziehl Neelsen staining. A tissue culture on Lowenstein–Jensen medium also failed to grow any mycobacterium. A diagnosis of GPA was made. Para-sinusal evaluation was normal with no signs of upper respiratory tract involvement. A pulmonary computed tomography scan was performed showing only lobar pulmonary emphysema without nodules neither ground glass opacities nor any sign of alveolar hemorrhage. The patient was treated with antituberculosis drugs: isoniazid (5 mg/kg daily); rifampicine (10 mg/kg daily); and pyrazinamide (30 mg/kg three times a week) in addition to corticosteroids (1 mg/kg); and in combination with cyclophosphamide (500 mg/d every 3 weeks). Renal function did not improve and the patient had to be started on chronic hemodialysis.{Figure 1}{Figure 2}{Figure 3}{Figure 4}{Figure 5}


Intravesical BCG for the treatment of superficial bladder cancer has been widely used since its introduction by Morales et al in 1976.[1] Its anti-tumor effect goes through the modulation of T-cell immunity. It can be associated to a local inflammation, with cystitis and hematuria. Systemic side effects vary from granulomatous complications to life-threatening sepsis.

Our case is characterized by its originality as a rare adverse effect of BCG therapy. To the best of our knowledge, ANCA-associated vasculitis following intravesical BCG has never been reported before in the literature. Our literature search revealed only three cases of vasculitis following BCG therapy: one case of cryoglobulinemia[3] and two cases of rheumatoid purpura.[4],[5]

Investigations on our patient confirmed a GPA with positive ANCA anti-MPO specificity. The diagnosis of an acute immunoallergic interstitial nephritis or renal tuberculosis was eliminated by renal biopsy, which also showed the absence of caseating necrosis and a negative mycobacterium culture.

Drug-induced vasculitis have been reported with systemic or oral intake drugs, such as hydralazine,[6] allopurinol, and especially in patients with a long-term antithyroid drug treatment. The most often implicated drug in the published works is propylthiouracil with most commonly a specificity for MPO, human leukocytes elastase ,or lactoferrine.[7] The pathogenesis of drug-induced vasculitis is still unclear and seems to be multifactorial with a particular role played by epigenetics and genetic predisposition.[8] In this particular case of local intravesical instillation of BCG, an intravenous absorption of BCG through an inflamed or disrupted urothelium could explain the initiation of a local inflammatory reaction.

Usually, the diagnosis of drug-induced ANCA-associated vasculitis is based on the temporal relationship between clinically evident vasculitis and administration of the offending drugs. Once the diagnosis of drug-induced ANCA-associated vasculitis is made, the offending drug must be withdrawn. Although there is no specific protocol therapy for induced vasculitis, some authors suggest the same therapy as a primary ANCA associated-vasculitis.[8] The place of an antituberculous treatment is unclear in the literature and seems to be limited to infectious granulomatosis following BCG instillations.

In conclusion, BCG-induced vasculitis is a severe disease. Diagnosis must be done early and treatment is crucial for improving prognosis especially renal one. Physicians should be aware of this complication to organize a renal function monitoring during the therapy.


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