Focal Xanthogranulomatous Pyelonephritis in Brachydactyly Mental Retardation Syndrome (2q37 Deletion Syndrome)

Abstract

Xanthogranulomatous pyelonephritis (XGP) is characterized by destruction of the renal parenchyma and granulomatous inflammation with lipid-laden foamy macrophages as well as inflammatory infiltration and intensive renal fibrosis. It generally occurs in adults, especially those in the fifth and sixth decades of life, but is occasionally seen in children as well. Brachydactyly mental retardation (BDMR) syndrome (OMIM 600430) is caused by a small deletion of chromosome 2q37 and is a rare condition, with roughly 100 cases reported worldwide. Here, we describe the case of a patient with deletion of chromosome 2q37, which is known as the BDMR syndrome, and XGP.

Introduction

A 3-year-old girl was admitted to our hospital with vomiting and fever over the previous 2 weeks. She had no history of major illness, urinary tract infection, injury, or surgery. There was no consanguinity between her parents and no other genetic or chronic disease in her family. Her physical examination findings were as follows: weight, 7,700 g (<3rd percentile); height, 72 cm (<3rd percentile); head circumference, 45.5 cm (<3rd percentile); and presence of dysmorphic features, including a boxy skull with a prominent forehead and relative macrocephaly, depressed nasal bridge, prominent columella, and short hands and feet without metacarpal/metatarsal shortening ( Fig. 1 ). Genetic analyses revealed 2q37 deletion, and she had been previously diagnosed with brachydactyly mental retardation (BDMR) syndrome. She was febrile, with a body temperature of 39°C, experienced tenderness in the right lumbar region, and had a palpable mass on the same side. Her laboratory findings were as follows: white blood cell (WBC) count, 27,500 cells/mm ³ (normal range, 4,000–12,000 cells/mm ³ ); C-reactive protein (CRP) level, 22.4 mg/dL (normal range, 0–0.5 mg/dL); and erythrocyte sedimentation rate (ESR), 49 mm/h (normal range, 0–15 mm/h). Results of biochemical analyses, including serum urea, creatinine, and electrolyte levels, were normal. Peripheral blood smear findings revealed polymorphonuclear leucocytes (74%), toxic granulation, and hypochromia (17%). Urinalysis results were as follows: density, 1,024; pH, 6.2; leukocytosis; and leukocyte clusters. Her urine culture was sterile, and her blood culture was positive for Escherichia coli . She was diagnosed as sepsis and was hospitalized and treated with intravenous antibiotic ertapenem 15 mg/kg every 12 hours. On the fifth day of therapy, she had fever and leukocytosis, and abdominal ultrasonography (USG) revealed horseshoe kidney with grade 4 hydronephrosis in her right kidney, dilated right ureter, and dilated and cystic right collecting duct system. Technetium-99m dimercaptosuccinic acid renal scan revealed a nonfunctioning left kidney ( Fig. 2A ). Abdominal computed tomography (CT) revealed horseshoe kidney, and cystic lesions that originated from the anteromedial right kidney, extended to the retroperitoneum, were associated with the lower pole of the left kidney (size: 11 × 10 × 7 cm ³ ), and were evaluated as an abscess. Percutaneous nephrostomy was performed to drain the abscess and correct the ureteropelvic junction obstruction. Following this, 600 mL of seropurulent fluid was evacuated and sent for culture. The pus cultures were sterile. She remained afebrile and demonstrated rapid clinical and laboratory recovery. Ertapenem treatment was completed after 10 days, and she was discharged.

Fig. 1.

( A, B ) Boxy skull with prominent forehead, relative macrocephaly, depressed nasal bridge, and prominent columella. ( C, D ) Short hands and feet without metacarpal/metatarsal shortening.

Fig. 2.

( A ) DMSA scan shows nonfunctional right kidney. ( B ) Computed tomography consistent with no normal renal parenchyma. ( C ) Macroscopic features of multilobulated XGP. ( D ) Histological features of XGP showing fibrosis, inflammatory infiltrate, and fat laden macrophages. DMSA, dimercaptosuccinic acid; XGP, xanthogranulomatous pyelonephritis.

One month after discharge, she was readmitted to our hospital with a body temperature of 39.5°C and tenderness in the left lumbar region. Pus draining was observed during nephrostomy. Her laboratory findings were as follows: WBC count, 24,510 cells/mm ³ ; CRP level, 62 mg/dL; and ESR, 68 mm/h. Serum urea, creatinine, and electrolyte levels were within the normal range. Her urine culture was positive for Pseudomonas aeruginosa , and ceftazidime was administered at a total dose of 150 mg/kg/d. On the fourth day of antibiotic therapy, her body temperature was still 39°C, and laboratory analyses revealed a WBC count of 24,000 cells/mm ³ along with high levels of acute-phase reactants (AFRs). Her nephrostomy catheter was changed, and the catheter culture was positive for Candida albicans . An antifungal agent (fluconazole 6 mg/kg/d) was added to her therapy. Abdominal USG revealed horseshoe kidney, and although the right kidney was not visualized, the right ureter was dilated. Three-phase abdominal CT revealed horseshoe kidney with no normal renal parenchyma of the right kidney, but the left kidney was normal ( Fig. 2B ). After 10 days of combination therapy, there was no improvement in her clinical and laboratory findings. She underwent right heminephrectomy without any complications. In the macroscopic examination of the specimen, the right nephrectomy specimen was noted as having a 6.5 × 4 × 3 cm ³ dimension and weighed 25 g. The outer layer of the specimen was multilobulated ( Fig. 2C ), and there was a remarkable loss of renal parenchyma. The whole calyceal lumen was dilated, and a 0.5 × 0.4 × 0.4 cm ³ area was full of yellow-colored pus. Histopathological examination revealed chronic interstitial nephritis, focal inflammatory cells infiltrated by giant cells, and lipid-laden macrophages (foam cells) in the cortical areas ( Fig. 2D ). She was diagnosed with xanthogranulomatous pyelonephritis (XGP). She felt better after surgery and gained weight. Her WBC count and AFR level decreased within the normal range. She has been followed up for 3 months in monthly intervals after discharge and is still free of symptoms.

Discussion

BDMR syndrome is a rare syndrome, with roughly 100 cases reported worldwide. ¹ Major malformations occur in ∼30% of patients with 2q37 deletions. Congenital heart malformations are the most frequent characteristics of this syndrome, followed by gastrointestinal and renal anomalies. ²

XGP is a rare response of the kidney to chronic infection. It is characterized by destruction of the renal parenchyma and replacement by granulomatous tissue containing lipid-laden foamy xanthoma cells. ³ XGP predominantly affects adults and is diagnosed sporadically in children. ⁴ Here, we report the case of a 3-year-old girl with BDMR syndrome who had a history of urinary tract infection and renal abscess that was subsequently diagnosed with XGP.

Renal anomalies have been reported in 11% of patients with 2q37 deletions. ⁵ Genitourinary malformations include renal cysts, horseshoe kidney, hypospadias, hypoplastic or dysgenetic gonads, bifid uterus, and undescended testis. ² Horseshoe kidney is a congenital malformation that predisposes patients to severe urinary tract infections due to pelvic ectasia, which is inherent in the malrotation of renal units. ⁶ Horseshoe kidney, cystic lesions, and ureteropelvic junction obstruction, which may hinder urinary flow, may have predisposed our patient to chronic infection and XGP. Aldred et al noted horseshoe kidney in individuals with 2q37 deletion, ⁷ whereas Falk and Casas noted renal cysts, ² but there are no reports of ureteropelvic junction obstruction due to this syndrome. Therefore, this might be the first report of ureteropelvic junction obstruction observed in this syndrome.

The etiology of XGP is still unclear; however, impairment of urinary flow and chronic bacterial infection have consistently been regarded as factors that are associated with XGP development. ⁸ XGP is most commonly associated with superinfections by bacteria such as E. coli , Proteus mirabilis , and occasionally Pseudomonas species. ⁹ The urine culture of our patient was sterile, but her blood culture was positive for E. coli at initial admission. After 1 month, her urine culture was positive for P. aeruginosa . Infections caused by multiple microorganisms may facilitate the development of XGP, as observed in our case.

Our patient presented with a 1-month history of urinary tract symptoms. The obstruction associated with XGP in the pediatric population is frequently linked to congenital urinary tract malformations than to obstructive calculi. Our patient had horseshoe kidney and ureteropelvic junction obstruction.

USG and other imaging modalities can be used when XGP is suspected, but CT and magnetic resonance imaging are thought to be more sensitive and usually reveal an enlarged nonfunctioning kidney with or without invasion to the neighboring structures. ¹⁰ In our patient, CT revealed horseshoe kidney with no normal renal parenchyma of the right kidney.

XGP is frequently misdiagnosed as inflammatory or renal disease, and preoperative diagnosis is complicated by nonspecific clinical and imaging features along with laboratory findings; it is confirmed by histopathology. ¹⁰ The correct diagnosis of XGP is typically confirmed by pathological examination following surgery, as in the present case.

It is recommended to resect all diseased tissues in cases of XGP. ^{8 11} A total nephrectomy was performed on our patient because of the involvement of her nonfunctioning kidney. It is generally accepted that the prognosis is excellent once the diseased kidney has been removed. ¹¹ Our patient had no symptoms in 3 months after nephrectomy.

Conclusion

This is the first case demonstrating concomitant BDMR syndrome and XGP in the literature. BDMR syndrome is a rare syndrome, with roughly 100 cases reported worldwide. In addition, this case may be the first in which ureteropelvic junction obstruction was observed in BDMR syndrome. Thus, ureteropelvic junction obstruction should be considered in cases of BDMR syndrome, in addition to other genitourinary anomalies. Genitourinary malformations may predispose the patient to urinary tract infection and XGP, as in the present case. It should be noted that more than one genitourinary malformation in BDMR syndrome may cause more aggressive infections and XGP.