Carolinas Research Day 2021

PURPLE URINE BAG SYNDROME : AN UNUSUAL CAUSE OF FEVER IN A PATIENT WITH BILATERAL NEPHROSTOMY Hunter Harrison , OMS-III, Chad Millwood , MD VCOM-Carolinas – Spartanburg, SC

Abstract # CBR-9

Abstract

Case Report

Discussion & Conclusions

A 78-year-old white male presented to an outpatient clinic complaining of three days of subjective fever in the absence of additional symptoms. His history was notable for prostate and bladder cancer managed with radical cystoprostatectomy, as well as oropharyngeal cancer, end-stage renal disease, recurrent urinary tract infections, COPD, and hypothyroidism. Additionally, the patient had bilateral percutaneous nephrostomy tubes due to previous ureteral obstruction. Upon presentation, the patient was afebrile. His blood pressure was 124/72 mmHg, pulse rate was 82 beats per minute, and respiratory rate was 18 breaths per minute. Beyond the reported fever, review of systems was negative, and he denied recent travel, hospitalization, sick contacts, new medications, or dietary changes. Physical exam was mostly unremarkable, although it was noted that the patient’s left nephrostomy tube and urinary bag appeared purple. He was aware of this recent change, but he dismissed it under the assumption that it was simply an issue with the plastic and ink.

Purple urine bag syndrome (PUBS) is a rare but distinctive cause of a discolored urinary bag, arising in the context of predisposing factors that influence tryptophan metabolism. We report the case of a 78-year-old male with a history of cystoprostatectomy and bilateral nephrostomy tube placement, presenting with a 3- day history of subjective fever. Purple discoloration within his urinary bag was observed on physical exam, prompting urinalysis and culture that revealed evidence of a urinary tract infection (UTI). Although our patient was successfully treated with a short course of ciprofloxacin, there have been reports of poor outcomes in patients with undetected – and thus unaddressed – PUBS. Notably, there are very few cases of PUBS reported in patients with nephrostomy; our case highlights the fact that PUBS can serve as an important clinical clue in these patients, who may lack the typical symptoms of UTI (e.g., dysuria). Recognition of this unusual entity allows timely intervention, preventing progression to far more concerning conditions such as Fournier gangrene, sepsis, or death. First reported in 1978, [1] purple urine bag syndrome (PUBS) is a striking manifestation of urinary tract infection that arises in the context of chronic catheterization and certain predisposing factors. The differential diagnosis for urine discoloration is quite broad; for this reason, prompt recognition of PUBS is crucial not only to reduce morbidity and mortality, but also to curtail medical expenditures by avoiding unnecessary investigations and treatments. The development of PUBS signifies an underlying infection in patients that are, by nature of their comorbidities, considered high-risk. It involves an aberration in the breakdown of dietary tryptophan, which begins in the intestines where gut flora metabolize it to indole. Via portal circulation, indole reaches the liver, where it is conjugated to form indoxyl sulfate for excretion into the urinary tract. In the urine, sulfatase- and phosphatase-producing bacteria convert indoxyl sulfate into indoxyl, which, in the setting of alkaline urine, is oxidized to indigo (blue) and indirubin (red). [2] When these pigments interact within the urinary drainage system, it culminates in the appearance of a purple urine bag. Introduction

A myriad of risk factors create a favorable environment for this condition, several of which were present in our patient. Sabanis et al devised the “ABCDEFGH rule” to characterize susceptible individuals. [3]

Figure 2. Risk factors for Purple Urine Bag Syndrome

ABCDEFGH Rule Alkaline urine Bedridden Constipation Dementia End-stage renal disease Female Growth of bacteria Hygiene poor (i.e., chronically-catheterized)

In the table above, our patient’s risk factors have been highlighted in purple. As a result of impaired clearance, his renal disease led to higher concentrations of indoxyl sulfate. Using indoxyl sulfate as a substrate, bacteria were able to form indoxyl; prolonged use of nephrostomy tubes enabled these bacteria to colonize our patient’s urinary tract. Additionally, his alkaline urine favored the conversion of indoxyl to indigo and indirubin. When these two pigments reacted within his catheter and urine bag, it formed a rich purple hue. Unfortunately, there are no formal guidelines for the diagnosis and treatment of PUBS. Given the spectrum of differential diagnoses for discolored urine, it is imperative to obtain a detailed history in order to exclude other etiologies such as hematuria, porphyria, medications, or diet. Failure to do so may result in tests and treatments that are not only costly, but also ineffective for the patient. When this condition is suspected, a urine dipstick is a quick and cost-effective tool that should be used to confirm an underlying UTI. [4] Culture and sensitivity may be warranted in some cases and can help tailor the antibiotic regimen, if needed. Several organisms have been implicated such as E. coli, Proteus spp., Providencia spp., K. pneumoniae, Enterococci, Morganella morganii, and Pseudomonas ; [4] interestingly, however, not all strains of the same species can produce these enzymes. [5] Because PUBS arises in patients with multiple coexisting risk factors, the morbidity and mortality are higher than with a typical UTI. [6,7] Failure to recognize this condition has resulted in Fournier gangrene, urosepsis, and even death in some cases. [8,9] For this reason, many sources recommend initiation of antibiotics once the diagnosis is made. [10] In addition to antibiotics, it is advisable that the patient’s urinary catheter and drainage bag be replaced. If additional risk factors are present and treatable (e.g., constipation), addressing these can significantly decrease the risk of recurrence.

Figure 1. Pathophysiology of Purple Urine Bag Syndrome

References

Acknowledgements

A urine specimen was subsequently obtained for urine dipstick, with leukocytes and nitrites indicative of a urinary tract infection. His urine was also found to be alkaline with a pH of 8.5, suggesting infection with a urea-splitting organism. While a urine culture was pending, the patient was treated empirically with a 10- day course of ciprofloxacin. In retrospect, his urinary collecting system should have also been replaced at that time; however, he followed up with nephrology shortly afterward and the issue was addressed at that time. Following these measures, the patient experienced resolution of his symptoms.

Acknowledge ments

Thank you to Dr. Millwood for your guidance, as well as the Center for Primary Care in Aiken, SC for allowing students to play a role in the patient care team!

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