Purple Urine Bag Syndrome in Rehabilitation

Rehabilitation physicians will occasionally encounter patients with urine discoloration. The spectrum of discoloration can vary from a red to orange to purple, and these discolorations may indicate a benign condition or potentially serious medical pathology. For example, green discoloration may indicate urinary tract infection, bile problems, or excess of B vitamins, whereas red discoloration may indicate acidic urine caused by certain foods, medications (eg, rifampin and doxorubicin), or a primary urological pathology [1-3]. Brown urine can represent a serious medical condition, such as liver disease, acute renal failure, melanoma, or copper and phenol poisoning [1-3]. Purple discoloration is a rare phenomenon and may be alarming to the patient, patient's family members, and rehabilitation staff. Etiologies include medications with iodine-containing compounds, consumption of beets, porphyria, methylene blue, and pseudomonas bacterial infection [1, 3]. One uncommon clinical entity that causes purple discoloration of the plastic urinary drainage bag and tubing without discoloration of the urine is known as purple urine bag syndrome (PUBS). PUBS occurs predominantly in elderly women with chronic urinary catheterization and constipation. Although this condition might be expected in a rehabilitation setting, we have not identified any reported cases of PUBS in rehabilitation patients. This report provides a review of the pathogenesis, clinical features, and management of PUBS, as well as rehabilitation implications. A 48-year-old man was admitted to the acute rehabilitation unit with ischemic encephalopathy status after cardiac arrest. His medical history included diabetes mellitus type 2, coronary artery disease, history of coronary artery bypass, a chronic indwelling urinary catheter secondary to his debilitation, and chronic urinary tract infections. The patient's social history was positive for smoking 1 pack per day for 30 years and alcohol abuse. He denied any history of illicit drug use. Medications included lisinopril, atorvastatin, colace, risperidone, insulin NPH, aspirin, carvedilol, pantoprazole, furosemide, and potassium chloride. On physical examination, the patient's vital signs were within normal limits. Palpation of his abdomen showed distention and a palpable bladder. There was trace pitting edema of the bilateral lower extremities. Visual inspection of the urinary drainage bag and tubing revealed purple discoloration (Figure 1); however, the color of the urine inside the bag was unremarkable. Laboratory data revealed a normal complete blood count. His urinalysis revealed a pH 8.0, protein of 100 mg/dL, too-numerous-to-count white blood cells per high power field, positive leukocyte esterase, negative nitrates, red blood cells 10 to 15 per high power field, and marked bacteria. His urine culture grew Escherichia coli (>100,000 colony-forming units/mL). An ultrasound of the urinary bladder demonstrated a distended urinary bladder and the presence of echogenic sediment, findings suggestive of chronic bladder obstruction. Subsequently, his indwelling urinary catheter and drainage bag were changed. Shortly afterwards, his collecting urine bag turned purple in color. Plastic urinary drainage bag and tubing with purple discoloration. A diagnosis of urinary tract infection was made, and he was appropriately treated with trimethoprim/sulfamethoxazole for 14 days. After 2 weeks of antibiotic treatment, the patient's urine bag purple discoloration disappeared. Urine discoloration is not an uncommon clinical feature seen in rehabilitation patients, but a purple discoloration of urinary drainage bag and tubing is a rare phenomenon. Purple urine has been implicated in medications with iodine-containing compounds, consumption of beets, porphyria, methylene blue, and pseudomonas bacterial infection [2, 3]. However, PUBS is the result of a different mechanism in which the urine discolors the plastic urinary bag, and the urine content itself is generally clear. Although PUBS is an infrequent finding, prevalence is as high as 9.8% in nursing facility patients [4]. Purple urinary bag discoloration was first reported by Barlow and Dickson in 1978 and was believed to be related to tryptophan metabolism in the setting of bowel obstruction and constipation [5, 6]. Early analysis suggested the presence of indigo related to the bacterial tryptophan metabolism in the intestinal tract, which results in the production of indole. Indole is further decomposed to indoxyl sulfate (indican) and ultimately excreted to the urine, where indican is oxidized into indigo blue [6]. Although this theory recognized the etiology of the purple discoloration, there was still controversy regarding the characterization of PUBS-causing factors. As a result, multiple theories have evolved to determine other possible factors leading to PUBS. The currently accepted theories on the pathogenesis of PUBS rely on multiple factors involving the intestinal tract, liver, and urinary tract. Initially, dietary tryptophan is metabolized to indole by intestinal bacterial flora containing tryptophanase, such as Escherichia coli [7]. Increased serum indole also may occur in patients with constipation, intestinal dysmotility, and bacterial overgrowth, increasing tryptophan metabolism which leads to abnormal absorption of indole into the blood circulation [8]. The indole produced is absorbed into the portal circulation, where the liver conjugates indole to indoxyl sulfate (indican). Indican is excreted in the urine and digested by bacterial phosphatase and sulfatase by certain bacteria to produce indoxyl. Oxidation of indoxyl occurs in an alkaline urine environment, resulting in the production of indigo (blue) and indirubin (red) [4, 6, 9]. These 2 pigments are then dissolved and react with plastic urinary bag and tubing, leading to the purple discoloration seen in urinary bag and tubing, while leaving the urine clear in color. Figure 2 displays the pathogenesis of PUBS [10]. The pathogenesis of purple urine bag syndrome. The purple discoloration occurs regardless of the type of material or manufacturer of urinary plastic drainage bags or catheter, as demonstrated by Su et al [11]. In addition, Su et al [11] showed the intensity of the purple stain varied with room temperature secondary to bacterial fermentation. Because intestinal bacterial metabolism is involved in this process, a diet high in tryptophan may increase the risk of developing PUBS [4, 11]. Several cases studies have described the relationship between PUBS and urinary tract infections, particularly gram-negative bacteria producing sulfatase and phosphatase, such as Providencia stuartii, Klebsiella pneumonaie, Proteus mirabilis, Escherichia coli, Pseudomonas aeruginosa, and Enterobacter agglomerans. These bacteria have been shown to produce blue-colored colonies [6, 12]. In addition, if more than one bacterial species is present in the urine, this could enhance enzymatic activity, ultimately leading to increased pigment formation [6]. Some bacterial species lacking sulfatase and phosphatase activities also have been isolated from urine in PUBS patients. The only consistent finding in these patients was that alkaline urine was present, suggesting that urine alkalinization and oxidation are important promoting factors in discoloration of the urinary plastic bag. Besides the bacterial species mentioned previously, a number of other bacterial species also have been isolated and have been proposed in the pathogenesis of PUBS, as shown in Table 1 [11, 13, 14]. The prevalence of PUBS in acute inpatient rehabilitation units appears low. As noted previously, elderly women are more prone to this disorder, likely related to anatomic considerations, increased rate of chronic catheterization compared with men, and the association of vaginal discharge and urinary infections [15-18]. The reason for the low frequency of PUBS overall may be attributable to the intense bladder and bowel programs offered in the rehabilitation facilities upon admission, including regular changing or discontinuation of indwelling urinary catheters to prevent urinary tract infections and bowel regimens to prevent constipation. Adequate bowel programs combined with balanced meals offered by dieticians to prevent excessive tryptophan ingestion may contribute to the low occurrence of PUBS in inpatient rehabilitation. However, patients transferred from an acute hospital or other setting to inpatient rehabilitation may have some of these conditions, which will predispose them to PUBS. The rehabilitation physician and staff play important roles to initiate bladder and bowel regimens and maintaining appropriate nutrition for these patients to prevent PUBS. PUBS also can be associated with other conditions that may be seen in certain rehabilitation settings. Barlow and Dickson [5] first reported PUBS in patients with spina bifida and urinary diversions. Hildreth and Cass [19] reported 5 cases of PUBS in patients with ileal diversion with urinary tract infections. Drummond et al [20] reported PUBS associated with the blue diaper syndrome, a condition related to tryptophan metabolism in the intestines causing indicanuria. PUBS also has been reported in patients with urostomies and hyperchloremic metabolic acidosis secondary to loss of bicarbonate through the ileal or sigmoid pouch, leading to increase in urine alkalinization [12, 13, 21]. Recently, Pillai et al [22] described PUBS related to a patient with intussusception, causing intestinal obstruction and increased tryptophan metabolism and indole absorption to the portal circulation. Also, Wang et al and Ting et al reported PUBS related with hemodialysis patients caused by the decreased removal of indoxyl sulfate during hemodialysis [23, 24]. Although the clinical feature of purple discoloration of urine may suggest a significant underlying pathology, most patients with PUBS are clinically asymptomatic [25, 26]. This is not to say that PUBS is totally benign syndrome because PUBS can rarely be associated with sepsis. However, some authors argue that aggressive treatment of PUBS is not necessary [11, 26]. Prevention of recurrence of PUBS involves the appropriate treatment of the urinary tract infection, changing of indwelling long-term urinary catheters (if needed) on a regular basis, and treating constipation or other underlying gastrointestinal disorders. The presence of purple discoloration of a urinary bag and catheter may appear alarming to the patient and rehabilitation physician. Although PUBS is a rare phenomenon, especially in the rehabilitation unit, it is helpful for clinicians to be aware of this condition. Multiple factors involving the gastrointestinal tract, liver, and urinary tract may cause PUBS, and these are usually easily treatable once identified. Because urinary tract infection is one of the predisposing factors, the selection of the appropriate antibiotic on the basis of culture and sensitivity is vital to treat this syndrome and to also prevent future bacterial resistance. Patients and the rehabilitation staff should be aware that purple discoloration may linger for at least a week after the initial antibiotic treatment [13]. Gastrointestinal disorders also are predisposing factor to PUBS; therefore, its occurrence may also be an indicator of a suboptimal bowel-management program.