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Unexplained leukocytosis in a hospitalized patient
A 70-year-old man is evaluated for a persistent leukocytosis. He was hospitalized 10 days ago for a severe exacerbation of chronic obstructive pulmonary disease. He was intubated for 3 days, was diagnosed with a left lower lobe pneumonia, and was treated with antibiotics. His white blood cell count on admission was 20,000 per mcL. It dropped as low as 15,000 on day 6 but is now 25,000, with 23,000 polymorphonuclear leukocytes (10% band forms). He is on oral prednisone 15 mg once daily. Chest x-ray shows no infiltrate. Urinalysis without WBCs.
What is the most likely cause of his leukocytosis?
A) Pulmonary embolus.
B) Lung abscess.
C) Perinephric abscess.
D) Prednisone.
E) Clostridium difficile infection.
The most likely diagnosis in otherwise unexplained leukocytosis in a hospitalized patient is C. difficile.
Anna Wanahita, MD, of the St. John Clinic in Tulsa, Okla., and her colleagues prospectively studied 60 patients admitted to a VA hospital who had unexplained leukocytosis.1 All patients had stool specimens sent for C. difficile toxin; in addition, 26 hospitalized control patients without leukocytosis also had stool sent for C. difficile toxin. For study purposes, leukocytosis was defined as a WBC greater than 15,000 per mcL. Any patient for whom C. difficile toxin was sent because of clinical suspicion and who was positive was excluded from the study results.
Almost 60% of the patients with unexplained leukocytosis (35 of 60) had a positive C. difficile toxin, compared with 12% of the controls (P less than .001). More than half of the patients with a positive C. difficile test had the onset of leukocytosis prior to any symptoms of colitis. Leukocytosis responded to treatment with metronidazole in 83% of the patients with a positive C. difficile toxin, and 75% of the patients who had leukocytosis did not have a positive C. difficile toxin.
In another study, Mamatha Bulusu, and colleagues did a retrospective study of 70 hospitalized patients who had diarrhea and underwent testing for C. difficile.2 They evaluated the pattern of white blood cell counts in patients who were positive and negative for C. difficile toxin. The mean WBC for C. difficile–positive patients was 15,800, compared with 7,700 for the patients who were C. difficile negative (P less than .01). They described three patterns: one in which leukocytosis occurred at the onset of diarrhea; a pattern in which unexplained leukocytosis occurred days prior to diarrhea; and a pattern in which patients treated for infection with leukocytosis had a worsening of their leukocytosis at the onset of diarrheal symptoms. Treatment with metronidazole led to a resolution of leukocytosis in all the C. difficile–positive patients.
Another possibility in this case was WBC elevation because of the patient’s prednisone. Prednisone can increase WBC as early as the first day of therapy.3 The elevation and rapidity of increase are dose related. The important pearl is that steroid-induced leukocytosis involves an increase of polymorphonuclear white blood cells with a rise in monocytes and a decrease in eosinophils and lymphocytes.
Importantly, increased band forms (greater than 6%) and toxic granulation rarely ever occur with steroid-induced leukocytosis, and the presence of these features should strongly suggest a different cause.4
Pearl: Think of underlying C. difficile infection in your hospitalized patient with unexplained leukocytosis.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.
References
1. Am J Med. 2003 Nov;115(7):543-6.
2. Am J Gastroenterol. 2000 Nov;95(11):3137-41.
3. J Clin Invest. 1975 Oct;56(4):808-13.
4. Am J Med. 1981 Nov;71(5):773-8.
A 70-year-old man is evaluated for a persistent leukocytosis. He was hospitalized 10 days ago for a severe exacerbation of chronic obstructive pulmonary disease. He was intubated for 3 days, was diagnosed with a left lower lobe pneumonia, and was treated with antibiotics. His white blood cell count on admission was 20,000 per mcL. It dropped as low as 15,000 on day 6 but is now 25,000, with 23,000 polymorphonuclear leukocytes (10% band forms). He is on oral prednisone 15 mg once daily. Chest x-ray shows no infiltrate. Urinalysis without WBCs.
What is the most likely cause of his leukocytosis?
A) Pulmonary embolus.
B) Lung abscess.
C) Perinephric abscess.
D) Prednisone.
E) Clostridium difficile infection.
The most likely diagnosis in otherwise unexplained leukocytosis in a hospitalized patient is C. difficile.
Anna Wanahita, MD, of the St. John Clinic in Tulsa, Okla., and her colleagues prospectively studied 60 patients admitted to a VA hospital who had unexplained leukocytosis.1 All patients had stool specimens sent for C. difficile toxin; in addition, 26 hospitalized control patients without leukocytosis also had stool sent for C. difficile toxin. For study purposes, leukocytosis was defined as a WBC greater than 15,000 per mcL. Any patient for whom C. difficile toxin was sent because of clinical suspicion and who was positive was excluded from the study results.
Almost 60% of the patients with unexplained leukocytosis (35 of 60) had a positive C. difficile toxin, compared with 12% of the controls (P less than .001). More than half of the patients with a positive C. difficile test had the onset of leukocytosis prior to any symptoms of colitis. Leukocytosis responded to treatment with metronidazole in 83% of the patients with a positive C. difficile toxin, and 75% of the patients who had leukocytosis did not have a positive C. difficile toxin.
In another study, Mamatha Bulusu, and colleagues did a retrospective study of 70 hospitalized patients who had diarrhea and underwent testing for C. difficile.2 They evaluated the pattern of white blood cell counts in patients who were positive and negative for C. difficile toxin. The mean WBC for C. difficile–positive patients was 15,800, compared with 7,700 for the patients who were C. difficile negative (P less than .01). They described three patterns: one in which leukocytosis occurred at the onset of diarrhea; a pattern in which unexplained leukocytosis occurred days prior to diarrhea; and a pattern in which patients treated for infection with leukocytosis had a worsening of their leukocytosis at the onset of diarrheal symptoms. Treatment with metronidazole led to a resolution of leukocytosis in all the C. difficile–positive patients.
Another possibility in this case was WBC elevation because of the patient’s prednisone. Prednisone can increase WBC as early as the first day of therapy.3 The elevation and rapidity of increase are dose related. The important pearl is that steroid-induced leukocytosis involves an increase of polymorphonuclear white blood cells with a rise in monocytes and a decrease in eosinophils and lymphocytes.
Importantly, increased band forms (greater than 6%) and toxic granulation rarely ever occur with steroid-induced leukocytosis, and the presence of these features should strongly suggest a different cause.4
Pearl: Think of underlying C. difficile infection in your hospitalized patient with unexplained leukocytosis.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.
References
1. Am J Med. 2003 Nov;115(7):543-6.
2. Am J Gastroenterol. 2000 Nov;95(11):3137-41.
3. J Clin Invest. 1975 Oct;56(4):808-13.
4. Am J Med. 1981 Nov;71(5):773-8.
A 70-year-old man is evaluated for a persistent leukocytosis. He was hospitalized 10 days ago for a severe exacerbation of chronic obstructive pulmonary disease. He was intubated for 3 days, was diagnosed with a left lower lobe pneumonia, and was treated with antibiotics. His white blood cell count on admission was 20,000 per mcL. It dropped as low as 15,000 on day 6 but is now 25,000, with 23,000 polymorphonuclear leukocytes (10% band forms). He is on oral prednisone 15 mg once daily. Chest x-ray shows no infiltrate. Urinalysis without WBCs.
What is the most likely cause of his leukocytosis?
A) Pulmonary embolus.
B) Lung abscess.
C) Perinephric abscess.
D) Prednisone.
E) Clostridium difficile infection.
The most likely diagnosis in otherwise unexplained leukocytosis in a hospitalized patient is C. difficile.
Anna Wanahita, MD, of the St. John Clinic in Tulsa, Okla., and her colleagues prospectively studied 60 patients admitted to a VA hospital who had unexplained leukocytosis.1 All patients had stool specimens sent for C. difficile toxin; in addition, 26 hospitalized control patients without leukocytosis also had stool sent for C. difficile toxin. For study purposes, leukocytosis was defined as a WBC greater than 15,000 per mcL. Any patient for whom C. difficile toxin was sent because of clinical suspicion and who was positive was excluded from the study results.
Almost 60% of the patients with unexplained leukocytosis (35 of 60) had a positive C. difficile toxin, compared with 12% of the controls (P less than .001). More than half of the patients with a positive C. difficile test had the onset of leukocytosis prior to any symptoms of colitis. Leukocytosis responded to treatment with metronidazole in 83% of the patients with a positive C. difficile toxin, and 75% of the patients who had leukocytosis did not have a positive C. difficile toxin.
In another study, Mamatha Bulusu, and colleagues did a retrospective study of 70 hospitalized patients who had diarrhea and underwent testing for C. difficile.2 They evaluated the pattern of white blood cell counts in patients who were positive and negative for C. difficile toxin. The mean WBC for C. difficile–positive patients was 15,800, compared with 7,700 for the patients who were C. difficile negative (P less than .01). They described three patterns: one in which leukocytosis occurred at the onset of diarrhea; a pattern in which unexplained leukocytosis occurred days prior to diarrhea; and a pattern in which patients treated for infection with leukocytosis had a worsening of their leukocytosis at the onset of diarrheal symptoms. Treatment with metronidazole led to a resolution of leukocytosis in all the C. difficile–positive patients.
Another possibility in this case was WBC elevation because of the patient’s prednisone. Prednisone can increase WBC as early as the first day of therapy.3 The elevation and rapidity of increase are dose related. The important pearl is that steroid-induced leukocytosis involves an increase of polymorphonuclear white blood cells with a rise in monocytes and a decrease in eosinophils and lymphocytes.
Importantly, increased band forms (greater than 6%) and toxic granulation rarely ever occur with steroid-induced leukocytosis, and the presence of these features should strongly suggest a different cause.4
Pearl: Think of underlying C. difficile infection in your hospitalized patient with unexplained leukocytosis.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.
References
1. Am J Med. 2003 Nov;115(7):543-6.
2. Am J Gastroenterol. 2000 Nov;95(11):3137-41.
3. J Clin Invest. 1975 Oct;56(4):808-13.
4. Am J Med. 1981 Nov;71(5):773-8.
Nocturia and sleep apnea
Author’s note: I have been writing “Myth of the Month” columns for the last several years. I will try to continue to write about myths when possible, but I would like to introduce a new column, “Pearl of the Month.” I want to share with you pearls that I have found really helpful in medical practice. Some of these will be new news, while some may be old news that may not be well known.
A 65-year-old man comes to a clinic concerned about frequent nocturia. He is getting up four times a night to urinate, and he has been urinating about every 5 hours during the day. He has been seen twice for this problem and was diagnosed with benign prostatic hyperplasia and started on tamsulosin.
He found a slight improvement when he started on 0.4 mg qhs, reducing his nocturia episodes from four to three. His dose was increased to 0.8 mg qhs, with no improvement in nocturia.
Exam today: BP, 140/94; pulse, 70. Rectal exam: Prostate is twice normal size without nodules. Labs: Na, 140; K, 4.0; glucose, 80; Ca, 9.6.
He is frustrated because he feels tired and sleepy from having to get up so often to urinate every night.
What is the best treatment/advice at this point?
A. Check hemoglobin A1C.
B. Start finasteride.
C. Switch tamsulosin to terazosin.
D. Evaluate for sleep apnea.
At this point, I think an evaluation for sleep apnea is the next appropriate step. It is unlikely that he has diabetes with high enough blood sugars to cause polyuria, with a random glucose of 80. His daytime sleepiness is a clue to a possible sleep disorder, and his nocturia is a symptom that is often overlooked or not appreciated in patients with sleep apnea.
Umpei Yamamoto, MD, of Kyushu University Hospital, Japan, and colleagues studied the prevalence of sleep-disordered breathing among patients who presented to a urology clinic with nocturia and in those who visited a sleep apnea clinic with symptoms of excessive daytime sleepiness.1 Sleep-disordered breathing was found in 91% of the patients from the sleep apnea clinic and 70% of the patients from the urology clinic. The frequency of nocturia was reduced with continuous positive airway pressure (CPAP) in both groups in the patients who had not responded to conventional therapy or nocturia.
The symptom of nocturia as a symptom of sleep apnea might be even more common in women.2 Ozen K. Basoglu, MD, and Mehmet Sezai Tasbakan, MD, of Ege University, Izmir, Turkey, described clinical similarities and differences based on gender in a large group of patients with sleep apnea. Both men and women with sleep apnea had similar rates of excessive daytime sleepiness, snoring, and impaired concentration. Women had more frequent nocturia.
Nocturia especially should be considered a possible clue for the presence of sleep apnea in younger patients who have fewer other reasons to have nocturia. Takahiro Maeda, MD, of Keio University, Tokyo, and colleagues found that men younger than 50 years had more nocturnal urinations the worse their apnea-hypopnea index was.3 Overall in the study, 85% of the patients had a reduction in nighttime urination after CPAP therapy.
Treatment of sleep apnea has been shown in several studies to improve the nocturia that occurs in patients with sleep apnea. Hyoung Keun Park, MD, of Konkuk University, Seoul, and colleagues studied whether surgical intervention with uvulopalatopharyngoplasty (UPPP) reduced nocturia in patients with sleep apnea.4 In the study, there was a 73% success rate in treatment for sleep apnea with the UPPP surgery, and, among those who had successful surgeries, nocturia episodes decreased from 1.9 preoperatively to 0.7 postoperatively (P less than .001).
Minoru Miyazato, MD, PhD, of University of the Ryukyus, Okinawa, Japan, and colleagues looked at the effect of CPAP treatment on nighttime urine production in patients with obstructive sleep apnea.5 In this small study of 40 patients, mean nighttime voiding episodes decreased from 2.1 to 1.2 (P less than .01).
I think that this information helps us increase our recognition of sleep apnea and also counsel patients on the benefits of treatment.
Pearl: Sleep apnea should be considered in the differential diagnosis of patients with nocturia, and treatment of sleep apnea may decrease nocturia.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.
References
1. Intern Med. 2016;55(8):901-5.
2. Sleep Breath. 2017 Feb 14. doi: 10.1007/s11325-017-1482-9.
3. Can Urol Assoc J. 2016 Jul-Aug;10(7-8):E241-5.
4. Int Neurourol J. 2016 Dec;20(4):329-34.
5. Neurourol Urodyn. 2017 Feb;36(2):376-9.
Author’s note: I have been writing “Myth of the Month” columns for the last several years. I will try to continue to write about myths when possible, but I would like to introduce a new column, “Pearl of the Month.” I want to share with you pearls that I have found really helpful in medical practice. Some of these will be new news, while some may be old news that may not be well known.
A 65-year-old man comes to a clinic concerned about frequent nocturia. He is getting up four times a night to urinate, and he has been urinating about every 5 hours during the day. He has been seen twice for this problem and was diagnosed with benign prostatic hyperplasia and started on tamsulosin.
He found a slight improvement when he started on 0.4 mg qhs, reducing his nocturia episodes from four to three. His dose was increased to 0.8 mg qhs, with no improvement in nocturia.
Exam today: BP, 140/94; pulse, 70. Rectal exam: Prostate is twice normal size without nodules. Labs: Na, 140; K, 4.0; glucose, 80; Ca, 9.6.
He is frustrated because he feels tired and sleepy from having to get up so often to urinate every night.
What is the best treatment/advice at this point?
A. Check hemoglobin A1C.
B. Start finasteride.
C. Switch tamsulosin to terazosin.
D. Evaluate for sleep apnea.
At this point, I think an evaluation for sleep apnea is the next appropriate step. It is unlikely that he has diabetes with high enough blood sugars to cause polyuria, with a random glucose of 80. His daytime sleepiness is a clue to a possible sleep disorder, and his nocturia is a symptom that is often overlooked or not appreciated in patients with sleep apnea.
Umpei Yamamoto, MD, of Kyushu University Hospital, Japan, and colleagues studied the prevalence of sleep-disordered breathing among patients who presented to a urology clinic with nocturia and in those who visited a sleep apnea clinic with symptoms of excessive daytime sleepiness.1 Sleep-disordered breathing was found in 91% of the patients from the sleep apnea clinic and 70% of the patients from the urology clinic. The frequency of nocturia was reduced with continuous positive airway pressure (CPAP) in both groups in the patients who had not responded to conventional therapy or nocturia.
The symptom of nocturia as a symptom of sleep apnea might be even more common in women.2 Ozen K. Basoglu, MD, and Mehmet Sezai Tasbakan, MD, of Ege University, Izmir, Turkey, described clinical similarities and differences based on gender in a large group of patients with sleep apnea. Both men and women with sleep apnea had similar rates of excessive daytime sleepiness, snoring, and impaired concentration. Women had more frequent nocturia.
Nocturia especially should be considered a possible clue for the presence of sleep apnea in younger patients who have fewer other reasons to have nocturia. Takahiro Maeda, MD, of Keio University, Tokyo, and colleagues found that men younger than 50 years had more nocturnal urinations the worse their apnea-hypopnea index was.3 Overall in the study, 85% of the patients had a reduction in nighttime urination after CPAP therapy.
Treatment of sleep apnea has been shown in several studies to improve the nocturia that occurs in patients with sleep apnea. Hyoung Keun Park, MD, of Konkuk University, Seoul, and colleagues studied whether surgical intervention with uvulopalatopharyngoplasty (UPPP) reduced nocturia in patients with sleep apnea.4 In the study, there was a 73% success rate in treatment for sleep apnea with the UPPP surgery, and, among those who had successful surgeries, nocturia episodes decreased from 1.9 preoperatively to 0.7 postoperatively (P less than .001).
Minoru Miyazato, MD, PhD, of University of the Ryukyus, Okinawa, Japan, and colleagues looked at the effect of CPAP treatment on nighttime urine production in patients with obstructive sleep apnea.5 In this small study of 40 patients, mean nighttime voiding episodes decreased from 2.1 to 1.2 (P less than .01).
I think that this information helps us increase our recognition of sleep apnea and also counsel patients on the benefits of treatment.
Pearl: Sleep apnea should be considered in the differential diagnosis of patients with nocturia, and treatment of sleep apnea may decrease nocturia.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.
References
1. Intern Med. 2016;55(8):901-5.
2. Sleep Breath. 2017 Feb 14. doi: 10.1007/s11325-017-1482-9.
3. Can Urol Assoc J. 2016 Jul-Aug;10(7-8):E241-5.
4. Int Neurourol J. 2016 Dec;20(4):329-34.
5. Neurourol Urodyn. 2017 Feb;36(2):376-9.
Author’s note: I have been writing “Myth of the Month” columns for the last several years. I will try to continue to write about myths when possible, but I would like to introduce a new column, “Pearl of the Month.” I want to share with you pearls that I have found really helpful in medical practice. Some of these will be new news, while some may be old news that may not be well known.
A 65-year-old man comes to a clinic concerned about frequent nocturia. He is getting up four times a night to urinate, and he has been urinating about every 5 hours during the day. He has been seen twice for this problem and was diagnosed with benign prostatic hyperplasia and started on tamsulosin.
He found a slight improvement when he started on 0.4 mg qhs, reducing his nocturia episodes from four to three. His dose was increased to 0.8 mg qhs, with no improvement in nocturia.
Exam today: BP, 140/94; pulse, 70. Rectal exam: Prostate is twice normal size without nodules. Labs: Na, 140; K, 4.0; glucose, 80; Ca, 9.6.
He is frustrated because he feels tired and sleepy from having to get up so often to urinate every night.
What is the best treatment/advice at this point?
A. Check hemoglobin A1C.
B. Start finasteride.
C. Switch tamsulosin to terazosin.
D. Evaluate for sleep apnea.
At this point, I think an evaluation for sleep apnea is the next appropriate step. It is unlikely that he has diabetes with high enough blood sugars to cause polyuria, with a random glucose of 80. His daytime sleepiness is a clue to a possible sleep disorder, and his nocturia is a symptom that is often overlooked or not appreciated in patients with sleep apnea.
Umpei Yamamoto, MD, of Kyushu University Hospital, Japan, and colleagues studied the prevalence of sleep-disordered breathing among patients who presented to a urology clinic with nocturia and in those who visited a sleep apnea clinic with symptoms of excessive daytime sleepiness.1 Sleep-disordered breathing was found in 91% of the patients from the sleep apnea clinic and 70% of the patients from the urology clinic. The frequency of nocturia was reduced with continuous positive airway pressure (CPAP) in both groups in the patients who had not responded to conventional therapy or nocturia.
The symptom of nocturia as a symptom of sleep apnea might be even more common in women.2 Ozen K. Basoglu, MD, and Mehmet Sezai Tasbakan, MD, of Ege University, Izmir, Turkey, described clinical similarities and differences based on gender in a large group of patients with sleep apnea. Both men and women with sleep apnea had similar rates of excessive daytime sleepiness, snoring, and impaired concentration. Women had more frequent nocturia.
Nocturia especially should be considered a possible clue for the presence of sleep apnea in younger patients who have fewer other reasons to have nocturia. Takahiro Maeda, MD, of Keio University, Tokyo, and colleagues found that men younger than 50 years had more nocturnal urinations the worse their apnea-hypopnea index was.3 Overall in the study, 85% of the patients had a reduction in nighttime urination after CPAP therapy.
Treatment of sleep apnea has been shown in several studies to improve the nocturia that occurs in patients with sleep apnea. Hyoung Keun Park, MD, of Konkuk University, Seoul, and colleagues studied whether surgical intervention with uvulopalatopharyngoplasty (UPPP) reduced nocturia in patients with sleep apnea.4 In the study, there was a 73% success rate in treatment for sleep apnea with the UPPP surgery, and, among those who had successful surgeries, nocturia episodes decreased from 1.9 preoperatively to 0.7 postoperatively (P less than .001).
Minoru Miyazato, MD, PhD, of University of the Ryukyus, Okinawa, Japan, and colleagues looked at the effect of CPAP treatment on nighttime urine production in patients with obstructive sleep apnea.5 In this small study of 40 patients, mean nighttime voiding episodes decreased from 2.1 to 1.2 (P less than .01).
I think that this information helps us increase our recognition of sleep apnea and also counsel patients on the benefits of treatment.
Pearl: Sleep apnea should be considered in the differential diagnosis of patients with nocturia, and treatment of sleep apnea may decrease nocturia.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.
References
1. Intern Med. 2016;55(8):901-5.
2. Sleep Breath. 2017 Feb 14. doi: 10.1007/s11325-017-1482-9.
3. Can Urol Assoc J. 2016 Jul-Aug;10(7-8):E241-5.
4. Int Neurourol J. 2016 Dec;20(4):329-34.
5. Neurourol Urodyn. 2017 Feb;36(2):376-9.