How can I tell if my febrile patient who uses IV drugs had cotton fever?

Although IV drug use (IVDU) is associated with febrile illness of numerous etiologies (eg, soft tissue infections, pneumonia, bacteremia, endocarditis), certain features of a febrile illness may be helpful in considering cotton fever (CF) as the cause.1-3

First, onset of fever—often associated with chills, shortness of breath, nausea, vomiting, headache, abdominal pain and myalgias—in CF is usually manifest within 10-30 minutes of drug injection. Second, infectious disease workup, including blood cultures and chest radiograph, are unrevealing despite clinical signs of systemic inflammatory response syndrome (SIRS), such as leukocytosis, tachypnea and tachycardia. Third, symptoms and clinical signs of inflammation usually resolve or improve within 6-12 h of onset (less commonly up to 24-48 h). Nevertheless, CF remains a diagnosis of exclusion.

As for the cause of CF, the most widely-held theory revolves around the endotoxin of Pentoea agglomerans (formerly Enterobacter agglomerans), a gram-negative rod that colonizes cotton plants. Since cotton is often used as a filter during injection of illicit substances, any endotoxin present in the cotton is also injected resulting in abrupt onset of a febrile illness. Of note, the toxin is water soluble and heating (often part of the preparation of the drug) enhances its toxic effect.3

References

  1. Zerr AM, Ku K, Kara A. Cotton Fever: a condition self-diagnosed by IV drug users. JABFM 2016;29: 276-279.PDF
  2. Xie Y, Pope BA, Hunter AJ. Cotton fever: does the patient know best? J Gen Intern Med 31:442-4. PDF
  3. Torka P, Gill S. Cotton fever: an evanescent process mimicking sepsis in an intravenous drug abuser. J Emerg Med 2013;44:e385-e387. PDF
How can I tell if my febrile patient who uses IV drugs had cotton fever?

How accurate are peripheral thermometers for estimating body temperature in my patient with chills?

Though convenient, oral, tympanic membrane, axillary, and temporal artery thermometers (AKA “peripheral thermometers”) may not be highly accurate in measuring body temperature.

A 2015 systematic review and meta-analysis of the performance of peripheral thermometers involving 75 studies (mostly in adults) found that compared to central thermometers (eg, pulmonary artery, urinary bladder, rectal), peripheral thermometers had a low sensitivity (64%, 95% CI 55%-72%), but much better specificity (96%, 95% CI 93%-97%) for fever (most commonly defined as 37.8° C [100° F] or greater).1

In the same study, for oral electronic thermometers, sensitivity was 74% with a specificity of 86%. For temporal artery thermometers, sensitivities ranged from 26% to 91%, while specificities ranged from 67% to 100%. For tympanic membrane thermometers, sensitivities ranged from 23% to 87%, with a specificity of 57% to 99%.

A 2016 study involving adult emergency department patients reported the sensitivity of peripheral thermometers (vs rectal temperature 38 C [100.4] or higher) as follows: oral (37%), tympanic membrane (68%), and temporal artery (71%). Specificity for fever was >90% for all peripheral thermometers. 2

So, it looks like while we may be pretty comfortable with a diagnosis of “fever” when our patient with chills has a high temperature recorded by a peripheral thermometer, lack of fever alone by these devices should not veer us away from the possibility of systemic infection. When in doubt and if possible, check a rectal temperature.

References

  1. Niven DJ, Gaudet JE, Laupland KB. Accuracy of peripheral thermometers for estimating temperature: A systematic and meta-analysis. Ann Intern Med 2015;163:768-777. https://www.ncbi.nlm.nih.gov/pubmed/26571241
  2. Bijur PE, Shah PD, Esses D. Temperature measurement in the adult emergency department: oral tympanic membrane and temporal artery temperatures versus rectal temperature. Emerg Med J 2016;33:843-7. https://www.ncbi.nlm.nih.gov/pubmed/27334759

 

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How accurate are peripheral thermometers for estimating body temperature in my patient with chills?

My elderly nursing home patient is admitted with recent poor oral intake, falls and oral temperatures of 99.1°-99.3° F(37.3°-37.4°C). Is she considered febrile at these temperatures?

Yes! Even though we often think of temperatures of 100.4°F (38° C) or greater as fever, older people often fail to mount an appropriate febrile response despite having a serious infection. 1

Infectious Diseases Society of America (IDSA) guideline on evaluation of fever in older adult residents of long-term care facilities has defined fever in this population as:2

  • Single oral temperature >100° F (>37.8° C) OR
  • Repeated oral temperatures >99° F (>37.2° C) OR
  • Rectal temperatures >99.5° F (>37.5° C) OR
  • Increase in temperature of >2° F (>1.1° C) over the baseline temperature

Even at these lower than traditional thresholds for defining fever, remember that many infected elderly patients may still lack fever. In a study involving bacteremic patients, nearly 40% of those 80 years of age or older did not have fever (defined as maximum temperature over 24 hrs 100° F [37.8°C] or greater).3  

So our patient meets the criteria for fever as suggested by IDSA guidelines and, particularly in light of her recent poor intake and falls, may need evaluation for a systemic source of infection.

Now that’s interesting! Did you know that blunted febrile response of the aged to infections may be related to the inability of cytokines (eg, IL-1) to reach the central nervous system?1

References 

  1. Norman DC. Fever in the elderly. Clin Infect Dis 2000;31:148-51. https://academic.oup.com/cid/article/31/1/148/318030
  2. High KP, Bradley SF, Gravenstein S, et al. Clinical practice guidelines for the evaluation of fever and infection in older adult residents of long-term care facilities: 2008 update by the Infectious Disease Society of America. Clin Infect Dis 2009;48:149-71. http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Fever%20and%20Long%20Term%20Care.pdf
  3. Manian FA. Fever, abnormal white blood cell count, neutrophilia, and elevated serum C-reactive protein in adult hospitalized patients with bacteremia. South Med J 2012;105;474-78. http://europepmc.org/abstract/med/22948327
My elderly nursing home patient is admitted with recent poor oral intake, falls and oral temperatures of 99.1°-99.3° F(37.3°-37.4°C). Is she considered febrile at these temperatures?

Can I rely on the physical exam to rule out symptomatic urinary tract infection (UTI) in my hospitalized patient?

Suprapubic tenderness, costovertebral angle tenderness (CVAT) and fever seem to be more helpful in ruling in than ruling out infection. And, before you hang your hat on the available data, remember that most of the studies involve women with uncomplicated UTI in primary care or emergency department settings, not our older hospitalized patients at risk of complicated infections.  With these caveats in mind….

Suprapubic tenderness has been reported in only about 15-20% of women with acute cystitis. 1

CVAT has been associated with symptomatic UTI but with only a weakly positive LR (1.7, 1.1-2.5), and an insignificant negative LR. 2  In a single center study involving hospitalized patients (mean age 53 y), CVAT was either absent or “obscure” in about 10% of patients with acute pyelonephritis on CT.3

Fever was associated with a positive likelihood ratio (1.6, 1.0-2.6) by 1 systematic study 2 but not another, 4 with insignificant negative LR in both. Fever was also absent in about 10% of hospitalized patients with pyelonephritis in the single center study above.3

So, when evaluating a patient with possible symptomatic UTI (particularly cystitis), the presence of physical exam findings  may be more helpful than their absence.

References

  1. Kurowski K. The woman with dysuria. Am Fam Physician 1998, 57:2155-2164. https://www.aafp.org/afp/1998/0501/p2155.html
  2. Bent S, Nallamothu BK, Simel DL, et al. Does this woman have an acute uncomplicated urinary tract infection? JAMA 2002;287:2701-2710. https://www.ncbi.nlm.nih.gov/pubmed/12020306
  3. Lee Y-J, Cho S, Kim SR. Unilateral and bilateral acute pyelonephritis: differences in clinical presentation, progress and outcome. Postgrad Med 2014;90:80-85. https://www.ncbi.nlm.nih.gov/pubmed/24255118
  4. Median-Bombardo D, Jover-Palmer A. Does clinical examination aid in the diagnosis of urinary tract infections in women? A systematic review and meta-analysis. BMC Family Practice 2011;12:111. https://bmcfampract.biomedcentral.com/articles/10.1186/1471-2296-12-111
Can I rely on the physical exam to rule out symptomatic urinary tract infection (UTI) in my hospitalized patient?

My previously healthy 55 year old patient is admitted with a respiratory tract infection and a respiratory rate of 22 breaths/min. Should I be concerned?

Any respiratory rate (RR) greater than 20/min in an adult patient may be cause for concern, particularly in the setting of potentially serious disease and absence of an obvious cause such as pain or fever.

Our patient’s RR is outside the commonly cited normal range of 12-20/min. It indicates increased alveolar ventilation which may in turn be caused by hypoxia, hypercapnea, or metabolic acidosis, all portending possibly poor outcome, if left untreated.It’s no surprise that an abnormal RR is often the first sign of clinical deterioration.2 RR is also the least likely of the vital signs to be affected by polypharmacy (eg, NSAIDs affecting temperature, beta-blockers affecting heart rate and blood pressure). 

Another reason for not dismissing an RR of 22 in our patient is the common practice of guessing rather than measuring the RR by healthcare providers in part likely due to the  more “labor-intensive” nature of measuring RRs compared to other vital signs and lack of appreciation for its importance in assessing severity of disease. 1 Of note, in an experimental study of doctors viewing videos of mock patients, over 50% failed to detect abnormal RR when using the “spot” technique of estimating without a timer.3 Even when presented with a RR of 30/min, over 20% of doctors reported it as normal (12-20/min)!

Final tidbit: Do you want to know what a RR of 20/min really feels like? Take a breath every 3 seconds.  If you are like most, it doesn’t feel “normal”!

References
1. Cretikos MA, Bellomo R, Hillman K. Respiratory rate: the neglected vital sign. MJA 2008;188:657-59. https://www.ncbi.nlm.nih.gov/pubmed/18513176
2. Flenady T, Dwer T, Applegarth J. Accurate respiratory rates count: So should you! Australas Emerg Nurs J 2017; 20:45-47. https://www.ncbi.nlm.nih.gov/pubmed/28073649
3. Philip KEJ, Pack E, Cambiano V et al. The accuracy of respiratory rate assessment by doctors in a London teaching hospital: a cross-sectional study. J Clin Monit Comput2015;29:455-60. https://www.ncbi.nlm.nih.gov/pubmed/25273624

My previously healthy 55 year old patient is admitted with a respiratory tract infection and a respiratory rate of 22 breaths/min. Should I be concerned?

My patient with aortic sclerosis has a loud systolic ejection murmur. What is the exact mechanism of this murmur?

We usually blame cardiac murmurs on the “turbulence” caused by blood flowing past an irregular valve surface but, believe it or not, how the murmur is created has been a matter of controversy. 1-4

For sure, murmurs are generated by disturbance of laminar blood flow (ie, turbulence) but over the years many have argued that turbulence per se fails to produce adequate acoustic force to be audible at the chest wall.2 Although challenged by some,1  the concept of “vortex shedding” borrowed from fluid dynamics is fascinating and has been proposed as a potential explanation.

Per this theory, just as a boulder causes a stream to separate and generate vortices, valves (particularly when abnormal) also create vortices. As the vortices are shed near the valve, they leave in their place relatively calm wakes which are then rapidly filled by flowing blood, creating the sound of a murmur.  

Two important variables in this theory are velocity and viscosity. When the velocity of blood flow increases substantially as in high cardiac output states (eg, fever, pregnancy), vortex shedding and the intensity of the murmur also increase. Similar phenomenon may be expected when the blood viscosity is lowered (eg, in anemia).

 

References

  1. Sabbah HN, Stein PD. Turbulent blood flow in humans: Its primary role in the production of ejection murmurs. Circ Res 1976;38: 513-24. https://www.ncbi.nlm.nih.gov/pubmed/1269101
  2. Alpert MA, Systolic murmurs. In Walker HK, Hall WD, Hurst JW. Clinical methods: The history, physical, and laboratory examinations. 3rd ed. Butterworths, Boston, 1990. https://www.ncbi.nlm.nih.gov/books/NBK345/
  3. Bruns D. A general theory of the causes of murmurs in the cardiovascular system. Am J Med 1959;27:360-74. http://www.amjmed.com/article/0002-9343(59)90002-6/fulltext
  4. Guntheroth WG. Innocent murmurs: A suspect diagnosis in non-pregnant adults. Am J Cardiol 2009;104:735-7. https://www.ncbi.nlm.nih.gov/pubmed/19699354
My patient with aortic sclerosis has a loud systolic ejection murmur. What is the exact mechanism of this murmur?

My patient with ulcerative colitis has had colectomy. Can she still get C. difficile infection?

Yes! Although a common cause of colitis, an increasing number of reports in the literature suggest C. difficile can cause enteritis as well.Antibiotic use is a major risk factor in most reports, with nearly one-half of the cases reported in patients with inflammatory bowel disease, many post-colectomy. 1-3

Mortality of C. difficile enteritis based on the first 83 cases in the literature appears to be 23%,1 but as high as 60%-83% depending on the report!2 Its diagnosis post-colectomy requires a high index of suspicion, as patients may not complain of “diarrhea” with chronically loose stools in the ileostomy bag.  Be particularly on the lookout for C. difficile enteritis in these patients when there is increased stool output, fever, hypotension, and/or leukocytosis2, and when in doubt, send a stool specimen from the ileostomy bag for C. difficile testing.

Although the pathophysiology of C. difficile enteritis is not fully understood, few observations are particularly intriguing: 

  • Small bowel mucosa may be colonized by C. difficile in about 3% of the population, potentially serving as a reservoir.2
  • Patients with ileostomy may develop a metaplasia of the terminal end mimicking colonic environment.4  
  • Exposure of rabbit ileum to C. difficile toxin A also causes significant epithelial necrosis with destruction of villi and neutrophil infiltration.5

 

References

  1. Dineen SP, Bailey SH, Pham TH, et al. Clostridium difficile enteritis: a report of two cases and systematic literature review. World J Gastrointest Surg 2013;5:37-42. https://www.wjgnet.com/1948-9366/full/v5/i3/37.htm
  2. Boland E, Thompson JS. Fulminant Clostridium difficile enteritis after proctocolectomy and ileal pouch-anal anastomosis. Gastroenterology Research and Practice 2008; 2008: Article ID 985658. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2633454/pdf/GRP2008-985658.pdf
  3. Freiler JF, Durning SJ, Ender PT. Clostridium difficile small bowel enteritis occurring after total colectomy. Clin Infect Dis 2001;33:1429-31. https://pdfs.semanticscholar.org/333b/d84978cfc4ac8fd21a15bc8fd26ff3160387.pdf
  4. Apel R, Cohen Z, Andrews CW, et al. Prospective evaluation of early morphological changes in pelvic ileal pouches. Gastroenterology 1994;107:435-43. http://www.gastrojournal.org/article/0016-5085(94)90169-4/pdf
  5. Triadafilopoulos G, Pothoulakis C, Obrien MJ, et al. Differential effects of Clostridium difficile toxins A and B on rabbit ileum. Gastroenterology 1987;93:273-279. https://www.ncbi.nlm.nih.gov/pubmed/3596162
My patient with ulcerative colitis has had colectomy. Can she still get C. difficile infection?