My patient with peripheral neuropathy was just diagnosed with monoclonal gammopathy of unclear significance (MGUS). Can these two conditions be related?

The presence of MGUS in patients with peripheral neuropathy (PN) may be either coincidental or causal. Younger age group (<50 y) and the presence of IgM MGUS increase the likelihood of a causal relationship between MGUS and peripheral neuropathy. 1

The likelihood of a causal relationship is higher in the younger age group because of the very low prevalence of M proteins (less than 1.5%) in this population making coincidental presence of MGUS and PN much less likely. In contrast, this relationship may just be coincidental in older patients because of higher baseline prevalence of MGUS (7% in those over 70 y old). 1  

Similarly, a causal relationship between MGUS and PN may be more likely when the M protein is IgM (vs IgG or IgA). In a study of patients with MGUS and peripheral neuropathy,  31% of patients with IgM MGUS had neuropathy vs 14% for IgA and 6% for IgG MGUS. In fact, among patients with PN without an obvious cause, the prevalence of an M protein may be as high as 10%.2  Whether the relationship between non-IgM MGUS and PN is causal remains unclear.3

Although the exact mechanism of MGUS-related PN is not known, pathologic studies in Waldenstrom macroglobulinemia and multiple myeloma have demonstrated demyelination and widened myelin lamellae associated with monoclonal IgM deposits.1

But before you implicate MGUS as the cause of PN, make sure to exclude common causes of PN, such as diabetes mellitus, alcoholism and potential drugs.

 

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References

  1. Chaudhry HM, Mauermann ML, Rajkumar SV. Monoclonal gammopathy—associated peripheral neuropathy: diagnosis and management. Mayo Clin Proc 2017; 92:838-50. https://www.mayoclinicproceedings.org/article/S0025-6196(17)30118-0/pdf
  2. Kelly JJ Jr, Kyle RA, O’Brien PC, et al. Prevalence of monoclonal protein in peripheral neuropathy. Neurology 1981;31:1480-83. https://www.ncbi.nlm.nih.gov/pubmed/6273767
  3. Nobile-Orazio E, Barbien L, Baldini L, et al. Peripheral neuropathy in monoclonal gammopathy of undetermined significance: prevalence and immunopathogenetic studies. Acta neurol Scand 1992;85:383-90. https://onlinelibrary.wiley.com/doi/10.1111/j.1600-0404.1992.tb06033.x
My patient with peripheral neuropathy was just diagnosed with monoclonal gammopathy of unclear significance (MGUS). Can these two conditions be related?

Why is my patient with diabetic ketoacidosis (DKA) and hypovolemia hypertensive?

Although we may expect patients with DKA to present with hypotension due to hypovolemia, many patients with DKA may actually be hypertensive. This finding is particularly intriguing because hyperinsulinemia, not insulinopenia as found in DKA, has been associated with hypertension. 1,2

Though not proven, potential explanations for hypertension in DKA include elevated serum levels of catecholamines, pro-inflammatory cytokines, renin, angiotension II and aldosterone.3-5 Hyperosmolality may also lead to the release of antidiuretic hormone (ADH) which increases blood pressure via V2 receptors.  Another possibility is that the high insulin levels associated with the treatment of DKA suppress the catecholamine-stimulated production of vasodilative eicosanoids (eg, prostaglandins) by adipose tissue. 1 It’s possible that in any given patient, 1 or more of these mechanisms may be enough to override the potential hypotensive effect of insulin deficiency in DKA.

We should note that reports of frequent hypertension in DKA have primarily involved pediatric patients. A 2011 study found that 82% of pediatric patients with DKA had hypertension during the first 6 hours of admission with no patient having hypotension.3  

On the other extreme, refractory hypotension without obvious cause (eg, sepsis, acute adrenal insufficiency, cardiogenic causes) has also been reported in DKA.5Because insulin inhibits the production of vasodilative prostaglandins (eg, PGI2 and PGE2), severe insulin deficiency in DKA can also contribute to hypotension along with volume depletion. 

Potential genetic polymorphism in the synthesis and metabolism of prostaglandins may at least partially explain the varied blood pressure response and whether a patient with DKA presents with hypertension or hypotension. 5  

The author would like to acknowledge the valuable contribution of Lloyd Axelrod MD, Massachusetts General Hospital, to this post.

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References

  1. Axelrod L. Insulin, prostaglandins, and the pathogenesis of hypertension. Diabetes 1991;40:1223-1227. https://diabetes.diabetesjournals.org/content/40/10/1223 
  2. Chatzipantelli K, Head C, Megerman J, et al. The relationship between plasma insulin level, prostaglandin productin by adipose tissue and blood pressure in normal rats and rats with diabetes mellitus and diabetic ketoacidosis. Metabolism 1996;45:691-98. https://www.sciencedirect.com/science/article/abs/pii/S002604959690133X 
  3. Deeter KH, Roberts JS, Bradford H, et al. Hypertension despite dehydration during severe pediatric diabetic ketoacidosis. Pediatr Diabetes 2011;12:295-301. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1399-5448.2010.00695.x 
  4. Ferris JB, O’Hare JA, Kelleher CM, et al. Diabetic control and the renin-angiotensin system, catecholamines and blood pressure. Hypertension 1985 7(Suppl II):II-58-II-63. https://www.ahajournals.org/doi/abs/10.1161/01.HYP.7.6_Pt_2.II58  
  5. Singh D, Cantu M, Marx MHM, et al. Diabetic ketoacidosis and fluid refractory hypotension. Clin Pediatrics 2016;55:182-84. https://journals.sagepub.com/doi/abs/10.1177/0009922815584549?journalCode=cpja 

 

Why is my patient with diabetic ketoacidosis (DKA) and hypovolemia hypertensive?

How strong is the evidence for IV contrast-induced nephropathy (CIN) following CT scans?

Not as strong as one might expect with an increasing number of investigators questioning the causative role of IV contrast in precipitating CIN.

A 2013 meta-analysis involving observational—mostly retrospective— studies concluded that the risks of AKI, death, and dialysis were similar between IV contrast and non-contrast patients, including those with diabetes or underlying renal insufficiency1.

Two retrospective studies2,3 designed to control for a variety of factors that may affect the risk of AKI by propensity matching found divergent results with the larger and better designed study finding no significant difference in AKI between the 2 groups3. A 2017 retrospective cohort analysis of emergency department patients utilizing a similar propensity-score analysis also failed to find a difference in post-CT AKI between those receiving and not receiving IV contrast4.

Further shedding doubt on the role of IV contrast in causing AKI, a study involving patients with chronic kidney disease found no difference in the rates of excretion of 2 biomarkers of AKI (neutrophil gelatinase-associated lipocalin-NGAL, and kidney injury molecule-1-KIM-1) between patients with and without presumed CIN5. Some have even criticized experimental animal studies supporting the existence of CIN due to their poor applicability to human renal disease1.

This is not to say that IV CIN does not exist. Rather, we should keep an open mind about the pathophysiology and epidemiology of CIN. Stay tuned!

Fun pearl: Did you know that the first case of CIN was described in a patient with multiple myeloma undergoing IV pyelography (before the CT era)?

References

  1. McDonald JS, McDonald RJ, Comin J, et al. Frequency of acute kidney injury following intravenous contrast medium administration: a systematic review and meta-analysis. Radiology. 2013;267(1):119-128. https://www.ncbi.nlm.nih.gov/pubmed/23319662
  2. Davenport MS, Khalatbari S, Dillman JR, et al. Contrast material-induced nephrotoxicity and intravenous low-osmolality iodinated contrast material. Radiology. 2013;267(1):94-105. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3606541/pdf/121394.pdf
  3. McDonald RJ, McDonald JS, Bida JP, et al. Intravenous contrast material-induced nephropathy: causal or coincident phenomenon? Radiology 2013;267:106-18. https://www.ncbi.nlm.nih.gov/pubmed/23360742
  4. Hinson JS, Ehmann MR, Fine DM, et al. Risk of acute kidney injury after intravenous contrast media administration. Ann Emerg Med 2017; 69:577-586. https://www.ncbi.nlm.nih.gov/pubmed/28131489
  5. Kooiman J, van de Peppel WR, Sijpkens YWJ, et al. No increase in kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin excretion following intravenous contrast enhanced-CT. Eur Radio 2015;25:1926-34. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457910/pdf/330_2015_Article_3624.pdf

Contributed by Ginger Jiang, Medical Student, Harvard Medical School

How strong is the evidence for IV contrast-induced nephropathy (CIN) following CT scans?

Is diabetes mellitus (DM) an independent risk factor for venous thromboembolism (VTE)?

Although DM was originally thought to be an independent risk factor for DM1,2, more recent data suggest otherwise.

A population-based study involving residents of Olmsted County, Minnesota, calculated the incidence of VTE among patients with DM over a 25-year period and found it to be higher than that of controls .   However, in the same study, after controlling for hospitalization for major surgery or medical illness and nursing home confinement, no association between DM and VTE was found2  .  

A recent systematic review and meta-analysis of case-control and cohort studies involving over 1 million patients found no significant association between DM and VTE when controlled for common risk factors (eg, obesity, sedentary life style, smoking, hypertension, or dyslipidemia)3.  The authors concluded that DM and its complications are not independent risk factors for incident VTE.  

Thus, it appears that much of the risk of DVT in DM may be related to its comorbidities and the need for hospitalization, surgery or nursing home stay.

References

  1. Petrauskiene V, Falk M, Waernbaum I, et al. The risk of venous thromboembolism is markedly elevated in patients with diabetes. Diabetologia 2005;48:1017-21. https://www.ncbi.nlm.nih.gov/pubmed/15778859
  2. Heit JA, Leibson CL, Ashrani AA, et al. Is diabetes mellitus an independent risk factor for venous thromboembolism? A population-based case-control study. Thromb Vasc Biol 2009; 29:1399-1405. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2735343/
  3. Gariani K, Mavrakanas T, Combescure C, et al. Is diabetes mellitus a risk factor for venous thromboembolism? A systematic review and meta-analysis of case-control and cohort studies. Eur J Intern Med 2016;28:52-58. https://www.ncbi.nlm.nih.gov/pubmed/26507303
Is diabetes mellitus (DM) an independent risk factor for venous thromboembolism (VTE)?

When should I seriously consider active tuberculosis (TB) in my newly-admitted HIV-negative patient with a cough?

Active TB should be suspected based on a combination of epidemiological (eg, exposure, travel to, or residence in a high prevalence area, history of prior TB), clinical (eg, cough lasting 2-3 weeks or longer, fever, night sweats, weight loss, fatigue, less commonly, chest pain, dyspnea, and hemoptysis), chest radiograph abnormalities (eg, infiltrates, fibrosis, cavitation), and histopathologic (eg, caseating granuloma)1.

Among HIV-negative patients, the highest prevalence of TB is found those who have been incarcerated, use intravenous drugs, have alcohol use disorder, or are immunocompromised (including diabetes mellitus)2,3

Patients suspected of TB based on clinical criteria should undergo chest radiography.  Reactivation pulmonary TB (~90% of TB in adults) classically presents with upper lobe and/or the superior segment of the lower lobe disease.  Remember that up to 5% of patients with active pulmonary TB have normal chest radiograph, however4.  

All hospitalized patients suspected of having active TB should be placed on appropriate isolation precautions.

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References

  1. Sia IG, Wieland ML. Current concepts in the management of tuberculosis. Mayo Clin Proc. 2011;86:348-361. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068897/
  2. Center for Disease Control. Tuberculosis: Data and Statistics. https://www.cdc.gov/tb/statistics/default.htm. Accessed October 3, 2016.
  3. World Health Organization. Tuberculosis. http://www.who.int/mediacentre/ factsheets/fs104/en/. Accessed October 3, 2016.
  4. Marciniuk, D, McNab, BD, Martin WT, Hoeppner, VH. Detection of pulmonary tuberculosis in patients with a normal chest radiograph. Chest 1999;115:445-452. https://journal.chestnet.org/article/S0012-3692(15)50590-4/abstract

 

 

Contributed by Charles C. Jain MD, Medical Resident, Massachusetts General Hospital

 

When should I seriously consider active tuberculosis (TB) in my newly-admitted HIV-negative patient with a cough?

My hospitalized patient has developed hyperkalemia while on heparin prophylaxis. Can heparin really cause hyperkalemia and what is its mechanism?

Heparin is one of the most overlooked causes of hyperkalemia in hospitalized patients, occurring in 5-8% of treated patients, including those on thromboprophylaxis1.

The mechanism of heparin-induced hyperkalemia appears to be through suppression of aldosterone synthesis by inhibiting the function of the glomerulosa zone of the adrenal medulla2,3.  Such inhibitory action is usually of no consequence when renal function is normal and potassium excretion is not otherwise impaired.

The risk of heparin-induced hyperkalemia is increased in the elderly, those with preexisting diabetes mellitus or renal insufficiency, as well patients on concomitant use of certain drugs such as spironolactone, ACE inhibitors, NSAIDs, and trimethoprim2

Hyperkalemia is usually detected after at least 3-4 days of treatment with subcutaneous heparin, and usually resolves within a few days of  discontinuation of therapy1,2.  Fractionated heparin products such as enoxaparin may also be associated with hyperkalemia2 but the risk appears to be lower1.

Fludrocortisone has been used to normalize serum potassium in patients who  remain on heparin.4

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References

  1. Potti A, Danielson B, Badreddine R, et al. Potassium homeostasis in patients receiving prophylactic enoxaparin therapy. J Thromb Haemost 2004;2:1208-9. http://onlinelibrary.wiley.com/doi/10.1111/j.1538-7836.2004.00791.x/pdf
  2. Thomas CM, Thomas J, Smeeton F, et al. Heparin-induced hyperkalemia. Diabetes Res Clin Pract 2008;80:e7-e8. https://www.ncbi.nlm.nih.gov/pubmed/18343525
  3.  Liu AA, Bui T, Nguyen HV, et al. Subcutaneous unfractionated heparin-induced hyperkalemia in an elderly patient. Australas J Ageing 2009;28:97. https://www.ncbi.nlm.nih.gov/pubmed/19566805
  4. Brown G. Fludrocortisone for heparin-induced hyperkalemia. CJHP 2011;64:463-4. https://www.cjhp-online.ca/index.php/cjhp/article/view/1091/1394

 

My hospitalized patient has developed hyperkalemia while on heparin prophylaxis. Can heparin really cause hyperkalemia and what is its mechanism?

How should I interpret an isolated elevated hemidiaphragm on chest x-ray?

In hospitalized patients, an elevated hemidiaphragm on chest x-ray is not a rare finding and is frequently asymptomatic. It has many potential causes, including lobar collapse or surgical resection of the lung, diaphragmatic eventration, distention of stomach or colon, or phrenic nerve paralysis (1).  Among patients with a paralyzed hemidiaphragm, damage to the phrenic nerve caused by surgery (e.g. cardiac), mediastinal tumors, cervical spine pathology, diabetes, autoimmune (e.g. vasculitis) and infectious causes (e.g. herpes zoster and polio viruses) are often cited as potential causes; most may be idiopathic, however (1,2,3). Chest x-ray has a high negative predictive value (93%) but a poor positive predictive value for diagnosis of hemidiaphragm paralysis (1).  When in doubt, the fluoroscopic “sniff” test should be used for confirmation.  

1. Chetta A, Rehman AK, Moxham J, et al. Chest radiography cannot predict diaphragm function. Resp Med 2005;99:39-44

2. Curtis J, Nawarawong W, Walls J, et al. Elevated hemidiaphragm after cardiac operations: incidence, prognosis, and relationship to the use of topical ice slush. Annals of Thoracic Surgery 1989;48:764-8.

3. Crausman RS, Summerhill EM, McCool FD. Idiopathic diaphragmatic paralysis: Bell’s palsy of the diaphragm? Lung 2009;187:153-157.

Contributed by Ethan Balgley, Harvard Medical Student

 

How should I interpret an isolated elevated hemidiaphragm on chest x-ray?

Should we routinely use broad spectrum empiric antibiotic therapy in our diabetic patients with cellulitis of the lower extremities?

The short answer is “No”!

The myth that diabetics with acute bacterial skin and skin structure infections should be routinely placed on antibiotics against gram-positives as well as gram-negatives and/or anaerobes probably originates from the extrapolation of data revolving around the frequent polymicrobial nature of diabetic foot infections.  These infections often originate from chronic ulcers and are complicated by deep tissue infection or gangrene (1), which is often not the case in our diabetic patients with cellulitis alone.  

In a recent study of the microbiology of cellulitis or cutaneous abscess in hospitalized patients, Staphylococcus and Streptococcus sp. accounted for 90% of cultured organisms in  diabetic patients, not significantly different than that of non-diabetics (1).

These finding support national guidelines which do not recommend routine use of broader spectrum antibiotics in diabetics with cellulitis or cutaneous abscess (2).  

References

1. Jenkins TC, Knepper BC, Moore SJ, et al. Comparison of the microbiology and antibiotic treatment among diabetic and nondiabetic patients hospitalized for cellulitis or cutaneous abscess. J Hosp Med 2014;9:788-794. https://www.ncbi.nlm.nih.gov/pubmed/25266293

2. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections. Clin Infect Dis 2014;59:e10-e52. https://www.ncbi.nlm.nih.gov/pubmed/24973422

Should we routinely use broad spectrum empiric antibiotic therapy in our diabetic patients with cellulitis of the lower extremities?

When should I consider treating my hospitalized patients with asymptomatic bacteruria (ASB)?

The great majority of hospitalized patients with ASB do not need treatment with antibiotics.

In fact, there are only a couple of conditions for which treatment of ASB is indicated:  pregnant women (due to risk of pyelonephritis and low-birth infants/pre-term delivery) and before  GU instrumentation, such as transurethral resection of the prostate or other GU procedures for which mucosal bleeding is anticipated (1).  

So for the great majority of our hospitalized patients, including the elderly, diabetic women, institutionalized residents of long-term facilities, and spinal cord injury patients treatment of ASB is not indicated.  Even in the case of renal transplant patients, supportive evidence for the  use of prophylactic antibiotics in ASB is so far lacking (2).  

The estimated prevalence of ASB varies widely in the population,  with rates of 15-20% among community-dwelling women > 70 yrs of age, and 5-10% for men>65 yrs for community-dwelling men. In long-term care facility residents, 25-50% of women, 15-40% of men, and 100% of those with chronic indwelling catheters have ASB (3).  

So keep these rates in mind before attributing patient’s symptoms to ASB (ie, patient’s presentation may have nothing to do with urine findings).  It’s also worth emphasizing that pyuria accompanying ASB is not an indication for treatment.

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References

1. Nicolle LE, Bradley S, Colgan R, et al. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis 2005;40:643-54.  https://academic.oup.com/cid/article/40/5/643/363229

2. Coussement J, Abramowicz D. Should we treat asymptomatic bacteriuria after renal transplantation? Nephrol Dial Transplant 2013;0:1-3. https://academic.oup.com/ndt/article/29/2/260/1913512

3. Nicolle LE. Asymptomatic bacteriuria in older adults. Geriatrics & Aging 2003;6:24-28. https://www.healthplexus.net/files/content/2003/October/0609bacteriuria.pdf

When should I consider treating my hospitalized patients with asymptomatic bacteruria (ASB)?