My patient with COPD on prednisone with recurrent pneumonia has a low serum IgG level.  Can corticosteroids lower serum immunoglobulin levels?

Yes! Both exogenous and endogenous hypercortisolism may be associated with a drop in serum immunoglobulin levels, particularly IgG, which may persist even after discontinuation of steroid treatment.1-4 This means that a low serum IgG level in a patient on corticosteroids should be interpreted with caution and may not necessarily suggest primary antibody deficiency.

Although some early studies did not find a significant impact of corticosteroids on immunoglobulin levels, several subsequent studies found otherwise.  A 1978 study involving atopic asthmatic patients (averaging 16.8 mg prednisone daily) found that mean serum IgG significantly decreased (-22%) with milder drop in IgA levels (-10%) and no drop in serum IgM levels.2 Of interest, IgE level increased significantly initially but later dropped as well. More importantly, mean serum IgG levels remained significantly decreased an average of 22 days after corticosteroids were discontinued.

More recently, in a study involving patients with giant cell arteritis and polymyalgia rheumatica on corticosteroids, 58% developed antibody deficiency with the great majority involving IgG, either alone or along with other immunoglobulins.3 The reduction of IgG persisted even after discontinuation of corticosteroids in nearly 50% of patients. Whether low serum immunoglobulins due to corticosteroids alone significantly increase susceptibility to infections is unclear, however.

In our patient with COPD on prednisone, if serum IgG level is found to be low and a primary antibody deficiency is still suspected, a functional assessment of the antibody production after active immunization (eg, polysaccharide pneumococcal vaccine, tetanus toxoid) may be necessary. 1 An adequate antibody response to active immunization makes primary immunodeficiency unlikely. 

 

Bonus Pearl: Did you know that corticosteroid-induced hypogammaglobulinemia may be in part related to reduced IgG production as well as an increase in IgG catabolism?1,4

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References

  1. Sarcevic J, Cavelti-Weder C, Berger CT, et al. Case report-secondary antibody deficiency due to endogenous hypercortisolism. Frontiers in Immunology 2020;11:1435. https://www.frontiersin.org/articles/10.3389/fimmu.2020.01435/full
  2. Settipane GA, Pudupakkam RK, McGowan JH. Corticosteroid effect on immunoglobulins. J Allergy Clin Immunol 1978;62: 162-6. https://www.jacionline.org/article/0091-6749(78)90101-X/pdf
  3. Wirsum C, Glaser C, Gutenberger S, et al. Secondary antibody deficiency in glucocorticoid therapy clearly differs from primary antibody deficiency. J Clin Immunol 2016;36:406-12. https://link.springer.com/article/10.1007/s10875-016-0264-7
  4. McMillan R, Longmire R, Yelenosky R. The effect of corticosteroids on human IgG synthesis. J Immunol 1976;116:1592-1595. https://www.jimmunol.org/content/116/6/1592

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

My patient with COPD on prednisone with recurrent pneumonia has a low serum IgG level.  Can corticosteroids lower serum immunoglobulin levels?

Why do we often prescribe ceftriaxone in preference to fluoroquinolones for prophylaxis of infections in patients with cirrhosis and upper GI bleed?

Preference of ceftriaxone over fluoroquinolones (FQs) for prophylaxis of infection in patients with cirrhosis and upper GI bleed (UGIB) can often be traced back to a small 2006 Spanish randomized controlled trial (RCT)1 which found a significantly lower rate of proved or possible bacterial infection and lower rate of fermentative Gram-negative bacilli infection in the ceftriaxone group (vs norfloxacin) over a 10-day period (11% vs 33% and 0% vs 11%, respectively). There was no significant difference in the incidence of proved bacterial infection (spontaneous bacterial peritonitis or bacteremia, P=0.07) or 10-day mortality between the 2 groups.   

It’s worth emphasizing that the primary impetus for this study was evaluation of the efficacy of ceftriaxone in patients with cirrhosis and UGIB in a setting where FQ Gram-negative bacilli was thought to be highly prevalent. Parenthetically, a similar RCT performed where the prevalence of FQ resistance was considered low failed to find a significant difference in breakthrough bacterial infection, rebleeding or mortality when ceftriaxone was compared to IV ciprofloxacin.2

Another caveat of the 2006 study was that an IV antibiotic (ceftriaxone) was compared to a oral antibiotic (norfloxacin) which, in the setting of active UGIB, may be problematic.

Despite these limitations, its favorable safety profile compared to FQs coupled with its ease of administration has often made ceftriaxone the drug of choice for prophylaxis of infections in patients with cirrhosis and UGIB. The 2016 Practice Guidance by the American Association for the Study of Liver Diseases considers ceftriaxone as the first choice in patients with advanced cirrhosis, on FQ prophylaxis, and in hospital settings with high prevalence of FQ resistant bacterial infection.3

Bonus Pearl: Did you know that the prevalence of FQ resistant in Enterobacteriaceae may be as high as 30% in certain regions of U.S. and >50% in certain regions of the world? 4

Also see related 2 P4P pearls (1, 2) on the association of UGIB bleed with infections in patients with cirrhosis.

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References

  1. Fernandez J, Del Arbol LR, Gomez C, et al. Norfloxacin vs ceftriaxone in the prophylaxis of infections in patients with advanced cirrhosis and hemorrhage. Gastroenterol 2006;131:1049-1056. https://pubmed.ncbi.nlm.nih.gov/17030175/
  2. Pittayanon R, Reknimir R, Kullavanijaya P, et al. Intravenous ciprofloxacin vs ceftriaxone for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding:A randomized controlled trial. Thai J Gastroenterol 2016;17:24-30. http://www.thaigastro.com/books.php?act=content&content_id=476&book_id=61
  3. Garcia-Tsao G, Abraldes JG, Berzigotti A, et al. Portal hypertensive bleeding in cirrhosis:risk stratification, diagnosis and management: 2016 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2017;65:310-335. https://pubmed.ncbi.nlm.nih.gov/27786365/
  4. Spellberg B, Doi Y. The rise of fluoroquinolone-resistant Escherichia coli in the community:scarier than we thought. J Infect Dis 2015;212:1853-1855. https://pubmed.ncbi.nlm.nih.gov/25969562/

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Why do we often prescribe ceftriaxone in preference to fluoroquinolones for prophylaxis of infections in patients with cirrhosis and upper GI bleed?

My 19-year-old patient wishes treatment for his chronic acne while waiting for his dermatology appointment. What treatment should I recommend?

Irrespective of your patient’s acne severity, a good starting point is over-the-counter topical benzoyl peroxide.1 Benzoyl peroxide not only kills the bacteria that causes acne (Cutibacterium acnes) through the release of free oxygen radicals, but also functions as a comedolytic.2

If your patient’s acne is mild to moderate (defined as non-inflammatory lesions [comedones] or less than 5 inflammatory lesions [papulopustules]), you may consider prescribing a topical retinoid such as tretinoin 0.025%, adapalene 0.1%, or tazarotene 0.05% in combination with the benzoyl peroxide.1,3 These agents have been shown to have both comedolytic and anti-inflammatory effects, and are the cornerstone of topical therapy for all acne cases, save for the most mild.1,4

In moderate to severe acne (defined as multiple inflammatory lesions), you can consider prescribing an oral antibiotic in combination with the retinoid and benzoyl peroxide.1,3 The first-line therapy in this situation is often a tetracycline, such as daily doxycycline in the 1.7 to 2.4 mg/kg dose range.5,6 

As with all medications, please familiarize yourself with contraindications and adverse side effects of these drugs before prescribing (eg, doxycycline-related photosensitivity or adverse impact on GI flora, or avoiding tretinoin in pregnancy).

For extremely severe acne (defined as widespread inflammatory lesions, nodules, and/or scarring), you should consider referral to a dermatologist for Accutane (isotretinoin) treatment.3 However, the aforementioned treatment options should be sufficient to control your patient’s symptoms until seen by a dermatologist!           

Bonus Pearl: Did you know that besides anabolic-androgenic steroids, dietary supplements containing vitamins B6/B12, iodine and whey have also been linked to acne?7

Contributed by Aditya Nellore, Fourth-Year Medical Student, St. Louis University Medical School, St. Louis, Missouri   

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References:

  1. Zaenglein AL, Pathy AL, Schlosser BJ, Alikhan A, Baldwin HE, Berson DS, Bowe WP, Graber EM, Harper JC, Kang S, Keri JE, Leyden JJ, Reynolds RV, Silverberg NB, Stein Gold LF, Tollefson MM, Weiss JS, Dolan NC, Sagan AA, Stern M, Boyer KM, Bhushan R. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016 May;74(5):945-73.e33. doi: 10.1016/j.jaad.2015.12.037. Epub 2016 Feb 17. Erratum in: J Am Acad Dermatol. 2020 Jun;82(6):1576. PMID: 26897386. https://www.jaad.org/article/S0190-9622(15)02614-6/fulltext#tbl6
  2. Cunliffe WJ, Holland KT. The effect of benzoyl peroxide on acne. Acta Derm Venereol. 1981;61(3):267-9. PMID: 6167116. https://pubmed.ncbi.nlm.nih.gov/6167116/
  3. Purdy S, Deberker D. Acne vulgaris. BMJ Clin Evid. 2008 May 15;2008:1714. PMID: 19450306; PMCID: PMC2907987. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907987/
  4. Cunliffe WJ, Caputo R, Dreno B, Förström L, Heenen M, Orfanos CE, Privat Y, Robledo Aguilar A, Meynadier J, Alirezai M, Jablonska S, Shalita A, Weiss JS, Chalker DK, Ellis CN, Greenspan A, Katz HI, Kantor I, Millikan LE, Swinehart JM, Swinyer L, Whitmore C, Czernielewski J, Verschoore M. Clinical efficacy and safety comparison of adapalene gel and tretinoin gel in the treatment of acne vulgaris: Europe and U.S. multicenter trials. J Am Acad Dermatol. 1997 Jun;36(6 Pt 2):S126-34. doi: 10.1016/s0190-9622(97)70056-2. PMID: 9204091. https://pubmed.ncbi.nlm.nih.gov/9204091/
  5. Tan J, Humphrey S, Vender R, Barankin B, Gooderham M, Kerrouche N, Audibert F, Lynde C; POWER study group. A treatment for severe nodular acne: a randomized investigator-blinded, controlled, noninferiority trial comparing fixed-dose adapalene/benzoyl peroxide plus doxycycline vs. oral isotretinoin. Br J Dermatol. 2014 Dec;171(6):1508-16. doi: 10.1111/bjd.13191. Epub 2014 Oct 28. PMID: 24934963. https://pubmed.ncbi.nlm.nih.gov/24934963/
  6. Leyden, James J., et al. “A randomized, phase 2, dose-ranging study in the treatment of moderate to severe inflammatory facial acne vulgaris with doxycycline calcium.” Journal of Drugs in Dermatology: JDD6 (2013): 658-663. https://pubmed.ncbi.nlm.nih.gov/23839182/
  7. Zamil DH, Perez-Sanchez A, Katta R. Acne related to dietary supplements. Dermatol Online J. 2020 Aug 15;26(8):13030/qt9rp7t2p2. PMID: 32941710. https://pubmed.ncbi.nlm.nih.gov/32941710/

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

My 19-year-old patient wishes treatment for his chronic acne while waiting for his dermatology appointment. What treatment should I recommend?

Is there a connection between nocturia and obstructive sleep apnea (OSA)?

Absolutely! Although seemingly unrelated medical conditions, nocturia is commonly associated with OSA. [1,2]

A retrospective study [1] (n = 138) reported pathologic nocturia (≥2 urination events per night) in 47.8% of patients with OSA-hypopnea-syndrome. In this study, nocturia was linked to increasing age, 02 desaturation and severity of OSA. In another study (n=30), OSA (defined as apnea-hypopnea index [AHI] ≥5) was diagnosed in 66% of patients with nocturia with increasing nocturia associated with higher AHI.[2]

Recall that repetitive apnea episodes in OSA expose cardiovascular system to cycles of exaggerated negative intrathoracic pressure. [3] This causes myocardial stretching which is likely the reason OSA has been linked to elevated nocturnal atrial natriuretic peptide (ANP) levels. [4] In turn, ANP as an aldosterone inhibitor, increases salt and water excretion causing nocturia. Of interest, use of continuous positive airway pressure (CPAP) has been shown to normalize ANP levels [5] which may explain CPAP’s favorable impact on the frequency of nocturia based on a meta-analysis. [6]

Although the role of screening for OSA in nocturia remains unclear, OSA should be considered in the differential diagnosis of nocturia, especially in men and women younger than 50 years of age. [7,8]

Bonus pearl: Did you know that OSA has been associated with recreational MDMA (“ecstasy”) use, with severity of OSA correlating with lifetime MDMA exposure? [9]

Contributed by Fahad Tahir, MD, Mercy Hospital-St. Louis, St. Louis, Missouri

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References:

  1. Hajduk IA, Strollo PJ Jr, Jasani RR, Atwood CW Jr, Houck PR, Sanders MH. Prevalence and predictors of nocturia in obstructive sleep apnea-hypopnea syndrome–a retrospective study. Sleep. 2003 Feb 1;26(1):61-4. PMID: 12627734. https://pubmed.ncbi.nlm.nih.gov/12627734/
  2. Umlauf MG, Chasens ER, Greevy RA, Arnold J, Burgio KL, Pillion DJ. Obstructive sleep apnea, nocturia and polyuria in older adults. Sleep. 2004 Feb 1;27(1):139-44. doi: 10.1093/sleep/27.1.139. PMID: 14998251.https://pubmed.ncbi.nlm.nih.gov/14998251/
  3. Bradley TD, Floras JS. Obstructive sleep apnoea and its cardiovascular consequences. Lancet. 2009 Jan 3;373(9657):82-93. doi: 10.1016/S0140-6736(08)61622-0. Epub 2008 Dec 26. PMID: 19101028. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)61622-0/fulltext
  4. Svatikova A, Shamsuzzaman AS, Wolk R, Phillips BG, Olson LJ, Somers VK. Plasma brain natriuretic peptide in obstructive sleep apnea. Am J Cardiol. 2004 Aug 15;94(4):529-32. doi: 10.1016/j.amjcard.2004.05.010. PMID: 15325948. https://www.ajconline.org/article/S0002-9149(04)00730-1/fulltext/
  5. Krieger J, Laks L, Wilcox I, Grunstein RR, Costas LJ, McDougall JG, Sullivan CE. Atrial natriuretic peptide release during sleep in patients with obstructive sleep apnea before and during treatment with nasal continuous positive airway pressure. Clin Sci (Lond). 1989 Oct;77(4):407-11. doi: 10.1042/cs0770407. PMID: 2530023. https://pubmed.ncbi.nlm.nih.gov/2530023/
  6. Wang T, Huang W, Zong H, Zhang Y. The Efficacy of Continuous Positive Airway Pressure Therapy on Nocturia in Patients With Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis. Int Neurourol J. 2015 Sep;19(3):178-84. doi: 10.5213/inj.2015.19.3.178. Epub 2015 Sep 22. PMID: 26620900; PMCID: PMC4582090. https://pubmed.ncbi.nlm.nih.gov/26620900/
  7. Lowenstein L, Kenton K, Brubaker L, Pillar G, Undevia N, Mueller ER, FitzGerald MP. The relationship between obstructive sleep apnea, nocturia, and daytime overactive bladder syndrome in women. Am J Obstet Gynecol. 2008 May;198(5):598.e1-5. doi: 10.1016/j.ajog.2008.02.024. PMID: 18455544. https://www.ajog.org/article/S0002-9378(08)00168-3/fulltext
  8. Moriyama Y, Miwa K, Tanaka H, Fujihiro S, Nishino Y, Deguchi T. Nocturia in men less than 50 years of age may be associated with obstructive sleep apnea syndrome. Urology. 2008 Jun;71(6):1096-8. doi: 10.1016/j.urology.2008.02.038. Epub 2008 Apr 8. PMID: 18400277.https://pubmed.ncbi.nlm.nih.gov/18400277/
  9. McCann UD, Sgambati FP, Schwartz AR, Ricaurte GA. Sleep apnea in young abstinent recreational MDMA (“ecstasy”) consumers. Neurology. 2009 Dec 8;73(23):2011-7. doi: 10.1212/WNL.0b013e3181c51a62. Epub 2009 Dec 2. PMID: 19955499; PMCID: PMC2790228. https://n.neurology.org/content/73/23/2011.long

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

 

 

Is there a connection between nocturia and obstructive sleep apnea (OSA)?

What’s the latest on second Covid vaccine boosters and should I recommend them to my adult patients?

On March 29, 2022, the CDC and the FDA approved second booster shots of Pfizer and Moderna Covid vaccines for everyone 50 years of age or older as well as people 12 years of age or older with moderate to severe immune deficiencies to be given at least 4 months following the first booster.1-3  This means a 4th dose of an mRNA vaccine for many adults and a 5th dose for those with moderate to severe immune deficiencies. 

Admittedly, these recommendations are made in the context of many uncertainties, including when the next Covid surge will arrive, what will be the predominant variant, and how will our immunity hold up if a surge occurs. 

Nevertheless, in discussing the merits of a 2nd booster, I would emphasize several “talking points”:

  • Covid hasn’t gone away with new cases still diagnosed daily, some still  requiring hospitalization, albeit at lower frequency than recent past. 
  • Our immunity against Covid wanes in the absence of boosters or natural infection.
  • SARS-CoV-2 has been unpredictable in its surges, as well as emergence of new variants with frequent changes in its virulence and ease of transmission. This means we don’t know when the next surge will hit us (summer, fall or later) and how the predominant variant will behave.
  • But let’s not get too hung up on surges! The fact is that as long as Covid is circulating around, maintaining a robust immunity against infection is the best way to avoid getting infected and the best way to do this is through boosters!
  • As more people go around without masks, the risk of unprotected exposure to SARS-CoV-2 is also likely to increase, particularly in indoor public gatherings.  Boosters may allow us the freedom to go maskless more often!
  • The risk of Long Covid even following mild infection is still real even between surges. This means even if we don’t get very sick from Covid, we are placing ourselves at risk of Long Covid. Remember, no Covid, no Long Covid!
  • Irrespective of whether it’s mild or even asymptomatic, Covid infection  can cause significant disruption in our lives, whether it be isolation at home, not being allowed to return to work or just the anxiety of having it or having passed it to others. This means that, at least currently, it’s premature to consider this virus as “just another respiratory virus.”  It’s impact on our everyday lives is still a lot different than typical respiratory viruses. 
  • mRNA vaccine boosters have been proven to be as safe as primary series. 
  • Last, but not the least, a preprint Israeli study involving volunteers 60 to 100 years old found a 78% reduction in mortality from Covid following a 2nd booster dose of Pfizer mRNA vaccine compared to those who only had 1 booster.This study has several limitations including self-selected volunteers who may already be at lower risk of Covid mortality due to their healthier lifestyle. Nevertheless, the data is very encouraging!

Ultimately, the decision to get a second booster, particularly during non-surge periods, will depend a lot on not only available facts but the individual’s threshold for acceptable risk of even mild disease, concern over transmission to others and more recently the cost of the vaccine, among other factors.  

Bonus Pearl: Did you know that each year there are plenty of uncertainties around which influenza A or B subtypes will be the predominant seasonal strain or what month they may surge but these questions never keep us from recommending the annual flu vaccine to the public as a means of reducing influenza cases and saving lives?   

 

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References

  1. D.A. Allows Second Covid Boosters for Everyone 50 and Older – The New York Times (nytimes.com)
  2. Coronavirus (COVID-19) Update: FDA Authorizes Second Booster Dose of Two COVID-19 Vaccines for Older and Immunocompromised Individuals | FDA
  3. CDC Recommends Additional Boosters for Certain Individuals | CDC Online Newsroom | CDC
  4. Arbel R, Sergienko R, Friger M, et al. Second booster vaccine and Covid-19 mortality in adults 60-100 years old. Preprint, posted March 24, 2022. 24514bba-2c9d-4add-9d8f-321f610ed199.pdf (researchsquare.com)

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

What’s the latest on second Covid vaccine boosters and should I recommend them to my adult patients?

My patient presents for evaluation of a mole on her arm. What features of the mole should I look for to help me distinguish a benign mole from melanoma?

Great question! Identifying a melanoma is a lot easier than you might think. A good starting point is the ABCDE criteria, which stands for Asymmetry, Border irregularity, Color variation, Diameter > 6 mm/Dark, and Evolution over time (see Fig 1 below). 1 Higher number of these characteristics in a particular lesion increases the probability of it being melanoma. For example, in the presence of just one characteristic, the positive likelihood ratio (LR) is 1.5 with the probability of melanoma of 7.4%. However, if all five characteristics are present, the positive LR rises to 107, while the probability of melanoma increases to 85%. 2,3,4

Another useful trick is looking for the “ugly duckling sign” (UDS), which refers to any pigmented lesion that appears obviously different than others on a patient’s body.5 For example, let’s say you’re seeing a patient with multiple small, circular, equally-sized moles on his forearm. A few inches away, he has a significantly larger mole with an irregular border. This would qualify as a positive UDS.  While the sensitivities of melanoma recognition are similar for the UDS and the ABCDE criteria (100% and 99%, respectively), the UDS has been shown to significantly improve specificity (88.3%) and accuracy (90.9%) when compared to the ABCDE criteria alone (57.4% and 66.7 %, respectively).6 So incorporating both sets of criteria into your approach to melanoma recognition may be prudent.

Once you suspect a melanoma, your should refer your patient to a dermatologist for an excisional biopsy, the gold standard for melanoma diagnosis.  This procedure consists of excising the entire lesion with 1-3 mm margins.7 The resulting sample can then be used to histologically confirm the diagnosis, prognosticate, and guide management.

Primary care providers play a crucial role in the early detection and treatment of melanoma, so keep your eyes open for any “unusual” looking moles, even if you’re seeing a patient for something unrelated!

Bonus Pearl

Did you know that cardiac involvement with melanoma is not uncommon, affecting an estimated 28% to 56% of patients with metastatic melanoma? 8

 

Figure 1: ABCDE criteria to help differentiate benign skin lesions from melanoma

i

 From Pawan Sonawane, Sahel Shardhul, Raju Mendhe, “Cloud based mobile solution for early detection of Skin Cancer using Artificial Intelligence”, International Journal of Scientific Research in Computer Science, Engineering and Information Technology (IJSRCSEIT), ISSN : 2456-3307, Volume 7 Issue 3, pp. 312-324, May-June 2021. Available at doi : https://doi.org/10.32628/CSEIT217327 Journal URL : https://ijsrcseit.com/CSEIT217327 (https://www.researchgate.net/publication/352394140_Cloud_based_mobile_solution_for_early_detection_of_Skin_Cancer_using_Artificial_Intelligence)

Contributed by Aditya Nellore, 4th year Medical Student, St. Louis University Medical School, St. Louis, Missouri

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References:

  1. Goldsmith SM. Why Is Darkness an Essential Feature for Melanoma Recognition? Skinmed. 2021 Oct 1;19(5):334-336. PMID: 34861912. (https://pubmed.ncbi.nlm.nih.gov/34861912/)
  2. Duarte AF, Sousa-Pinto B, Azevedo LF, Barros AM, Puig S, Malvehy J, Haneke E, Correia O. Clinical ABCDE rule for early melanoma detection. Eur J Dermatol. 2021 Dec 1;31(6):771-778. doi: 10.1684/ejd.2021.4171. PMID: 35107069. (https://pubmed.ncbi.nlm.nih.gov/35107069/)
  3. Thomas L, Tranchand P, Berard F, Secchi T, Colin C, Moulin G. Semiological value of ABCDE criteria in the diagnosis of cutaneous pigmented tumors. Dermatology. 1998;197(1):11-7. doi: 10.1159/000017969. PMID: 9693179. (https://pubmed.ncbi.nlm.nih.gov/9693179/)
  4. Ebell M. Clinical diagnosis of melanoma. Am Fam Physician. 2008 Nov 15;78(10):1205, 1208. PMID: 19035070. (https://pubmed.ncbi.nlm.nih.gov/19035070/)
  5. Gaudy-Marqueste C, Wazaefi Y, Bruneu Y, Triller R, Thomas L, Pellacani G, Malvehy J, Avril MF, Monestier S, Richard MA, Fertil B, Grob JJ. Ugly Duckling Sign as a Major Factor of Efficiency in Melanoma Detection. JAMA Dermatol. 2017 Apr 1;153(4):279-284. doi: 10.1001/jamadermatol.2016.5500. PMID: 28196213. (https://pubmed.ncbi.nlm.nih.gov/28196213/)
  6. Ilyas M, Costello CM, Zhang N, Sharma A. The role of the ugly duckling sign in patient education. J Am Acad Dermatol. 2017 Dec;77(6):1088-1095. doi: 10.1016/j.jaad.2017.06.152. Epub 2017 Sep 28. PMID: 28964538. (https://pubmed.ncbi.nlm.nih.gov/28964538/)
  7. Swetter SM, Tsao H, Bichakjian CK, Curiel-Lewandrowski C, Elder DE, Gershenwald JE, Guild V, Grant-Kels JM, Halpern AC, Johnson TM, Sober AJ, Thompson JA, Wisco OJ, Wyatt S, Hu S, Lamina T. Guidelines of care for the management of primary cutaneous melanoma. J Am Acad Dermatol. 2019 Jan;80(1):208-250. doi: 10.1016/j.jaad.2018.08.055. Epub 2018 Nov 1. PMID: 30392755. (https://pubmed.ncbi.nlm.nih.gov/30392755/)
  8. Goldberg AD, Blankstein R, Padera RF. Tumors metastatic to the heart. Circulation. 2013 Oct 15;128(16):1790-4. doi: 10.1161/CIRCULATIONAHA.112.000790. PMID: 24126323. (https://pubmed.ncbi.nlm.nih.gov/24126323/)

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

My patient presents for evaluation of a mole on her arm. What features of the mole should I look for to help me distinguish a benign mole from melanoma?

Is it safe to use diltiazem or verapamil for treatment of my hospitalized patient with heart failure with reduced ejection fraction (HFrEF) and atrial fibrillation?

Short answer, no! It is generally recommended to avoid the use of diltiazem or verapamil, both a non-dihydropyridine calcium channel blocker (CCB), in patients with HFrEF.  Multiple randomized controlled trials involving patients with HFrEF have shown that use of diltiazem [1] or verapamil [2] is associated with increased cardiovascular mortality and morbidity, especially congestive heart failure (CHF) exacerbations.

Although you might argue that most studies [1,2] on HFrEF on CCBs have been based on patients on chronic (weeks to months) therapy, these agents are also sometimes used in the acute inpatient setting for rate control in atrial fibrillation and even blood pressure control. Even in acute settings, avoidance of these agents–or at least using them with great caution— in patients with HFrEF is prudent. Fortunately, for blood pressure control, another CCB, amlodipine [3] has been deemed safe to use in patients with HFrEF.

Adverse effects of diltiazem and verapamil are often attributed to their negative inotropic effects. As a result, patients with preexisting left ventricular dysfunction may be expected to have worse outcomes. In contrast, amlodipine primarily acts on the peripheral vasculature without significant negative inotropic effect. [4]

What about the use of these agents in patients with heart failure and preserved ejection fraction? Studies to date have found that CCBs are safe in this setting, although no mortality benefit has been shown with their use either [1]

Bonus Pearl: Did you know that use of another CCB, nifedipine, a close cousin of amlodipine (both 1,4- dihydropyridines), has been associated with increased cardiovascular morbidity (worsening CHF and increased hospitalizations) in patients with HFrEF? [5]

Contributed by Fahad Tahir, MD, Mercy Hospital-St. Louis, St. Louis, Missouri

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References:

  1. Goldstein RE, Boccuzzi SJ, Cruess D, Nattel S. Diltiazem increases late-onset congestive heart failure in postinfarction patients with early reduction in ejection fraction. The Adverse Experience Committee; and the Multicenter Diltiazem Postinfarction Research Group. Circulation. 1991 Jan;83(1):52-60. doi: 10.1161/01.cir.83.1.52. PMID: 1984898.https://www.ahajournals.org/doi/epdf/10.1161/01.CIR.83.1.52
  2. Effect of verapamil on mortality and major events after acute myocardial infarction (the Danish Verapamil Infarction Trial II–DAVIT II). Am J Cardiol. 1990 Oct 1;66(10):779-85. doi: 10.1016/0002-9149(90)90351-z. PMID: 2220572.https://www.ajconline.org/article/0002-9149(90)90351-Z/pdf
  3. Packer M, Carson P, Elkayam U, Konstam MA, Moe G, O’Connor C, Rouleau JL, Schocken D, Anderson SA, DeMets DL; PRAISE-2 Study Group. Effect of amlodipine on the survival of patients with severe chronic heart failure due to a nonischemic cardiomyopathy: results of the PRAISE-2 study (prospective randomized amlodipine survival evaluation 2). JACC Heart Fail. 2013 Aug;1(4):308-314. doi: 10.1016/j.jchf.2013.04.004. Epub 2013 Aug 5. PMID: 24621933.https://reader.elsevier.com/reader/sd/pii/S2213177913001844?token=510153852A5AEBBDF5CA9F8B16C671C4E2F4B511B6F723227BA1D2180CDAA4726EC329D5ABC4118738CB1D8B67A3CF6B&originRegion=us-east-1&originCreation=20220316135803
  4. Zamponi, G. W., Striessnig, J., Koschak, A., & Dolphin, A. C. (2015). The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential. Pharmacological reviews, 67(4), 821–870.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630564/
  5. Elkayam U, Amin J, Mehra A, Vasquez J, Weber L, Rahimtoola SH. A prospective, randomized, double-blind, crossover study to compare the efficacy and safety of chronic nifedipine therapy with that of isosorbide dinitrate and their combination in the treatment of chronic congestive heart failure. Circulation. 1990 Dec;82(6):1954-61. doi: 10.1161/01.cir.82.6.1954. PMID: 2242521.https://www.ahajournals.org/doi/epdf/10.1161/01.CIR.82.6.1954

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Is it safe to use diltiazem or verapamil for treatment of my hospitalized patient with heart failure with reduced ejection fraction (HFrEF) and atrial fibrillation?

My patient on chronic oral baclofen began having mental status changes and hallucinations soon after hospitalization while still receiving baclofen. Could a lower than home-dose of baclofen have caused his withdrawal symptoms?

Absolutely! Although we usually think of withdrawal symptoms in the setting of complete discontinuation of certain CNS depressants, even a reduced dose of baclofen1,2 in a patient who has been on a higher dose chronically can precipitate full-blown withdrawal symptoms, such as delirium, fevers, hallucinations, hyperspasticity, autonomic instability and even respiratory failure, multiorgan failure, cardiac arrest and death.1-5

Recall that baclofen is a GABA-B agonist and a potent inhibitor of neuronal synapses with resultant decreased excitation of muscle spindles and muscle spasticity.6 Similar to other benzodiazepines, baclofen is also a CNS depressant and bears many similarities with alcohol in its physiologic effects.  For example, baclofen and alcohol both produce unsteady gait, dizziness, mood alterations and impairment in attention and memory and reduce anxiety, among others.  Not surprisingly, abrupt withdrawal from baclofen may produce similar symptoms as those associated with alcohol withdrawal, such as confusion, hallucination and delirium (observed in our patient) as well as seizures.3 Withdrawal symptoms typically occur 24-48 hours after discontinuation or reduction in the dose of baclofen.1,2

Of course, many of our hospitalized patients are already at risk of mental status changes or sedation from their underlying conditions or from medications needed to treat them.  In this setting, consideration in reducing the home dose of certain CNS depressants, such as baclofen, is understandable and reasonable. However, we should also keep in mind that even a reduction in the chronic dose of baclofen carries a risk of withdrawal!  Unfortunately, healthcare facilities often lack established management protocols for anticipated interruption of oral baclofen.7

In our patient, the home dose of baclofen had been reduced by one-half following his admission. Worsening delirium and new onset visual and auditory hallucinations were noted within a few days of hospitalization. Thankfully, no further bouts of confusion or hallucination was observed after resuming his home dose.

Bonus Pearl:

Did you know that baclofen is often used (off label) to treat intractable hiccups of central origin? 8,9

Contributed by Fahad Tahir, MD, Mercy Hospital-St. Louis, St. Louis, Missouri

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References:

  1. Terrence CF, Fromm GH. Complications of Baclofen Withdrawal. Arch Neurol. 1981;38(9):588–589. doi:10.1001/archneur.1981.00510090082011. https://jamanetwork.com/journals/jamaneurology/article-abstract/580084
  1. O’Rourke, F., Steinberg, R., Ghosh, P., & Khan, S. (2001). Withdrawal of baclofen may cause acute confusion in elderly patients. BMJ (Clinical research ed.), 323(7317), 870.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1121408/ 
  1. de Beaurepaire R. A review of the potential mechanisms of action of baclofen in alcohol use disorder. Front. Psychiatry 2018; 9:506). In fact, baclofen may be a promising treatment for alcohol use disorder. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232933/pdf/fpsyt-09-00506.pdf
  2. Cardoso AL, Quintaneiro C, Seabra H, Teixeira C. Cardiac arrest due to baclofen withdrawal syndrome. BMJ Case Rep. 2014;2014:bcr2014204322. Published 2014 May 14.doi:10.1136/bcr-2014-204322 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4025399/pdf/bcr-2014-204322.pdf
  1. Green LB, Nelson VS. Death after acute withdrawal of intrathecal baclofen: case report and literature review. Arch Phys Med Rehabil. 1999 Dec;80(12):1600-4. doi: 10.1016/s0003-9993(99)90337-4. PMID: 10597813. https://www.archives-pmr.org/article/S0003-9993(99)90337-4/pdf
  1. Allerton CA, Boden PR, Hill RG. Actions of the GABAB agonist, (-)-baclofen, on neurones in deep dorsal horn of the rat spinal cord in vitro. Br J Pharmacol. 1989;96(1):29-38. doi:10.1111/j.1476-5381.1989.tb11780.x https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1854300/
  1. Schmitz NS, Krach LE, Coles LD, Schrogie J, Cloyd JC, Kriel RL. Characterizing Baclofen Withdrawal: A National Survey of Physician Experience. Pediatr Neurol. 2021 Sep;122:106-109. doi: 10.1016/j.pediatrneurol.2021.06.007. Epub 2021 Jul 28. PMID: 34330615. https://www.pedneur.com/article/S0887-8994(21)00129-6/fulltext
  1. Zhang, C., Zhang, R., Zhang, S. et al. Baclofen for stroke patients with persistent hiccups: a randomized, double-blind, placebo-controlled trial. Trials 15, 295 (2014). https://doi.org/10.1186/1745-6215-15-295
  1. Jeon YS, Kearney AM, Baker PG Management of hiccups in palliative care patients BMJ Supportive & Palliative Care 2018;8:1-6. https://spcare.bmj.com/content/8/1/1.long

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

My patient on chronic oral baclofen began having mental status changes and hallucinations soon after hospitalization while still receiving baclofen. Could a lower than home-dose of baclofen have caused his withdrawal symptoms?

Should healthy adults receive a Covid vaccine booster shot and why?

A booster shot of Covid vaccine (eg, mRNA, Pfizer or Moderna) is now recommended by the CDC even for healthy adults as follows:1

  • If you received Pfizer vaccine as your primary series, are ≥12 years old and at least 5 months after your 2nd dose
  • If you received Moderna vaccine as your primary series, are ≥18 years old and at least 5 months after your 2nd dose
  • If you received J&J vaccine, are ≥18 years old and at least 2 months after your 1st dose

There are at least 3 reasons for receiving a Covid vaccine booster: 1

  • Waning immunity after primary vaccine series
  • Emergence of Omicron variant which seems to be less responsive to the existing immunity from the vaccine
  • Recent data from clinical trials showing that a booster shot increased the immune response in trial participants who completed an either Pfizer or Moderna mRNA vaccine primary series 6 months earlier or had J&J vaccine single dose 2 months earlier

Here is the data from CDC on the vaccine effectiveness against Covid based on epidemiologic data on emergency department (ED)/urgent care (UC) encounters or hospitalization during the recent Omicron-predominant period:2

 Vaccine effectiveness against ED/Urgent care encounters 

  • 2 doses of mRNA vaccine: 41% (69% <2 months vs 37% ≥5 months after last dose)
  • 3 doses of mRNA vaccine: 83% (87% < 2 months vs 66% 4 months vs 31% ≥5 months)

Vaccine effectiveness against hospitalization 

  • 2 doses of mRNA vaccine: 55% (71% < 2months vs 54% ≥5 months)
  • 3 doses of mRNA overall 88% (91% if < 2 months, 78% if ≥4 months)

So take full advantage of available Covid vaccines and maximize your chance of not getting Covid!

 

Bonus Pearl: Did you know that a recent CDC study found that people 18 years and older who received the same mRNA vaccine brand for all their vaccinations experienced fewer adverse reactions following the booster dose than they did after their second dose of mRNA vaccine, with 92% of reported reactions not considered serious?3

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References

  1. Covid-19 vaccine booster shots. Feb 2, 2022. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/booster-shot.html#:~:text=It%20depends.,after%20the%20J%26J%2FJanssen%20vaccine. Accessed Feb 24, 2022
  2. Waning 2-dose and 3-dose effectiveness of mRNA vaccines against Covid-19-associated emergency department and urgent care encounters and hospitalizations among adults during periods of delta and omicron variant predominance-VISION network, 110 states, August 2021-Jan 2022. Feb 18, 2022 https://www.cdc.gov/mmwr/volumes/71/wr/mm7107e2.htm#T1_down. Accessed Feb 24, 2022.
  3. New CDC studies: Covid-19 boosters remains safe, continue to offer high levels of protection against severe disease over time and during Omicron and delta waves. Feb 11, 2022. https://www.cdc.gov/media/releases/2022/s0211-covid-19-boosters.html. Accessed Feb 24, 2022

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Should healthy adults receive a Covid vaccine booster shot and why?

My middle-age immunocompromised patient receiving immunosuppressants has had 3 doses of mRNA Covid vaccine and is now 4 months out from her 3rd dose.  Should she consider a fourth dose of Covid vaccine?

Yes! According to the Centers for Disease Control and Prevention (CDC) of the U.S.,1 persons who are “moderately or severely immunocompromised” and have received 3 doses of an mRNA vaccine (either Pfizer [12+ years old) or Moderna (18+ years old]) should receive a 4th dose (“booster”) at least 3 months after the 3rd dose.  Similarly, those who initially received a J&J vaccine followed by one of the aforementioned mRNA vaccines and are at least 2 months from the 2nd dose should also receive a 3rd dose (booster. 

The following are considered moderately or severely immunocompromised conditions by CDC: 

  • Active cancer treatment for tumors or cancers of the blood
  • Organ transplant with immunosuppressants on board
  • Stem cell transplant within the last 2 years or taking immunosuppressants
  • Moderate or severe primary immunodeficiency (eg, DiGeorge or Wiskott-Aldrich syndromes)
  • Advanced or untreated HIV infection
  • Active treatment with high-dose corticosteroids or other immunosuppressants

A published study2 of Covid-19-associated emergency department (ED) and urgent care (UC) encounters and hospitalization among adults during a period including Omicron variant predominance in 10 states found vaccine effectiveness for ED/UC visits dropping to 66% and for hospitalization to 78% by the 4th month after a 3rd dose (vs 87% and 91%, respectively during the 2 months after a 3rd dose).  This study did not distinguish immunocompromised from non-immunocompromised persons, however.  More data on the vaccine effectiveness in non-immunocompromised persons at high risk of Covid-19 related complications would be welcome.

Bonus Pearl: Did you know that of American adults who are fully vaccinated against Covid-19, only about 30% have received an additional Covid vaccine dose beyond the primary series3 

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References

  1. Covid-19 vaccines for moderately or severely immunocompromised people (Updated Feb 17, 2022). Accessed Feb 21, 2022.  https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/immuno.html?s_cid=10483:immunocompromised%20and%20covid%20vaccine:sem.ga:p:RG:GM:gen:PTN:FY21
  2. Waning 2-doe and 3-dose effectiveness of mRNA vaccines against Covid-10-associated emergency department and urgent care encounters and hospitalizations among adults during periods of delta and omicron variant predominance—Vision Network, 10 states, August 2021-January 2022. MMWR 2022; 71:255-63. https://www.cdc.gov/mmwr/volumes/71/wr/mm7107e2.htm?s_cid=mm7107e2_w
  3. Hubler S, Harman A. As Cov id surges, experts say U.S. booster effort is falling behind. NY Times, December 18, 2021. https://www.nytimes.com/2021/12/18/us/omicron-booster-shots-americans.html

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

My middle-age immunocompromised patient receiving immunosuppressants has had 3 doses of mRNA Covid vaccine and is now 4 months out from her 3rd dose.  Should she consider a fourth dose of Covid vaccine?