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S-nitrosohemoglobin deficiency: A mechanism for loss of physiological activity in banked blood
S-nitrosohemoglobin deficiency: A mechanism for loss of physiological activity in banked blood
James D. Reynolds*, Gregory S. Ahearn{dagger}, Michael Angelo{dagger}, Jian Zhang{dagger}, Fred Cobb{dagger},{ddagger}, and Jonathan S. Stamler  Published online before print October 11, 2007
James D. Reynolds*, Gregory S. Ahearn{dagger}, Michael Angelo{dagger}, Jian Zhang{dagger}, Fred Cobb{dagger},{ddagger}, and Jonathan S. Stamler  Published online before print October 11, 2007
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0707958104  Accessed 10/15/07</ref><br>    ❑Blood transfusion,<br>    ❑Iron transfusion<br>    ❑Folate therapy<br>    ❑Vit B12|C05=<div style="float: left; text-align: left; width: 10em; padding:1em;">'''Fatigue due to [[Mononucleosis]]'''<ref>{{cite journal | author=Candy B, Hotopf M. | year=2006 | issue=4 | pages=CD004402 | journal=Cochrane Database Sys Rev | title=Steroids for symptom control in infectious mononucleosis | pmid=16856045 | doi=10.1002/14651858.CD004402.pub2 }}</ref><br><ref name="TGAntibiotic13">Antibiotic Expert Group. Therapeutic guidelines: Antibiotic. 13th ed. North Melbourne: Therapeutic Guidelines; 2006.</ref><ref name="WebMD">{{cite web |title=Infectious Mononucleosis |url=http://www.webmd.com/hw/infection/hw168622.asp |date= Jan 24, 2006 |publisher=WebMD |accessdate=2006-07-10}}</ref><ref name="Torre1999">{{cite journal |author=Torre D, Tambini R |title=Acyclovir for treatment of infectious mononucleosis: a meta-analysis |journal=Scand. J. Infect. Dis. |volume=31 |issue=6 |pages=543–7 |year=1999 |pmid=10680982 |doi=}}</ref><ref name="pmid17369082">{{cite journal |author=Balfour HH, Hokanson KM, Schacherer RM, ''et al'' |title=A virologic pilot study of valacyclovir in infectious mononucleosis |journal=J. Clin. Virol. |volume=39 |issue=1 |pages=16–21 |year=2007 |pmid=17369082 |doi=10.1016/j.jcv.2007.02.002}}</ref><ref>{{cite journal |author=Simon et al. |title=The Effect of Valacyclovir and Prednisolone in Reducing Symptoms of EBV Illness In Children: A Double-Blind, Placebo-Controlled Study. |journal=International Pediatrics |volume=18 |issue=3 |pages=164-169 |year=2003 |month=March}}</ref><ref>{{cite journal |author=Balfour HH, Hokanson KM, Schacherer RM, ''et al'' |title=A virologic pilot study of valacyclovir in infectious mononucleosis |journal=J. Clin. Virol. |volume=39 |issue=1 |pages=16–21 |year=2007 |pmid=17369082 |doi=10.1016/j.jcv.2007.02.002}}</ref> <br>    ❑[[NSAID]]<br>    ❑Intravenous corticostreoid<br>    ❑[[Acyclovir]]<br>    ❑Opioid analgesics <br>'''Fatigue due to [[Viral Hepatitis]]'''.<ref name="pmid11799479">{{cite journal| author=Vargas HE, Dodson FS, Rakela J| title=A concise update on the status of liver transplantation for hepatitis B virus: the challenges in 2002. | journal=Liver Transpl | year= 2002 | volume= 8 | issue= 1 | pages= 2-9 | pmid=11799479 | doi=10.1053/jlts.2002.29765 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11799479  }} </ref><ref name="pmid2202639">{{cite journal| author=Omata M| title=Significance of extrahepatic replication of hepatitis B virus. | journal=Hepatology | year= 1990 | volume= 12 | issue= 2 | pages= 364-6 | pmid=2202639 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2202639  }} </ref><ref name="pmid8629297">{{cite journal| author=McGory RW, Ishitani MB, Oliveira WM, Stevenson WC, McCullough CS, Dickson RC et al.| title=Improved outcome of orthotopic liver transplantation for chronic hepatitis B cirrhosis with aggressive passive immunization. | journal=Transplantation | year= 1996 | volume= 61 | issue= 9 | pages= 1358-64 | pmid=8629297 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8629297  }} </ref><ref name="pmid15776431">{{cite journal| author=Marzano A, Gaia S, Ghisetti V, Carenzi S, Premoli A, Debernardi-Venon W et al.| title=Viral load at the time of liver transplantation and risk of hepatitis B virus recurrence. | journal=Liver Transpl | year= 2005 | volume= 11 | issue= 4 | pages= 402-9 | pmid=15776431 | doi=10.1002/lt.20402 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15776431  }} </ref>:<br>    ❑Entecavir<br>    ❑Tenofovir<br>    ❑Interferon-α 2b<br>    ❑PegIFNα<br>    ❑Telbivudine<br>    ❑Adefovir<br>    ❑Lamivudine<br>'''Fatigue due to [[Endocarditis]]'''<ref name="pmid24603192">{{cite journal |vauthors=Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP, Guyton RA, O'Gara PT, Ruiz CE, Skubas NJ, Sorajja P, Sundt TM, Thomas JD |title=2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines |journal=J. Am. Coll. Cardiol. |volume=63 |issue=22 |pages=2438–88 |year=2014 |pmid=24603192 |doi=10.1016/j.jacc.2014.02.537 |url=}}</ref>:<br>    ❑Empiric antibiotics<br>    ❑Antithrombotic therapy|C06=<div style="float: left; text-align: left; width: 10em; padding:1em;">'''Fatigue due to [[Fibromyalgia]]''':<ref name="pmid14661675">{{cite journal|author=Plotnikoff GA, Quigley JM |title=Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain |journal=Mayo Clin. Proc.|volume=78 |issue=12 |pages=1463–70 |year=2003 |pmid=14661675 |doi=}}</ref>; more recent studies make this doubtful.<ref name="pmid18431091">{{cite journal|author=Warner AE, Arnspiger SA |title=Diffuse musculoskeletal pain is not associated with low vitamin D levels or improved by treatment with vitamin D |journal=J Clin Rheumatol |volume=14 |issue=1 |pages=12–6 |year=2008 |month=February |pmid=18431091 |doi=10.1097/RHU.0b013e31816356a9 |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?an=00124743-200802000-00003 |issn=}}</ref><ref name="pmid19364687">{{cite journal| author=Arvold DS, Odean MJ, Dornfeld MP, Regal RR, Arvold JG, Karwoski GC et al.| title=Correlation of symptoms with vitamin D deficiency and symptom response to cholecalciferol treatment: a randomized controlled trial. | journal=Endocr Pract | year= 2009 | volume= 15 | issue= 3 | pages= 203-12 | pmid=19364687 | doi= | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19364687  }} </ref><br>    ❑Amitriptiline<br>    ❑Cyclobenzaprine<br>    ❑Dulexitine<br>    ❑Minlacipran<br>    ❑Pregabalin<br>'''Fatigue due to [[Polymyalgia]]''':<ref name="pmid23051717">{{cite journal| author=Kermani TA, Warrington KJ| title=Polymyalgia rheumatica. | journal=Lancet | year= 2013 | volume= 381 | issue= 9860 | pages= 63-72 | pmid=23051717 | doi=10.1016/S0140-6736(12)60680-1 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23051717  }} </ref><ref name="pmid23051717">{{cite journal| author=Kermani TA, Warrington KJ| title=Polymyalgia rheumatica. | journal=Lancet | year= 2013 | volume= 381 | issue= 9860 | pages= 63-72 | pmid=23051717 | doi=10.1016/S0140-6736(12)60680-1 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23051717  }} </ref><br>    ❑Glucocorticosteroids<br>'''Fatigue due to  [[Rheumatoid arthritis]]:<ref name="pmid29129326">{{cite journal |vauthors=Xu C, Peng H, Li R, Chai W, Li X, Fu J, Liu K, Yu B, Jia C, Chen J |title=Risk factors and clinical characteristics of deep knee infection in patients with intra-articular injections: A matched retrospective cohort analysis |journal=Semin. Arthritis Rheum. |volume= |issue= |pages= |date=October 2017 |pmid=29129326 |doi=10.1016/j.semarthrit.2017.10.013 |url=}}</ref><ref name="pmid16258899">{{cite journal |vauthors=Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM, Zwinderman AH, Ronday HK, Han KH, Westedt ML, Gerards AH, van Groenendael JH, Lems WF, van Krugten MV, Breedveld FC, Dijkmans BA |title=Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial |journal=Arthritis Rheum. |volume=52 |issue=11 |pages=3381–90 |date=November 2005 |pmid=16258899 |doi=10.1002/art.21405 |url=}}</ref><br><ref name="pmid18662933">{{cite journal |vauthors=van der Kooij SM, Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Güler-Yüksel M, Zwinderman AH, Kerstens PJ, van der Lubbe PA, de Beus WM, Grillet BA, Ronday HK, Huizinga TW, Breedveld FC, Dijkmans BA, Allaart CF |title=Drug-free remission, functioning and radiographic damage after 4 years of response-driven treatment in patients with recent-onset rheumatoid arthritis |journal=Ann. Rheum. Dis. |volume=68 |issue=6 |pages=914–21 |date=June 2009 |pmid=18662933 |doi=10.1136/ard.2008.092254 |url=}}</ref>'''<br>    ❑Leflunomide<br>    ❑Sulfasalazine<br>    ❑Hydroxycloroquine<br>    ❑Rituximab<br>    ❑Tocolizumab<br>    ❑Azathioprim<br>    ❑Cyclosporine<br>    ❑Anakirna<br>    ❑Abatacept<br>    ❑Baricitinib<br>    ❑DMARDS<br>'''Fatigue due to [[Sjögren's syndrome]]<ref name="pmid18984418">{{cite journal |vauthors=Wu AJ |title=Optimizing dry mouth treatment for individuals with Sjögren's syndrome |journal=Rheum. Dis. Clin. North Am. |volume=34 |issue=4 |pages=1001–10, x |date=November 2008 |pmid=18984418 |doi=10.1016/j.rdc.2008.08.013 |url=}}</ref><ref name="pmid17714766">{{cite journal |vauthors=Thanou-Stavraki A, James JA |title=Primary Sjogren's syndrome: current and prospective therapies |journal=Semin. Arthritis Rheum. |volume=37 |issue=5 |pages=273–92 |date=April 2008 |pmid=17714766 |doi=10.1016/j.semarthrit.2007.06.002 |url=}}</ref><ref name="pmid22549247">{{cite journal |vauthors=Ramos-Casals M, Brito-Zerón P, Sisó-Almirall A, Bosch X, Tzioufas AG |title=Topical and systemic medications for the treatment of primary Sjögren's syndrome |journal=Nat Rev Rheumatol |volume=8 |issue=7 |pages=399–411 |date=May 2012 |pmid=22549247 |doi=10.1038/nrrheum.2012.53 |url=}}</ref><br><ref name="pmid22161442">{{cite journal |vauthors=Furness S, Worthington HV, Bryan G, Birchenough S, McMillan R |title=Interventions for the management of dry mouth: topical therapies |journal=Cochrane Database Syst Rev |volume= |issue=12 |pages=CD008934 |date=December 2011 |pmid=22161442 |doi=10.1002/14651858.CD008934.pub2 |url=}}</ref>'''<br>    ❑Pilocarpine<br>    ❑Cevimeline<br>    ❑Methotroxate|C07=<div style="float: left; text-align: left; width: 10em; padding:1em;">'''Fatigue due to [[Mood disorders]]:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>'''<br>    ❑CBT<br>    ❑Anti depresant therapy<br>    ❑Anxiolytic therapy }}
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0707958104  Accessed 10/15/07</ref><br>    ❑Blood transfusion,<br>    ❑Iron transfusion<br>    ❑Folate therapy<br>    ❑Vit B12|C05=<div style="float: left; text-align: left; width: 10em; padding:1em;">'''Fatigue due to [[Mononucleosis]]'''<ref>{{cite journal | author=Candy B, Hotopf M. | year=2006 | issue=4 | pages=CD004402 | journal=Cochrane Database Sys Rev | title=Steroids for symptom control in infectious mononucleosis | pmid=16856045 | doi=10.1002/14651858.CD004402.pub2 }}</ref><br><ref name="TGAntibiotic13">Antibiotic Expert Group. Therapeutic guidelines: Antibiotic. 13th ed. North Melbourne: Therapeutic Guidelines; 2006.</ref><ref name="WebMD">{{cite web |title=Infectious Mononucleosis |url=http://www.webmd.com/hw/infection/hw168622.asp |date= Jan 24, 2006 |publisher=WebMD |accessdate=2006-07-10}}</ref><ref name="Torre1999">{{cite journal |author=Torre D, Tambini R |title=Acyclovir for treatment of infectious mononucleosis: a meta-analysis |journal=Scand. J. Infect. Dis. |volume=31 |issue=6 |pages=543–7 |year=1999 |pmid=10680982 |doi=}}</ref><ref name="pmid17369082">{{cite journal |author=Balfour HH, Hokanson KM, Schacherer RM, ''et al'' |title=A virologic pilot study of valacyclovir in infectious mononucleosis |journal=J. Clin. Virol. |volume=39 |issue=1 |pages=16–21 |year=2007 |pmid=17369082 |doi=10.1016/j.jcv.2007.02.002}}</ref><ref>{{cite journal |author=Simon et al. |title=The Effect of Valacyclovir and Prednisolone in Reducing Symptoms of EBV Illness In Children: A Double-Blind, Placebo-Controlled Study. |journal=International Pediatrics |volume=18 |issue=3 |pages=164-169 |year=2003 |month=March}}</ref><ref>{{cite journal |author=Balfour HH, Hokanson KM, Schacherer RM, ''et al'' |title=A virologic pilot study of valacyclovir in infectious mononucleosis |journal=J. Clin. Virol. |volume=39 |issue=1 |pages=16–21 |year=2007 |pmid=17369082 |doi=10.1016/j.jcv.2007.02.002}}</ref> <br>    ❑[[NSAID]]<br>    ❑Intravenous corticostreoid<br>    ❑[[Acyclovir]]<br>    ❑Opioid analgesics <br>'''Fatigue due to [[Viral Hepatitis]]'''.<ref name="pmid11799479">{{cite journal| author=Vargas HE, Dodson FS, Rakela J| title=A concise update on the status of liver transplantation for hepatitis B virus: the challenges in 2002. | journal=Liver Transpl | year= 2002 | volume= 8 | issue= 1 | pages= 2-9 | pmid=11799479 | doi=10.1053/jlts.2002.29765 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11799479  }} </ref><ref name="pmid2202639">{{cite journal| author=Omata M| title=Significance of extrahepatic replication of hepatitis B virus. | journal=Hepatology | year= 1990 | volume= 12 | issue= 2 | pages= 364-6 | pmid=2202639 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2202639  }} </ref><ref name="pmid8629297">{{cite journal| author=McGory RW, Ishitani MB, Oliveira WM, Stevenson WC, McCullough CS, Dickson RC et al.| title=Improved outcome of orthotopic liver transplantation for chronic hepatitis B cirrhosis with aggressive passive immunization. | journal=Transplantation | year= 1996 | volume= 61 | issue= 9 | pages= 1358-64 | pmid=8629297 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8629297  }} </ref><ref name="pmid15776431">{{cite journal| author=Marzano A, Gaia S, Ghisetti V, Carenzi S, Premoli A, Debernardi-Venon W et al.| title=Viral load at the time of liver transplantation and risk of hepatitis B virus recurrence. | journal=Liver Transpl | year= 2005 | volume= 11 | issue= 4 | pages= 402-9 | pmid=15776431 | doi=10.1002/lt.20402 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15776431  }} </ref>:<br>    ❑Entecavir<br>    ❑Tenofovir<br>    ❑Interferon-α 2b<br>    ❑PegIFNα<br>    ❑Telbivudine<br>    ❑Adefovir<br>    ❑Lamivudine<br>'''Fatigue due to [[Endocarditis]]'''<ref name="pmid24603192">{{cite journal |vauthors=Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP, Guyton RA, O'Gara PT, Ruiz CE, Skubas NJ, Sorajja P, Sundt TM, Thomas JD |title=2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines |journal=J. Am. Coll. Cardiol. |volume=63 |issue=22 |pages=2438–88 |year=2014 |pmid=24603192 |doi=10.1016/j.jacc.2014.02.537 |url=}}</ref>:<br>    ❑Empiric antibiotics<br>    ❑Antithrombotic therapy|C06=<div style="float: left; text-align: left; width: 10em; padding:1em;">'''Fatigue due to [[Fibromyalgia]]''':<ref name="pmid14661675">{{cite journal|author=Plotnikoff GA, Quigley JM |title=Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain |journal=Mayo Clin. Proc.|volume=78 |issue=12 |pages=1463–70 |year=2003 |pmid=14661675 |doi=}}</ref>; <ref name="pmid18431091">{{cite journal|author=Warner AE, Arnspiger SA |title=Diffuse musculoskeletal pain is not associated with low vitamin D levels or improved by treatment with vitamin D |journal=J Clin Rheumatol |volume=14 |issue=1 |pages=12–6 |year=2008 |month=February |pmid=18431091 |doi=10.1097/RHU.0b013e31816356a9 |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?an=00124743-200802000-00003 |issn=}}</ref><ref name="pmid19364687">{{cite journal| author=Arvold DS, Odean MJ, Dornfeld MP, Regal RR, Arvold JG, Karwoski GC et al.| title=Correlation of symptoms with vitamin D deficiency and symptom response to cholecalciferol treatment: a randomized controlled trial. | journal=Endocr Pract | year= 2009 | volume= 15 | issue= 3 | pages= 203-12 | pmid=19364687 | doi= | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19364687  }} </ref><br>    ❑Amitriptiline<br>    ❑Cyclobenzaprine<br>    ❑Dulexitine<br>    ❑Minlacipran<br>    ❑Pregabalin<br>'''Fatigue due to [[Polymyalgia]]''':<ref name="pmid23051717">{{cite journal| author=Kermani TA, Warrington KJ| title=Polymyalgia rheumatica. | journal=Lancet | year= 2013 | volume= 381 | issue= 9860 | pages= 63-72 | pmid=23051717 | doi=10.1016/S0140-6736(12)60680-1 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23051717  }} </ref><ref name="pmid23051717">{{cite journal| author=Kermani TA, Warrington KJ| title=Polymyalgia rheumatica. | journal=Lancet | year= 2013 | volume= 381 | issue= 9860 | pages= 63-72 | pmid=23051717 | doi=10.1016/S0140-6736(12)60680-1 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23051717  }} </ref><br>    ❑Glucocorticosteroids<br>'''Fatigue due to  [[Rheumatoid arthritis]]:<ref name="pmid29129326">{{cite journal |vauthors=Xu C, Peng H, Li R, Chai W, Li X, Fu J, Liu K, Yu B, Jia C, Chen J |title=Risk factors and clinical characteristics of deep knee infection in patients with intra-articular injections: A matched retrospective cohort analysis |journal=Semin. Arthritis Rheum. |volume= |issue= |pages= |date=October 2017 |pmid=29129326 |doi=10.1016/j.semarthrit.2017.10.013 |url=}}</ref><ref name="pmid16258899">{{cite journal |vauthors=Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM, Zwinderman AH, Ronday HK, Han KH, Westedt ML, Gerards AH, van Groenendael JH, Lems WF, van Krugten MV, Breedveld FC, Dijkmans BA |title=Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial |journal=Arthritis Rheum. |volume=52 |issue=11 |pages=3381–90 |date=November 2005 |pmid=16258899 |doi=10.1002/art.21405 |url=}}</ref><br><ref name="pmid18662933">{{cite journal |vauthors=van der Kooij SM, Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Güler-Yüksel M, Zwinderman AH, Kerstens PJ, van der Lubbe PA, de Beus WM, Grillet BA, Ronday HK, Huizinga TW, Breedveld FC, Dijkmans BA, Allaart CF |title=Drug-free remission, functioning and radiographic damage after 4 years of response-driven treatment in patients with recent-onset rheumatoid arthritis |journal=Ann. Rheum. Dis. |volume=68 |issue=6 |pages=914–21 |date=June 2009 |pmid=18662933 |doi=10.1136/ard.2008.092254 |url=}}</ref>'''<br>    ❑Leflunomide<br>    ❑Sulfasalazine<br>    ❑Hydroxycloroquine<br>    ❑Rituximab<br>    ❑Tocolizumab<br>    ❑Azathioprim<br>    ❑Cyclosporine<br>    ❑Anakirna<br>    ❑Abatacept<br>    ❑Baricitinib<br>    ❑DMARDS<br>'''Fatigue due to [[Sjögren's syndrome]]<ref name="pmid18984418">{{cite journal |vauthors=Wu AJ |title=Optimizing dry mouth treatment for individuals with Sjögren's syndrome |journal=Rheum. Dis. Clin. North Am. |volume=34 |issue=4 |pages=1001–10, x |date=November 2008 |pmid=18984418 |doi=10.1016/j.rdc.2008.08.013 |url=}}</ref><ref name="pmid17714766">{{cite journal |vauthors=Thanou-Stavraki A, James JA |title=Primary Sjogren's syndrome: current and prospective therapies |journal=Semin. Arthritis Rheum. |volume=37 |issue=5 |pages=273–92 |date=April 2008 |pmid=17714766 |doi=10.1016/j.semarthrit.2007.06.002 |url=}}</ref><ref name="pmid22549247">{{cite journal |vauthors=Ramos-Casals M, Brito-Zerón P, Sisó-Almirall A, Bosch X, Tzioufas AG |title=Topical and systemic medications for the treatment of primary Sjögren's syndrome |journal=Nat Rev Rheumatol |volume=8 |issue=7 |pages=399–411 |date=May 2012 |pmid=22549247 |doi=10.1038/nrrheum.2012.53 |url=}}</ref><br><ref name="pmid22161442">{{cite journal |vauthors=Furness S, Worthington HV, Bryan G, Birchenough S, McMillan R |title=Interventions for the management of dry mouth: topical therapies |journal=Cochrane Database Syst Rev |volume= |issue=12 |pages=CD008934 |date=December 2011 |pmid=22161442 |doi=10.1002/14651858.CD008934.pub2 |url=}}</ref>'''<br>    ❑Pilocarpine<br>    ❑Cevimeline<br>    ❑Methotroxate|C07=<div style="float: left; text-align: left; width: 10em; padding:1em;">'''Fatigue due to [[Mood disorders]]:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>'''<br>    ❑CBT<br>    ❑Anti depresant therapy<br>    ❑Anxiolytic therapy }}
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Revision as of 22:43, 28 August 2020

Fatigue
Resident Survival Guide
Overview
Causes
Diagnosis
Treatment
Do's
Don'ts

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Tayyaba Ali, M.D.[2]Mounika Lakhmalla, MBBS[3]Ramyar Ghandriz MD[4]

Synonyms and keywords:Approach to weakness, Approach to tiredness, Approach to lethargy, Approach to debility

Overview

Fatigue is a common nonspecific symptom due to a wide range of etiologies. Patients often use this term to describe a range of issues such as difficulty initiating activity, decreased capacity to maintain activity, trouble with concentration, memory, and emotional stability; or sleepiness or an uncontrollable need to sleep. The term fatigue can sometimes be used synonymously with tiredness. Fatigue can present alone as a primary symptom or in association with other localizing symptoms.

Causes

Life Threatening Causes

Life-threatening causes include conditions that may result in death or permanent disability within 24 hours if left untreated.

Common Causes

  • Multiple sclerosis
  • After malignancy treatment, patients can experience different patterns of fatigue from chemotherapy, radiation treatment, or surgery.

Diagnosis

The approach to the diagnosis of fatigue is based on a step-wise testing strategy. Below is an algorithm summarizing the identification and laboratory diagnosis of fatigue.

  • Diagnostic evaluation of fatigue when it presents as a predominant symptom includes a detailed history and physical examination, basic laboratory studies, and updated cancer screening interventions.
  • Additional diagnostic testing depends on associated localized findings.
  • Extensive laboratory studies without a suggestive history or physical exam findings is of limited diagnostic utility while evaluating chronic fatigue.


 
 
 
 
 
 
 
 
 
 
 
 
Seek proper history, ask patients to describe in their own words, what do they mean by fatigue?
This will help distinguish fatigue from
somnolence
muscle weakness
The history should also determine the characteristics, severity, and temporal pattern of fatigue:
❑ Onset – Abrupt or gradual, relationship to illness or life event
❑ Course – Stable, improving, or worsening
❑ Duration and daily pattern
❑ Factors that alleviate or exacerbate it
❑ Impact on daily life – Ability to work, socialize, participate in family activities
❑ Accommodations that the patient/family has had to make to deal with symptom
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Characterize the cardiac symptoms:
Dyspnea on exertion
Orthopnea
❑ Leg swelling
 
Characterize the pulmonary symptoms:
❑ Dyspnea
❑ Chronic cough
❑ Sputum production
❑ Snoring
❑ Interrupted breathing during sleep
 
Characterize the endocrinologic / metabolic symptoms:
Cold intolerance
Weight gain
Constipation
❑ Dry skin
Heat intolerance
Weight loss
❑ Diarrhea
❑ Moist skin
❑ Nausea/vomiting
❑ Mental status changes
❑ Decreased urine
❑ Abdominal distention
❑ Gastrointestinal bleeding
❑ Salt craving
❑ Gastrointestinal complaints
❑ Malaise
❑ Cognitive dysfunction
Anorexia
Polydipsia/polyuria
 
Characterize the hematologic / neoplastic symptoms:
❑ Dizziness
❑ Weakness
Palpitations
Dyspnea
❑ Weight loss
 
Characterize the Infectious diseases symptoms:
❑ Fever/chills
❑ Sore throat
❑ Tender lymph nodes
❑ Nausea/vomiting
❑ Abdominal discomfort
Weight loss
Night sweats
❑ Myalgias
 
Characterize the rheumatologic symptoms:
❑ Chronic diffuse muscle pain
❑ Aching/morning stiffness of shoulders, neck, and hips
 
Characterize the psychological symptoms:
❑ Sad mood
Anhedonia
❑ Altered sleep
❑ Cognitive dysfunction
❑ Generalized nervousness
Panic attacks
Phobias
❑ Multiple chronic constitutional and localized complaints
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Examine the patient:
❑ Elevated jugular venous distension
❑ Peripheral edema
❑ S3 gallop
❑ Inspiratory rales
 
Examine the patient:
❑ Evidence of hyperinflation
Wheezing
Rales
Obesity
❑ Hypertension
 
Examine the patient:
Bradycardia
Goiter
❑ Slow deep tendon reflex relaxation phase
Tachycardia
❑ Ophthalmopathy
❑ Hypertension
❑ Peripheral edema
Jaundice
Palmar erythema
Gynecomastia
Splenomegaly
❑ Evidence of ascites
❑ Hypotension
❑ Hyperpigmentation
❑ Vitiligo
 
Examine the patient:
Tachycardia
Pallor
 
Examine the patient:
Fever
❑ Exudate pharyngitis
❑ Tender cervical adenopathy
Jaundice
❑ Tender hepatomegaly
❑ New (regurgitant) murmur
Cough
Chest pain
❑ Dyspnea
Hemoptysis
 
Examine the patient:
❑ Multiple "tender points" on palpation
❑ Decreased range of motion of shoulders, neck, and hips
 
Examine the patient:
❑ Tachycardia
❑ Muscle tension
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Diagnostic work-up:
❑ Chest radiograph
❑ Echocardiogram
 
Diagnostic work-up:
❑ Chest radiograph
❑ Sleep study
 
Diagnostic work-up:
Thyroid function tests
Renal function tests/ serum electrolytes
Hepatic function tests
❑ Morning cortisol/ACTH, ACTH stimulation test
❑Serum sodium level
❑Serum calcium level
 
Diagnostic work-up:
Complete blood count
 
Diagnostic work-up:
❑ Complete blood/differential count
❑ Monospot
Hepatic function tests
❑ Viral hepatitis serologies
HIV serology
❑ Blood cultures
Echocardiogram
❑ PPD/gamma-interferon assay
❑ Chest radiograph
 
Diagnostic work-up:
Erythrocyte sedimentation rate
 
Diagnostic work-up:
❑ Screening tests (eg, PHQ-2, PHQ-9, GAD-7, SSS-8
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Consider differential diagnosis:
Congective heart failure
Atypical angina [1]
 
Consider differential diagnosis:
Chronic obstructive pulmonary disease [2]
Sleep apnea [3]
 
Consider differential diagnosis:
Hypothyroidism [4]
Hyperthyroidism [5]
❑ Inflammatory bowel disease [6]
Chronic renal disease [7]
Chronic hepatic disease [8]
Adrenal insufficiency [9]
Hyponatremia [10]
Hypercalcemia [11]
 
Consider differential diagnosis:
Anemia [11]
Occult malignancy [12]
 
 
 
Consider differential diagnosis:
Depression [20]
Anxiety disorder [21]
Somatization disorder [22]

Treatment

.

 
 
 
 
 
 
 
 
 
 
 
 
Treat the underlying causes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fatigue due to heart failure[23][24][25][26] :
❑Diuretics
❑Vasodilator Therapy
❑Inotropic Therapy
❑Vasopressor Support
❑ACE Inhibition
❑Beta Blockers
❑Aldosterone Antagonism
❑Morphine
Fatigue due to stable angina[27]:
❑Antiplatelet agents
❑Antianginal agents
❑ACEI/RAAS Blockers
 
Ftigue due to Chronic obstructive pulmonary disease[28][29][30].:
❑Beta Adrenergic Receptor Agonists
❑Long Acting Beta-2 Adrenergic Receptor Agonist
❑Anticholinergics
❑Phosphodiesterase Inhibitor
❑Steroid
❑Antibiotics
❑Mucolytic
Fatigue due to sleep apnea:[31].[32][33][34][35]
❑Weight loss
❑Continuous positive airway pressure
❑Oral appliances
❑Modafinil 200-400 mg per day
❑Acetazolamide
 
Fatigue due to hypothyroidism:.[36][37]
[38]:
❑Synthetic T4(Levothyroxin)
Fatigue due to hyperthyroidism:[39]
❑Beta blockers
❑Methimazole
❑Propylthiouracil
Fatigue due to Chronic Renal Failure:[40]
❑Blood pressure management
❑Kidney Transplant
 
Fatigue due to anemia:[41][42] [43]
❑Blood transfusion,
❑Iron transfusion
❑Folate therapy
❑Vit B12
 
Fatigue due to Mononucleosis[44]
[45][46][47][48][49][50]
NSAID
❑Intravenous corticostreoid
Acyclovir
❑Opioid analgesics
Fatigue due to Viral Hepatitis.[51][52][53][54]:
❑Entecavir
❑Tenofovir
❑Interferon-α 2b
❑PegIFNα
❑Telbivudine
❑Adefovir
❑Lamivudine
Fatigue due to Endocarditis[55]:
❑Empiric antibiotics
❑Antithrombotic therapy
 
Fatigue due to Fibromyalgia:[56]; [57][58]
❑Amitriptiline
❑Cyclobenzaprine
❑Dulexitine
❑Minlacipran
❑Pregabalin
Fatigue due to Polymyalgia:[59][59]
❑Glucocorticosteroids
Fatigue due to Rheumatoid arthritis:[60][61]
[62]

❑Leflunomide
❑Sulfasalazine
❑Hydroxycloroquine
❑Rituximab
❑Tocolizumab
❑Azathioprim
❑Cyclosporine
❑Anakirna
❑Abatacept
❑Baricitinib
❑DMARDS
Fatigue due to Sjögren's syndrome[63][64][65]
[66]

❑Pilocarpine
❑Cevimeline
❑Methotroxate
 
Fatigue due to Mood disorders:[67]
❑CBT
❑Anti depresant therapy
❑Anxiolytic therapy

Do's

  • Though most of the conditions presenting with fatigue have the luxury of time for appropriate evaluation & treatment, a few may require immediate diagnosis & treatment to prevent death or serious sequelae.
  • In case of Cardiovascular emergencies: In symptomatic Heart failure secondary to atrial fibrillation, hemodynamically unstable patients require urgent direct-current cardioversion.
  • Endocrine disorders: Diabetic ketoacidosis or nonketotic hyperglycemic states require urgent correction of blood sugar levels, acidosis, electrolyte & Fluid imbalances.
  • Infectious disease
    • Untreated tuberculosis: respiratory failure and systemic spread of disease in immunocompromised individuals.
    • HIV, if not diagnosed or treated appropriately with antiretroviral drugs, may result in overt AIDS and eventually death.
    • Coronavirus disease 2019 (COVID-19)
      • Patients may develop severe viral pneumonia leading to acute respiratory distress syndrome that is potentially fatal.
      • Suspected COVID-19 infection should be isolated from others, along with contact and droplet precautions, airborne precautions if performing aerosol-generating procedures.

Don'ts

  • Extensive laboratory work-up is rarely helpful in the absence of suggestive signs and symptoms.
  • Mannitol is contraindicated in fatigue treatment.

References

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