1 / 48

Non-infectious causes of fever in the critical care unit

Introduction. Defining a feverPathophysiology of feverNon-infectious causes of feverClinical vignettesMarkers of infections/rapid diagnosticsConclusionsReferences. Learning objectives. State several non-infectious causes of fever in ICU patientsIdentify some rapid and specific tests that mig

lita
Download Presentation

Non-infectious causes of fever in the critical care unit

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

    1. Non-infectious causes of fever in the critical care unit Marion J. Skalweit, MD PhD Case Western Reserve University School of Medicine and the Cleveland VA Medical Center

    2. Introduction Defining a fever Pathophysiology of fever Non-infectious causes of fever Clinical vignettes Markers of infections/rapid diagnostics Conclusions References

    3. Learning objectives State several non-infectious causes of fever in ICU patients Identify some rapid and specific tests that might be used to detect pathogens Appreciate that non-infectious causes of fever may coexist with infectious causes of fever

    4. Disclosures None that are relevant to today’s presentation

    5. What is a fever?

    6. Pathophysiology of fever Adaptive response evolved to help host rid self of pathogens Cytokines released by monocytic cells (IL-1, IL-6 and TNF-a) Bind to receptors in the pre-optic region of the anterior hypothalamus which activates phospholipase A releasing tissue arachadonic acid, a substrate of the cyclo-oxygenase pathway Some cytokines cause direct liberation of Prostaglandin E2, a small molecule that crosses the blood brain barrier and causes the firing of warm sensitive neurons Marik, P. E. “Fever in the ICU” Chest (2000): 117; 855-869.

    8. Marik Chest 2000

    9. “Drug fever” Malignant hyperthermia Neuroleptic malignant syndrome (NMS) “Drug fever” with triad of fever, rash, eosinophilia Stevens-Johnson?toxic epidermal necrolysis MH genetic testing, ryanodine receptor 1 gene polymorphisms, auto dom family predisposition, dantrolene NMS unpredictable? Genetic predisp? bromocriptine Drug fever allergic reaction SJ also idiopathic but known with some agents Abacavir hypersensitivity HLA type B5701MH genetic testing, ryanodine receptor 1 gene polymorphisms, auto dom family predisposition, dantrolene NMS unpredictable? Genetic predisp? bromocriptine Drug fever allergic reaction SJ also idiopathic but known with some agents Abacavir hypersensitivity HLA type B5701

    11. A patient recently started on ziprasadone develops fever, rhabdomyolysis and acute renal failure 47 y/o male found down, somnolent, unable to follow simple commands or walk, BP 68/40, T 39.4ºC Admit 6 d prior for acute decompensation of schizoaffective disorder vs mania, received haloperidol x 1 dose, cont’d on lithium, valproic acid, ziprasadone initiated

    12. A patient recently started on ziprasadone develops fever, rhabdomyolysis and acute renal failure Transferred to MICU, intubated, pressors, fluids and antibiotics started, activated protein C administered for presumed sepsis Labs notable for leukocytosis and markedly elevated CPK and troponin, serum Na, K and Cr; elevated Li level and mild transaminitis Lytes na 161 k 5.3 cl 120 hco3 24 glucose 68 bun 112 cr 6.8 Wbcs 21 nl diff Abg 7.28/45/85 on ac 40%Lytes na 161 k 5.3 cl 120 hco3 24 glucose 68 bun 112 cr 6.8 Wbcs 21 nl diff Abg 7.28/45/85 on ac 40%

    13. Day 3 -Restart Lithium 900mg qhs change from bid to increase compliance with once daily dosing -Increase Depakote 1500mg for further improvement in manic symptoms not completely resolved with lithium -Start Geodon 80mg Bid with meals -Ativan PRN for agitation -Geodon IM 20mg Q4 max 3 dose in 24hrs prn agitation On admission to UH lytes: 161/5.3/120/24/68/6.8/112 VA level 28 lithium 2.07 CK 24K INR 1.17 trop 8.47 Day 8 2/16 to MICU UH febrile with elevated wbc, also with evidence rhabdomyolysis and hepatic/renal dysfunction. Pt was treated with piptazo, vanco, and activated protein C for presumed sepsis. With aggressive hydration, sodium decreased and was weaned from pressors. D22 MICU SPECIFIC FINDINGS Vallecula - Abnormal - extensive subepiglottic edema Trachea - Abnormal - Upper part of trachea showed extensive granulation tissue above the tracheostomy site. There was a piece of sloughed mucosa still attached to the trachea. This piece of mucosa was removed when ETT was placed. COMPLICATIONS None IMPRESSION/DIAGNOSIS - sloughed necrotic tracheal mucosa RECOMMENDATIONS - repeat bronchoscopy tomorrow D29 Report ---- MICROBIOLOGY ---- Accession: MIC 05 4728 Received: Mar 12, 2005 10:21 Collection sample: URINE Collection date: Mar 11, 2005 00:00 Provider: BALGUDE,AMIT * BACTERIOLOGY FINAL REPORT => Mar 15, 2005 TECH CODE: 384 CULTURE RESULTS: 1. >50,000 - <75,000 CFU/ML ESCHERICHIA COLI Comment: *** AMENDED SUSCEPTIBILITY REPORT *** 2. >100,000 CFU/ML ESCHERICHIA COLI Comment: ***AMENDED SUSCEPTIBILITY REPORT *** ANTIBIOTIC SUSCEPTIBILITY TEST RESULTS: 1. ESCHERICHIA COLI : 2. ESCHERICHIA COLI : : SUSC INTP SUSC INTP AMPICILLIN >=32 R >=32 R MCG/ML CEFAZOLIN >=64 R >=64 R MCG/ML CEFTAZIDIME <=1 S <=1 S MCG/ML TRIMETH/SULFA >=320 R >=320 R MCG/ML MEROPENEM <=0.25S <=0.25S GENTAMICIN <=1 S <=1 S MCG/ML IMIPENEM <=1 S <=1 S MCG/ML NITROFURANTOIN128 R 128 R AMPICILLIN/SUL>=32 R >=32 R MCG/ML LEVOFLOXACIN >=8 R >=8 R CEFOTETAN <=4 S <=4 S CEFEPIME <=1 S <=1 S PIP/TAZO 64 I 8 S MCG/ML Facility: CLEVELAND VAMC =============================================================================== Day 3 -Restart Lithium 900mg qhs change from bid to increase compliance with once daily dosing -Increase Depakote 1500mg for further improvement in manic symptoms not completely resolved with lithium -Start Geodon 80mg Bid with meals -Ativan PRN for agitation -Geodon IM 20mg Q4 max 3 dose in 24hrs prn agitation On admission to UH lytes: 161/5.3/120/24/68/6.8/112 VA level 28 lithium 2.07 CK 24K INR 1.17 trop 8.47 Day 8 2/16 to MICU UH febrile with elevated wbc, also with evidence rhabdomyolysis and hepatic/renal dysfunction. Pt was treated with piptazo, vanco, and activated protein C for presumed sepsis. With aggressive hydration, sodium decreased and was weaned from pressors. D22 MICU SPECIFIC FINDINGS Vallecula - Abnormal - extensive subepiglottic edema Trachea - Abnormal - Upper part of trachea showed extensive granulation tissue above the tracheostomy site. There was a piece of sloughed mucosa still attached to the trachea. This piece of mucosa was removed when ETT was placed. COMPLICATIONS None IMPRESSION/DIAGNOSIS - sloughed necrotic tracheal mucosa RECOMMENDATIONS - repeat bronchoscopy tomorrow D29 Report ---- MICROBIOLOGY ---- Accession: MIC 05 4728 Received: Mar 12, 2005 10:21 Collection sample: URINE Collection date: Mar 11, 2005 00:00 Provider: BALGUDE,AMIT * BACTERIOLOGY FINAL REPORT => Mar 15, 2005 TECH CODE: 384 CULTURE RESULTS: 1. >50,000 - <75,000 CFU/ML ESCHERICHIA COLI Comment: *** AMENDED SUSCEPTIBILITY REPORT *** 2. >100,000 CFU/ML ESCHERICHIA COLI Comment: ***AMENDED SUSCEPTIBILITY REPORT *** ANTIBIOTIC SUSCEPTIBILITY TEST RESULTS: 1. ESCHERICHIA COLI : 2. ESCHERICHIA COLI : : SUSC INTP SUSC INTP AMPICILLIN >=32 R >=32 R MCG/ML CEFAZOLIN >=64 R >=64 R MCG/ML CEFTAZIDIME <=1 S <=1 S MCG/ML TRIMETH/SULFA >=320 R >=320 R MCG/ML MEROPENEM <=0.25S <=0.25S GENTAMICIN <=1 S <=1 S MCG/ML IMIPENEM <=1 S <=1 S MCG/ML NITROFURANTOIN128 R 128 R AMPICILLIN/SUL>=32 R >=32 R MCG/ML LEVOFLOXACIN >=8 R >=8 R CEFOTETAN <=4 S <=4 S CEFEPIME <=1 S <=1 S PIP/TAZO 64 I 8 S MCG/ML Facility: CLEVELAND VAMC ===============================================================================

    14. A patient recently started on ziprasadone develops fever, rhabdomyolysis and acute renal failure Patient responded to supportive care and bromocriptine Final diagnosis: NMS and diabetes insipidus

    15. NMS Neuroleptic malignant syndrome (NMS) life threatening rare neurological disorder caused by adverse reaction to neuroleptic or anti-psychotic drugs. presents with muscle rigidity,fever, autonomic instability and cognitive changes such as delirium associated with elevated CPK Incidence has declined since discovery (due to proactive prescription habits ) still dangerous to patients treated with antipsychotics. generally, removal of the antipsychotic drug treatment, along with medical management, lead to a positive outcome. Fever, Encephalopathy, Vitals (unstable), Enzymes elevated, Rigidity of muscles Caroff, Psychiatric Annals, 1991,21:130-147. www.nmsis.org [edit] Signs and symptoms The first symptom to develop is usually muscular cramps, fever, symptoms of instability of the autonomic nervous system such as unstable blood pressure, and changes in cognition, including agitation, delirium and coma. Other symptoms may include muscle tremors and pharyngitis. Once symptoms do appear, they rapidly progress and can reach peak intensity in as little as three days. These symptoms can last anywhere from eight hours to forty days.[2] The muscular symptoms are most likely caused by the blockade of D2 which cause problems in the motor loop of the brain similar to a problem with Parkinson's Disease.[3] A raised white blood cell count and creatine phosphokinase (CPK) plasma concentration will be reported due to increased muscular activity and rhabdomyolysis (destruction of muscle tissue).[4] The patient may suffer hypertensive crisis and metabolic acidosis. A non-generalised slowing on an EEG is reported in around 50% of cases. The fever is believed to be caused by hypothalamic dopamine receptor blockade. The peripheral problems (the white blood cell and CPK count) are caused by the antipsychotic drugs. They cause an increased calcium release from the sarcoplasmic reticulum of muscle cells which can result in rigidity and eventual cell breakdown. No major studies have reported an explanation for the abnormal EEG, but it is likely also attributable to dopamine blockage leading to changes in neuronal pathways.[5] Unfortunately, symptoms are sometimes misinterpreted by doctors as symptoms of mental illness, delaying treatment.[6] NMS is less likely if a person has previously been stable for a period of time on antipsychotics, especially in situations where the dose has not been changed and there are no issues of noncompliance or consumption of psychoactive substances known to worsen psychosis. [edit] Symptoms overview Increased body temperature >100.4 degrees °F, or >38 °C Confused or altered consciousness Diaphoresis "sweat shock" Rigid muscles Autonomic imbalance [edit] Mnemonic A mnemonic used to remember the features of NMS is FEVER.[7] F—Fever E—Encephalopathy V—Vitals unstable E—Elevated enzymes (elevated CPK) R—Rigidity of muscles [edit] Differential diagnosis Differentiating NMS from other neurological disorders can be very difficult. It requires expert judgement to separate symptoms of NMS from other diseases. Some of the most commonly mistaken diseases are: encephalitis, toxic encephalopathy, status epilepticus, heat stroke, and malignant hyperthermia. Due to the comparative rarity of NMS, it is often overlooked and immediate treatment for the syndrome is delayed. Drugs such as cocaine and amphetamine may also produce similar symptoms.[2][8][9] The differential diagnosis is similar to that of hyperthermia. It includes serotonin syndrome[10] Features that are present in NMS and not serotonin syndrome are:[11] Bradykinesia Muscle rigidity Laboratory values (WBC & CK) [edit] Causes NMS is usually caused by neuroleptic drug use, and a wide range of drug potencies can result in NMS.[1] It has been reported that individuals using haloperidol and chlorpromazine are at greatest risk. NMS may also occur in people (such as patients with Parkinson's disease) who are taking a class of drugs known as dopaminergics (e.g., Levodopa) when the dosage is abruptly reduced.[12] In addition, other drugs which are not used as neuroleptics, but which have anti-dopaminergic activity, can induce NMS (e.g., metoclopramides).[13] Even drugs which do not have known anti-dopaminergic activity (e.g., amoxapines and lithium) have been associated with NMS. Also, the treatment of individuals with desipramine, dothiepin, lithium and phenelzine, tetrabenazine, and reserpine have been known to result in NMS.[14] At the molecular level, the NMS is caused by a marked and sudden reduction in dopamine activity that is induced either by withdrawal of dopaminergic agents or by blocking dopamine receptors. [edit] Risk Factors One of the clearest risk factors in the development of NMS is the course of drug therapy chosen to treat a condition. Use of high-potency neuroleptics, rapid increase in dosage of neuroleptics, and use of long-acting forms of neuroleptics are all known to increase the risk of developing NMS.[15] It has been purported that there is a genetic risk factor for NMS, since identical twins have both presented with NMS in one case, and a mother and two of her daughters have presented with NMS in another case.[16] Demographically, it appears that males, especially those under forty, are at greatest risk for developing NMS, although it is unclear if the increased incidence is a result of greater neuroleptic use in men under forty.[1] It has also been suggested that postpartum women may be at a greater risk for NMS.[17] An important risk factor for this condition is Lewy body dementia. these patients are extremely sensitive to neuroleptics. As a result, nueroleptic should be used cautiously in all cases of dementia. [edit] Pathophysiology The mechanism is thought to depend on decreased levels of dopamine due to: Dopamine receptor blockade Genetically reduced function of dopamine receptor D2[18] However, the failure of D2 dopamine receptor antagonism or dopamine receptor dysfunction does not fully explain the presenting symptoms and signs of NMS, as well as the occurrence of NMS with atypical antipsychotic drugs with lower D2 dopamine activity.[19] This has led to the hypothesis of sympathoadrenal hyperactivity (results from removing tonic inhibition from the sympathetic nervous system) as an etiological mechanism for NMS.[20] Release of calcium is increased from the sarcoplasmic reticulum with antipsychotic usage. This can result in increased muscle contractility, which can play a role in breakdown of muscle, muscle rigidity, and hyperthermia. Some antipsychotic drugs, such as typical neuroleptics, are known to block dopamine receptors; other studies have shown that when drugs supplying dopamine are withdrawn, symptoms similar to NMS present themselves.[2] There is also thought to be considerable overlap between malignant catatonia and NMS in their pathophysiology, the former being idiopathic and the latter being the drug-induced form of the same syndrome.[21] [edit] Treatment NMS is an emergency, and can lead to death if untreated. The first step is to stop neuroleptic drugs and to treat the hyperthermia aggressively, such as with cooling blankets or ice packs to the axillae and groin. Many cases require intensive care and circulatory and ventilatory support. Medications such as dantrolene sodium and bromocriptine may be used[22]. Apomorphine may be used however its use is supported by little evidence.[3] Benzodiazepines may be used to control agitation. Highly elevated CPK can damage the kidneys, therefore aggressive hydration may be required. Volume resuscitation is paramount. Benzodiazepines, dantrolene, and dopaminergic agents are a few pharmaceutical families that can be used to treat various degrees of NMS. If it is recognized early enough, NMS is not fatal, but still, 10% of cases do result in patient death.[2][23] [edit] Prognosis The prognosis is best when identified early and treated aggressively. In these cases NMS is not usually fatal. In previous studies the mortality rates from NMS have ranged from 20-38%,however in the last two decades mortality rates have fallen below 10% due to early recognition and improved management.[24] Re-introduction to the drug that originally caused NMS to develop may also trigger a recurrence, although in most cases it does not. [edit] Research While the pathophysiology of NMS remains unclear, the two most prevalent theories are: Reduced dopamine activity due to receptor blockade Sympathodrenal hyperactivity and autonomic dysfunction In the past, research and clinical studies seemed to corroborate the D2 receptor blockade theory in which antipsychotic drugs were thought to significantly reduce dopamine activity by blocking the D2 receptors associated with this neurotransmitter. However, recent studies indicate a genetic component to the condition.[25] In support of the Sympathoadrenal Hyperactivity model proposed, it has been hypothesized that a defect in calcium regulatory proteins within the sympathetic neurons may bring about the onset of NMS.[26]. This model of NMS strengthens its suspected association with Malignant hyperthermia in which NMS may be regarded as a neurogenic form of this condition which itself is linked to defective calcium-related proteins. The introduction of atypical antipsychotic drugs, which do not act on the D2 dopamine receptors were thought to have reduced the incidence of NMS. However, recent studies suggest that the decrease in mortality may be the result of increased physician awareness and earlier initiation of treatment rather than the action of the drugs themselves.[19] NMS induced by atypical drugs also resembles "classical" NMS (induced by typical psychotic drugs), further questioning the overall efficacy of these drugs.[27] [edit] Epidemiology Pooled data suggests the incidence of NMS is between 0.2% - 3.23%.[28] However, more physician awareness coupled with increased use of atypical anti-psychotics have likely reduced the prevalence of NMS.[1] Additionally, young males are particularly susceptible and the male:female ratio has been reported to be as high as 2:1.[1][29][28] [edit] History NMS was known about as early as 1956, shortly after the introduction of the first phenothiazines.[30] NMS was first described in 1960 by French clinicians who had been working on a study involving haloperidol. They characterized the condition that was associated with the side effects of haloperidol “syndrome malin des neuroleptiques”, which was translated to Neuroleptic malignant syndrome.[14] [edit] References ^ a b c d e Theodore I. Benzer, MD, PhD (2005). "Neuroleptic Malignant Syndrome". Emedicine. http://www.emedicine.com/EMERG/topic339.htm.  ^ a b c d e Jeffrey R. Strawn, M.D., Paul E. Keck Jr., M.D., and Stanley N. Caroff, M.D., "Neuroleptic Malignant Syndrome" The American Journal of Psychiatry http://ajp.psychiatryonline.org/cgi/content/full/164/6/870 ^ a b http://www.uptodate.com/online/content/topic.do?topicKey=medneuro/5946&selectedTitle=1~123&source=search_result#26 ^ Joshua Latham, DO; Darren Campbell, MD The Journal of Family Practice "How much can exercise raise creatine kinase level—and does it matter?" http://www.jfponline.com/Pages.asp?AID=6497&issue=August_2008&UID= ^ http://emedicine.medscape.com/article/288482-overview ^ Stacy Milbouer, "Quest for the truth", Nashua Telegraph http://www.nashuatelegraph.com/apps/pbcs.dll/article?AID=/20050424/NEWS01/104240081 ^ Identify neuroleptic malignant syndrome. schizophrenia.com URL:http://www.schizophrenia.com/sznews/archives/002054.html. Accessed: July 2, 2006. ^ Perminder S. Sachdev "A rating scale for neuroleptic malignant syndrome" Psychiatry Research http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TBV-4GJK849-3&_user=521319&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000026018&_version=1&_urlVersion=0&_userid=521319&md5=bb8d0c8c30ba18cee1c5f69bc2c04589 ^ http://ajp.psychiatryonline.org/cgi/content-nw/full/164/6/870/T1 ^ Christensen V, Glenthøj B (2001). "[Malignant neuroleptic syndrome or serotonergic syndrome]". Ugeskr Laeger 163 (3): 301–2. PMID 11219110.  ^ Birmes P, Coppin D, Schmitt L, Lauque D (2003). "Serotonin syndrome: a brief review.". CMAJ 168 (11): 1439–42. PMID 12771076.  Full Free Text. ^ Daniel L. Keyser and Robert L. Rodnitzky Neuroleptic Malignant Syndrome in Parkinson's Disease After Withdrawal or Alteration of Dopaminergic Therapy Arch Intern Med, APRIL 1991; 151: 794 - 796. ^ Lawrence S. Friedman, Larry A. Weinrauch, and John A. D'Elia Metoclopramide-Induced Neuroleptic Malignant Syndrome Arch Intern Med, August 1987; 147: 1495 - 1497. ^ a b Buckley PF and Hutchinson M: Neuroleptic Malignant Syndrome. J. Neurol. Neurosurg. Psychiatry 1995; 58; 271-273 ^ Keck PE Jr, Pope HG Jr, Cohen BM. Risk factors for neuroleptic malignant syndrome. A case-control study. Arch Gen Psychiatry. Oct 1989;46(10):914-8. ^ Otani K, Horiuchi M, Kondo T. Is the predisposition to neuroleptic malignant syndrome genetically transmitted?. Br J Psychiatry. Jun 1991;158:850-3. ^ Alexander PJ, Thomas RM, Das A. Is risk of neuroleptic malignant syndrome increased in the postpartum period?. J Clin Psychiatry. May 1998;59(5):254-5. ^ Mihara K, Kondo T, Suzuki A, et al. (2003). "Relationship between functional dopamine D2 and D3 receptors gene polymorphisms and neuroleptic malignant syndrome". Am. J. Med. Genet. B Neuropsychiatr. Genet. 117 (1): 57–60. doi:10.1002/ajmg.b.10025. PMID 12555136.  ^ a b Ananth J, Parameswaran S, Gunatilake S, Burgoyne K, Sidhom T (2004). "Neuroleptic malignant syndrome and atypical antipsychotic drugs". J. Clin. Psychiatry 65 (12): 1722–3. PMID 15119907.  ^ Gurrera RJ (1999). "Sympathoadrenal hyperactivity and the etiology of neuroleptic malignant syndrome". Am. J. Psychiatry 156 (2): 169–81. PMID 9989551.  ^ "Catatonia and neuroleptic malignant syndrome: psychopathology and pathophysiology". J Neural Transm 109: 1453–1467. 2002. doi:10.1007/s00702-002-0762-z. PMID 12486486.  ^ http://www.ncbi.nlm.nih.gov/pubmed/3804991 ^ http://ajp.psychiatryonline.org/cgi/content-nw/full/164/6/870/T2) ^ Niraj Ahuja and Andrew J. Cole Hyperthermia syndromes in psychiatry Adv Psychiatr Treat 2009 15:181-191. ^ http://www.ingentaconnect.com/content/adis/dsf/1998/00000019/00000001/art00006 ^ Gurrera RJ (2002) " Neuroleptic Malignant Syndrome a Neurogenic Form of Malignant Hyperthermial" Clinical Neuropharmacology 25(4): 183-193 ^ Samia Hasan and Peter Buckley (1998) "Novel Antipsychotics and the Neuroleptic Malignant Syndrome: A Review and Critique" Am J Psychiatry 155: 1113-111 ^ a b Anthony L. Pelonero, M.D., James L. Levenson, M.D. and Anand K. Pandurangi, M.D (1998). "Neuroleptic Malignant Syndrome: A Review". http://psychservices.psychiatryonline.org/cgi/content/full/49/9/1163.  ^ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2431511/pdf/postmedj00156-0013.pdf ^ Friedberg JM. Neuroleptic malignant syndrome. URL: http://www.idiom.com/~drjohn/biblio.html. Accessed: July 3, 2006. [edit] External links NMSIS—Neuroleptic Malignant Syndrome Information Service Canadian Movement Disorder Group—cmdg.org. NMS—counsellingresource.com. NINDS Neuroleptic Malignant Syndrome Information Page—NIH. NMS—currentpsychiatry.com Instructional Video for Detection of NMS—Medical Instructional Media. [hide] v • d • e Pathology of the nervous system, primarily CNS (G04–G47, 323–349) Inflammation Brain Encephalitis (Viral encephalitis, Herpesviral encephalitis) · Cavernous sinus thrombosis · Brain abscess (Amoebic) Spinal cord Myelitis: Poliomyelitis · Demyelinating disease (Transverse myelitis) · Tropical spastic paraparesis · Epidural abscess Both/either Encephalomyelitis (Acute disseminated) Meningoencephalitis Brain/ encephalopathy Degenerative Extrapyramidal and movement disorders Basal ganglia disease: Parkinsonism (PD, Postencephalitic, NMS) · PKAN · Tauopathy (PSP) · Striatonigral degeneration · Hemiballismus · HD · OA Dyskinesia: Dystonia (Status dystonicus, Spasmodic torticollis, Meige's, Blepharospasm) · Chorea (Choreoathetosis) · Myoclonus (Myoclonic epilepsy) · Akathesia Tremor (Essential tremor, Intention tremor) · Restless legs · Stiff person Dementia Tauopathy: Alzheimer's (Early-onset) · Frontotemporal dementia/Frontotemporal lobar degeneration (Pick's, Dementia with Lewy bodies) Multi-infarct dementia Mitochondrial disease Leigh's Demyelinating autoimmune (Multiple sclerosis, Neuromyelitis optica, Schilder's disease) · hereditary (Adrenoleukodystrophy, Alexander, Canavan, Krabbe, ML, PMD, VWM, MFC, CAMFAK syndrome) · Central pontine myelinolysis · Marchiafava-Bignami disease · Alpers' Episodic/ paroxysmal Seizure/epilepsy Focal · Generalised · Status epilepticus · Myoclonic epilepsy Headache Migraine (Familial hemiplegic) · Cluster · Tension Cerebrovascular TIA (Amaurosis fugax, Transient global amnesia) Stroke (MCA, ACA, PCA, Foville's, Millard-Gubler, Lateral medullary, Weber's, Lacunar stroke) Sleep disorders Insomnia · Hypersomnia · Sleep apnea (Obstructive, Ondine's curse) · Narcolepsy · Cataplexy · Kleine-Levin · Circadian rhythm sleep disorder (Advanced sleep phase syndrome, Delayed sleep phase syndrome, Non-24-hour sleep-wake syndrome, Jet lag) CSF Intracranial hypertension (Hydrocephalus/NPH, Idiopathic intracranial hypertension) · Cerebral edema · Intracranial hypotension Other Brain herniation · Reye's · Hepatic encephalopathy · Toxic encephalopathy Spinal cord/ myelopathy Syringomyelia · Syringobulbia · Morvan's syndrome · Vascular myelopathy (Foix-Alajouanine syndrome) · Spinal cord compression Both/either Degenerative SA Friedreich's ataxia · Ataxia telangiectasia MND UMN only: PLS · PP · HSP LMN only: PMA · PBP (Fazio-Londe, Infantile progressive bulbar palsy) · SMA (SMN-linked, Kennedy disease, SMAX2, DSMA1) both: ALS CNS: anat/physio/dev, noncongen/congen/neoplasia, symptoms+signs/eponymous, proc, medsN (1A/2AB/2C/3/4/7A/7B/7C/7D) Retrieved from "http://en.wikipedia.org/wiki/Neuroleptic_malignant_syndrome" Categories: Antipsychotics | Extrapyramidal and movement disorders | Medical emergencies | Mental illness diagnosis by DSM and ICD | Psychiatry | Syndromes Views Article Discussion Edit this page History Personal tools Try Beta Log in / create account Navigation Main page Contents Featured content Current events Random article Search   Interaction About Wikipedia Community portal Recent changes Contact Wikipedia Donate to Wikipedia Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Català Deutsch Español ????? Français Nederlands ??? Polski ??????? Suomi Svenska This page was last modified on 29 March 2010 at 19:03. Text is available under the Creative Commons Attribution-ShareAlike License; additional terms may apply. See Terms of Use for details. Wikipedia® is a registered trademark of the Wikimedia Foundation, Inc., a non-profit organization. Contact us Privacy policy About Wikipedia Disclaimers [edit] Signs and symptoms The first symptom to develop is usually muscular cramps, fever, symptoms of instability of the autonomic nervous system such as unstable blood pressure, and changes in cognition, including agitation, delirium and coma. Other symptoms may include muscle tremors and pharyngitis. Once symptoms do appear, they rapidly progress and can reach peak intensity in as little as three days. These symptoms can last anywhere from eight hours to forty days.[2] The muscular symptoms are most likely caused by the blockade of D2 which cause problems in the motor loop of the brain similar to a problem with Parkinson's Disease.[3] A raised white blood cell count and creatine phosphokinase (CPK) plasma concentration will be reported due to increased muscular activity and rhabdomyolysis (destruction of muscle tissue).[4] The patient may suffer hypertensive crisis and metabolic acidosis. A non-generalised slowing on an EEG is reported in around 50% of cases. The fever is believed to be caused by hypothalamic dopamine receptor blockade. The peripheral problems (the white blood cell and CPK count) are caused by the antipsychotic drugs. They cause an increased calcium release from the sarcoplasmic reticulum of muscle cells which can result in rigidity and eventual cell breakdown. No major studies have reported an explanation for the abnormal EEG, but it is likely also attributable to dopamine blockage leading to changes in neuronal pathways.[5] Unfortunately, symptoms are sometimes misinterpreted by doctors as symptoms of mental illness, delaying treatment.[6] NMS is less likely if a person has previously been stable for a period of time on antipsychotics, especially in situations where the dose has not been changed and there are no issues of noncompliance or consumption of psychoactive substances known to worsen psychosis. [edit] Symptoms overview Increased body temperature >100.4 degrees °F, or >38 °C Confused or altered consciousness Diaphoresis "sweat shock" Rigid muscles Autonomic imbalance [edit] Mnemonic A mnemonic used to remember the features of NMS is FEVER.[7] F—Fever E—Encephalopathy V—Vitals unstable E—Elevated enzymes (elevated CPK) R—Rigidity of muscles [edit] Differential diagnosis Differentiating NMS from other neurological disorders can be very difficult. It requires expert judgement to separate symptoms of NMS from other diseases. Some of the most commonly mistaken diseases are: encephalitis, toxic encephalopathy, status epilepticus, heat stroke, and malignant hyperthermia. Due to the comparative rarity of NMS, it is often overlooked and immediate treatment for the syndrome is delayed. Drugs such as cocaine and amphetamine may also produce similar symptoms.[2][8][9] The differential diagnosis is similar to that of hyperthermia. It includes serotonin syndrome[10] Features that are present in NMS and not serotonin syndrome are:[11] Bradykinesia Muscle rigidity Laboratory values (WBC & CK) [edit] Causes NMS is usually caused by neuroleptic drug use, and a wide range of drug potencies can result in NMS.[1] It has been reported that individuals using haloperidol and chlorpromazine are at greatest risk. NMS may also occur in people (such as patients with Parkinson's disease) who are taking a class of drugs known as dopaminergics (e.g., Levodopa) when the dosage is abruptly reduced.[12] In addition, other drugs which are not used as neuroleptics, but which have anti-dopaminergic activity, can induce NMS (e.g., metoclopramides).[13] Even drugs which do not have known anti-dopaminergic activity (e.g., amoxapines and lithium) have been associated with NMS. Also, the treatment of individuals with desipramine, dothiepin, lithium and phenelzine, tetrabenazine, and reserpine have been known to result in NMS.[14] At the molecular level, the NMS is caused by a marked and sudden reduction in dopamine activity that is induced either by withdrawal of dopaminergic agents or by blocking dopamine receptors. [edit] Risk Factors One of the clearest risk factors in the development of NMS is the course of drug therapy chosen to treat a condition. Use of high-potency neuroleptics, rapid increase in dosage of neuroleptics, and use of long-acting forms of neuroleptics are all known to increase the risk of developing NMS.[15] It has been purported that there is a genetic risk factor for NMS, since identical twins have both presented with NMS in one case, and a mother and two of her daughters have presented with NMS in another case.[16] Demographically, it appears that males, especially those under forty, are at greatest risk for developing NMS, although it is unclear if the increased incidence is a result of greater neuroleptic use in men under forty.[1] It has also been suggested that postpartum women may be at a greater risk for NMS.[17] An important risk factor for this condition is Lewy body dementia. these patients are extremely sensitive to neuroleptics. As a result, nueroleptic should be used cautiously in all cases of dementia. [edit] Pathophysiology The mechanism is thought to depend on decreased levels of dopamine due to: Dopamine receptor blockade Genetically reduced function of dopamine receptor D2[18] However, the failure of D2 dopamine receptor antagonism or dopamine receptor dysfunction does not fully explain the presenting symptoms and signs of NMS, as well as the occurrence of NMS with atypical antipsychotic drugs with lower D2 dopamine activity.[19] This has led to the hypothesis of sympathoadrenal hyperactivity (results from removing tonic inhibition from the sympathetic nervous system) as an etiological mechanism for NMS.[20] Release of calcium is increased from the sarcoplasmic reticulum with antipsychotic usage. This can result in increased muscle contractility, which can play a role in breakdown of muscle, muscle rigidity, and hyperthermia. Some antipsychotic drugs, such as typical neuroleptics, are known to block dopamine receptors; other studies have shown that when drugs supplying dopamine are withdrawn, symptoms similar to NMS present themselves.[2] There is also thought to be considerable overlap between malignant catatonia and NMS in their pathophysiology, the former being idiopathic and the latter being the drug-induced form of the same syndrome.[21] [edit] Treatment NMS is an emergency, and can lead to death if untreated. The first step is to stop neuroleptic drugs and to treat the hyperthermia aggressively, such as with cooling blankets or ice packs to the axillae and groin. Many cases require intensive care and circulatory and ventilatory support. Medications such as dantrolene sodium and bromocriptine may be used[22]. Apomorphine may be used however its use is supported by little evidence.[3] Benzodiazepines may be used to control agitation. Highly elevated CPK can damage the kidneys, therefore aggressive hydration may be required. Volume resuscitation is paramount. Benzodiazepines, dantrolene, and dopaminergic agents are a few pharmaceutical families that can be used to treat various degrees of NMS. If it is recognized early enough, NMS is not fatal, but still, 10% of cases do result in patient death.[2][23] [edit] Prognosis The prognosis is best when identified early and treated aggressively. In these cases NMS is not usually fatal. In previous studies the mortality rates from NMS have ranged from 20-38%,however in the last two decades mortality rates have fallen below 10% due to early recognition and improved management.[24] Re-introduction to the drug that originally caused NMS to develop may also trigger a recurrence, although in most cases it does not. [edit] Research While the pathophysiology of NMS remains unclear, the two most prevalent theories are: Reduced dopamine activity due to receptor blockade Sympathodrenal hyperactivity and autonomic dysfunction In the past, research and clinical studies seemed to corroborate the D2 receptor blockade theory in which antipsychotic drugs were thought to significantly reduce dopamine activity by blocking the D2 receptors associated with this neurotransmitter. However, recent studies indicate a genetic component to the condition.[25] In support of the Sympathoadrenal Hyperactivity model proposed, it has been hypothesized that a defect in calcium regulatory proteins within the sympathetic neurons may bring about the onset of NMS.[26]. This model of NMS strengthens its suspected association with Malignant hyperthermia in which NMS may be regarded as a neurogenic form of this condition which itself is linked to defective calcium-related proteins. The introduction of atypical antipsychotic drugs, which do not act on the D2 dopamine receptors were thought to have reduced the incidence of NMS. However, recent studies suggest that the decrease in mortality may be the result of increased physician awareness and earlier initiation of treatment rather than the action of the drugs themselves.[19] NMS induced by atypical drugs also resembles "classical" NMS (induced by typical psychotic drugs), further questioning the overall efficacy of these drugs.[27] [edit] Epidemiology Pooled data suggests the incidence of NMS is between 0.2% - 3.23%.[28] However, more physician awareness coupled with increased use of atypical anti-psychotics have likely reduced the prevalence of NMS.[1] Additionally, young males are particularly susceptible and the male:female ratio has been reported to be as high as 2:1.[1][29][28] [edit] History NMS was known about as early as 1956, shortly after the introduction of the first phenothiazines.[30] NMS was first described in 1960 by French clinicians who had been working on a study involving haloperidol. They characterized the condition that was associated with the side effects of haloperidol “syndrome malin des neuroleptiques”, which was translated to Neuroleptic malignant syndrome.[14] [edit] References ^ a b c d e Theodore I. Benzer, MD, PhD (2005). "Neuroleptic Malignant Syndrome". Emedicine. http://www.emedicine.com/EMERG/topic339.htm.  ^ a b c d e Jeffrey R. Strawn, M.D., Paul E. Keck Jr., M.D., and Stanley N. Caroff, M.D., "Neuroleptic Malignant Syndrome" The American Journal of Psychiatry http://ajp.psychiatryonline.org/cgi/content/full/164/6/870 ^ a b http://www.uptodate.com/online/content/topic.do?topicKey=medneuro/5946&selectedTitle=1~123&source=search_result#26 ^ Joshua Latham, DO; Darren Campbell, MD The Journal of Family Practice "How much can exercise raise creatine kinase level—and does it matter?" http://www.jfponline.com/Pages.asp?AID=6497&issue=August_2008&UID= ^ http://emedicine.medscape.com/article/288482-overview ^ Stacy Milbouer, "Quest for the truth", Nashua Telegraph http://www.nashuatelegraph.com/apps/pbcs.dll/article?AID=/20050424/NEWS01/104240081 ^ Identify neuroleptic malignant syndrome. schizophrenia.com URL:http://www.schizophrenia.com/sznews/archives/002054.html. Accessed: July 2, 2006. ^ Perminder S. Sachdev "A rating scale for neuroleptic malignant syndrome" Psychiatry Research http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TBV-4GJK849-3&_user=521319&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000026018&_version=1&_urlVersion=0&_userid=521319&md5=bb8d0c8c30ba18cee1c5f69bc2c04589 ^ http://ajp.psychiatryonline.org/cgi/content-nw/full/164/6/870/T1 ^ Christensen V, Glenthøj B (2001). "[Malignant neuroleptic syndrome or serotonergic syndrome]". Ugeskr Laeger 163 (3): 301–2. PMID 11219110.  ^ Birmes P, Coppin D, Schmitt L, Lauque D (2003). "Serotonin syndrome: a brief review.". CMAJ 168 (11): 1439–42. PMID 12771076.  Full Free Text. ^ Daniel L. Keyser and Robert L. Rodnitzky Neuroleptic Malignant Syndrome in Parkinson's Disease After Withdrawal or Alteration of Dopaminergic Therapy Arch Intern Med, APRIL 1991; 151: 794 - 796. ^ Lawrence S. Friedman, Larry A. Weinrauch, and John A. D'Elia Metoclopramide-Induced Neuroleptic Malignant Syndrome Arch Intern Med, August 1987; 147: 1495 - 1497. ^ a b Buckley PF and Hutchinson M: Neuroleptic Malignant Syndrome. J. Neurol. Neurosurg. Psychiatry 1995; 58; 271-273 ^ Keck PE Jr, Pope HG Jr, Cohen BM. Risk factors for neuroleptic malignant syndrome. A case-control study. Arch Gen Psychiatry. Oct 1989;46(10):914-8. ^ Otani K, Horiuchi M, Kondo T. Is the predisposition to neuroleptic malignant syndrome genetically transmitted?. Br J Psychiatry. Jun 1991;158:850-3. ^ Alexander PJ, Thomas RM, Das A. Is risk of neuroleptic malignant syndrome increased in the postpartum period?. J Clin Psychiatry. May 1998;59(5):254-5. ^ Mihara K, Kondo T, Suzuki A, et al. (2003). "Relationship between functional dopamine D2 and D3 receptors gene polymorphisms and neuroleptic malignant syndrome". Am. J. Med. Genet. B Neuropsychiatr. Genet. 117 (1): 57–60. doi:10.1002/ajmg.b.10025. PMID 12555136.  ^ a b Ananth J, Parameswaran S, Gunatilake S, Burgoyne K, Sidhom T (2004). "Neuroleptic malignant syndrome and atypical antipsychotic drugs". J. Clin. Psychiatry 65 (12): 1722–3. PMID 15119907.  ^ Gurrera RJ (1999). "Sympathoadrenal hyperactivity and the etiology of neuroleptic malignant syndrome". Am. J. Psychiatry 156 (2): 169–81. PMID 9989551.  ^ "Catatonia and neuroleptic malignant syndrome: psychopathology and pathophysiology". J Neural Transm 109: 1453–1467. 2002. doi:10.1007/s00702-002-0762-z. PMID 12486486.  ^ http://www.ncbi.nlm.nih.gov/pubmed/3804991 ^ http://ajp.psychiatryonline.org/cgi/content-nw/full/164/6/870/T2) ^ Niraj Ahuja and Andrew J. Cole Hyperthermia syndromes in psychiatry Adv Psychiatr Treat 2009 15:181-191. ^ http://www.ingentaconnect.com/content/adis/dsf/1998/00000019/00000001/art00006 ^ Gurrera RJ (2002) " Neuroleptic Malignant Syndrome a Neurogenic Form of Malignant Hyperthermial" Clinical Neuropharmacology 25(4): 183-193 ^ Samia Hasan and Peter Buckley (1998) "Novel Antipsychotics and the Neuroleptic Malignant Syndrome: A Review and Critique" Am J Psychiatry 155: 1113-111 ^ a b Anthony L. Pelonero, M.D., James L. Levenson, M.D. and Anand K. Pandurangi, M.D (1998). "Neuroleptic Malignant Syndrome: A Review". http://psychservices.psychiatryonline.org/cgi/content/full/49/9/1163.  ^ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2431511/pdf/postmedj00156-0013.pdf ^ Friedberg JM. Neuroleptic malignant syndrome. URL: http://www.idiom.com/~drjohn/biblio.html. Accessed: July 3, 2006. [edit] External links NMSIS—Neuroleptic Malignant Syndrome Information Service Canadian Movement Disorder Group—cmdg.org. NMS—counsellingresource.com. NINDS Neuroleptic Malignant Syndrome Information Page—NIH. NMS—currentpsychiatry.com Instructional Video for Detection of NMS—Medical Instructional Media. [hide] v • d • e Pathology of the nervous system, primarily CNS (G04–G47, 323–349) Inflammation Brain Encephalitis (Viral encephalitis, Herpesviral encephalitis) · Cavernous sinus thrombosis · Brain abscess (Amoebic) Spinal cord Myelitis: Poliomyelitis · Demyelinating disease (Transverse myelitis) · Tropical spastic paraparesis · Epidural abscess Both/either Encephalomyelitis (Acute disseminated)Meningoencephalitis Brain/encephalopathy Degenerative Extrapyramidal andmovement disorders Basal ganglia disease: Parkinsonism (PD, Postencephalitic, NMS) · PKAN · Tauopathy (PSP) · Striatonigral degeneration · Hemiballismus · HD · OA Dyskinesia: Dystonia (Status dystonicus, Spasmodic torticollis, Meige's, Blepharospasm) · Chorea (Choreoathetosis) · Myoclonus (Myoclonic epilepsy) · Akathesia Tremor (Essential tremor, Intention tremor) · Restless legs · Stiff person Dementia Tauopathy: Alzheimer's (Early-onset) · Frontotemporal dementia/Frontotemporal lobar degeneration (Pick's, Dementia with Lewy bodies) Multi-infarct dementia Mitochondrial disease Leigh's Demyelinating autoimmune (Multiple sclerosis, Neuromyelitis optica, Schilder's disease) · hereditary (Adrenoleukodystrophy, Alexander, Canavan, Krabbe, ML, PMD, VWM, MFC, CAMFAK syndrome) · Central pontine myelinolysis · Marchiafava-Bignami disease · Alpers' Episodic/paroxysmal Seizure/epilepsy Focal · Generalised · Status epilepticus · Myoclonic epilepsy Headache Migraine (Familial hemiplegic) · Cluster · Tension Cerebrovascular TIA (Amaurosis fugax, Transient global amnesia)Stroke (MCA, ACA, PCA, Foville's, Millard-Gubler, Lateral medullary, Weber's, Lacunar stroke) Sleep disorders Insomnia · Hypersomnia · Sleep apnea (Obstructive, Ondine's curse) · Narcolepsy · Cataplexy · Kleine-Levin · Circadian rhythm sleep disorder (Advanced sleep phase syndrome, Delayed sleep phase syndrome, Non-24-hour sleep-wake syndrome, Jet lag) CSF Intracranial hypertension (Hydrocephalus/NPH, Idiopathic intracranial hypertension) · Cerebral edema · Intracranial hypotension Other Brain herniation · Reye's · Hepatic encephalopathy · Toxic encephalopathy Spinal cord/myelopathy Syringomyelia · Syringobulbia · Morvan's syndrome · Vascular myelopathy (Foix-Alajouanine syndrome) · Spinal cord compression Both/either Degenerative SA Friedreich's ataxia · Ataxia telangiectasia MND UMN only: PLS · PP · HSP LMN only: PMA · PBP (Fazio-Londe, Infantile progressive bulbar palsy) · SMA (SMN-linked, Kennedy disease, SMAX2, DSMA1) both: ALS CNS: anat/physio/dev, noncongen/congen/neoplasia, symptoms+signs/eponymous, proc, medsN (1A/2AB/2C/3/4/7A/7B/7C/7D) Retrieved from "http://en.wikipedia.org/wiki/Neuroleptic_malignant_syndrome" Categories: Antipsychotics | Extrapyramidal and movement disorders | Medical emergencies | Mental illness diagnosis by DSM and ICD | Psychiatry | Syndromes Views Article Discussion Edit this page History Personal tools Try Beta Log in / create account Navigation Main page Contents Featured content Current events Random article Search   Interaction About Wikipedia Community portal Recent changes Contact Wikipedia Donate to Wikipedia Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Català Deutsch Español ????? Français Nederlands ??? Polski ??????? Suomi Svenska This page was last modified on 29 March 2010 at 19:03. Text is available under the Creative Commons Attribution-ShareAlike License; additional terms may apply. See Terms of Use for details.Wikipedia® is a registered trademark of the Wikimedia Foundation, Inc., a non-profit organization. Contact us Privacy policy About Wikipedia Disclaimers

    16. NMS Genetic association studies and polymorphisms influencing susceptibility to NMS dopamine D(2) receptor serotonin receptor, cytochrome p450 2D6. While a few candidate polymorphisms were associated with NMS, a large controlled study is needed to attain statistical power. Kawanishi, C. Am J Pharmacogenomics. 2003;3(2):89-95

    17. Rheumatologic diseases and fever Gout Vasculitis Hereditary fevers Drug related Dtsch Med Wochenschr. 2010 Jan;135(4):125-8. Epub 2010 Jan 25. [Fever and back pain--a case report of spinal gout] [Article in German] Schorn C, Behr C, Schwarting A. Zentrales Röntgeninstitut des Sana Rheumazentrums Rheinland-Pfalz. c.schorn@sana-rz.de HISTORY AND PHYSICAL FINDINGS: A 67-years-old man suffered from relapsing moderate fever and back pain after arthroscopy of the knee under peridural anaesthesia. Antibiotics given for suspected iatrogenic infection was started, but was without improvement. After 4 months under several antibiotic regimes his condition rapidly deteriorated with high fever, excruciating lumbar back pain associated with elevated ESR/WBC (ESR = erythrocyte sedimentation rate, WBC = white blood cell count) along with arthritis of the shoulders, wrists, knees and ankles. Physical findings comprised swelling and restricted movement of the affected joints as well as pain related stiffness and immobility of the spine, but no neurological abnormalities. CLINICAL INVESTIGATIONS: An magnetic resonance imaging (MRI) of the lumbar spine revealed the uncommon finding of multilevel facet joint arthritis at lumbar L2/3 and L4/5, accompanied by cystic erosions of the lamina and widespread dorsal soft tissue edema. Serum uric acid was 11 mg/dl. Uric acid was found in the synovial fluid of the knees. DIAGNOSIS, TREATMENT AND FOLLOW UP: The fever, spinal symptoms as well as imaging findings improved together with the peripheral arthritis when treatment with colchicine and steroids was started, establishing the diagnosis of spinal gout. In the following year, no further or back pain or fever occurred. Despite continued allopurinol therapy the gouty arthritis of the peripheral joints re-occurred. CONCLUSION: Despite its rarity, spinal gout should be considered in the differential diagnosis of intractable back pain and fever especially when imaging studies reveal posterior element involvement. Georg Thieme Verlag KG Stuttgart.New York. PMID: 20101555 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances Publication Types: Case Reports English Abstract MeSH Terms: Aged Allopurinol/therapeutic use Arthritis, Gouty/diagnosis* Arthritis, Gouty/drug therapy Arthroscopy Back Pain/etiology* Colchicine/therapeutic use Diagnosis, Differential Drug Therapy, Combination Fever of Unknown Origin/etiology* Follow-Up Studies Glucocorticoids/therapeutic use Gout Suppressants/therapeutic use Humans Knee/surgery Lumbar Vertebrae/pathology Magnetic Resonance Imaging Male Postoperative Complications/diagnosis Postoperative Complications/drug therapy Prednisolone/analogs & derivatives Prednisolone/therapeutic use Spondylarthritis/diagnosis* Spondylarthritis/drug therapy Tomography, X-Ray Computed Ultrasonography Uric Acid/urine Substances: Glucocorticoids Gout Suppressants prednisolone hemisuccinate Allopurinol Prednisolone Colchicine Uric Acid LinkOut - more resources Full Text Sources: Georg Thieme Verlag Stuttgart, New York EBSCO Swets Information Services Education: New England Research Institutes Inc. Medical: Back Pain - MedlinePlus Health Information Joint Disorders - MedlinePlus Health Information Molecular Biology Databases: ALLOPURINOL - HSDB COLCHICINE - HSDB PREDNISOLONE - HSDB Dtsch Med Wochenschr. 2010 Jan;135(4):125-8. Epub 2010 Jan 25. [Fever and back pain--a case report of spinal gout] [Article in German] Schorn C, Behr C, Schwarting A. Zentrales Röntgeninstitut des Sana Rheumazentrums Rheinland-Pfalz. c.schorn@sana-rz.de HISTORY AND PHYSICAL FINDINGS: A 67-years-old man suffered from relapsing moderate fever and back pain after arthroscopy of the knee under peridural anaesthesia. Antibiotics given for suspected iatrogenic infection was started, but was without improvement. After 4 months under several antibiotic regimes his condition rapidly deteriorated with high fever, excruciating lumbar back pain associated with elevated ESR/WBC (ESR = erythrocyte sedimentation rate, WBC = white blood cell count) along with arthritis of the shoulders, wrists, knees and ankles. Physical findings comprised swelling and restricted movement of the affected joints as well as pain related stiffness and immobility of the spine, but no neurological abnormalities. CLINICAL INVESTIGATIONS: An magnetic resonance imaging (MRI) of the lumbar spine revealed the uncommon finding of multilevel facet joint arthritis at lumbar L2/3 and L4/5, accompanied by cystic erosions of the lamina and widespread dorsal soft tissue edema. Serum uric acid was 11 mg/dl. Uric acid was found in the synovial fluid of the knees. DIAGNOSIS, TREATMENT AND FOLLOW UP: The fever, spinal symptoms as well as imaging findings improved together with the peripheral arthritis when treatment with colchicine and steroids was started, establishing the diagnosis of spinal gout. In the following year, no further or back pain or fever occurred. Despite continued allopurinol therapy the gouty arthritis of the peripheral joints re-occurred. CONCLUSION: Despite its rarity, spinal gout should be considered in the differential diagnosis of intractable back pain and fever especially when imaging studies reveal posterior element involvement. Georg Thieme Verlag KG Stuttgart.New York. PMID: 20101555 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances Publication Types: Case Reports English Abstract MeSH Terms: Aged Allopurinol/therapeutic use Arthritis, Gouty/diagnosis* Arthritis, Gouty/drug therapy Arthroscopy Back Pain/etiology* Colchicine/therapeutic use Diagnosis, Differential Drug Therapy, Combination Fever of Unknown Origin/etiology* Follow-Up Studies Glucocorticoids/therapeutic use Gout Suppressants/therapeutic use Humans Knee/surgery Lumbar Vertebrae/pathology Magnetic Resonance Imaging Male Postoperative Complications/diagnosis Postoperative Complications/drug therapy Prednisolone/analogs & derivatives Prednisolone/therapeutic use Spondylarthritis/diagnosis* Spondylarthritis/drug therapy Tomography, X-Ray Computed Ultrasonography Uric Acid/urine Substances: Glucocorticoids Gout Suppressants prednisolone hemisuccinate Allopurinol Prednisolone Colchicine Uric Acid LinkOut - more resources Full Text Sources: Georg Thieme Verlag Stuttgart, New York EBSCO Swets Information Services Education: New England Research Institutes Inc. Medical: Back Pain - MedlinePlus Health Information Joint Disorders - MedlinePlus Health Information Molecular Biology Databases: ALLOPURINOL - HSDB COLCHICINE - HSDB PREDNISOLONE - HSDB

    18. Patient with painful knees, ankles, wrists, fever and leukocystosis 62 y/o man with prostate cancer, APA on warfarin, h/o gout and recent drainage of a scrotal abscess and treated with oral TMP/SMX Returned to ED on POD 5 with hypotension, leukocytosis, did not complete antibiotic treatment; scrotal area is normal in appearance Admitted to ICU for sepsis, pan-cultured, antibiotics, vanco/zosyn; all cx are negative. Patient noted to have very high ESR and CRP values. No obvious etiology on exam. TTE negative.

    19. Patient with painful knees, ankles, wrists, fever and leukocystosis WBCs shown in yellow ranged from 12?20.WBCs shown in yellow ranged from 12?20.

    20. Patient with painful knees, ankles, wrists, fever and leukocystosis Patient continues to do well off antibiotics, tapered from steroids and is continued on his allopurinol and colchicine. Diagnosis: scrotal abscess resolved, gout flare Once the patient was on the floor, patient was found to have an elevatated WBC ct. Patient was continued on Vancomycin and Zosyn. The antibiotics were then stopped, patient developed a fever, antibiotics were re-started. An extensive workup was done for the fever, leukocytosis, and also increased ESR (>140) and CRP 11.5. Pt. got a TTE and TEE which were negative for endocarditis. Patient also had blood cultures, urine cx that were all negative and NGTD. Ultimately, after negative work-up, consult by ID and Rheumatology, patient was found to have all these abnormalities due to gout flare and not do to an infectious etiology. The scrotum was looked at daily, and the abscess had healed once the patient was on the floor. BID dressing changes on the scrotum were performed. Patient also use nystatin powder on his candidal infection in the groin. For his gout, patient was started on 40 mg of prednisone, and then went to 20 daily, then finally 10 mg daily for 5 days. Patient also continued allopurinol 100 mg 4 times a week, and 200 mg 3 times a week, colchicine 3 times a week. Pt's creatine was monitored, but do to severity of flare its important patient stay on this medicine for long-term to prevent flares from patient. Pt was also hyperkalemia and started on soduim bicarab and kayexalte. Pt. had no EKG changes from hyperkalemia (most likey thought to be due to RTA type 4). Pt. was also started on a heparin drip until his INR was theraputic with the coumadin. Pt. also developed some thrush in the mouth, and was started on nystatin. Pt. got daily PT and will need that in rehab due to his extensive gout flare and impact it had on his knees. Once the patient was on the floor, patient was found to have an elevatated WBC ct. Patient was continued on Vancomycin and Zosyn. The antibiotics were then stopped, patient developed a fever, antibiotics were re-started. An extensive workup was done for the fever, leukocytosis, and also increased ESR (>140) and CRP 11.5. Pt. got a TTE and TEE which were negative for endocarditis. Patient also had blood cultures, urine cx that were all negative and NGTD. Ultimately, after negative work-up, consult by ID and Rheumatology, patient was found to have all these abnormalities due to gout flare and not do to an infectious etiology. The scrotum was looked at daily, and the abscess had healed once the patient was on the floor. BID dressing changes on the scrotum were performed. Patient also use nystatin powder on his candidal infection in the groin. For his gout, patient was started on 40 mg of prednisone, and then went to 20 daily, then finally 10 mg daily for 5 days. Patient also continued allopurinol 100 mg 4 times a week, and 200 mg 3 times a week, colchicine 3 times a week. Pt's creatine was monitored, but do to severity of flare its important patient stay on this medicine for long-term to prevent flares from patient. Pt was also hyperkalemia and started on soduim bicarab and kayexalte. Pt. had no EKG changes from hyperkalemia (most likey thought to be due to RTA type 4). Pt. was also started on a heparin drip until his INR was theraputic with the coumadin. Pt. also developed some thrush in the mouth, and was started on nystatin. Pt. got daily PT and will need that in rehab due to his extensive gout flare and impact it had on his knees.

    21. Autoinflammatory diseases and fever Curr Opin Rheumatol. 2008 Jan;20(1):66-75. The spectrum of autoinflammatory diseases: recent bench to bedside observations. Ryan JG, Goldbach-Mansky R. Genetics and Genomics Branch, Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. PURPOSE OF REVIEW: The autoinflammatory diseases are a group of conditions that include the hereditary fever syndromes, and result from upregulated innate immune responses. The discovery of the genetic basis for these conditions led to the description of novel intracellular receptors for infectious and noninfectious danger signals. This article focuses on recent progress in our understanding of autoinflammatory syndromes, and how insights into these conditions have triggered the exploration of the role of innate immunity in common rheumatologic diseases. RECENT FINDINGS: New models for the pathogenesis of several autoinflammatory syndromes have been proposed, including the role of pyrin and cryopyrin in regulating inflammation. Robust evidence has emerged that IL-1beta oversecretion is pivotal in cryopyrin-associated periodic syndromes, and that IL-1 inhibition ameliorates the clinical features of these syndromes. Monosodium urate crystals stimulate IL-1beta secretion via cryopyrin, which led to the addition of gout to the spectrum of autoinflammatory diseases. SUMMARY: Advances in our understanding of the autoinflammatory diseases have led to renewed interest in the innate immune system, and its role in the pathogenesis of more common rheumatic diseases. PMID: 18281860 [PubMed - indexed for MEDLINE] Joint Bone Spine. 2007 Dec;74(6):571-6. Epub 2007 Aug 21. The inflammasome, autoinflammatory diseases, and gout. Pétrilli V, Martinon F. Department of Biochemistry, Lausanne University, Lausanne, Switzerland. virginie.petrilli@unil.ch IL-1beta is a cytokine with major roles in inflammation and innate immune responses. IL-1beta is produced as an inactive proform that must be cleaved within the cell to generate biologically active IL-1beta. The enzyme caspase-1 catalyzes the reaction. Recent work showed that caspase-1 must be activated by a complex known as the inflammasome. The inflammasome comprises NALP, which is an intracellular receptor involved in innate immunity, and an ASC adapter that ensures caspase-1 recruitment to the receptor. The most extensively described inflammasome to date is formed by the NALP3 receptor within monocytes. Mutations involving the NALP3 gene cause hereditary periodic fever syndromes in humans. Increased inflammasome activity responsible for uncontrolled IL-1beta production occurs in these syndromes. Inhibition of the IL-1beta pathway by IL-1 receptor antagonist (anakinra) is a highly effective treatment for inherited periodic fever syndromes. A major role for inflammasome activity in the development of gout attacks was established recently. Urate monosodium crystals are specifically detected via the NALP3 inflammasome, which results in marked IL-1beta overproduction and initiation of an inflammatory response. This finding opens up new possibilities for the management of gouty attacks. PMID: 17714972 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances Publication Types: Review MeSH Terms: Autoimmune Diseases/genetics Autoimmune Diseases/immunology Autoimmune Diseases/metabolism* Carrier Proteins/genetics Carrier Proteins/immunology Carrier Proteins/metabolism* Caspase 1/metabolism Familial Mediterranean Fever/genetics Familial Mediterranean Fever/immunology Familial Mediterranean Fever/metabolism* Genetic Predisposition to Disease Gout/genetics Gout/immunology Gout/metabolism* Humans Inflammation/genetics Inflammation/immunology Inflammation/metabolism* Interleukin-1beta/immunology Interleukin-1beta/metabolism* Monocytes/immunology Monocytes/metabolism Mutation Substances: Carrier Proteins Interleukin-1beta NLRP3 protein, human Caspase 1 LinkOut - more resources Full Text Sources: Elsevier Science EBSCO OhioLINK Electronic Journal Center Swets Information Services Other Literature Sources: COS Scholar Universe Medical: Genetics Home Reference - NLRP3 Gene - Genetics Home Reference Autoimmune Diseases - MedlinePlus Health Information Gout - MedlinePlus Health Information Joint Disorders - MedlinePlus Health Information Curr Opin Rheumatol. 2008 Jan;20(1):66-75. The spectrum of autoinflammatory diseases: recent bench to bedside observations. Ryan JG, Goldbach-Mansky R. Genetics and Genomics Branch, Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. PURPOSE OF REVIEW: The autoinflammatory diseases are a group of conditions that include the hereditary fever syndromes, and result from upregulated innate immune responses. The discovery of the genetic basis for these conditions led to the description of novel intracellular receptors for infectious and noninfectious danger signals. This article focuses on recent progress in our understanding of autoinflammatory syndromes, and how insights into these conditions have triggered the exploration of the role of innate immunity in common rheumatologic diseases. RECENT FINDINGS: New models for the pathogenesis of several autoinflammatory syndromes have been proposed, including the role of pyrin and cryopyrin in regulating inflammation. Robust evidence has emerged that IL-1beta oversecretion is pivotal in cryopyrin-associated periodic syndromes, and that IL-1 inhibition ameliorates the clinical features of these syndromes. Monosodium urate crystals stimulate IL-1beta secretion via cryopyrin, which led to the addition of gout to the spectrum of autoinflammatory diseases. SUMMARY: Advances in our understanding of the autoinflammatory diseases have led to renewed interest in the innate immune system, and its role in the pathogenesis of more common rheumatic diseases. PMID: 18281860 [PubMed - indexed for MEDLINE] Joint Bone Spine. 2007 Dec;74(6):571-6. Epub 2007 Aug 21. The inflammasome, autoinflammatory diseases, and gout. Pétrilli V, Martinon F. Department of Biochemistry, Lausanne University, Lausanne, Switzerland. virginie.petrilli@unil.ch IL-1beta is a cytokine with major roles in inflammation and innate immune responses. IL-1beta is produced as an inactive proform that must be cleaved within the cell to generate biologically active IL-1beta. The enzyme caspase-1 catalyzes the reaction. Recent work showed that caspase-1 must be activated by a complex known as the inflammasome. The inflammasome comprises NALP, which is an intracellular receptor involved in innate immunity, and an ASC adapter that ensures caspase-1 recruitment to the receptor. The most extensively described inflammasome to date is formed by the NALP3 receptor within monocytes. Mutations involving the NALP3 gene cause hereditary periodic fever syndromes in humans. Increased inflammasome activity responsible for uncontrolled IL-1beta production occurs in these syndromes. Inhibition of the IL-1beta pathway by IL-1 receptor antagonist (anakinra) is a highly effective treatment for inherited periodic fever syndromes. A major role for inflammasome activity in the development of gout attacks was established recently. Urate monosodium crystals are specifically detected via the NALP3 inflammasome, which results in marked IL-1beta overproduction and initiation of an inflammatory response. This finding opens up new possibilities for the management of gouty attacks. PMID: 17714972 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances Publication Types: Review MeSH Terms: Autoimmune Diseases/genetics Autoimmune Diseases/immunology Autoimmune Diseases/metabolism* Carrier Proteins/genetics Carrier Proteins/immunology Carrier Proteins/metabolism* Caspase 1/metabolism Familial Mediterranean Fever/genetics Familial Mediterranean Fever/immunology Familial Mediterranean Fever/metabolism* Genetic Predisposition to Disease Gout/genetics Gout/immunology Gout/metabolism* Humans Inflammation/genetics Inflammation/immunology Inflammation/metabolism* Interleukin-1beta/immunology Interleukin-1beta/metabolism* Monocytes/immunology Monocytes/metabolism Mutation Substances: Carrier Proteins Interleukin-1beta NLRP3 protein, human Caspase 1 LinkOut - more resources Full Text Sources: Elsevier Science EBSCO OhioLINK Electronic Journal Center Swets Information Services Other Literature Sources: COS Scholar Universe Medical: Genetics Home Reference - NLRP3 Gene - Genetics Home Reference Autoimmune Diseases - MedlinePlus Health Information Gout - MedlinePlus Health Information Joint Disorders - MedlinePlus Health Information

    22. Malignancy and fever “Tumor fever” “Neutropenic fever” “Drug fever”

    23. A patient with MDS/AML, fever, resp distress and nodular infiltrates 60 y/o male with MDS admitted for Broviac placement cytarabine and idarubicin chemotherapy Developed neutropenia on day 12 of hospitalization followed by diarrhea, abd pain, fever and found to have Gram negative bacteremia (C. freundii); Develops SOB, nodular infiltrates ?septic emboli, transfer to ICU day notes 1 plts infused acyclovir flucon 2 broviac placement 3 AML Cycle 1 day 1 Idarubicin/Cytarabine 4 soreness bleeding at broviac site noted 5 6 MDS, Cycle 1, Day 4, Cytarabine/Idarubacin doe 7 8 receives blood 9 10 11 diarrhea chills abd pain 12 2/2 bc gnrs 13 vanco zosyn cipro; developed fever tachycardia with tx 14 2/2 bc with gnrs; previous set is citrobacter freundii; zosyn to imipenem 15 16 17 18 desaturation tranfer to ICU; debate re source of bactermia; line is removed 19 imi to mero + amikacin; ct chest nodular densities 20 cath no growth; voriconazole added; serum galactomannan sent 21 intubated for resp failure; pulm edema vs emboli vs fungal 22 bactrim added; bronched 23 negative smears on BAL pressors started 24 wbcs rising; renal failure; cefepeime vori acyclovir vanc 25 26 off pressors , extubated 27 28 negative serum galactomannan 29 diarrhea; oral vanco started 30 31 32 33 34 35 back to micu sepsis resp failure 36 back to micu 38 death OCAL TITLE: ID INFECTIOUS DISEASE INPATIENT NOTE STANDARD TITLE: INFECTIOUS DISEASE INPATIENT NOTE DATE OF NOTE: MAR 09, 2010@22:13 ENTRY DATE: MAR 09, 2010@22:13:29 AUTHOR: GREENBERG,LIOR EXP COSIGNER: URGENCY: STATUS: COMPLETED *** ID INFECTIOUS DISEASE INPATIENT NOTE Has ADDENDA *** Called back by MICU team to help with evaluation of Mr. Sanker. This is a 60 y.o. male with MDS admitted 2/2/10 for chemotherapy - received Cytarabine (Ara-C) and Idarubicin on 2/4/10 - tolerated chemotherapy well, but then started developing reduction in the WBC count. (On admit 2/2 WBC=12.2, dropped on 2/12/10 to WBC=1.13, PMN's=0.9%). Around this time with fevers to 102F during this time. Blood cultures taken, growing repeatedly citrobacter freundii (2/12-2/18) - eventually found to be due to line infection --> broviac removed 2/19/10 by surgery. Had deterioration of respiratory status, CT of chest 2/19 with new pulmonary nodules suggestive of septic emboli - however cause of respiratory deterioration not found: PCP and invasive aspergillosis essentially ruled out as etiology of pulm nodules. Had BMBx 2/18 - showed transformation of MDS to AML; at that time intubated and on pressors, did not think that he'd survive and end of life/palliative course taken with thoughts of palliate extubation. However, his neutropenic fever resolved ~2/26, C.freundii line-associated bacteremia cleared (negative blood cx 2/22), and was extubated and sent back to floors, with hopes of possible reinduction of chemotherapy. Our plan at that time was to con't IV cefepime until 3/4/10 to complete 14 day course for citrobacter bacteremia/line infection, and con't acyclovir/fluconazole prophylaxis (and d/c this once no longer neutropenic). On floors initially feeling better, less anxious, with more SOB and green productive cough (?with some blood). Had CT of chest 3/5 which showed interval progression of the nodules (more in lower lobes), as well as increase in peripheral LLL consolidation - "tree in bud" appearance (suggestive of airway process rather than septic emboli source). Seen by pulmonary service, who recommended sputum cx - if not revealing, plan for bronch/BAL. On 3/8 1:30 AM had acute deterioration, RR=40, however later that day more comfortable (RR=20's); was planned to have bronch/BAL, however this was cancelled due to tenuous respiratory status. Later that day with again respiratory distress, temp=100.4, tx to MICU and started on vanco/pip-tazo in addition to acyclovir/fluconazole. Today started on empiric voriconazole in light of overally deterioration. Per Heme-onc notes, not fit for further chemo at this time, and talk of hospice/comfort care is underway. PE: 97.16 F [36.2 C] (03/09/2010 22:48) 20 (03/09/2010 22:48) 61 (03/09/2010 22:48) 110/51 (03/09/2010 22:48) General: intubated, mildly responsive HEENT: MM, PERL. (+) conj. pallor HEART: RRR, no murmurs LUNGS: anteriorly - CTA ABD: decreased bowel sounds. Liquid feces on bed. EXT: (+) edema, old LLE wound without warmth \ 7.3 / 0.95 ------- 13 (03/09/2010) / 24.0 \ MCV: 94.1 (03/09/10 21:10) BLOOD NEUT. %: 54.7 (03/09/10 21:10) BLOOD 145 | 106 | 85 / ------------------- 181 (03/09/2010) 5.9 | 30.0 | 4.0 \ Micro: 3/9 stool, c.diff: pending 3/8 blood cx: NGTD x2 3/8 urine cx: pending 3/8 sputum: rare upper resp. flora, mod GNR 3/7 sputum: rare upper resp. flora, mod GNR 3/3 c.diff (-) 3/2 c.diff: (-) 3/1 nares: no MRSA 2/28 Serum galactomannan: negative 2/23 sputum cytology: no PCP 2/23 BAL KOH prep: NG 2/23 BAL cx: NG 2/23 blood cx: NG 2/22 blood cx: NG 2/21 blood cx: 1/1 Coag negative staph 2/20 blood cx: NG 2/19 cath tip cx: NG 2/19 nares: no MRSA 2/18 blood cx: 1/3 Citrobacter freundii (from Broviac) 2/17 blood cx: NG 2/17 urine cx: NG 2/15 blood cx: 1/1 Citrobacter freundii 2/14 blood cx: 1/2 Citrobacter freundii 2/12 blood cx: 1/2 Citrobacter freundii 2/12, 2/13, 2/14 c.diff (-) 2/12 urine cx: c.koseri, enterococcus sp. ABX: Vanco (2/12-2/25, 3/9-now) Pip-tazo (2/12-2/15, 3/9-now) Voriconazole (2/21-2/28, 3/9-now) Acyclovir 400mg PO BID (2/2-now) Fluconazole 400mg PO daily (2/3-2/22; 2/28-now) Metronidazole (3/9-now) Cefepime (2/24-3/5) Bactrim (2/22-2/24) Meropenem (2/19-2/24) Gentamicin (2/19-2/22) Cipro (2/12-2/21) Imipenem (2/15-2/19) Imaging: 3/8/10 CXR: Diffuse interstitial infiltrate. Question of patchy consolidation at the left lung base, especially posterior to the cardiac silhouette. Allowing for difference in technique the appearance is similar to prior study dated 03/03/2010. Heart size is mildly increased but unchanged. Impression: No significant change from prior study 3/9/10 CXR: Prominence of the pulmonary vascularity the interstitial markings similar to prior study. Endotracheal tube in satisfactory position. Heart enlarged unchanged. Impression: No change from prior study ASSESSMENT: 60 y.o. male with MDS, s/p chemo 2/4/10 with persistent neutropenia since 2/11/10, complicated by c.freundii line infection and most recently with second event of respiratory failure. His first event of respiratory failure was not explained, as our workup at that time did not reveal any infectious source; at this time, he is intubated with CT changes which indicate an airway process which is likely infectious. His prolonged neutropenia not only puts him a very high risk category for bacterial infections (such as PSDA and other hospital pathogens), but also fungal infections. This all said, the hematology service does not think that he will be fit enough for another round of chemotherapy - and therefore recommend hospice/comfort care. RECOMMEND: Should a more aggressive approach be taken, would recommend following: 1. Con't broad spectrum antibiotics - pip/tazo, vanco, metronidazole, acyclovir and voriconazole 2. Bronchoscopy with BAL - eval for fungi/PCP/AFB/bacteria 3. Repeat chest CT 4. Serum galactomannin This is only if an aggressive approach is to be taken. Otherwise, all antibiotics should be stopped if patient is to be made comfort care. Discussed with MICU senior resident on call. Will discuss with Dr. Blanton, ID attending. /es/ LIOR GREENBERG INFECTIOUS DISEASE FELLOW Signed: 03/09/2010 23:19 Receipt Acknowledged By: 03/10/2010 16:55 /es/ RONALD E BLANTON PHYSICIAN 03/10/2010 ADDENDUM STATUS: COMPLETED Pt. seen and examined with ID fellow, Greenberg. Agree with assessment and plans. All recommendations are conditioned on service's plans for agressive interventions for this patitent. /es/ RONALD E BLANTON PHYSICIAN Signed: 03/10/2010 16:55 day notes 1 plts infused acyclovir flucon 2 broviac placement 3 AML Cycle 1 day 1 Idarubicin/Cytarabine 4 soreness bleeding at broviac site noted 5 6 MDS, Cycle 1, Day 4, Cytarabine/Idarubacin doe 7 8 receives blood 9 10 11 diarrhea chills abd pain 12 2/2 bc gnrs 13 vanco zosyn cipro; developed fever tachycardia with tx 14 2/2 bc with gnrs; previous set is citrobacter freundii; zosyn to imipenem 15 16 17 18 desaturation tranfer to ICU; debate re source of bactermia; line is removed 19 imi to mero + amikacin; ct chest nodular densities 20 cath no growth; voriconazole added; serum galactomannan sent 21 intubated for resp failure; pulm edema vs emboli vs fungal 22 bactrim added; bronched 23 negative smears on BAL pressors started 24 wbcs rising; renal failure; cefepeime vori acyclovir vanc 25 26 off pressors , extubated 27 28 negative serum galactomannan 29 diarrhea; oral vanco started 30 31 32 33 34 35 back to micu sepsis resp failure 36 back to micu 38 death OCAL TITLE: ID INFECTIOUS DISEASE INPATIENT NOTE STANDARD TITLE: INFECTIOUS DISEASE INPATIENT NOTE DATE OF NOTE: MAR 09, 2010@22:13 ENTRY DATE: MAR 09, 2010@22:13:29 AUTHOR: GREENBERG,LIOR EXP COSIGNER: URGENCY: STATUS: COMPLETED *** ID INFECTIOUS DISEASE INPATIENT NOTE Has ADDENDA *** Called back by MICU team to help with evaluation of Mr. Sanker. This is a 60 y.o. male with MDS admitted 2/2/10 for chemotherapy - received Cytarabine (Ara-C) and Idarubicin on 2/4/10 - tolerated chemotherapy well, but then started developing reduction in the WBC count. (On admit 2/2 WBC=12.2, dropped on 2/12/10 to WBC=1.13, PMN's=0.9%). Around this time with fevers to 102F during this time. Blood cultures taken, growing repeatedly citrobacter freundii (2/12-2/18) - eventually found to be due to line infection --> broviac removed 2/19/10 by surgery. Had deterioration of respiratory status, CT of chest 2/19 with new pulmonary nodules suggestive of septic emboli - however cause of respiratory deterioration not found: PCP and invasive aspergillosis essentially ruled out as etiology of pulm nodules. Had BMBx 2/18 - showed transformation of MDS to AML; at that time intubated and on pressors, did not think that he'd survive and end of life/palliative course taken with thoughts of palliate extubation. However, his neutropenic fever resolved ~2/26, C.freundii line-associated bacteremia cleared (negative blood cx 2/22), and was extubated and sent back to floors, with hopes of possible reinduction of chemotherapy. Our plan at that time was to con't IV cefepime until 3/4/10 to complete 14 day course for citrobacter bacteremia/line infection, and con't acyclovir/fluconazole prophylaxis (and d/c this once no longer neutropenic). On floors initially feeling better, less anxious, with more SOB and green productive cough (?with some blood). Had CT of chest 3/5 which showed interval progression of the nodules (more in lower lobes), as well as increase in peripheral LLL consolidation - "tree in bud" appearance (suggestive of airway process rather than septic emboli source). Seen by pulmonary service, who recommended sputum cx - if not revealing, plan for bronch/BAL. On 3/8 1:30 AM had acute deterioration, RR=40, however later that day more comfortable (RR=20's); was planned to have bronch/BAL, however this was cancelled due to tenuous respiratory status. Later that day with again respiratory distress, temp=100.4, tx to MICU and started on vanco/pip-tazo in addition to acyclovir/fluconazole. Today started on empiric voriconazole in light of overally deterioration. Per Heme-onc notes, not fit for further chemo at this time, and talk of hospice/comfort care is underway. PE: 97.16 F [36.2 C] (03/09/2010 22:48) 20 (03/09/2010 22:48) 61 (03/09/2010 22:48) 110/51 (03/09/2010 22:48) General: intubated, mildly responsive HEENT: MM, PERL. (+) conj. pallor HEART: RRR, no murmurs LUNGS: anteriorly - CTA ABD: decreased bowel sounds. Liquid feces on bed. EXT: (+) edema, old LLE wound without warmth \ 7.3 / 0.95 ------- 13 (03/09/2010) / 24.0 \ MCV: 94.1 (03/09/10 21:10) BLOOD NEUT. %: 54.7 (03/09/10 21:10) BLOOD 145 | 106 | 85 / ------------------- 181 (03/09/2010) 5.9 | 30.0 | 4.0 \ Micro: 3/9 stool, c.diff: pending 3/8 blood cx: NGTD x2 3/8 urine cx: pending 3/8 sputum: rare upper resp. flora, mod GNR 3/7 sputum: rare upper resp. flora, mod GNR 3/3 c.diff (-) 3/2 c.diff: (-) 3/1 nares: no MRSA 2/28 Serum galactomannan: negative 2/23 sputum cytology: no PCP 2/23 BAL KOH prep: NG 2/23 BAL cx: NG 2/23 blood cx: NG 2/22 blood cx: NG 2/21 blood cx: 1/1 Coag negative staph 2/20 blood cx: NG 2/19 cath tip cx: NG 2/19 nares: no MRSA 2/18 blood cx: 1/3 Citrobacter freundii (from Broviac) 2/17 blood cx: NG 2/17 urine cx: NG 2/15 blood cx: 1/1 Citrobacter freundii 2/14 blood cx: 1/2 Citrobacter freundii 2/12 blood cx: 1/2 Citrobacter freundii 2/12, 2/13, 2/14 c.diff (-) 2/12 urine cx: c.koseri, enterococcus sp. ABX: Vanco (2/12-2/25, 3/9-now) Pip-tazo (2/12-2/15, 3/9-now) Voriconazole (2/21-2/28, 3/9-now) Acyclovir 400mg PO BID (2/2-now) Fluconazole 400mg PO daily (2/3-2/22; 2/28-now) Metronidazole (3/9-now) Cefepime (2/24-3/5) Bactrim (2/22-2/24) Meropenem (2/19-2/24) Gentamicin (2/19-2/22) Cipro (2/12-2/21) Imipenem (2/15-2/19) Imaging: 3/8/10 CXR: Diffuse interstitial infiltrate. Question of patchy consolidation at the left lung base, especially posterior to the cardiac silhouette. Allowing for difference in technique the appearance is similar to prior study dated 03/03/2010. Heart size is mildly increased but unchanged. Impression: No significant change from prior study 3/9/10 CXR: Prominence of the pulmonary vascularity the interstitial markings similar to prior study. Endotracheal tube in satisfactory position. Heart enlarged unchanged. Impression: No change from prior study ASSESSMENT: 60 y.o. male with MDS, s/p chemo 2/4/10 with persistent neutropenia since 2/11/10, complicated by c.freundii line infection and most recently with second event of respiratory failure. His first event of respiratory failure was not explained, as our workup at that time did not reveal any infectious source; at this time, he is intubated with CT changes which indicate an airway process which is likely infectious. His prolonged neutropenia not only puts him a very high risk category for bacterial infections (such as PSDA and other hospital pathogens), but also fungal infections. This all said, the hematology service does not think that he will be fit enough for another round of chemotherapy - and therefore recommend hospice/comfort care. RECOMMEND: Should a more aggressive approach be taken, would recommend following: 1. Con't broad spectrum antibiotics - pip/tazo, vanco, metronidazole, acyclovir and voriconazole 2. Bronchoscopy with BAL - eval for fungi/PCP/AFB/bacteria 3. Repeat chest CT 4. Serum galactomannin This is only if an aggressive approach is to be taken. Otherwise, all antibiotics should be stopped if patient is to be made comfort care. Discussed with MICU senior resident on call. Will discuss with Dr. Blanton, ID attending. /es/ LIOR GREENBERG INFECTIOUS DISEASE FELLOW Signed: 03/09/2010 23:19 Receipt Acknowledged By: 03/10/2010 16:55 /es/ RONALD E BLANTON PHYSICIAN 03/10/2010 ADDENDUM STATUS: COMPLETED Pt. seen and examined with ID fellow, Greenberg. Agree with assessment and plans. All recommendations are conditioned on service's plans for agressive interventions for this patitent. /es/ RONALD E BLANTON PHYSICIAN Signed: 03/10/2010 16:55

    24. A patient with MDS/AML, fever, resp distress and nodular infiltrates T CHEST WITH CONTRAST Proc Ord: CT CHEST W/O CONTRAST Exm Date: FEB 19, 2010@15:21 Req Phys: SHAH,SAPNA S Pat Loc: OP Unknown/03-30-2010@15:41 Img Loc: W CT SCAN Service: MEDICAL-(W) (Case 2151 COMPLETE) CT CHEST WITH CONTRAST (CT Detailed) CPT:71260 Contrast Media : Non-ionic Iodinated Reason for Study: sob, concern for septic emboli Clinical History: Is this procedure to screen for malignancy? No 6056 PORTER RD NORTH OLMSTED, OHIO 44070 440 734 2916 Clinical History: persistent bacteremia now with sob, concern for septic emboli. Report Status: Verified Date Reported: FEB 19, 2010 Date Verified: FEB 19, 2010 Verifier E-Sig:/ES/HOSSAM K. SAAD Report: Comparison: No previous studies available for comparison. Procedure: Scans were made from the thoracic inlet through the upper abdomen. I.V. contrast was given. Findings: Extrathoracic: No axillary adenopathy. No subcutaneous nodules are seen. Pleura: Trace bilateral pleural effusions. No pneumothorax. No pleural calcifications. Lungs: Multiple subcentimeter ill-defined peripheral nodular densities are seen in both lungs. In a patient with septicemia septic emboli, is of primary concern. Simple inflammatory pulmonary nodules is another possibility. There are multiple peribronchovascular and centrilobular nodular densities seen in bilateral lower lobes suggestive of small airway infection. Patch of pulmonary infiltrate seen at the left lung base. There is mild smooth septal thickening seen in left upper lobe which may represent early developing edema. Major airways are patent Mediastinum/hila: Subcentimeter paratracheal and subcarinal lymph nodes, considered nonpathological by CT size criteria. Borderline hilar lymph nodes, nonspecific and could be reactive. No masses. Heart/Vessels: Unremarkable. Upper Abdomen: Splenomegaly. Osseous structures: No aggressive osseous lesions are seen. Impression: 1. Multiple subcentimeter ill-defined peripheral nodular densities are seen in both lungs. In a patient with septicemia, septic emboli is of primary concern. Simple inflammatory pulmonary nodules is another possibility. 2. Multiple peribronchovascular and centrilobular nodular densities seen in bilateral lower lobes suggestive of small airway infection. Patch of pulmonary infiltrate seen at the left lung base. 3. Trace bilateral pleural effusions. 4. Mild smooth septal thickening in left upper lobe which may represent early developing edema. 5. Borderline hilar lymph nodes, nonspecific and could be reactive. 6. Splenomegaly. Primary Diagnostic Code: Primary Interpreting Staff: HOSSAM K. SAAD, PHYSICIAN (Verifier) /HKS CT CHEST W/O CONTRAST Exm Date: MAR 05, 2010@10:15 Req Phys: BHAVSAR,HILONI M Pat Loc: OP Unknown/03-30-2010@15:34 Img Loc: W CT SCAN Service: MEDICAL-(W) (Case 2538 COMPLETE) CT CHEST W/O CONTRAST (CT Detailed) CPT:71250 Reason for Study: MDS, history of bacteremia and septic lung emboli Clinical History: Is this procedure to screen for malignancy? No 6056 PORTER RD NORTH OLMSTED, OHIO 44070 440 734 2916 Clinical History: 60 year old gentelman with MDS, history of bacteremia, neutropenic fever, septic emboli on last chest CT, currently requiring 50% venti mask. Report Status: Verified Date Reported: MAR 05, 2010 Date Verified: MAR 05, 2010 Verifier E-Sig:/ES/VORAVAN SHOTELERSUK Report: Comparison study: 2/19/2010. Technique: Axial thoracic CT images were obtained from the base of the neck through the lungs without intravenous contrast administration. Report: Scout images were reviewed. There has been interval progression of peribronchovascular nodules in both lungs, more prominent in the lower lobes. These are suggestive of bronchiolitis/pneumonitis. No dominant peripheral pulmonary nodules can be separated from the rest of peribronchovascular nodules to suggest that there are septic emboli in the current study. No bronchiectasis or peribronchial thickening. No mucus plugging. Interval increase in peripheral left lower lobe consolidation/atelectasis. Interval resolution of interlobular septal thickening in the left apex. Interval increase in size of small bilateral pleural effusions. The heart is not enlarged. Trace pericardial effusion. Mildly dilated central pulmonary artery. Aorta is normal in caliber. Mild coronary artery calcifications. Patent major airway. No enlarged mediastinal or hilar lymph nodes. Degenerative changes of the spine. Limited images of the included upper abdomen show marked splenomegaly. The liver is borderline enlarged. No adrenal nodule. Trace ascites. Impression: Interval progression of peribronchovascular nodules, more prominent in the lower lobes. Infectious/inflammatory bronchiolitis or pneumonitis is the first consideration. Increase in peripheral left lower lobe consolidation/atelectasis and small lateral pleural effusions. Marked splenomegaly. Primary Diagnostic Code: Primary Interpreting Staff: VORAVAN SHOTELERSUK, RADIOLOGIST (Verifier) /VS T CHEST WITH CONTRAST Proc Ord: CT CHEST W/O CONTRAST Exm Date: FEB 19, 2010@15:21 Req Phys: SHAH,SAPNA S Pat Loc: OP Unknown/03-30-2010@15:41 Img Loc: W CT SCAN Service: MEDICAL-(W) (Case 2151 COMPLETE) CT CHEST WITH CONTRAST (CT Detailed) CPT:71260 Contrast Media : Non-ionic Iodinated Reason for Study: sob, concern for septic emboli Clinical History: Is this procedure to screen for malignancy? No 6056 PORTER RD NORTH OLMSTED, OHIO 44070 440 734 2916 Clinical History: persistent bacteremia now with sob, concern for septic emboli. Report Status: Verified Date Reported: FEB 19, 2010 Date Verified: FEB 19, 2010 Verifier E-Sig:/ES/HOSSAM K. SAAD Report: Comparison: No previous studies available for comparison. Procedure: Scans were made from the thoracic inlet through the upper abdomen. I.V. contrast was given. Findings: Extrathoracic: No axillary adenopathy. No subcutaneous nodules are seen. Pleura: Trace bilateral pleural effusions. No pneumothorax. No pleural calcifications. Lungs: Multiple subcentimeter ill-defined peripheral nodular densities are seen in both lungs. In a patient with septicemia septic emboli, is of primary concern. Simple inflammatory pulmonary nodules is another possibility. There are multiple peribronchovascular and centrilobular nodular densities seen in bilateral lower lobes suggestive of small airway infection. Patch of pulmonary infiltrate seen at the left lung base. There is mild smooth septal thickening seen in left upper lobe which may represent early developing edema. Major airways are patent Mediastinum/hila: Subcentimeter paratracheal and subcarinal lymph nodes, considered nonpathological by CT size criteria. Borderline hilar lymph nodes, nonspecific and could be reactive. No masses. Heart/Vessels: Unremarkable. Upper Abdomen: Splenomegaly. Osseous structures: No aggressive osseous lesions are seen. Impression: 1. Multiple subcentimeter ill-defined peripheral nodular densities are seen in both lungs. In a patient with septicemia, septic emboli is of primary concern. Simple inflammatory pulmonary nodules is another possibility. 2. Multiple peribronchovascular and centrilobular nodular densities seen in bilateral lower lobes suggestive of small airway infection. Patch of pulmonary infiltrate seen at the left lung base. 3. Trace bilateral pleural effusions. 4. Mild smooth septal thickening in left upper lobe which may represent early developing edema. 5. Borderline hilar lymph nodes, nonspecific and could be reactive. 6. Splenomegaly. Primary Diagnostic Code: Primary Interpreting Staff: HOSSAM K. SAAD, PHYSICIAN (Verifier) /HKS CT CHEST W/O CONTRAST Exm Date: MAR 05, 2010@10:15 Req Phys: BHAVSAR,HILONI M Pat Loc: OP Unknown/03-30-2010@15:34 Img Loc: W CT SCAN Service: MEDICAL-(W) (Case 2538 COMPLETE) CT CHEST W/O CONTRAST (CT Detailed) CPT:71250 Reason for Study: MDS, history of bacteremia and septic lung emboli Clinical History: Is this procedure to screen for malignancy? No 6056 PORTER RD NORTH OLMSTED, OHIO 44070 440 734 2916 Clinical History: 60 year old gentelman with MDS, history of bacteremia, neutropenic fever, septic emboli on last chest CT, currently requiring 50% venti mask. Report Status: Verified Date Reported: MAR 05, 2010 Date Verified: MAR 05, 2010 Verifier E-Sig:/ES/VORAVAN SHOTELERSUK Report: Comparison study: 2/19/2010. Technique: Axial thoracic CT images were obtained from the base of the neck through the lungs without intravenous contrast administration. Report: Scout images were reviewed. There has been interval progression of peribronchovascular nodules in both lungs, more prominent in the lower lobes. These are suggestive of bronchiolitis/pneumonitis. No dominant peripheral pulmonary nodules can be separated from the rest of peribronchovascular nodules to suggest that there are septic emboli in the current study. No bronchiectasis or peribronchial thickening. No mucus plugging. Interval increase in peripheral left lower lobe consolidation/atelectasis. Interval resolution of interlobular septal thickening in the left apex. Interval increase in size of small bilateral pleural effusions. The heart is not enlarged. Trace pericardial effusion. Mildly dilated central pulmonary artery. Aorta is normal in caliber. Mild coronary artery calcifications. Patent major airway. No enlarged mediastinal or hilar lymph nodes. Degenerative changes of the spine. Limited images of the included upper abdomen show marked splenomegaly. The liver is borderline enlarged. No adrenal nodule. Trace ascites. Impression: Interval progression of peribronchovascular nodules, more prominent in the lower lobes. Infectious/inflammatory bronchiolitis or pneumonitis is the first consideration. Increase in peripheral left lower lobe consolidation/atelectasis and small lateral pleural effusions. Marked splenomegaly. Primary Diagnostic Code: Primary Interpreting Staff: VORAVAN SHOTELERSUK, RADIOLOGIST (Verifier) /VS

    25. A patient with MDS/AML, fever, resp distress and nodular infiltrates presumed source is Broviac which is removed on day 19; shows no growth Patient is intubated, voriconazole and then TMP/SMX are added; serum galactomannan is sent BAL is negative for bacteria, mycobacteria, fungi, P. jirovecii, viruses Post chemo BMBx still shows blasts Initially worsens with MOSF but eventually is off pressors, extubated and is sent to ward to await decision re further chemotx, complete antibiotics Serum galactomannan returns…negative. On day 29, has diarrhea, oral vanco started; C. diff antigen is negative but is continued. Day 35 respiratory distress, worsening of nodular process, receives pip/tazo/vanco/acyclovir/voriconazole debate re source of bactermia; line is removed 19 imi to mero + amikacin; ct chest nodular densities 20 cath no growth; voriconazole added; serum galactomannan sent 21 intubated for resp failure; pulm edema vs emboli vs fungal 22 bactrim added; bronched 23 negative smears on BAL pressors started 24 wbcs rising; renal failure; cefepeime vori acyclovir vanc 25 26 off pressors , extubated 27 28 negative serum galactomannan 29 diarrhea; oral vanco started 30 31 32 33 34 35 back to micu sepsis resp failure 36 back to micu 38 death debate re source of bactermia; line is removed 19 imi to mero + amikacin; ct chest nodular densities 20 cath no growth; voriconazole added; serum galactomannan sent 21 intubated for resp failure; pulm edema vs emboli vs fungal 22 bactrim added; bronched 23 negative smears on BAL pressors started 24 wbcs rising; renal failure; cefepeime vori acyclovir vanc 25 26 off pressors , extubated 27 28 negative serum galactomannan 29 diarrhea; oral vanco started 30 31 32 33 34 35 back to micu sepsis resp failure 36 back to micu 38 death

    26. A patient with MDS/AML, fever, resp distress and nodular infiltrates T CHEST WITH CONTRAST Proc Ord: CT CHEST W/O CONTRAST Exm Date: FEB 19, 2010@15:21 Req Phys: SHAH,SAPNA S Pat Loc: OP Unknown/03-30-2010@15:41 Img Loc: W CT SCAN Service: MEDICAL-(W) (Case 2151 COMPLETE) CT CHEST WITH CONTRAST (CT Detailed) CPT:71260 Contrast Media : Non-ionic Iodinated Reason for Study: sob, concern for septic emboli Clinical History: Is this procedure to screen for malignancy? No 6056 PORTER RD NORTH OLMSTED, OHIO 44070 440 734 2916 Clinical History: persistent bacteremia now with sob, concern for septic emboli. Report Status: Verified Date Reported: FEB 19, 2010 Date Verified: FEB 19, 2010 Verifier E-Sig:/ES/HOSSAM K. SAAD Report: Comparison: No previous studies available for comparison. Procedure: Scans were made from the thoracic inlet through the upper abdomen. I.V. contrast was given. Findings: Extrathoracic: No axillary adenopathy. No subcutaneous nodules are seen. Pleura: Trace bilateral pleural effusions. No pneumothorax. No pleural calcifications. Lungs: Multiple subcentimeter ill-defined peripheral nodular densities are seen in both lungs. In a patient with septicemia septic emboli, is of primary concern. Simple inflammatory pulmonary nodules is another possibility. There are multiple peribronchovascular and centrilobular nodular densities seen in bilateral lower lobes suggestive of small airway infection. Patch of pulmonary infiltrate seen at the left lung base. There is mild smooth septal thickening seen in left upper lobe which may represent early developing edema. Major airways are patent Mediastinum/hila: Subcentimeter paratracheal and subcarinal lymph nodes, considered nonpathological by CT size criteria. Borderline hilar lymph nodes, nonspecific and could be reactive. No masses. Heart/Vessels: Unremarkable. Upper Abdomen: Splenomegaly. Osseous structures: No aggressive osseous lesions are seen. Impression: 1. Multiple subcentimeter ill-defined peripheral nodular densities are seen in both lungs. In a patient with septicemia, septic emboli is of primary concern. Simple inflammatory pulmonary nodules is another possibility. 2. Multiple peribronchovascular and centrilobular nodular densities seen in bilateral lower lobes suggestive of small airway infection. Patch of pulmonary infiltrate seen at the left lung base. 3. Trace bilateral pleural effusions. 4. Mild smooth septal thickening in left upper lobe which may represent early developing edema. 5. Borderline hilar lymph nodes, nonspecific and could be reactive. 6. Splenomegaly. Primary Diagnostic Code: Primary Interpreting Staff: HOSSAM K. SAAD, PHYSICIAN (Verifier) /HKS CT CHEST W/O CONTRAST Exm Date: MAR 05, 2010@10:15 Req Phys: BHAVSAR,HILONI M Pat Loc: OP Unknown/03-30-2010@15:34 Img Loc: W CT SCAN Service: MEDICAL-(W) (Case 2538 COMPLETE) CT CHEST W/O CONTRAST (CT Detailed) CPT:71250 Reason for Study: MDS, history of bacteremia and septic lung emboli Clinical History: Is this procedure to screen for malignancy? No 6056 PORTER RD NORTH OLMSTED, OHIO 44070 440 734 2916 Clinical History: 60 year old gentelman with MDS, history of bacteremia, neutropenic fever, septic emboli on last chest CT, currently requiring 50% venti mask. Report Status: Verified Date Reported: MAR 05, 2010 Date Verified: MAR 05, 2010 Verifier E-Sig:/ES/VORAVAN SHOTELERSUK Report: Comparison study: 2/19/2010. Technique: Axial thoracic CT images were obtained from the base of the neck through the lungs without intravenous contrast administration. Report: Scout images were reviewed. There has been interval progression of peribronchovascular nodules in both lungs, more prominent in the lower lobes. These are suggestive of bronchiolitis/pneumonitis. No dominant peripheral pulmonary nodules can be separated from the rest of peribronchovascular nodules to suggest that there are septic emboli in the current study. No bronchiectasis or peribronchial thickening. No mucus plugging. Interval increase in peripheral left lower lobe consolidation/atelectasis. Interval resolution of interlobular septal thickening in the left apex. Interval increase in size of small bilateral pleural effusions. The heart is not enlarged. Trace pericardial effusion. Mildly dilated central pulmonary artery. Aorta is normal in caliber. Mild coronary artery calcifications. Patent major airway. No enlarged mediastinal or hilar lymph nodes. Degenerative changes of the spine. Limited images of the included upper abdomen show marked splenomegaly. The liver is borderline enlarged. No adrenal nodule. Trace ascites. Impression: Interval progression of peribronchovascular nodules, more prominent in the lower lobes. Infectious/inflammatory bronchiolitis or pneumonitis is the first consideration. Increase in peripheral left lower lobe consolidation/atelectasis and small lateral pleural effusions. Marked splenomegaly. Primary Diagnostic Code: Primary Interpreting Staff: VORAVAN SHOTELERSUK, RADIOLOGIST (Verifier) /VS T CHEST WITH CONTRAST Proc Ord: CT CHEST W/O CONTRAST Exm Date: FEB 19, 2010@15:21 Req Phys: SHAH,SAPNA S Pat Loc: OP Unknown/03-30-2010@15:41 Img Loc: W CT SCAN Service: MEDICAL-(W) (Case 2151 COMPLETE) CT CHEST WITH CONTRAST (CT Detailed) CPT:71260 Contrast Media : Non-ionic Iodinated Reason for Study: sob, concern for septic emboli Clinical History: Is this procedure to screen for malignancy? No 6056 PORTER RD NORTH OLMSTED, OHIO 44070 440 734 2916 Clinical History: persistent bacteremia now with sob, concern for septic emboli. Report Status: Verified Date Reported: FEB 19, 2010 Date Verified: FEB 19, 2010 Verifier E-Sig:/ES/HOSSAM K. SAAD Report: Comparison: No previous studies available for comparison. Procedure: Scans were made from the thoracic inlet through the upper abdomen. I.V. contrast was given. Findings: Extrathoracic: No axillary adenopathy. No subcutaneous nodules are seen. Pleura: Trace bilateral pleural effusions. No pneumothorax. No pleural calcifications. Lungs: Multiple subcentimeter ill-defined peripheral nodular densities are seen in both lungs. In a patient with septicemia septic emboli, is of primary concern. Simple inflammatory pulmonary nodules is another possibility. There are multiple peribronchovascular and centrilobular nodular densities seen in bilateral lower lobes suggestive of small airway infection. Patch of pulmonary infiltrate seen at the left lung base. There is mild smooth septal thickening seen in left upper lobe which may represent early developing edema. Major airways are patent Mediastinum/hila: Subcentimeter paratracheal and subcarinal lymph nodes, considered nonpathological by CT size criteria. Borderline hilar lymph nodes, nonspecific and could be reactive. No masses. Heart/Vessels: Unremarkable. Upper Abdomen: Splenomegaly. Osseous structures: No aggressive osseous lesions are seen. Impression: 1. Multiple subcentimeter ill-defined peripheral nodular densities are seen in both lungs. In a patient with septicemia, septic emboli is of primary concern. Simple inflammatory pulmonary nodules is another possibility. 2. Multiple peribronchovascular and centrilobular nodular densities seen in bilateral lower lobes suggestive of small airway infection. Patch of pulmonary infiltrate seen at the left lung base. 3. Trace bilateral pleural effusions. 4. Mild smooth septal thickening in left upper lobe which may represent early developing edema. 5. Borderline hilar lymph nodes, nonspecific and could be reactive. 6. Splenomegaly. Primary Diagnostic Code: Primary Interpreting Staff: HOSSAM K. SAAD, PHYSICIAN (Verifier) /HKS CT CHEST W/O CONTRAST Exm Date: MAR 05, 2010@10:15 Req Phys: BHAVSAR,HILONI M Pat Loc: OP Unknown/03-30-2010@15:34 Img Loc: W CT SCAN Service: MEDICAL-(W) (Case 2538 COMPLETE) CT CHEST W/O CONTRAST (CT Detailed) CPT:71250 Reason for Study: MDS, history of bacteremia and septic lung emboli Clinical History: Is this procedure to screen for malignancy? No 6056 PORTER RD NORTH OLMSTED, OHIO 44070 440 734 2916 Clinical History: 60 year old gentelman with MDS, history of bacteremia, neutropenic fever, septic emboli on last chest CT, currently requiring 50% venti mask. Report Status: Verified Date Reported: MAR 05, 2010 Date Verified: MAR 05, 2010 Verifier E-Sig:/ES/VORAVAN SHOTELERSUK Report: Comparison study: 2/19/2010. Technique: Axial thoracic CT images were obtained from the base of the neck through the lungs without intravenous contrast administration. Report: Scout images were reviewed. There has been interval progression of peribronchovascular nodules in both lungs, more prominent in the lower lobes. These are suggestive of bronchiolitis/pneumonitis. No dominant peripheral pulmonary nodules can be separated from the rest of peribronchovascular nodules to suggest that there are septic emboli in the current study. No bronchiectasis or peribronchial thickening. No mucus plugging. Interval increase in peripheral left lower lobe consolidation/atelectasis. Interval resolution of interlobular septal thickening in the left apex. Interval increase in size of small bilateral pleural effusions. The heart is not enlarged. Trace pericardial effusion. Mildly dilated central pulmonary artery. Aorta is normal in caliber. Mild coronary artery calcifications. Patent major airway. No enlarged mediastinal or hilar lymph nodes. Degenerative changes of the spine. Limited images of the included upper abdomen show marked splenomegaly. The liver is borderline enlarged. No adrenal nodule. Trace ascites. Impression: Interval progression of peribronchovascular nodules, more prominent in the lower lobes. Infectious/inflammatory bronchiolitis or pneumonitis is the first consideration. Increase in peripheral left lower lobe consolidation/atelectasis and small lateral pleural effusions. Marked splenomegaly. Primary Diagnostic Code: Primary Interpreting Staff: VORAVAN SHOTELERSUK, RADIOLOGIST (Verifier) /VS

    27. A patient with MDS/AML, fever, resp distress and nodular infiltrates ABX: Vanco (2/12-2/25, 3/9-now) Pip-tazo (2/12-2/15, 3/9-now) Voriconazole (2/21-2/28, 3/9-now) Acyclovir 400mg PO BID (2/2-now) Fluconazole 400mg PO daily (2/3-2/22; 2/28-now) Metronidazole (3/9-now) Cefepime (2/24-3/5) Bactrim (2/22-2/24) Meropenem (2/19-2/24) Gentamicin (2/19-2/22) Cipro (2/12-2/21) Imipenem (2/15-2/19) GRAM STAIN: MODERATE WBC'S FEW EPITHELIAL CELLS MANY GRAM NEGATIVE RODS MODERATE GRAM POSITIVE COCCI CULTURE RESULTS: MODERATE PSEUDOMONAS AERUGINOSA ANTIBIOTIC SUSCEPTIBILITY TEST RESULTS: PSEUDOMONAS AERUGINOSA : SUSC INTP AMIKACN 4 S MCG/ML CIPROFLOXACIN >=4 R MCG/ML GENTAMICIN >=16 R MCG/ML IMIPENEM. 8 I CEFEPIME 8 S PIP/TAZO 32 S MCG/ML

    28. A patient with MDS/AML, fever, resp distress and nodular infiltrates day notes 1 plts infused acyclovir flucon 2 broviac placement 3 AML Cycle 1 day 1 Idarubicin/Cytarabine 4 soreness bleeding at broviac site noted 5 6 MDS, Cycle 1, Day 4, Cytarabine/Idarubacin doe 7 8 receives blood 9 10 11 diarrhea chills abd pain 12 2/2 bc gnrs 13 vanco zosyn cipro; developed fever tachycardia with tx 14 2/2 bc with gnrs; previous set is citrobacter freundii; zosyn to imipenem 15 16 17 18 desaturation tranfer to ICU; debate re source of bactermia; line is removed 19 imi to mero + amikacin; ct chest nodular densities 20 cath no growth; voriconazole added; serum galactomannan sent 21 intubated for resp failure; pulm edema vs emboli vs fungal 22 bactrim added; bronched 23 negative smears on BAL pressors started 24 wbcs rising; renal failure; cefepeime vori acyclovir vanc 25 26 off pressors , extubated 27 28 negative serum galactomannan 29 diarrhea; oral vanco started 30 31 32 33 34 35 back to micu sepsis resp failure 36 back to micu 38 death day notes 1 plts infused acyclovir flucon 2 broviac placement 3 AML Cycle 1 day 1 Idarubicin/Cytarabine 4 soreness bleeding at broviac site noted 5 6 MDS, Cycle 1, Day 4, Cytarabine/Idarubacin doe 7 8 receives blood 9 10 11 diarrhea chills abd pain 12 2/2 bc gnrs 13 vanco zosyn cipro; developed fever tachycardia with tx 14 2/2 bc with gnrs; previous set is citrobacter freundii; zosyn to imipenem 15 16 17 18 desaturation tranfer to ICU; debate re source of bactermia; line is removed 19 imi to mero + amikacin; ct chest nodular densities 20 cath no growth; voriconazole added; serum galactomannan sent 21 intubated for resp failure; pulm edema vs emboli vs fungal 22 bactrim added; bronched 23 negative smears on BAL pressors started 24 wbcs rising; renal failure; cefepeime vori acyclovir vanc 25 26 off pressors , extubated 27 28 negative serum galactomannan 29 diarrhea; oral vanco started 30 31 32 33 34 35 back to micu sepsis resp failure 36 back to micu 38 death

    29. A patient with MDS/AML, fever, resp distress and nodular infiltrates Non-infectious etiologies: Acute leukemia Pulm infarcts, emboli Pneumonitis without infection Untreated infection?

    31. Galactomannan vs ß-1,3-D-glucan

    32. Blood and fever Transfusions Transfusion reactions Blood where it doesn’t belong Thrombosis and fever CVA and fever MI and fever

    33. A patient 19 days post-op from wedge biopsy of right lower lobe 79 y/o male with CAD, severe AS, a. fib on warfarin developed hemoptysis CT scan showed RLL infiltrate vs mass

    34. A patient 19 days post-op from wedge biopsy of right lower lobe

    35. A patient 19 days post-op from wedge biopsy of right lower lobe Underwent bronchoscopy which showed chronic inflammation and bleeding from medial basilar segment of rll Washings were negative for afb, cytology Needed 2v CABG and AVR but CT surgery service felt patient was not safe to put on CPB given the degree of hemoptysis so underwent RLL lobectomy; path showed bronchiolitis, focal organizing pneumonia

    36. A patient 19 days post-op from wedge biopsy of right lower lobe POD#14 patient has a new RML infiltrate and is intubated for respiratory failure. He is afebrile and has a normal WBC count. Has a fever spike to 38.5ºC

    37. A patient 19 days post-op from wedge biopsy of right lower lobe

    38. A patient 19 days post-op from wedge biopsy of right lower lobe

    39. A patient 19 days post-op from wedge biopsy of right lower lobe Dressler syndrome Fever and CVA Fever and DVT Noncontrast enhanced CT of the brain reveals focal lucency in the left cerebral hemisphere compatible with subacute infarction. There is no evidence of hemorrhagic transformation. There is mild parenchymal volume loss. Noncontrast enhanced CT of the brain reveals focal lucency in the left cerebral hemisphere compatible with subacute infarction. There is no evidence of hemorrhagic transformation. There is mild parenchymal volume loss.

    41. Examples of rapid and direct pathogen specific tests that are useful for detecting pathogens that cause fever Clostridium difficile antigen test HIV rapid test Rapid antigen panels for respiratory viruses DFA for HSV Urine antigen for legionella and histoplasma Serum cryptococcal antigen Serum urine pneumococcal antigen Serum galactomannan B-1,3-D-glucan PCR methods

    42. Direct PCR detection of pathogens

    43. Technology The Ibis T5000™ Biosensor System interrogates common sequences among classes of organisms for non-diagnostic use. Despite the enormous class diversity of organisms, Ibis scientists have carefully selected and curated genetic sequences that allow this interrogation to produce powerful results for surveillance, epidemiology, forensic, and biological research. For example, bacteria have highly conserved sequences in a number of genomic locations, including the universally conserved regions of ribosomal and other non-coding RNAs and essential protein-encoding genes. These conserved sequences can serve as priming sites for sequence amplification in PCR tests. When the regions between these conserved PCR primer-binding sites contain sequences that are variable depending on the class of organism, the base compositions of the PCR products can be used as identification markers. Mass spectrometry rapidly determines the precise weights of the nucleic acids present and the A, C, T, and G content (i.e., base composition) of each amplicon. The base compositions of the PCR products are used to help identify the organisms present. In addition to broad-range organism identification, the Ibis T5000 Biosensor System can be used with specific assay kits from Ibis Biosciences to provide strain genotyping information, for human forensics and other non-diagnostic purposes. Technology The Ibis T5000™ Biosensor System interrogates common sequences among classes of organisms for non-diagnostic use. Despite the enormous class diversity of organisms, Ibis scientists have carefully selected and curated genetic sequences that allow this interrogation to produce powerful results for surveillance, epidemiology, forensic, and biological research. For example, bacteria have highly conserved sequences in a number of genomic locations, including the universally conserved regions of ribosomal and other non-coding RNAs and essential protein-encoding genes. These conserved sequences can serve as priming sites for sequence amplification in PCR tests. When the regions between these conserved PCR primer-binding sites contain sequences that are variable depending on the class of organism, the base compositions of the PCR products can be used as identification markers. Mass spectrometry rapidly determines the precise weights of the nucleic acids present and the A, C, T, and G content (i.e., base composition) of each amplicon. The base compositions of the PCR products are used to help identify the organisms present. In addition to broad-range organism identification, the Ibis T5000 Biosensor System can be used with specific assay kits from Ibis Biosciences to provide strain genotyping information, for human forensics and other non-diagnostic purposes.

    44. Biomarkers of infection Procalcitonin ESR, CRP, ferritin

    45. Procalcitonin

    47. Conclusions Not all fever is infectious Careful clinical evaluation and chart review are imperative in determining sources of fever Always consider non-infectious etiologies in the differential and evaluate accordingly; diagnosis of exclusion or inclusion. “A man can have as many diseases as he damn well pleases!” Both non-infectious and infectious causes can be present. “Just say no to drugs” (antibiotics) when appropriate. Stop everything and reevaluate off antibiotics if you can.

    48. References Dimopoulos G. and Falagas M. E. “Approach to the febrile patient in the ICU” Infect. Dis. Clin. N. Am. (2009): 23; 471-84. O’Grady, N. P. et al., “Guidelines for evaluation of new fever in critically ill adult patients: 2008 update from the American College of Critical Care Medicine and the Infectious Diseases Society of America”, Crit. Care Med., (2008) Apr;36(4):1330-49. Marik, P. E. “Fever in the ICU” Chest (2000): 117; 855-869. Patel, R. A. and Gallagher, J. C. “Drug Fever” Pharmacotherapy (2010): 30(1);57-69. Caroff, Psychiatric Annals, 1991,21:130-147. www.nmsis.org Kawanishi, C. “Genetic Predisposition to NMS” Am J Pharmacogenomics. 2003;3(2):89-95 Church, LD, Cook GP and McDermott MF, Nature Clinical Practice Rheumatology (2008): 4; 34-42. Hachem RY, Kontoyiannis DP, Chemaly RF, Jiang Y, Reitzel R, Raad I. J Clin Microbiol. 2009 Jan;47(1):129-33. Epub 2008 Nov 12. Malhotra-Kumar, S., et al., J. Clin. Micro. (2008):46;1577-1587 Christ-Crain M and Muller B, Eur. Respir. J (2007): 30; 556-573.

More Related