Should my patient with COPD and recurrent exacerbations undergo evaluation for antibody deficiency?

Although there are no consensus guidelines on when to evaluate patients with COPD for antibody deficiency, we should at least consider this possibility in patients with recurrent exacerbations despite maximal inhaled therapy (long-acting beta-2 agonist-LABA, long-acting muscarinic antagonist-LAMA and inhaled corticosteroids).1

Couple of retrospective studies of common variable immunodeficiency (CVID) in patients with COPD have reported a prevalence ranging from 2.4% to 4.5%. 1 In another study involving 42 patients thought to have had 2 or more moderate to severe COPD exacerbations per year—often despite maximal inhaled therapy— 29 were diagnosed  with antibody deficiency syndrome, including 20 with specific antibody deficiency (SAD), 8 with CVID and 1 with selective IgA deficiency.2  Although systemic corticosteroids may lower IgG and IgA levels, the majority of the patients in this study were not taking any corticosteroids at the time of their evaluation.

In another study involving patients undergoing lung transplantation, pre-transplant mild hypogammaglobulinemia was more prevalent among those with COPD (15%) compared to other lung conditions (eg, cystic fibrosis), independent of corticosteroid use.3  A favorable impact of immunoglobulin therapy or chronic suppressive antibiotics on reducing recurrent episodes of COPD exacerbation in patients with antibody deficiency has also been reported, supporting the clinical relevance of hypogammaglobulinemia in these patients. 2,4 

Remember that even normal quantitative serum immunoglobulin levels (IgG, IgA, and IgM) do not necessarily rule out antibody deficiency. Measurement of IgG subclasses, as well as more specific antibodies, such as those against pneumococcal polysaccharides may be required for further evaluation.

See a related pearl at https://pearls4peers.com/2015/07/12/my-65-year-old-patient-has-had-several-bouts-of-bacterial-pneumonia-in-the-past-2-years-her-total-serum-immunoglobulins-are-within-normal-range-could-she-still-be-immunodeficient/.

Contributed in part by Sydney Montesi, MD, Mass General Hospital, Boston, MA.

References

  1. Berger M, Geng B, Cameron DW, et al. Primary immune deficiency diseases as unrecognized causes of chronic respiratory disease. Resp Med 2017;132:181-188. https://www.sciencedirect.com/science/article/pii/S0954611117303554
  2. McCullagh BN, Comelias AP, Ballas ZK, et al. Antibody deficiency in patients with frequent exacerbations of chronic obstructive pulmonary disease (COPD). PLoS ONE 2017; 12: e0172437. https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0172437
  3. Yip NH, Lederer DJ, Kawut SM, et al. Immunoglobulin G levels before and after lung transplantation 2006;173:917-21.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2662910/
  4. Cowan J, Gaudet L, Mulpuru S, et al. A retrospective longitudinal within-subject risk interval analysis of immunoglobulin treatment for recurrent acute exacerbation of chronic obstructive pulmonary disease. PLoS ONE 2015;10:e0142205. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0142205

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Should my patient with COPD and recurrent exacerbations undergo evaluation for antibody deficiency?

Should I choose a bactericidal over bacteriostatic antibiotic in the treatment of my patient with pneumonia complicated by bacteremia?

You don’t have too!  Although “bacteriostatic” antibiotics have traditionally been regarded as inferior to “bactericidal” antibiotics in the treatment of serious infections, a 2018 “myth busting” systemic literature review1 concluded that bacteriostatic antibiotics are just as effective against a variety of infections, including pneumonia, non-endocarditis bacteremia, skin and soft tissue infections and genital infections; no conclusion can be made in regards to endocarditis or bacterial meningitis, however, due insufficient clinical evidence.1-3

Interestingly, most of the studies included in the same systemic review showed that bacteriostatic antibiotics were more effective compared to bactericidal antibiotics.1 So, for most infections in hospitalized patients, including those with non-endocarditis bacteremia, the choice of antibiotic among those that demonstrate in vitro susceptibility should not be based on their “cidal” vs “static” label.

Such conclusion should not be too surprising since the definition of bacteriostatic vs bactericidal is based on arbitrary in vitro constructs and not validated by any available in vivo data. In addition, static antibiotics may kill bacteria as rapidly as cidal antibiotics in vitro at higher antibiotic concentrations.3

Another supportive evidence is a 2019 study finding similar efficacy of sequential intravenous-to-oral outpatient antibiotic therapy for MRSA bacteremia compared to continued IV antibiotic therapy despite frequent use of bacteriostatic oral antibiotics (eg, linezolid, clindamycin and doxycycline). 4

 

References

  1. Wald-Dickler N, Holtom P, Spellberg B. Busting the myth of “static vs cidal”: as systemic literature review. Clin Infect Dis 2018;66:1470-4. https://academic.oup.com/cid/article/66/9/1470/4774989
  2. Steigbigel RT, Steigbigel NH. Static vs cidal antibiotics. Clin Infect Dis 2019;68:351-2. https://academic.oup.com/cid/article-abstract/68/2/351/5067395
  3. Wald-Dickler N, Holtom P, Spellberg B. Static vs cidal antibiotics; reply to Steigbigel and Steigbigel. Clin Infect Dis 2019;68:352-3. https://academic.oup.com/cid/article-abstract/68/2/352/5067396?redirectedFrom=fulltext
  4. Jorgensen SCJ, Lagnf AH, Bhatia S, et al. Sequential intravenous-to-oral outpatient antbiotic therapy for MRSA bacteraemia: one step closer.  J Antimicrob Chemother 2019;74:489-98.  https://www.ncbi.nlm.nih.gov/pubmed/30418557

 

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Should I choose a bactericidal over bacteriostatic antibiotic in the treatment of my patient with pneumonia complicated by bacteremia?

When should I consider prophylaxis for Pneumocystis pneumonia (PCP) in my patient on prednisone?

It is generally recommended that patients on ≥20 mg of daily prednisone (or its equivalent) for ≥1 month be considered for PCP prophylaxis. 1

Couple of studies in 1990s helped define the dose and duration of corticosteroids (CS) that should prompt PCP prophylaxis. A Mayo Clinic study of patients without AIDS but PCP found median daily CS dose of 30 mg of prednisone or equivalent, with 25% of patients receiving as little as 16 mg of prednisone daily among patients with PCP.The median duration of CS therapy before PCP was 12 weeks. A similar study found a mean CS dose of 33 mg of prednisone or equivalent with mean duration of 7 months (range 1-154 months) among patients with PCP. 3

A 2018 retrospective study4  of patients with rheumatic diseases receiving prolonged high-dose CS therapy (≥30 mg prednisone for ≥4 weeks) found that PCP prophylaxis with trimethoprim/sulfamethoxazole (TMP/STX) resulted in 93% reduction in the incidence of PCP with an overall number needed to treat (NNT) of 52. It was suggested that PCP prophylaxis could be discontinued in patients receiving < 15 mg of prednisone daily.

Bonus Pearl: Did you know that TMP/STX may be given either as double-strength 3x/week or single-strength daily? 5,6

 

References

1. Limper AH, Knox KS, Sarosi SA, et al. An official American Thoracic Society statement: Treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med 2011;183:96-128. https://www.ncbi.nlm.nih.gov/pubmed/21193785

2. Yale SH, Limper AH. Pneumocystis carinii pneumonia in patients without acquired immunodeficiency syndrome: associated illness and prior corticosteroid therapy. Mayo Clin Proc 1996;71:5-13. https://www.sciencedirect.com/science/article/abs/pii/S0025619611649148

3. Arend SM, Kroon FP, van’t Wout JW. Pneumocystis carinii pneumonia in patients without AIDS, 1980 through 1993: An analysis of 78 cases. Arch Intern Med 1995;155:2436-2441. https://www.ncbi.nlm.nih.gov/pubmed/7503602

4. Park JW, Curtis JR, Moon J, et al. Prophylactic effect of trimethoprim-sulfamethoxazole for Pneumocystis pneumonia in patients with rheumatic diseases exposed to prolonged high-dose glucocorticoieds. Ann Rheum Dis 2018;77:664-9. https://www.ncbi.nlm.nih.gov/pubmed/29092853

5. Anevlavis S, Kaltsas K, Bouros D. Prophylaxis for pneumocystis pneumonia (PCP) in non-HIV infected patients. PNEUMON 2012;25, October-December.http://www.pneumon.org/assets/files/789/file483_273.pdf

6. Stern A, Green H, Paul M, Leibovici L. Prophylaxis for pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients (Review). Cochrane data of Systematic Reviews 2014, issue 10. DOI: 10.1002/14651858.CD005590.pub3. https://www.ncbi.nlm.nih.gov/pubmed/25269391

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When should I consider prophylaxis for Pneumocystis pneumonia (PCP) in my patient on prednisone?

My hospitalized patient with pneumonia has now suffered an acute myocardial infarction (MI). Can acute infection and MI be related?

Yes! Ample epidemiological studies implicate infection as an important risk factor for MI.1 The increased risk of MI has been observed during the days, weeks, months or even years following an infection.

A 2018 paper reported a several-fold risk of MI during the week after laboratory-confirmed infection caused by a variety of respiratory pathogens such as influenza virus (6-fold), respiratory syncytial virus (4-fold), and other respiratory viruses (3-fold). 2 Among patients hospitalized for pneumococcal pneumonia, 7-8% may suffer an MI.3,4 One study found a 48-fold increase in the risk of MI during the first 15 days after hospitalization for acute bacterial pneumonia.5 Similarly, an increase in the short-term risk of MI has been observed in patients with urinary tract infection and bacteremia.6

The risk of MI appears to be the highest at the onset of infection and correlates with the severity of illness, with the risk being the highest in patients with pneumonia complicated by sepsis, followed by pneumonia and upper respiratory tract infection. Among patients with pneumonia, the risk exceeds the baseline risk for up to 10 years after the event, particularly with more severe infections.1

Potential mechanisms of MI following infections include release of inflammatory cytokines (eg, interleukins 1, 6, tumor necrosis factor alpha) causing activation of inflammatory cells in atherosclerotic plaques, in turn resulting in destabilization of the plaques. In addition, the thrombogenic state of acute infections, platelet and endothelial dysfunction may increase the risk of coronary thrombosis at sites of plaque disruption beyond clinical resolution of the acute infection. 1

References

  1. Musher DM, Abers MS, Corrales-Medina VF. Acute infection and myocardial infarction. N Engl J Med 2019;380:171-6. https://www.ncbi.nlm.nih.gov/pubmed/30625066
  2. Kwong JC, Schwartz KL, Campitelli MA, et al. Acute myocardial infarction after laboratory-confirmed influenza infection. N Engl J Med 2018;378:345-53. https://www.nejm.org/doi/full/10.1056/NEJMoa1702090
  3. Musher DM, Alexandraki I, Graviss EA, et al. Bacteremic and nonbacteremic pneumococcal pneumonia: a prospective study. Medicine (Baltimore) 2000;79:210-21. https://www.ncbi.nlm.nih.gov/pubmed/10941350
  4. Musher DM, Rueda Am, Kaka As, Mapara SM. The association between pneumococcal pneumonia and acute cardiac events. Clin Infect Dis 2007;45:158-65. https://www.ncbi.nlm.nih.gov/pubmed/17578773
  5. Corrales-Medina VF, Serpa J, Rueda AM, et al. Acute bacterial pneumonia is associated with the occurrence of acute coronary syndromes. Medicine (Baltimore) 2009;88:154-9. https://www.ncbi.nlm.nih.gov/pubmed/19440118
  6. Dalager-Pedersen M, Sogaard M, Schonheyder HC, et al. Risk for myocardial infarction and stroke after community-acquired bacteremia: a 20-year population-based cohort study. Circulation 2014;129:1387-96. https://www.ncbi.nlm.nih.gov/pubmed/24523433

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My hospitalized patient with pneumonia has now suffered an acute myocardial infarction (MI). Can acute infection and MI be related?

My patient with no known liver disease appears to have bilateral asterixis. What other causes should I consider?

Although originally described in 1949 in patients with liver disease and labelled as “liver flap”, numerous other causes of asterixis exist aside from severe liver disease (1,2). As early as 1950s, asterixis was observed among some patients with heart failure and pulmonary insufficiency but without known significant liver disease (3). Azotemia has also been associated with asterixis.

 
Don’t forget about medication-associated asterixis . Commonly used drugs such as gabapentin, pregabalin, phenytoin, and metoclopramide have been associated with asterixis (1,4) . Even antibiotics such as ceftazidime and high dose trimethoprim-sulfamethoxazole may be culprits (1,5). There are many psychiatric drugs including lithium, carbamazepine, clozapine, and valproic acid that have been implicated (1,6) as well. Some reviews have also included hypomagnesemia and hypokalemia on the list of causes of asterixis (1).

 
Although asterixis is essentially a negative myoclonus with episodic loss of electrical activity of muscle and its tone, its exact pathophysiology remains unclear (7). 

 

Bonus Pearl: Did you know that the origin of the word asterixis is An (negative)-iso (equal)-sterixis (solidity) which was shortened by Foley and Adams, its original discoverers, to what we now refer to as “asterixis” (1).

 

References
1. Agarwal R, Baid R. Asterixis. J Postgrad Med 1016;62:115-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944342/ 2. Pal G, Lin MM, Laureno R. Asterixis: a study of 103 patients. Metab Brain Dis; 2014:29:813-24. https://link.springer.com/article/10.1007%2Fs11011-014-9514-7
3. Conn HO. Aterixis—Its occurrence in chronic pulmonary disease, with a commentary on its general mechanism. N Engl J Med 1958;259:564-569. https://www.nejm.org/doi/full/10.1056/NEJM195809182591203
4. Kim JB, Jung JM, Park MH. Negative myoclonus induced by gabapentin and pregabalin: a case series and systemic literature review. J Neurol Sci 2017;382:36-9. https://www.sciencedirect.com/science/article/pii/S096758681830225X
5. Gray DA, Foo D. Reversible myoclonus, asterixis, and tremor associated with high dose trimethoprim-sulfamethoxazole: a case report. J Spinal Cord Med 2016; Vol. 39 (1), pp. 115-7. https://www.ncbi.nlm.nih.gov/pubmed/26111222
6. Nayak R, Pandurangi A, Bhogale G, et al. Aterixis (flapping tremors) as an outcome of complex psychotropic drug interaction. J Neuropsychiatry Clin Neurosci 2012;24: E26-7. https://neuro.psychiatryonline.org/doi/pdf/10.1176/appi.neuropsych.101102667. Ugawa Y, Shimpo T, Mannen T. Physiological analysis of asterixis: silent period locked averaging. J Neurol Neurosurg Psych 1989;52:89-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1032663/pdf/jnnpsyc00523-0104.pdf

 

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My patient with no known liver disease appears to have bilateral asterixis. What other causes should I consider?

My patient with community-acquired pneumonia (CAP) will be going home on an oral antibiotic. Is there a significant difference in the risk of Clostridium difficile infection among the usual CAP antibiotics?

Not all antibiotics are equal in their risk of CDI. Among the common antibiotics used for respiratory tract infections, doxycycline appears to be the least likely to be associated with CDI. 

A population-based case-control study of community-acquired CDI found that while recent exposure increased the risk of CDI for fluoroquinolones, macrolides, cephalosporins, sulfonamides and trimethoprim and penicillins, the risk of CDI with tetracycline use was not increased (1).  Similar findings (with the exception of sulfonamides also appearing risk-neutral) have been reported by others (2). 

Among patients receiving ceftriaxone, receipt of doxycycline has been associated with protection against development of CDI (3).  A 2018 systematic review and meta-analysis also concluded that tetracyclines were associated with a decreased risk of CDI; OR 0.55 (95% CI 0,40-0.75) for doxycycline alone (4). 

 

The most likely explanation for why doxycycline may be associated with lower risk of CDI is its in vitro activity against anaerobes, including C. difficile. Additionally, because of its ability to inhibit protein synthesis, doxycycline may attenuate C. difficile toxin production. Its high bioavailability and maximal absorption from the upper gastrointestinal tract may also mitigate its impact on gut flora, further reducing its risk of CDI (3). 

 

References
1. Delaney JAC, Dial S, Barkun A et al. Antimicrobial drugs and community-acquired Clostridium difficile-associated disease-UK. Emerg Infect Dis 2007:13;761-63. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2738472
2. Kuntz JL, Chirchilles EA, et al. Incidence of and risk factors for community-associated Clostridium difficile infection : A nested case-control study. BMC Infect Dis 2011;11:194. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154181/ 
3. Doernberg SB, Winston LG, Deck DH, et al. Does doxycycline protect against development of Clostridium difficile infection. Clin Infec Dis 2012;44:615-20. https://www.academia.edu/7814406/Does_Doxycycline_Protect_Against_Development_of_Clostridium_difficile_Infection
4. Tariq R, Cho J, Kapoor S, et al. Low risk of primary Clostridium difficile infection with tetracyclines: a systematic review and metanalysis. Clin Infect Dis 2018; 766:514-27. https://academic.oup.com/cid/article/66/4/514/4161552 

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My patient with community-acquired pneumonia (CAP) will be going home on an oral antibiotic. Is there a significant difference in the risk of Clostridium difficile infection among the usual CAP antibiotics?

My patient with erythema multiforme has tested positive for Mycoplasma pneumoniae IgM antibody. Does this mean she has an acute M. pneumonia infection as the cause of her acute illness?

Not necessarily! Although detection of IgM in the serum of patients has proven valuable in diagnosing many infections during their early phase, particularly before IgG is detected, less well known is that false-positive IgM results are not uncommon. 1

More specific to M. pneumoniae IgM, false-positive results have been reported in 10-80% of patients without a clinical diagnosis of acute M. pneumoniae infection 2-4 and 3-15% of blood donors. 4

False-positive IgM results may also occur when testing for other infectious agents, such as the agent of Lyme disease (Borrelia burgdorferi), arboviruses (eg, Zika virus), and herpes simplex, Epstein-Barr, cytomegalovirus, hepatitis A and measles viruses. 1,5  

Reports of false positive IgM results include a patient with congestive heart failure and mildly elevated liver enzymes who had a false-positive hepatitis IgM which led to unnecessary public health investigation and exclusion from an adult day care center. 1 Another patient with sulfa rash had a false-positive measles IgM antibody resulting in callback of >100 patients and healthcare providers for testing!5

There are many potential mechanisms for false-positive IgM results, including polyclonal B cell activation, “vigorous immune response”, cross-reactive antibodies, autoimmune disease, subclinical reactivation of latent viruses, influenza vaccination, overreading weakly reactive results, and persistence of antibodies long after the resolution of the acute disease. 1,2

In our patient, a significant rise in M. pneumoniae IgG between acute and convalescent samples several weeks apart may be more helpful in diagnosing an acute infection accounting for her erythema multiforme.

 

References

  1. Landry ML. Immunoglobulin M for acute infection: true or false? Clin Vac Immunol 2016;23:540-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933779/
  2. Csango PA, Pedersen JE, Hess RD. Comparison of four Mycoplasma pneumoniae IgM-, IgG- and IgA-specific enzyme immunoassays in blood donors and patients. Clin Micro Infect 2004;10:1089-1104. https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(14)63853-2/pdf
  3. Thacker WL, Talkington DF. Analysis of complement fixation and commercial enzyme immunoassays for detection of antibodies to Mycoplasma pneumoniae in human serum. Clin Diag Lab Immunol 2000;7:778-80. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC95955/
  4. Ryuta U, Juri O, Inoue Y, et al. Rapid detection of Mycoplasma pneumoniae IgM antibodies using immunoCard Mycoplasma kit compared with complement fixation (CF) tests and clinical application. European Respiratory Journal 2012; 40: P 2466 (Abstract). https://erj.ersjournals.com/content/40/Suppl_56/P2466 
  5. Woods CR. False-positive results for immunoglobulin M serologic results: explanations and examples. J Ped Infect Dis Soc 2013;2:87-90. https://www.ncbi.nlm.nih.gov/pubmed/26619450

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My patient with erythema multiforme has tested positive for Mycoplasma pneumoniae IgM antibody. Does this mean she has an acute M. pneumonia infection as the cause of her acute illness?

My patient with history of intravenous drug use has noticed excessive growth of thick hair at the site of a previous abscess on her arm. Is there a connection between skin and soft tissue infections and localized hypertrichosis?

Localized hypertrichosis after infectious rash or “HAIR”, has been reported following a variety of skin and soft tissue infections (SSTIs), including sites of previous septic thrombophlebitis, cellulitis and olecranon bursitis. 1,2  A similar phenomenon has also been described in infants with recent chicken pox, as well non-infectious skin conditions arising from repeated irritation, friction, burns, excoriated insect bites, and fractures with cast application.1,2

Although heat and hyperemia have been implicated as growth stimulants for the hair follicle, 3 the exact mechanism of this intriguing phenomenon is unclear. It is possible that the sustained inflammatory process associated with chronic or more severe SSTIs leads to protracted stimulation of certain growth receptors in the human hair follicles (eg, transient vanilloid receptor-1) through heat and inflammation, as observed in mice in vivo.4

Aside from its possibly undesirable esthetic effects, localized HAIR appears to have no adverse health consequences, is reversible, and should require no further evaluation.

Note: 2 of the publications cited were written by the author of this post.

References

  1. Manian, FA. Localized hypertrichosis after infectious rash in adults. JAAD Case Reports 2015; 1:106-7. https://www.jaadcasereports.org/article/S2352-5126(15)00051-X/pdf
  2. Manian, FA. Localized hypertrichosis after infectious rash (“HAIR”) in adults: a report of 5 cases. Open Forum Infect Dis 2014;1 (Suppl 1):S195-S195. http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC5782143&blobtype=pdf
  3. Leung AK, Kiefer GN. Localized acquired hypertrichosis associated with fracture and cast application. J Natl Med Assoc 1989;81:65-7. https://www.ncbi.nlm.nih.gov/pubmed/2724357
  4. Bodo E, Biro T, Telek A, et al. A hot new twist to hair biology; involvement of vanilloid receptor-1 (VR1/TRPV1) signaling in human hair growth control. Am J Pathol 1005;166:985-8. https://www.sciencedirect.com/science/article/pii/S0002944010623206

 

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My patient with history of intravenous drug use has noticed excessive growth of thick hair at the site of a previous abscess on her arm. Is there a connection between skin and soft tissue infections and localized hypertrichosis?

My patient with cocaine and alcohol addiction is admitted with repeated convulsions during which he seems totally conscious. What could I be missing?

Consider strychnine poisoning as a cause of recurrent generalized tonic clonic seizures and muscle spasm with clear sensorium either during or following the episode. 1-4 In contrast to the cortical source of most seizures, convulsions due to strychnine poisoning are due to the blocking of the action of spinal and brain-stem inhibitory neurons resulting in overwhelming muscle rigidity, not unlike that seen in tetanus.

Although strychnine was found in various tonics and cathartic agents and was a common cause of accidental death in children under 5 years of age in early 20th century, it is still used in various rodenticides and pesticides.3  Today, it may be used intentionally in suicide attempts as well as an adulterant in street drugs, such as amphetamines, heroin and especially cocaine. 1,3,5

The initial symptoms of strychnine poisoning include nervousness, a hyperalert state, and confusion. These symptoms may be followed by severe muscle rigidity throughout the body often in response to minimal stimuli, such as physical contact, bright lights, noise and medical procedures.3, 6,7  Interestingly, strychnine also has an excitatory action on the medulla and enhances the sensation of touch, smell, hearing and sight.6  The cause of death is usually respiratory arrest due to prolonged muscle spasms, often complicated by rhabdomyolysis and associated renal failure.1

So among the numerous causes of seizures, think of strychnine as another potential cause when there is no concurrent loss of consciousness or the expected postictal state.

Bonus Pearl: Did you know that strychnine may be present in street drugs with a variety of names such as “back breakers”, “homicide”, “red rock opium”, “red stuff” and “spike”? 7

References

  1. Wood DM, Webser E, Martinez D, et al. Case report: survival after deliberate strychnine self-poisoning, with toxicokinetic data. Critical Care 2002;6:456-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC130147/
  2. Santhosh GJ, Joseph W, Thomas M. Strychnine poisoning. J Assoc Physicians India 2003;51:736. https://www.ncbi.nlm.nih.gov/pubmed/14621058
  3. Libenson MH, Young JM. Case records of Massachusetts General Hospital. A 16 years boy with an altered mental status and muscle rigidity. N Engl J Med 2001;344:1232-9. https://www.nejm.org/doi/full/10.1056/NEJM200104193441608
  4. Smith BA. Strychnine poisoning. J Emerg Med 1990;8: 321-25. https://www.ncbi.nlm.nih.gov/pubmed/2197324
  5. O’Callaghan WG, Ward M, Lavelle P, et al. Unusual strychnine poisoning and its treatment: report of eight cases. B Med J 1982;285:478. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1499293/
  6. Burn DJ, Tomson CRV, Seviour J, et al. Strychnine poisoning as an unusual cause of convulsions. Postgrad Med J 1989;65:563-64. https://www.ncbi.nlm.nih.gov/pubmed/2602253
  7. Radosavljevic J, Jeffries WS, Peter JV. Intentional strychnine use and overdose—an entity of the past? Crit Care Resusc 2006;8: 260-61. https://www.ncbi.nlm.nih.gov/pubmed/16930120

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My patient with cocaine and alcohol addiction is admitted with repeated convulsions during which he seems totally conscious. What could I be missing?

My patient with headache following a fall has a pink cerebrospinal fluid but the lab reports it xanthochromic. Isn’t xanthochromia supposed to describe yellow discoloration only?

Although xanthochromia literally means yellow color, when it comes to describing the color of the cerebrospinal fluid (CSF), a more liberal—but perhaps misleading— definition of xanthochromia extending to other colors, such as pink and orange, is commonly found in the literature. 1-5

In the presence of red blood cells (RBCs) in the subarachnoid space, as seen in subarachnoid hemorrhage (SAH), 3 pigments are formed by the breakdown of hemoglobin in the CSF: oxyhemoglobin, methemoglobin, and bilirubin. Oxyhemoglobin is typically red but has also been reported to appear orange or orange-yellow with dilution.6  Methemoglobin is brown and bilirubin is yellow. Of these pigments, only bilirubin can be formed solely from in vivo conversion, while oxyhemoglobin and methemoglobin may also form after CSF has been obtained (eg, in tubes).  Due to the suboptimal reliability of visual inspection, some have argued for the routine use of spectrophotometry of the CSF instead in patients with suspected SAH.7

In our patient, the “pink xanthochromia” may be related to RBC breakdown either due to a SAH or as a result of hemolysis in the sample tubes themselves, especially if there was a delay in processing the specimen. Even if he had “true xanthochromia” with yellow discoloration of CSF, make sure to exclude other causes besides SAH, such as high CSF protein, hyperbilirubinemia, rifampin therapy, and high carotenoid intake (eg, carrots).

 

References

  1. Seehusen DA, Reeves MM, Fomin DA. Cerebrospinal fluid analysis. Am Fam Phys 2003;68:1103-8. https://www.aafp.org/afp/2003/0915/p1103.pdf
  2. Edlow JA, Bruner KS, Horowitz GL. Xanthochromia. A survey of laboratory methodology and its clinical implications. Arch Pthol Lab Med 2002;126:413-15.
  3. Lo BM, Quinn SM. Gross xanthochromia on lumbar puncture may not represent an acute subarachnoid hemorrhage. Am J Emerg Med 2009;27:621-23.
  4. Koenig M. Approach to the patient with bloody or pigmented cerebrospinal fluid. In Irani DN, ed, Cerebrospinal fluid in clinical practice. 2009. https://doi.org/10.1016/B978-1-4160-2908-3.X0001-6
  5. Welch H, Hasbun R. Bacterial infections of the central nervous system. In Handbook of Clinical Neurology, 2010. https://www.sciencedirect.com/handbook/handbook-of-clinical-neurology/vol/96/suppl/C
  6. Barrows LJ, Hunter FT, Banker BQ. The nature and clinical significance of pigments in the cerebrospinal fluid. Brain 1955; 58: 59-80. https://www.ncbi.nlm.nih.gov/pubmed/14378450
  7. Cruickshank A, Auld P, Beetham R, et al. Revised national guidelines for analysis of cerebrospinal fluid for bilirubin in suspected subarachnoid haemorrhage. Ann Clin Biochem 2008;45:238-44. https://www.ncbi.nlm.nih.gov/pubmed/18482910

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My patient with headache following a fall has a pink cerebrospinal fluid but the lab reports it xanthochromic. Isn’t xanthochromia supposed to describe yellow discoloration only?