My patient has developed isolated eosinophilia without symptoms while receiving an antibiotic. Should I consider discontinuing the antibiotic or can I just continue it as long as she has no symptoms?

Short answer: We don’t really know what’s the best way to manage patients with  isolated (asymptomatic) eosinophilia (IE) that develops during antibiotic therapy. We do know that the majority of patients with IE may never develop hypersensitivity reaction such as rash, renal or liver injuries, but predicting who will or will not get HSRs is a challenge.1-3 Couple of studies may help us in our decision making, however.

In a 2015 study1 involving patients receiving outpatient parenteral antibiotics, eosinophilia was present in 25% of patients during their course of treatment, of whom 30% subsequently developed HSR and 5% developed more than 1 sign of HSR. Patients with IE and subsequent HSR developed eosinophilia earlier in their course of treatment (median 11 vs 17 days) and had a higher peak absolute eosinophil count (~ 850 vs ~700/ ml).  The authors suggested that close monitoring for rash and renal injury in patient with IE during antibiotic therapy be considered, and that medication changes may be necessary when IE is associated with earlier onset of eosinophilia or higher absolute eosinophil count.

In a 2017 prospective study2 of patients with eosinophilic drug reactions (~20% related to antibiotics), the majority (56%) were asymptomatic. Earlier onset of eosinophilia and higher eosinophil count were associated with symptomatic eosinophilia, similar to the aforementioned study. The frequency of patients with IE who went on to have symptomatic eosinophilia when the suspect drug was continued vs those in whom it was not continued remains unclear from these studies.

Ultimately, the decision to continue or discontinue a suspect antibiotic when your patient has new-onset IE should be made on a case-by-case basis, taking into account the severity of the patient’s infection, availability of equally effective and tolerated alternative drugs and the ability to closely monitor for symptomatic disease. The timing of onset of eosinophilia and its peak absolute count may also play a role.

Bonus pearl: Did you know that only 18% of inpatients with cutaneous drug eruptions may have peripheral eosinophilia?4

The author acknowledges the invaluable input of Kimberly Blumenthal, MD in composing this pearl.

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References

  1. Blumenthal KG, Youngster I, Rabideau DJ, et al. Peripheral blood eosinophilia and hypersensitivity reactions among patients receiving outpatient parenteral antibiotics. J Allergy Clin Immunol 2015;136:1288.1294. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640981/
  2. Ramirez E, Mdrano-Casique N, Tong HY, et al. Eosinophilic drug reactions detected by a prospective pharmacovigilance programme in a tertiary hospital. Br J Pharmacol 2017;83:400-15. https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/bcp.13096
  3. Rauscher C, Freeman A. Drug-induced eosinophilia. Allergy Asthma Proc 2018;39:252-56. https://www.ncbi.nlm.nih.gov/pubmed/29669671
  4. Romagosa R, Kapoor S, Sanders J, et al. inpatient adverse cutaneous drug erutpions and eosinophilia. Arch Dermatol 2001; 137:511-12. https://www.ncbi.nlm.nih.gov/pubmed/11295947   

 

 

My patient has developed isolated eosinophilia without symptoms while receiving an antibiotic. Should I consider discontinuing the antibiotic or can I just continue it as long as she has no symptoms?

My patient just developed a fixed drug reaction from ibuprofen. What is the mechanism of this type of skin reaction?

Although its mechanism is not full elucidated, fixed drug eruption (FDE) is thought to result from the drug-induced cytotoxic activation of CD8+ memory T cells.1 ,2

In this context, the culprit medication behaves as a hapten that adheres to basal keratinocytes which in turn results in the recruitment of T cells and inflammation.  However, as the inflammation resolves, CD8+  effector-memory T cells remain in the area in question,  setting the stage for more rapid immunologic reaction when the drug is reintroduced.

Why a systemic drug triggers a reaction only at specific sites in the body is a fascinating question. Prior herpes simplex virus (HSV) infection (eg, on the lips or genitalia) may explain some cases.1 Interestingly, despite the absence of prior herpetic lesions, most patients with FDE are seropositive for HSV. Previously traumatized body sites (e.g. from burns or insect bites) may also create an immune microenvironment conducive to FDE.

The classic presentation of FDE is reappearance of a rash in the genitals, perianal areas, hands, and feet within 30 min to 8 hours of taking the culprit medication.3 Look specifically for NSAIDs, tetracyclines, sulfonamides, and aspirin on the patient’s drug list. 4

References

  1. Shiohara, T. Fixed drug eruption: Pathogenesis and diagnostic tests. Curr Opin Allergy Clin Immunol 2009; 9:316-21. https://www.ncbi.nlm.nih.gov/pubmed/19474709
  2. Butler, DF. Fixed Drug Eruptions. Medscape. http://emedicine.medscape.com/article/1336702-overview#a4. Accessed March 26, 2018.
  3. Korkij W, Soltani K. Fixed drug eruptions: A brief review. Arch Dermatol 1984;120:520. https://www.ncbi.nlm.nih.gov/pubmed/6231004
  4. Oakley, A. Fixed Drug Eruption. https://www.dermnetnz.org/topics/fixed-drug-eruption Accessed March 26, 2018.

 

Contributed by Amir Hossein Ameri, Medical Student, Harvard Medical School

My patient just developed a fixed drug reaction from ibuprofen. What is the mechanism of this type of skin reaction?

When evaluating for an esophageal perforation, is a water-soluble contrast agent such as Gastrografin a better and safer alternative to barium swallow study?

Water-soluble contrast agents (WCAs) (eg, meglumine diatrizoate or Gastrografin) are often ordered as the initial radiographic test for evaluation of esophageal perforation or leaks, followed by barium swallow if the test is negative because small leaks are better detected with the more radiopaque barium1.  Such practice, however, is based on extrapolation of data on the deleterious effect of barium when extravasated into the peritoneal cavity, not the mediastinum1.   In fact, clinical evidence linking mediastinitis to extravasated barium is lacking, and even in experimental studies, injection of barium into the mediastinum of cats have failed to cause clinically significant mediastinitis2.

When ordering a contrast swallow study, no medium should be considered totally safe or effective in detecting esophageal perforations or leaks and WCAs are no different. Potential disadvantages of WCAs include: 1. Inferior sensitivity (as low as 50%)—due to decreased radio-opacity—when compared to barium3; 2. Risk of pulmonary edema—occasionally lethal— when aspirated into the lung due to high osmolality (analogous to salt water drowning) and intense inflammatory reaction4,5; 3. Contraindication in the setting of tracheoesophageal fistula,6; 4. Risk of serious allergic reaction due to reabsorption of iodinated compounds1; and 5. Added exposure to radiation and cost of testing when the swallow study is repeated with barium.  For these reasons, the standard practice of an initial WCA followed by a barium swallow`study if the former is negative, has been questioned, with some centers foregoing the WCA study altogether in favor of barium swallow in certain patients 1,6.

In short, when evaluating for esophageal perforation, WCAs should not categorically be considered a “better” or “safer” alternative to barium; in certain situations, barium may be the preferred agent. When in doubt, input from a thoracic surgeon is recommended.  

 

References

  1. Gollub MJ, Bains MS. Barium sulfate: a new (old) contrast agent for diagnosis of postoperative esophageal leaks. Radiology 1997;202:360-62. https://www.ncbi.nlm.nih.gov/pubmed/9015057
  2. James AE, Montali RJ, Chaffee V, et al. Barium or gastrografin: which contrast media for diagnosis of esophageal tears? Gastroenterology 1975;68:1103-1113. https://www.ncbi.nlm.nih.gov/pubmed/1126592
  3. Berry BE, Ochsner JL. Perforation of the esophagus: a 30 year review. J Thorac Cardiovasc Surg 1973;65:1-7. http://www.jpedsurg.org/article/0022-3468(73)90248-0/abstract
  4. Trulzsch DV, PenmetsaA, Karim A, et al. Gastrografin-induced aspiration pneumonia: A lethal complication of computed tomography. South Med J 1992;85:1255-56. https://www.ncbi.nlm.nih.gov/pubmed/1470976
  5. Tuladhar R, Patole S, Whitehall J. Gastrografin aspiration in a neonate with tracheoesophageal fistula. J Paediatr Child Health 2000; 36:94-6. https://www.ncbi.nlm.nih.gov/pubmed/10723703
  6. FDA https://www.drugs.com/pro/gastrografin.html.
  7. Roh S, Iannettoni MD, Keech JC, et al. Role of barium swallow in diagnosing clinically significant anastomotic leak following esophagectomy. Korean J Thorac Cardiovasc Surg 2016;49:99-109. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4825910/pdf/kjtcv-49-099.pdf

 

When evaluating for an esophageal perforation, is a water-soluble contrast agent such as Gastrografin a better and safer alternative to barium swallow study?

My previously healthy 25 year old patient is admitted because of an anaphylactic reaction 4 hours after having a hamburger. Could it really have been the hamburger?

Absolutely! It could be related to alpha-gal (galactose-alpha-1, 3-galactose) allergy (AGA), a condition found in thousands of Americans1.  AGA (also known as red meat or mammalian allergy) is a novel form of IgE-mediated anaphylaxis that typically occurs 3-6 hrs (not immediately) after ingestion of mammalian meat (beef, pork, lamb, bison, goat, vension); turkey, chicken, and fish do not contain alpha-gal1,2 . Another unique feature of AGA is that it seems to develop in adult life3.

What’s even more fascinating about AGA is its presumed causal relationship with prior bites of Amblyomma americanum (the lone star tick)4,5, found in many southern, midwestern and eastern states in the US (Figure).    The proposed mechanism of sensitization is that tick saliva contains alpha-gal (possibly from feeding on deer or other mammals), which causes production of IgE to this oligosaccharide5.  When mammalian meat (in our patient, a hamburger) is ingested by the sensitized individual, an anaphylactic  reaction may ensue.  The delay in reaction is thought to be due to the time it takes for alpha-gal to be absorbed from the gut4

The story doesn’t end here! Some medications contain alpha-gal due to inert ingredients such as gelatin or magnesium stearate of bovine sources. At least one report of anaphylaxis in a patient with AGA has been blamed on medications with bovine-derived magnesium stearate6.  Measles-mumps-rubella and zoster vaccines may also contain alpha-gal, with zoster vaccine implicated in a case of anaphylaxis. 7

 Currently,  the FDA does not require manufacturers to disseminate this information, so when  in doubt, individual drug manufacturers should be contacted. 

lgmap-lone_star_tick

tick

Figure: Lone start tick and its distribution in USA (Courtesy of CDC).

Updated Nov 11, 2019.

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References

  1. Van Nunen S. Galactose-alpha-1, 3-galactose, mammalian meat and anaphylaxis:a world-wide phenomenon? Curr Treat Options Allergy 2014;1:262-77. https://link.springer.com/article/10.1007%2Fs40521-014-0022-0
  2. Kar I, Gong M, Muglia C, et al. Alpha-gal (mammalian meat) allergy: implications for pharmacists. Pharmacy Times, May 27, 2015. https://www.pharmacytimes.com/publications/issue/2015/may2015/alpha-gal-mammalian-meat-allergy-implications-for-pharmacists
  3. Commins SP, Platts-Mills TAE. Anaphylaxis syndromes related to a new mammalian cross-reactive carbohydrate determinant. J Allergy Clin Immunol 2009;124:652-57. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774206/
  4. Commins SP, Platts-Mills TA. Delayed anaphylaxis to red meat in patients with IgE specific for galactose alpha-1, 3-galactose (alpha-gal). Curr Allergy Asthma Res 2013;13:72-77. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3545071/
  5. Steinke JW, Platts-Mills TAE, Commins SP. The alpha gal story: lessons learned from connecting the dots. J Allergy Clin Immunol 2015;135:589-97. This is a must read for anyone interested in the subject! https://www.ncbi.nlm.nih.gov/pubmed/25747720
  6. Muglia C, Kar I, Gong M, et al. Anaphylaxis to medications containing meat byproducts in an alpha-gal sensitized individual. J Allergy Clin Immunol Pract 2015; 3: 796-97.
  7. Stone CA, Hemler JA, Commins SP, et al. Anaphylaxis after zoster vaccine:implicating alpha-gal allergy as a possible mechanism. J All Clin Immunol 2016;139 (5). DOI:10.1016/j.jaci.2016.10.037
My previously healthy 25 year old patient is admitted because of an anaphylactic reaction 4 hours after having a hamburger. Could it really have been the hamburger?

My patient with abdominal pain needs a CT scan with IV iodinated contrast, but reports a “shellfish” allergy? Is she at high risk of allergic reaction to IV contrast?

Patients with shellfish allergy appear not to have a significantly higher rate of allergic reactions to iodinated contrast media compared to patients with history of atopy, such as asthma or other food allergies 1,2.  When true shellfish allergy occurs, it is caused by an immunological reaction to the protein, not iodine, content of the food ingested.  “Iodine allergy” cannot exist because iodine is found throughout our bodies and is essential to life. 

The typical IV contrast-related adverse reaction is caused by non-IgE-mediated mast cell and basophil degranulation due to the high osmolality of these agents. Because the resultant “anaphylactoid” reaction is not associated with prior immune system memory, its risk is not increased by previous exposure to IV contrast.  Premedication with corticosteroids and diphenhydramine may be effective in reducing the risk of such reactions, but is not routinely recommended in patients with isolated history of shellfish allergy2.

 

References

  1. Schabelman E, Witting M. The relationship of radioconstrast, iodine, and seafood allergies: a medical myth exposed. J Emerg Med 2010;39: 701-707.
  2. Westermann-Clark E, Pepper AN, Talreja N, Lockey RF. Debunking myths about “allergy” to radioconstrast media in an academic institution. Postgrad Med 2015;127:295-300.
My patient with abdominal pain needs a CT scan with IV iodinated contrast, but reports a “shellfish” allergy? Is she at high risk of allergic reaction to IV contrast?