A 60 y.o. male with a hx of severe asthma, and diabetes comes to the ED with a rash.

What is in your differential?

Hint: a second patient has a similar problem except the second patient is paranoid. He has an anion gap of -21.

The patient pictured had been taking Atrovent (ipratropium bromide) for his asthma.   He developed angiomas associated with bromide use.   The second patient,  with the negative anion gap,  also had bromide toxicity but with a little more complicated problem.

 The second patient was an extreme vegan and  very careful about his diet, using only filtered water.  He  decided salt was bad for him and  consulted  ChatGPT asking what could be substituted for chloride.  The response was “bromide”  so he began to ingest sodium bromide instead of NaCl.  He developed  paranoia and psychosis requiring hospitalization.  This is postulated to be from the GABA-ergic manifestiations of bromine. He had a negative anion gap  and metabolic alkalosis because there is interference of chloride ion determination in the presence of bromide causing both ions to be counted leading to a factious elevation of chloride.

THE KEY TO THE DIAGNOSIS IS A CAREFUL HISTORY OF MEDICATIONS AND AWARENESS OF THE SIGNIFICANCE OF A NEGATIVE ANION GAP.

Potassium bromide was first discovered in 1826, and believed to have  anti- inflammatory and sedative effects. It was widely used to treat epilepsy.  The use of bromides to treat epilepsy only declined in 1912 when phenobarbital was introduced. Bromides remained in use as a sedatives in Bromo-Seltzer and Nervine.   In 1965  up to 10% of patients admitted to psychiatric hospitals had measurable bromine concentrations.  Because of its negative psychiatric effects it was banned by the FDA in 1975 from OTC products and in 1989 from sleep aids. They are still used, however,  in Europe and other parts of the world.  Bromism  is still seen in the US in  those who abuse  dextromethorphan hydrobromide.

mestinon was given to soldiers in the first gulf war

A controversy exists whether Gulf War syndrome which included memory defects and neurologic problems was partly due to bromism.  Gulf War soldiers were given Mestinon( pyridostigmine bromide) as a  protective measure against organophosphate poisoning by Soman gas. It  reversibly binds to the acetylcholinesterase enzyme (AChE) preventing the more toxic organophosphate from binding.  Mestinon has caused documented bromism in myasthenia gravis patients.

Our first patient was taken off ipratropium and his bromide level dropped .  The rash improved.

The second patient had a negative anion gap  and spurious chloride result was hydrated with normal saline.  His mental status cleared.

Lippman S, Klein E, Goodman P et al.  JAMA 2009;301:39-51.

Vasuyattakul S, Lertpattanasuwan N, Vareesangthip S et al.  A negative anion gap as a clue to diagnose bromide intoxication. Case Reports Nephron 1995;69(3):311-3.

Lugassy D, Nelson L. Case files of the medical toxicology fellowship at the New York City Poison control: bromism: forgotten but not gone. Case Reports J Med Toxicol. 2009 Sep;5(3):151-7.

Samlaka C, Rackhan A. Bromangiomas-ipratropium bromide-associated angiomas.  JAAD Case Rep. 2019 Aug 29;5(9):776-778.

Jih D, Khanna V, Somach S. Bromoderma after excessive ingestion of Ruby Red Squir.  N Engl J Med 2003;348(10):1932-1934.

Gutschmidt K, Haefliger G, Zilter T. Outbreak or neurological illness of unknown etiology in Cacuaco municipality angola 2008.u  WHO.