In the past few months, I have seen a few patients referred to me with chronic cough treated with these medications with minimal or no improvement. OR... the cough initially improved with such medications, but than over time, stopped working.
All these patients reportedly had a full workup with everything being normal and as such, was diagnosed with LSN. These patients were being solely treated with neuropathic medications and nothing else.
On review of their old records, it became apparent to me that these unfortunate patients actually suffered from MULTIPLE causes of cough that was not being treated. A common condition missed or not treated in these patients was non-acid reflux which can only be diagnosed on 24 hour multichannel impedance testing. Another more common scenario was the presence of mild acid reflux and allergies based on minimal reactivity on allergy testing and reflux that was present, but within normal range on 24 hour testing. Medications for allergies and reflux were tried, but didn't help and so was stopped. (Of note, none of the patients (prior to cough) ever had symptoms of reflux or allergies.)
WRONG!!! Treatment for both should have continued and very aggressively. Why?
Patients need to keep in mind that it is not unusual that a patient may have SEVERAL factors of cough as well, ALL of which need to be treated in order to resolve a persistent cough. Because laryngeal sensory neuropathy results in a hypersensitized larynx, problems with reflux and allergies which ordinarily would not cause a cough (or any other symptoms) in normal patients, will now cause a persistent cough. (This situation is even applicable in patients who have NEVER had any symptoms of allergies and reflux in the past.) In other words, though allergy testing may reveal only mild allergies and 24 hour pH study may show reflux episodes within normal range, these "mild" problems now need to be treated aggressively along with the neuropathy. To reiterate... laryngeal sensory neuropathy is a hypersensitized larynx. In this hypersensitized state, even a little bit of reflux or allergies will trigger a cough which normally would not. Each and every one of these conditions need to be treated aggressively to cure a persistent chronic cough.
The lack of treatment for each and every known cause of cough (even if mild) is the most common reason why treatment of laryngeal sensory neuropathy fails with neuropathic medication.
Case Report:
To illustrate, here is one case I saw a few months back...
Middle-aged patient who has had a chronic cough for about 15 years. Had a full workup done and found to have mild allergies to only alternaria mold (class 1) and dust (class 2). He did not respond to allergy medications and so these meds were stopped. Reflux workup did show significant reflux and so underwent nissen fundoplication which did help the cough by about 30%. His doctor than diagnosed him with LSN and tried him on a variety of neuropathic medication with some, but incomplete improvement. I was than asked to help figure things out.
The first thing I did was to instruct the patient to continue with the neuropathic medication that seemed to work the best for him (elavil 50mg twice a day). I also started the patient on allergy shots as well as an antihistamine and steroid nasal spray. I repeated a 24 hour pH and impedance testing to see if there was STILL reflux going on in spite of the reflux surgery. Lo and behold, there WAS both acid and non-acid reflux occurring, but on the high end of normal (much better than before his surgery). Based on this result, I restarted him on reflux medications daily.
Within 3 months, his cough completely resolved. I slowly tapered the elavil off. Once we both were convinced that his LSN was cured, the daily reflux medication was stopped and used only as needed. Allergy shots could have been stopped as well, but patient elected to continue them, but he no longer needed the daily allergy medications.
SO... what happened?
This patient apparently had allergies, reflux, and laryngeal sensory neuropathy causing his cough. Given he was being treated for only LSN prior to seeing me, that was why he had incomplete improvement of his cough.
I aggressively treated for all 3 factors of his cough. The mild allergies and reflux were brought under tight control preventing them from constantly (even if mildly) irritating his hypersensitized voicebox. Once his voicebox was in an "clean" environment, it was able to heal and desensitize with elavil. Once the voicebox was returned to a normal state, the reflux and allergy was now able to be treated like any other normal person.
The key thing to remember is that patients with LSN belong to a totally different sub-population of patients with a cough. One can NOT treat them as if they are part of the normal population. "Normal ranges" of reflux and allergies do not apply which actually makes sense if one realizes the voicebox in patients with LSN is hypersensitized.
What if EVERYTHING truly did come back normal?
There are 2 things I've done in this situation where there's absolutely no evidence for any abnormalities on any testing, mild or otherwise.
Botox injections to the thyroarytenoid muscle of the voicebox (similarly for spasmodic dysphonia treatment).
OR
Starting combo therapy using two different neuropathic medications, each of which seemed to help singly.
To read more about chronic cough due to LSN, click here.
Of note, SELSAP is a promising test to evaluate for laryngeal sensory neuropathy.
References
- Management of Recurrent Laryngeal Sensory Neuropathic Symptoms. Norris BK, Schweinfurth JM. Ann Otol Rhinol Laryngol. 2010; 119:188-191. Link
- Chronic cough as a sign of laryngeal sensory neuropathy: diagnosis and treatment. Lee B, Woo P. Ann Otol Rhinol Laryngol. 2005 Apr;114(4):253-7. Link
- Gabapentin in the Treatment of Intractable Idiopathic Chronic Cough. Mintz S, Lee JK. Am J Med. 2006; 119(5):e13-15. Link
- Laryngeal Neuropathy as a Cause of Chronic Intractable Cough. Mishriki YY. Am J Med. 2006; 119(5):e5. Link
- Sensory neuropathic cough: a common and treatable cause of chronic cough. Bastian RW, Vaidya AM, Delsupehe KG. Otolaryngol Head Neck Surg. 2006 Jul;135(1):17-21. Link
- Effectiveness of amitriptyline versus cough suppressants in the treatment of chronic cough resulting from postviral vagal neuropathy. 2006. Jeyakumar A, Brickman TM, Haben M. Laryngoscope 116(12):2108-2112. Link
- The irritable larynx syndrome. Morrison M, Rammage L, Emami AJ. Journal of Voice. 1999;13:447-55. Link
- Vagal neuropathy after upper respiratory infection: a viral etiology? Amin MR, Kaufman JA. American Journal of Otolaryngology, 2001;22(4):251-256. Link
- Cough and paradoxical vocal fold motion. Altman KW, Simpson CB, Amin MR. Otolaryngology-Head & Neck Surgery. 2002;127(6):501-11. Link
- Botulinum Toxin A: A novel adjunct treatment for debilitating habit cough in children. Sipp JA, Haver KE, Masek BJ, Hartnick CJ. ENT Journal 2007;86(9):570-572. Link
- Use of botulinum toxin type A for chronic cough: a neuropathic model. Archives of Otolaryngology-Head & Neck Surgery. 2010;136(5):447-452. Link
- A new treatment option for laryngeal sensory neuropathy. Halum SL, Sycamore DL, McRae BR. Laryngoscope. 2009. Link
- Postviral vagal neuropathy. Rees CJ, Henderson AH, Belafsky PC. Annals Otol Laryngol Rhinol. 118(4):247-52, 2009. Link
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