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Month: December 2019

Ligelizumab

Ligelizumab

Ligelizumab is a “next generation” humanized monoclonal antibody to IgE.  It was designed to be a “better mousetrap” to treat people with severe chronic urticaria.  Chronic urticaria (recurrent hives) is fairly common, occurring in 1 case per 200 people.  In most cases it can be controlled with oral medications primarily in the form of antihistamines.

 

Many people gain control with a single H1 receptor antihistamine such as Allegra or Zyrtec.  Some patients require the addition of an H2 receptor antihistamine such as Pepcid.

 

However, the patients unable to gain control with these simple/safe medications have had to resort to oral steroids, not a good long-term strategy.  Then a few years ago, the earliest developed monoclonal antibody for IgE, Omalizumab, which has been used to treat asthma for many years, was found to be very helpful for chronic severe urticaria.  It truly has been a Godsend, and up until now it was the best resource for these severe patients.

 

Now comes Ligelizumab which seems to be even more effective.  In fact, in head to head comparison studies of Ligelizumab and Omalizumab 51% of the Ligelizumab study group had complete resolution of their hives compared to 26% of the Omalizumab group.  There was a greater frequency of injection site reactions with Ligelizumab then with Omalizumab.  Also, Ligelizumab is so new, its long-term safety is yet to be determined whereas Omalizumab having been available for many years is known to have a fairly safe track record.

Hatfield’s and McCoy’s

Hatfield’s and McCoy’s

The “stolen pig” that set-in motion the famous Hatfield and McCoy feud may have been (excuse the pun) a scapegoat for the underlying medical condition that probably caused all the anger.

 

Because of rural family dynamics and inbreeding among relatives it seems many of these people, especially the McCoy’s may have suffered from a genetic disease, von Hippel-Lindau, that causes tumors on the adrenal glands called pheochromocytoma.

 

The adrenal glands are a normal part of our adaption to stress called the fight or flight response.  However, when a tumor is involved the amount of adrenalin that is released is abnormal in two ways.  Instead of normal “adrenal release” that is just occasional and in response to a threat, these tumors continually release adrenalin.  But then when there is a threat, they release way more than the normal gland does.

 

The excess adrenalin can not only cause chronic irritability but in surges can cause “reactive – combative behavior”.  Sometimes the surges cause a sensation of panic and occasionally people felt to have psychologically caused panic attacks actually have pheochromocytoma.  The low-grade irritability can sometimes cause children to appear to have ADDHD (attention deficit disorder/hyperactivity) SSRI’s used to treat some patients with panic attacks can cause a person with pheochromocytoma to release more adrenalin.

 

Some people who have pheochromocytoma consult allergists thinking that their sudden symptoms of flushing, heart racing, sweating and panic are indications of an allergy attack.  Albeit this condition is extremely rare, but if the Hat(fields) fits you might discuss this rare condition with your doctor.

Dear Dr. K – I heard that there is a new drug to treat flu. Is that true? And, does it work?

Dear Dr. K – I heard that there is a new drug to treat flu. Is that true? And, does it work?

Yes, and yes.  The new drug is Xofluza and it is the first flu drug with a new mechanism of action to come along in 20 years.  It is (hold on to your hat) a polymerase acidic endonuclease inhibitor, (PAEI).  PAEI is essential for the viral RNA messenger that allows the flu virus to replicate itself.  By shutting down viral replication, it shuts down the infection.  It is effective for both influenza A and B.

 

The only other available drugs for influenza all work by the same, but different than Xofluza, mechanism which is to inhibit neuraminidase.  These drugs are:  Tamiflu, Relenza and Rapivab.  Neuraminidase is an enzyme of the virus that allows it to escape from one human cell so it can invade the next cell.  By inhibiting neuraminidase these drugs also shut down the infection.  Tamiflu is oral, Relenza is a nasal spray and Rapivab is IV (used in hospitalized, severely ill patients).

 

The new drug works as well, but not better than the other three.  However, one dose is sufficient.  It works best if started within 48 hours of becoming ill.  Being new it is naturally more expensive.  Unfortunately, influenza seems to be able to develop resistance to the new drug fairly quickly.  Ten percent of patients developed resistance after a single dose.

 

Resistance is also a problem with the neuraminidase inhibitors, so the FDA is studying the possibility of combining both families of drugs for their synergism (killing virus by different mechanisms) and as a means to prevent resistance.

Post-Lyme Disease

Post-Lyme Disease

Some compelling research on Lyme disease was recently published in the Proceedings of the National Academy of Science.  The focus for the research was to try and elucidate the reason that in some patients with Lyme disease they continue to have symptoms despite prompt and appropriate treatment with antibiotics.  It turns out to be caused by post-infection inflammation caused by ongoing immune response against part of the bacteria.

 

Lyme disease is caused by the tick born bacteria Borrelia burgdorferi.  This bacterium contains a peptidoglycan (PG) molecule in its cell wall that is released but not degraded when the bacteria die.  Since the bacteria invades the skin, brain, joints, and heart, the PG molecules remain in these areas.  The immune system “sees” these foreign proteins and tries to eliminate them, but in so doing creates inflammation.  The immune inflammation is caused by cytokines especially one called tumor necrosis factor (TNF).  The presence of TNF especially in the joints can cause a chronic arthritis, which is the most common post–Lyme complication.  But, other less common complications include chronic skin rash, cardiac problems and chronic fatigue.  The latter is felt to be due to chronic meningeal inflammation.

 

Research is ongoing on two fronts.  One focus is to try and find a way to degrade the residual PG “debris” and remove it from the body.  The other is to try and find a way to stop the post–infection inflammation by schooling the immune system to stop targeting the PG protein.

Q – Tips: appendix

Q – Tips: appendix

  • Researchers at Duke University have discovered a new and important function for the appendix. It turns out that the appendix contains special “nurturing” immune cells that protect the healthy gut bacteria.  Thus, when people suffer severe diarrheal illness the “sheltered bacteria” can be a healthy source to repopulate the colon.
Q – Tips: fire ant venom

Q – Tips: fire ant venom

  • Not to be outdone by Duke, scientists at Emory have discovered two beneficial aspects of a protein in fire ant venom: solenopsin. This protein helps human skin maintain its resilient barrier function and may be useful in people experiencing thinning and easy bruisability of the skin.  Solenopsin also seems to have anti-cancer properties and may provide a mechanism to lessen skin cancers.
Q – Tips: PPI’s and Cough

Q – Tips: PPI’s and Cough

  • If you were prescribed a PPI for chronic reflux-induced-cough, but aren’t seeing any results, be patient. PPI’s will alleviate heartburn sensation within a few days, but they can take up to a month to do the same for a cough.  This is because your throat takes time to heal and repair itself from the acid injury.  So, don’t start looking for another cause of your cough until at least a month has elapsed.
Q – Tips: Reflux and laparoscopic surgery

Q – Tips: Reflux and laparoscopic surgery

  • Speaking of reflux, the New England Journal of Medicine just published a research project on people with “refractory” heart burn. The patients studied were people with severe reflux that weren’t adequately controlled using PPI’s.   One group was given a second medicine: Baclofen, a muscle relaxer, the other group had laparoscopic surgery called fundoplication.  The surgical group had a much better resolution of their symptoms.