I recently was asked to serve as a medical expert in a
class-action suit against several major providers of bathroom and kitchen
The allegations were so outlandish that I giggled, until
I was told that a good friend and admired clinical investigator was a major
expert assisting the plaintiffs.
Thus, with an open mind, I perused literature that had
previously escaped my notice — although I noted blushingly that one
seminal paper was published in The Journal of Laboratory and Clinical
Medicine while I was its editor-in-chief.
The allegation: Excessive use of denture adhesives,
primarily Poligrip and Fixodent, can cause anemia, neutropenia and a
myelodysplastic-appearing marrow with vacuolated myelo- and erythroblasts, as
well as ringed sideroblasts. Moreover, these patients often demonstrate
significant myelopathies and neuropathies, even affecting optic nerves. In
fact, the myelopathy may mimic vitamin B12 deficiency with dorsal and lateral
column derangement, yet B12 and methylmalonate levels are normal.
Recognizing that severe copper deficiency —
sometimes manifested in patients with intestinal malabsorption after bariatric
bypass surgery, those on prolonged IV nutritional feedings (without copper
supplementation) or in patients with Wilson’s disease who are
over-chelated — Rob McKenna and his Dallas colleagues in 2005 described
three patients with typical marrow findings of copper deficiency.
They indeed were found to be profoundly deficient.
Additionally, they were significantly neurologically damaged. Hematologic
abnormalities, but not nerve damage, disappeared with copper treatment.
Zincemia and copper deficiency
The cause of the deficiency in these otherwise
nutritionally uncompromised patients was hypothesized to be due to zinc
toxicity. That is, one of the three was treated with large amounts of zinc for
acrodermatitis enteropathica and a second was found to use huge amounts of
zinc-containing dental adhesives for his ill-fitting dentures.
Harry S. Jacob
In fact, the denture wearer admitted to eating pellets
of Poligrip (containing polymethylvinylether maleic acid calcium-zinc salt) for
4 to 5 years, besides using a 65-g tube of the adhesive daily. Within 3 weeks
of discontinuing his adhesive obsession, extreme levels of serum zinc
normalized, as did deficient copper levels. Anemia and neutropenia remitted,
although sensory neuropathy and leg weakness persisted.
Prasad and Brewer first noted the relationship between
excess zincemia and copper deficiency more than 30 years ago. At that time,
patients with sickle cell anemia were being treated with supplemental zinc, and
several were noted to become copper-deficient while developing microcytosis and
neutropenia. Copper restitution corrected these abnormalities.
Brewer’s group much later provided a rational
hypothesis for copper malabsorption in zinc-supplemented patients. In the
aforementioned 1992 Journal of Laboratory and Clinical Medicine article,
they sought the mechanism by which zinc treatment beneficially lowers serum
copper levels in Wilson’s disease. They demonstrated that ingestion of
large quantities of zinc salts promotes synthesis of metallothioneins in
enterocytes. These, in turn, bind copper, preventing its absorption and, thus,
its ultimate fecal excretion during enterocyte turnover. I wonder whether these
metal-binding proteins might also be iron-reactive and, thereby, be responsible
somehow for siderocyte formation in myelodysplastic marrows.
Several case reports
That large amounts of zinc present in some dental
adhesives might cause copper deficiency and its known neuropathic and
hematologic disorders was first suggested by Spinazzi and colleagues in 2007.
Their gastrectomized patient developed myelodysplasia and a
myelo-opticoneuropathy while utilizing large amounts of dental adhesives for
his ill-fitting dentures.
Within the past 2 years or so, several single-case
reports of this astounding association have appeared, and neurologists and
hematologists from Vanderbilt University and the University of Michigan
published a compendium of 11 such patients. I’m told that several more
affected patients have now been identified by tort lawyers (surprised?).
Lest one wonder whether the syndrome is caused by copper
deficiency or from direct zinc toxicity, the lack of hematologic or neurologic
problems in rare patients with hereditary hyperzincemia indicts mainly copper
deficiency — but also the requirement for ingested excess zinc.
Therefore, dermatologists might be cautioned to use
injected — rather than oral — zinc in their patients with
acrodermatitis, whereas hematologists need to add two words to their lexicon
when evaluating patients with siderocytic myelodysplasia: to wit, “Open
wide.” Perhaps universal decent dental care in the future will extinguish
this uncommon, albeit evocative, syndrome.
- Brewer GJ. Zinc metabolism: Current aspects in health and
disease. New York: Alan R. Liss Inc., 1977.
- Hedera P. Neurotoxicology. 2009;30:996-999.
- Prasad AS. JAMA. 1978;240:2166-2168.
- Spinazzi M. J Neurol. 2007;254:1012-1027.
- Willis MS. Am J Clin Pathol. 2005;123:125-131.
- Yuzbasiyan-Gurkan V. J Lab Clin Med. 1992;120:380-386.
For more information:
- Harry S. Jacob, MD, FRCPath(Hon), is HemOnc Today’s
Chief Medical Editor. Disclosure: Dr. Jacob reports no relevant