Strategies for managing granulation tissue.

During this session, formal presentations were made b3 Dr. Coates, Prof. Hawke, Dr. Manning, Dr. Vesterhauge, Dr. Haynes, and Prof. Deitmer. These presentations were followed by a general discussion.

Harvey Coates, MS, FRCS, FRACS

Granulation polyps that form around ventilation tubes are relatively common in Western Australia (figure 1, A) They are difficult to prevent, because swimming is such a popular activity there and ear protection is not always, effective. In my practice, I see many granulation polyps in children who have Paparella tubes, which have a wide bore. Paparella tubes are usually used for children who are undergoing a second placement, and they are left in the ear longer. Hence the higher incidence of granulation polyps.

[FIGURE 1A OMITTED]

When I see a granulation polyp next to a ventilation tube, I treat it with ciprofloxacin/hydrocortisone otic solution. The use of hydrocortisone is important for reducing the polyp. I start with 3 drops three times a day for 7 days. After l week, I re-examine the patient and start a second course. Some of my colleagues prescribe a 3-week regimen before they examine their patients, but I prefer to monitor the response to treatment earlier. This regimen has been effective in most patients. I use the same regimen for a granulation polyp that extrudes from a tube (figure 1, B).

[FIGURE 1B OMITTED]

The number of patients who require surgery for grommet and polyp removal is very low--less than 3%. My most recent case that required surgery involved an Aboriginal child who had had a constant discharge for months and a middle ear granulation polyp that was ballvalving because of the pressure of the discharge. This child had not responded well to topical therapy with another agent. I removed the granulation polyp and took biopsies to look for biofilm. I switched the patient to ciprofloxacin/hydrocortisone, and the ear dried up in 1 week.

I don't use silver nitrate sticks to treat granulation tissue, because most cases resolve with ciprofloxacin/ hydrocortisone and because there is a high degree of patient resistance to these sticks.

Michael Hawke, MD

Histologic examination of tube granuloma tissue will reveal its cause quickly. Inside the granulation tissue is series of keratin squames that are surrounded by foreign-body giant cells. By the time the basal cell of the epithelium reaches the surface of the skin, it has been so transformed that the body recognizes it as foreign tissue and it incites a foreign-body reaction. We do not know how the keratin reached the ear. It might have been picked up during the myringotomy and tube insertion, or it might have developed as a reaction to the tube.

Clinically, tube granulomas are usually asymptomatic. Patients sometimes experience spontaneous bleeding from the ear canal. The bright red blood, of course, is frightening to the child's parents. But if the otolaryngologist knows that the child has a history of tube insertion, we can reassure the parents before they come to the office. Regardless of the clinical manifestation, almost all tube granulomas arise from the tympanic membrane. Some might appear to originate in the lumen of the tube, but they are actually attached to the eardrum. Some granulomas appear as a flowering around the collar of the tube and some appear as a dome that completely covers the tube.

Treatment should be administered as Dr. Coates recommends: with a safe topical antibiotic/steroid eardrop and occasionally mechanical removal of the granulation tissue. In the past, our institution treated tube granulomas with a gentamicin/steroid eardrop. But we now know that gentamicin can damage the labyrinthine portion of the inner ear, so we have been very reluctant to use it in children. This is unfortunate, because the gentamicin/ steroid solution was a simple and effective treatment. Therefore, there is a great need in Canada for an antibiotic/steroid combination that is not ototoxic. We need an agent that will not cause vestibular or cochlear damage if it passes through the lumen of the tube. 1 agree with Dr. Coates that the steroid component of the combination is important.

In some cases, granulation tissue must be removed by suction, which is a simple procedure. Removal of the tube is rarely necessary, unless it appears that the tube has migrated to the outside of the drum. In that case, it is probably prudent to remove the granulation tissue and the tube in one procedure.

Scott C. Manning, MD

At the Seattle Children' s Hospital, once or twice a year we find that what appears to be granulation tissue is actually a rhabdomyosarcoma of the temporal bone. These patients exhibit two characteristics that are not common in patients with granulation tissue: (1) they do not have a tympanostomy tube and (2) they often have an ipsilateral, rock-hard, metastatic cervical node. Oddly enough, on cologists don't always look at the neck in children. Another indication of possible cancer of the temporal lobe in a child with apparent granulation tissue is a parent's observation that the child is not feeling well, not eating complaining of pain, being fussy, etc. In the Pacific Northwest, which has a sizable number of migrant fruit workers, another possibility in a patient with no tube is tuberculosis.

When granulation tissue is actually present, it is critical to emphasize to the child's parents the importance of keeping the ear dry. Some parents have their children insert an earplug, but children do not always keep them clean. For bathing, I prefer that the parent insert a cotton ball that's been dipped in petroleum jelly. This can be somewhat messy, but it's simple, comfortable, inexpensive, and disposable.

Another area of concern is the formation of granulation tissue on tracheotomy tubes. At any given time in our institution, our nurse respiratory therapists are following 60 to 100 children who have tracheotomy tubes. The nurses are very careful to change tubes more often than usual if granulation tissue appears to be a problem. We clean the stoma with simple saline on a cotton-tipped applicator. If the skin of the patient's neck is excoriated culture will almost always identify Candida spp. We treat this with a steroid and nystatin.

Soren Vesterhauge, MD, DMSc

Very often, we have no hint of what might be hidden behind granulation tissue. A polyp could conceal chronic otitis media with a central perforation, a cholesteatoma granular or necrotizing external otitis, or a planocellular carcinoma of the ear canal. Therefore, the first step is to look for clues by obtaining a good history.

The next steps are to obtain a sample of the granulation polyp for culture and to clean the ear canal. I use a 3% silver nitrate solution to reduce the size of the granulation tissue. At that point, I decide which definitive therapy to administer. Frequently, I obtain a biopsy sample to rule out cancer.

If the tympanic membrane is still not visible, I mechanically remove the polyp. I use the 3% silver nitrate solution to control bleeding and topical ciprofloxacin to control infection.

For patients with tube granulnmas, I have not used a steroid in combination with the antibiotic. However, the discussion here has persuaded me to begin doing so. Perhaps it is thelack of an adjunctive steroid that accounts for the relatively high rate of tube removal at our clinic.

I recently operated on a 15-year-old boy from Greenland, who was sent to us in Denmark for treatment of a virtually lifelong history of discharging ears. He had been referred to me for "unspecified ear surgery." The referring physician noted that the patient had undergone a type II tympanoplasty, an incus autograft, and a mastoidectomy on the left ear 3 years earlier. Unfortunately, the language barrier prevented me from obtaining more of a history. Examination revealed that both discharging ears were occluded by granulation polyps.

I treated the right ear conservatively with cleaning and eardrops while waiting for further word from the referring physician regarding the need for surgery on that ear. In the left ear, I removed the granulation tissue with instruments until I could reach the remnants of his tympanic membrane. I administered adrenalin by a wick to control the bleeding. The problem with granulation tissue is that any manipulation will cause bleeding. Once the operative field was stabilized, I performed a posterior tympanostomy and removed the remainder of the granulation tissue from the middle ear and located the stapes. I cleaned the stapes and discovered more granulation tissue covering remnants of the posterior crus of the superstructure. The footplate was normal. I didn't want to put anything into the middle ear at this point, not even adrenalin, because if a perilymphatic fistula is present, the introduction of adrenalin into the middle ear might damage the inner ear.

I next performed a revision mastoidectomy and found fibrous granulation tissue in the mastoid process (figure 2). It appeared that there were two stages of granulation present; the mastoid cavity contained old fibrous granulation tissue, and the ear canal contained very active granulation tissue, as well as infection. I then performed a type III reconstruction of the ossicular chain and a myringoplasty with a sliced tragal perichondrium-cartilage graft.

[FIGURE 2 OMITTED]

David S. Haynes, MD

Most of the patients we see at Vanderbilt University have already been on multiple drops by the time they come to us. Our first step is to discoutinue those medications. In many cases, stopping the drug will lead to improvement, particularly when the drops contain neomycin. We have seen patients who were taking neomycin-containing drops develop reactions that range from mild erythema to fulminant reactions.

Following surgery, some patients develop large polyps. In such cases, we apply silver nitrate to cauterize the tissue, and then we remove the polyp with microscissors. Because the tissue is vascular and bleeds easily, we may need to cauterize the tissue again with silver nitrate or control bleeding with phenylephrine applied to a small cotton ball. Then we apply gentian violet as a drying agent. Gentian violet has been found to be ototoxic, as has acetic acid. Nevertheless, we use both because there really is not an equal alternative. The key to using gentian violet is to wait until its drying effect reduces the granulation tissue before using any other drops. This usually takes approximately 5 days. After 5 days, we will have the patient begin an antibiotic-containing drop.

We use acetic acid for two purposes: (1) to flush the car mechanically and remove debris and (2) to take advantage of its antibacterial effect. We also use steroid-containing drops, which play an important role in ears with granulation tissue. We prefer not to use silver nitrate too often because it may impair epithelialization, and we no longer use gentamicin, neomycin, or any aminoglycoside-containing drops because of their ototoxic effects, especially now that better alternatives are available.

Thomas Deitmer, MD, PhD

In Germany, we often see granulation tissue in patients with long-standing external otitis, possibly as a result of a bacterial infection. We see it following middle ear surgery as a consequence of poor healing. We see it in the large cavities that we create when treating a cholesteatoma, and, of course, we see it as a signal polyp for cholesteatoma. Finally, we see it as perhaps a foreign-body reaction in patients with grommets. However, since we have switched from silicone grommets to titanium tubes, we have noticed a decline in the incidence of granulation tissue.

One particular problem that I've seen in my practice is that ears with longstanding otitis externa develop granulation tissue on the surface of the entire tympanic membrane. The presence of granulation tissue in the anterior angle might increase the risk of blunting and subsequent severe conductive hearing loss.

Our initial therapy is to clean the meatus or the cavity by dry mopping. We later instill antibiotic and steroid drops. If the tympanic membrane is closed, we administer some ototoxic antibiotics with steroids that are available in Germany. I prefer to use a wick to instill the drops, and I meticulously apply them on the granulation tissue. I do not use cautery in the middle ear.

Discussion

Prof. Hawke: There is a host of substances that we are beginning to realize are ototoxic. Gentamicin and aminoglycosides are not the only offending agents. Others include preparation solutions, which we used to splash over the ear quite liberally, and some ointments. I would be very careful about placing anything in the middle ear that has not been proved to be safe. The risk of ototoxicity is too great.

Dr. Haynes: In the past, all of us have used an agent--be it gentamicin, neomycin, or an aminoglycoside--that was known to be ototoxie simply because we had no other options. But now that the quinolone drops have been introduced, we finally have a safe alternative.

The use of powders is also common, but we do not always know whether the individual components of these powders have ototoxic potential.

Dr. Roland: I use a powder that I am almost certain not ototoxie. It is made up of ciprofloxacin, clotrimazole, and dexamethasone in a boric acid vehicle. The antifungals have been studied, and none has been found to be ototoxic. The most effective antifungal for treating ear pathogens is clotrimazole. Amphotericin is adequate, but clotrimazole is better for eradicating the Aspergillus that we see in ear canals. Boric acid and beclomethasone have also been found not to be ototoxic.

Prof. Hawke: Regardless of whether you are treating otitis externa or otitis media with a perforation, it is so important to use a topical medication that is not ototoxic, for legal reasons as well as medical reasons. In Canada, we have seen malpractice cases in which a patient with acute otitis externa and an intact tympanic membrane developed a perforation as a result of vestibulotoxicity. If this situation is difficult for otolaryngologists, imagine how difficult it must be for family practitioners and pediatricians. They, too, would benefit from a product that is safe to use in a perforated ear.

Dr. Poole: I'm surprised by how rarely bacterial infection is mentioned in discussions of tube granulomata. I doubt that granulomata occur without bacterial infection Others apparently are not as certain. I suspect we can cure most granulomata with an antibacterial agent alone. It might take longer without a steroid, but it will eventually be successful. The bacteriology of the granulomata that I have cultured is somewhat different from the bacteriology we see in other types of draining ears. We find that Staphylococcus aureus is present in a disproportionate number of granulomatous ears.

Dr. Stroman: We studied the association of various pathogens in granulomas and found that S aureus and Pseudomonas aeruginosa were the most common. But we found others, as well.

Dr. Poole: Yes, in most cases, cultures will grow both S aureus and P aeruginosa. If only one grows, it's most likely to be S aureus. S aureus appears to be more "granulomatogenic" than other bacteria, which is important to keep in mind when selecting an antibiotic preparation.

Dr. Schapowal: Quite often the cause is not just S aureus but "super antigens" of S aureus endotoxins, which stimulate specific T cells. The same is true for Aspergillus fumigatus and Alternaria alternata. Of course, we also see granulomas in patients with allergies to food or metals. I saw one extreme case of food allergy in woman who frequently ate raw potatoes. Uncooked potatoes can be a potent allergen, whereas cooked potatoes are not. The woman's allergic reaction manifested as an inflammation of the left ear and the development of granulation in the external ear canal.

Dr. Dohar: The overwhelming majority of cases are infectious, but not all of them are. We shouldn't consider granulation tissue to be strictly an infectious disease and treat it only as such. In fact, at the University of Pittsburgh laboratory, we have accumulated some experimental evidence that infection might be a consequence of granulation tissue rather than its cause. The presence of granulation tissue can change the entire ecology and physiology of the ear canal. If conditions become favorable, secondary infections can occur. The cause-and-effect issue is tricky.

Prof. Hawke: How should we treat chronic granular myringitis that has completely covered the surface of the tympanic membrane?

Dr. Roland: I use the ciprofloxacin, clotrimazole, and dexamethasone powder that I mentioned earlier. One nice feature of this powder is that it sticks to the wet surfaces and its dwell time is very long. Therefore, these patients usually need an application only once or twice a week for the first 2 or 3 weeks. Thereafter, I treat them once a month. But my experience is that 85% of patients experience a recurrence within several months. I have found no way to eradicate this granulation tissue permanently--not even by resecting the involved segments. This is a condition that must just be treated with maintenance therapy. We can control it, but patients require years of care.

Dr. Manning: We still use chloramphenicol, amphotericin B, and sulfacetamide in boric acid. We don't use this in an open tympanic membrane, but otherwise it works.

Dr. Rutka: Granulation tissue can represent just one part of a spectrum of disease. For example, granular myringitis can progress to medial meatal fibrosis or what is often called a "false fondus." Is there a good treatment for this condition?

Prof. Hawke: The case that Dr. Vesterhauge presented reminded me that I have surgically opened several stenotic ear canals only to see them quickly restenose. Probably the only way to prevent this from happening is to perform a mastoidectomy.

Dr. Haynes: Some mature polyps contain large blood vessels, and we can't expect a topical antibiotic to treat them. Some of the polyps require mechanical removal in some fashion.