Bulletin Board of Oral Pathology
Bulletin Board of Oral Pathology
Forum for Clinical and Surgical Oral Pathology
Case BBOPF 08-9
MESSAGE FROM THE MANAGER
The following is the summary of the 29 responses elicited by Dr. Baratz's case. In addition, Dr. Baratz is giving us "..the rest of the story."
In case you may wish to view this case again, The URL is:
http://www.sdm.buffalo.edu/bbop/forum/case200809.asp
DIAGNOSIS
THE REST OF THE STORY
The patient has a long history of rheumatoid arthritis, which has mainly affected her major joints (elbows, shoulders, and knees) and her fingers. She has not had rheumatoid nodules in the skin, and has not shown evidence of other connective tissue diseases, such as Wegener's granulomatosis. A skilled and diligent rheumatologist sees her regularly and has followed her for a long time. She is quite stable on very low dose prednisone (5mg) and periodic methotrexate at low dose. There were no changes in these medications which occurred at all, nor which coincided with the appearance of her nasal mucosal problems.
The current problem began after she was hospitalized for a total knee replacement and was put on prophylactic warfarin post-operatively, to avoid DVT. Shortly thereafter, while still in the hospital recovering from her surgery, she had epistaxis on the left, and upon inspection by ENT a small, 3-4 mm lesion was noted on her nasal septum. The case description details the progressive course of the loss of her septal nasal mucosa and columella.
We (me, her primary physician, the two ENT specialists she saw, her rheumatologist, and a senior infectious disease specialist) have discussed this case extensively, and reviewed it with two pathologists. Both biopsies, as noted, did not show vasculitis or granulomas. No infectious source was found, and the biopsy material did not reveal evidence of infection.
Nasal mucosal erosions and mucosal necrosis are linked to connective tissue diseases, including rheumatoid arthritis, but usually linked to vasculitis. We looked and looked, and did multiple tests for vasculitis, including ANCA, sed rates, and more, and there was not a scintilla of evidence for vasculitis. Because we could not find a source for her necrosis we empirically raised her prednisone to 20mg a day and then tapered it slowly. It made no difference in her nose. She noted, of course, that her joint aches improved while on the higher doses of prednisone. As related above, she had no evidence of Wegener's granulomatosis, rheumatoid nodules, or similar, all of which can undergo necrosis and lead to nasal (skin and other mucosal) erosions.
A review of the etiology of nasal erosions/mucosal necrosis yields many possibilities, many are very rare, if not dubious. Common causes are:
Drugs. Cocaine and, more recently, powdered Oxycontin (r) are known to cause nasal mucosal necrosis. She received neither. Newer agents such as Rituximab can also do it.
Trauma. Prongs of oxygen canulae, nasal intubation, nasal packings for epistaxis, foreign bodies (e.g. beads and watch batteries), also can cause nasal mucosal death. Continuous CPAP, BiPAP, and high flow oxygen (via drying) can also cause mucosal problems.
Infectious. TB and other granulomatous conditions such as sarcoidosis can also cause mucosal problems in the nose. Klebsiella, diptheroids, psdudomonas, and other gram negative bacteria are possible, but, as noted, no evidence of infection was found, including fungal infections.
Atrophic rhinitis. (also known as ozena) This is unlikely as it occurs in young individuals and often remits in later life. The cause is unknown. Her circumstances do not fit the description of ozena.
Vitamin Deficiency. All other mucosae, including conjunctivae, were normal and this too is unlikely. She shows no skin or other signs of vitamin deficiency and eats a balanced diet.
Vascular. The area affected (columella and distal nasal septum) received most of its blood supply from the nasal septal branches of sphenoid vessels in the maxillary artery territory, with anastamoses from the palatal vessels through the incisive canal. This is "distal" circulation and, one might speculate that it somehow was cut off for a time, producing what was seen. The palate, however, is entirely normal, and given the dual blood supply of the region, infarction is an unlikely etiology. The slow, sputtering course of the necrosis also argues against infarction. Further, the initial lesion was not at the distal nasal septum, nor at the columella. As noted above, no signs of vascultis were seen. Empiric treatment for vasculitis had no benefit.
Further clinical course and management. As noted above, increasing her steroid dose had no effect. Various anti-infective agents had no effect. I elected to try merely covering the area with plain Orabase (R). For the first week of use this seemed to help and the lesions began to dry up. Given the apparent arrest of progression, and what seemed to be early healing, I recommended that she continue this "therapy" and use the Orabase (r) liberally, reapplying it throughout the day. She missed her next follow-up (set for two weeks later) and, when I saw her next (another week later) she reported she was using the Orabase (R) only once a day. She is very head-strong and decided that was all she needed. When I examined her the lesions had not progressed, but had not healed either. I requested that she use the Orabase (R) as directed, keep the lesions well covered, and see me in a few more weeks. So far so good.
As for an etiology, we are still somewhat baffled. Since her initial lesion appeared with the onset of warfarin use, soon discontinued when she had epistaxis, and never restarted, we considered that to be the most likely culprit. Warfarin-induced mucosal and skin necrosis are known to occur. Most reports note that this response appears associated with various coagulopathies, notably Protein S/Protein C deficiency, and similar entities; malignancy related hypercoagulation, and heparin-induced thrombocytopenia. High initial loading doses of warfarin are linked to this problem, particularly in individuals with coagulopathies. Based on her medical history and current diagnoses she has none of these associated conditions. Coagulopaties are known to occur with connective tissue diseases, notably Lupus. Most texts include rheumatoid arthritis in discussions of connective tissue disease associated coagulopathy. As most of you appreciate, connective tissue diseases are commonly not "pure entities" and mixed features regularly occur. So far this construct is the only one that fits the facts.
Once the nasal septum is denuded, especially with loss of the columella, healing is problematical, as is grafting since there is not a consistent blood supply.
We have discussed this case with numerous colleagues, including several hematologists. Our current thinking is summarized above. We welcome your ideas and input.
Bob Baratz
Robert S. Baratz, MD, PhD, DDS
Department of Medicine
Boston University School of Medicine
Medical Director, South Shore Health Care
Departments of Medicine and Surgery
Quincy Medical Center
baratz@bu.edu
The views above are my own
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12/5/2008