A 64-year-old woman was diagnosed by her ophthalmologist with acute zonal occult outer retinopathy (AZOOR) and referred for rheumatologic consultation.
The patient presented with blurred vision, worsening night vision, sensitivity to light and decreasing visual fields. Her ophthalmologist documented an “abnormal full-field electroretinogram with significant cone dysfunction and mild rod dysfunction in both eyes.” A detailed history and physical examination revealed no extraocular symptoms or signs. Extensive evaluation, including acute phase reactants and autoantibody testing, revealed no other abnormalities. Her ophthalmologist established the diagnosis of AZOOR and prescribed prednisone 50 mg daily. No comments on steroid-sparing agents or a prednisone taper were found in the ophthalmologist’s notes. The reason for referral was documented as “immunosuppression management.”
Dilemma
Patients with autoimmune or inflammatory ocular disease are often referred for rheumatologic consultation by their treating ophthalmologist. Ophthalmologists are often unfamiliar with the immunosuppressive medications used to manage these patients, and rheumatologists are often unfamiliar with the primary ocular diseases requiring immunosuppressive treatment. Managing these patients is difficult when the condition is rare and the medical literature provides minimal guidance. As of 2011, fewer than 150 cases of AZOOR had been reported in the English medical literature.1 Although AZOOR is described as an autoimmune retinopathy, the pathogenesis and the specific role of the immune system in this condition are unclear.
A lack of familiarity with these disorders makes members of both subspecialties hesitant to take ownership of such diseases as AZOOR. This raises a number of issues, both ethical and practical. The most pressing: How do we, as rheumatologists, define our moral and professional obligations to help a patient when their condition is not clearly within the scope of our discipline? Is it ethically appropriate to send the patient back to the referring physician without rheumatologic follow-up or even decline to see the patient if their condition is not one we consider to be “ours”? How can we best meet the needs of our patients when therapeutic roles are in question?
Discussion
Beyond the question of how to treat this patient, there is the question of who is ultimately responsible for making treatment decisions. This is especially challenging when there is no known effective treatment (as with AZOOR), the stakes are high (vision is on the line) and the physicians involved may never have seen a similar case. If there were a proven therapy, the providers’ roles might be clearer: The ophthalmologist could recommend a well-accepted treatment and monitor the ocular response, while the rheumatologist could monitor the safety of the chosen treatment.
For a condition such as AZOOR in which there is no well-established standard of care, off-label use of medications is often initiated. It’s important to keep in mind that the greatest risk for harm arises when “an off-label use lacks a solid evidentiary basis.”2 With the substantial risks involved in using off-label medications, how do we appropriately define the roles of the rheumatologist and ophthalmologist in making these difficult decisions?
According to the American College of Physicians (ACP) Ethics Manual, 6th edition:
In almost all circumstances, patients should be encouraged to initially seek care from their principal physician. Physicians should in turn obtain competent consultation whenever they and their patients feel the need for assistance with care. The purpose, nature and expectation of the consult should be clear to all.
The major dilemma in this case is that the principal physician has not been established. Patients with “autoimmune retinopathy” do not fall exclusively under either subspecialty. The ACP Ethics Manual addresses complex clinical situations where multiple subspecialists are involved in a patient’s care. However, these guidelines again reference the principal physician as the provider who should “assure a coordinated effort that is in the best interest of the patient …” and that “unless authority has been formally transferred elsewhere, the responsibility of the patient’s care lies with the principal physician.”3
Unfortunately, these guidelines do not outline a course of action when roles are not established. Similarly, the American College of Rheumatology’s Code of Ethics does not address this issue.4 Keeping in mind that the “physician’s primary commitment must always be to the patient’s welfare and interest,”3 one would hope that after an open discussion between the involved clinicians, a reasonable plan could be established. In reality however, once physicians start to consider the liability of prescribing off-label medications for rare diseases that fall outside the normal scope of their subspecialty, everyone gets nervous. The issue becomes more complex when the clinicians involved do not agree on what agent or agents should be used or how they should be used.
When providers do not agree on treatment and high-quality studies are not available, a few strategies may be considered. With regard to off-label steroid-sparing agents, providers should follow responsible off-label prescribing practices. These include:
- Evaluating whether there is sufficient evidence to justify an off-label use;
- Pressing for additional information from experienced experts or institutions when adequate published evidence is lacking; and
- Informing patients about the uncertainties, risks and potential costs of medications under consideration.2
Although the patient should not be put in a position of arbiter of any disagreement, all recommendations should be thoroughly reviewed with the patient. Good documentation, including details of obtaining the patient’s informed consent, is essential.
When addressing uncertainty about clinicians’ roles, the physician should consider consultation with peers or even with their own ethics committee. Another resource could be an institutional review board (IRB). Traditionally IRBs address issues directly related to human-subject research. However, some boards are willing to weigh in if all other resources have been exhausted and a thorny issue remains unresolved.
For a primary ophthalmologic disease, the principal physician should probably be the ophthalmologist. However, this should be agreed upon early. Even when the rheumatologist is not the principal physician, he or she plays an important role. The patient’s needs should be paramount. These needs are not served well when the rheumatologist refuses to get involved. This is especially true when the referring clinician and patient need help and there is no obvious better alternative.
For the patient described, the best approach is a coordinated effort between the rheumatologist, ophthalmologist and patient. Continued open communication with coordinated treatment and close follow-up has the potential to produce the best outcome.
Back to the Patient
In the case above, the patient’s ophthalmologist initiated corticosteroid monotherapy. After evaluation by the rheumatologist, a collective decision was made to add mycophenolate mofetil and conservatively reduce the steroid dose. The ophthalmologist monitored the patient’s vision regularly during the slow steroid taper. The patient’s rheumatologist contributed by recommending therapies to help reduce bone loss, scheduling regular laboratory tests and monitoring for both prednisone and mycophenolate mofetil toxicity. The patient’s vision has remained stable over several months.
Questions for the Reader
How have you resolved cases in which clinicians’ roles were unclear? How would you have handled the case described above?
If you have comments or questions about this case, or if you have a case that you’d like to see in Ethics Forum, e-mail us at [email protected].
Kirk D. Jenkins, MD, is a first-year rheumatology fellow at the University of Kentucky in Lexington, Ky., and a member of the ACR’s Committee on Ethics and Conflict of Interest.
Robert H. Shmerling, MD, is the clinical chief of rheumatology at Beth Israel Deaconess Medical Center in Boston and the chair of the ACR’s Committee on Ethics and Conflict of Interest.
Rebecca B. Yarrison, PhD, is an assistant professor with the Program for Bioethics and a clinical ethicist at the University of Kentucky.
Kristine M. Lohr, MD, MS, is the rheumatology training program director, interim chief of the Division of Rheumatology and professor of medicine at the University of Kentucky.
References
- Monson DM, Smith JR. Acute zonal occult outer retinopathy. Surv Ophthalmol. 2011 Jan-Feb;56(1):23–35.
- Dresser R, Frader J. Off-label prescribing: A call for heightened professional and government oversight. J Law Med Ethics. 2009 Fall;37(3):476–486, 396.
- Snyder L, American College of Physicians Ethics, Professionalism, and Human Rights Committee. American College of Physicians Ethics Manual, 6th ed. Ann Intern Med. 2012 Jan 3;156(1 Pt 2):73–104.
- American College of Rheumatology. Code of Ethics of the American College of Rheumatology Inc. http://www.rheumatology.org/about/governance/code_ethics.asp. Published August 2011. Accessed March 10, 2014.
