MANAGEMENT OF GCA PATIENTS

These recommendations are based on my experience of dealing with these patients for more than 30 years. In the treatment of GCA, one always has to keep in mind that, as stressed above, GCA is an ocular emergency. If there is a reasonable index of suspicion that the patient has GCA or arteritic AION, start treatment immediately. Do not wait for the results of temporal artery biopsy, because by the time the result comes, the patient may have developed irreversible visual loss in both eyes. If the biopsy is negative, treatment can be stopped without harm to the patient.

CORTICOSTEROID THERAPY

It is universally agreed that the treatment of choice for GCA is systemic corticosteroids. However, the exact regimen of steroids in GCA has become highly controversial. Perhaps the most important reason is that rheumatologists and ophthalmologists differ in their perspective on GCA. The former see patients with rheumatologic manifestations (many of them with polymyalgia rheumatica), and the latter see only GCA patients with visual loss and occult GCA. The steroid therapy regimen advocated by rheumatologists may be appropriate for polymyalgia rheumatica (with no risk of blindness), but I have found that there is no set formula of regimen of steroids for GCA patients because of the infinite variation between individuals.

The main issues of conflict and confusion are the dosage and duration of corticosteroid therapy required, and how to regulate steroid therapy? I have recently reviewed these and other aspects of steroid therapy in the management of GCA,⁷ and also reported findings of my 27-year planned clinical study on steroid therapy in GCA.⁷ Following are the findings of this study:

Intravenous megadose steroid therapy (equivalent to 1 gram of Prednisone every 6-8 hours, repeated for 3-4 doses in the form of an intravenous drip) was initially given to 33% followed by oral steroids, while the rest had only the oral therapy. The median starting oral Prednisone dose was 80 mg/day, with 40% on 100-120 mg/day. I found that the most reliable and sensitive parameters to regulate and taper down steroid therapy were the levels of ESR and CRP, and NOT systemic symptoms. All patients were maintained at the high dose of Prednisone till both the ESR and CRP had stabilized at low levels (that usually took 2-3 weeks - CRP came down much faster than ESR - see figures 3 and 4); after that very gradual tapering of Prednisone was started, guided by the ESR and CRP levels only. The median time to reach the lowest maintenance dose of Prednisone at which the ESR and CRP stayed low and stable was 48.7 months, and the median lowest Prednisone maintenance dose achieved was 7 mg/day (interquartile range of 1 to 16 mg/day). There was no significant difference in the time to reach the lowest maintenance dose among patients with and without visual loss. My study showed that no generalization at all is possible for tapering down of Prednisone and there is no set formula because of the infinite variation between individuals. Only 10 of 145 patients were able to stop the therapy and maintain stable ESR and CRP levels during a median follow-up time of 2.43 years (inter-quartile range of 1 to 6 years). I found that the vast majority of GCA patients need a small dose of steroid therapy for years, if not for the rest of their life. The study showed no evidence that intravenous megadose steroid therapy was more effective than oral therapy in improving vision⁴ or preventing visual deterioration⁵ due to GCA. In view of that new finding, I have now altered my intravenous regimen, giving only one initial intravenous loading dose, followed by oral Prednisone. My indications for intravenous corticosteroid therapy in GCA have always been any of the following ocular signs or symptoms:
(1) History of amaurosis fugax.
(2) Complete loss of vision in one eye.
(3) Early signs of involvement of the second eye, e.g., amaurosis fugax, visual field defects, optic disc edema, or sluggish retinal circulation in that eye. The objective is to try to prevent further visual loss in this high-risk group of patients by aggressive steroid therapy.

Figure 3: Graph of CRP levels in 6 patients with GCA, showing initial responses to high doses of systemic corticosteroid therapy.

Figure 4: Graph of ESR (Westergren) rate in 6 patients with GCA, showing initial responses to high doses of systemic corticosteroid therapy. (Reproduced from Hayreh¹¹)

Maintenance dose and duration of steroid therapy

My study has shown that determining the maintenance dose of steroid therapy is a slow, laborious, painstaking job, taking months or even years. The guiding principle, obviously, is to maintain the lowest level of ESR and CRP with the lowest dose of Prednisone. As mentioned above, my study showed marked inter-individual variation among GCA patients in: (a) the amount and duration of steroid required to control the active disease, (b) the time needed to reach a maintenance dose, (c) the maintenance dose required to keep the disease under control to prevent blindness, and (d) the total length of treatment.^4,5,7,8 Therefore, steroid therapy for GCA has to be individualized. I have found that most GCA patients require a virtually life-long, very small maintenance dose, which has little or no systemic side-effects.⁷ A common mistake made by physicians in these cases is to taper the steroids down rapidly to a very low dosage and then discontinue it. There is a common belief among rheumatologists that GCA burns itself out in a year or two, and steroids can then be tapered off unless the patient develops systemic symptoms.^7,8 As discussed above, I have found this notion to be completely wrong, and can prove disastrous, because repeat temporal artery biopsy has shown evidence of active disease even after 9 years of steroid therapy.^7,8 The advice to base treatment on the clinical picture, rather than laboratory tests (i.e. ESR and CRP) may be true for polymyalgia rheumatica patients. But it can be dangerous for patients with GCA, who may lose vision irrevocably without developing any warning systemic symptoms at all; moreover, 21% of patients with visual loss have occult GCA. I have found that the only trustworthy and safe parameters to regulate the steroid therapy and to prevent visual loss are the levels of ESR and CRP, and nothing else.^4,5,7

To have the full co-operation of the patient in the management of GCA, it is very important to explain the objectives of the treatment clearly to the patient. In my experience there is usually no useful recovery of visual function in the already involved eye (see next page).⁴ The patient needs to know this, to avoid having unrealistic expectations from the aggressive steroid therapy. The primary objective of treatment is to prevent loss of vision in the fellow eye. I have found that in spite of the starting intensive corticosteroid treatment, there are a few patients who are still likely to lose further vision during the first 5 days of treatment (see next page).⁵ However, I have not had anyone lose any more vision after that, if treated properly and adequately. Thus, the treatment is extremely effective, and about 5 days after the start of treatment one can almost guarantee that the patient will not lose any further vision. To maintain that vision, however, maintenance treatment with adequate oral corticosteroids is absolutely essential, and that is usually lifelong.

Alternate Day Corticosteroid Therapy in GCA

There is much misunderstanding among physicians about this mode of steroid therapy, and many of these patients are given alternate day therapy from the start. This mode of therapy has no place in the treatment of almost any active disease (including GCA) and is indicated only for maintaining suppression of disease activity and prevention of flare-up. Therefore, alternate day corticosteroid therapy has no place at all in the treatment of active GCA. In my experience, and that of others,⁷ it is not even effective as a maintenance therapy regimen in GCA patients.

Corticosteroid Resistant GCA

Corticosteroid resistant GCA has been reported in the rheumatologic literature. I have reviewed the subject.⁷ My study does not support this concept. I have had many patients referred to me over the years by outside physicians with that diagnosis; but when I treated them with adequate steroid doses, every single one immediately responded to steroid therapy. I feel that “corticosteroid resistant GCA” simply reflects a patient who has not been given an adequate amount of steroids. The basis for this erroneous impression may be mixing polymyalgia rheumatica and GCA patients in rheumatologic studies, with more of the former than the letter. An initial dose of Prednisone as low as 20 mg/day or even less may be adequate to manage polymyalgia rheumatica, but is totally inadequate to control active GCA and prevent visual loss.

STEROID SPARING AGENTS

I have reviewed the literature on this subject.⁷ The most common steroid sparing agent discussed is Methotrexate. The unanimous conclusion of all the randomized clinical trials is that there is no real benefit in using methotrexate as a steroid sparing agent or to control GCA.

ASPIRIN OR ANTICOAGULANTS

Use of aspirin or anticoagulants in treatment of GCA to prevent ischemic lesions has been suggested by some, because of the presence of thrombocytosis in GCA (see above). I have reviewed the subject.⁷ It seems the whole controversy on the association of thrombocytosis in GCA and ischemic lesions has emerged from a confusion between essential thrombocytosis (a chronic, progressive, myeloproliferative disorders of insidious onset with much higher platelet count) and reactive thrombocytosis (seen in GCA with a rather moderate increase in platelets). It is well known that patients with essential thrombocytosis have a high risk of thrombotic involvement of major vessels and the microcirculation. However, reactive thrombocytosis associated with GCA is not the same as essential thrombocytosis. There is no convincing evidence that ischemic manifestations occur as a direct consequence of reactive thrombocytosis in GCA. This would indicate that there is little justification for giving aspirin or other platelet anti-aggregating agents to prevent visual loss in GCA. Moreover, to date there are no studies which support the efficacy of anti-platelet agents or anticoagulants in the treatment of GCA to prevent blindness.

CONCLUSIONS

GCA is the most important medical emergency in ophthalmology, because of its high risk of visual loss, which is preventable if these patients are diagnosed early and treated immediately and aggressively. Thus, in patients aged over 55 years, if symptoms and/or signs suggest GCA or they have amaurosis fugax, AION, central retinal artery occlusion, cilioretinal artery occlusion or posterior ischemic optic neuropathy, always rule out GCA first before embarking on expensive and time-consuming investigations and treatments. If GCA is suspected, treat it as an emergency with systemic corticosteroids - temporal artery biopsy can wait. The management of GCA is highly complex, taxing and life-long; it should be undertaken with care and with the full understanding and co-operation of the patient and his/her internist.

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