Diagnostic Algorithm for Patients With Suspected Giant Cell Arteritis: Comment

Letters to the Editor REFERENCES 1. Khan K, Malik AI, Almarzouqi SJ, Morgan ML, Yalamanchili S, Chevez-Barrios P, Lee AG. Optic neuropathy due to chronic lymphocytic leukemia proven with optic nerve sheath biopsy. J Neuroophthalmol. 2016;36:61-66. 2. Mbekeani JN, Fattah MA, Nounou RA, Chebbo W, Dogar MA. Chronic myelogenous leukemia relapse presenting with central nervous system blast crisis and bilateral optic nerve infiltration. J Neuroophthalmol. 2016;36:73-77. 3. Hon C, Ma ES, Yau K, Au WY. CNS manifestations of malignancies: case 3. Leukemic optic neuropathy Diagnostic Algorithm for Patients With Suspected Giant Cell Arteritis: Comment B ecause of my long term interest in giant cell arteritis (GCA), I feel compelled to comment on the study by El-Dairi et al (1) dealing with "Diagnostic algorithm for patients with suspected giant cell arteritis." Their conclusions were based on retrospective study of 204 patients with temporal artery biopsy (TAB) for GCA. We did a similar, but a prospective study of 363 patients with TAB for GCA (2), and other studies of GCA patients examining ocular manifestations (3), occult GCA (4), and also in 408 patients (121 with positive and 287 with negative TAB) with thrombocytosis (5). To begin with, the report by El-Dairi et al was based on retrieval of a "pathology electronic data base" and "corresponding electronic and paper medical records" of 204 patients-49 with positive TAB results and 12 "suggestive." The authors admit that "medical records reviewed may have had incomplete documentation of symptoms, signs, and laboratory results and a number of patients were not tested for C-reactive protein (CRP) and platelet count, and the clinical examination of the superficial temporal artery was not always documented." In our study of 363 patients (106 with positive and 257 with negative TAB for GCA), at initial visit all underwent a complete physical and hematologic evaluation, and TAB, in our department. Length of temporal artery specimen and serial sectioning are important to eliminate "skip areas." In the study by El-Dairi and colleagues, pathologic study of TAB was based on retrospective retrieval of the biopsy information. The length of most of the biopsy specimens was less than 1 inch and in one case only "9 mm" (0.36 inch); they examined 10 slides and "500 mm" of "6-10 cross sections" only. In our study, TAB specimen was at least 1 inch long and all had serial sectioning. In addition, two-thirds of their patients with positive TAB were on corticosteroid therapy before TAB-10 of them for more than 3 weeks, 8 for more than 2 months, and 2 for more than 1 year. We know that corticosteroid therapy rapidly ameliorates systemic, hematologic, and histopathologic parameters. Our patients were evaluated before the start of corticosteroid therapy. 224 complicating leukemia cutis. J Clin Oncol. 2005;23:4229- 4230. 4. Lin YC, Wang AG, Yen MY, Hsu WM. Leukaemic infiltration of the optic nerve as the initial manifestation of leukaemic relapse. Eye (Lond). 2004;18:546-550. 5. Madani A, Christophe C, Ferster A, Dan B. Peri-optic nerve infiltration during leukaemic relapse: MRI diagnosis. Pediatr Radiol. 2000;30:30-32. 6. Sharma T, Grewal J, Gupta S, Murray PI. Ophthalmic manifestations of acute leukaemias: the ophthalmologist's role. Eye (Lond). 2004;18:663-672. Our study showed a very different prevalence of systemic signs and symptoms from that in the study by El-Dairi et al. We found the following statistically significant differences between those with positive TAB for GCA and those with negative biopsy: jaw claudication (P , 0.0001), neck pain (P = 0.0003), anorexia/weight loss (P = 0.0005), and fever (P = 0.040). Scalp tenderness was almost significant (P = 0.058). On further analysis, we found that odds of a positive TAB were 9.0 times greater with jaw claudication (P , 0.0001), 3.4 times with neck pain (P = 0.0085), 2.0 times with an erythromycin sedimentation rate (ESR) of 47- 107 mm/hour (P = 0.0454), 3.2 times with CRP above 2.45 mg/dL (P = 0.0208) and 2.0 times for age 75 years or more (P = 0.0105). In addition, we reported our findings on occult GCA (4), where patients have no systemic symptoms at all and visual loss is the only presenting symptom; in them GCA is sometime missed, because of a firm belief that all GCA patients must have systemic symptoms and/or elevated ESR. With regard to headache, El-Dairi et al attributed the following statement to our study: "A new onset of severe headache had been reported in approximately two-thirds of patients with GCA"; this is not true. We stated that a history of any type of headache (not "new onset of severe headache") was present in 55.7% of patients with positive TAB and 45.5% with negative TAB (P = 0.084). El-Dairi et al concluded that when a patient had only 1 positive finding in their algorithm for TAB, "evaluate for alternative diagnosis." Yet according to our study, in persons 50 years and older, the presence of jaw claudication alone is a strong indication for TAB. Also, in persons 50 years and older, suspicion for GCA should be high in patients presenting with recent onset of recurrent episodes of amaurosis fugax, anterior ischemic optic neuropathy, central retinal artery occlusion, cilioretinal artery, or ocular ischemic syndrome. Fundus fluorescein angiography should be performed promptly in all of them to demonstrate evidence of posterior ciliary artery occlusion, because its presence indicates GCA unless proven otherwise. El-Dairi et al performed fluorescein angiography in only 7 of their patients. However, it is not clear when in the clinical course, angiography was performed. If it was done weeks after the onset of visual loss, collateral circulation in the choroid may have been established, which can result in misleading information (6). Letters to the Editor: J Neuro-Ophthalmol 2016; 36: 221-229 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Letters to the Editor Regarding hematological tests, the findings of thrombocytosis in our study are very different from those by El-Dairi et al, who stated that "the strongest association with positive TAB was an elevated platelet count," and that elevated CRP or an elevated ESR were not associated with a positive TAB. However, they went on to state that elevation of platelet count and CRP "was highly predictive of a positive TAB." Our studies (2-5) do not fully support these conclusions. Our study (5) showed that the predictive ability of elevated platelet count did not surpass elevated ESR or CRP as a diagnostic marker for GCA. The most important consideration is that GCA is an ophthalmic emergency, where early diagnosis and aggressive treatment with high-dose corticosteroid therapy prevents visual loss. The conclusion by El-Dairi et al that "None of the patients with a clinical score less than 2 had a positive TAB" is somewhat misleading. It may be valid in many GCA patients but not by any means in all. I would caution the reader to be skeptical of many of the conclusions reported by El-Dairi et al in evaluating patients suspected of having GCA. Sohan S. Hayreh, MD, MS, PhD, DSc, FRCS, FRCOphth (Hon) Diagnostic Algorithm for Suspected Giant Cell Arteritis: Response W e thank Dr. Hayreh for sharing his comments on our study. Dr. Hayreh's illustrious academic career elevated him to the status of a thought leader in many ocular vascular diseases, such as retinal vein occlusion, retinal artery occlusion, ischemic optic neuropathy, and giant cell arteritis (GCA). With such credentials, it can be a daunting task to provide a rebuttal to some of his criticisms, but we do so with great respect and admiration. Dr. Hayreh invokes the findings from his article published in 1997 (prospectively performed from 1973 to 1994) (1) to compare and contrast the results to our study (2). We will respond in a structured fashion and discuss each point made in the order presented in his letter. Pathology Electronic Database As should be done in all reports, we discussed the limitations of our study, which included a lack of complete clinical and paraclinical information in the medical records of some patients. Such shortcomings are often the situation in many retrospective studies. Even in Dr. Hayreh's prospective study, C-reactive protein (CRP) values were not available for all patients. Letters to the Editor: J Neuro-Ophthalmol 2016; 36: 221-229 Department of Ophthalmology and Visual Sciences, College of Medicine, University of Iowa, Iowa city, IA The author reports no conflict of interest. REFERENCES 1. El-Dairi MA, Chang L, Proia AD, Cummings TJ, Stinnett SS, Bhatti MT. Diagnostic algorithm for patients with suspected giant cell arteritis. J Neuroophthalmol. 2015;35:246-253. 2. Hayreh SS, Podhajsky PA, Raman R, Zimmerman B. Giant cell arteritis: validity and reliability of various diagnostic criteria. Am J Ophthalmol. 1997;123:285-296. 3. Hayreh SS, Podhajsky PA, Zimmerman B. Ocular manifestations of giant cell arteritis. Am J Ophthalmol. 1998;125:509-520. 4. Hayreh SS, Podhajsky PA, Zimmerman B. Occult giant cell arteritis: ocular manifestations. Am J Ophthalmol. 1998;125:521-526, 893. 5. Costello F, Zimmerman MB, Podhajsky PA, Hayreh SS. Role of thrombocytosis in diagnosis of giant cell arteritis and differentiation of arteritic from non-arteritic anterior ischemic optic neuropathy. Eur J Ophthalmol. 2004;14:245-257. 6. Hayreh SS, Baines JAB. Occlusion of the posterior ciliary artery I. Effects on choroidal circulation. Br J Ophthalmol. 1972;56:719- 735. We used the Department of Pathology electronic database to identify patients who had been evaluated for GCA at Duke University Medical Center based on the results of temporal artery biopsy (TAB). We chose to use this data set because it allowed us to capture for analysis as many patients as possible who underwent a TAB from the entire medical center and not just from the Department of Ophthalmology. In comparison, it seems to be somewhat of a unique situation that at the University of Iowa Hospitals and Clinics, all TABs were performed by ophthalmologists during the period of Dr. Hayreh's study. Length of Temporal Artery Specimen, Serial Sectioning, and Previous Corticosteroid Therapy We agree with Dr. Hayreh's statement that length of the temporal artery specimen and serial sectioning are important to eliminate "skip areas." We also agree that the optimal length of a TAB should be at least 1 inch. To explain the variation in the length of TAB in our study, it should be kept in mind that there were not only multiple ophthalmologists who performed the TAB but also surgeons from other specialties (otolaryngology, neurosurgery, vascular surgery, and general surgery). However, we did not find that a longer TAB was associated with a higher rate of a positive TAB (mean biopsy length, 225 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.