Journal of Neuro-Ophthalmology, December 1992, Volume 12, Issue 4

Renal causes of elevated sedimentation rate in suspected temporal arteritis.

The erythrocyte sedimentation rate (ESR) is a frequently used but nonspecific indicator of inflammation or infection. Clinicians often check an ESR in patients with symptoms of headache, facial or jaw pain, and visual loss, as an aid in the diagnosis of temporal arteritis. We present two patients with these complaints, who did not have temporal arteritis, nor any other inflammatory condition or infection, but had ESRs near or above 100 mm/h, leading to diagnostic confusion. An occult nephrotic syndrome, with or without renal insufficiency, can cause such a highly elevated ESR, and was discovered in these patients.

! ounlal 0,- Clilllcal Nt'UflI-( Il", 111tllmoloxy 121. JJ. 2~!.- 2~- l, 1992. © 1992 Raven Press, Ltd., :-': e". York Renal Causes of Elevated Sedimentation Rate in Suspected Temporal Arteritis Gregory Gruener, M. D. and Michael P. Merchut, M. D., F. A. C. P. The erythrocyte sedimentation rate ( ESR) is a frequently used but nonspecific indicator of inflammation or infec­tion. Clinicians often check an ESR in patients with symptoms of headache, facial or jaw pain, and visual loss, as an aid in the diagnosis of temporal arteritis. We present two patients with these complaints, who did not have temporal arteritis, nor any other inflammatory con­dition or infection, but had ESRs near or above 100 mm/ h, leading to diagnostic confusion. An occult nephrotic syndrome, with or without renal insufficiency, can cause such a highly elevated ESR, and was discovered in these patients. Key Words: Sedimentation rate- Temporal arteritis. CASE REPORTS Patient 1 A 62- year- old woman was hospitalized for acute throat pain and dyspnea, presumably from an­gina. She had a 2- hour episode of bifrontal head­ache, similar to prior headaches, but now followed by an several minute episode of transient left mon­ocular blindness. There were no arthralgias, jaw claudication, rash, or febrile illnesses. She was a diabetic with retinopathy and renal insufficiency, and had a left inferior frontal cerebral infarction 5 months ago. There was a history of coronary artery disease with myocardial infarction and ventricular tachycardia, amputation of the left leg due to isch­emia 2 years previously, and hyperlipidemia. Visual fields were normal, with an acuity of 20/ 200 OS, 20/ 100 00, reactive pupils without a rela­tive afferent pupillary defect ( RAPO), and normal optic discs with small retinal hemorrhages and mi­croaneurysms. The rest of the cranial nerves were normal and her temporal arteries were not tender. There was a mild right hemiparesis with dimin- From the Department of Neurology, Loyola University Med­ical Center, Maywood, Illinois, U. s. A. Address correspondence and reprint requests to Dr. Gregory P. Gruener, Department of Neurology, Loyola University Med­ical Center. 2160 S. First Ave, Maywood, IL 60153, U. S. A. 272 ished sensation in the distal foot, and generalized hyporeflexia. Minimal pedal edema was found. The erythrocyte sedimentation rate ( Wester­gren) was 114 mm/ h, having been 139 mmfh 3 months ago. Pertinent laboratory results included hemoglobin, 10.2 g/ dl; BUN, 17 mg/ dl; serum cre­atinine, 2.2 mg/ dl; serum albumin, 2.1 g/ dl; and 3 to 4+ protein on random urine samples. Fasting blood glucoses were 95 and 220 mg/ dl. A creatinine clearance of 8 ml/ min, and significant proteinuria, 4.83 g over 24 hours, was later demonstrated. A left temporal artery biOpsy was performed to exclude temporal arteritis as the cause of her tem­porary blindness, and was normal. She had no fur­ther neurological symptoms, and her headaches subsequently resolved, but she died 1 year later from septicemia. Patient 2 A 54- year- old woman had a 2- year history of " stabbing" right- sided headaches and was hospi­talized for a severe one. Pain involved the right temple, cheek, and jaw, lasting hours to days, and was worsened by chewing or touching the right face. There were no arthralgias, rash, or febrile ill­nesses. She was hypertensive, and had diabetes mellitus with retinopathy. The right temple was diffusely tender, with nor­mal jaw motion. Her funduscopic examination demonstrated a proliferative diabetic retinopathy with fibrous proliferation along the arcades 00 and bilateral peripheral laser photocoagulation. Neovascularization of both discs was also seen. Her pupils were 3 mm bilaterally with a normal reaction to light and no RAPO. Visual acuity was 20/ 40000,20/ 50 as. The remainder of her cranial nerves were normal, including facial and corneal sensation. No peripheral edema was evident. RENAL- INDUCED HIGH ESR IN TEMPORAL ARTERITIS 273 The erythrocyte sedimentation rate was 82- 90 mm/ h ( Westergren), with normal ANA and DNA titers as well as rheumatoid factor. The hemoglo­bin was 11.1 g/ dl, with BUN, 12 mg/ dl; serum cre­atinine, 1.3 mg/ dl; serum albumin, 3.1 g/ dl; and 3+ protein on urinalysis. Fasting blood glucoses were 180 and 281 mg/ dl. Later, a creatinine clear­ance of 94 mUmin with an increased 24- hour uri­nary protein of 8.42 g was demonstrated. A right temporal artery biopsy was performed and was normal. Her headaches ceased after 2 weeks of indomethacin, 25 mg t. i. d. Renal func­tion remained stable. DISCUSSION The ESR reflects red blood cell ( RBC) aggrega­tion, and is the measured fall or settling of a ver­tical column of erythrocytes within 1 hour when held vibration- free and at room temperature. For uncertain reasons it does increase slightly with age, but in patients over the age of 50 the sug­gested upper limits of normal are 30 mm/ h in women and 20 mm/ h in men ( 1). Usually electrostatic forces cause RBCs to repel each other and inhibit their aggregation. However, increased amounts of plasma fibrinogen or globu­lins coat the RBCs, fostering their aggregation, and hasten their settling in a glass tube. Thus fibrino­gen and globulins as the " acute phase reactants" of inflammatory and infectious states may be re­sponsible for the elevated ESR detected in these cases. Such a mechanism is proposed in the case of polymyalgia rheumatica and temporal arteritis, and an elevated ESR is one of the major clinical criteria which support the diagnosis. In our pa­tients it was this elevation of the ESR, their age, and the complaints of headache and visual symp­toms that prompted a tentative diagnosis of tem­poral arteritis and led to temporal artery biopsy. In each of our cases the biopsy was negative, and subsequent follow- up, without steroid use, did not support this initial clinical diagnosis. While, earlier studies have also suggested that there is an in­creased incidence of neoplasm in polymyalgia rheumatica. However, epidemiologic data now suggest that, although individuals with malig­nancy and polymyalgia rheumatica share similar complaints ( musculoskeletal pain, malaise, ele­vated ESR), there is no evidence of an increased rate of malignancy in individuals with polymyalgia rheumatica ( 2). Despite this assumed relationship, there was no evidence of malignancy discovered on follow- up of our cases, and hence occult neo­plasm was not a cause of their elevated ESRs. Diabetics, without evidence of inflammatory or infectious disease, may also have mildly elevated ESRs. A group of 34 such diabetics were found to have a mean ESR of 32 mm/ h, significantly greater than their control group's mean ESR of 9 mm/ h ( 3). Concentrations of serum proteins, such as fibrino­gen and globulins, were no different between these two groups. This moderate ESR elevation was instead attributed to the increased glycosy­lated hemoglobin ( HbA 1c) in the diabetics, which facilitates the sedimentation of RBCs ( 3). Since both of our patients were diabetic, this may partly account for their ESR elevations, but is unlikely to be the primary explanation. We believe that renal disease, and particularly the nephrotic syndrome, was the cause of the strikingly elevated ESRs in our patients. Both had proteinuria in the nephrotic range, over 3.5 g in 24 hours, but lacked findings of nephritis, such as gross hematuria or urinary RBC casts ( 4). The cre­atinine clearance, while decreased in patient 1, was normal in patient 2, which can occur early in the nephrotic syndrome. In two studies of patients with stable, chronic renal failure, but no other complicating disease, average ESRs of 56 and 69 mm/ h were found ( 5,6). Markedly elevated ESRs were not uncommon, with ESRs over 60 mm/ h in 57% and over 100 mm/ h in 20% of one uremic group ( 6). While most uremic patients are anemic, which itself can raise the ESR since effective RBC repulsion is decreased, the zeta sedimentation ra­tio, which is independent of hematocrit, was also significantly elevated. This implies that another factor in uremic plasma, most likely fibrinogen or certain globulins, accounts for these elevated ESRs ( 5). However, the effect of proteinuria itself on ESR elevation in renal disease has not been thoroughly studied. ESR elevation appears unrelated to the etiology of renal failure, duration or type of dialy­sis, and level of serum creatinine or BUN ( 6). High ESRs were not due to chronic inflammation in dis­eased kidneys, since there was no significant dif­ference between nephrectomized patients and those with their own kidneys ( 7). In a Singapore study of patients with very elevated ESRs of 100 mm/ h or more, 5.6% was attributed to the neph­rotic syndrome and 4.7% to uremia of various causes ( 8). Despite this finding, infections ( 44.2%), connective tissue diseases ( 24.2%), and neoplasm ( 11 %) remain the most common causes for these markedly elevated ESRs. Therefore, we wonder whether an accelerated, compensatory overpro­duction of fibrinogen and globulin proteins in neph­rotic patients creates these highly elevated ESRs. Renal failure, or the nephrotic syndrome with or , C/ i" Nl'UTo- ophthalmol, Vol. 12. No. 4. 1992 274 G. GRUENER AND M. P. MERCHUT without renal failure, can result in markedly ele­vated ESRs, in the absence of infection or inflam­mation. While there may be few or no clinical clues of renal disease, the discovery of an unexplained 3+ or 4+ proteinuria on a random urinalysis ap­pears to be a helpful screening test. Especially in patients where there is a low clinical suspicion of temporal arteritis, yet a markedly elevated ESR without explanation, renal dysfunction and pro­teinuria should be excluded prior to urgent steroid therapy and temporal artery biopsy. This possibil­ity should be considered in the clinical evaluation of all patients with suspected temporal arteritis. REFERENCES 1. Sox HC Jr, Liang MH. The erythrocyte sedimentation rate: Guidelines for rational use. Ann Intern Med 1986; 104: 515­23. / Clin Neuro- ophthalmol, Vol. 12, No. 4. 1992 2. Chuang TY, Hunder Gc, Ilstrup DM, Kurland LT. . Poly­myalgia rheumatica: A lO- year epidemiologic and chmcal study. Ann Intern Med 1982; 97: 672~ O. 3. Elias AN, Domurat E. Erythrocyte sedimentation rate in diabetic patients: Relationship to glycosylated hemoglobin and serum proteins. JMed 1989; 20: 297- 302. 4. Couser WG. Glomerular diseases. In Wyngaarden JB, Smith LH Jr, eds. Cecil textbook of medicine. Philadelphia: Harcourt Brace Jovanovich, 1988: 591- 3. 5. Shusterman N, Kimmel PL, Kiechle FL, Williams S, Morri­son G, Singer I. Factors influencing erythrocyte sedimen­tation in patients with chronic renal failure. Arch Intern Med 1985; 145: 1796- 9. 6. Bathon J, Graves J, Jens P, Hamrick R, Mayes M. The eryth­rocyte sedimentation rate in end- stage renal failure. Am J Kidney Dis 1987; 10: 34- 40. 7. Warner DM, George CRP. Erythrocyte sedimentation rate and related factors in end- stage renal failure. Nephron 1991; 57: 248. 8. Cheah JS, Ransom GA. Significance of very high erythro­cyte sedimentation rate ( lOO mm or above in one hour) in 360 cases in Singapore. JTrap Med Hyg 1971; 74: 2~ 30.