Central retinal vein occlusion due to hyperviscosity syndrome

The Journal of Emergency Medicine, Vol. 18, No. 1, pp. 23–26, 2000 Copyright © 2000 Elsevier Science Inc. Printed in the USA. All rights reserved 0736-4679/00 $–see front matter

PII S0736-4679(99)00157-2

Clinical Communications CENTRAL RETINAL VEIN OCCLUSION DUE TO HYPERVISCOSITY SYNDROME Charles C. Chiang,

MD,*

Sean Begley,† and Sean O. Henderson,

MD†

*Department of Emergency Medicine, LAC⫹USC Medical Center and †Department of Emergency Medicine, University of Southern California School of Medicine, Los Angeles, California Reprint Address: Sean O. Henderson, MD, Department of Emergency Medicine, LAC⫹USC Medical Center, Unit #1, Room 1011, 1200 N. State Street, Los Angeles, CA 90033

e Abstract—A 57-year-old man with no previous medical history entered the emergency department with 2 days of painless vision loss in the left eye. The patient was diagnosed with central retinal vein occlusion (CRVO) and admitted for treatment. Further work-up revealed that the cause of his CRVO was a hyperviscosity syndrome secondary to multiple myeloma. The patient received two rounds of plasmapheresis with slight recovery of vision and was discharged 28 days later. © 2000 Elsevier Science Inc.

present a case of hyperviscosity syndrome in a patient with sudden, painless loss of vision. The diagnosis was made based upon physical examination and laboratory data. Prompt treatment led to a partial recovery of vision.

CASE REPORT A 57-year-old man entered the emergency department (ED) with a 2-day history of painless vision loss of the left eye. He reported the sensation of a sheet being pulled down over the left eye. There was no photophobia, scotoma, headache, nausea, vomiting, or fever. The patient denied using glasses or contact lenses. He also denied any head or ocular trauma and, until this episode, reportedly had good vision. He was easily fatigued and had lost ten pounds over the past few months. Also, he was concerned about numerous episodes of epistaxis over recent weeks. He denied hematemesis, gingival bleeding, melena, or any bleeding problems in the past. The patient’s past medical history was negative for hypertension, diabetes mellitus, coronary disease, and pulmonary disease. Family history was noncontributory. The patient had been incarcerated for 3 months. Before that, he lived in a shelter for the homeless. He denied ever being exposed to toxic chemicals. He had smoked a half-pack of cigarettes a day for 40 years, drank a sixpack of beer a day for the past 10 years, and admitted to having used crack cocaine in the past—the last time 5 months previously. He denied i.v. drug use. He reported

e Keywords— emergency; central retinal vein occlusion; hyperviscosity syndrome

INTRODUCTION Hyperviscosity syndrome (HVS) is a rare complication of malignancy. It is a potentially lethal disease that requires prompt recognition and treatment. Symptoms include mucous membrane bleeding, retinopathy, loss of vision, and neurologic disorders associated with elevated serum viscosity (1). Laboratory analysis may be difficult because of serum stasis in blood analyzers, and initial values may confuse the presentation. Patients may have anemia, rouleau formation on a peripheral blood smear, “factitious” hyponatremia, and hypercalcemia as well as markedly high serum viscosity (2). Initial therapy includes rehydration, treatment of associated diseases, and plasmapheresis. Hyperviscosity syndrome should be sought in any cancer patient who presents with insidious bleeding, visual symptoms, and neurologic manifestations. We

RECEIVED: 16 December 1998; FINAL ACCEPTED: 25 May 1999

SUBMISSION RECEIVED:

27 April 1999;

23

24

C. C. Chiang et al.

a negative HIV test 3 months previously. He took no medications and had no allergies. The patient was a tall, thin man who was alert and oriented but slow to respond to questions. Vital signs were: blood pressure 114/60 mmHg, pulse of 76 beats per minute, a respiratory rate of 16 breaths per minute, and temperature of 36.1°C (97°F). His gait was steady, but he would veer to the right while walking a straight line. Visual acuity out of the right eye with pinhole was 20/50. He was unable to read the chart with the left eye but could count fingers at ten feet, and light perception was intact. On slit lamp examination, the conjunctiva, cornea, anterior chamber, and lens were intact. Funduscopic examination revealed multiple microhemorrhages in all quadrants. The rest of the physical examination was unremarkable. After a consultation by ophthalmology, the patient was diagnosed with central retinal vein occlusion of the left eye. Further work-up with fluorescein angiography confirmed the diagnosis and also revealed impending central retinal vein occlusion of the right eye (Figure 1). Admission laboratories were significant for a WBC of 5,700 per mm3, Hgb 6.9%, Hct 20.0%, and platelets 178,000 per mm3. MCV was 88.3 and RDW 16.9. The patient’s sodium was 128 mmol/L, potassium 4.4 mmol/L, C1 102 mmol/L, CO 21 mmol/l, glucose 76 mg/dl, BUN 31, and creatinine 2.5 mg/dL. Calcium level was 11.1 mg/dL (8.8 –10.3 mg/dL), albumin 2.2 g/dL (3.5–5.0 g/dL), uric acid 9.0 mg/dL (2.4 –7.4 mg/dL), and serum viscosity was 3.1 (1.4 –1.8 cp). Hematology was then consulted. Further workup included x-ray studies of the skull, chest, and long bones that revealed no lytic lesions. Serum protein electrophoresis was elevated with an IgG and kappa protein spike. A bone marrow biopsy revealed 50 –70% myeloma cells. The patient’s definitive treatment was plasmapheresis. He underwent two rounds before symptomatic improvement. Other treatment modalities included hydration and diuresis to treat hypercalcemia, blood transfusion to treat anemia, and chemotherapy to treat the underlying malignancy. The patient’s total hospital stay was 28 days, with his course being complicated by bacterial pneumonia. He felt subjectively better at the time of discharge. Visual acuity at that time was 20/200 in the left eye and 20/30 in the right. The patient was followed by ophthalmology and hematology on an outpatient basis. Final serum viscosity was equal to 2.0 cp. DISCUSSION Hyperviscosity syndrome (HVS) is a constellation of symptoms and clinical findings that reflect the increased

Table 1. Differential Diagnosis of Monocular Vision Loss Optic neuritis (e.g., sarcoidosis) Temporal arteritis Retinal detachment Macular degeneration Central retinal vein occlusion Cataracts Lens dislocation Ruptured globe Hyphema Hysteria Diabetic retinopathy

interactions of the hematologic components as a result of their increased serum concentrations (3). The syndrome is most commonly associated with Waldenstrom’s macroglobulinemia but also has been known to occur with multiple myeloma, ␬-light chain disease, cryoglobulinemia, and, rarely, rheumatoid arthritis (1–5). The symptoms of HVS occur as increased immunoglobulins interact with other blood products such as erythrocytes, platelets, and other globulins to impede flow. The immunoglobulins are most commonly IgM molecules, and, to a lesser degree, IgA and IgG3 (6). Serum viscosity is described clinically by the centipoise (cp), and reflects the ability of the serum to flow through narrow tubes such as the capillary system. Although there are different means of measuring the serum viscosity, it is generally agreed that blood samples collected in EDTA-containing tubes have plasma values at 25°C ranging from 1.50 to 1.72 cp (7). A “relative viscosity” compares the serum viscosity to that of water and has a normal ratio value of 1.4 to 1.8 (3). Symptoms of HVS are thought to occur only infrequently at values less than 4 cp (relative viscosity 2 to 4), at an increased frequency between 6 cp and 7 cp (relative viscosity 5 to 8), and in nearly all patients with a relative viscosity greater than 8.1 (1,3). Acute neurologic manifestations such as altered mental status, headache, vertigo, obtundation, or coma that are due to intracerebral vascular occlusions may be the initial reason that the patient or patient’s family seeks emergency medical care (1,16). Other neurologic effects, such as seizures with resultant intracerebral hemorrhages, have been described, as have peripheral neuropathies that are thought to be due to occlusion of the small vessels that supply the nerve (3). In all, it appears that these changes are nonfocal, and the ability to reverse them is thought to depend largely on the length of time they have persisted. Visual changes are common in patients with hyperviscosity syndrome. The differentiation of this entity from others that cause monocular blindness (Table 1) depends on a thorough medical history and the funduscopic examination. Early funduscopic findings are dila-

Hyperviscosity Syndrome and CRVO

Figure 1. Fluorescein angiography of affected eye. Note characteristic “sausage link” (engorged) retinal vessels secondary to hyperviscosity syndrome (arrow).

tation and tortuosity of veins secondary to stasis of blood flow (8). A pathognomonic funduscopic finding for the hyperviscosity syndrome is fundus paraproteinaemicus. Fundus paraproteinaemicus describes the engorged, torturous retinal veins that take on a boxcar or “sausagelink” appearance (Figure 1). Left untreated, this entity may then progress to complete central retinal vein occlusion, flame-shaped hemorrhages, microaneurysms, or proteinacious exudates. Resultant visual loss, blurring, or decreased visual acuity may occur from these retinal changes (8). Bleeding disorders occur because of the increase in serum proteins that are thought to affect the hematologic system directly by coating platelets, thus hindering their ability to form a clot (10). As a result, mucosal bleeds are common. The ability of some types of immunoglobulins to interact with clotting factors further compromises clotting. In some types of gammopathies, there is an increased susceptibility for infection as a monoclonal rise

25

in one immunoglobulin may have a suppressive effect on other immunoglobulin fractions (11). In HVS patients, anemia of chronic disease may be exaggerated by an increase in the plasma volume. The anemia is in part dilutional, and careful consideration should precede an attempt to correct the anemia by blood transfusion. Volume from both the blood transfusion and the increased plasma volume may precipitate cardiac failure in some patients (2,3). Electrolyte disturbances such as hypercalcemia and asymptomatic pseudohyponatremia are common in patients with HVS. These electrolyte abnormalities may present in the ED as altered mental status, headache, confusion, or coma. HVS should be suspected when there is history of a known malignancy or when other more common causes of electrolyte imbalances such as diabetes, nephrotic syndrome, or hyperparathyroidism have been ruled out (12). Attempts to correct the manifestations of HVS in the ED fall into two therapeutic regimens, hydration with diuresis and phlebotomy or plasmapheresis. Rehydration of the patient with normal saline as loop diuretics are being infused has been recommended to correct the hypercalcemia as well as to reduce the effective protein concentration (13). Phlebotomy with the removal of 100 –200 cc whole blood has been found to effectively reduce the acute symptoms and is more accessible in the ED than other modes of therapy such as plasmapheresis (13). However, plasmapheresis remains the treatment of choice, and involvement by hematology should be expedited (14). Because the increase in proteins with HVS is largely confined to the intravascular space, the removal of these components via plasmapheresis is successful in at least temporarily reversing the symptoms and reducing the serum viscosity itself. A drawback to this therapy is the relatively large volume of plasma, usually 2 to 4 liters, that must be exchanged weekly to relieve symptoms. Hyperviscosity syndrome should be sought in any cancer patient who presents with the triad of bleeding, visual signs and symptoms, and neurologic manifestations (15). The diagnosis may be difficult because of nonspecific symptoms such as fatigue, anorexia, weakness, and visual changes. Laboratory findings include anemia, hypercalcemia, and electrolyte abnormalities. Measurement of the serum viscosity is diagnostic. Treatment includes rehydration with diuresis, phlebotomy, and emergent plasmapheresis.

REFERENCES 1. Fahey JL, Werner FB, Solomon A. Serum hyperviscosity syndrome. JAMA 1965;192:120 –3.

26 2. Patterson WP, Caldwell CW, Doll DC. Hyperviscosity syndromes and coagulopathies. Semin Oncol 1990;17:210 – 6. 3. Bloch JK, Maki DG. Hyperviscosity syndromes associated with immunoglobulin abnormalities. Semin Hematol 1973;10:113–24. 4. Hayasaka S, Ugomori S, Kodama T, Noda S, Setogawa T. Central retinal vein occlusion in two patients with immunoglobulin G multiple myeloma associated with blood hyperviscosity. Ann Ophthalmol 1993;25:191– 4. 5. Enzenauer RW, Brozetti JJ, Dragoo RA. Central retinal vein occlusion in a patient with IgG lambda monoclonal gammopathy. Arch Ophthalmol 1999;117:134 –5. 6. Carter PW, Cohen HJ, Crawford J. Hyperviscosity syndrome in association with kappa light chain myeloma. Am J Med 1989;86: 591–5. 7. Phillips MJ. Plasma and whole blood viscosity. Br J Haematol 1976;34:347–51. 8. Friedman AH. Ocular manifestations of hematologic disorders. Hosp Pract 1984;19:131–9. 9. Robinson MK, Halpern JI. Retinal vein occlusion. Am Fam Physician 1992;45:2661– 6.

C. C. Chiang et al. 10. Godal HC, Borchgrevink CF. The effect of plasmapheresis on the hemostatic function in patients with macroglobulinemia Waldenstrom and multiple myeloma. Scand J Clin Lab Invest 1965: 17(Suppl 84):134 – 6. 11. Kyle RA. Multiple myeloma: a review of 869 cases. Mayo Clin Proc 1975;50:29 –39. 12. Pollack CV. Medical etiologies of altered mental status. Top Emerg Med 1991;13:54 – 68. 13. Avnstorp C, Nielsen H, Drachman O, Hippe E. Plasmapheresis in hyperviscosity syndrome. Acta Med Scand 1991;217:133–37. 14. Dequeker J, Walravens M, Leys A, Pieters R. Arteritis associated with hyperviscosity-like syndrome in rheumatoid arthritis, treated by intermittent plasma-exchange for 2.5 years. Rheumatol Rehabil 1981;20:203–7. 15. Crawford J, Edwin CB, Harvey JC. Evaluation of hyperviscosity in monoclonal gammopathies. Am J Med 1985;79:13–21. 16. Case Records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 13–1994. A 62-year-old man with epistaxis, confusion, renal failure, and bilateral central retinal vein thrombosis. N Engl J Med 1994;330:920 –7.