BRIEF REPORT

CHRONIC MONOCYTIC ARTHRITIS

DAVID GEORGE, SUSAN HOCH, EVAN COHEN, FRED KANTROWITZ, and MICHAEL WEINBLATT

A predominance of monocyte-derived cells in inflammatory synovial fluid has been described in patients with self-limited arthritides such as viral ar- thritis (1-3) and serum sickness (4). These patients generally experienced an acute, rapidly resolving ill- ness. It has been suggested that the presence of a monocyte-predominant inflammatory synovial fluid may be predictive of a self-limited process (5). We report a case of a patient with a persistent monocytic arthritis in association with a chronic rheumatic ill- ness.

Case report. A 27-year-old Puerto Rican-born man experienced 2 months of fever, weight loss, skin rash, and symmetric polyarthritis. He denied sore throat, cough, diarrhea, drug exposure, or recent travel. There was no history of sicca syndrome or Raynaud's phenomenon. The patient had been seen at another hospital 1 month after onset of his illness. At that time a left knee aspiration revealed a white blood cell count of 52,800 cells/mm3 with a differential of 88% monocytes. No therapy was instituted, and the illness persisted.

Two months after onset of illness he was seen at our institution because of increasing fatigue, fever, and arthritis. He had a temperature of 102"F, a malar

From the Department of Rheumatology and Immunology, Beth Israel and Brigham and Women's Hospitals, Harvard Medical School, Boston, Massachusetts.

Supported in part by NIH grants AM1 1414 and A05577. David George, MD: Clinical Fellow in Medicine; Susan

Hoch, MD: Instructor in Medicine; Evan Cohen, MD: Medical Resident; Fred Kantrowitz, MD: Assistant Professor of Medicine; Michael Weinblatt, MD: Assistant Professor of Medicine.

Address reprint requests to Michael Weinblatt, MD, Beth Israel Hospital, 330 Brookline Avenue, Boston, MA 02215.

Submitted for publication July 12, 1982; accepted in revised form November 9. 1982.

rash, and periorbital erythema and swelling. There was diffuse erythema, as well as indurated hypopig- mented plaques over sun exposed areas of the chest. Erythema and hyperpigmentation were present over extensor surfaces of the elbows and metacarpal joints. There was generalized lymphadenopathy and active synovitis of peripheral joints.

The hematocrit was 44% and the leukocyte count was 3,500 cells/mm3, with a normal differential. Results of platelet count and coagulation studies were normal. Serum chemistry values included glutamic oxaloacetic transaminase 131 unitslliter, serum glu- tamic pyruvic transaminase 177 unitdliter, creatine phosphokinase 250 unitdliter, and normal renal func- tion. Urinalysis results were normal. Blood cultures and titers for selected viruses were negative. Immuno- logic findings included normal total hemolytic comple- ment, complement components C2-C4, rapid plasma reagin, and negative antinuclear antibody (ANA). Rheumatoid factor was positive at a titer of 1 : 640, and the anti-Ro antibody was positive. Hand and knee radiographs showed only soft tissue swelling.

Arthrocentesis of both knees continued to yield inflammatory fluid composed principally of monocytes (Figure 1 and Table 1). The synovial fluid glucose was markedly low on 2 occasions. Total hemolytic comple- ment in the synovial fluid was not dramatically de- pressed. Identification of the cells is described below. Synovial biopsy of the left knee showed a diffuse fibrin exudate on the synovial surface with areas denuded of synovial lining cells. There was no synovial prolifera- tion or cellular infiltrate. The capillary and venular walls showed edema and degeneration, but no fibri- noid necrosis. Immunofluorescence was negative and electron microscopy showed synoviocyte degenera-

Arthritis and Rheumatism, Vol. 26, No. 5 (May 1983)

BRIEF REPORTS 675

Figure 1. Wright’s stain of synovial fluid, showing abundance of macrophages (original magnification X 800).

Figure 2. Nonspecific esterase stain of synovial fluid (original mzp- nification x 320).

tion, vascular thrombosis, and some loss of capillary endothelium. Skin biopsies of lesions on the face and extensor surface of the elbow showed penvascular lymphocytic infiltration with negative immunofluores- cence. Lymph node and bone marrow biopsies were consistent with a reactive process, and deltoid muscle biopsy was normal.

The patient was believed to have a systemic rheumatic disease most consistent with systemic lupus erythematosus. He was treated with antimalarials, nonsteroidal antiinflammatory drugs, topical cortico- steroids, and low dose prednisone. Four months after the start of this regimen the rash and polyarthritis remain, but are improved. Monocytosis in the synovial fluid, however, persists.

Materials and methods. ANA testing was per- formed by a standard immunofluorescence technique using mouse liver. Precipitating antibodies for the cytoplasmic antigen, Ro, were detected by a double immunodiffusion technique.

Synovial fluid cells (SFC) were washed 3 times in Earl’s Balanced Salt Solution (Flow Laboratories, McLean, VA) and resuspended to a concentration of 5

x lo6 cells/ml in RPMI 1640 supplemented with 10% heat inactivated AB serum. Studies of cell morpholo- gy, enzymes, and presence of Fc and C3 receptors were performed. Aliquots of cell suspension were spread on glass slides, air dried and stained with Wright’s stain, and for peroxidase (6) and nonspecific esterase (7). SFC were layered onto cover glasses and incubated for 1 hour in a 37°C C02 incubator. They were then overlaid with suspensions of IgG-coated (EA) or IgM and complement-coated (EAC) sheep erythrocytes prepared as previously described (8). The SFC were incubated with red cell suspensions for an additional hour. They were then washed and fixed in 1.25% glutaraldehyde in phosphate buffered saline for assessment of Fc and C3 receptors under phase mi- croscopy.

Frozen sections of rheumatoid synovium were stained for nonspecific esterase and peroxidase (9).

Results. Synovial fluid cells were evaluated for morphologic appearance, phagocytic properties, histo- chemical staining, and rosette formation. On Wright’s stain examination (Figure 1) the cells of interest were typically large (12-15p) and highly vacuolated, with

Table 1.

Duration of

Results of synovial fluid analyses*

illness Amount WBC PMN L Mon Mac Glucose? Protein CH5Ot (months) Source (cc) (ceils/mrn’) (%) (%) (%) (%) (mg/dl) (gmldl) (unitslml)

~ - - 1 Left knee 52,800 8% - - - 2 Left knee 30 18,600 1 2 4 87 18/80 5.7 9 1 I228 2 Left knee 20 21,750 2 5 4 89 18/14 5.9 2% Left knee 20 16.200 2 8 29 61 39/86 4.0 7912 1 3 2% Right knee 5 3,500 7 1 1 82$ 39/86 6.0 6912 13 4 Left knee 0.5 1 5 23 71 - - - -

* WBC = white blood count; PMN = polymorphonuclear leukocytes; L = lymphocytes; Mon = monocytes; Mac = macrophages. t Glucose and CH5O results listed as synovial fluid valueslblood values. $ Monocytes and macrophages not distinguished on these analyses.

676 BRIEF REPORTS

abundant blue-gray cytoplasm. Distinction of mono- cytes and monocyte-derived macrophages (Table 1) was made on the basis of vacuolization and size. Nuclei were large, oval, and pale blue-violet in color. Violet and pink staining material was present in the vacuoles of a number of cells. Further evidence that these cells were phagocytic was derived from the observation that they ingested IgG-coated red blood cells. In addition to the presence of Fc receptors, C3 receptors were present on these cells, as determined by their ability to form EAC-rosettes. Greater than 90% of the synovial fluid cells stained positive with nonspecific esterase (Figure 2) and peroxidase. These findings confirm that the majority of synovial fluid cells belonged to the monocyte series.

The esterase and peroxidase stains were also performed on rheumatoid synovium. The majority of synovial lining cells were esterase and peroxidase negative.

Discussion. Polymorphonuclear leukocytes and lymphocytes are usually the predominant cell types in inflammatory joint effusions. Synovial analysis find- ings of greater than 50% monocyte-like cells may occasionally be seen in noninflammatory effusions in scleroderma (10) and sickle cell disease (1 1). Howev- er, it is distinctly uncommon to have a predominance of monocytes in more inflammatory synovial fluids. Ropes and Bauer (12) reported fluid analyses in rheu- matic fever and Reiter’s syndrome, in which monocyt- oid cells were transiently as high as 68% of 2,600 cells/mm3 and 71% of 2,250 cells/mm3, respectively. Synovial fluid monocytosis has been reported in some cases of serum sickness (4), and certain viral infections including hepatitis B (l), rubella (2), and arbovirus A (3). Brawer and Cathcart (5) described 5 patients with fever, skin rash, transient polyarthritis, and synovial fluid monocytosis. All symptoms and signs resolved within 4 weeks. Although a viral etiology seemed most likely, viral cultures and titers were negative. The authors suggested that synovial fluid monocytosis might be helpful on a prognostic basis, suggesting a self-limited illness.

This is the first report of documented mono- cyte-predominant arthritis in a patient with a chronic

features of the illness, as described by Maddeson (14). However, the presence of periorbital erythema and rash on extensor surfaces emphasizes the overlap nature of our patient’s illness.

Characteristic morphology, histochemical staining, EA- and EAC-rosette formation, and phago- cytosis proved that the majority of synovial fluid cells were monocytic in nature. Absence of synovial lining cells on the patient’s synovial biopsy precluded paral- lel histochemical studies on that tissue. However, esterase and peroxidase staining performed on rheu- matoid synovium was generally negative, as previous- ly reported by Theofilopoulos (9). Therefore, it is unlikely that the cells described are dissociated phago- cytic synovial lining cells. Persistence of monocytosis for over 4 months argues against a concurrent typical viral illnesses.

Synovial fluid glucose has only rarely been recorded (1 1) in monocyte-predominant arthritis, and was normal in those 2 cases. An impressive depression of synovial fluid glucose is noted here. Synovial biop- sy showed diminished synovial lining cells, some endothelial degeneration, and minimal inflammation, in marked contrast to the inflammatory joint fluid. Such biopsy findings are, however, nonspecific, and similar biopsies have been described in scleroderma (lo), lupus (15), and dermatomyositis (16).

The present case of documented monocytic arthritis in a patient with a chronic rheumatic illness emphasizes that monocytic arthritis does not define a disease entity and, in itself, is not of prognostic value. The stimulus for an absolute monocyte count as high as 46,000/mm3 in the present case, as well as the somewhat lower counts in other cases of monocytic arthritis, is not apparent. That the differential count was maintained shows that the stimulus or unusual host response need not be only transient, and may be present for months.

Acknowledgments. The authors would like to thank Dr. M. Reichlin who performed the anti-Ro antibody assay, and Dr. M. Corson for his assistance in the preparation of this paper.

REFERENCES rheumatic illness. He fulfilled 3 criteria for systemic lupus erythematosus (13): leukopenia, polyarthritis,

on multiple occasions, but the rheumatoid factor and anti-Ro antibody were positive. Our patient is similar to those with ANA-negative lupus in whom systemic symptoms and photosensitive dermatitis are major

1. Onion D, Crumpacker C, Gilliland B: Arthritis of hepati- tis associated with Australia antigen. Ann Intern Med

2. Chambers R, Bywaters E: Rubella synovitis. Ann Rheum Dis 22:263-268, 1963

3. Clarris B, Doherty R, Fraser J , French E, Muirden K: Epidemic polyarthritis: a cytochemical, virological and

and a photosensitive skin rash. The ANA was negative 75:29-33, 1971

BRIEF REPORTS

4.

5.

6.

7.

8.

9.

10.

immunochemical study. Aust NZ J Med 5(5):450-457, 1975 Boots R, Swift H: The arthritis of serum sickness.

Brawer AE, Cathcart ES: Acute monocytic arthritis. Arthritis Rheum 22:294-300, 1979 Kaplow LS: Simplified myeloperoxidase stain using benzidine hydrochloride. Blood 26:215-219, 1%5 Tucker SB, Pierre R, Jordan R: Rapid identification of monocytes in a mixed mononuclear cell preparation. J Immunol Methods 14:267-269, 1977 Hoch S, Schur PH: Monocyte receptor function in patients with rheumatoid arthritis. Arthritis Rheum

Theofilopoulos AN, Carson DA, Tavassoli M, Slavin SF, Speers WC, Jensen FB, Vaughan JH: Evidence for the presence of receptors for C3 and IgG Fc on human synovial cells. Arthritis Rheum 23: 1-9, 1980 Schumacher HR: Joint involvement in progressive sys- temic sclerosis. Am J Clin Pathol 60593-600. 1973

JAMA 80~12-15, 1923

2411268-1277, 1981

11.

12.

13.

14.

15.

16.

677

Schumacher HR: Arthropathy of sickle cell disease. Ann Intern Med 78:203-211, 1973 Ropes M, Bauer W: Synovial Fluid Changes in Joint Disease. Cambridge, Harvard University Press, 1953, p 25 Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Tala1 N, Winchester RJ: The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25: 1271-1277, 1982 Maddeson P, Provost T, Reichlin M: Serological find- ings in patients with “ANA-negative” systemic lupus erythematosus. Medicine 60:87-94, 1981 Cruickshank B: Lesions of joints and tendon sheaths in systemic lupus erythematosus. Ann Rheum Dis 18: 11 1- 129, 1959 Schumacher HR, Schimmer H, Gordon G , Bookspan M, Brogadir S, Dorwart B: Articular manifestations of polymyositis-dermatomyositis. Am J Med 67:287-292, 1979