LETTERS

Letters that report new clinical or laboratory observations, cases of unusual importance, and new developments in medical care will be considered for publication in this section. Manuscripts must be typed double-spaced. Text length must not exceed 750 words; no more than five references and one figure or table can be used. See "Information for Authors" on page 1-6 for form of references. Manuscripts should include an abstract of length not exceeding 100 words. Letters will be reviewed by consultants when, in the opinion of the editors, such review is needed. The Editor reserves the right to shorten letters and to make changes that accord with our style. Veillonella parvula Septicemia and Osteomyelitis IN THE PAST DECADE there has been much interest in the significance and role that nonsporulating anaerobes have in.various types of clinical infections. Implicating these bacteria as pathogens in most septic conditions is impossible without first demonstrating them in vitro ( 1 ) . Whereas a diversity of soft-tissue infections involves anaerobes, these bacteria are neither common pathogens in osteomyelitis nor in pyogenic arthritis ( 2 ) . This is the first case report of osteomyelitis involving the Gram-negative anaerobic coccus Veillonella parvula. A 54-year-old diabetic Indian woman attempted to shave a callus on the ball of her right foot, which subsequently became infected. The site had drained an odorless pus for approximately 2 months. The patient was admitted with a diagnosis of cellulitis and

treated with dicloxacillin, 250 mg four times a day. Admission medication included acetohexamide, 500 mg twice daily; liothyronine sodium, three times daily; conjugated estrogen, 1.25 mg daily; and amitriptyline HC1, 50 mg orally, twice daily. At physical examination, the woman was obese, afebrile, and in mild distress. Except for the slightly edematous right foot (Figure \a), physical examination findings were unremarkable. After initial cultures of the wound were positive for Escherichia coli and Streptococcus faecalis, dicloxacillin therapy was discontinued, and 80 mg of gentamicin four times daily was substituted. The wound was incised and drained, manually debrided daily, irrigated with peroxide solution, and then packed with iodoform gauze. Wound cultures taken 9 days after admission showed E. coli, S. faecalis, Proteus vulgaris, and Proteus morganii. Although the ulcer appeared to be healing, edema persisted on the dorsum of the right foot. Fourteen days after admission the patient spiked a temperature to 39.4 °C [103 °F] orally and experienced a shaking chill. After blood cultures were obtained, the gentamicin dosage was increased to 135 mg every 8 h intravenously, and penicillin G therapy, one million units intravenously every 4 h, was begun. Three days later the gentamicin dosage was decreased to 80 mg three times daily. Blood cultures were positive in 5 days for V. parvula. The organism was identified by methods suggested by The Center for Disease Control, Atlanta, Georgia (3), and subsequently confirmed by their Anaerobe Laboratory. Even though the patient was afebrile and appeared to be improving, another X ray (Figure 16) taken after the febrile episode showed some periosteal reaction. Orthopedic consultation recommended radical surgical treatment. Wound cultures 2 days before surgery showed V. parvula and P. morganii. An X ray of the foot taken before surgery is shown in Figure \c. Thirty-two days after admission, incision and debridement of the right foot, with excision of the proximal third phalanx

Figure l a . At admission. Shows neither evidence of bone injury nor pathologic change, b. Fourteen days after admission. Shows destruction of the proximal aspect of the proximal phalanx of the third toe, with some destruction of the head of the third metatarsal. C. Before surgery. Shows further resorption of the proximal two thirds of the proximal phalanx of the third toe along the great toe side. There is resorption of the adjacent distal end of the third metatarsal along its great toe side. Letters

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and the head of the third metatarsal, were done under general anesthesia. Cultures from excised tissue grew V. parvula, E. coli, and P. morganii. Intravenous antibiotics were continued for a 4-week period during which the patient remained afebrile. The patient was fitted with a special orthopedic shoe, which removed weight-bearing from the area of incision and debridement. At hospital discharge she had no evidence of local or systemic infection, and she is well 1 year later. Veillonella species represent part of the normal flora of the mouth, vagina, urine, and distal portion of the alimentary tract of some persons. The pathogenic role of Veillonella species is nebulous, although V. parvula has been isolated in pure culture from a 60-year-old male patient with a liver abscess discovered at laparotomy for resection of adenocarcinoma of the colon ( 4 ) . There has been a dearth of previously reported cases of anaerobic osteomyelitis. In a study of 247 patients, anaerobic bacteria were involved in five ( 2 ) . In another study of 82 patients, seven were positive for anaerobes ( 5 ) . Ziment, Miller, and Finegold (6) recovered nonsporulating anaerobic bacteria from 17 patients with osteomyelitis, and except for one patient the infections were polymicrobic. Bacteroides melaninogenicus and Bacteroides fragilis were isolated most frequently. Eight patients had foot infections, and seven were diabetic. Anaerobic bacteria commonly complicate diabetic gangrene, and our patient may have been similarly predisposed to anaerobic infection at other sites because of diabetes mellitus. The septic episode while the patient was receiving an aminoglycoside antibiotic was an important indicator of possible anaerobic infection. The importance of a Gram's stain must be remembered in anaerobic infections. It can be difficult to visualize the different organisms microscopically in a polymicrobic infection. This shows the importance of requesting appropriate anaerobic wound and blood cultures. Additionally, it is important that clinicians be cognizant of the methods necessary for obtaining and transporting specimens for anaerobic culture. This paper was presented in part at the 13th International Conference in Internal Medicine, Helsinki, Finland, 18 August 1976. K E N N E T H A. BORCHARDT, PH.D. MICHAEL BAKER, M.D. ROBERT GELBER, M.D.

U.S. Public Health Service Hospital 15th and Lake Streets San Francisco, CA 94118 Received 28 June J 976. REFERENCES 1. GORBACH SL, BARTLETT JG: Anaerobic infections. N Engl J Med

290:1177-1184, 1974 2. WALDVOGEL FA, MEDOFF G, SWARTZ MN: Osteomyelitis: a review

of clinical features, therapeutic considerations and unusual aspects. N Engl J Med 282:198-206, 1970 3. DOWELL VR, HAWKINS TM: Laboratory Methods In Anaerobic

Bacteriology. CDC Laboratory Disease Control, 1974, p. 34

Manual. Atlanta, Center for

4. LAMBE DW, DEL BEVE VE: The incidence and clinical significance

of anaerobic cocci in certain infections. Presented at the 72nd Annual Meeting of the American Society for Microbiology, 23-28 April 1972, Philadelphia 5. KELLY PJ, WILOWSKE CJ, WASHINGTON J A II: Comparison of

gram-negative bacillary and staphylococcal osteomyelitis of the femur and tibia. Clin Orthop 96:70-75, 1973 6. ZIMENT I, MILLER LG, FINEGOLD SM: Nonsporulating anaerobic

bacteria in osteomyelitis. Antimicrob Agents Chemother 7:77-85, 1968 54

Anti-Cephalothin Antibody and Coombs'-Positive Hemolytic Anemia CEPHALOTHIN THERAPY is associated with a positive direct

antiglobulin test in 3 % to 6 5 % of patients receiving this drug (1, 2 ) . Most often the responsible mechanism is nonimmune adsorption of serum proteins to cephalothinexposed erythrocytes ( 3 ) . Cephalothin-related hemolysis has been reported and is associated with specific anticephalothin antibodies (4, 5 ) . We describe here a case of cephalothin-related Coombs' positive hemolytic anemia in which IgG antibody has been identified in the patient's serum and on erythrocytes. A 64-year-old white man was admitted to Thomas Jefferson University Hospital on 3 August 1975, for evaluation of chills and fever. He gave a history of hypernephroma treated by surgery and radiation and without evidence of recurrence. He denied drug allergies. He had a temperature of 38.3 °C and mild left lower quadrant tenderness. His hemoglobin concentration was 11.0 g/dl; hematocrit, 33%; and leukocyte count, 10 500/mm3. Blood urea nitrogen, creatinine, and urinalysis findings were normal. After appropriate cultures were obtained, therapy with intravenous ampicillin, 2 g daily, was started. On the second hospital day his temperature was 40 °C. Two separate blood cultures grew Staphylococcus aureus sensitive to nafcillin and cephalothin. Therapy was changed to intravenous nafcillin, 2 g every 4 h. No source for the bacteremia was found. By the fifteenth day all cultures were negative. His hemoglobin concentration was 9.8 g/dl. The persistent fever suggested the possibility of drug fever. Nafcillin therapy was stopped, and cephalothin, 2 g every 6 h, and gentamicin, 60 mg every 8 h, were started. On the twenty-first day his hemoglobin concentration was 9.5 g/dl, and erythrocyte polychromatophilia was noted on peripheral blood smears. The Reticulocytes were 6%. Within 72 h his hemoglobin level dropped from 9.5 to 7.0 g/dl, and the reticulocytes increased to 12%. The direct Coombs' test became positive. Total bilirubin concentration was 2.2 mg/dl (indirect, 1.5). Urine and stools were negative for blood. Cephalothin therapy was stopped and nafcillin restarted. His hemoglobin concentration gradually increased to 9.5g/dl, and reticulocytes decreased to 4%. The direct Coombs' test became negative on the thirtieth hospital day. The patient was discharged on the thirty-fifth day with a hemoglobin value of lOg/dl and reticulocytes of 2%. In-vitro testing of the patient's erythrocytes, serum, and eluate from erythrocytes was done. Type O penicillin-coated cells and cephalothin-coated cells were prepared by the method of Spath, Garratty, and Petz (2). The patient's sera and normal sera were tested for anti-cephalothin activity and anti-penicillin activity as outlined by Gralnick and associates (4). Adsorption studies were done and eluates prepared by Gralnick's method (4). Aliquots of serum were mixed with monospecific anti-IgM and anti-IgG, and, after centrifugation, the supernatants were used for testing. Direct antiglobulin tests were performed with monospecific anti-IgG and anticomplement Coombs' sera (Behring Diagnostics, Department of Hoechst Pharmaceuticals, Inc., Somerville, New Jersey). Only sera monospecific for anti-IgG caused agglutination. The indirect antiglobulin test using normal donor erythrocytes was negative, and the patient's serum, when tested against a panel for all common blood group systems, did not show a specific alloantibody. Normal donor erythrocytes tested with the patient's serum and eluate did not agglutinate. However, when normal donor erythrocytes were pretreated with cephalothin and retested with eluates from the patient's erythrocytes or serum, the antiglobulin test was positive. The

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eluate lost its agglutinating activity against cephalothincoated normal erythrocytes when absorbed beforehand by incubation with cephalothin-coated cells. The patient's serum agglutinated penicillin-coated and cephalothin-coated cells. Serum titers were 1:64 for penicillin-coated erythrocytes and 1:128 for cephalothincoated erythrocytes. Inhibition of agglutination by absorption of sera with antibiotic-coated cells showed that the anti-penicillin and anti-cephalothin antibodies were two distinct molecules (Table 1). Agglutination activity against antibiotic-coated cells of either type was also removed by incubating serum with monospecific anti-IgG but not with anti-IgM. These data are consistent with an immune hemolytic state induced by cephalothin therapy. The patient had received nafcillin and cephalothin, but the evidence of a hemolytic state was related in time to administration of cephalothin. Discontinuance of cephalothin therapy led to prompt recovery, even though nafcillin treatment was reinstituted. The in-vitro data identified anti-cephalothin antibodies in the patient's serum. Eluate studies from the patient's erythrocytes showed in-vivo attachment of anti-cephalothin antibodies to the patient's erythrocytes. The coexistant anti-penicillin and anti-cephalothin antibodies were two specific molecules without cross-reactivity (Table 1). The anti-cephalothin antibody was the IgG type, as in previous reports of cephalothin-induced hemolytic anemia (4, 5 ) . Cephalothin can cause positive direct antiglobulin tests, without hemolysis, by altering erythrocyte membrane proteins, which results in nonimmune adsorption of plasma proteins ( 3 ) . High dosage and renal impairment have been cited as predisposing factors in this process ( 1 ) , but our patient had no renal impairment and received cephalothin dosages that were not excessive. This report indicates that cephalothin also can induce an immune hemolysis similar to that which occurs with penicillin ( 3 ) ; it may occur in the presence of normal renal function with nonexcessive doses of drug. This paper was supported in part by NIH Program Project Grant H6374 and NIH Training Grant. RONALD N. RUBIN, M.D. EDWARD R. BURKA, M.D.

Cardeza Foundation for Hematologic Research Thomas Jefferson University Hospital 1015 Walnut Street Philadelphia, PA 19107 Received 16 July 1976. Table 1. Agglutination < 3f Antibiotic-TretJted Erythrocytes by Patient's Absorbed Serum Patient's Serum Absorbed With

Normal Erythrocytes

Antiglobulin Test Against PenicillinCephalothinCoated Coated Erythrocytes Erythrocytes

Normal erythrocytes Penicillin-treated erythrocytes Cephaloth in-treated erythrocytes Anti-IgG Anti-IgM

Negative

1:64

1:128

Negative

Negative

1:128

Negative Negative Negative

1:32

Negative Negative 1:128

REFERENCES

1. MOLTHAN

L, REIDENBERG

M, EICHMAN

M F : Positive

2. SPATH P, GARRATTY G, PETZ LD: Studies on the immune response

to penicillin and cephalothin in humans. II. Immunohematologic reactions to cephalothin administration. J Immunol 107:860-869, 1971 3. GARRATTY G, PETZ LD: Drug-induced hemolytic anemia. Am J Med 58:398-407, 1975 4. GRALNICK HR, MCGINNISS M, ELTON W, et al: Hemolytic anemia

associated with cephalothin. JAMA 217:1193-1197, 1971 5. JEANNET M, DAYER JM, FARQUET JJ, et al: Cephalothin-induced

immune hemolytic anemia. Acta Haematol (Basel) 55:109-117, 1976

Amylase/Creatinine Clearance Fraction in Patients on Chronic Hemodialysis THE IMPORTANCE of the amylase/creatinine clearance fraction (Cam/Ccr) in differentiating acute pancreatitis from the hyperamylasemia of renal failure was first shown in 1969 by Levitt, Rapoport, and Cooperbrand ( 1 ) . The specificity of this ratio in acute pancreatitis was recently documented by Warshaw and Fuller ( 2 ) . However, there have been other studies suggesting an increased Cam/Ccr in situations other than acute pancreatitis, such as diabetic ketoacidosis or extensive burns ( 3 ) . Because Levitt's paper (1) used patients with mild renal failure, we elected to ascertain the extent to which the Cam/Ccr would apply in patients on chronic hemodialysis with severe renal failure. Reports of elevated serum amylase in dialysis patients have been docmented ( 4 ) , but we could find no description of the clearance fraction in these patients. Eight outpatients on chronic hemodialysis were chosen from the Dialysis Unit at Thomas Jefferson University Hospital. The only criterion for inclusion in the study was a measurable urine output during the time period chosen. There was no clinical evidence of pancreatitis in any of the patients studied. The cause of renal failure included pyelonephritis (2), nephrosclerosis (1), chronic glomerulonephritis (4), and systemic lupus erythematosus (1). Although pancreatitis can be seen in lupus erythematosus, this latter patient's disease had been in remission for years and she was not receiving steroid medication. None of the patients was receiving any medication (such as opiates or diuretics) that are associated with pancreatitis, and none had chronic alcoholism or hypercalcemia. Amylase values were measured by a modification of the starch-iodide method and creatinine measurements were made with the picric acid technique. The serum levels reflected a mean of a postdialysis measurement and a repeat test 48 to 72 h later, at the start of the next dialysis. The patients voided at the end of dialysis and then saved all subsequent urine until the next dialysis. The control patients were chosen from our staff and had no evidence of renal or pancreatic disease. Twohour clearances were done in the controls by the method of Levitt (1). The results are listed in Table 1. As can be seen, the geometric mean of the Cam/Ccr in the dialysis patients was greater than in the control subjects. This was statistically significant at a P value of less than 0.02. The results for patients on dialysis were also well above the normal ratios defined by both Levitt and Warshaw and associates ( 1 , 2 ) , whereas the clearance fractions of the control patients were within their normal range. Amylase is a protein of such dimensions (molecular weight, 50 000) that glomerular filtration should be limited. Accordingly, most theories about the increased amylase clearance in pancreatitis have concerned themselves with Letters

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direct

Coombs tests due to cephalothin. N Engl J Med 277:123-125, 1967

65

Table 1 . Findings in Asymptomatic Patients on Hemodialysis and Normal Subjects* Serum an .

Serum cr

Ccrf

Cam/Ccr

Urine Output

U/dl

mg/dl

ml/min

%

ml 24/h

Patients 10.4 258 0.8 1 10.2 2 367 0.07 4.9 3 137 6.4 136 8.4 3.7 4 9.2 5 317 1.8 6 13.5 0.22 150 7 11.3 0.47 450 9.0 0.71 8 245 Arithmetic 9.8 mean 1.22 257.5 Geometric mean (after log transformation) Normal subjects 0.7 1 78 0.9 2 35 3 55 1.1 0.7 4 50 0.8 5 125 Arithmetic 68.6 0.84 mean Geometric mean

7.7 8.1 7.2 5.9 3.4 13.2 7.2 30.1

360 15 400 670 263 35 88 90

10.35 8.40

239

2.7 4.7 4.3 5.2 2.3 3.84 3.60

* Cam = amylase clearance; Ccr = creatinine clearance. t Clearances done on 48-h samples on Patients 1, 2, 5, 6, and 8 and on 72-h samples on Patients 3, 4, and 7.

either circulating small molecular weight species of amylase that are more easily cleared, or an increased glomerular permeability in pancreatitis ( 2 ) . However, there is evidence that the increased clearance may relate to increased tubular rejection of normally filtered amylase ( 5 ) . If the intact nephron theory is operative in chronic renal failure, there should be higher filtered loads of amylase per functioning nephron. This should lead to an increased rejection fraction of amylase per tubule. Our findings could, therefore, support the tubular rejection theory of increased amylase clearance. Although speculative, this idea could be tested in experimentally uremic animal preparations, using standard clearance and micropuncture techniques with substances that are similar to amylase, but known to be handled primarily by either glomerular filtration or tubular reabsorption. We have also studied one separate patient on dialysis whose urine output was enough to permit sequential clearances during 8-h periods between dialyses. Six consecutive 8-h clearances of amylase and creatinine were done during a 48-h period between two dialyses. The Cam/Ccr rose from 8.7% to 12.5%. When analyzed separately, it was found that both the amylase and creatinine clearances rose progressively between dialyses, but the rise in amylase was greater than that for creatinine, (0.06 to 0.17 ml/min for amylase and 0.69 to 1.36 ml/min for creatinine). This could be expected because clearances should be lower in the volume-contracted state postdialysis and would tend to rise to their maximum as volume expansion progressed up to the next dialysis. Whatever the mechanism of increased clearance, certain points are worthy of emphasis. Although patients with mild renal failure have a normal Cam/Ccr, asymptomatic patients on hemodialysis clearly have an abnormally elevated clearance fraction. There would be no need to treat an asymptomatic patient on dialysis simply on the 55

basis of an increased clearance fraction. We realize that the diagnosis of pancreatitis can be very difficult, requiring surgical confirmation in some cases. However, our findings are consistent enough to suggest that our patients do not have asymptomatic pancreatitis, but, rather, that chronic hemodialysis represents another situation in which an elevated Cam/Ccr is not diagnostic of pancreatitis. CHARLES F. SCHIFFER, M.D. JAMES F. BURKE, JR., M.D. ANATOLE BESARAB, M.D. NORMAN LASKER, M.D., F.A.C.P. MICHAEL L. SIMENHOFF, M.D., M.R.C.P.

Dialysis Unit Thomas Jefferson University Hospital 11th and Walnut Streets Philadelphia, PA 19107 REFERENCES 1. LEVITT MD, RAPOPORT M, COOPERBAND SR: The renal clearance of amylase in renal insufficiency, acute pancreatitis, and macroamylasemia. Ann Intern Med 71:919-925, 1969 2. WARSHAW AL, FULLER AF JR: Specificity of increased renal clearance of amylase in diagnosis of acute pancreatitis. N Engl J Med 292:325-328, 1975 3. LEVINE RI, GLAUSER FL, BERK JE: Enhancement of the amylasecreatinine clearance ratio in disorders other than acute pancreatitis. N Engl J Med 292:329-332, 1975 4. SCHONEBECK J, SODERBERG M: Serum amylase in renal failure. Scand J Urol Nephrol 5:257-262, 1971 5. FREDRIKSSON A, JACOBSON G: Influence of renal function on the urinary excretion of amylase. Scand J Clin Lab Invest 33:313-321, 1974

Absence of Increased Frequency of Bone and Joint Disease with Hemoglobin AS and AC BONE AND JOINT DISEASE with hemoglobin SS, hemoglobin

SC, and S-thalassemia has been well documented and includes aseptic necrosis, medullary bone infarcts, periostitis, and articular involvement ( 1 ) . In sickle cell trait (hemoglobin AS) sporadic cases ot aseptic necrosis have been reported ( 2 ) . No studies of the prevalence of joint abnormalities in sickle trait compared with age-matched controls having AA hemoglobin have, however, been published. We report on such a study of 94 patients with hemoglobin AS, 20 with hemoglobin AC, and 114 controls with normal AA hemoglobin. All black patients admitted to the Philadelphia Veterans Administration Hospital for 15 months through December 1975, who had AS or AC hemoglobin, and inpatient control subjects, who had AA hemoglobin by cellulose acetate electrophoresis, were examined for rheumatic signs and symptoms. Rheumatologists evaluating the patients were unaware of the hemoglobin type. Of the 114 cases with AS or AC hemoglobin, clinical data were obtained from the hospital chart in 19 (17, AS and two, AC) instead of by direct examination by the authors. In patients with joint abnormalities or rheumatic complaints during hospitalization, the following were done when appropriate: joint aspiration with analysis of synovial fluid including compensated polarized microscopy, X rays of symptomatic joints, rheumatoid factor, antinuclear antibody, lupus erythematosus preps, erythrocyte sedimentation rate, serum uric acid, and bone scans. Raytheon rectilinear scans were done in 12 patients and five controls using 15 mCi of technetium polyphosphate (",JmTc PP) (3). Frequency among controls and hemoglobinopathy groups of occupations requiring heavy labor (construction, truck loaders) or less exertion (clerks, domestic workers, painters), as well as alcohol consumption, was similar.

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All findings were tested for statistical significance by exact probabilistic calculation, a test applied in the same situations as the Chi square test but valid for small samples such as ours. Findings are summarized in Table 1. There were no statistically significant differences in joint complaints when control subjects were compared with patients with hemoglobin AS or AC or to the total number with AS and AC hemoglobin. Several rheumatic diseases were noted in both groups without apparent relation to hemoglobinopathy. Twelve diagnoses of gout (five, AS; two, AC; five, AA) were documented by identifying monosodium urate crystals in synovial fluid or by classical podagra coupled with characteristic X-ray findings. Other diseases were rheumatoid arthritis (one, AS; one, A A ) , systemic lupus erythematosus (one, A A ) , Reiter's syndrome (one, AS; one, A A ) , ankylosing spondylitis (one, AS), osteoarthritis (five, AS; three, AC; 11, A A ) , traumatic arthritis (two, AS; four, AA) Paget's disease (one, A C ) , amyloidosis (one, AS), multiple myeloma (one, A A ) , osteomyelitis (two, A A ) , frozen shoulder/diabetes (one, AS), and shoulder-hand syndrome (one, A A ) . However, in a number of patients with rheumatic complaints (but normal physical examinations, laboratory tests, and X rays), a definitive diagnosis could not be made. These, subdivided into primary peripheral joint or primary axial pain, are labeled "cause uncertain" in the table. Of special interest were episodes of self-limited joint pain and swelling without antecedent trauma and without residua, reminiscent of those caused by infarcts of bone marrow (3) and synovial membrane (1) in patients with SS and SC disease. Single bouts of such pain and swelling were reported by eight patients in our study with AS hemoglobin, one patient with AC hemoglobin, and by four control subjects. None were witnessed by us. The prevalence of these self-limited symptoms in AS or AC subjects was not significantly different when compared with control subjects. Latex fixation tests, uric acids, X rays, and bone scans provided no clues to pathogenesis. Our only two cases of aseptic necrosis occurred in AC hemoglobin-bearing patients. One, with osteonecrosis of the hip verified at surgery, had imbibed alcohol heavily for 15 years. The other developed pain proximal to an amputation site at the distal ankle; X rays and bone scanning with " m T c PP were consistent with aseptic necrosis of the tibia. No patient had a history of febrile or painful crises typical of homozygous sickle cell disease. X-rays were taken in 24 of 35 symptomatic patients with sickle trait, and in all nine with hemoglobin AC and joint symptoms. None of the radiologic features seen in sickle cell anemia (1) or reported in one series with sickle trait (4) was present. Unlike homozygous sickle (SS) hemoglobin, SC, and S-thalassemia combinations, the presence of sickle trait and AC hemoglobin does not predispose to objectively demonstrable joint disease. Although occasional cases of aseptic necrosis of bone in patients with sickle cell trait have been reported ( 2 ) , our present study fails to document an increased prevalence when compared to a control population. Furthermore, AS or AC hemoglobin does not interfere with the performance of physical labor. Our con-

Table 1. Joint Abnormalities in Patients with Hemoglobins AS, AC, and AA AS Age, yrs Range 20 to 81 Mean 55.3 Patients examined, no. 94 Joint complaints Patients, no. 35 37.2 Patients, % Abnormal joint examination, 19 Patients, no. Type of disease; patients, no. Gout, traumatic, and 17 so forth (see text) Axial pain, cause uncertain 5 Peripheral joint pain, cause uncertain 13

AC

AS and AC

AA

28 to 61 49.3 20

20 to 81 54.5 114

20 to 81 55.3 114

9 45.0

44 38.6

39 34.2

6

25

21

8

25

27

0

5

4

1

14

8

trol subjects and patients with hemoglobinopathy had similar occupations and work records; these findings are similar to those of Murphy (5) among professional football players. The transient episodes of joint swelling that were slightly more prominent in the patients with AS are unexplained. No patient has yet presented during such a bout for study. Ideally our sample should have included a larger number of patients. However, recent termination of the national Veterans Administration hemoglobin-typing program has precluded further study. Because the opportunity to do such a controlled study of consecutive admissions may not again arise, we report the data at this time. Drs. Dorwart and Goldberg served as fellows in rheumatology at the University of Pennsylvania School of Medicine and the Veterans Administration Hospital, Philadelphia, Pennsylvania, while this study was done. BONNIE B. DORWART, M.D., F.A.C.P.

Lankenau Hospital Philadelphia, PA 19151 MARC A. GOLDBERG, M.D. H. RALPH SCHUMACHER, M.D., F.A.C.P. ABASS ALAVI, M.D.

Veterans Administration Hospital Philadelphia, PA 19104 Received 27 May 1976. REFERENCES 1. SCHUMACHER HR, ANDREWS R, MCLAUGHLIN G: Arthropathy in sickle-cell disease. Ann Intern Med 78:203-211, 1973 2. NACHAMIE BA, DORFMAN HD: Ischemic necrosis of bone in sickle cell trait. Mt Sinai J Med NY 41:527-536, 1974 3. ALAVI A, SCHUMACHER HR, DORWART B et al: Bone marrow scan evaluation of arthropathy in sickle cell disorders. Arch Intern Med 136:436-440, 1976 4. BONDZI-SIMPSON BK: Clinical, pathological and radiological features of sickle cell trait. / Trop Med Hyg 65:269-275, 1962 5. MURPHY JR: Sickle cell hemoglobin (Hb AS) in black football players. JAMA 225:981-982, 1973

Letters

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