246 LETTERS

The patient, a 29-year-old black woman, was admit- ted to the hospital in February 1990, because of left wrist pain and swelling of 6 days’ duration. She could not recall having injured the wrist. Three weeks previously, she had undergone laser surgery for cervical dysplasia. Since that time, she had noted a scant vaginal discharge. She was menstruating at the time of admission. She had I sexual partner, and neither she nor her sexual partner had traveled in the preceding 3 months. She was a native of Cleveland, Ohio.

Results of physical examination included tenderness, erythema, and increased warmth over the dorsum of the patient’s left wrist. An effusion was present, and the patient exhibited decreased and painful extension and flexion of the wrist. She had a 5.5 x 2.2-cm raised, warm erythematous lesion on the right medial thigh, approximately 6 cm proxi- mal to the knee joint. Results of examination of the right knee were unremarkable. On pelvic examination, she was markedly tender to palpation of the uterus. Her cervix appeared to be healing well.

Aspiration of the wrist effusion yielded a leukocyte count of 22,5W/mm3, with 95% polymorphonuclear cells. Beta- lactamase-positive N gonorrhoeae grew from the culture of cervical mucosa. No organisms grew from cultures of material from the synovium, blood, throat, rectum, or urine. Radio- graphs of the left wrist showed only soft tissue swelling.

Penicillin was administered intravenously at admis- sion, but treatment with ceftriaxone was substituted once culture results were known. Although there was some im- provement in the patient’s rash and arthritis with initial penicillin treatment, a more rapid improvement ensued with ceftriaxone therapy. The patient was discharged after sev- eral days of treatment with intravenous antibiotics.

Pelvic inflammatory disease caused by N gonor- rhoeae is often caused by a penicillinase-producing strain of this organism (3). The pelvic inflammatory disease in this patient with disseminated lesions suggested that it was caused by a penicillin-resistant strain. Results of our case study suggest that initial empiric treatment for disseminated gonorrhea should include antibiotic coverage of penicilli- nase-producing strains.

Kimberly Stewart, MD Marilyn Carlson, MD Allen M. Segal, DO Constance S. White, MD The Cleveland Clinic Foundation Cleveland. OH

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2.

3.

4.

5 .

McCord WC, Nies KM, Louie JS: Acute venereal arthritis: comparative study of acute Reiter’s syndrome and acute gono- coccal arthritis. Arch Intern Med 137:858-862, 1977 Eisenstein B , Masi A: Disseminated gonococcal infection and gonococcal arthritis. Semin Arthritis Rheum 10: 155-197, 1981 Hook E, Holmes K: Gonococcal infections. Ann Intern Med

Britigan B, Cohen M, Sparling PF: Gonococcal infection: a model of molecular pathogenesis. N Engl J Med 312:1683-1694, 1985 Holmes K. Counts G, Beaty H: Disseminated gonococcal infec- tion. Ann Intern Med 74.979-993, 1971

102:229-243, 1985

6. O’Brien J, Goldenberg D, Rice P: Disseminated gonococcal infection: a progressive analysis of 49 patients and a review of pathophysiology and immune mechanisms. Medicine 62:395406, 1983

7. Rinaldi R, Harrison W, Fan PT: Penicillin-resistant gonococcal arthritis: a report of four cases. Ann Intern Med 97:43-45, 1982

8. Leftik M, Miller J, Brown J: Penicillin-resistant polyarthritis. JAMA 239: 134, 1978

9. Percival A, Rowlands J, Corkill JE, Alergant CD, Arya OP, Rees E, Annels EH: Penicillinase-producing gonococci in Liverpool. Lancet 2:1379-1382. 1976

Regression of an expanded subpopulation of large granular lymphocytes in a patient with rheumatoid arthritis

To the Editor: There is evidence to indicate that patients with large

granular lymphocyte (LGL) proliferation have a neoplastic disorder, including clonal cytogenic abnormalities, and, in most cases, a clonal rearrangement of the T cell receptor p gene (1). However, the clinical course is usually benign.

We have previously described (2) a 34-year-old woman with rheumatoid arthritis who developed a typical LGL proliferation in December 1984. These cells had a uniform phenotype: CD2+, CD8+, HNKl +, Fc receptor+. She had general sickness, neutropenia, and liver involve- ment, but no splenomegaly and no infection. She was treated with prednisone (30 mg daily) and showed rapid clinical improvement, but the lymphocytosis and neutropenia re- mained unchanged during the first 6 months.

In August 1985, the lymphocytosis (2,470/mm3) and neutropenia (1 ,716/mm3) improved, and liver test results were almost normal. After the prednisone dosage was re- duced from 15 mg to 10 mg daily, she had a relapse of the cytopenia (Table I). The dosage of prednisone was increased to 15 mg daily, and in September 1987, her white blood cell count had returned to normal. In 1990, her neutrophil count and lymphocyte count are still normal, and the regression of LGL proliferation was confirmed by studies of cell surface markers with monoclonal antibodies (Table 1). Because of her arthritis, it was not possible to reduce the prednisone dosage to less than 5 mg daily. Southern blot analysis, which was performed in 1989, did not demonstrate clonal T cell receptor gene rearrangement in peripheral blood lympho- cytes.

Spontaneous regression of a monoclonal prolifera- tion of LGL, with reversal of neutropenia, has been reported in only a few cases (3-5) and never in a patient with rheumatoid arthritis, a disease frequently associated with LGL proliferation (6). These observations confirm the be- nign potential of such T cell proliferation. In the only previously reported case of clinical regression studied by Southern blot analysis, the abnormal clone had diminished but was still demonstrable (5 ) . The effect of steroids on this lymphoproliferative disorder is uncertain (1). We were un- able to stop the prednisone therapy because of articular inflammation, but it is unlikely that as low a dosage as 5 mg/day is able to suppress the LGL clone. However, the

LETTERS 247

Table 1. with large granular lymphocyte proliferation*

Five-year followup of peripheral blood hemoglobin levels and neutrophil, lymphocyte, and lymphocyte subset counts in a patient

Dec. Apr. Mar. June Aug. Sept. Sept. Feb. 1984 1985 1986 1986 1986 1987 1988 1990

Hemoglobin, 10.6 11.2 11.6 11.2 11.7 11.3 11.9 11.8

Neutrophils, 1,000 1,340 2,700 1,320 2,890 2,720 4,590 6,640

Lymphocytes, 8,500 4,600 4,110 4,520 3,100 3,530 2,870 1,666

CD4+ 12 - - - - 32 43 46

gm/lOO ml

/mm3

/mm3

(normal 35-50)

(normal 2&30)

(normal 10-18)

CD8+ 70 - - - - 49 44 34

HNKl+ 68 - - - - 37 12 19

Prednisone, 30 20 15 10 15 10 10 7 mgidav

* CD4+, CD8+, and HNKl + values are the percentages of the total mononuclear cells stained positive by direct immunofluorescence using specific monoclonal antibodies and measured by flow cytometry (FACScan; Becton Dickinson, Mountain View, CA).

relapse of neutropenia after the dosage of steroids was reduced, as reported in our case and by McKenna et a1 (3), suggests the efficacy of steroid therapy, at least for treating cytopenia.

Bernard Combe, MD, PhD Catherine Didry, MD Monique Andary, MD Thierry Reme, PhD Jacques Clot, MD, PhD Jacques Sany, MD Hdpital Saint-Eloi Montpellier, France

1. Loughran TP Jr, Starkebaum G: Large granular lymphocyte leukemia: report of 38 cases and review of the literature. Medi- cine (Baltimore) 66:397405, 1987

2. Combe B, Andary M, Caraux J , Baldet P, Barchechath F, Clot J , Sany J: Characterization of an expanded subpopulation of large granular lymphocytes in a patient with rheumatoid arthritis. Arthritis Rheum 29:675-679, 1986

3. McKenna RW, Arthur DC, Gajl-Pezalska KJ, Flynn P, Brunning RD: Granulated T cell lymphocytosis with neutropenia: malig- nant or benign chronic T lymphoproliferative disorder? Blood 66:259-266, 1985

4. Pandolfi F, Semenzato G, de Rossi G: Chronic lymphocytosis due to the expansion of granular lymphocytes. Br J Haematol

5. Winton EF, Chan WC, Check 1, Colenda KW, Bongiovanni KF, Waldmann TA: Spontaneous regression of a monoclonal prolif- eration of large granular lymphocytes associated with reversal of anemia and neutropenia. Blood 67: 1427-1432, 1986

6. Saway PA, Prasthoffer EF, Barton JC: Prevalence of granular lymphocyte proliferation in patients with rheumatoid arthritis and neutropenia. Am J Med 86:303-307, 1989

60 177 1-775, 1985

Comment on the article by Robinson et a1

To the Editor: We have read with interest the results reported by

Robinson et al ( I ) , in which the distribution of the non-B27 alleles at the HLA-B locus in 585 patients with B27+ ankylosing spondylitis (AS), from 5 different countries, was analyzed. Surprisingly, AS patients from the various popu- lations studied showed an increase in the Bw60 allele (sta- tistically significant in 4 populations) over the expected frequency for this allele in B27+ individuals, assuming the Hardy-Weinberg equilibrium between antigens B27 and Bw60. Similarly, the frequency of the Bw60 allele in patients with B27+ AS was significantly greater than that found among the population of the patients’ relatives. In accor- dance with these data, the authors concluded that B27+ individuals have a 3 times greater risk of developing AS if they also have the Bw60 antigen. This increased risk is not produced in the absence of the B27 antigen.

With the aim of analyzing this possible association in our population, we studied the frequency of the Bw60 allele in a group of patients with B27+ AS and in the following 3 control groups: 1) a group of unrelated blood donors having the B27 antigen, 2) a B27- healthy control population, and 3 ) a group of patients with diffuse idiopathic skeletal hyper- ostosis (all of them B27-). Many of the patients and B27+ controls were previously described elsewhere (2). Both the patients and the controls were Caucasian.

Table 1 shows that the frequency of the Bw60 antigen was similar in the 4 groups. Because the distribution of this allele between the 2 B27+ populations (patients and con- trols) was practically the same, we conclude that the risk of the disease developing in B27+ individuals in our population