Keywords: Klinefelter's syndrome; systemic lupus erythematosus; autoimmunity. The striking preponderance of systemic lupus erythematosus. (SLE) in females ...
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Journal of the Royal Society of Medicine Volume 82 September 1989
Klinefelter's syndrome associated with autoimmune disease
A SchattnerMD
A Berrebia MD
Departments
of Medicine and aHematology, Kaplan Hospital, Rehovot, affiliated the Hebrew University and Hadassah Medical School, Jerusalem, Israel
system was normal and circulating immune complexes were not found. He was given aspirin as needed and danazol (200 mg twice a day) with significant symptomatic improvement. Serum testosterone levels increased (5.4 ng/ml) and LH levels decreased, but not to normal (35 iu/l). Latex fixation test became negative and ANA could no longer be detected. In addition, some improvement was noted in the cytopenia and the eosinophilia gradually disappeared (140-340 total). There were no skin or mucous membrane manifestations and neither serositis nor central nervous system involvement developed over the years, until his death at the age of 81 of ischaemic heart disease.
Keywords: Klinefelter's syndrome; systemic lupus erythematosus; autoimmunity
The striking preponderance of systemic lupus erythematosus (SLE) in females is a constant reminder of the importance ofthe sex-hormonal factor in the multifactorial pathogenesis of autoimmunityl. This is supported by several experimental studies in lupus-prone mice and in vitro2' demonstrating a facilitating effect of oestrogens on the immune system, predisposing to autoimmunity, while androgens may have a protective effect3. In this light, the association of SLE and Klinefelter's syndrome" is of special interest. We report another example ofthe ssiation in which the findings of leukopenia in an elderly patient led to the diagnosis of both conditions. Case report A 73-year-old Ashkenazi man with anginal syndrome and normal physical examination was referred for consultation due to leukopenia. Haemoglobin was 12.1-13 g/dl, platelets 92.103/m13 and white blood cell 3.103/ml3 (33% segment, 42% lymphocytes, 3% monocytes, 20% eosinophils, 2% basophils). Stool and urinanalysis, and kidney and liver function tests were normal. Bone marrow (BM) aspiration showed a polymorphic picture with marked eosinophilia. To rule out a myelodysplastic syndrome, serum lysosyme, vitamin B12, granulocyte peroxidase and leucocyte alkaline phosphatase were tested and found to be normal. Chromosome analysis revealed a karyotype of 47,XXY with no structural changes of the chromosomes. Body habitus, hair pattern and hypogonadism were then noted to be characteristic of Klinefelter's syndrome; the patient was married with no children. Endocrine profile showed normal plasma cortisol, thyroid hormones, prolactin and oestradiol levels with 1.1 ng/ml testosterone and follicle-stimulating hormone (FSH), luteinizing hormone (LH) of 59 and 80 iu/l. Leukopenia (2500-4700/ml3) and eosinophilia (total 600-1200) with episodic thrombocytopenia (60-90xl01/ml3, coinciding with maximal leukopenia) persisted, but remained ill-understood. Erythrocyte sedimentation rate (ESR) was 20 mm/h (Westergren), and autoantibodies were not found. After three years of uneventful follow-up the patient presented with polyarthralgia and morning stiffness affecting both hands and elbows, one shoulder, and later, one knee. Over the next three years these complaints persisted with occasional flares and on one occasion frank arthritis ofthe shoulder and wrist was found with no erosions on X-ray. Laboratory studies at that time revealed an ESR of 67 mm/h, with strongly positive antinuclear antibodies (ANA) (1: 250), and latex fixation test (1/2560). Rose-Waaler, anti-DNA antibodies, LE cells, VDRL, Coomb's test and cryoglobulins were negative, and prothrombin time/partial thromboplastin time, liver and kidney function, lymphocyte subsets and serum Ig levels were normal. The complement
Discussion
Our patient with Klinefelter's syndrome had a haematologcal disorder - leukopenia, thrombocytopenia and possbly eosinophilia, and developed polyarthralgia, morning stiffhess and nonerosive arthritis, as well as an abnormal titre of ANA. While not sufficient for an unequivocal diagnosis of SLE, this combination of three ARA criteria is highly suggestive of an autimmune disorder, possibly SLE, which partially responded to danaZO17. The absence of renal disease and good survival is characteristic of elderly patients with late-onset SLE. At this age group more male patients are encountered, possibly as a result of an increase in harmful oestrogenic metabolitesal° and senescence of the immune system leading to hyperactivity11. When in addition, deficiency in androgens exists, as in patients with Klinefelter's syndrome4' , liability to develop SLE increases. As our case illustrates, many more patients with Klinefelter's syndrome may have subclinical forms of autoimmunity. Further study ofthis intriguing aspect may afford a key for understanding an important factor in the pathogenesis of SLE, and may also have implications for therapy. References 1 Alarcon-Segovia D. The pathogenesis of systemic lupus erythematosus. A troika. J Rheumatol 1984;11:585-90 2 Roubinian JR, Talal N, Greenspan JS, et aL Sex hormone modulation of autoimmunity1 in NZB/NZW mice. Arthritis Rheum 1979;22:1162-9 3 Grosman CJ. Regulation of the immune system by sex steroids. - Endocr Rev 1984;5:435-55 4 Fam AG, Izsak M, Saiphoo C. SLE and Klinefelter's syndrome.
Arthritis Rheum 1980;23:124-6 5 Stern R, Fishman J, Brunsman H, Kunkel HG. SLE a ted with Klinefelter's syndrome. Arthritis- Rheum 1977;20.18-22 ; Dubois EL, Kaplan BJ. SLE and Klinefelter's syndrome. Lancet
1976;i:93 7 Morley KD, Parke A, Hughes GRV. SLE: Two patients treated with danazol. Br Med J 1982;284:1431-2 8 Lahita RG, Bradlow HL, Kunkel HG, Fishman J. Increased 16-alpha-hydroxylation of estradiol in systemic lupus erythematosus. J Clin Endocrinol Metab 1981;53:174-8 9 Miller MH, Urowitz M, Gladman D, Killinger DW. Systemic lupus erythematosus in males. Medicine 1983;,2:327-34 10 Bucala R, Fishman J, Cerami A. Formation ofcovalent adducts between cortisol and 16-alpha-hydroxyestrone and protein, possible role in the pathogenesis of cortisol toxicity and SLE. Proc Nati Acad Sci USA 1982;79:33204 11 Lahita RG. Sex and age in systemic lupus erythematosus.. In: Lahita RG, ed. Systemic lupus erythematosus. New York: John Wiley, 1987:523-39
(Accepted 3 August 1989. Correspondence to Dr A Schattner, Department of Medicine, Kaplan Hospital, P0 Box 1, Rehovot 76100, Israel)
0141.0768/89/ 090560-01/$02.00/0 o 1989 The Royal Society of Medicine
