A 65-year-old female began experiencing arthralgia, morning stiffness and psychroesthesia in April 2000. She visited a rheumatologist and was suspected of having early-stage rheumatoid arthritis. She was referred to our hospital, and was admitted in December 2000. At that time, sclerosis of the skin was advanced, and Raynaud's phenomenon was confirmed. The patient also exhibited nailfold bleeding, and was diagnosed as having systemic scleroderma. She visited a gynecologist for screening and cervical uteri carcinoma was confirmed. She underwent surgery in March 2001, and subsequently, sclerosis in her skin was almost stopped. We believe that these clinical symptoms were related to paraneoplastic syndrome. We therefore immunochemically investigated the pathogenesis of paraneoplastic syndrome and found that connective tissue growth factor (CTGF) might be involved and transforming growth factor-β (TGF-β) might not be involved in this case.

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A 2-month-old boy with a characteristic elfin face was diagnosed as having Williams syndrome by means of specific fluorescence in situ hybridization (FISH) analysis for a chromosomal microdeletion located in 7q11.23. He was suspected to have immunodeficiency because of a persistent enlargement of axillary lymphnodes after immunization with Bacille Calmette-Guerin (BCG) vaccine since 7 month-old of age.
The nitroblue tetrazolium test (NBT) and the chemiluminescence test revealed an absence of superoxide production. Western blotting and DNA sequence analysis confirmed the diagnosis of p47-phox-deficient autosomal recessive chronic granulomatous disease (CGD) (A47⁰CGD). The predominant genetic defect in A47⁰CGD was a GT deletion at the beginning of exon 2 in neutrophil cytosol factor 1 gene (NCF1) located in 7q11.23. It suggests that CGD in this patient resulted from the hemizygosity of recessive genetic mutation in NCF1 located at 7q11.23 associated with Williams syndrome. In such a disease with the chromosomal microdeletion like Williams syndrome, we should consider a combination with autosomal recessive diseases, the genes of which are located in the hemizygous region.

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(Case 1) A 13-years-old female had multiple arthralgia and butterfly rush, when she admitted in our hospital in May 2001. Nephropathy, hemolytic anemia (Hb 6.3g/dl and direct Coombs 3+) and high titers of antinuclear antibodies and anti-ds-DNA antibody were disclosed and she was diagnosed as systemic lupus erythematosus (SLE). Although combination therapy of PSL 60mg/day with a steroid pulse therapy, cyclosporine or an immunosorbent treatment, severe hemolytic anemia remained. However, monthly cyclophosphamide pulse therapy (IV-CY), which was started for the steroid-resistant hemolytic anemia, has gradually become effective and Hb improved up to 11.4g/dl after 6 courses of IV-CY. (Case 2) A 53-years-old woman diagnosed as SLE in 1978 and she had PSL 5mg for over 10 years. Severe anemia (Hb 5.9g/dl) was disclosed with a slight fever in June 2001, and she admitted in our hospital for further examinations. Progressive hemolytic anemia was revealed with marked decrease of Hb (3.4g/dl) and high titer of direct Coombs (3+). Neither PSL (50mg/day) nor steroid pulse therapy were effective against hemolytic anemia. In contrast, 3 courses of monthly IV-CY (500mg/day) resulted in the resolution of hemolysis. It is well known that the steroid-resistant hemolytic anemia is extremely hard to treat and leads to miserable prognosis, but we here propose IV-CY as an alternative and invaluable choice for the treatment of refractory hemolytic anemia complicated with SLE.

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