LAUSR

Dear Editor, Mixed connective tissue disease (MCTD) is a connective tissue disease characterized by the presence of anti-RNP (anti-U1 ribonucleoprotein) antibodies, and by a set of signs and symptoms that it shares with other connective tissue diseases, such as systemic lupus erythematosus (SLE) [1]. Because of this clinical overlap of syndromes, the presence of high titer anti-RNP antibodies is a central feature of the diagnosis of MCTD [2]. Importantly, one of the most distinctive features of MCTD is the absence of severe renal or central nervous system involvement, which may be present in other connective tissue diseases, such as SLE, and this is a focal and key point of MCTD [3]. In fact, high anti-RNP titers appear to be protective against renal involvement, particularly diffuse proliferative glomerulonephritis, even when they occur at lower titers, in other connective tissue diseases [4]. Renal involvement mandating intense immunosuppressive therapy has been reported seldomly [3]. Mixed connective tissue disease treatment is largely empirical, since there have been no randomized controlled trials on the treatment of MCTD and no specific guidelines exist either [5]. We report a case of a female patient, 32 years old, who presented with a 2-month history of polyarthritis. Laboratory tests showed a high erythrocyte sedimentation rate (ESR, 69 mm/h), antinuclear antibodies (ANA) with a 1 : 1280 titer, speckled pattern, and strongly positive anti-U1 RNP antibodies. There was no complement decrease, and the results of other immunological testing, comprising anti-double stranded DNA (anti-dsDNA), rheumatoid factor, antineutrophil cytoplasmic antibodies (ANCA), and other autoantibodies to extractable nuclear antigens (ENAs), were normal. The diagnosis of MCTD was made and the patient was started on hydroxychloroquine 400 mg/day and a short course of low-dose steroids. The patient then missed follow-up appointments due to being pregnant. When the patient presented again, she had abandoned all her medications due to pregnancy-related concerns, and had fatigue, new onset of Raynaud phenomenon and puffy hands. Blood tests revealed anemia (hemoglobin 10.3 g/dl) high ESR (97 mm/h), and hypoalbuminemia (32 g/l), and repeated immunological testing was remarkable only for high ANA and anti-RNP antibodies. Urine studies showed proteinuria of 2.5 g/24 h and microscopic hematuria (142/μl). The patient underwent renal biopsy, which showed “segmental sclerosis lesions and presence of mesangial and membrane immune-type deposits by immunofluorescence”, with a full-house pattern on immunofluorescence but absence of mesangial or endocapillary proliferation. Therapy with prednisolone 1 mg/kg/day (60 mg/day) in a progressive dose reduction regimen, hydroxychloroquine 400 mg/day, mycophenolate mofetil (titrating dose up to 3000 mg/day), and captopril was started. At 6 months, prednisolone was reduced to 7.5 mg/day, and she was in renal remission, as renal function was normal, proteinuria had decreased to 370 mg/24 h, serum albumin was normal, and hematuria had resolved. At 24 months after this admission, prednisolone was suspended, and the patient remains in remission. Anti-RNP antibodies are associated with a protective role in MCTD and in other systemic connective tissue diseases where they are present, namely regarding severe renal or central nervous system involvement [4]. Renal disease in MCTD has been described, but is usually in the form of low grade proteinuria or hematuria; in fact,