To the Editor: Limited systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs. Circulant anticentromere antibody is usually positive.1 Antinucleolar antibodies are positive less frequently (15%–40%),2 having prognostic significance on the overall course of the patients. We present a case of limited SSc with negative serologic test for extractable nuclear antigens in which direct immunofluorescence revealed positive antinuclear antibodies (ANA) with nucleolar pattern. A 54-year-old man was referred to the dermatology department because of a 5-year history of multiple asymptomatic telangiectasias on the face and neckline. Clinical examination revealed the presence of sclerodactyly and multiple scars of ulcers in the fingertips that appeared when the patient worked in a frigorific chamber. Capillaroscopy showed predominance of areas of angiogenesis and some small avascular areas. The patient complained about mild interphalangeal arthralgias without inflammatory changes. Unspecific gastrointestinal symptoms and dyspnea were also present. High-resolution chest computed tomography showed mild pulmonary fibrosis predominantly in peripheral areas and bases of the lungs. Echocardiography confirmed the clinical suspicion of pulmonary hypertension, and bosentan therapy was initiated. Circulant ANA resulted positive at 1:1280 dilution. The determinations of extractable nuclear antigens, antibodies against parietal cells, against smooth muscle, and against double-stranded DNA were all negative. A skin biopsy of the neckline area with telangiectasia revealed lymphocytic perifolliculitis, with no other alterations. Direct immunofluorescence study (DIF) performed on lesional skin showed the presence of IgG ANA with a nucleolar pattern (Fig. 1).FIGURE 1.: Direct immunofluorescence on a skin biopsy from an area with telangiectasia in the patient's neckline. IgG resulted positive with a nucleolar pattern (×100).Circulating autoantibodies are found in as many as 95% of patients with SSc and carry greater weight in the newly proposed ACR/EULAR classification system. Centromere (CEN) proteins (P), topoisomerase I, and RNA polymerase III autoantibodies closely reflect patterns of organ involvement and disease progression.3 Circulating anti-Th/To type antinucleolar antibodies are detectable mainly by immunoprecipitation, which is not performed routinely in most clinical laboratories. Its positivity is related to limited skin involvement and frequent fibrosis of internal organs (interstitial lung disease, pericarditis, and renal involvement). Frequency of negative circulating antibodies with positive DIF findings is largely unknown because the last is not routinely performed. In the study by Kulthanan et al,4 a subgroup of patients with SSc presented positive DIF findings in 77% of the cases with the dermoepidermal junction and epidermal nuclei as the most common site, and of these patients, 45% presented negative serum ANA. Shibeshi et al5 reported a DIF positivity rate of 25,7% in 63 patients with SSc, with only one case with no circulating autoantibodies at all, and another with positive serum ANA but no characteristic antibodies of SSc. Antinucleolar pattern has been rarely reported in DIF of patients with SSc. Only 6 cases were found in the literature, all of them with high ANA titles. As these cases date from the 1980s, only circulating anti-ribonucleoprotein was performed, resulting positive in one of the patients.6,7 Our patient had ANA in peripheral blood, but more specific antibodies were not detected (antinucleolar, Scl70, or anticentromere). However, a skin biopsy with DIF was allowed to demonstrate the fixation of antibodies with a nucleolar pattern. Nucleolar pattern ANA in DIF of a skin biopsy is an unusual finding. We believe this technique can help to confirm clinical diagnosis and assess prognosis on individual patients.
Read full abstract