Localized scleroderma.

Localized scleroderma can be divided into three main subtypes: morphea, linear scleroderma, and generalized morphea. Plaque morphea usually has a good prognosis. Variants of morphea, including guttate morphea and atrophoderma of Pasini and Pierini, are seen. Linear scleroderma, whether involving an extremity or the face, is often associated with serological abnormalities. Cosmetic and functional prognosis may be poor. Therapy is usually ineffective. Generalized morphea may be difficult to differentiate from systemic scleroderma. However, progression to systemic scleroderma is uncommon.

Systemic scleroderma.

Scleroderma encompasses a wide variety of diseases, including localized scleroderma, overlap syndromes, sclerodermoid conditions, and systemic scleroderma. This article emphasizes the systemic scleroderma.

Limited Wegener's granulomatosis. Report of a case with oral, renal, and skin involvement.

Limited Wegener's granulomatosis is a form of the disease in which only one or two organ systems are involved. A rare case is reported in which the initial symptoms were in the skin and the lip, complicated by skin lesions exhibiting features of a clinical variant of lupus erythematosus.

Nodular (keloidal) scleroderma.

Two patients with progressive systemic sclerosis (PSS) developed keloidal-like nodules within areas of thickened skin. This extremely unusual event is most likely a keloidal response to the early inflammatory component of scleroderma in patients who are either genetically at risk for keloid formation or in areas of the skin that have a high predilection for keloid formation such as the chest.

An immunohistochemical study of nuclear proteins in differentiating epidermal cells.

Both DNA and RNA disappear from the nucleus during differentiation of granular cells into cornified cells but the fate of nuclear proteins remains unknown. We investigated localization of nuclear proteins in rat epidermis by light and electron microscopic immunoperoxidase techniques. As a probe, three sera that reacted, respectively, with the nucleoplasm, nucleolus, and nuclear envelope of basal cells of rat epidermis were used. In granular cells both the antinucleoplasm serum and antinucleolus serum increased intensity of the nuclear staining, but they reacted also with ribosomes, filaments, and periphery of keratohyalin granules in the cytoplasm. The staining appeared diffusely in cornified cells and identification of nuclear components became impossible. In contrast, the antinuclear envelope serum stained only the nuclear outline in granular cells and continued to stain the nuclear contour in cornified cells of the fourth and fifth proximal cell layers. The antigenic components surrounded amorphous but not filamentous materials in cornified cells. These findings suggest that some nuclear proteins become immunologically indistinguishable from cytoplasmic protein. However, the nuclear envelope protein maintains its localization even after nucleic acids are lost and the nuclear space is detectable in cornified cells by use of autoantibody directed to this protein(s).

The redistribution of a conserved nuclear envelope protein during the cell cycle suggests a pathway for chromosome condensation.

We describe a human autoantiserum that recognizes specific determinants present both on the nuclear envelope of interphase cells and the periphery of metaphase chromosomes. These determinants are highly conserved through evolution and present on a protein with an apparent molecular weight of 33,000. This 33 kd protein, which we call "perichromin," appears to be directly or indirectly bound to both interphase and metaphase DNA. Studies of the transformation of perichromin from a nuclear envelope association to a perichromosomal position during prophase suggests a pathway for chromosome organization throughout the cell cycle.

Autoimmune response directed against conserved determinants of nuclear envelope proteins in a patient with linear scleroderma.

We have studied the autoantibodies in the serum of a patient with linear scleroderma that specifically recognize the nuclear envelope of cultured cells. These antibodies bind to conserved determinants of nuclear lamins, the predominant mammalian nuclear envelope proteins. Of the three mammalian nuclear lamin proteins (970, P68, and P60), only P70 and P60 bind the autoantibodies. In addition, two proteins of the Drosophila embryonic nuclear matrix, P70 and P68, bind these autoantibodies. We have used nuclear matrices to isolate the autoantibodies from the patient's serum that react to the nuclear lamins. At least three different IgG heavy chains were found to be involved in this autoimmune response to nuclear lamins, indicating that this response is not due to the expansion of a single B-cell clone.

Anticentromere and anticentriole antibodies in the scleroderma spectrum.

We studied serum samples from 106 patients, including 80 in the scleroderma spectrum, by indirect immunofluorescent microscopy, using PtK1 rat kangaroo tissue culture cells as substrate. Anticentromere (Kinetochore) antibodies were present in 28 patients, and anticentriole antibodies were present in four patients. Anticentromere antibodies were usually present in patients with a benign, chronic form of systemic scleroderma, which has been termed the CREST (Calcinosis, Raynaud's phenomenon, esophageal involvement, sclerodactyly, and telangiectasia) syndrome. The four patients with a previously undescribed anticentriole antibody were all in the scleroderma spectrum. Possibly, these antibodies may have diagnostic and prognostic importance. Further, they will be useful in studying the structure and function of these cellular organelles.