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478 LETTERS RANA and anti-EBNA may differ is in the parts of the 80K peptide seen as antigenic by the 2 types of antibodies. In this respect, we very much agree with the interest of Venables et al in that part of the 80K peptide specified by the IR3 sequence in the Epstein-Barr virus (EBV) DNA, since homologous sequences can be detected in non-EBV-infect- ed cells. These sequences may ultimately be shown to encode a normal cellular protein. We also agree with their interest in the multiple EBNAs described by Sculley et al(3), which may conceivably represent metabolically altered or complexed EBNA. The question of whether EBV is important in the pathogenesis of rheumatoid arthritis will not be answered by studies of RANAEBNA alone, since this will necessitate knowing the entire profile of cellular, as well as humoral responses in rheumatoid arthritis to EBV, in addition to whether EBV related antigens are present in the tissues. Unveiling the RANAEBNA story is an important part of this process, however, and is likely to give us interesting new information about immune responsiveness in rheuma- toid arthritis generally, as well as the response to the Epstein-Bam virus. Peter B. Billings, PhD Sdie 0. Hoch, PhD Dennis A. Carson, MD John H. Vaughan, MD Scripps Clinic and Research Foundation La Jolla, CA 1. Billings PB. Hoch SO, White PJ, Carson DA, Vaughan JH: Antibodies to the Epstein-Barr virus nuclear antigen and to rheumatoid arthritis nuclear antigen identify the same polypep- tide. Proc Natl Acad Sci USA 80:7104-7108, 1983 2. Cohen JHM, Lenoir GM: Epstein-Barr virus and rheumatoid arthritis: are rheumatoid arthritis associated nuclear antigen and Epstcin-Barr virus nuclear antigen different? Biomedicine 36:246-249, 1982 3. Sculley TB. Kreofsky T, Pearson GR, Spelsberg TC: Partial purification of the Epstein-Bm virus nuclear antigen(s). J Biol Chem 258339163982, 1983 SS-B antibodks and isolated glandular fibrosis in progressive systemic sclerosisSjiigren’s syndrome To the Editor: In the April 1983 issue of Arthritis and Rheumatism, Osial et al examined frequencies of serum antibodies to SS-A and SS-B in patients with progressive systemic sclerosis (PSS) and Sjogren’s syndrome. They found that these anti- bodies were absent in PSS patients who had fibrosis of minor salivary glands without any apparent inflammation (Osial TA Jr, Whiteside TL, Buckingham RB, Singh G, Barnes EL, Pierce JM, Rodnan GP: Clinical and serologic study of Sjogren’s syndrome in patients with progressive systemic sclerosis. Arthritis Rheum 26:500-508. 1983). We wish to report a patient in whom the findings were different. A 53-year-old woman presented with acrosclerosis, Raynaud’s phenomenon, and shortness of breath. Labora- tory test results were not remarkable, but chest roentgeno- grams showed interstitial markings in both bases, and a barium study showed an abnormal motility of the esophagus. A severely reduced pulmonary dsusion was also disclosed. Direct immunofluorescence examination of a skin biopsy displayed I& directed to the epidermal nuclei in a speckled pattern. Antinuclear antibodies with speckled and nucleolar patterns in high titers (14,280) were also detected. Search for extractable nuclear antigen antibodies revealed only antibodies to SS-B antigen. The patient then admitted experiencing mouth dry- ness and a sandy sensation in her eyes. Schirmer’s test result was below 5 m d 5 minutes in both eyes. Histopathology of a minor salivary gland showed a peri- and intralobular fibrosis (1+ according to the scoring method described by Osial). PSS-Sjogren’s patients with glandular fibrosis are said to have a higher mortality rate (Cipoletti JF, Bucking- ham RB, Barnes EL, Peel RL, Mahmood K, Cignetti FE, Pierce JM, Rabin BS, Rodnan GP: Sjogren’s syndrome in progressive systemic sclerosis. Ann Intern Med 87:535-541, 1977). The paper by Osial et al may leave the impression that PSSSjogren’s patients with SS-B antibodies do not have isolated glandular fibrosis and consequently have a benign disease. The findings in our patient suggest, to the contrary, that SS-B positivity may well correlate with glandular fibro- sis alone and possibly have a severe prognosis. F. Rongioletti Aurora Parodi A. Rebora University of Genoa Genoa, Italy Digital sclerosis and juvenile diabetes To the Editor: In the November 1982 issue of Arthritis and Rheuma- tism, Seibold (1) reported that in 34% of 137 children with insulin-dependent diabetes mellitus (IDDM), there was pal- pable thickening and induration of the skin of the fingers. Mild flexion contractures of the interphalangeal joints were also seen in 26% of the patients. In the same issue, Sherry et al (2) reported a case of joint contractures in a child, where contractures preceded the manifestation of IDDM. Digital sclerosis in children with IDDM satisfies, in certain cases (I), some American Rheumatism Association preliminary criteria for the classification of scleroderma (3). Therefore, it is of interest to report histopathology studies and determination of autoantibodies which might contribute to the characterization of digital sclerosis in children with IDDM. The patient selected for this study, a 14-year-oldboy, has had IDDM from the age of 8 years, with good control of

Digital sclerosis and juvenile diabetes

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478 LETTERS

RANA and anti-EBNA may differ is in the parts of the 80K peptide seen as antigenic by the 2 types of antibodies. In this respect, we very much agree with the interest of Venables et al in that part of the 80K peptide specified by the IR3 sequence in the Epstein-Barr virus (EBV) DNA, since homologous sequences can be detected in non-EBV-infect- ed cells. These sequences may ultimately be shown to encode a normal cellular protein. We also agree with their interest in the multiple EBNAs described by Sculley et al(3), which may conceivably represent metabolically altered or complexed EBNA.

The question of whether EBV is important in the pathogenesis of rheumatoid arthritis will not be answered by studies of RANAEBNA alone, since this will necessitate knowing the entire profile of cellular, as well as humoral responses in rheumatoid arthritis to EBV, in addition to whether EBV related antigens are present in the tissues. Unveiling the RANAEBNA story is an important part of this process, however, and is likely to give us interesting new information about immune responsiveness in rheuma- toid arthritis generally, as well as the response to the Epstein-Bam virus.

Peter B. Billings, PhD S d i e 0. Hoch, PhD Dennis A. Carson, MD John H. Vaughan, MD Scripps Clinic and Research Foundation La Jolla, CA

1 . Billings PB. Hoch SO, White PJ, Carson DA, Vaughan JH: Antibodies to the Epstein-Barr virus nuclear antigen and to rheumatoid arthritis nuclear antigen identify the same polypep- tide. Proc Natl Acad Sci USA 80:7104-7108, 1983

2. Cohen JHM, Lenoir GM: Epstein-Barr virus and rheumatoid arthritis: are rheumatoid arthritis associated nuclear antigen and Epstcin-Barr virus nuclear antigen different? Biomedicine 36:246-249, 1982

3. Sculley TB. Kreofsky T, Pearson GR, Spelsberg TC: Partial purification of the Epstein-Bm virus nuclear antigen(s). J Biol Chem 258339163982, 1983

SS-B antibodks and isolated glandular fibrosis in progressive systemic sclerosisSjiigren’s syndrome

To the Editor: In the April 1983 issue of Arthritis and Rheumatism,

Osial et al examined frequencies of serum antibodies to SS-A and SS-B in patients with progressive systemic sclerosis (PSS) and Sjogren’s syndrome. They found that these anti- bodies were absent in PSS patients who had fibrosis of minor salivary glands without any apparent inflammation (Osial TA Jr, Whiteside TL, Buckingham RB, Singh G, Barnes EL, Pierce JM, Rodnan GP: Clinical and serologic study of Sjogren’s syndrome in patients with progressive systemic sclerosis. Arthritis Rheum 26:500-508. 1983). We wish to report a patient in whom the findings were different.

A 53-year-old woman presented with acrosclerosis, Raynaud’s phenomenon, and shortness of breath. Labora- tory test results were not remarkable, but chest roentgeno- grams showed interstitial markings in both bases, and a barium study showed an abnormal motility of the esophagus. A severely reduced pulmonary dsusion was also disclosed.

Direct immunofluorescence examination of a skin biopsy displayed I& directed to the epidermal nuclei in a speckled pattern. Antinuclear antibodies with speckled and nucleolar patterns in high titers (14,280) were also detected. Search for extractable nuclear antigen antibodies revealed only antibodies to SS-B antigen.

The patient then admitted experiencing mouth dry- ness and a sandy sensation in her eyes. Schirmer’s test result was below 5 m d 5 minutes in both eyes. Histopathology of a minor salivary gland showed a peri- and intralobular fibrosis (1+ according to the scoring method described by Osial).

PSS-Sjogren’s patients with glandular fibrosis are said to have a higher mortality rate (Cipoletti JF, Bucking- ham RB, Barnes EL, Peel RL, Mahmood K, Cignetti FE, Pierce JM, Rabin BS, Rodnan GP: Sjogren’s syndrome in progressive systemic sclerosis. Ann Intern Med 87:535-541, 1977). The paper by Osial et al may leave the impression that PSSSjogren’s patients with SS-B antibodies do not have isolated glandular fibrosis and consequently have a benign disease. The findings in our patient suggest, to the contrary, that SS-B positivity may well correlate with glandular fibro- sis alone and possibly have a severe prognosis.

F. Rongioletti Aurora Parodi A. Rebora University of Genoa Genoa, Italy

Digital sclerosis and juvenile diabetes To the Editor:

In the November 1982 issue of Arthritis and Rheuma- tism, Seibold (1) reported that in 34% of 137 children with insulin-dependent diabetes mellitus (IDDM), there was pal- pable thickening and induration of the skin of the fingers. Mild flexion contractures of the interphalangeal joints were also seen in 26% of the patients. In the same issue, Sherry et al (2) reported a case of joint contractures in a child, where contractures preceded the manifestation of IDDM.

Digital sclerosis in children with IDDM satisfies, in certain cases ( I ) , some American Rheumatism Association preliminary criteria for the classification of scleroderma (3). Therefore, it is of interest to report histopathology studies and determination of autoantibodies which might contribute to the characterization of digital sclerosis in children with IDDM.

The patient selected for this study, a 14-year-old boy, has had IDDM from the age of 8 years, with good control of

LETTERS 479

Figure 1. Electron microscopy showing A, thickening of the base- ment membrane of dermal vessels and B, reduplication.

his blood glucose. Physical examination results were unre- markable with the following exceptions. The skin on the fingers, palms, and dorsa of both hands was adherent and indurated, with 4+ clinical skin thickening ( I ) and flexion contractures of the metacarpophalangeal, proximal, and distal interphalangeal joints. There was also thickening of the skin on the toes and forefoot with bilateral contracture of the interphalangeal joint of the first digit of both feet. The patient had grade I1 diabetic retinopathy.

The HLA study showed that the patient was homo- zygous for the HLA haplotype A2,Bw35,DR3,MT2.

Skin biopsy obtained from an affected area disclosed a marked deposition of compact collagen fibers in the dermis, but no atrophy of dermal appendages, and thicken- ing of the basement membrane of the vessels. Electron microscopic examination revealed marked thickening and reduplication of the basement membrane (Figure 1).

The determinations of antinuclear, antdouble- stranded DNA, anti-single-stranded DNA, anti-Sm, anti- nuclear ribonucleoprotein, and other antibodies significantly related to scleroderma (anticentromere, anti-RNA, and anti- Scl-70) were all negative.

The morphologic findings suggest that in this case, digital sclerosis could be linked to diabetic microangiopathy. Moreover, the negative results of autoantibody determina- tions do not supprt a diagnosis of scleroderma.

Tomas GonAez Marian Gantes Lucio Dim-Flores Hospital General y Clinico de Tenerife Universidad de La Laguna Canary Islands, Spain

1 . Seibold JR: Digital sclerosis in children with insulin-dependent diabetes mellitus. Arthritis Rheum 25:1357-1361, 1982

2. Sherry DD, Rothstein RRL, Petty RE: Joint contractures preced- ing insulin-dependent diabetes mellitus. Arthritis Rheum

3. Masi AT, Rodnan GP, Medsger TA Jr, Altman RD. D’Angelo WA, Fries JF. LeRoy EC, Kirsner AB, MacKenzie AH, McShane DJ, Myers AR, Sharp GC: Preliminary criteria for the classification of systemic sclerosis (scleroderma). Bull Rheum Dis 31:1-6, 1981

25:1362-1364, 1982

BOOK REVIEWS

American Academy of Orthopedic Surgeons: Symposium on Heritable Disorders of Connective Tissue. Wayne H. Akeson, Paul Bornstein, and Melvin J . Clincher, editors. St. Louis, C . V . Mosby, 1982. 380 pages. Illustrated.

This symposium, held in 1980, canvassed the state of the art on the heritable connective tissue diseases. It was sponsored by the American Academy of Orthopedic Sur- geons, the Orthopedic Research Society, and the National Institutes of Health. Sixty-nine authors contributed 30

manuscripts. By design, the symposium included both basic scientists and clinicians.

Because of the diffuse nature of the subject matter, the material was divided into 6 distinct categories.

The section on collagen chemistry contained a dis- cussion of animal genes and collagen production, including structure, transcription, and messenger RNA utilization. An excellent review of collagen structure and synthesis ad- dressed specific collagenases and defects of heritable dis- eases. For example, in Ehlers-Danlos syndrome aldehydes cannot undergo Amadori rearrangement of stable crosslinks because of a defect in hydroxylation of lysyl residues. This