Advertisement

Familial clustering of scleroderma spectrum disease

  • Andrew R McGregor
    Footnotes
    Affiliations
    Division of Rheumatology and Immunology, Department of Medicine, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA
    Search for articles by this author
  • Ada Watson
    Affiliations
    Harvard Medical School, Dana-Farber Cancer Institute, Center for Blood Research, Boston, Massachusetts, USA
    Search for articles by this author
  • Edmund Yunis
    Affiliations
    Harvard Medical School, Dana-Farber Cancer Institute, Center for Blood Research, Boston, Massachusetts, USA
    Search for articles by this author
  • Janardan P Pandey
    Affiliations
    Division of Rheumatology and Immunology, Department of Medicine, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA
    Search for articles by this author
  • Kazuhiko Takehara
    Footnotes
    Affiliations
    Division of Rheumatology and Immunology, Department of Medicine, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA
    Search for articles by this author
  • J.Thomas Tidwell
    Footnotes
    Affiliations
    Division of Rheumatology and Immunology, Department of Medicine, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA
    Search for articles by this author
  • Alexander Ruggieri
    Footnotes
    Affiliations
    Division of Rheumatology and Immunology, Department of Medicine, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA
    Search for articles by this author
  • Richard M Silver
    Affiliations
    Division of Rheumatology and Immunology, Department of Medicine, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA
    Search for articles by this author
  • E.Carwile LeRoy
    Affiliations
    Division of Rheumatology and Immunology, Department of Medicine, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA
    Search for articles by this author
  • Hildegard R Maricq
    Correspondence
    Requests for reprints should be addressed to Dr. Hildegard R. Maricq, Division of Rheumatology and Immunology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, South Carolina 29425.
    Affiliations
    Division of Rheumatology and Immunology, Department of Medicine, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA
    Search for articles by this author
  • Author Footnotes
    ∗ Current address: 80 Sutton Court, Sutton Court Road, Chiswick, London, W.4., England.
    † Current address: University of Tokyo, Branch Hospital, Dermatology, 3-28-6, Mejirodai, Bunkyo, Tokyo, Japan.
    § Current address: Department of Rheumatology, General Internal Medicine, 2007 Harrison Avenue, Panama City, Florida 32405.
      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      This is the second case report of familial scleroderma (systemic sclerosis) in South Carolina. The family includes two cases of scleroderma meeting American Rheumatism Association criteria, one of systemic sclerosis sine scleroderma, and two other cases of undifferentiated connective tissue disease with features of scleroderma spectrum disorders; there are also two cases of Raynaud's phenomenon (one associated with rheumatoid arthritis), for a total of seven affected relatives. Evidence of scleroderma spectrum disorders was sought in six siblings of the two co-index cases and in 23 of the 35 offspring. Laboratory studies included antinuclear antibody determinations and typing for the following genetic markers: HLA (A, B, C, DR), complotypes, Gm and Km allotypes, and alpha-1 antitrypsin phenotypes. No common genetic markers restricted to affected members of this family were found, and no environmental exposures were detected that could explain this familial clustering of cases. This report should however, add to the slowly accumulating information on the genetic characteristics of families at unusually high risk for scleroderma spectrum disorders. Positive antinuclear antibody tests at a titer of Math Eq or higher were present in 57 percent of the first-degree relatives of the affected cases.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to The American Journal of Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Blanchard R.E.
        • Speed E.M.
        Scleroderma: periodontal membrane manifestations in two brothers.
        Periodontics. 1965; 3: 77-80
        • McAndrew G.M.
        • Barnes E.G.
        Familial scleroderma.
        Ann Physiol Med. 1965; 8: 128-131
        • Schimke R.N.
        • Kirkpatrick C.H.
        • Delp M.H.
        Calcinosis, Raynaud's phenomenon, sclerodactyly, and telangiectasia.
        Arch Intern Med. 1967; 119: 365-370
        • Burge K.M.
        • Perry H.O.
        • Stickler G.B.
        “Familial” scleroderma.
        Arch Dermatol. 1969; 99: 681-687
        • Camus J.-P.
        • Emerit I.
        • Reinert P.
        • Guillien P.
        • Crouzet J.
        • Fourot J.
        Sclerodermie familiale avec syndrome de Sjogren et anomalies lymphocytaires et chromosomiques.
        Ann Med Interne (Paris). 1970; 121: 149-161
        • Cavalieri R.
        La sclerodermia familiare.
        Chronica Dermatologica. 1971; 2: 92-103
        • Szczepanski A.
        • Jakubowicz K.
        On the familial occurrence of scleroderma.
        Przegl Dermatol. 1972; 59: 361-364
        • Rendall J.R.
        • McKenzie A.W.
        Familial scleroderma.
        Br J Dermatol. 1974; 91: 517-522
        • Greger R.E.
        Familial progressive systemic scleroderma.
        Arch Dermatol. 1975; 111: 81-85
        • Frayha R.A.
        • Tabbara K.F.
        • Geha R.S.
        Familial CRST syndrome with sicca complex.
        J Rheumatol. 1977; 4: 53-58
        • Gray R.G.
        • Altman R.D.
        Progressive systemic sclerosis in a family.
        in: Case report of a mother and son and review of the literature. 2nd ed. Arthritis Rheum. 20. 1977: 35-41
        • Sasaki S.
        • Yoshino H.
        Systemic scleroderma in mother and daughter.
        Arch Dermatol. 1977; 113: 378-379
        • Strosberg J.M.
        • Peck B.
        • Harris Jr, E.D.
        Scleroderma with intestinal involvement: fatal in two of a kindred.
        J Rheumatol. 1977; 4: 46-52
        • Mund D.J.
        • Greenwald R.A.
        The CREST syndrome variant of scleroderma in a mother-daughter pair.
        J Rheumatol. 1978; 5: 307-310
        • Muralidar K.
        • Siddaraj K.S.
        • Sankaran K.
        • Gupta G.D.
        Familial scleroderma.
        J Assoc Physicians India. 1978; 26: 307-310
        • Sheldon W.B.
        • Lurie D.P.
        • Maricq H.R.
        • et al.
        Three siblings with scleroderma (systemic sclerosis) and two with Raynaud's phenomenon from a single kindred.
        Arthritis Rheum. 1981; 24: 668-676
        • Soppi E.
        • Lehtonen A.
        • Toivanen A
        Familial progressive systemic sclerosis (scleroderma): immunological analysis of two patients and six siblings from a single kindred.
        Clin Exp Immunol. 1982; 50: 275-282
        • Rodnan G.P.
        • Fennell R.H.
        Progressive systemic sclerosis sine scleroderma.
        JAMA. 1962; 180: 665-670
        • Maricq H.R.
        Widefield capillary microscopy.
        Arthritis Rheum. 1981; 24: 1159-1165
        • Maricq H.R.
        Comparison of quantitative and semiquantitative estimates of nailfold capillary abnormalities in scleroderma spectrum disorders.
        Microvasc Res. 1986; 32: 271-276
        • Maricq H.R.
        The microcirculation in scleroderma and allied diseases.
        in: 2nd ed. Advances in microcirculation. Karger, Basel1982: 17-52
        • Chen Z.
        • Silver R.M.
        • Ainsworth S.K.
        • Dobson R.L.
        • Rust P.
        • Maricq H.R.
        Association between fluorescent antinuclear antibodies, capillary patterns, and clinical features in scleroderma spectrum disorders.
        Am J Med. 1984; 77: 812-822
        • Fleischnick E.
        • Raum D.
        • Alosco S.M.
        • et al.
        Extended MHC haplotypes in 21-hydroxylase-deficiency congenital adrenal hyperplasia: shared genotypes in unrelated patients.
        Lancet. 1983; I: 152-156
        • Schanfield M.S.
        • van Loghem E.
        Human immunoglobulin allotypes.
        in: Weir D.M. 2nd ed. Handbook of experimental immunology. 3. Blackwell, Boston1986: 94.1-94.8
        • Pandey J.P.
        • Shannon B.T.
        • Arala-Chaves M.P.
        • Fudenberg H.H.
        Gm and Km frequencies in a Portugese population.
        Hum Genet. 1982; 61: 154-156
      1. WHO meeting on human immunoglobulin allotypic markers: review of the notation for the allotypic and related markers of human immunoglobulins. 2nd ed. Eur J Immunol. 6. 1976: 599-601
        • Allen R.C.
        • Harley R.A.
        • Talamo R.C.
        A new method for determination of alpha-1-antitrypsin phenotypes using isoelectric focusing on polyacrylamide gel slabs.
        Am J Clin Pathol. 1974; 6: 732-739
        • Masi A.T.
        • Rodnan G.P.
        • Medsger T.A.
        • et al.
        Preliminary criteria for the classification of systemic sclerosis (scleroderma).
        Arthritis Rheum. 1980; 23: 581-590
        • Allen E.V.
        • Brown G.E.
        Raynaud's disease: a critical review of minimal requisites for diagnosis.
        Am J Med Sci. 1931; 183: 187-200
        • Leonhardt T.
        Familial occurrence of collagen diseases. II. Progressive systemic sclerosis and dermatomyositis.
        Acta Med Scand. 1961; 169: 735-742
        • Horn J.R.
        • Kapur J.J.
        • Walker S.E.
        Mixed connective tissue disease in siblings.
        Arthritis Rheum. 1978; 21: 709-714
        • Maricq H.R.
        • LeRoy E.C.
        • D'Angelo W.A.
        • et al.
        Diagnostic potential of in vivo capillary microscopy in scleroderma and related disorders.
        Arthritis Rheum. 1980; 23: 183-189
        • Maricq H.R.
        • Weinberger A.B.
        • LeRoy E.C.
        Early detection of scleroderma-spectrum disorders by in vivo capillary microscopy: a prospective study of patients with Raynaud's phenomenon.
        J Rheumatol. 1982; 9: 289-291
        • Carpentier P.
        • Franco A.
        • Beani J.-C.
        • Reymond J.-L.
        • Amblard P.
        Interet de la capillaroscopie periungueale dans le diagnostic precoce de la sclerodermie systemique.
        Ann Dermatol Venereol. 1983; 110: 11-20
        • Vayssairat M.
        • Fiessinger J.-N.
        • Priollet P
        • Goldberg J
        • Housset E
        Interet de la capillaroscopie pour le diagnostic de la sclerodermie generalisee.
        Rev Med Interne. 1981; 2: 333-340
        • Houtman P.M.
        • Kallenberg C.G.M.
        • Fidler V.
        • Wouda A.A.
        Diagnostic significance of nailfold capillary patterns in patients with Raynaud's phenomenon.
        in: An analysis of patterns discriminating patients with and without connective tissue disease. 2nd ed. J Rheumatol. 13. 1986: 556-563
        • Pan S.F.
        • Rodnan G.P.
        • Deutsch M.
        • Wald N.
        Chromosomal abnormalities in progressive systemic sclerosis (scleroderma) with consideration of radiation effects.
        J Lab Clin Med. 1975; 86: 300-308
        • Emerit I
        • Housset E
        • Feingold J
        Chromosomal breakage and scleroderma: studies in family members.
        J Lab Clin Med. 1976; 88: 81-86
        • Emerit I
        Chromosomal breakage in systemic sclerosis and related disorders.
        Dermatologica. 1976; 153: 145-156
        • Sherer G.K.
        • Jackson B.B.
        • LeRoy E.C.
        Chromosome breakage and sister chromatid exchange frequencies in scleroderma.
        Arthritis Rheum. 1981; 24: 1409-1413
        • Palmer R.G.
        • Pereira R.S.
        • Dore C.J.
        • Denman A.M.
        Sister chromatid exchange frequencies in patients with scleroderma and their relatives.
        Ann Rheum Dis. 1986; 45: 409-411
        • Huet-Warembourg E.
        • Legoff D.
        • Jalbert H
        • et al.
        Aspects cytogenetiques de la sclerodermie generalisee.
        in: Anomalies structurales et echanges de chromatides-soeurs. 2nd ed. Ann Genet (Paris). 25. 1982: 32-35
        • Laurent M.R.
        • Welsh K.I.
        Genetic markers in rheumatological diseases.
        J Immunogenet. 1983; 10: 275-291
        • Rabin B.S.
        • Rodnan G.P.
        • Bassion S.
        • Gill III, T.J.
        HL-A antigens in progressive systemic sclerosis (scleroderma).
        Arthritis Rheum. 1975; 18: 381-382
        • Birnbaum N.S.
        • Rodnan G.P.
        • Rabin B.S.
        • Bassion S.
        Histocompatibility antigens in progressive systemic sclerosis (scleroderma).
        J Rheumatol. 1977; 4: 425-428
        • Freudenberg J.
        • Holzmann H.
        • Schneider S.
        • Korting G.W.
        HLA-Antigenfrequenzen bei Patienten mit progressiver Sklerodermie und Morphaea.
        Arch Dermatol Res. 1978; 263: 197-205
        • Hughes P
        • Gelsthorpe K
        • Doughty R.W.
        • Rowell N.R.
        • Rosenthal F.D.
        • Sneddon W.B.
        The association of HLA-B8 with visceral disease in systemic sclerosis.
        Clin Exp Immunol. 1978; 31: 351-356
        • Clements P.J.
        • Opelz G.
        • Terasaki P.I.
        • Mickey R.M.
        • Furst D.
        Association of HLA antigen A9 with progressive systemic sclerosis (scleroderma).
        Tissue Antigens. 1978; 11: 357-361
        • Giordano M
        • Magri D
        • Valentini G
        • Tirri G
        • De Biasi R
        HLA-SD antigens in progressive systemic sclerosis.
        Arch Dermatol Res. 1979; 266: 213
        • Majsky A
        • Kobikova M
        • Stava Z
        HLA and scleroderma.
        Tissue Antigens. 1979; 14: 359-360
        • Ercilla M.G.
        • Arriaga F.
        • Gratacos M.R.
        • et al.
        HLA antigens and scleroderma.
        Arch Dermatol Res. 1981; 271: 381-385
        • Germain B.F.
        • Espinoza L.R.
        • Bergen L.L.
        • Vagesh M.
        • Vasey F.B.
        Increased prevalence of DRw3 in the CREST syndrome.
        Arthritis Rheum. 1981; 24: 857-859
        • Gladman D.D.
        • Keystone E.C.
        • Baron M.
        • Lee P
        • Cane D
        • Mervert H
        Increased frequency of HLA-DR5 in scleroderma.
        Arthritis Rheum. 1981; 24: 854-856
        • Heidrich H
        • Malchus R
        HLA-antigen in the differential diagnosis of the Raynaud-phenomenon.
        Vasa. 1982; 11: 29-31
        • Kallenberg C.G.M.
        • van der Voort-Beelen J.M.
        • D'Amaro J.
        • The T.H.
        Increased frequency of B8/DR3 in scleroderma and association of the haplotype with impaired cellular immune response.
        Clin Exp Immunol. 1981; 43: 478-485
        • Lynch C.J.
        • Singh G.
        • Whiteside T.L.
        • Rodnan G.P.
        • Medsger Jr, T.A.
        • Rabin B.S.
        Histocompatibility antigens in progressive systemic sclerosis (PSS; scleroderma).
        J Clin Immunol. 1982; 2: 314-318
        • Whiteside T.L.
        • Medsger Jr, T.A.
        • Rodnan G.P.
        HLA-DR antigens in progressive systemic sclerosis (scleroderma).
        J Rheumatol. 1983; 10: 128-131
        • Black C.M.
        • Welsh K.I.
        • Maddison P.J.
        • Jayson M.I.V.
        • Bernstein R.M.
        HLA antigens, autoantibodies and clinical subsets in scleroderma.
        Br J Rheumatol. 1984; 23: 267-271
        • Mollenhauer E.
        • Schmidt R.
        • Heinrichs M.
        • Rittner C
        Scleroderma: possible significance of silent alleles at the C4B locus.
        Arthritis Rheum. 1984; 27: 711-712
        • Chen Z.-Y.
        • Fedrick J.A.
        • Pandey J.P.
        • et al.
        Anticentromere antibody and immunoglobulin allotypes in scleroderma.
        Arch Dermatol. 1985; 121: 339-344
        • Black C.M.
        • Walker A.E.
        • Catoggio L.J.
        • et al.
        Genetic susceptibility to scleroderma-like syndrome induced by vinyl chloride.
        Lancet. 1983; I: 53-56
        • Fennell Jr, R.H.
        • Rodnan G.P.
        • Vazquez J.J.
        Variability of tissue-localized properties of serum from patients with different disease states.
        Lab Invest. 1962; 11: 24-31
        • Rothfield N.F.
        • Rodnan G.P.
        Serum antinuclear antibodies in progressive systemic sclerosis (scleroderma).
        Arthritis Rheum. 1968; 11: 607-617
        • Tuffanelli D.L.
        Scleroderma, immunological and genetic disease in three families.
        Dermatologica. 1969; 138: 93-104
        • Takehara K.
        • Moroi Y.
        • Ishibashi Y.
        Antinuclear antibodies in the relatives of patients with systemic sclerosis.
        Br J Dermatol. 1985; 112: 23-33
        • Maddison P.J.
        • Skinner R.P.
        • Pereira R.S.
        • et al.
        Antinuclear antibodies in the relatives and spouses of patients with systemic sclerosis.
        Ann Rheum Dis. 1986; 45: 793-799
        • Bencze K.
        • Sabatke L.
        • Fruhmann G.
        Alpha1-antitrypsin: the PiMM subtypes.
        in: Do they play a role in development of chronic obstructive pulmonary diseases?2nd ed. Chest. 77. 1980: 761-763
        • Seibold J.R.
        • Iammarino R.M.
        • Rodnan G.P.
        Alpha-1-antitrypsin in progressive systemic sclerosis.
        Arthritis Rheum. 1980; 23: 367-370
        • Michalski J.P.
        • McCombs C.C.
        • Scopelitis E.
        • Biundo Jr, J.J.
        • Medsger Jr, T.A.
        Alpha1-antitrypsin phenotypes, including M subtypes, in pulmonary disease associated with rheumatoid arthritis and systemic sclerosis.
        Arthritis Rheum. 1986; 29: 586-591
        • Erasmus L.D.
        Scleroderma in gold-miners on the Witwatersrand with particular reference to pulmonary manifestations.
        S Afr J Lab Clin Med. 1957; 3: 209-231
        • Bernstein R.
        • Prinsloo I.
        • Zwi S.
        • Andrew M.J.A.
        • Dawson B.
        • Jenkins T
        Chromosomal aberrations in occupation-associated progressive systemic sclerosis.
        S Afr Med J. 1980; 58: 235-237
        • Rodnan G.P.
        • Benedek T.G.
        • Medsger Jr, T.A.
        • Cammarata R.J.
        The association of progressive systemic sclerosis (scleroderma) with coal miners' pneumoconiosis and other forms of silicosis.
        Ann Intern Med. 1967; 66: 323-334
        • Haustein U.F.
        • Ziegler V.
        Environmentally induced systemic sclerosis-like disorders.
        Int J Dermatol. 1985; 24: 147-151
        • Fessel W.J.
        Scleroderma and welding.
        N Engl J Med. 1977; 296: 1537
        • Lange C.-E.
        • Juhe S
        • Stein G
        • Veitman G
        Die sogenannte Vinylchlorid-Krankheit—eine berufsbedingte Systemskle—rose?.
        Int Arch Arbeitsmed. 1974; 32: 1-32
        • Rush P.J.
        • Bell M.J.
        • Fam A.G.
        Toxic oil syndrome (Spanish oil disease) and chemically induced scleroderma-like conditions.
        J Rheumatol. 1984; 11: 262-264
        • Gilsanz V.
        • Alvarez J.L.
        • Serrano S.
        • Simon J
        Evolution of the alimentary toxic oil syndrome due to ingestion of denatured rapeseed oil.
        Arch Intern Med. 1984; 144: 254-256