Cutaneous Manifestations of Scleroderma and Scleroderma-Like Disorders: a Comprehensive Review

Abstract

Scleroderma refers to an autoimmune connective tissue fibrosing disease, including three different subsets: localized scleroderma, limited cutaneous systemic sclerosis, and diffuse cutaneous systemic sclerosis with divergent patterns of organ involvement, autoantibody profiles, management, and prognostic implications. Although systemic sclerosis is considered the disease prototype that causes cutaneous sclerosis, there are many other conditions that can mimic and be confused with SSc. They can be classified into immune-mediated/inflammatory, immune-mediated/inflammatory with abnormal deposit (mucinoses), genetic, drug-induced and toxic, metabolic, panniculitis/vascular, and (para)neoplastic disorders according to clinico-pathological and pathogenetic correlations. This article reviews the clinical presentation with emphasis on cutaneous disease, etiopathogenesis, diagnosis, and treatment options available for the different forms of scleroderma firstly and for scleroderma-like disorders, including scleromyxedema, scleredema, nephrogenic systemic fibrosis, eosinophilic fasciitis, chronic graft-versus-host disease, porphyria cutanea tarda, diabetic stiff-hand syndrome (diabetic cheiroartropathy), and other minor forms. This latter group of conditions, termed also scleroderma mimics, sclerodermiform diseases, or pseudosclerodermas, shares the common thread of skin thickening but presents with distinct cutaneous manifestations, skin histology, and systemic implications or disease associations, differentiating each entity from the others and from scleroderma. The lack of Raynaud’s phenomenon, capillaroscopic abnormalities, or scleroderma-specific autoantibodies is also important diagnostic clues. As cutaneous involvement is the earliest, most frequent and characteristic manifestation of scleroderma and sclerodermoid disorders, dermatologists are often the first-line doctors who must be able to promptly recognize skin symptoms to provide the affected patient a correct diagnosis and appropriate management.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Abbreviations

SSc:

Systemic sclerosis

LSc:

Localized scleroderma

lcSSc:

Limited cutaneous systemic scleroderma

dcSSc:

Diffuse cutaneous systemic scleroderma

Anti-RNAP III:

anti-RNA polymerase III

TGF-ß:

Transforming growth factor-ß

TNF:

Tumor necrosis factor

Fli1:

Friend leukemia integration factor 1

PDGF:

Platelet-derived growth factor

ACR:

American College of Rheumatology

EULAR:

European League Against Rheumatism

EUSTAR:

European Scleroderma Trials and Research

ANA:

Anti-nuclear antibody

MES:

Microangiopathy evolutiontion score

NVC:

Nailfold videocapillaroscopy

CT:

Cutaneous telangectasias

mRSS:

Modified Rodnan skin score

DUs:

Digital ulcers

ENA:

Extractable nuclear antigens

ACA:

Anti-centromere antibody

Anti-Scl-70:

Anti-topoisomerase I

PM/Scl:

Polymiositis/scleroderma

PFH:

Progressive hemifacial atrophy

LoSSI:

Localized scleroderma Skin Severity Index

MTX:

Methotrexate

NSF:

Nephrogenic systemic fibrosis

GBCAs:

Gadolinium-based contrast agents

MRI:

Magnetic resonance imaging

EF:

Eosinophilic fasciitis

HLA:

Human leukocyte antigens

IFN gamma:

Interferon gamma

TIMP-1:

Metalloproteinase

ESR:

Erythrocyte sedimentation rate

PET-CT:

Positron emission tomography

GVHD:

Graft-versus-host disease

La/SSB:

Anti-lupus anti-coagulant Sjögren’s syndrome-related antigen B

PUVA:

Psoralen plus ultraviolet A

GVT:

Graft versus tumor

PCT:

Porphyria cutanea tarda

UROD:

Uroporphyrinogen decarboxylase

HFE:

Hemochromatosis

HIV:

Human immunodeficiency virus

URO:

Uroporphyrin

COPRO:

Coproporphyrin

ALA:

Aminolevulinic acid

PBG:

Porphobilinogen

DM:

Diabetes mellitus

AGEs:

Advanced glycosylation end-products

WS:

Werner syndrome

References

  1. 1.

    Gabrielli A, Avvedimento EV, Krieg T (2009) Scleroderma. N Engl J Med 360:1989–2003

    CAS  PubMed  Article  Google Scholar 

  2. 2.

    Mayes MD (2003) Scleroderma epidemiology. Rheum Dis Clin North Am 29:239–254

    PubMed  Article  Google Scholar 

  3. 3.

    Elhai M, Avouac J, Walker UA, Matucci-Cerinic M, Riemekasten G, Airo P et al (2016) A gender gap in primary and secondary heart dysfunctions in systemic sclerosis: a EUSTAR prospective study. Ann Rheum Dis 75:163–169

    PubMed  Article  Google Scholar 

  4. 4.

    Steen V, Domsic RT, Lucas M, Fertig N, Medsger TA Jr (2012) A clinical and serologic comparison of African American and Caucasian patients with systemic sclerosis. Arthritis Rheum 64:2986–2994

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  5. 5.

    Scalapino K, Arkachaisri T, Lucas M, Fertig N, Helfrich DJ, Londino AV Jr, Steen VD, Medsger TA Jr (2006) Childhood onset systemic sclerosis: classification, clinical and serologic features, and survival in comparison with adult onset disease. J Rheumatol 33:1004–1013

    PubMed  Google Scholar 

  6. 6.

    Pattanaik D, Brown M, Postlethwaite BC, Postlethwaite AE (2015) Pathogenesis of systemic sclerosis. Front Immunol 6:272

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  7. 7.

    Gladman DD, Kung TN, Siannis F, Pellett F, Farewell VT, Lee P (2005) HLA markers for susceptibility and expression in scleroderma. J Rheumatol 32:1481–1487

    CAS  PubMed  Google Scholar 

  8. 8.

    Radstake TR, Gorlova O, Rueda B et al (2010) Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus. Nat Genet 42:426–429

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  9. 9.

    Distler O, Cozzio A (2016) Systemic sclerosis and localized scleroderma—current concepts and novel targets for therapy. Semin Immunopathol 38:87–95

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Laxer RM, Zulian F (2006) Localized scleroderma. Curr Opin Rheumatol 18:606–613

    PubMed  Article  Google Scholar 

  11. 11.

    Grabell D, Hsieh C, Andrew R, Martires K, Kim A, Vasquez R et al (2014) The role of skin trauma in the distribution of morphea lesions: a cross-sectional survey of the morphea in adults and children cohort IV. J Am Acad 71:493–498

    Article  Google Scholar 

  12. 12.

    Matucci-Cerinic M, Kahaleh B, Wigley FM (2013) Evidence that systemic sclerosis is a vascular disease. Arthritis Rheum 65:1953–1962

    CAS  PubMed  Article  Google Scholar 

  13. 13.

    Pattanaik D, Brown M, Postlethwaite AE (2011) Vascular involvement in systemic sclerosis (scleroderma). J Inflamm Res 4:105–125

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Varga J (2008) Systemic sclerosis an update. Bull NYU Hosp Jt Dis 66:198–202

    PubMed  Google Scholar 

  15. 15.

    Kraaij MD, van Laar JM (2008) The role of B cells in systemic sclerosis. Biologics 2:389–395

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Yoshizaki A, Sato S (2015) Abnormal B lymphocyte activation and function in systemic sclerosis. Ann Dermatol 27:1–9

    PubMed  PubMed Central  Article  Google Scholar 

  17. 17.

    Stern EP, Denton CP (2015) The pathogenesis of systemic sclerosis. Rheum Dis Clin N Am 41:367–382

    Article  Google Scholar 

  18. 18.

    van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A et al (2013) Classification criteria for systemic sclerosis: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 72:1747–1755

    PubMed  Article  Google Scholar 

  19. 19.

    Jaeger VK, Wirz EG, Allanore Y, Rossbach P, Riemekasten G, Hachulla E, Distler O, Airò P, Carreira PE, Balbir Gurman A, Tikly M, Vettori S, Damjanov N, Müller-Ladner U, Distler JH, Li M, Walker UA, EUSTAR Co-authors (2016) Incidences and risk factors of organ manifestations in the early course of systemic sclerosis: a longitudinal EUSTAR study. PLoS One 11:e0163894

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  20. 20.

    Desbois AC, Cacoub P (2016) Systemic sclerosis: an update in 2016. Autoimmun Rev 15:417–426

    PubMed  Article  Google Scholar 

  21. 21.

    Meier FM, Frommer KW, Dinser R et al (2012) Update on the profile of the EUSTAR cohort: an analysis of the EULAR scleroderma trials and research group database. Ann Rheum Dis 71:1355e60

    Article  Google Scholar 

  22. 22.

    Hughes M, Herrick AL (2016) Raynaud’s phenomenon. Best Pract Res Clin Rheumatol 30:112–132

    PubMed  Article  Google Scholar 

  23. 23.

    Avouac J, Fransen J, Walker UA et al (2011) Preliminary criteria for the very early diagnosis of systemic sclerosis: results of a Delphi consensus study from EULAR scleroderma trials and research group. Ann Rheum Dis 70:476e81

    Google Scholar 

  24. 24.

    Minier T, Guiducci S, Bellando-Randone S, Bruni C, Lepri G, Czirjak L et al (2014) Preliminary analysis of the very early diagnosis of systemic sclerosis (VEDOSS) EUSTAR multicentre study: evidence for puffy fingers as a pivotal sign for suspicion of systemic sclerosis. Ann Rheum Dis 73:2087–2093

    PubMed  Article  Google Scholar 

  25. 25.

    Clements PJ, Lachenbruch PA, Seibold JR, Zee B, Steen VD, Brennan P et al (1993) Skin thickness score in systemic sclerosis: an assessment of interobserver variability in 3 independent studies. J Rheumatol 20:1892–1896

    CAS  PubMed  Google Scholar 

  26. 26.

    Barsotti S, Stagnaro C, Della Rossa A (2015) Systemic sclerosis: a critical digest of the recent literature. Clin Exp Rheumatol 33(Suppl. 91):S3–14

    PubMed  Google Scholar 

  27. 27.

    Czirják L, Nagy Z, Aringer M et al (2007) The EUSTAR model for teaching and implementing the modified Rodnan skin score in systemic sclerosis. Ann Rheum Dis 66:966–969

    PubMed  PubMed Central  Article  Google Scholar 

  28. 28.

    Hesselstrand R, Carlestam J, Wildt M, Sandqvist G, Andréasson K (2015) High frequency ultrasound of skin involvement in systemic sclerosis—a follow-up study. Arthritis Res Ther 17:329

    PubMed  PubMed Central  Article  Google Scholar 

  29. 29.

    Santiago T, Alcacer-Pitarch B, Salvador MJ, Del Galdo F, Redmond AC, da Silva JAP (2016) A preliminary study using virtual touch imaging and quantification for the assessment of skin stiffness in systemic sclerosis. Clin Exp Rheumatol 34(Suppl. 100):S137–S141

    Google Scholar 

  30. 30.

    Salem B, Rim BH, Sihem BK, Maher B (2013) Oral manifestations of systemic sclerosis. Pan Afr Med J 16:114

    PubMed  PubMed Central  Article  Google Scholar 

  31. 31.

    Bajraktari IH, Kryeziu A, Sherifi F, Bajraktari H, Lahu A, Bajraktari G (2015) Oral manifestations of systemic sclerosis and correlation with anti-topoisomerase I antibodies (SCL-70). Med Arch 69:153–156

    PubMed  PubMed Central  Article  Google Scholar 

  32. 32.

    Maddali Bongi S, Del Rosso A, Galluccio F, Tai G, Sigismondi F, Passalacqua M, Landi G, Baccini M, Conforti ML, Miniati I et al (2009) Efficacy of a tailored rehabilitation program for systemic sclerosis. Clin Exp Rheumatol 27:S44–S50

    Google Scholar 

  33. 33.

    Silvestre-Rangil J, Martinez-Herrera M, Silvestre FJ (2015) Dental management of patients with microstomia. A review of the literature and update on the treatment. J Oral Res 4:340–350

    Article  Google Scholar 

  34. 34.

    Crincoli V, Fatone L, Fanelli M, Rotolo RP, Chialà A, Favia G, Lapadula G (2016) Orofacial manifestations and temporomandibular disorders of systemic scleroderma: an observational study. Int J Mol Sci 17:1189

    PubMed Central  Article  CAS  Google Scholar 

  35. 35.

    Jagadish R, Mehta DS, Jagadish P (2012) Oral and periodontal manifestations associated with systemic sclerosis: a case series and review. J Indian Soc Periodontol 16:271–274

    PubMed  PubMed Central  Article  Google Scholar 

  36. 36.

    Aliko A, Ciancaglini R, Alushi A, Tafaj A, Ruci D (2011) Temporomandibular joint involvement in rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis. Int J Oral Maxillofac Surg 40:704–709

    CAS  PubMed  Article  Google Scholar 

  37. 37.

    Denton CP (2015) Systemic sclerosis: from pathogenesis to targeted therapy. Clin Exp Rheumatol 33:S3–S7

    PubMed  Google Scholar 

  38. 38.

    Pizzorni C, Giampetruzzi AR, Mondino C, Facchiano A, Abeni D, Paolino S, Ruaro B, Smith V, Sulli A, Cutolo M (2016) Nailfold capillaroscopic parameters and skin telangiectasia patterns in patients with systemic sclerosis. Microvasc Res 111:20–24

    PubMed  Article  Google Scholar 

  39. 39.

    Smith V, Decuman S, Sulli A, Bonroy C, Piettte Y, Deschepper E et al (2012) Do worsening scleroderma capillaroscopic pattern predict future severe organ involvement? A pilot study. Ann Rheum Dis 71:1636–1639

    PubMed  Article  Google Scholar 

  40. 40.

    Elmansour I, Chiheb S, Benchikhi H (2014) Nail changes in connective tissue diseases: a study of 39 cases. Pan Afr Med J 18:150

    PubMed  PubMed Central  Article  Google Scholar 

  41. 41.

    Marie I, Gremain V, Nassermadji K, Richard L, Joly P, Menard JF, Levesque H (2016) Nail involvement in systemic sclerosis. J Am Acad Dermatol. doi:10.1016/j.jaad.2016.11.024

  42. 42.

    Nabil PA, Rao RA, Shrutakirti Shenoi D, Balachandran C (2006) Nail unit in collagen vascular diseases: a clinical, histopathological and direct immunofluorescence study. Indian J Dermatol 51:265–268

    Article  Google Scholar 

  43. 43.

    Tunc SE, Ertam I, Pirildar T, Turk T, Ozturk M, Doganavsargil E (2007) Nail changes in connective tissue diseases: do nail changes provide clues for the diagnosis? J Eur Acad Dermatol Venereol 21:497–503

    CAS  PubMed  Google Scholar 

  44. 44.

    Sultan-Bichat N, Menard J, Perceau G, Staerman F, Bernard P, Reguia Z (2012) Treatment of calcinosis cutis by extracorporeal shock-wave lithotripsy. J Am Acad Dermatol 66:424–429

    PubMed  Article  Google Scholar 

  45. 45.

    Johnstone EM, Hutchinson CE, Vail A, Chevance A, Herrick AL (2012) Acro-osteolysis in systemic sclerosis is associated with digital ischemia and severe calcinosis. Rheumatology 51:2234–2238

    CAS  PubMed  Article  Google Scholar 

  46. 46.

    Avouac J, Mogavero G, Guerini H et al (2011) Predictive factors of hand radiographic lesions in systemic sclerosis: a prospective study. Ann Rheum Dis 70:630–633

    CAS  PubMed  Article  Google Scholar 

  47. 47.

    Koutaissoff S, Vanthuyne M, Smith V et al (2011) Hand radiological damage in systemic sclerosis: comparison with a control group and clinical and functional correlations. Semin Arthritis Rheum 40:455–460

    PubMed  Article  Google Scholar 

  48. 48.

    Giampetruzzi AR, Mondino C, Facchiano A, Bono R, Puddu P, Didona B, Abeni D, Cutolo M (2013) Association of dermoscopic profiles of telangiectases with nailfold videocapillaroscopic patterns in patients with systemic sclerosis. J Rheumatol 40:1630–1632

    PubMed  Article  Google Scholar 

  49. 49.

    Hurabielle C, Avouac J, Lepri G, de Risi T, Kahan A, Allanore Y (2016) Skin telangiectasia and the identification of a subset of systemic sclerosis patients with severe vascular disease. Arthritis Care Res 68:1021–1027

    Article  Google Scholar 

  50. 50.

    Matucci-Cerinic M, Denton CP, Furst DE, Mayes MD, Hsu VM, Carpentier P et al (2011) Bosentan treatment of digital ulcers related to systemic sclerosis: results from the RAPIDS-2 randomised, double-blind, placebo-controlled trial. Ann Rheum Dis 70:32–38

    CAS  PubMed  Article  Google Scholar 

  51. 51.

    Walker UA, Tyndall A, Czirjak L, Denton C, Farge-Bancel D, Kowal-Bielecka O et al (2007) Clinical risk assessment of organ manifestations in systemic sclerosis: a report from the EULAR scleroderma trials and research group database. Ann Rheum Dis 66:754–763

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  52. 52.

    Almeida C, Almeida I, Vasconcelos C (2015) Quality of life in systemic sclerosis. Auto Immun Rev 14:1087–1096

    Article  Google Scholar 

  53. 53.

    Denton CP, Krieg T, Guillevin L, Schwierin B, Rosenberg D, Silkey M et al (2012) De- mographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO registry. Ann Rheum Dis 71:718–721

    PubMed  PubMed Central  Article  Google Scholar 

  54. 54.

    Brand M, Hollaender R, Rosenberg D, Scott M, Hunsche E, Tyndall A, Denaro V, EUSTAR Co-investigators et al (2015) An observational cohort study of patients with newly diagnosed digital ulcer disease secondary to systemic sclerosis registered in the EUSTAR database. Clin Exp Rheumatol 33(4 Suppl 91):S47–S54

    PubMed  Google Scholar 

  55. 55.

    Mihai C, Landewe R, van der Heijde D, Walker UA, Constantin PI, Gherghe AM et al (2016) Digital ulcers predict a worse disease course in patients with systemic sclerosis. Ann Rheum Dis Ann Rheum Dis 75:681–686

    CAS  PubMed  Article  Google Scholar 

  56. 56.

    Cutolo M, Sulli A, Secchi ME, Paolino S, Pizzorni C (2006) Nailfold capillaroscopy is useful for the diagnosis and follow-up of autoimmune rheumatic diseases. A future tool for the analysis of microvascular heart involvement? Rheumatology 45:43–46

    Article  Google Scholar 

  57. 57.

    Sebastiani M, Manfredi A, Colaci M, D’amico R, Malagoli V, Giuggioli D et al (2009) Capillaroscopic skin ulcer risk index: a new prognostic tool for digital skin ulcer development in systemic sclerosis patients. Arthritis Rheum 61:688–694

    CAS  PubMed  Article  Google Scholar 

  58. 58.

    Ruaro B, Sulli A, Smith V, Paolino S, Pizzorni C, Cutolo M (2015) Short-term follow-up of digital ulcers by laser speckle contrast analysis in systemic sclerosis patients. Microvasc Res 101:82–85

    PubMed  Article  Google Scholar 

  59. 59.

    Barbano B, Marra AM, Quarta S, Gigante A, Barilaro G, Gasperini ML, Rosato E (2016) In systemic sclerosis skin perfusion of hands is reduced and may predict the occurrence of new digital ulcers. Microvasc Res 110:1–4

    PubMed  Article  Google Scholar 

  60. 60.

    Anderson ME, Moore TL, Lunt M, Herrick AL (2007) The ‘distal-dorsal difference’: a thermographic parameter by which to differentiate between primary and secondary Raynaud’s phenomenon. Rheumatology 46:533–538

    CAS  PubMed  Article  Google Scholar 

  61. 61.

    Onishi S, Homma Y, Hasegawa H, Yasukawa M (2013) Multiple tumoral calcinosis in systemic sclerosis. Intern Med 52:2689

    PubMed  Article  Google Scholar 

  62. 62.

    Valenzuela A, Chung L (2015) Calcinosis: pathophysiology and management. Curr Opin Rheumatol 27:542–548

    CAS  PubMed  Article  Google Scholar 

  63. 63.

    Zimmermann AF, Pizzichini MM (2013) Update on etiopathogenesis of systemic sclerosis. Rev Bras Reumatol 53:516–524

    PubMed  Article  Google Scholar 

  64. 64.

    Vachiramon V (2011) Approach to reticulate hyperpigmentation. Clin Exp Dermatol 36:459–466

    CAS  PubMed  Article  Google Scholar 

  65. 65.

    Ee HL, Tan SH (2005) Reticulate hyperpigmented scleroderma: a new pigmentary manifestation. Clin Exp Dermatol 30:131–133

    CAS  PubMed  Article  Google Scholar 

  66. 66.

    Ziemek J, Man A, Hinchcliff M, Varga J, Simms RW, Lafyatis R (2016) The relationship between skin symptoms and the scleroderma modification of the health assessment questionnaire, the modified Rodnan skin score, and skin pathology in patients with systemic sclerosis. Rheumatology 55:911–917

    PubMed  Article  Google Scholar 

  67. 67.

    Krieg T, Takehara K (2009) Skin disease: a cardinal feature of systemic sclerosis. Rheumatology (Oxford). doi:10.1093/rheumatology/kep108

  68. 68.

    Rongioletti F, Gambini C, Micalizzi C, Pastorino A, Rebora A (1994) Mucin deposits in morphea and systemic scleroderma. Dermatology 189:157–158

    CAS  PubMed  Article  Google Scholar 

  69. 69.

    Fett N, Werth VP (2011) Update on morphea: part I. Epidemiology, clinical presentation, and pathogenesis. J Am Acad Dermatol 64:217–228

    PubMed  Article  Google Scholar 

  70. 70.

    Kreuter A, Krieg T, Worm M et al (2009) AWMF guideline no. 013/066. Diagnosis and therapy of circumscribed scleroderma. J Dtsch Dermatol Ges 7:1–14

    Google Scholar 

  71. 71.

    Ho KT, Reveille JD (2003) The clinical relevance of autoantibodies in scleroderma. Arthritis Res Ther 5:80–93

    CAS  PubMed  Google Scholar 

  72. 72.

    Kelly A, Derk CT (2015) Anti-RNA polymerase III antibodies in systemic sclerosis. Open J Rheumatol Autoimmune Dis 5:81–86

    Article  Google Scholar 

  73. 73.

    Arkachaisri T, Fertig N, Pino S, Medsger TA Jr (2008) Serum autoantibodies and their clinical associations in patients with childhood- and adult-onset linear scleroderma. A single-center study. J Rheumatol 35:2439–2444

    CAS  PubMed  Article  Google Scholar 

  74. 74.

    Walker KM, Pope J, participating members of the Scleroderma Clinical Trials Consortium (SCTC), Canadian Scleroderma Research Group (CSRG) (2012) Treatment of systemic sclerosis complications: what to use when first-line treatment fails—a consensus of systemic sclerosis experts. Semin Arthritis Rheum 42:42–55

    CAS  PubMed  Article  Google Scholar 

  75. 75.

    Pope JE, Bellamy N, Seibold JR et al (2001) A randomized, controlled trial of methotrexate versus placebo in early diffuse scleroderma. Arthritis Rheum 44:1351–1358

    CAS  PubMed  Article  Google Scholar 

  76. 76.

    Denton CP, Khanna D (2017) Systemic sclerosis. Lancet. doi:10.1016/S0140-6736(17)30933-9

  77. 77.

    Tashkin DP, Elashoff R, Clements PJ, the Scleroderma Lung Study Research Group (2006) Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med 354:2655–2666

    CAS  PubMed  Article  Google Scholar 

  78. 78.

    Connolly KL, Griffith JL, McEvoy M, Lim HW (2015) Ultraviolet A1 phototherapy beyond morphea: experience in 83 patients. Photodermatol Photoimmunol Photomed 31:289–295

    PubMed  Article  Google Scholar 

  79. 79.

    Kowal-Bielecka O, Landewé R, Avouac J, Chwiesko S, Miniati I et al (2009) EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR scleroderma trials and research group (EUSTAR). Ann Rheum Dis 68:620–628

    CAS  PubMed  Article  Google Scholar 

  80. 80.

    Mouthon L, Bussone G, Berezné A, Noël LH, Guillevin L (2014) Scleroderma renal crisis. J Rheumatol 41:1040–1048

    CAS  PubMed  Article  Google Scholar 

  81. 81.

    Papp G, Horvath IF, Barath S et al (2012) Immunomodulatory effects of extracorporeal photochemotherapy in systemic sclerosis. Clin Immunol 142:150–159

    CAS  PubMed  Article  Google Scholar 

  82. 82.

    Knobler R, Berlin G, Calzavara-Pinton P et al (2014) Guidelines on the use of extracorporeal photopheresis. J Eur Acad Dermatol Venereol 28:1–37

    CAS  PubMed  Article  Google Scholar 

  83. 83.

    Thompson AE, Shea B, Welch V, Fenlon D, Pope JE (2001) Calcium-channel blockers for Raynaud’s phenomenon in systemic sclerosis. Arthritis Rheum 44:1841–1847

    CAS  PubMed  Article  Google Scholar 

  84. 84.

    Hughes M, Ong VH, Anderson ME et al (2015) Consensus best practice pathway of the UK scleroderma study group: digital vasculopathy in systemic sclerosis. Rheumatology 54:2015–2024

    CAS  PubMed  Article  Google Scholar 

  85. 85.

    Fries R, Shariat K, von Wilmowsky H, Bohm M (2005) Sildenafil in the treatment of Raynaud’s phenomenon resistant to vasodilatory therapy. Circulation 112:2980–2985

    CAS  PubMed  Google Scholar 

  86. 86.

    Foti R, Visalli E, Amato G et al (2017) Long-term clinical stabilization of scleroderma patients treated with a chronic and intensive IV iloprost regimen. Rheumatol Int 37:245–249

    PubMed  Article  Google Scholar 

  87. 87.

    Tingey T, Shu J, Smuczek J et al (2013) Meta-analysis of healing and prevention of digital ulcers in systemic sclerosis. Arthritis Care Res (Hoboken) 65:1460–1471

    CAS  Article  Google Scholar 

  88. 88.

    De Cata A, Inglese M, Molinaro F et al (2016) Digital ulcers in scleroderma patients: a retrospective observational study. Int J Immunopathol Pharmacol 29:180–187

    PubMed  Article  CAS  Google Scholar 

  89. 89.

    Balin SJ, Wetter DA, Andersen LK, Davis MD (2012) Calcinosis cutis occurring in association with autoimmune connective tissue disease: the Mayo Clinic experience with 78 patients, 1996–2009. Arch Dermatol 148:455–462

    CAS  PubMed  Article  Google Scholar 

  90. 90.

    Gutierrez A Jr, Wetter DA (2012) Calcinosis cutis in autoimmune connective tissue diseases. Dermatol Ther 25:195–206

    PubMed  Article  Google Scholar 

  91. 91.

    Dinsdale G, Murray A, Moore T et al (2014) A comparison of intense pulsed light and laser treatment of telangiectases in patients with systemic sclerosis: a within-subject randomized trial. Rheumatology 53:1422–1430

    PubMed  Article  Google Scholar 

  92. 92.

    Denton CP, Khanna D (2017) Systemic sclerosis. Autoimmun Rev 16:377–384

    Article  CAS  Google Scholar 

  93. 93.

    Sanges S, Rivière S, Mekinian A et al (2017) Intravenous immunoglobulins in systemic sclerosis: data from a French nationwide cohort of 46 patients and review of the literature. Autoimmun Rev 16:377–384

    CAS  PubMed  Article  Google Scholar 

  94. 94.

    Lee JJ, Pope JE (2016) Emerging drugs and therapeutics for systemic sclerosis. Expert Opin Emerg Drugs 21:421–430

    CAS  PubMed  Article  Google Scholar 

  95. 95.

    Tyndall AJ, Bannert B, Vonk M et al (2010) Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis 69:1809

    PubMed  Article  Google Scholar 

  96. 96.

    Rubio-Rivas M, Royo C, Simeón CP, Corbella X, Fonollosa V (2014) Mortality and survival in systemic sclerosis: systematic review and meta-analysis. Semin Arthritis Rheum 44:208–219

    PubMed  Article  Google Scholar 

  97. 97.

    Careta MF, Romiti R (2015) Localized scleroderma: clinical spectrum and therapeutic update. An Bras Dermatol 90:62–73

    PubMed  PubMed Central  Article  Google Scholar 

  98. 98.

    Peterson LS, Nelson AM, Su WP, Mason T, O’Fallon WM, Gabriel SE (1997) The epidemiology of morphea (localized scleroderma) in Olmsted County 1960–1993. J Rheumatol 24:73–80

    CAS  PubMed  Google Scholar 

  99. 99.

    Zulian F, Athreya BH, Laxer R, Nelson AM, Feitosa de Oliveira SK, Punaro MG et al (2006) Juvenile localized scleroderma: clinical and epidemiological features in 750 children. An international study. Rheumatology (Oxford) 45:614–620

    CAS  Article  Google Scholar 

  100. 100.

    Murray KJ, Laxer RM (2002) Scleroderma in children and adolescents. Rheum Dis Clin N Am 28:603–624

    Article  Google Scholar 

  101. 101.

    Christen-Zaech S, Hakim MD, Afsar FS, Paller AS (2008) Pediatric morphea (localized scleroderma): review of 136 patients. J Am Acad Dermatol 59:385–396

    PubMed  Article  Google Scholar 

  102. 102.

    Leitenberger JJ, Cayce RL, Haley RW, Adams-Huet B, Bergstresser PR, Jacobe HT (2009) Distinct autoimmune syndromes in morphea: a review of 245 adult and pediatric cases. Arch Dermatol 145:545–550

    PubMed  PubMed Central  Article  Google Scholar 

  103. 103.

    Marzano AV, Menni S, Parodi A, Borghi A, Fuligni A, Fabbri P et al (2003) Localized scleroderma in adults and children. Clinical and laboratory investigations on 239 cases. Eur J Dermatol 13:171–176

    PubMed  Google Scholar 

  104. 104.

    Zulian F, Cuffaro G, Sperotto F (2013) Scleroderma in children: an update. Curr Opin Rheumatol 25:643–650

    PubMed  Article  Google Scholar 

  105. 105.

    Slobodin G, Rimar D (2017) Regulatory T cells in systemic sclerosis: a comprehensive review. Clin Rev Allergy Immunol 52:194–201

    CAS  PubMed  Article  Google Scholar 

  106. 106.

    Peterson LS, Nelson AM, Su WP (1995) Classification of morphea (localized scleroderma). Mayo Clin Proc 70:1068–1076

    CAS  PubMed  Article  Google Scholar 

  107. 107.

    Zulian F, Vallongo C, Woo P, Russo R, Ruperto N, Harper J et al (2005) Localized scleroderma in childhood is not just a skin disease. Arthritis Rheum 52:2873–2881

    PubMed  Article  Google Scholar 

  108. 108.

    Batista CM, Lemos MO, Franceschi LE, Basilio CB, Reis CM (2014) Case for diagnosis. An Bras Dermatol 89:671–673

    PubMed  PubMed Central  Article  Google Scholar 

  109. 109.

    Avancini J, Valente NY, Romiti R (2015) Generalized lenticular atrophoderma of Pasini and Pierini. Pediatr Dermatol 32:389–391

    PubMed  Article  Google Scholar 

  110. 110.

    Zheng Y, Zhang R, Kang D, Zhu W (2015) Atrophoderma of Pasini and Pierini in zosteriform distribution. G Ital Dermatol Venereol 150:753–755

    CAS  PubMed  Google Scholar 

  111. 111.

    Tas B, Sar M (2015) Linear atrophoderma of Moulin: a distinct entity or blaschko-linear variant of atrophoderma of Pasini and Pierini? G Ital Dermatol Venereol 150:636–638

    CAS  PubMed  Google Scholar 

  112. 112.

    Zahedi Niaki O, Sissons W, Nguyen VH, Zargham R, Jafarian F (2015) Linear atrophoderma of Moulin: an underrecognized entity. Pediatr Rheumatol Online J 13:39

    PubMed  PubMed Central  Article  Google Scholar 

  113. 113.

    Bielsa I, Ariza A (2007) Deep morphea. Semin Cutan Med Surg 26:90–95

    CAS  PubMed  Article  Google Scholar 

  114. 114.

    Kobayashi KA, Lui H, Prendiville JS (1991) Solitary morphea profunda in a 5-year-old girl: case report and review of the literature. Pediatr Dermatol 8:292–295

    CAS  PubMed  Article  Google Scholar 

  115. 115.

    Kirsner RS, Pardes JB, Falanga V (1993) Solitary fibrosing paraspinal plaque: solitary morphea profunda. Br J Dermatol 128:99–101

    CAS  PubMed  Article  Google Scholar 

  116. 116.

    Azad J, Dawn G, Shaffrali FC, Holmes SC, Barnetson RJ, Forsyth A (2004) Does solitary morphea profunda progress? Clin Exp Dermatol 29:25–27

    CAS  PubMed  Article  Google Scholar 

  117. 117.

    Blaszczyk M, Krysicka-Janiger K, Jabłońska S (2000) Primary atrophic profound linear scleroderma. Dermatology 200:63–66

    CAS  PubMed  Article  Google Scholar 

  118. 118.

    Malandrini A, Dotti MT, Federico A (1997) Selective ipsilateral neuromuscular involvement in a case of facial and somatic hemiatrophy. Muscle Nerve 20:890–892

    CAS  PubMed  Article  Google Scholar 

  119. 119.

    Herrick AL, Ennis H, Bhushan M, Silman AJ, Baildam EM (2010) Incidence of childhood linear scleroderma and systemic sclerosis in the UK and Ireland. Arthritis Care Res (Hoboken) 62:213–218

    Article  Google Scholar 

  120. 120.

    Hatzis JA, Stratigos AJ, Dimopoulos JC, Tzermias CK, Orfanidou A, Bassioukas KC (1992) Linear scleroderma with severe leg deformity. Australas J Dermatol 33:155–157

    CAS  PubMed  Article  Google Scholar 

  121. 121.

    Tuffanelli DL (1998) Localized scleroderma. Semin Cutan Med Surg 17:27–33

    CAS  PubMed  Article  Google Scholar 

  122. 122.

    Chiang KL, Chang KP, Wong TT, Hsu TR (2009) Linear scleroderma “en coup de sabre”: initial presentation as intractable partial seizures in a child. Pediatr Neonatol 50:294–298

    PubMed  Article  Google Scholar 

  123. 123.

    Tollefson MM, Witman PM (2007) En coup de sabre morphea and Parry-Romberg syndrome: a retrospective review of 54 patients. J Am Acad Dermatol 56:257–263

    PubMed  Article  Google Scholar 

  124. 124.

    Chung MH, Sum J, Morrell MJ, Horoupian DS (1995) Intracerebral involvement in scleroderma en coup de sabre: report of case with neuropathologic findings. Ann Neurol 37:679–681

    CAS  PubMed  Article  Google Scholar 

  125. 125.

    Lüer W, Jöckel D, Henze T, Schipper HI (1990) Progressive inflammatory lesions of the brain parenchyma in localized scleroderma of the head. J Neurol 237:379–381

    PubMed  Article  Google Scholar 

  126. 126.

    Jappe U, Hölzle E, Ring J (1996) Parry Romberg syndrome. Review and new observations based on a case with unusual features. Hautarzt 47:599–603

    CAS  PubMed  Article  Google Scholar 

  127. 127.

    Jablonska S, Blaszczyk M, Rosinska D (1998) Progressive facial hemiatrophy and sclero- derma en coup de sabre: clinical presentation and course as related to the onset in early childhood and young adults. Arch Argent Dermatol 48:125–128

    Google Scholar 

  128. 128.

    Lehmann TJA (1992) The Parry-Romberg syndrome of progressive facial hemiatrophy and linear scleroderma en coup de sabre. Mistaken diagnosis or overlaping conditions? J Rheumatol 19:844–845

    Google Scholar 

  129. 129.

    DeFelipe J, Segura T, Arellano JI, Merchán A, DeFelipe-Oroquieta J, Martín P et al (2001) Neuropathological findings in a patient with epilepsy and the Parry-Romberg syndrome. Epilepsia 42:1198–1203

    CAS  PubMed  Article  Google Scholar 

  130. 130.

    Woolfenden AR, Tong DC, Norbash AM, Albers GW (1998) Progressive facial hemiatrophy: abnormality of intracranial vasculature. Neurology 50:1915–1917

    CAS  PubMed  Article  Google Scholar 

  131. 131.

    Gambichler T, Kreuter A, Hoffmann K, Bechara FG, Altmeyer P, Jansen T (2001) Billateral linear scleroderma “en coup de sabre” associated with facial atrophy and neurological complications. BMC Dermatol 1:9

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  132. 132.

    Wartenberg R (1945) Progressive facial hemiatrophy. Arch Neurol Psychiatr 54:75–96

    Article  Google Scholar 

  133. 133.

    Wolf HG, Ehrenclou AH (1927) Trophic disorders of central origin: report of a case of progressive facial hemiatrophy associated with a lipodistrophy and other metabolic derangements. JAMA 88:991–994

    Article  Google Scholar 

  134. 134.

    Parry CH (1825) Collections from unpublished papers, vol 178. Underwood, London, p 47

    Google Scholar 

  135. 135.

    Blaszczyk M, Królicki L, Krasu M, Glinska O, Jablonska S (2003) Progressive facial hemi- atrophy: central nervous system involvement and relationship with scleroderma en coup de sabre. J Rheumatol 30:1997–2004

    PubMed  Google Scholar 

  136. 136.

    Blaszczyk M, Jablonska S (1999) Linear scleroderma en coup de sabre. Relationship with progressive facial hemiatrophy (PFH). Adv Exp Med Biol 455:101–104

    CAS  PubMed  Article  Google Scholar 

  137. 137.

    Sánchez-Pérez S, Escandell-González I, Pinazo-Canales MI, Jordá-Cuevas E (2017) Bullous morphea: description of a new case and discussion of etiologic and pathogenic factors in bulla formation. Actas Dermosifiliogr 108:75–76

    PubMed  Article  Google Scholar 

  138. 138.

    Fernández Flores A, Gatica Torres M, Tinoco Fragoso F, García Hidalgo F, García Hidalgo L, Monroy E et al (2015) Three cases of bullous morphea: histopathologic findings with implications regarding pathogenesis. J Cutan Pathol 42:144–149

    PubMed  Article  Google Scholar 

  139. 139.

    Martinez SB, Gargallo V, Romero FT, Martinez LA, Peralto JL, Martín RL (2016) Generalized morphea with development of bullous lesions at the site of surgical scars. J Dtsch Dermatol Ges 14:827–829

    Google Scholar 

  140. 140.

    Qu T, Fang K (2014) Bullous morphea arising at the site of a healed herpes zoster. J Dermatol 41:553–554

    PubMed  Article  Google Scholar 

  141. 141.

    Falanga V, Medsger TA Jr, Reichlin M (1987) Antinuclear and anti-single-stranded DNA antibodies in morphea and generalized morphea. Arch Dermatol 123:350–353

    CAS  PubMed  Article  Google Scholar 

  142. 142.

    Arkachaisri T, Pino S (2008) Localized scleroderma severity index and global assessments: a pilot study of outcome instruments. J Rheumatol 35:650–657

    PubMed  Article  CAS  Google Scholar 

  143. 143.

    Kreuter A, Krieg T, Worm M, Wenzel J, Moinzadeh P, Kuhn A, Aberer E, Scharffetter-Kochanek K, Horneff G, Reil E, Weberschock T, Hunzelmann N (2016) German guidelines for the diagnosis and therapy of localized scleroderma. J Dtsch Dermatol Ges 14:199–216

    PubMed  Article  Google Scholar 

  144. 144.

    Cunningham BB, Landells ID, Langman C et al (1998) Topical calcipotriolo for morphea/linear scleroderma. J Am Acad Dermatol 39:211–215

    CAS  PubMed  Article  Google Scholar 

  145. 145.

    Stefanaki C, Stefanaki K, Kontochristopoulos G et al (2008) Topical tacrolimus 0.1% ointment in the treatment of localized scleroderma. An open label clinical and histological study. J Dermatol 35:712–718

    PubMed  Article  Google Scholar 

  146. 146.

    Kroft EB, Groeneveld TJ, Seyger MM, de Jong EM (2009) Efficacy of topical tacrolimus 0.1% in active plaque morphea: randomized, double-blind, emollient-controlled pilot study. Am J Clin Dermatol 10:181–187

    PubMed  Article  Google Scholar 

  147. 147.

    Kroft EB, Creemers MC, van den Hoogen FH, Boezeman JB, de Jong EM (2009) Effectiveness, side-effects and period of remission after treatment with methotrexate in localized scleroderma and related sclerotic skin diseases: an inception cohort study. Br J Dermatol 160:1075–1082

    CAS  PubMed  Article  Google Scholar 

  148. 148.

    Li SC, Torok KS, Pope E et al (2012) Development of consensus treatment plans for juvenile localized scleroderma: a roadmap toward comparative effectiveness studies in juvenile localized scleroderma. Arthritis Care Res (Hoboken) 64:1175–1185

    CAS  Google Scholar 

  149. 149.

    Mertens JS, Marsman D, van de Kerkhof PC, Hoppenreijs EP, Knaapen HK, Radstake TR, de Jong EM, Seyger MM (2016) Use of mycophenolate Mofetil in patients with severe localized scleroderma resistant or intolerant to methotrexate. Acta Derm Venereol 96:510–513

    CAS  PubMed  Article  Google Scholar 

  150. 150.

    Joly P, Bamberger N, Crickx B, Belaich S (1994) Treatment of severe forms of localized scleroderma with oral corticosteroids: follow-up study on 17 patients. Arch Dermatol 130:663–664

    CAS  PubMed  Article  Google Scholar 

  151. 151.

    Wright NA, Mazori DR, Patel M, Merola JF, Femia AN, Vleugels RA (2016) Epidemiology and treatment of eosinophilic fasciitis: an analysis of 63 patients from 3 tertiary care centers. JAMA Dermatol 152:97–99

    PubMed  Article  Google Scholar 

  152. 152.

    Rongioletti F (2006) Lichen myxedematosus (papular mucinosis): new concepts and perspectives for an old disease. Semin Cutan Med Surg 25:100–104

    CAS  PubMed  Article  Google Scholar 

  153. 153.

    Rongioletti F, Merlo G, Cinotti E et al (2013) Scleromyxedema: a multicenter study of characteristics, comorbidities, course, and therapy in 30 patients. J Am Acad Dermatol 69:66

    PubMed  Article  Google Scholar 

  154. 154.

    Kim JS, Werth VP (2011) Identification of specific chondroitin sulfate species in cutaneous autoimmune disease. J Histochem Cytochem 59:780–790

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  155. 155.

    Rongioletti F, Cattarini G, Sottofattori E, Rebora A (2003) Granulomatous reaction after intradermal injections of hyaluronic acid gel. Arch Dermatol 139:815–816

    PubMed  Article  Google Scholar 

  156. 156.

    Dinneen AM, Dicken CH (1995) Scleromyxedema. J Am Acad Dermatol 33:37–43

    CAS  PubMed  Article  Google Scholar 

  157. 157.

    Rongioletti F, Merlo G, Carli C et al (2016) Histopathologic characteristics of scleromyxedema: a study of a series of 34 cases. J Am Acad Dermatol 74:1194–1200

    PubMed  Article  Google Scholar 

  158. 158.

    Rongioletti F, Cozzani E, Parodi A (2010) Scleromyxedema with an interstitial granulomatous-like pattern: a rare histologic variant mimicking granuloma annulare. J Cutan Pathol 37:1084–1087

    PubMed  Article  Google Scholar 

  159. 159.

    Bidier M, Zschoche C, Gholam P et al (2012) Scleromyxoedema: clinical follow-up after successful treatment with high-dose immunoglobulins reveals different long-term outcomes. Acta Derm Venereol 92:408

    CAS  PubMed  Article  Google Scholar 

  160. 160.

    Nashel J, Steen V (2012) Scleroderma mimics. Curr Rheumatol Rep 14:39

    PubMed  Article  Google Scholar 

  161. 161.

    Blum M, Wigley FM, Hummers LK (2008) Scleromyxedema: a case series highlighting long-term outcomes of treatment with intravenous immunoglobulin (IVIG). Medicine (Baltimore) 87:10–20

    Article  Google Scholar 

  162. 162.

    Rey JB, Luria RB (2009) Treatment of scleromyxedema and dermatoneuro syndrome with intravenous immunoglobulin. J Am Acad Dermatol 60:1037–1041

    PubMed  Article  Google Scholar 

  163. 163.

    Bidier M, Zschoche C, Gholam P et al (2012) Scleromyxoedema: clinical follow-up after successful treatment with high-dose immunoglobulins reveals different long-term outcomes. Acta Derm Venereol 92:408–409

    CAS  PubMed  Article  Google Scholar 

  164. 164.

    Sansbury JC, Cocuroccia B, Jorizzo JL et al (2004) Treatment of recalcitrant scleromyxedema with thalidomide in 3 patients. J Am Acad Dermatol 51:126–131

    PubMed  Article  Google Scholar 

  165. 165.

    Efthimiou P, Blanco M (2008) Intravenous gammaglobulin and thalidomide may be an effective therapeutic combination in refractory scleromyxedema: case report and discussion of the literature. Semin Arthritis Rheum 38:188–194

    CAS  PubMed  Article  Google Scholar 

  166. 166.

    Bos R, de Waal EG, Kuiper H et al (2011) Thalidomide and dexamethasone followed by autologous stem cell transplantation for scleromyxoedema. Rheumatology (Oxford) 50:1925–1926

    CAS  Article  Google Scholar 

  167. 167.

    Cañueto J, Labrador J, Román C et al (2012) The combination of bortezomib and dexamethasone is an efficient therapy for relapsed/refractory scleromyxedema: a rare disease with new clinical insights. Eur J Haematol 88:450

    PubMed  Article  CAS  Google Scholar 

  168. 168.

    Horn KB, Horn MA, Swan J et al (2004) A complete and durable clinical response to high-dose dexamethasone in a patient with scleromyxedema. J Am Acad Dermatol 51:S120–S123

    PubMed  Article  Google Scholar 

  169. 169.

    Rongioletti F, Kaiser F, Cinotti E et al (2015) Scleredema. A multicentre study of characteristics, comorbidities, course and therapy in 44 patients. J Eur Acad Dermatol Venereol 29:2399–2404

    CAS  PubMed  Article  Google Scholar 

  170. 170.

    Beers WH, Ince A, Moore TL (2006) Scleredema adultorum of Buschke: a case report and review of the literature. Semin Arthritis Rheum 35:355–359

    PubMed  Article  Google Scholar 

  171. 171.

    Lewerenz V, Ruzicka T (2007) Scleredema adultorum associated with type 2 diabetes mellitus: a report of three cases. J Eur Acad Dermatol Venereol 21:560–561

    CAS  PubMed  Google Scholar 

  172. 172.

    Varga J, Gotta S, Li L, Sollberg S, Di Leonardo M (1995) Scleredema adultorum: case report and demonstration of abnormal expression of extracellular matrix genes in skin fibroblasts in vivo and in vitro. Br J Dermatol 132:992–999

    CAS  PubMed  Article  Google Scholar 

  173. 173.

    Ioannidou DI, Krasagakis K, Stefanidou MP et al (2001) Scleredema adultorum of Buschke presenting as periorbital edema: a diagnostic challenge. J Am Acad Dermatol 65:41–44

    Google Scholar 

  174. 174.

    Morais P, Almeida M, Santos P, Azevedo F (2011) Scleredema of Buschke following mycoplasma pneumoniae respiratory infection. Int J Dermatol 50:454–457

    PubMed  Article  Google Scholar 

  175. 175.

    Rongioletti F, Rebora A (2001) Cutaneous mucinoses: microscopic criteria for diagnosis. Am J Dermatopathol 23:257–267

    CAS  PubMed  Article  Google Scholar 

  176. 176.

    Miyares FJ, Kuriakose R, Deleu DT, El-Wahad NA, Al-Hail H (2008) Scleredema diabeticorum with unusual presentation and fatal outcome. Indian J Dermatol 53:217–219

    PubMed  PubMed Central  Article  Google Scholar 

  177. 177.

    Xiao T, Yang ZH, He CD, Chen HD (2007) Scleredema adultorum treated with narrow-band ultraviolet B phototherapy. J Dermatol 34:270–272

    PubMed  Article  Google Scholar 

  178. 178.

    Yüksek J, Sezer E, Köseoğlu D, Markoç F, Yıldız H (2010) Scleredema treated with broad-band ultraviolet a phototherapy plus colchicine. Photodermatol Photoimmunol Photomed 26:257–260

    PubMed  Article  Google Scholar 

  179. 179.

    Szturz P, Adam Z, Vašků V, Feit J, Krejčí M, Pour L, Hájek R, Mayer J (2013) Complete remission of multiple myeloma associated scleredema after bortezomib-based treatment. Leuk Lymphoma 54:1324–1326

    CAS  PubMed  Article  Google Scholar 

  180. 180.

    Lee FY, Chiu HY, Chiu HC (2011) Treatment of acquired reactive perforating collagenosis with allopurinol incidentally improves scleredema diabeticorum. J Am Acad Dermatol 65:e115–e117

    PubMed  Article  Google Scholar 

  181. 181.

    Stables GI, Taylor PC, Highet AS (2000) Scleredema associated with paraproteinaemia treated by extracorporeal photopheresis. Br J Dermatol 142:781–783

    CAS  PubMed  Article  Google Scholar 

  182. 182.

    Bowen AR, Smith L, Zone JJ (2003) Scleredema adultorum of Buschke treated with radiation. Arch Dematol 139:780–784

    Article  Google Scholar 

  183. 183.

    Aichelburg MC, Loewe R, Schicher N, Sator PG, Karlhofer FM, Stingl G, Jalili A (2012) Successful treatment of poststreptococcal scleredema adultorum Buschke with intravenous immunoglobulins. Arch Dermatol 148:1126–1128

    PubMed  Article  Google Scholar 

  184. 184.

    Cowper SE, Robin HS, Steinberg SM, Su LD, Gupta S, LeBoit PE (2000) Scleromyxoedema-like cutaneous diseases in renal-dialysis patients. Lancet 356:1000–1001

    CAS  PubMed  Article  Google Scholar 

  185. 185.

    Girardi M, Kay J, Elston DM, LeBoit PE, Abu-Alfa A, Cowper SE (2011) Nephrogenic systemic fibrosis: clinicopathological definition and workup recommendations. J Am Acad Dermatol 65:1095–1106.e7

    PubMed  Article  Google Scholar 

  186. 186.

    Knopp EA, Cowper SE (2008) Nephrogenic systemic fibrosis: early recognition and treatment. Semin Dial 21:123–128

    PubMed  Article  Google Scholar 

  187. 187.

    Thomsen HS, Marckmann P (2008) Extracellular Gd-CA: differences in prevalence of NSF. Eur J Radiol 66:180–183

    PubMed  Article  Google Scholar 

  188. 188.

    Thomsen HS, Morcos SK, Almen T et al (2013) Nephrogenic systemic fibrosis and gadolinium-based contrast media: updated ESUR contrast medium safety committee guidelines. Eur Radiol 23:307–318

    PubMed  Article  Google Scholar 

  189. 189.

    Jan F, Segal JM, Dyer J, LeBoit P, Siegfried E, Frieden IJ (2003) Nephrogenic fibrosing dermopathy: two pediatric cases. J Pediatr 143:678–681

    PubMed  Article  Google Scholar 

  190. 190.

    Perazella MA, Rodby RA (2007) Gadolinium use in patients with kidney disease: a cause for concern. Semin Dial 20:179–185

    PubMed  Article  Google Scholar 

  191. 191.

    Newton BB, Jimenez SA (2009) Mechanism of NSF: new evidence challenging the prevailing theory. J Magn Reson Imaging 30:1277–1283

    PubMed  Article  Google Scholar 

  192. 192.

    Cowper SE (2003) Nephrogenic fibrosing dermopathy: the first 6 years. Curr Opin Rheumatol 15:785–790

    PubMed  Article  Google Scholar 

  193. 193.

    Larson KN, Gagnon AL, Darling MD, Patterson JW, Cropley TG (2015) Nephrogenic systemic fibrosis manifesting a decade after exposure to gadolinium. JAMA Dermatol 151:1117–1120

    PubMed  Article  Google Scholar 

  194. 194.

    Chopra T, Kandukurti K, Shah S, Ahmed R, Panesar M (2012) Understanding nephrogenic systemic fibrosis. Int J Nephrol 912189. doi:10.1155/2012/912189

  195. 195.

    Swaminathan S, High WA, Ranville J, Horn TD, Hiatt K, Thomas M et al (2008) Cardiac and vascular metal deposition with high mortality in nephrogenic systemic fibrosis. Kidney Int 73:1413–1418

    CAS  PubMed  Article  Google Scholar 

  196. 196.

    High WA, Ayers RA, Chandler J et al (2007) Gadolinium is detectable within the tissue of patients with nephrogenic systemic fibrosis. J Am Acad Dermatol 56:21

    PubMed  Article  Google Scholar 

  197. 197.

    Madke B, Khopkar U (2011) Nephrogenic systemic fibrosis. Indian Dermatol Online J 2:51–56

    PubMed  PubMed Central  Article  Google Scholar 

  198. 198.

    Bhawan J, Perez-Chua TA, Goldberg L (2013) Sclerotic bodies beyond nephrogenic systemic fibrosis. J Cutan Pathol 40:812–817

    PubMed  Article  Google Scholar 

  199. 199.

    Boyd AS, Zic JA, Abraham JL (2007) Gadolinium deposition in nephrogenic fibrosing dermopathy. J Am Acad Dermatol 56:27

    PubMed  Article  Google Scholar 

  200. 200.

    High WA, Ayers RA, Cowper SE (2007) Gadolinium is quantifiable within the tissue of patients with nephrogenic systemic fibrosis. J Am Acad Dermatol 56:710

    PubMed  Article  Google Scholar 

  201. 201.

    Igreja AC, Mesquita Kde C, Cowper SE, Costa IM (2012) Nephrogenic systemic fibrosis: concepts and perspective. An Bras Dermatol 87:597–607

    PubMed  Article  Google Scholar 

  202. 202.

    Elmholdt TR, Buus NH, Ramsing M, Olesen AB (2013) Antifibrotic effect after low-dose imatinib mesylate treatment in patients with nephrogenic systemic fibrosis: an open-label non-randomized, uncontrolled clinical trial. J Eur Acad Dermatol Venereol 27:779–784

    CAS  PubMed  Article  Google Scholar 

  203. 203.

    Mendoza FA, Artlett CM, Sandorfi N et al (2006) Description of 12 cases of nephrogenic fibrosing dermopathy and review of the literature. Semin Arthritis Rheum 35:238

    PubMed  PubMed Central  Article  Google Scholar 

  204. 204.

    Cuffy MC, Singh M, Formica R et al (2011) Renal transplantation for nephrogenic systemic fibrosis: a case report and review of the literature. Nephrol Dial Transplant 26:1099–1101

    PubMed  Article  Google Scholar 

  205. 205.

    Waikhom R, Taraphder A (2011) Nephrogenic systemic fibrosis: a brief review. Indian J Dermatol 56:54–58

    PubMed  PubMed Central  Article  Google Scholar 

  206. 206.

    Shulman LE (1974) Diffuse fasciite with hypergammaglobulinemia and eosinophilia: a new syndrome? J Rheumatol 1:46–49

    Google Scholar 

  207. 207.

    Lebeaux D, Sène D (2012) Eosinophilic fasciitis (Shulman disease). Best Pract Res Clin Rheumatol 26:449–458

    CAS  PubMed  Article  Google Scholar 

  208. 208.

    Mertens JS, Seyger MM, Thurlings RM, Radstake TR, de Jong EM (2017) Morphea and eosinophilic fasciitis: an update. Am J Clin Dermatol. doi:10.1007/s40257-017-0269-x

  209. 209.

    Sène D (2015) Eosinophilic fasciitis (Shulman’s disease): diagnostic and therapeutic review. Rev Med Interne 36:738–745

    PubMed  Article  Google Scholar 

  210. 210.

    Pinal-Fernandez I, Selva-O’ Callaghan A, Grau JM (2014) Diagnosis and classification of eosinophilic fasciitis. Autoimmun Rev 13:379–3824

    CAS  PubMed  Article  Google Scholar 

  211. 211.

    Endo Y, Tamura A, Matsushima Y, Iwasaki T, Hasegawa M, Nagai Y, Ishikawa O (2007) Eosinophilic fasciitis: report of two cases and a systematic review of the literature dealing with clinical variables that predict outcome. Clin Rheumatol 26:1445–1451

    PubMed  Article  Google Scholar 

  212. 212.

    Bischoff L, Derk CT (2008) Eosinophilic fasciitis: demographics, disease pattern and response to treatment: report of 12 cases and review of the literature. Int J Dermatol 47:29–35

    PubMed  Article  Google Scholar 

  213. 213.

    Toquet C, Hamidou MA, Renaudin K, Jarry A, Foulc P, Barbarot S, Laboisse C, Mussini JM (2003) In situ immunophenotype of the inflammatory infiltrate in eosinophilic fasciitis. J Rheumatol 30:1811–1815

    PubMed  Google Scholar 

  214. 214.

    Asano Y, Ihn H, Jinnin M, Tamaki Z, Tamaki K, Sato S (2014) Serum levels of matrix metalloproteinase-13 in patients with eosinophilic fasciitis. J Dermatol 41:746–748

    CAS  PubMed  Article  Google Scholar 

  215. 215.

    Daniel RS, Lavery S, Maize JC Jr, Brown AN, Bolster MB (2009) Unilateral eosinophilic fasciitis: an under-recognized subtype? J Clin Rheumatol 15:247–249

    PubMed  Article  Google Scholar 

  216. 216.

    Patterson J (2016) Disorders of collagen. In: Weedon’s skin pathology, 4th edn. Elsevier, pp 348–379

  217. 217.

    Nashel J, Steen V (2015) The use of an elevated aldolase in diagnosing and managing eosinophilic fasciitis. Clin Rheumatol 34:1481–1484

    PubMed  Article  Google Scholar 

  218. 218.

    Jinnin M, Ihn H, Yamane K, Asano Y, Yazawa N, Tamaki K (2004) Serum levels of tissue inhibitor of metalloproteinase-1 and 2 in patients with eosinophilic fasciitis. Br J Dermatol 151:407–412

    CAS  PubMed  Article  Google Scholar 

  219. 219.

    Dybowski F, Neuen-Jacob E, Braun J (2008) Eosinophilic fasciitis and myositis: use of imaging modalities for diagnosis and monitoring. Ann Rheum Dis 67:572–574

    CAS  PubMed  Article  Google Scholar 

  220. 220.

    Kurimoto R, Ikeda K, Nakagomi D, Nakajima H (2016) Eosinophilic fasciitis illustrated by [(18)F] FDG-PET/CT. Intern Med 55:2321–2322

    PubMed  Article  Google Scholar 

  221. 221.

    Mondal S, Goswami RP, Sinha D, Ghosh A (2015) Ultrasound is a useful adjunct in diagnosis of eosinophilic fasciitis. Rheumatology 54:2041

    CAS  PubMed  Article  Google Scholar 

  222. 222.

    Oza VS, Walsh R, North J, Berger TG, Murase JE (2016) Treatment of eosinophilic fasciitis with Sirolimus. JAMA Dermatol 152:488–490

    PubMed  Article  Google Scholar 

  223. 223.

    Mertens JS, Zweers MC, Kievit W, Knaapen HK, Gerritsen M, Radstake TR, van den Hoogen FH, Creemers MC, de Jong EM (2016) High-dose intravenous pulse methotrexate in patients with eosinophilic fasciitis. JAMA Dermatol 152:1262–1265

    PubMed  Article  Google Scholar 

  224. 224.

    Kroft EB, Berkhof NJ, van de Kerkhof PC, Gerritsen RM, de Jong EM (2008) Ultraviolet a phototherapy for sclerotic skin diseases: a systematic review. J Am Acad Dermatol 59:1017–1030

    PubMed  Article  Google Scholar 

  225. 225.

    Romano C, Rubegni P, De Aloe G, Stanghellini E, D’Ascenzo G, Andreassi L, Fimiani M (2003) Extracorporeal photochemotherapy in the treatment of eosinophilic fasciitis. J Eur Acad Dermatol Venereol 17:10–13

    CAS  PubMed  Article  Google Scholar 

  226. 226.

    Hymes SR, Alousi AM, Cowen EW (2012) Graft-versus-host disease: part I. Pathogenesis and clinical manifestations of graft-versus-host disease. J Am Acad Dermatol 66:515.e1–515.18

    Article  Google Scholar 

  227. 227.

    Chosidow O, Bagot M, Vernant JP, Roujeau JC, Cordonnier C, Kuentz M, Wechsler J, André C, Touraine R, Revuz J (1992) Sclerodermatous chronic graft-versus-host disease. Analysis of seven cases. J Am Acad Dermatol 26:49–55

    CAS  PubMed  Article  Google Scholar 

  228. 228.

    Zhang J, Chen F, Ueki T, Date H (2015) Imatinib for sclerodermatous graft-versus-host disease in lung transplantation. Interact Cardiovasc Thorac Surg 21:260–262

    PubMed  Article  Google Scholar 

  229. 229.

    Lazzeri L, Tripo L, Pescitelli L, Ricceri F, Prignano F (2016) A pediatric case of Sclerodermatous graft-versus-host disease responsive to ultraviolet A1 phototherapy. Pediatr Dermatol 33:e99–102

    PubMed  Article  Google Scholar 

  230. 230.

    Bisaccia E, Palangio M, Gonzalez J (2011) Long-term extracorporeal photochemotherapy in a pediatric patient with refractory sclerodermatous chronic graft-versus-host disease. Transfus Apher Sci 45:187–190

    PubMed  Article  Google Scholar 

  231. 231.

    Bell SA, Faust H, Mittermüller J, Kolb HJ, Meurer M (1996) Specificity of antinuclear antibodies in scleroderma-like chronic graft-versus-host disease: clinical correlation and histocompatibility locus antigen association. Br J Dermatol 134:848–854

    CAS  PubMed  Article  Google Scholar 

  232. 232.

    Higman MA, Vogelsang GB (2004) Chronic graft versus host disease. Br J Haematol 125:435–454

    PubMed  Article  Google Scholar 

  233. 233.

    White JM, Devereux S, Pagliuca A, Salisbury JR, du Vivier AW, Creamer D (2006) Koebnerizing sclerodermatous graft-versus-host disease caused by donor lymphocyte infusion and interferon-alpha. Br J Dermatol 155:621–623

    CAS  PubMed  Article  Google Scholar 

  234. 234.

    Delaney TA, Morehouse C, Brohawn PZ, Groves C, Colonna M, Yao Y, Sanjuan M, Coyle AJ (2016) Type I IFNs regulate inflammation, vasculopathy, and fibrosis in chronic cutaneous graft-versus-host disease. J Immunol 197:42–50

    CAS  PubMed  Article  Google Scholar 

  235. 235.

    Sarantopoulos S, Ritz J (2015) Aberrant B-cell homeostasis in chronic GVHD. Blood 125:1703–1707

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  236. 236.

    Kharfan-Dabaja MA, Mhaskar AR, Djulbegovic B, Cutler C, Mohty M, Kumar A (2009) Efficacy of rituximab in the setting of steroid-refractory chronic graft-versus-host disease: a systematic review and meta-analysis. Biol Blood Marrow Transplant 15:1005–1013

    CAS  PubMed  Article  Google Scholar 

  237. 237.

    White JM, Creamer D, du Vivier AW, Pagliuca A, Ho AY, Devereux S, Salisbury JR, Mufti GJ (2007) Sclerodermatous graft-versus-host disease: clinical spectrum and therapeutic challenges. Br J Dermatol 156:1032–1038

    CAS  PubMed  Article  Google Scholar 

  238. 238.

    Peñas PF, Jones-Caballero M, Aragués M, Fernández-Herrera J, Fraga J, Garcia-Diez A (2002) Sclerodermatous graft-vs-host disease. Clinical and pathological study of 17 patients. Arch Dermatol 138:924–934

    PubMed  Article  Google Scholar 

  239. 239.

    Schaffer JV, McNiff JM, Seropian S, Cooper DL, Bolognia JL (2005) Lichen sclerosus and eosinophilic fasciitis as manifestations of chronic graft-versus-host disease: expanding the sclerodermoid spectrum. J Am Acad Dermatol 53:591–601

    PubMed  Article  Google Scholar 

  240. 240.

    Jachiet M, de Masson A, Peffault de Latour R, Rybojad M, Robin M, Bourhis JH, Xhaard A, Dhedin N, Sicre de Fontbrune F, Suarez F, Barete S, Parquet N, Nguyen S, Ades L, Rubio MT, Wittnebel S, Bagot M, Socié G, Bouaziz JD (2014) Skin ulcers related to chronic graft-versus-host disease: clinical findings and associated morbidity. Br J Dermatol 171:63–68

    CAS  PubMed  Article  Google Scholar 

  241. 241.

    Akay BN, Sanli H, Topcuoglu P, Arat M, Akyol A (2010) Nailfold capillary abnormalities are prevalent in sclerodermoid graft-versus-host disease and readily detected with dermatoscopy. Br J Dermatol 162:1076–1082

    CAS  PubMed  Article  Google Scholar 

  242. 242.

    Man J, Man J, Kalisiak M, Birchall IW, Salopek TG (2010) Chronic cutaneous graft-versus-host disease manifesting as calcinosis cutis universalis on a background of widespread sclerodermatoid changes. J Cutan Med Surg 14:249–253

    PubMed  Article  Google Scholar 

  243. 243.

    Osmola-Mańkowska A, Silny W, Dańczak-Pazdrowska A, Polańska A, Olek-Hrab K, Sadowska-Przytocka A, Żaba R, Jenerowicz D (2013) Assessment of chronic sclerodermoid graft-versus-host disease patients, using 20 MHz high-frequency ultrasonography and cutometer methods. Skin Res Technol 19:e417–e422

    PubMed  Article  Google Scholar 

  244. 244.

    Carcagnì MR, De Aloe G, D’Ascenzo G, Rubegni P, Fimiani M (2008) Extracorporeal photopheresis in graft-versus-host disease. J Dtsch Dermatol Ges 6:451–457

    PubMed  Article  Google Scholar 

  245. 245.

    Calzavara Pinton P, Porta F, Izzi T, Venturini M, Capezzera R, Zane C, Notarangelo LD (2003) Prospects for ultraviolet A1 phototherapy as a treatment for chronic cutaneous graft-versus-host disease. Haematologica 88:1169–1175

    PubMed  Google Scholar 

  246. 246.

    Lazar J, Poonawalla T, Teng JM (2011) A case of sclerodermatous graft-versus-host disease responsive to imatinib therapy. Pediatr Dermatol 28:172–175

    PubMed  Article  Google Scholar 

  247. 247.

    Pines M, Snyder D, Yarkoni S, Nagler A (2003) Halofuginone to treat fibrosis in chronic graft-versus-host disease and scleroderma. Biol Blood Marrow Transplant 9:417–425

    CAS  PubMed  Article  Google Scholar 

  248. 248.

    Kauppinen R (2005) Porphyrias. Lancet 365:241–252

    CAS  PubMed  Article  Google Scholar 

  249. 249.

    Amezyane T, Abouzahir A, Fatihi J, Sekkach Y, Mahassin F, Sedrati O, Ghafir D, Ohayon V (2010) A sclerodermiform porphyria cutanea tarda. Intern Med 49:205–206

    PubMed  Article  Google Scholar 

  250. 250.

    Kranzelbinder B, Wiednig M, El-Shabrawi-Caelen L, Aberer W, Aberer E (2015) Sclerodermiform porphyria cutanea tarda after torasemide. Eur J Dermatol 25:484–485

    CAS  PubMed  Google Scholar 

  251. 251.

    Wallaeys E, Thierling U, Lang E, Neumann NJ, Frank J (2014) Porphyria cutanea tarda with sclerodermatous changes and hemochromatosis. Hautarzt 65:272–274

    CAS  PubMed  Article  Google Scholar 

  252. 252.

    Lim HW (1989) Mechanisms of phototoxicity in porphyria cutanea tarda and erythropoietic protoporphyria. Immunol Ser 46:671–685

    CAS  PubMed  Google Scholar 

  253. 253.

    Torinuki W, Kudoh K, Tagami H (1989) Increased mast cell numbers in the sclerotic skin of Porphyria Cutanea Tarda. Dermatologica 178:75–78

    CAS  PubMed  Article  Google Scholar 

  254. 254.

    Thomas CL, Badminton MN, Rendall JR, Anstey AV (2008) Sclerodermatous changes of face, neck and scalp associated with familial porphyria cutanea tarda. Clin Exp Dermatol 33:422–442

    CAS  PubMed  Article  Google Scholar 

  255. 255.

    Khayat R, Dupuy A, Pansé I, Bagot M, Cordoliani F (2013) Sclerodermatous changes in porphyria cutanea tarda: six cases. Ann Dermatol Venereol 140:589–597

    CAS  PubMed  Article  Google Scholar 

  256. 256.

    Zemtsov R, Zemtsov A (2010) Porphyria cutanea tarda presenting as scleroderma. Cutis 85:203–205

    PubMed  Google Scholar 

  257. 257.

    Bulaj ZJ, Phillips JD, Ajioka RS, Franklin MR, Griffen LM, Guinee DJ et al (2000) Hemochromatosis genes and other factors contributing to the pathogenesis of porphyria cutanea tarda. Blood 95:1565–1571

    CAS  PubMed  Google Scholar 

  258. 258.

    Vieira FM, Aoki V, Oliveira ZN, Martins JE (2010) Study of direct immunofluorescence, immunofluorescence mapping and light microscopy in porphyria cutanea tarda. An Bras Dermatol 85:827–837

    PubMed  Article  Google Scholar 

  259. 259.

    Singal AK, Kormos-Hallberg C, Lee C, Sadagoparamanujam VM, Grady JJ, Freeman DH Jr, Anderson KE (2012) Low-dose hydroxychloroquine is as effective as phlebotomy in treatment of patients with porphyria cutanea tarda. Clin Gastroenterol Hepatol 10:1402–1409

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  260. 260.

    Singal AK, Kormos-Hallberg C, Lee C et al (2012) Low-dose hydroxychloroquine is as effective as phlebotomy in treatment of patients with porphyria cutanea tarda. Clin Gastroenterol Hepatol 10:1402

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  261. 261.

    Monastirli A, Georgiou S, Bolsen K et al (1999) Treatment of porphyria cutanea tarda with oral thalidomide. Skin Pharmacol Appl Ski Physiol 12:305

    CAS  Article  Google Scholar 

  262. 262.

    Ayres S Jr, Mihan R (1978) Porphyria cutanea tarda: response to vitamin E. A review and two case reports. Cutis 22:50

    PubMed  Google Scholar 

  263. 263.

    Ballantyne JA, Hooper G (2004) The hand and diabetes. Curr Orthop 18:118–125

    Article  Google Scholar 

  264. 264.

    Ravindran Rajendran S, Bhansali A, Walia R et al (2011) Prevalence and pattern of hand soft-tissue changes in type 2 diabetes mellitus. Diabetes Metab 37:312–317

    CAS  PubMed  Article  Google Scholar 

  265. 265.

    Chen LH, Li C-Y, Kuo LC, Wang L-Y, Kuo KN, Jou IM, Hou W-H (2015) Risk of hand syndromes in patients with diabetes mellitus. A population-based cohort study in Taiwan. Medicine 94:e1575

    PubMed  PubMed Central  Article  Google Scholar 

  266. 266.

    Al-Matubsi HY, Hamdan F, Alhanbali OA et al (2011) Diabetic hand syndromes as a clinical and diagnostic tool for diabetes mellitus patients. Diabetes Res Clin Pract 94:225–229

    PubMed  Article  Google Scholar 

  267. 267.

    Somai P (2011) Limited joint mobility in diabetes mellitus: the clinical implications. J Musculoskel Med 28:118–124

    Google Scholar 

  268. 268.

    Ishibashi Y, Matsui T, Maeda S, Higashimoto Y, Yamagishi S (2013) Advanced glycation end products evoke endothelial cell damage by stimulating soluble dipeptidyl peptidase-4 production and its interaction with mannose 6-phosphate/insulin-like growth factor II receptor. Cardiovasc Diabetol 12:125

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  269. 269.

    Yokote K, Chanprasert S, Lee L, Eirich K, Takemoto M, Watanabe A et al (2017) WRN mutation update: mutation spectrum, patient registries, and translational prospects. Hum Mutat 38:7–15

    CAS  PubMed  Article  Google Scholar 

  270. 270.

    Davis T, Brook AJ, Rokicki MJ, Bagley MC, Kipling D (2016) Evaluating the role of p38 MAPK in the accelerated cell senescence of Werner syndrome fibroblasts. Pharmaceuticals 9:23

    PubMed Central  Article  CAS  Google Scholar 

  271. 271.

    Goto M, Ishikawa Y, Sugimoto M, Furuichi Y (2013) Werner syndrome: a changing pattern of clinical manifestations in Japan (1917–2008). BioScience Trends 7:13–22

    CAS  PubMed  Google Scholar 

  272. 272.

    Monnat RJ Jr (2015) “...rewritten in the skin”: clues to skin biology and aging from inherited disease. J Invest Dermatol 135:1484–1490

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  273. 273.

    Lee YA, Stevens HP, Delaporte E, Wahn U, Reis A (2000) A gene for an autosomal dominant scleroatrophic syndrome predisposing to skin cancer (Huriez syndrome) maps to chromosome 4q23. Am J Hum Genet 66:326–330

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  274. 274.

    Massip L, Garand C, Paquet ER, Cogger VC, O’Reilly JN, Tworek L, Hatherell A, Taylor CG, Thorin E, Zahradka P, Le Couteur DG, Lebel M (2010) Vitamin C restores healthy aging in a mouse model for Werner syndrome. FASEB J 24:158–172

    PubMed  Article  CAS  Google Scholar 

  275. 275.

    Tokita M, Kennedy SR, Risques RA, Chun SG, Pritchard C, Oshima J, Liu Y, Bryant-Greenwood PK, Welcsh P, Monnat RJ (2016) Werner syndrome through the lens of tissue and tumour genomics. Sci Rep 6:32038

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  276. 276.

    Kikuchi K, Hoashi T, Yazawa N, Tamaki K (2006) Pseudoscleroderma associated with cancer. Clin Exp Dermatol 31:381–383

    CAS  PubMed  Article  Google Scholar 

  277. 277.

    Juarez M, Marshall R, Denton C, Evely R (2008) Paraneoplastic scleroderma secondary to hairy cell leukaemia successfully treated with cladribine. Rheumatology 47:1734–1735

    CAS  PubMed  Article  Google Scholar 

  278. 278.

    Querfeld C, Sollberg S, Huerkamp C, Eckes B, Krieg T (2000) Pseudoscleroderma associated with lung cancer: correlation of collagen typ 1 and connective tissue growth factor gene expression. Br J Dermatol 142:1228–1233

    CAS  PubMed  Article  Google Scholar 

  279. 279.

    Jedlickova H, Durčanská V, Vašků V (2016) Paraneoplastic scleroderma: are there any clues? Acta Dermatovenerol Croat 24:78–80

    PubMed  Google Scholar 

  280. 280.

    Marek M, Rudny R (2016) Scleroderma of geriatric age and scleroderma-like paraneoplastic syndrome—description of two cases. Reumatologia 54:91–94

    PubMed  PubMed Central  Article  Google Scholar 

  281. 281.

    Allen JA, Peterson A, Sufit R et al (2011) Post-epidemic eosinophilia-myalgia syndrome associated with L-tryptophan. Arthritis Rheum 63:3633–3639

    CAS  PubMed  Article  Google Scholar 

  282. 282.

    Rongioletti F, Rebora A (1992) Cutaneous toxic mucinosis. J Am Acad Dermatol 26:788–790

    Article  Google Scholar 

  283. 283.

    D’Cruz D (2000) Autoimmune diseases associated with drugs, chemicals and environmental factors. Toxicol Lett 112:421–432

    PubMed  Article  Google Scholar 

  284. 284.

    Foti R, Leonardi R, Rondinone R et al (2008) Scleroderma-like disorders. Autoimmun Rev 7:331–339

    CAS  PubMed  Article  Google Scholar 

  285. 285.

    Kaufman LD, Gruber BL, Gomez-Reino JJ et al (1994) Fibrogenic growth factors in the eosinophilia–myalgia syndrome and the toxic oil syndrome. Arch Dermatol 130:41–47

    CAS  PubMed  Article  Google Scholar 

  286. 286.

    Sharma SK, Handa R, Sood R et al (2004) Bleomycin-induced scleroderma. J Assoc Physicians India 52:76–77

    PubMed  Google Scholar 

  287. 287.

    Niklas K, Niklas AA, Majewski D, Puszczewicz M (2016) Rheumatic diseases induced by drugs and environmental factors: the state-of-the-art—part one. Reumatologia 54:122–127

    PubMed  PubMed Central  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Caterina Ferreli.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Funding

None.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ferreli, C., Gasparini, G., Parodi, A. et al. Cutaneous Manifestations of Scleroderma and Scleroderma-Like Disorders: a Comprehensive Review. Clinic Rev Allerg Immunol 53, 306–336 (2017). https://doi.org/10.1007/s12016-017-8625-4

Download citation

Keywords

  • Scleroderma
  • Systemic sclerosis
  • Morphea
  • Scleroderma-like disorders
  • Cutaneous sclerosis