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Scleroderma Mimics

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Scleroderma

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Abstract

Scleroderma is named for the presence of its most characteristic quality, namely, skin sclerosis, in addition to symptoms that are commonly encountered in a general population such as the Raynaud phenomenon and gastroesophageal reflux. Therefore, having an appropriate level of suspicion for the diagnosis will help facilitate getting patients to the appropriate specialist. However, there are other patients who present with features considered to be typical of scleroderma, such as Raynaud and skin thickening, and who may have a syndrome mimicking scleroderma. The new American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for systemic sclerosis necessitate the exclusion of scleroderma mimics [1]. So familiarity with these mimickers is critical for rheumatologists and other physicians who evaluate patients with scleroderma. The Raynaud phenomenon and/or digital ischemia can be associated with multiple different etiologies and rheumatic and non-rheumatic conditions should be considered. Skin thickening (including skin fibrosis) may be seen in a variety of conditions ranging from minor skin irritations (i.e., lichenification from scratching) to a number of systemic diseases that require expert evaluation (scleredema, scleromyxedema). This chapter will focus on the differential diagnosis of these two common presentations, Raynaud phenomenon and skin thickening.

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References

  1. 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. 2013;72(11):1747–55.

    Article  PubMed  Google Scholar 

  2. Gelber AC, Wigley FM, Stallings RY, Bone LR, Barker AV, Baylor I, et al. Symptoms of Raynaud’s phenomenon in an inner-city African-American community: prevalence and self-reported cardiovascular comorbidity. J Clin Epidemiol. 1999;52(5):441–6.

    Article  CAS  PubMed  Google Scholar 

  3. Jones GT, Herrick AL, Woodham SE, Baildam EM, Macfarlane GJ, Silman AJ. Occurrence of Raynaud’s phenomenon in children ages 12-15 years: prevalence and association with other common symptoms. Arthritis Rheum. 2003;48(12):3518–21.

    Article  PubMed  Google Scholar 

  4. Voulgari PV, Alamanos Y, Papazisi D, Christou K, Papanikolaou C, Drosos AA. Prevalence of Raynaud’s phenomenon in a healthy Greek population. Ann Rheum Dis. 2000;59(3):206–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Maricq HR, Carpentier PH, Weinrich MC, Keil JE, Palesch Y, Biro C, et al. Geographic variation in the prevalence of Raynaud’s phenomenon: a 5 region comparison. J Rheumatol. 1997;24(5):879–89.

    CAS  PubMed  Google Scholar 

  6. Koenig M, Joyal F, Fritzler MJ, Roussin A, Abrahamowicz M, Boire G, et al. Autoantibodies and microvascular damage are independent predictive factors for the progression of Raynaud’s phenomenon to systemic sclerosis: a twenty-year prospective study of 586 patients, with validation of proposed criteria for early systemic sclerosis. Arthritis Rheum. 2008;58(12):3902–12.

    Article  PubMed  Google Scholar 

  7. Liu A, Zhang W, Tian X, Zhang X, Zhang F, Zeng X. Prevalence, risk factors and outcome of digital gangrene in 2684 lupus patients. Lupus. 2009;18(12):1112–8.

    Article  CAS  PubMed  Google Scholar 

  8. Kalluri M, Sahn SA, Oddis CV, Gharib SL, Christopher-Stine L, Danoff SK, et al. Clinical profile of anti-PL-12 autoantibody. Cohort study and review of the literature. Chest. 2009;135(6):1550–6.

    Article  CAS  PubMed  Google Scholar 

  9. Piette Y, Reynaert V, Vanhaecke A, Bonroy C, Gutermuth J, Sulli A, et al. Standardised interpretation of capillaroscopy in autoimmune idiopathic inflammatory myopathies: a structured review on behalf of the EULAR study group on microcirculation in rheumatic diseases. Autoimmun Rev. 2022;21(6):103087.

    Article  PubMed  Google Scholar 

  10. Glendenning JL, Barbachano Y, Norman AR, Dearnaley DP, Horwich A, Huddart RA. Long-term neurologic and peripheral vascular toxicity after chemotherapy treatment of testicular cancer. Cancer. 2010;116(10):2322–31.

    Article  CAS  PubMed  Google Scholar 

  11. Maricq HR, Johnson MN, Whetstone CL, LeRoy EC. Capillary abnormalities in polyvinyl chloride production workers. Examination by in vivo microscopy. Jama. 1976;236(12):1368–71.

    Article  CAS  PubMed  Google Scholar 

  12. Rustin MH, Bull HA, Ziegler V, Mehlhorn J, Haustein UF, Maddison PJ, et al. Silica-associated systemic sclerosis is clinically, serologically and immunologically indistinguishable from idiopathic systemic sclerosis. Br J Dermatol. 1990;123(6):725–34.

    Article  CAS  PubMed  Google Scholar 

  13. Belongia EA, Hedberg CW, Gleich GJ, White KE, Mayeno AN, Loegering DA, et al. An investigation of the cause of the eosinophilia-myalgia syndrome associated with tryptophan use. N Engl J Med. 1990;323(6):357–65.

    Article  CAS  PubMed  Google Scholar 

  14. Kaufman LD, Krupp LB. Eosinophilia-myalgia syndrome, toxic-oil syndrome, and diffuse fasciitis with eosinophilia. Curr Opin Rheumatol. 1995;7(6):560–7.

    Article  CAS  PubMed  Google Scholar 

  15. Posada de la Paz M, Díaz-Guerra E, Alonso-Ferreira V, Villaverde-Hueso A, Arias-Merino G, Garrido-Estepa M. Toxic oil syndrome: health-related quality-of-life assessment using the SF-36 health survey. Int J Epidemiol. 2022;51(2):491–500.

    Article  PubMed  Google Scholar 

  16. Kilbourne EM, Posada de la Paz M, Abaitua Borda I, Diez Ruiz-Navarro M, Philen RM, Falk H. Toxic oil syndrome: a current clinical and epidemiologic summary, including comparisons with the eosinophilia-myalgia syndrome. J Am Coll Cardiol. 1991;18(3):711–7.

    Article  CAS  PubMed  Google Scholar 

  17. Fonseca E, Contreras F. Cutaneous mucinosis in the toxic oil syndrome. J Am Acad Dermatol. 1987;16(1 Pt 1):139–40.

    Article  CAS  PubMed  Google Scholar 

  18. Piera-Velazquez S, Wermuth PJ, Gomez-Reino JJ, Varga J, Jimenez SA. Chemical exposure-induced systemic fibrosing disorders: novel insights into systemic sclerosis etiology and pathogenesis. Semin Arthritis Rheum. 2020;50(6):1226–37.

    Article  CAS  PubMed  Google Scholar 

  19. Cowper SE, Robin HS, Steinberg SM, Su LD, Gupta S, LeBoit PE. Scleromyxoedema-like cutaneous diseases in renal-dialysis patients. Lancet. 2000;356(9234):1000–1.

    Article  CAS  PubMed  Google Scholar 

  20. Bennett CL, Qureshi ZP, Sartor AO, Norris LB, Murday A, Xirasagar S, et al. Gadolinium-induced nephrogenic systemic fibrosis: the rise and fall of an iatrogenic disease. Clin Kidney J. 2012;5(1):82–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Bennett CL, Starko KM, Thomsen HS, Cowper S, Sartor O, Macdougall IC, et al. Linking drugs to obscure illnesses: lessons from pure red cell aplasia, nephrogenic systemic fibrosis, and Reye’s syndrome. A report from the southern network on adverse reactions (SONAR). J Gen Intern Med. 2012;27(12):1697–703.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Weinreb JC, Rodby RA, Yee J, Wang CL, Fine D, McDonald RJ, et al. Use of intravenous gadolinium-based contrast media in patients with kidney disease: consensus statements from the American College of Radiology and the National Kidney Foundation. Kidney Med. 2021;3(1):142–50.

    Article  PubMed  Google Scholar 

  23. Rongioletti F, Kaiser F, Cinotti E, Metze D, Battistella M, Calzavara-Pinton PG, et al. Scleredema. A multicentre study of characteristics, comorbidities, course and therapy in 44 patients. J Eur Acad Dermatol Venereol. 2015;29(12):2399–404.

    Article  CAS  PubMed  Google Scholar 

  24. Cole GW, Headley J, Skowsky R. Scleredema diabeticorum: a common and distinct cutaneous manifestation of diabetes mellitus. Diabetes Care. 1983;6(2):189–92.

    Article  CAS  PubMed  Google Scholar 

  25. Ghosh A, Shah SV, Dave JN, Vora NS, Roy K, Cardoso BJ. Scleredema. Indian J Dermatol Venereol Leprol. 1995;61(5):324–5.

    CAS  PubMed  Google Scholar 

  26. Wright RA, Bernie H. Scleredema adultorum of Buschke with upper esophageal involvement. Am J Gastroenterol. 1982;77(1):9–11.

    CAS  PubMed  Google Scholar 

  27. Barnes M, Kumar V, Le TH, Nabeel S, Singh J, Rana V, et al. A case of paraproteinemia-associated scleredema successfully treated with thalidomide. JAAD Case Rep. 2020;6(10):1039–41.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Mark PB, Dekkers I, Blankestijn PJ, Leiner T, Roditi G. Letter on ‘European dermatology forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, part 2: Scleromyxedema, scleredema and nephrogenic systemic fibrosis’. J Eur Acad Dermatol Venereol. 2018;32(2):e84–e5.

    Article  CAS  PubMed  Google Scholar 

  29. Eastham AB, Femia AN, Velez NF, Smith HP, Vleugels RA. Paraproteinemia-associated scleredema treated successfully with intravenous immunoglobulin. JAMA Dermatol. 2014;150(7):788–9.

    Article  PubMed  Google Scholar 

  30. Dinneen AM, Dicken CH. Scleromyxedema. J Am Acad Dermatol. 1995;33(1):37–43.

    Article  CAS  PubMed  Google Scholar 

  31. Blum M, Wigley FM, Hummers LK. Scleromyxedema: a case series highlighting long-term outcomes of treatment with intravenous immunoglobulin (IVIG). Medicine (Baltimore). 2008;87(1):10–20.

    Article  PubMed  Google Scholar 

  32. Berger JR, Dobbs MR, Terhune MH, Maragos WF. The neurologic complications of scleromyxedema. Medicine (Baltimore). 2001;80(5):313–9.

    Article  CAS  PubMed  Google Scholar 

  33. Mahévas T, Arnulf B, Bouaziz JD, Livideanu CB, Osio A, Servy A, et al. Plasma cell-directed therapies in monoclonal gammopathy-associated scleromyxedema. Blood. 2020;135(14):1101–10.

    PubMed  Google Scholar 

  34. Sala AC, Cunha PR, Pinto CA, Alves CA, Paiva IB, Araujo AP. Scleromyxedema: clinical diagnosis and autopsy findings. An Bras Dermatol. 2016;91(5 suppl 1):48–50.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Kalli F, Cioni M, Parodi A, Altosole T, Ferrera F, Barra G, et al. Increased frequency of interleukin-4 and reduced frequency of interferon-γ and IL-17-producing CD4+ and CD8+ cells in scleromyxedema. J Eur Acad Dermatol Venereol. 2020;34(5):1092–7.

    Article  CAS  PubMed  Google Scholar 

  36. Mecoli CA, Talbot CC Jr, Fava A, Cheadle C, Boin F, Wigley FM, et al. Clinical and molecular phenotyping in Scleromyxedema pretreatment and posttreatment with intravenous immunoglobulin. Arthritis Care Res (Hoboken). 2020;72(6):761–7.

    Article  CAS  PubMed  Google Scholar 

  37. Rongioletti F, Merlo G, Cinotti E, Fausti V, Cozzani E, Cribier B, et al. Scleromyxedema: a multicenter study of characteristics, comorbidities, course, and therapy in 30 patients. J Am Acad Dermatol. 2013;69(1):66–72.

    Article  PubMed  Google Scholar 

  38. Mahevas T, Arnulf B, Bouaziz JD, Livideanu CB, Osio A, Servy A, et al. Plasma cell-directed therapies in monoclonal gammopathy-associated scleromyxedema. Blood. 2020;135(14):1101–10.

    PubMed  Google Scholar 

  39. Shulman LE. Diffuse fasciitis with eosinophilia: a new syndrome? Trans Assoc Am Phys. 1975;88:70–86.

    CAS  PubMed  Google Scholar 

  40. Lakhanpal S, Ginsburg WW, Michet CJ, Doyle JA, Moore SB. Eosinophilic fasciitis: clinical spectrum and therapeutic response in 52 cases. Semin Arthritis Rheum. 1988;17(4):221–31.

    Article  CAS  PubMed  Google Scholar 

  41. Salamaliki C, Solomou EE, Liossis SC. Immune checkpoint inhibitor-associated scleroderma-like syndrome: a report of a pembrolizumab-induced “eosinophilic fasciitis-like” case and a review of the literature. Rheumatol Ther. 2020;7(4):1045–52.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Chan KK, Magro C, Shoushtari A, Rudin C, Rotemberg V, Rossi A, et al. Eosinophilic fasciitis following checkpoint inhibitor therapy: four cases and a review of literature. Oncologist. 2020;25(2):140–9.

    Article  CAS  PubMed  Google Scholar 

  43. Cao XY, Zhao JL, Hou Y, Wang FD, Lu ZH. Janus kinase inhibitor tofacitinib is a potential therapeutic option for refractory eosinophilic fasciitis. Clin Exp Rheumatol. 2020;38(3):567–8.

    PubMed  Google Scholar 

  44. Lebeaux D, Francès C, Barete S, Wechsler B, Dubourg O, Renoux J, et al. Eosinophilic fasciitis (Shulman disease): new insights into the therapeutic management from a series of 34 patients. Rheumatology (Oxford). 2012;51(3):557–61.

    Article  CAS  PubMed  Google Scholar 

  45. Primitivo A, Madeira N, Lopez D, Afonso D. Eosinophilic fasciitis (Shulman disease) with clinical, imaging and pathological correlation. BMJ Case Rep. 2021;14(12).

    Google Scholar 

  46. Mango RL, Bugdayli K, Crowson CS, Drage LA, Wetter DA, Lehman JS, et al. Baseline characteristics and long-term outcomes of eosinophilic fasciitis in 89 patients seen at a single center over 20 years. Int J Rheum Dis. 2020;23(2):233–9.

    Article  CAS  PubMed  Google Scholar 

  47. Nashel J, Steen V. The use of an elevated aldolase in diagnosing and managing eosinophilic fasciitis. Clin Rheumatol. 2015;34(8):1481–4.

    Article  PubMed  Google Scholar 

  48. Li SC, Higgins GC, Chen M, Torok KS, Rabinovich CE, Stewart K, et al. Extracutaneous involvement is common and associated with prolonged disease activity and greater impact in juvenile localized scleroderma. Rheumatology (Oxford). 2021;60(12):5724–33.

    Article  CAS  PubMed  Google Scholar 

  49. Ulc E, Rudnicka L, Waśkiel-Burnat A, Warszawik-Hendzel O, Niemczyk A, Olszewska M. Therapeutic and reconstructive management options in scleroderma (morphea) en coup de sabre in children and adults. A systematic literature review. J Clin Med. 2021;10(19):4517.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Medicine, Division of Rheumatology, Johns Hopkins University, Baltimore, MD, USA

    Laura K. Hummers

  2. Department of Rheumatology, University Hospital Basel, Basel, Switzerland

    Alan Tyndall

Authors
  1. Laura K. Hummers
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  2. Alan Tyndall
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Correspondence to Laura K. Hummers .

Editor information

Editors and Affiliations

  1. INSERMU1016, Université Paris Cité,, Service de Rhumatologie, Hôpital Cochin,, Paris, France

    Yannick Allanore

  2. Department of Internal Medicine, University of Michigan–Ann Arbor, Ann Arbor, MI, USA

    John Varga

  3. Centre for Rheumatology, University College London, Royal Free Campus, London, UK

    Christopher P. Denton

  4. Department of Allergy and Rheumatology, Nippon Medical School, Tokyo, Tokyo, Japan

    Masataka Kuwana

  5. Rheumatology, Stanford Medicine, Redwood City, CA, USA

    Lorinda Chung

  6. Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Ami A. Shah

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Hummers, L.K., Tyndall, A. (2024). Scleroderma Mimics. In: Allanore, Y., Varga, J., Denton, C.P., Kuwana, M., Chung, L., Shah, A.A. (eds) Scleroderma. Springer, Cham. https://doi.org/10.1007/978-3-031-40658-4_11

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  • DOI: https://doi.org/10.1007/978-3-031-40658-4_11

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