Multiple-autoimmune syndrome causing interstitial lung disease in the presence of pulmonary hypertension and Erasmus syndrome


Multiple-autoimmune syndrome
Interstitial lung disease
Connective tissue disease
Pulmonary hypertension
Non-specific interstitial pneumonia
Systemic lupus erythematosus
Rheumatoid arthritis
Systemic sclerosis
Sjögren syndrome
Erasmus syndrome

How to Cite

Corredor-Orlandelli, D., Borda, C., Sierra, J., & Fernández-Ávila, D. (2024). Multiple-autoimmune syndrome causing interstitial lung disease in the presence of pulmonary hypertension and Erasmus syndrome. Rheumatology (Bulgaria), 31(4), 123-128.


Connective tissue diseases constitute a group of inflammatory disorders that can concurrently affect multiple organs. Pulmonary manifestations of connective tissue diseases include interstitial lung disease, pulmonary hypertension, pleural diseases, and airway compromise. Both interstitial lung disease and pulmonary arterial hypertension have high morbidity and mortality in these patients. Interstitial lung disease affects 40 % - 50 % of patients with connective tissue diseases, predominantly systemic sclerosis, rheumatoid arthritis, and inflammatory myopathies. Parenchymal compromise is heterogeneous and depends on the underlying disease. Conversely, pulmonary arterial hypertension is found mostly in systemic sclerosis, systemic lupus erythematosus and mixed connective tissue disease. Delays and the diagnosis of connective tissue disorder associated interstitial lung disease are frequent as evidence is limited and as they often present concomitantly or overlap with other pulmonary diseases. Timely diagnosis and treatment are fundamental to decrease mortality. Treatment varies by the type of connective tissue disease, nevertheless, evidence of these complications in the context of multiple-autoimmune syndrome is still limited.

We present a complex case of a 47-year-old male with a multiple-autoimmune syndrome (systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, Sjögren syndrome and mixed connective tissue disease) complicated by interstitial lung disease and pulmonary hypertension,   and occurring concurrently with silicosis (Erasmus syndrome), and pulmonary embolism. This case shows the diverse manifestations of connective tissue of the lungs, emphasizes the intricate nature of diagnosing and managing connective tissue disorder-related pulmonary complications in the context of multiple autoimmune syndromes, and the importance of a multidisciplinary team for the diagnostic and therapeutic approach of the patient.


  1. Ortiz-Fernandez L, Martín J, Alarcon-Riquelme ME. A Summary on the Genetics of Systemic Lupus Erythematosus, Rheumatoid Arthritis, Systemic Sclerosis, and Sjögren’s Syndrome. Clin Rev Allergy Immunol; 64.
  2. Conrad N, Misra S, Verbakel JY, et al. Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK. The Lancet 2023; 401: 1878–1890.
  3. Anaya J-M. The diagnosis and clinical significance of polyautoimmunity. Autoimmun Rev 2014; 13: 423–426.
  4. Mohan MP, Ramesh TC. Multiple autoimmune syndrome. Indian J Dermatol Venereol Leprol 2003; 69: 298–299.
  5. Humbert P, Dupond JL. [Multiple autoimmune syndromes]. Ann Med Interne (Paris) 1988; 139: 159–168.
  6. Wielosz E, Majdan M, Zychowska I, et al. Coexistence of five autoimmune diseases: diagnostic and therapeutic difficulties. Rheumatol Int 2008; 28: 919–923.
  7. Anaya J-M, Corena R, Castiblanco J, et al. The kaleidoscope of autoimmunity: multiple autoimmune syndromes and familial autoimmunity. Expert Rev Clin Immunol 2007; 3: 623–635.
  8. Rojas-Villarraga A, Amaya-Amaya J, Rodriguez-Rodriguez A, et al. Introducing Polyautoimmunity: Secondary Autoimmune Diseases No Longer Exist. Autoimmune Dis 2012; 2012: 1–9.
  9. Makol A, Reilly MJ, Rosenman KD. Prevalence of connective tissue disease in silicosis (1985–2006)—a report from the state of michigan surveillance system for silicosis. Am J Ind Med 2011; 54: 255–262.
  10. Cooper GS, Wither J, Bernatsky S, Claudio JO, Clarke A, Rioux JD; CaNIOS GenES Investigators; Fortin PR. Occupational and environmental exposures and risk of systemic lupus erythematosus: silica, sunlight, solvents. Rheumatology (Oxford). 2010 Nov;49(11):2172-80
  11. Lee S, Hayashi H, Mastuzaki H, et al. Silicosis and autoimmunity. Curr Opin Allergy Clin Immunol 2017; 17: 78–84.
  12. Mehri F, Jenabi E, Bashirian S, et al. The association Between Occupational Exposure to silica and Risk of Developing Rheumatoid Arthritis: A Meta-Analysis. Saf Health Work 2020; 11: 136–142.
  13. McCormic ZD, Khuder SS, Aryal BK, et al. Occupational silica exposure as a risk factor for scleroderma: a meta-analysis. Int Arch Occup Environ Health 2010; 83: 763–769.
  14. Hogan SL, Cooper GS, Savitz DA, et al. Association of silica exposure with anti-neutrophil cytoplasmic autoantibody small-vessel vasculitis: a population-based, case-control study. Clin J Am Soc Nephrol CJASN 2007; 2: 290–299.
  15. Klockars M, Koskela RS, Järvinen E, et al. Silica exposure and rheumatoid arthritis: a follow up study of granite workers 1940-81. Br Med J Clin Res Ed 1987; 294: 997–1000.
  16. Azevedo S, Sousa-Neves J, Santos-Faria D, et al. Prevalence and clinical manifestations of Erasmus syndrome in systemic sclerosis: a cross-sectional study. Acta Reumatol Port 2020; 45: 183–190.
  17. Tyndall AJ, Bannert B, Vonk M, et al. Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis 2010; 69: 1809–1815.
  18. Mathai SC, Danoff SK. Management of interstitial lung disease associated with connective tissue disease. BMJ 2016; 352: h6819.
  19. Kamenova A, Tzouvelekis A, Margaritopoulos GA. Recent advances in the treatment of systemic sclerosis associated interstitial lung disease. Front Med 2023; 10: 1155771.
  20. Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheumatol Hoboken NJ 2019; 71: 1400–1412.
  21. Aletaha D, Neogi T, Silman AJ, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 2010; 69: 1580–1588.
  22. van den Hoogen F, Khanna D, Fransen J, et al. 2013 classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis 2013; 72: 1747–1755.
  23. Shiboski CH, Shiboski SC, Seror R, et al. 2016 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Primary Sjögren’s Syndrome: A Consensus and Data-Driven Methodology Involving Three International Patient Cohorts. Arthritis Rheumatol Hoboken NJ 2017; 69: 35–45.
  24. Alarcón-Segovia D, Cardiel MH. Comparison between 3 diagnostic criteria for mixed connective tissue disease. Study of 593 patients. J Rheumatol 1989; 16: 328–334.
  25. Cojocaru M, Cojocaru IM, SILOSI I. Multiple autoimmune syndrome. Mædica 2010; 5: 132–134.
  26. Elhai M, Avouac J, Kahan A, et al. Systemic sclerosis at the crossroad of polyautoimmunity. Autoimmun Rev 2013; 12: 1052–1057.
  27. Avouac J, Airò P, Dieude P, et al. Associated autoimmune diseases in systemic sclerosis define a subset of patients with milder disease: results from 2 large cohorts of European Caucasian patients. J Rheumatol 2010; 37: 608–614.
  28. Mira-Avendano I, Abril A, Burger CD, et al. Interstitial Lung Disease and Other Pulmonary Manifestations in Connective Tissue Diseases. Mayo Clin Proc 2019; 94: 309–325.
  29. Jeganathan N, Sathananthan M. Connective Tissue Disease-Related Interstitial Lung Disease: Prevalence, Patterns, Predictors, Prognosis, and Treatment. Lung. 2020 Oct 11;198(5):735–59.
  30. Wijsenbeek M, Cottin V. Spectrum of Fibrotic Lung Diseases. N Engl J Med 2020; 383: 958–968.
  31. Bazan IS, Mensah KA, Rudkovskaia AA, et al. Pulmonary arterial hypertension in the setting of scleroderma is different than in the setting of lupus: A review. Respir Med 2018; 134: 42–46.
  32. Lettieri CJ, Nathan SD, Barnett SD, et al. Prevalence and outcomes of pulmonary arterial hypertension in advanced idiopathic pulmonary fibrosis. Chest 2006; 129: 746–752.
  33. Gunnarsson R, Andreassen AK, Molberg Ø, et al. Prevalence of pulmonary hypertension in an unselected, mixed connective tissue disease cohort: results of a nationwide, Norwegian cross-sectional multicentre study and review of current literature. Rheumatol Oxf Engl 2013; 52: 1208–1213.
  34. Launay D, Mouthon L, Hachulla E, et al. Prevalence and characteristics of moderate to severe pulmonary hypertension in systemic sclerosis with and without interstitial lung disease. J Rheumatol 2007; 34: 1005–1011.
  35. Waxman A, Restrepo-Jaramillo R, Thenappan T, et al. Inhaled Treprostinil in Pulmonary Hypertension Due to Interstitial Lung Disease. N Engl J Med 2021; 384: 325–334.
  36. Lee S, Hayashi H, Kumaga-Takei N, et al. Autoantibodies in Silicosis Patients: Silica-Induced Dysregulation of Autoimmunity. In: Autoantibodies and Cytokines. IntechOpen. Epub ahead of print 20 December 2017.
  37. Zaghi G, Koga F, Nisihara RM, et al. Autoantibodies in silicosis patients and in silica-exposed individuals. Rheumatol Int 2010; 30: 1071–1075.
  38. Pollard KM. Silica, Silicosis, and Autoimmunity. Front Immunol 2016; 7: 97.
  39. Caplan A. Certain unusual radiological appearances in the chest of coal-miners suffering from rheumatoid arthritis. Thorax 1953; 8: 29–37.
  40. Erasmus LD. Scleroderma in goldminers on the Witwatersrand with particular reference to pulmonary manifestations. South Afr J Lab Clin Med Suid-Afr Tydskr Vir Lab- En Kliniekw 1957; 3: 209–231.
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