Systemic sclerosis and related disorders

2018 ◽  
pp. 401-424
Author(s):  
Gavin Clunie ◽  
Nick Wilkinson ◽  
Elena Nikiphorou ◽  
Deepak R. Jadon
Keyword(s):  
Systemic Sclerosis ◽  
Connective Tissue ◽  
Connective Tissue Disease ◽  
Broad Spectrum ◽  
Clinical Manifestations ◽  
Life Threatening

This chapter focuses on systemic sclerosis, a generalized autoimmune connective tissue disease. It describes the epidemiology and classification of systemic sclerosis, along with its pathophysiology and potential triggers of disease. It also discusses the condition’s broad spectrum of clinical manifestations and highlights its potential for multiorgan involvement and life-threatening complications. Furthermore, the chapter provides insights into the definitions for related conditions such as morphoea and its different subtypes. Complexities around the treatment and a discussion on the prognosis and outcomes of systemic sclerosis and related conditions are also included.

scholarly journals 14. A severe case of connective tissue disease related interstitial lung disease in a young woman

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Kate Grant ◽  
Patrick McShane ◽  
Kathryn Kerr ◽  
Martin Kelly ◽  
Philip Gardiner ◽  
...  
Keyword(s):  
Weight Loss ◽  
Systemic Sclerosis ◽  
Connective Tissue ◽  
Connective Tissue Disease ◽  
Lung Biopsy ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Connective Tissue Disorder ◽  
Young Age ◽  
History Of

Abstract Introduction Interstitial lung disease (ILD) can occur in any connective tissue disease, with varying degrees of respiratory clinical manifestations. In the majority of cases, patients have an established connective tissue diagnosis that precedes the development of ILD by many years. This discussion will focus on the unusual presentation of an 18 year old female admitted with a short history of weight loss and breathlessness. Investigations showed extensive established ILD with strongly positive autoantibodies, but in the absence of clinical signs of an underlying connective tissue disorder apart from Raynaud’s phenomenon. Case description 18-year-old female presented with a three-month history of unintentional 25kg weight loss, six weeks of fatigue/malaise, and a two-week history of worsening breathlessness. She was a student, non-smoker, with no past medical history except for class I obesity, and not on regular medications. On examination she had fine bibasal end-inspiratory crackles, SaO2 96% RA and Raynaud’s phenomenon was observed. Her CXR demonstrated bibasal consolidation. CT imaging identified bilateral symmetrical peripheral patchy ground glass opacities and patchy consolidation with basal predominance. Bloods revealed rheumatoid factor 491.2, anti-RNP A ab 7.91, anti-Sm ab > 8 and anti-chromatin ab 7.3, speckled ANA positive titre of 40, Complement C4 0.08, ESR 29 and HIV negative. Pulmonary function tests demonstrated a restrictive pattern FEV1 2.08L (72%), FVC 2.43L (73%), Ratio 85% and reduced transfer factor - DLCO 41%, KCO 61%. Ambulatory oxygen assessment showed desaturation to 77% RA. Bronchoscopy revealed inflamed airways and a bronchoalveolar lavage (BAL) cell count of 0.6 x 106 - 42% macrophages, 32% neutrophils, 24% eosinophils, 2% lymphocytes. At the local ILD MDT a differential diagnosis of LIP or NSIP was considered. Following discussion with rheumatology she was referred to the thoracic surgical team for lung biopsy. She proceeded to surgical biopsy of her right lung without complication. Unfortunately, she continued to experience worsening breathlessness and myalgia and she was commenced on prednisolone (40mg), with some radiological improvement but no symptomatic benefit. The pathology from her lung biopsy demonstrated significant fibrosis with scattered lymphoid aggregates, microscopic honeycombing with multiple fibroblastic foci and diffuse changes, in keeping with a fibrotic NSIP pattern. Her case was discussed at Freeman Hospital Newcastle ILD MDT who advised that her presentation was in keeping with a mixed connective tissue/lupus-related NSIP, and suggested commencing methylprednisolone, cyclophosphamide and rituximab. Discussion On initial assessment, the patient’s age and symptoms of rapid weight loss and profound exertional dyspnoea were concerning. Her resting oxygen saturations were satisfactory, but she became markedly hypoxic on ambulating short distances, indicating serious respiratory pathology. The initial CXR showed ‘faint patchy consolidation’, but CT scan showed extensive interstitial changes, accounting for her dyspnoea and desaturation on exertion. Further investigations including rheumatoid factor, anti-RNP and anti-Sm antibody were found to be strongly positive, suggesting an underlying mixed connective tissue disorder. However, the patient did not complain of any symptoms related to arthritis, SLE, systemic sclerosis or polymyositis and no positive clinical findings were noted on examination in support of these diagnoses. The BAL analysis was consistent with CT-ILD but not specific enough for diagnosis. A lung biopsy was performed on advice of the ILD lung MDT as the abnormalities on CT imaging could be in keeping with several pathologies with very different associated prognosis and management. The biopsy appearance correlated poorly with the cell count in BAL fluid. Discussion at local and regional ILD MDTs was particularly helpful given the severity of ILD and her young age. The ILD MDT provided a consensus of expert advice on optimal management and confirmed our concern about the extent of established fibrosis and the need for aggressive management. This obviously has significant implications for the patient in many ways, but particularly regarding fertility given her young age and she was therefore referred to the regional fertility clinic for counselling. Key learning points This was a particularly unusual case because the patient presented acutely at a very young age with established fibrotic damage on lung biopsy. It is also noteworthy that she presented so acutely with advanced ILD even though there were no positive clinical signs on examination, and no symptoms or signs of an underlying connective tissue disease. Lung biopsy is not routinely indicated in patients with progressive (respiratory) clinical manifestations of CT ILD, particularly in patients with an established diagnosis of rheumatoid arthritis or systemic sclerosis, as corticosteroids and/or immunosuppression are the mainstay of treatment regardless of the underlying CT pathology. However, lung biopsy is indicated where there is diagnostic uncertainty due to atypical presentations. In this case the biopsy findings were unexpected and resulted in a change to the initial management plan. Considerations about fertility and long term toxicity further complicated our choice of optimal therapy. This was a challenging case and highlighted the importance of multidisciplinary management of complex ILD cases. Discussions between local rheumatology, radiology and respiratory clinicians led to the decision that a biopsy was necessary. Subsequently the ILD MDT in the Freeman hospital provided clear expert guidance on in favour of a more aggressive treatment regimen than may have been otherwise initially considered. Conflict of interest The authors declare no conflicts of interest.

scholarly journals AB0411 CHALLENGES IN THE MANAGEMENT OF MIXED CONNECTIVE TISSUE DISEASE: A RETROSPECTIVE ANALYSIS OF THE MCTD COHORT IN A TERTIARY REFERRAL CENTRE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1233.3-1234
Author(s):  
A. Wanzenried ◽  
A. Garaiman ◽  
S. Jordan ◽  
O. Distler ◽  
B. Maurer
Keyword(s):  
Connective Tissue ◽  
International Symposium ◽  
Diagnostic Criteria ◽  
Connective Tissue Disease ◽  
Lupus Erythematosus ◽  
Mixed Connective Tissue Disease ◽  
Activity Index ◽  
Referral Centre ◽  
Tertiary Referral Centre

Background:As a rare, complex, and heterogeneous disease, mixed connective tissue disease (MCTD) represents a challenge for clinical practice.Objectives:We aimed to unravel potential pitfalls including correct referral diagnosis, fulfilment of diagnostic criteria, distinction from other CTDs, disease course and activity, and treatment modalities.Methods:We analysed the prospectively collected MCTD cohort at our tertiary referral centre. The patients’ medical histories were investigated for fulfilment of Sharp’s (1), Kasukawa’s (2), and Alarcón-Segovia’s (3) diagnostic MCTD criteria. We defined overlap syndromes as simultaneous fulfilment of clinical as well as immunological criteria of two defined rheumatic diseases. Disease conversion was defined as emergence of new symptoms and autoantibodies consistent with another rheumatic disease. Remission was defined by simultaneous systemic lupus erythematosus disease activity index 2000 (SLEDAI-2 K) of 0 and European League Against Rheumatism scleroderma trial and research (EUSTAR) activity index <2.5. Disease phenotype and disease activity were monitored over time and all patients were evaluated for fulfilment of classification criteria of various connective tissue diseases.Results:Out of 85 patients initially referred as MCTD, only one third fulfilled the diagnostic MCTD criteria. Most of the remaining patients had undifferentiated CTD (29%) or overlap syndromes (20%). In our final cohort of 33 MCTD patients, 6 (48%) also met the classification criteria of systemic sclerosis, 13 (39%) those of systemic lupus erythematosus (SLE), 6 (18%) those of rheumatoid arthritis, and 3 (9%) those of primary myositis. Over the median observation period of 4.6 (1.6, 9.9) years, only two patients (6%) underwent disease conversion from MCTD to SLE and no patient converted towards other diseases. The number of patients in remission increased from 6 (18%) to 15 (45%) due to introduction of immune modulatory treatment. Combination therapy was favoured in most cases (17 patients, 52%), whereas monotherapy was less frequent (12 patients, 36%), and only 4 (12%) patients remained without immune modulators until the end of the follow-up period. Hydroxychloroquine, prednisone, and methotrexate were the most frequently used medications in our cohort.Conclusion:Our study showed a high risk for misdiagnosis for patients with MCTD. Phenotype conversion was a very rare event. As a multi-organ disease, MCTD required prolonged (combined) immunosuppressive therapy to achieve remission. The establishment of an international registry with longitudinal data from observational multi-centre cohorts might represent a first step to address the many unmet needs of MCTD.References:[1]Sharp GC. Diagnostic criteria for classification of MCTD. In: Kasukawa R, Sharp GC, editors. Mixed connective tissue disease and anti-nuclear antibodies: proceedings of the International Symposium on Mixed Connective Tissue Disease and Anti-nuclear Antibodies, Tokyo, 29-30 August 1986. no. 719. Amsterdam: Elsevier Science Publishers B.V. (Biomedical Division); 1987. p. 23-30.[2]Kasukawa R, Tojo T, Miyawaki S, Yoshida H, Tanimoto K, Nobunaga M, et al. Preliminary diagnostic criteria for classification of mixed connective tissue disease. In: Kasukawa R, Sharp GC, editors. Mixed connective tissue disease and anti-nuclear antibodies: proceedings of the International Symposium on Mixed Connective Tissue Disease and Anti-nuclear Antibodies, Tokyo, 29-30 August 1986. no. 719. Amsterdam: Elsevier Science Publishers B.V. (Biomedical Division); 1987. p. 41-7.[3]Alarcón-Segovia D, Villarreal M. Classification and diagnostic criteria for mixed connective tissue disease. In: Kasukawa R, Sharp GC, editors. Mixed connective tissue disease and anti-nuclear antibodies: proceedings of the International Symposium on Mixed Connective Tissue Disease and Anti-nuclear Antibodies, Tokyo, 29-30 August 1986. no. 719. Amsterdam: Elsevier Science Publishers B.V. (Biomedical Division); 1987. p. 33-40.Disclosure of Interests:Adrian Wanzenried: None declared, Alexandru Garaiman: None declared, Suzana Jordan: None declared, Oliver Distler Consultant of: O.D. had consultancy relationship and/or has received research funding from Abbvie, Actelion, Acceleron Pharma, Amgen, AnaMar, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, Catenion, Competitive Drug Development International Ltd, CSL Behring, ChemomAb, Curzion Pharmaceuticals, Ergonex, Ga-lapagos NV, Glenmark Pharmaceuticals, GSK, Inventiva, Italfarmaco, iQone, iQvia, Lilly, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Target Bio Science and UCB in the area of potential treatments of scleroderma and its complications., Britta Maurer Consultant of: Boehringer-Ingelheim, Grant/research support from: AbbVie, Protagen, and Novartis Biomedical Research as well as congress support from Pfizer, Roche, Actelion, mepha, and MSD.

Overlap/undifferentiated syndromes

2013 ◽  
pp. 1069-1078 ◽  
Author(s):  
Ariane Herrick
Keyword(s):  
Connective Tissue ◽  
Connective Tissue Disease ◽  
Clinical Features ◽  
Lupus Erythematosus ◽  
Raynaud’S Phenomenon ◽  
Clinical Manifestations ◽  
Raynaud's Phenomenon ◽  
Overlap Syndromes ◽  
Clear Cut ◽  
Positive Treatment

Undifferentiated connective tissue disease (UCTD) and overlap syndromes both form part of the broad spectrum of connective tissue disease. They are difficult to define, as the boundaries between them and specific diseases such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and myositis are often not clear-cut. This chapter gives a broad overview of diagnosis, clinical features, outcomes, and management. Patients with UCTD have clinical and/or serological features of connective tissue disease but do not fulfil the criteria for any one defined disease. Raynaud’s phenomenon and puffy fingers are often the presenting features but there are many possible others, including arthralgia, sicca symptoms, and breathlessness due to pulmonary fibrosis, usually in the context of a positive anti-nuclear antibody (ANA). A proportion of patients evolve into a defined connective tissue disease: in those who do, this is generally within 5 years of onset. Treatment is dependent upon the clinical features: for examplem vasodilators for Raynaud’s phenomenon, or hydroxychloroquine for arthralgia/arthritis. Patients with overlap syndromes have features of more than one defined connective tissue disease. Overlap syndromes are therefore highly heterogeneous as many combinations of clinical and serological features can occur. Mixed connective tissue disease (MCTD) is the overlap syndrome that has been most described and includes overlapping features of SLE, SSc, and myositis in patients who are anti-U1 ribonucleoprotein (RNP) antibody positive. Treatment is of the specific clinical manifestations. Patients with overlap syndromes should be kept under regular review to allow early identification of internal organ involvement.

Life-threatening acute pneumonitis in mixed connective tissue disease: a case report and literature review

2015 ◽  
Vol 127 (19-20) ◽  
pp. 792-794 ◽  
Author(s):  
Eva Rath ◽  
Shahin Zandieh ◽  
Alexander Löckinger ◽  
Mirko Hirschl ◽  
Klaus Klaushofer ◽  
...  
Keyword(s):  
Case Report ◽  
Connective Tissue ◽  
Literature Review ◽  
Connective Tissue Disease ◽  
Mixed Connective Tissue Disease ◽  
Life Threatening

scholarly journals Interpretation of autoantibody positivity in interstitial lung disease and lung-dominant connective tissue disease

2013 ◽  
Vol 39 (6) ◽  
pp. 728-741 ◽  
Author(s):  
Daniel Antunes Silva Pereira ◽  
Alexandre de Melo Kawassaki ◽  
Bruno Guedes Baldi
Keyword(s):  
Interstitial Lung Disease ◽  
Connective Tissue ◽  
Lung Disease ◽  
Connective Tissue Disease ◽  
Current Knowledge ◽  
Pulmonary Involvement ◽  
Pathophysiological Role ◽  
History Of

The initial evaluation of patients with interstitial lung disease (ILD) primarily involves a comprehensive, active search for the cause. Autoantibody assays, which can suggest the presence of a rheumatic disease, are routinely performed at various referral centers. When interstitial lung involvement is the condition that allows the definitive diagnosis of connective tissue disease and the classical criteria are met, there is little debate. However, there is still debate regarding the significance, relevance, specificity, and pathophysiological role of autoimmunity in patients with predominant pulmonary involvement and only mild symptoms or formes frustes of connective tissue disease. The purpose of this article was to review the current knowledge of autoantibody positivity and to discuss its possible interpretations in patients with ILD and without clear etiologic associations, as well as to enhance the understanding of the natural history of an allegedly new disease and to describe the possible prognostic implications. We also discuss the proposition of a new term to be used in the classification of ILDs: lung-dominant connective tissue disease.

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