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Differentiating disease activity from damage in systemic sclerosis: it’s still early days!
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  1. Siddharth Jain1,
  2. Shefali Khanna Sharma2
  1. 1 Clinical Immunology and Rheumatology, Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
  2. 2 Clinical Immunology and Rheumatology, Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, Indiaa
  1. Correspondence to Dr Shefali Khanna Sharma, Clinical Immunology and Rheumatology, Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India; sharmashefali{at}hotmail.com

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We read with great interest the article ‘Development and validation of the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI): a novel instrument to quantify organ damage in systemic sclerosis’ by Ferdowsi et al.1 We commend the authors’ to have come up with the much-needed concept of a damage index in systemic sclerosis. Differentiating activity from chronicity or damage is one of the key aspects in treatment of all rheumatological disorders and dictates the aggressiveness of treatment strategies employed. This differentiation is especially difficult in systemic sclerosis, owing to our incomplete understanding of the multifaceted pathogenesis of this complex disorder. What is currently believed to be irreversible (ie, damage) may in fact be reversible (ie, activity).

The SCTC-DI offers a promising outcome assessment tool for future clinical trials, but its clinical utility seems limited at present. Role of a damage index is to define, for a clinician, a point of ‘no return’ in the natural history of a disease or its clinical manifestation(s), where giving additional therapy is unlikely to benefit. This, however, does not hold true for many manifestations included in the SCTC-DI like interstitial lung disease (ILD), proximal muscle weakness, pulmonary hypertension (PH), myocardial systolic dysfunction, etc. Presence of these manifestations in the manner suggested in SCTC-DI may not help a clinician in taking the decision to ‘de-escalate’ and ‘not treat further’. For example, as the Scleroderma Lung Studies have shown, treatment in systemic sclerosis–ILD does lead to a mild improvement or at least stabilisation of lung function.2 3 As a corollary, denying immunosuppression to a patient of systemic sclerosis–ILD with >20% involvement of lung parenchyma in high-resolution CT that has persisted for last 6 months, by classifying it as damage (as suggested in the SCTC-DI) may be ill-founded.

Also, a low forced vital capacity (FVC), besides being due to ILD or respiratory muscle weakness, may also be secondary to tightening of skin over the chest causing extraparenchymal restriction and should be factored in before attributing a low observed FVC to ILD.

A significant proportion of patients with systemic sclerosis have overlap inflammatory myositis,4 which is reversible with immunosuppression, as opposed to the classical fibrosing myopathy of systemic sclerosis. This differentiation is critical and needs to be emphasised to all practising internists and rheumatologists, before attributing any/all proximal muscle weakness in patients with systemic sclerosis to non-reversible fibrosing myopathy (‘damage’).

The aetiopathogenesis of PH in systemic sclerosis is multifactorial, with multiple phenotypes recently been defined.5 Although as a group, the outcomes of systemic sclerosis–PH are poor,6 advancements in our current understanding of the underlying mechanisms may help identify subsets/endotypes of patients likely to have a favourable response to vasodilators, anticoagulation and/or immunosuppression, as seen in some patients of systemic lupus erythematosus–PH or mixed connective tissue disease–PH.7 In our experience as well, a few patients of systemic sclerosis–PH showed considerable reduction in pulmonary artery systolic pressures with therapy.8

In a minority of patients, systolic myocardial dysfunction in systemic sclerosis may be due to myocarditis, especially in the setting of concomitant myositis.9 This recovers dramatically with immunosuppression, if instituted timely.9 On the contrary, low grade ongoing chronic myocardial inflammation, if unrecognised and left untreated, may be the cause of myocardial fibrosis seen commonly in patients with systemic sclerosis.10 Using persistence for 6 months as the criteria to classify irreversibility or damage may not be appropriate in this setting. Detecting this myocardial inflammation at an early stage offers hope for salvageability of myocardial function with immunosuppression in this subset of patients.

Low body mass index <18.5 kg/m2 as a surrogate for damage might be inappropriate in a non-Caucasian third world population, where undernutrition is widely prevalent especially in females.

Lastly, we believe that digital pitting scars could also be considered for inclusion as a more pragmatic indicator for disease damage in the skin, in addition to digital ulcers.

Thus, these are still early days in our understanding of ‘reversible’ disease activity and ‘irreversible’ disease damage in systemic sclerosis, with this laudable effort by the authors being the beginning.

References

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Footnotes

  • Contributors SJ drafted the manuscript. SKS critically reviewed it and provided valuable suggestions.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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