Diagnosis and management of systemic sclerosis-related calcinosis

ABSTRACT

Introduction

Calcinosis is common in patients with systemic sclerosis (SSc) and refers to the sub-epidermal deposition of calcium salts in the skin. SSc-related calcinosis is associated with significant morbidity, including through cutaneous ulceration and predisposition to become infected.

Areas covered

After briefly addressing aetiopathogenesis, we describe the clinical burden of SSc-associated calcinosis and provide a structured and practical clinical approach to diagnosis and assessment, including discussion of the role of different imaging modalities. The multi-faceted treatment of SSc-associated calcinosis is presented under three broad headings of ‘general measures,’ and ‘medical treatment’ and ‘surgical treatment.’ We adopted a narrative approach to identify relevant manuscripts to inform our review.

Expert opinion

SSc-related calcinosis is an area of major unmet clinical need and for too long has been a neglected area of research. Safe and effective treatments are badly needed to improve patient quality of life and outcomes. To facilitate future clinical trials, we require increased understanding of pathogenesis (to inform selection of potential targeted therapies) and reliable outcome measures, including those which will measure the impact and severity of calcinosis from the patient perspective. International collaborative research is ongoing to develop outcome measures and treatments for this potentially devastating complication of SSc.

KEYWORDS:

• Calcinosis
• imaging
• management
• pathophysiology
• pharmacological treatment
• scleroderma
• systemic sclerosis

Article highlights

• Calcinosis is common, affecting approximately 20–40% of patients with SSc, and is associated with significant disease-related morbidity.

• The aetiopathogenesis of calcinosis in SSc remains incompletely understood.

• The skin of patients with SSc is believed to be a ‘primed’ microenvironment for the development of calcification.

• Associates of calcinosis include severe digital ischemia, autoantibody status, and disease duration.

• Calcinosis can ulcerate through the skin and become infected, and calcinosis can compress local structures.

• Research is ongoing to develop reliable outcome measures, including those involving different imaging modalities.

• Patient education to promote early recognition of infected calcinosis is a cornerstone of current management, to allow early antibiotic treatment.

• Currently, there is no known disease-modifying treatment for SSc-related calcinosis, and this represents an area of major unmet clinical need.

• Surgery to debulk calcinotic lesions may be indicated in selected patients.

• Future research is required to develop novel treatment approaches (based upon better understanding the underlying pathogenesis) and reliable and meaningful outcome measures (to facilitate clinical trials).

Acknowledgments

We thank Professor Jonathan Harris for providing the CT and MRI figure images.

Declaration of interest

M Hughes reports speaking fees from Actelion Pharmaceuticals, Eli Lilly, and Pfizer, outside of the submitted work (all <$10,000). He is a member of the Data and Safety Monitoring Board for Certa Therapeutics. A Herrick has received consultancy fees from Arena, Boehringer-Ingelheim, Camurus, CSL Behring, and Gesynta Pharma, speaker fees from Actelion and Janssen, and research funding from Actelion and Gesynta Pharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.