Puffy fingers and skin thickening is associated with what disease?

May 23, 2017

Systemic sclerosis. Its rarity could lead to delays in diagnosis which, according to a review, may not be fully understood by inexperienced physicians.

Systemic sclerosis, also known as scleroderma, is an immune-mediated disease with mortality rates higher than any other rheumatic disease. Due to the fact that systemic sclerosis is uncommon, managing the disease remains a major clinical challenge for both physicians and patients.

For physicians, properly diagnosing systemic sclerosis is difficult because of their limited experiences seeing such cases. For example, making a diagnosis usually involves meeting the 2013 European League Against Rheumatism and American College of Rheumatology classification criteria. However, systemic sclerosis symptoms can be diverse and not all patients with the condition will meet these criteria.  For patients, the absence of ample evidence-based treatment options leads to anxiety and concerns about how best to manage their disease. 

To help give context to the challenges and opportunities within systemic sclerosis, researchers provide a review of clinical features of the disease and practice approaches. This review, published online April 13 in The Lancet, also discusses areas for future research.

Led by Christopher Denton, M.D. of the University College London in the United Kingdom, the review included a literature search in PubMed for systemic sclerosis or scleroderma and key terms including management, classification, pulmonary, renal, cardiovascular and epidemiology.

“Since systemic sclerosis is an uncommon disease for most physicians, the implications of a new diagnosis might be shaped by limited experiences of the disease. Even at expert centers, challenges exist around making the diagnosis and determining the extent of disease and activity (ie, rate of disease worsening), which might affect decision making about treatment,” the authors wrote.

The review is comprehensive, so here, we highlight some of the key points.

Signs and symptoms of systemic sclerosis

Multiple organ-based manifestations are a hallmark of systemic sclerosis and are important in the diagnosis and classification of the disease. Weight loss and exertion-related breathlessness are also common symptoms.

Major subsets of systemic sclerosis and their related features

Limited cutaneous systemic sclerosis: distal skin sclerosis, a long history of Raynaud’s phenomenon, pulmonary arterial hypertension, and severe gut disease.

Diffuse cutaneous systemic sclerosis: high frequency of severe lung fibrosis, proximal limb or trunk involvement with skin sclerosis, short history of Raynaud’s phenomenon, and increased risk for renal crisis and cardiac involvement.

Sine scleroderma: Raynaud’s phenomenon, systemic sclerosis serology or capillaroscopic features, no skin thickening, and organ-based or other vascular manifestations.

Systemic sclerosis overlap syndrome: One of the three subsets along with clinical and investigational features of another autoimmune rheumatic disease.

Pathophysiology

Historically, systemic sclerosis was viewed as a prototypical fibrotic disease within the family of autoimmune rheumatic disorders. However, this systemic sclerosis is evolving to be considered as a disease of dysregulated or dysfunctional repair of connective tissue in response to injury. Although the underlying pathology is still not completely understood, it is hypothesized that autoimmunity may be central to the initiation or progression of the disease.

Management

Comprehensive baseline assessments and thorough initial diagnostic investigations are important for a proper diagnosis. It should be noted that the majority of organ involvement will occur early in the disease and that no disease-modifying drugs for systemic sclerosis exist. Nevertheless, early screening and management of patients appears to improve mortality.

Other key points

  • Skin is almost always involved with systemic sclerosis and may be associated with increased mortality and organ involvement.
  • Immune-modulating therapies are used to manage skin-associated complications. Moreover, clinical trials have demonstrated clinical benefits for the use of methotrexate (15–25 mg/week) or mycophenolate mofetil (up to 3 g/day).
  • Lung fibrosis or interstitial lung disease is present in 80% of patients with systemic sclerosis; however, only 25–30% of patients develop progressive interstitial lung disease.
  • Pulmonary arterial hypertension affects approximately 15% of patients who have systemic sclerosis
  • Occult cardiac involvement almost certainly contributes to sudden death in patients and is associated with undercurrent sepsis.
  • Gastrointestinal tract involvement is typically present with systemic sclerosis.

 

Disclosures:

CPD received grants from CSL Behring, GlaxoSmithKline, and Inventiva (paid to his institution); consultancy fees from Bristol-Myers Squibb, Merck-Serono, GlaxoSmithKline, Inventiva, and Genentech (Roche); and speaker fees from Actelion and Bayer. DK received grants from Bristol-Myers Squibb, Genentech (Roche), the National Institute of Allergy and Infectious Diseases, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Patient-Centered Outcomes Research Institute, and the Scleroderma Foundation; and consultancy fees from Actelion, Bayer, Cytori, EMD Serono, Genkyotex, Gilead, GlaxoSmithKline, Genentech (Roche), Sanofi-Aventis, and Seattle Genetics.

 

References:

Christopher P. Denton and Dinesh Khanna. "Systemic sclerosis," The Lancet. Published April 13, 2017. DOI: http://dx.doi.org/10.1016/S0140-6736(17)30933-9.

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