June is Scleroderma Awareness Month: Understanding the Challenges and Advancements in Systemic Sclerosis

Systemic sclerosis (SSc), also known as scleroderma, is a chronic autoimmune disease that affects connective tissue throughout the body. This condition can manifest in various ways, impacting the skin, blood vessels, and internal organs. While SSc is relatively rare, its effects can be debilitating and even life-threatening.

Understanding Systemic Sclerosis

SSc is characterized by excessive collagen production, leading to fibrosis (thickening and hardening) of the skin and internal organs. It's a heterogeneous disease, meaning it can present differently in each individual. Common symptoms include:

• Raynaud's phenomenon: Discoloration and numbness in fingers and toes due to cold exposure.
• Skin thickening: Tightening and hardening of the skin, particularly on the hands and face.
• Digestive problems: Difficulty swallowing, acid reflux, bloating, and constipation.
• Lung problems: Shortness of breath, cough, and scarring of lung tissue.
• Heart problems: Arrhythmias, heart failure, and inflammation of the heart muscle.
• Kidney problems: High blood pressure and kidney failure (scleroderma renal crisis).

Causes of systemic sclerosis

The exact cause of systemic sclerosis remains unknown, but it is believed to be a complex interplay of genetic predisposition, environmental triggers, and immune system dysregulation. In genetically susceptible individuals, exposure to certain environmental factors, such as silica dust, solvents, or certain medications, may initiate an autoimmune response that leads to excessive collagen production and fibrosis.? This immune response also involves the production of autoantibodies, which are directed against the body's own tissues and contribute to the characteristic features of the disease.

The Challenge of Diagnosis

Diagnosing SSc can be challenging due to the diversity of symptoms and the fact that it can mimic other conditions. There's no single definitive test for SSc, and the diagnosis is often made based on a combination of:

• Clinical evaluation: A thorough medical history and physical exam to identify characteristic signs and symptoms.
• Laboratory tests: Blood tests to detect autoantibodies, markers of inflammation, and organ function abnormalities.
• Imaging studies: X-rays, CT scans, or MRI scans to assess the extent of organ involvement.

Diagnostic Tools for Systemic Sclerosis

Laboratory Tests for Systemic Sclerosis: Technologies and Applications

Laboratory Tests:

• Antinuclear antibodies (ANA): Positive in most SSc patients.
• SSc-specific antibodies: Anti-centromere antibodies (ACA) and anti-topoisomerase I / Scl 70 antibodies (ATA) are strongly associated with SSc and can help determine the subtype.
• Other autoantibodies: Anti-RNA polymerase III antibodies and anti-U3 RNP antibodies can be present.
• Biomarkers of inflammation and organ function: ESR, CRP, creatinine, liver enzymes, etc.

Antinuclear Antibodies (ANA):

• Indirect Immunofluorescence Assay (IFA): The most common initial screening test for ANA. Patient serum is incubated with cells on a slide, and fluorescent-labeled antibodies are used to detect the presence of ANAs.

• Enzyme-Linked Immunosorbent Assay (ELISA): A quantitative method for measuring specific ANA subtypes, such as anti- antibodies.
• Chemiluminescence Immunoassays (CLIA): Offers high sensitivity and specificity for detecting ACA and ATA antibodies.

SSc-Specific Antibodies:

• ELISA: Commonly used to detect ACA and ATA antibodies, as well as other SSc-related autoantibodies.
• Line Immunoassays (LIA): A semi-quantitative method that provides a visual confirmation of the presence of specific antibodies.
• Multiplex Bead Assays: Allows for simultaneous detection of multiple ANAs and other autoantibodies, offering a more comprehensive profile.

Other Autoantibodies:

• Immunoprecipitation: Used to detect antibodies to specific cellular components, such as RNA polymerase III or U3 RNP.
• Immunoblotting (Western Blot): Can confirm the presence of specific autoantibodies by separating proteins and identifying the antibody-antigen complexes.

Biomarkers of Inflammation and Organ Function:

• Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP): These are non-specific markers of inflammation and can be measured using automated analyzers.
• Creatinine and Liver Enzymes: These markers of kidney and liver function are typically measured using standard clinical chemistry analyzers.

Other Potential Tests:

• Nailfold capillaroscopy: Microscopic examination of nail bed capillaries to detect changes associated with SSc.
• Artificial Intelligence Shows Potential for Accurate Assessment of Nailfold Changes in Systemic Sclerosis Patients
• Pulmonary function tests (PFTs): Assess lung function and detect early signs of lung involvement.
• Echocardiogram: Evaluate heart function and detect potential complications.
• Gastrointestinal tests: Endoscopy or barium swallow to assess the digestive system.

ACR/EULAR classification criteria

The most widely used criteria are the 2013 classification criteria developed by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). These criteria are based on a point system that considers:

Scleroderma is a rare autoimmune condition that results in tight, thickened skin. A common complication of Scleroderma is the formation of digital ulcers, which are featured above.

• Clinical features: skin thickening, Raynaud's phenomenon, SSc-specific antibodies, nailfold capillary changes, and specific internal organ involvement.
• Laboratory findings: presence of SSc-specific autoantibodies.

A certain number of points is required for a diagnosis of SSc. These criteria have high sensitivity and specificity, making them a valuable tool for clinicians in diagnosing SSc.

While there is no single definitive test for SSc, the combination of clinical evaluation, laboratory tests, and imaging studies, along with the ACR/EULAR classification criteria, helps guide clinicians in making an accurate diagnosis.

Challenges in Systemic Sclerosis:

Early diagnosis:?

Early detection can be difficult due to non-specific initial symptoms.

Subtyping:?

Determining the SSc subtype is crucial for predicting disease course and guiding treatment.

• Limited systemic sclerosis (lSSc): also known as CREST syndrome, is a subtype of scleroderma characterized by skin thickening limited to the hands, face, feet, and forearms.? It often presents with Raynaud's phenomenon, where fingers and toes turn white or blue in response to cold. While internal organ involvement is less common than in diffuse SSc, lSSc can still affect the esophagus, lungs, and blood vessels, leading to complications like pulmonary hypertension.
• Diffuse systemic sclerosis (dSSc): subtype of scleroderma characterized by widespread skin thickening that can extend beyond the hands and face to involve the trunk and upper arms or legs. It often has a rapid onset and a higher risk of internal organ involvement, particularly the lungs, heart, and kidneys. Early diagnosis and aggressive treatment are crucial to manage complications and improve outcomes for dSSc patients.?

Important Resources for Patients and Researchers:

• National Scleroderma Foundation: Provides information, support, and advocacy for people with scleroderma.
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): Conducts and supports research on SSc and other rheumatic diseases.
• The Scleroderma Clinical Trials Consortium (SCTC): A network of research centers dedicated to conducting clinical trials for new SSc treatments.

Treatment and Management of Systemic Sclerosis

Limited treatment options:?

While there is no cure for systemic sclerosis, various treatment approaches aim to manage symptoms, slow disease progression, and improve patients' quality of life. These approaches vary depending on the subtype and severity of the disease, as well as the specific organs involved.??

• For skin involvement, medications like methotrexate, mycophenolate mofetil, and cyclophosphamide may be used to suppress the immune system and reduce inflammation. Vasodilators can help manage Raynaud's phenomenon, while physical and occupational therapy can improve joint mobility and skin flexibility.
• For internal organ involvement, specific therapies are targeted towards the affected organ. For example, ACE inhibitors may be used to treat kidney problems, while immunosuppressants or antifibrotic agents may be used for lung involvement. In severe cases, organ transplantation may be considered.
• Emerging therapies, such as stem cell transplantation and targeted biologic therapies, are being investigated as potential future treatment options. Additionally, lifestyle modifications like exercise, stress management, and a healthy diet can play a crucial role in managing symptoms and improving overall well-being for individuals living with systemic sclerosis.?

PSG Systemic Sclerosis Biobank: Advancing Research and Diagnostics in SSc

Plasma Services Group (PSG) is proud to introduce our Systemic Sclerosis (SSc) Biobank, a comprehensive resource designed to empower clinical labs, researchers, and IVD manufacturers in their pursuit of innovative diagnostic and therapeutic solutions. Our unique direct-to-patient recruitment model has enabled us to assemble a diverse cohort of over 35 SSc patients across the United States, providing access to matched serum, alongside extensive clinical data. With in-depth auto-antibody profiles (ANA, SSc-associated, SSc-specific) and comprehensive clinical snapshots, our Biobank serves as an invaluable tool for advancing research, accelerating product development, and enhancing diagnostic capabilities in the field of SSc.

Conclusion

Systemic sclerosis is a complex and challenging disease, but with ongoing research and the development of new diagnostic tools and treatments, there is hope for improved outcomes for patients. PSG's SSc Biobank represents a significant step forward in this effort, providing researchers and clinicians with the resources they need to better understand and combat this debilitating condition.

Disclaimer: This article is for informational purposes and not medical advice. Always consult a healthcare professional for personalized guidance on Systemic Sclerosis diagnosis and treatment.