Exploring the Rare Disease Scleroderma
Summary
- Scleroderma is a rare autoimmune disease characterized by excessive collagen production.
- It can affect only the skin, or both skin and internal organs. It leads to the thickening of connective tissue and potential complications in organs such as the lungs, heart, and kidneys, which can ultimately result in death.
- Early signs, like excessive vessels constricting (called Raynaud’s phenomenon) and puffy fingers, serve as crucial indicators for early detection.
Scleroderma is a rare autoimmune disease characterized by excessive collagen production and tissue scarring caused by a specific cell type called fibroblasts. Scleroderma has two types, localized and systemic.
In both types, collagen accumulation leads to thickening and hardening of the skin and connective tissues. In the systemic subtype, which is more severe, scleroderma also affects internal organs, blood vessels, and muscles.
In general, scleroderma has a very high mortality rate and can strongly impair the quality of life [1].
Prevalence and Gender Distribution
Scleroderma is a rare disease, with estimates suggesting a prevalence of around 17.6 cases per 100,000 people. The occurrence varies among different populations and regions [2]. Similar to most autoimmune diseases, scleroderma predominantly affects women with a female-to-male ratio of 5:1. Additionally, scleroderma can be more active during pregnancy due to hormone changes that occur during that time [3].
While the exact causes of the disease are unclear, several factors that play a role in its development have been identified. These include immunological imbalance, environment, genetic factors, and oxidative stress. For example, it has been found that two particular cell types – endothelial cells and fibroblasts – are involved in producing an excessive amount of reactive oxygen species (oxidative stress) and other inflammatory signals [1].
The Two Subtypes: Localized vs. Systemic Scleroderma
There are two types of scleroderma. The first, milder form, localized scleroderma – also called morphea – typically only involves the skin. To assess the skin involvement, skin scoring is performed using a scoring system, called Modified Rodnan skin score (mRSS) [4]. The higher the skin score, the more active or severe the disease is.
The second scleroderma subtype, called systemic sclerosis (SSc), also involves internal organs. The affected organs involved include lungs, heart, kidneys, and the gastrointestinal tract. SSc is then further split into “limited cutaneous” SSc, which affects limited regions of the skin, while “diffuse cutaneous” affects the whole skin and can affect organs (the interested reader is referred to here: [5]) [1]. When scleroderma affects organs, it can lead to kidney failure, difficulty in swallowing, diarrhoea/constipation, breathing problems, heart failure, and many other complications.
However, scleroderma is a complex disease which is often difficult to diagnose. It takes 0.8-1.1 years from first symptoms to diagnosis. And even once diagnosed, scleroderma often comes with comorbidities, such as >90% of individuals also have Raynaud’s phenomenon. The diagnosis is often based on the mRSS, antibody testing (specific antibodies are associated with Scleroderma subtypes), and additional medical testing; meaning that diagnosis is based on multiple factors. Once diagnosed, a comprehensive management approach is needed to ensure personalized care and enhancing the outcomes for those affected [5], [8].
Raynaud’s Phenomenon and Scleroderma Diagnosis
Early signs of scleroderma often include Raynaud’s phenomenon. Raynaud’s is characterized by vessels contracting excessively (called vasoconstriction) in response to cold or stress, leading to colour changes in fingers and other body parts, i.e. fingers turn white, red, and blue.
Additionally, individuals with scleroderma may experience puffy fingers, indicative of swelling and collagen accumulation. These initial symptoms can serve as crucial indicators that may precede more extensive manifestations of scleroderma and are often used together with antibody testing and nailfold capillaroscopy for early detection and intervention [6], [7]. In the near future, we will add an article about Raynaud’s phenomenon here!
There are still many unknowns regarding scleroderma, such as its subtypes, and disease course. As each patient’s case is highly different, understanding disease progression early on is critical to direct the best course of treatment.
Quality of Life
As with many other diseases, scleroderma affects each patient differently, and the disease is very dynamic, meaning that some days are better than others. For most patients, scleroderma impacts the quality of life significantly due to impaired physical function, bodily pain, social function, and mental health impacts [8]. But while these points sound rather clinical, there are individuals behind these numbers and assessments. You can read some of the stories here.
From personal experience, I can add that pain and reduced physical function are the main factors that impact my quality of life. However, I currently also have 26 medicine prescriptions, of which I take about 20 every day. My life is not in the slightest “normal” due to fatigue, pain, reduced ability to walk, and being immunocompromised. In addition to that, there are the things that are invisible, like reduced lung function or gastrointestinal problems which often go unnoticed by others, but have a major impact on my life. Lastly, there are the little things, like not being able to open flasks, cutting meat with a knife, or bending down to tie up shoe laces, impacting my quality of life.
Conclusion
In summary, scleroderma is a rare autoimmune disorder that involves excessive collagen production, which can affect both skin and internal organs. With a prevalence of around 17.6 cases per 100,000 people and a higher incidence in women, it poses significant challenges, impacting mortality and quality of life. The exact causes, including immunological imbalance and environmental factors, remain unclear.
Autoimmune diseases are on a steep rise globally, and they often overlap with other comorbidities. Thus, raising awareness of autoimmune disease impacts, diagnostics, and treatments is critical for a wider understanding of global health.
References
- D. Singh, A. K. Parihar, S. Patel, S. Srivastava, P. Diwan, and M. R. Singh, “Scleroderma: An insight into causes, pathogenesis and treatment strategies,” Pathophysiology, vol. 26, no. 2, pp. 103–114, Jun. 2019, doi: 10.1016/j.pathophys.2019.05.003.
- M. Bairkdar, M. Rossides, H. Westerlind, R. Hesselstrand, E. V. Arkema, and M. Holmqvist, “Incidence and prevalence of systemic sclerosis globally: a comprehensive systematic review and meta-analysis,” Rheumatology, vol. 60, no. 7, pp. 3121–3133, Jul. 2021, doi: 10.1093/rheumatology/keab190.
- S. Munira and L. Christopher-Stine, “Pregnancy in myositis and scleroderma,” Best Practice & Research Clinical Obstetrics & Gynaecology, vol. 64, pp. 59–67, Apr. 2020, doi: 10.1016/j.bpobgyn.2019.10.004.
- D. E. Furst et al., “The modified Rodnan skin score is an accurate reflection of skin biopsy thickness in systemic sclerosis,” J Rheumatol, vol. 25, no. 1, pp. 84–88, Jan. 1998.
- “Classification of Scleroderma | University of Michigan Health.” Accessed: Dec. 06, 2023. [Online]. Available: https://www.uofmhealth.org/conditions-treatments/rheumatology/classification-scleroderma
- E. Blaja et al., “The Challenge of Very Early Systemic Sclerosis: A Combination of Mild and Early Disease?,” The Journal of Rheumatology, vol. 48, no. 1, pp. 82–86, Jan. 2021, doi: 10.3899/jrheum.190976.
- A. Freixo, C. Abreu, A. Freixo, and C. A. Sr, “Early Diagnosis of Systemic Sclerosis: The Role of General Practitioner,” Cureus, vol. 14, no. 12, Dec. 2022, doi: 10.7759/cureus.32291.
- Park, E.H., Strand, V., Oh, Y.J. et al. Health-related quality of life in systemic sclerosis compared with other rheumatic diseases: a cross-sectional study. Arthritis Res Ther 21, 61 (2019). https://doi.org/10.1186/s13075-019-1842-x