Systemic sclerosis is a chronic, autoimmune connective tissue disease. It is characterised by extensive fibrosis (scarring) of the skin and internal organs, a dysregulated immune system, and vasculopathy (blood vessel disease). It is also called scleroderma (hard skin) which is actually a clinical feature of systemic sclerosis.
Another common presenting feature of systemic sclerosis is secondary Raynaud's phenomenon. This is implicated in over 95% of systemic sclerosis patients.
Raynaud's phenomenon
Raynaud phenomenon is an exaggerated and recurring response to cold or emotional stress, resulting in abnormal spasms (vasospasms) in the small blood vessels of the fingers, toes, ears, nose, nipples and even the knees. The vasospasms reduce blood circulation, leading to discomfort, numbness, tingling and even skin colour changes such as white, blue and red.
The majority (80–90%) of individuals have primary Raynaud's' Phenomenon which is a functional disorder and does not progress to tissue damage. Secondary Raynaud's Phenomenon however, may be an early symptom of systemic sclerosis.
Some Possible Causes:
Occupational exposure to vibratory tools.
Chemicals such as vinyl chloride monomer, arsenic, and organic solvents.
Alcohol abuse and smoking.
Fluctuations in female sex hormones, since Raynaud's is predominant in pre-menopausal women.
A low body mass index, since this may increase a patient’s sensitivity to cold.
Primary Raynaud's phenomenon symptoms can be controlled by avoiding the triggers that may cause an attack.
Evidence based non-pharmacological management strategies include:
Avoiding the cold and keeping the body warm with thick clothing.
Alleviation of emotional stress and anxiety can decrease frequency of attacks.
Cessation of smoking and alcohol.
Low level laser therapy can mitigate the severity and frequency of Raynaud’s attacks.
N-acetylcysteine (NAC), has antioxidant properties and has been recognised to mitigate the severity and lessen the number of Raynaud’s attacks.
Herbal drugs including Ginkgo biloba extract.
Essential rosemary oil applied topically has a vasodilatory and a warming effect.
Acupuncture has demonstrated reduction in the frequency of attacks and pain relief.
Behavioural therapies, including biofeedback.
Beetroot supplementation improves thumb blood flow, endothelial function and anti-inflammatory status in people with Raynaud’s.
Careful assessment of patients with symptoms of Raynaud's Phenomenon can provide an opportunity for early diagnosis of systemic sclerosis.
Systemic Sclerosis (Scleroderma)
Systemic sclerosis is an autoimmune disease, with a prevalence of around 100–250 per million, approximately 10,000 people in the UK are affected. It is more common in females than males (approx. ratio is 7:1). The disease is most prevalent in individuals aged 30-50 yrs.
There are two clinical subsets of systemic sclerosis:
Limited cutaneous systemic sclerosis - This is more common, is slower in its development and there is often a long history of Raynaud's beforehand. It involves skin thickening which is generally limited to the hands, face, feet, and forearms.
Diffuse cutaneous systemic sclerosis - Has faster disease progression. It affects more skin areas such as the chest, stomach, legs and arms. It also has a high risk of internal organs involvement (heart, lung and kidney).
The complex pathogenesis of the disease is a combination of: vascular endothelial damage, autoimmunity, and tissue fibrosis. Antinuclear antibodies are the most frequently detected autoantibodies in patients (90–95% of cases). Swollen, tight fingers and abnormal nail fold capillaries are often early clinical features, together with a history of Raynaud's phenomenon.
Some Possible Causes:
Studies identify various genetic loci associated with systemic sclerosis.
Oxidative stress markers in the blood of systemic sclerosis patients were abnormal, indicating imbalanced states of oxidation and antioxidation. Reactive Oxygen Species including superoxide anion, hydrogen peroxide and nitric oxide can stimulate pro-inflammatory & pro-fibrotic cytokines such as TGF-β, IL6, IL4 and IL33.
Environmental factors - silica exposure, chlorinated solvents, trichloroethylene, welding fumes, organic solvents, heavy metals: cadmium, lead, mercury.
Systemic sclerosis patients present with lower levels of vitamin D.
Since the disease mostly affects adult females, sex hormones may play a role.
Infections incriminated in systemic sclerosis are: Parvovirus B19, CMV, H Pylori.
Alterations in the gastrointestinal microbiome of patients with systemic sclerosis was found compared to healthy controls (HC).
Current medical treatments target inflammation, fibrosis, and vascular dysfunction. This may include systemic and topical treatments. Systemic treatments consist of glucocorticoids, immunosuppressants, biological agents, small molecule compounds, and hematopoietic stem cell transplantation.
Evidence based non-pharmacological management strategies include:
Dietary fruits, vegetables and herbs abundant in polyphenols and flavonoids (especially apigenin) may combat oxidative stress, fibrosis and support the gut microbiome. Vitamin E, vitamin D, vitamin C, selenium, zinc, evening primrose oil, N-acetylcysteine, green tea, bromelain, the herb Gotu Kola and various Chinese herbs have been studied to be effective for systemic sclerosis.
Vascular endothelial repair - Rhamnan Sulfate Extract from green algae is effective for vascular dysfunction.
Fibrosis inhibition - the cytokine TGFβ, is a key driver of fibroblast activation and is also made by fibroblasts. TGFβ is downregulated by the antioxidant glutathione.
Autoimmune regulation - regulation of cytokines and immune cells using immune modulating nutraceuticals such as: berberine, baicalin, sulforaphane, astragalus, quercetin, resveratrol, curcumin, fish oil and vitamin D.
Avoiding food triggers such as gluten & dairy that may be causing inflammation.
Complementary therapies such as acupuncture, transcutaneous electrical neural stimulation, and mind-body therapy (relaxation, meditative, imagery) were associated with higher perceived physical and mental functioning in systemic sclerosis.
Patients with systemic sclerosis have been shown to be at risk of nutritional decline and possibly leading to malnutrition, if there is involvement with the gastrointestinal system. Systemic sclerosis patients may therefore benefit hugely from personalised nutritional therapy.
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