With Scleroderma Awareness month in June, we would like to outline some of the main clinical diagnostic procedures of this relatively rare, yet incredibly debilitating disease in hopes of increasing early detection and awareness in the naturopathic community.
The word scleroderma is derived from two Greek works: “scleros” and “derma”, which translate to thickened skin. The pathophysiology of scleroderma involves increased fibroblast activity leading to excess collagen production and buildup. Scleroderma is only one part of a spectrum of disorders that can be classified into three groups (systemic sclerosis, localized scleroderma and scleroderma-like conditions) all of which involve skin thickening and hardening of tissues in various areas of the body. Two of the groups, localized scleroderma and systemic sclerosis, have notable differentiating characteristics in patient presentation.
Common in children, localized scleroderma is generally considered more mild than systemic sclerosis; it is commonly described as an idiopathic and self-limiting condition that only affects the skin and underlying tissues, including muscle and bone. It can present as dermatomal distribution on one side of the body, or as patchy areas of sclerotic skin that develop on the trunk and limbs.
Common in adults, systemic sclerosis is the more well-known form of scleroderma. It is especially problematic and causes internal organ damage and dysfunction along with skin thickening. Most physicians refer to systemic sclerosis (SSc) when using the term scleroderma. For the remainder of this article, we will be discussing systemic sclerosis and how to diagnose this in office.
The incidence of systemic sclerosis has been growing. This is attributed to increased awareness and diagnostic criteria. SSc has an annual incidence of 1-2 cases per 100,000 individuals in the US; this is higher than other developed countries, including Europe and Japan. The peak onset of symptoms generally occurs between the ages of 30 and 50, similar to other autoimmune conditions. However, this is neither exclusive nor diagnostic as symptoms can appear at any age. SSc is more common in women than men (7:1) and most common in those of Native American and African American descent. Keeping this information in mind may help to identify patients that suffer from scleroderma when they present in office.
Systemic sclerosis can be divided into two principal classifications: limited cutaneous systemic sclerosis (lcSSc) and diffuse cutaneous systemic sclerosis (dcSSC).1 The differentiation of these two forms of SSc is important for patient prognosis and monitoring internal involvement.
Limited cutaneous SSc is associated with sclerosis restricted to the hands, lower legs, face and neck. Those with limited cutaneous SSc suffer from CREST syndrome (Calcinosis, Raynaud’s syndrome, Esophageal dysmotility, Sclerodactyly, Telangiectasia). There is minimal to moderate organ involvement. Diffuse cutaneous scleroderma (dcSSC) is associated with extensive skin sclerosis and greater risk for developing significant lung, renal, and cardiac complications1. With this condition, it is important to establish an early diagnosis which can greatly improve life expectancy with early intervention and treatment.
Diagnosis of both forms of systemic scleroderma is complicated and made primarily with clinical signs and symptoms. The presence of autoantibodies in the blood is used to confirm a suspected diagnosis but unfortunately cannot provide a definitive diagnosis of SSc. The most common clinical signs and symptoms seen in early stages of SSc include fatigue, stiff joints, loss of strength, pain, sleep difficulties and skin discoloration. Skin thickening and hardening is not typically the first symptom patients report in systemic scleroderma, but its presentation confirms most diagnoses. Other skin involvement can include pruritis and edema, sclerodactyly, digital ulcers, pitting at the fingertips, telangiectasia, and soft tissue calcifications.
Along with skin thickening, a main diagnostic indicator of systemic scleroderma is the presence of Raynaud’s Phenomenon. Raynaud’s is characterized by color changes and ischemia of the fingers, often precipitated by cold, stress or sudden change in temperature. Coexistence of Raynaud’s Phenomenon and esophageal reflux is strongly suggestive of SSc.
Suspected diagnosis can be confirmed through laboratory testing by the presence of autoantibodies in the blood. The most common autoantibodies in scleroderma are anti-topoisomerase I (anti-topo I), anti-centromere (ACA), and anti-RNA polymerase I, II and III (ARA)1. Anti-topo-1 antibodies are associated with diffuse cutaneous SSc and higher rates of organ involvement compared to ACA; ACA antibodies are correlated to limited cutaneous SSc. Other autoantibodies such as rheumatoid factor, anti-citrullinated peptides, anti-Ro, anti-La, or anti-neutrophil cytoplasmic antibodies are uncommon in scleroderma and usually point to overlapping symptoms from concurrent autoimmune disease. Approximately 95% of patients with systemic scleroderma have at least one of these associated autoantibodies present in their blood1.
If scleroderma is suspected or confirmed, a thorough physical exam must be done to assess for any organ involvement. The most common organs involved in SSc include the lungs, the heart, the kidneys and the GI tract. Common signs and symptoms of sclerotic internal organ damage include dysphagia, heartburn, hoarseness, breathlessness or dyspnea on exertion, arrhythmias, non-productive cough and erectile dysfunction. Mortality in late stage disease is often contributed to pulmonary arterial hypertension, interstitial lung disease, cardiac death or other complications.5
Prognosis for patients with systemic scleroderma is dependent on the type of SSc they have (limited vs diffuse), as well as how much organ involvement is present. Patients that have cardiac involvement have a very poor prognosis, with 2 and 5 year mortality rates around 60% and 75%, respectively. Though many patients with SSc have renal involvement, it rarely progresses to renal failure. Apart from organ complications, there is also an increased risk for cancers of the lung, skin, liver and blood in patients with SSc that is not fully understood.
Overall, scleroderma is a serious autoimmune condition that presents with general signs and symptoms and is often not diagnosed until late stage when organ involvement has occurred. It is important as physicians that we are thorough with our physical exam and laboratory analysis. We can raise our awareness of these types of complicated systemic autoimmune diseases to help increase early detection of these conditions.
Denton, Christopher. “Classification of Scleroderma Disorders.” Classification of Scleroderma Disorders. Up To Date, 9 Nov. 2012. Web. 24 May 2013
2  Jacobe, Heidi. “Pathogenesis, Clinical Manifestations, and Diagnosis of Morphea (localized Scleroderma) in Adults.” Pathogenesis, Clinical Manifestations, and Diagnosis of Morphea (localized Scleroderma) in Adults. Up To Date, 15 May 2013. Web. 24 May 2013
  Varga, John. “Diagnosis and Differential Diagnosis of Systemic Sclerosis (scleroderma) in Adults.” Diagnosis and Differential Diagnosis of Systemic Sclerosis (scleroderma) in Adults. Up To Date, 19 Nov. 2012. Web. 24 May 2013
 University of Melbourne, and St. Vincent Department of Rheumatology. “Epidemiology of Systemic Sclerosis.” Best Practice and Research Clinical Rheumatology 24 (2010): 857-69. Print
 Varga, John. “Overview of the Clinical Manifestations of Systemic Sclerosis (scleroderma) in Adults.” Overview of the Clinical Manifestations of Systemic Sclerosis (scleroderma) in Adults. Up To Date, 19 Nov. 2012. Web. 24 May 2013
 B. Shine Rheumatology Unit. “Scleroderma – New Aspects in Pathogenesis and Treatment.” Best Practice and Research Clinical Rheumatology 26 (2012): 13-24. Print