Systemic sclerosis (scleroderma): Clinical sciences

Systemic sclerosis, also known as scleroderma, is a chronic connective tissue disorder characterized by microvascular damage and fibrosis in various organs and tissues, including the skin. When damage is limited to the skin, that’s simply called scleroderma, which is the hallmark feature of the disease. Based on the pattern of skin fibrosis, systemic sclerosis can be categorized as limited cutaneous, which is the more common type, and diffuse cutaneous systemic sclerosis. However, when the disease affects the skin and the internal organs, it’s called systemic sclerosis, and it can affect any organ system.

When a patient presents with a chief concern suggesting systemic sclerosis, the first step is to obtain a focused history and physical exam. Most patients with systemic sclerosis are biological females. They usually report hand swelling and pain. Patients often experience Raynaud phenomenon, which is a condition that affects blood flow, usually in the fingers and toes. When exposed to  cold temperature or emotional stress, the blood vessels narrow, leading to reduced blood supply to certain areas, causing them to turn white or blue and feel cold and numb. Once the circulation improves, the affected areas might turn red and tingle, before going back to normal. Additionally, patients might have gastrointestinal symptoms related to acid reflux, like heartburn and voice hoarseness.

Physical examination reveals skin thickening, also known as scleroderma. There might also be sclerodactyly, which refers to the hardening of the skin of the hands, causing the fingers to flex inward. Some patients might also have digital ulcerations, and telangiectasia, which refers to dilated blood vessels visible under the skin.

With these findings, you should suspect systemic sclerosis. To confirm the diagnosis, you need to order labs, including an antinuclear antibody, or ANA for short, as well as anticentromere, anti-topoisomerase, and anti-RNA polymerase III antibodies. If these antibodies are positive, you can diagnose systemic sclerosis.

Here are some clinical pearls you should keep in mind! When a patient with systemic sclerosis presents with features of another systemic rheumatic disease, such as rheumatoid arthritis or polymyositis, that’s called systemic sclerosis with overlap syndrome. Additionally, when they have systemic sclerosis without skin involvement, that’s called sclerosis sine scleroderma.

Now once you diagnose systemic sclerosis, your next step is to assess the pattern of skin involvement, to help establish whether your patient has limited, or diffuse cutaneous systemic sclerosis.

If your patient has skin thickening distal to the knees and elbows, diagnose limited cutaneous systemic sclerosis. 

Here’s a high-yield fact! Patients with limited cutaneous systemic sclerosis may present with CREST syndrome. CREST stands for calcinosis cutis, which is calcium salts deposition in the skin; Raynaud phenomenon, esophageal dysmotility; sclerodactyly; and telangiectasia.

On the other hand, if your patient has skin thickening proximal to the knees and elbows, diagnose diffuse cutaneous systemic sclerosis. 

Here’s another high-yield fact! Patients with limited cutaneous systemic sclerosis often test positive for anti-centromere antibodies, whereas those with diffuse cutaneous systemic sclerosis usually have positive anti-topoisomerase and anti-RNA polymerase antibodies.

Now, your next step is to assess organ involvement, beginning with the musculoskeletal system. Common musculoskeletal manifestations of systemic sclerosis include Raynaud phenomenon and inflammatory arthritis.

Let’s start with the Raynaud phenomenon! These patients will typically report finger color changes, which are triggered by vasospasm in response to cold temperature or emotional stress. In this case, you can diagnose Raynaud's phenomenon, and treat your patient with calcium channel blockers like nifedipine; and phosphodiesterase-5 inhibitors, like sildenafil.

On the flip side, if your patient reports hand swelling and pain, and the physical exam reveals small joint swelling and tenderness to palpation, diagnose inflammatory arthritis. Treatment involves methotrexate or hydroxychloroquine.