Systemic sclerosis (scleroderma): Clinical sciences

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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.Alright, next, all patients with systemic sclerosis should be assessed for pulmonary conditions, including pulmonary artery hypertension and interstitial lung disease.Let’s start with pulmonary artery hypertension.
These patients typically report chest pain and shortness of breath on exertion. The physical exam might reveal an augmented S2 heart sound, jugular venous distention, and/or bilateral lower extremity edema.
In this case, suspect pulmonary artery hypertension and obtain a transthoracic echocardiogram to confirm. If it reveals elevated pulmonary artery systolic pressure, you can diagnose pulmonary artery hypertension.
Treatment includes phosphodiesterase-5 inhibitors like sildenafil, endothelin receptor blockers like bosentan, or prostacyclin pathway agonists like treprostinil.Now, let’s switch our focus to interstitial lung disease.
These patients typically present with shortness of breath on exertion and chronic, dry cough. Physical examination reveals wheezing and diffuse inspiratory crackles.
In this case, suspect interstitial lung disease and order pulmonary function tests, and a chest CT scan to confirm. If the pulmonary function tests show reduced diffusing capacity for carbon monoxide and a restrictive pattern, with a chest CT showing ground glass opacities, diagnose interstitial lung disease.
Treatment includes immunosuppressive therapy, with medications like mycophenolate mofetil or cyclophosphamide.Now, let’s have a look at renal involvement.
In this case, patients might report a history of rapidly progressive diffuse skin sclerosis. Additionally, the physical exam reveals elevated blood pressure, sometimes associated with features of end-organ damage like pulmonary edema, blurred vision or severe headaches.
With these findings, you should suspect scleroderma renal crisis. Next, order labs, including a BMP along with urinalysis.
If the BMP reveals elevated creatinine, with or without mild proteinuria on urinalysis, you can diagnose scleroderma renal crisis.
This is a medical emergency, and treatment should begin immediately with an angiotensin-converting enzyme inhibitor to control blood pressure.Alright, let's shift our focus to gastrointestinal involvement, which can include conditions like gastroesophageal reflux disease or GERD, esophageal strictures, and gastric antral vascular ectasia.Let’s start with GERD!
If your patient has a history of heartburn, acid regurgitation, or a sour or bitter taste in their mouth, you can diagnose GERD.
Next, initiate treatment with proton pump inhibitors or PPIs, like omeprazole. You can also add a promotility agent like metoclopramide to manage associated esophageal dysmotility that could exacerbate the reflux.Here’s a clinical pearl!
Patients with systemic sclerosis may experience small bowel hypomotility, which can lead to a functional small bowel obstruction, also called ileus or pseudoobstruction.
The combination of bowel hypomotility, chronic PPI use, and ileus can increase the risk of small intestinal bowel overgrowth, or SIBO for short, which refers to an abnormally large number of bacteria like Escherichia coli, Klebsiella, and anaerobes in the gastrointestinal tract.Now, let’s say your patient presents with a GERD that is not responsive to PPIs.
They might also report dysphagia; melena, meaning black, tar-like stools; and hematemesis, meaning bloody vomit. In this case, you should perform an esophagogastroduodenoscopy or EGD, and order a CBC.
If the EGD reveals stricture in the esophagus, diagnose esophageal stricture, which can be treated with endoscopic dilatation.
In some cases, the EGD can reveal rows of ectatic, dilated blood vessels in the gastric mucosa, also known as watermelon stomach, and the CBC shows low hemoglobin caused by chronic blood loss through the gastrointestinal tract.
In this case, diagnose gastric antral vascular ectasia, or GAVE for short, which requires management with radiofrequency ablation.Finally, let’s have a look at the cardiac involvement, which includes pericarditis and myocarditis.
Let’s start with pericarditis! If your patient presents with pleuritic chest pain, and the physical exam reveals pericardial friction rub on heart auscultation, you should suspect pericarditis.
To confirm, obtain an electrocardiogram or ECG, which reveals diffuse ST elevation; and a transthoracic echocardiogram, which can show a pericardial effusion.
In this case, diagnose pericarditis, and treat with medications like NSAIDs and colchicine.Finally, there’s myocarditis!
If your patient has a history of fatigue and chest pain, with or without jugular venous distention or peripheral edema, you should suspect myocarditis.
Next, obtain a transthoracic echocardiogram, and if it reveals left ventricular dilation and systolic dysfunction, diagnose myocarditis.
Treatment involves immunosuppressive therapy with mycophenolate mofetil or cyclophosphamide.One last clinical pearl! Patients with systemic sclerosis may also present with several other cardiac manifestations, including conduction abnormalities, arrhythmias, microvascular coronary artery disease, and heart failure.Alright, as a quick recap...
Systemic sclerosis is a chronic connective tissue disorder characterized by microvascular damage and organ fibrosis. Diagnosis requires confirming the presence of antibodies including ANA, anticentromere, anti-topoisomerase, and anti-RNA polymerase III.
Based on skin involvement, there are two subtypes of systemic sclerosis. The first one is the limited type characterized by skin thickening distal to the knees and elbows; while the second is the diffuse type characterized by skin thickening proximal to the knees and elbows.
Additionally, systemic sclerosis can affect various organ systems, including the musculoskeletal, pulmonary, renal, gastrointestinal, and cardiovascular systems, and management depends on the