Systemic Sclerosis

Scleroderma is a challenging disease to manage as it affects multiple organ systems. The hallmark of scleroderma is clinical heterogeneity with subsets that vary in the degree of disease expressions, organ involvement, and prognosis. The 2 cases to follow illustrate the diverse nature of the disease. Following the cases there is a competency based curriculum with hyperlinks to images, and references that will help you answer questions relevant to the cases.

CASE 1

A 35 year old female presents with a 2 year history of Raynaud's phenomenon. She reports gastroesophageal reflux for a similar duration of time. She also has noted that her skin is diffusely pruritic for the past year. Physical examination reveals a P 90 BP 160/90. HEENT is remarkable for furrowing around the mouth and decreased oral aperture. Cardiac exam is normal. Pulmonary exam is normal. Skin reveals sclerodactyly with digital pitting scars. There is mild diffuse skin tightening including the proximal upper and lower extremities, abdomen and chest.

What physical examination findings are concerning in this patient and why?

  • Patients with diffuse cutaneous SSc with rapidly progressive skin disease are at risk for hypertensive renal crisis and for interstitial lung disease.
  • The heralding sign for scleroderma renal involvement is elevation of the blood pressure. This may be a mild increase to 120/80 in a patient with a usual much lower blood pressure (such as 100/70).
  • These patients need aggressive treatment with angiotensin converting enzyme (ACE) inhibitors at the first sign of renal involvement.
  • Patients need home BP monitoring.
  • Although crackles are not heard on lung examination, this patient has early diffuse skin involvement and should undergo screening for interstitial lung disease. Testing should include pulmonary function tests for spirometry, lung volumes and diffusion capacity.

CASE 2

A 55 year old female with a 15 year history of Raynaud's phenomenon presents with increasing shortness of breath. She has noticed tightening of the skin on her finger tips with intermittent digital ulcerations. She additionally reports hard bumps over the elbows and red spots on her face and neck. Physical exam confirms the presence of sclerodactyly, digital pitting scars, calcinosis over the elbows, and telangiectasias over the face and chest. Cardiac exam reveals a regular rate and rhythm and a loud P2 component of S2.

What is the diagnosis and what is a possible etiology for her shortness of breath? How would you evaluate it?

  • This patient has limited cutaneous systemic sclerosis or CREST syndrome (Calcinosis, Raynaud's phenomenon, Esophageal dysmotility, Sclerodactyly and Telangiectasia).
    • Patients with limited cutaneous SSc (CREST syndrome) are at increased risk for developing pulmonary hypertension.
  • These patients should undergo yearly screening with PFTs, including DLCO and echocardiogram.
  • Pulmonary hypertension is most commonly vascular in origin (a vasculopathy, and not of an inflammatory etiology), but may alternatively be related to the presence of interstitial lung disease, diastolic dysfunction or valvular heart disease.

Patient Care

  1. Implement appropriate clinical and laboratory screening for diagnosis and defining organ involvement including serologies, upper endoscopy, barium esophagram, pulmonary function tests, echocardiogram, high resolution chest CT scan, and right heart catheterization.
  2. Recognize the importance of the finding of digital pitting and the role of nailfold capillary microscopy in the evaluation of a patient with Raynaud's phenomenon.
  3. Identify the presenting features and clinical setting of scleroderma renal crisis.
  4. Describe the appropriate pharmacologic and non pharmacologic management of Raynaud's phenomenon and digital ulcers, GI involvement, interstitial lung disease, pulmonary hypertension, and scleroderma renal crisis.
  5. Explain the risks and benefits of medications used to treat the clinical manifestations of scleroderma: Proton pump inhibitors, angiotensin converting enzyme (ACE) inhibitors, calcium channel blockers, endothelin receptor blockers, prostaglandin analogues, phosphodiesterase inhibitors, and immune modulators (mycophenolate mofetil, cyclophosphamide, methotrexate).
  6. Identify web based patient resources.

Medical Knowledge

  1. Review the new classification criteria for SSc.
  2. Understand how to define the clinical phenotype of the patient with scleroderma with appropriate clinical examination and laboratory testing.
  3. Differentiate the 2 major subtypes of scleroderma by the extent of skin involvement including: Limited (hands, forearms, feet, lower legs, face), and diffuse(proximal and distal limb and trunk involvement).
  4. Learn how the clinical phenotype determines organ involvement and prognosis.
  5. Discuss the differential diagnosis of SSc including the scleroderma mimics such as eosinophilic fasciitis, scleredema of Buschke, scleromyxedema, and nephrogenic systemic fibrosis.
  6. Recognize the clinical features of scleroderma including:
    1. Cutaneous :skin induration, acrosclerosis (sclerodactyly), acro-lysis (terminal digital tuft resorption), diffuse skin tightening, telangiectasias, and calcinosis
    2. Vascular : Raynaud's phenomenon, pulmonary hypertension and renal involvement
    3. GI including esophageal dysmotility, intestinal pseudo-obstruction, colonic wide- mouthed diverticulae, and watermelon stomach (gastric antral vascular ectasia, GAVE)
    4. Pulmonary: interstitial lung disease (ILD) in SSc and how it may be treated
  7. Describe the underlying pathology and pathophysiology of scleroderma renal crisis.
  8. Identify and differentiate systemic from localized cutaneous scleroderma including morphea and linear scleroderma.

Interpersonal Communication

  1. Discuss the need for close monitoring of disease activity particularly skin thickening, blood pressure and dyspnea.
  2. Summarize the information to be provided to a specialist to whom you might refer a patient with suspected scleroderma.
  3. Explain the prognosis and expected visceral involvement for limited vs diffuse cutaneous disease.
  4. Utilize a patient-centered approach in developing a treatment and follow-up plan.
  5. Advise on vocational and non vocational activities.

Professionalism

  1. Recognize the importance of patient privacy, informed consent and equal care.
  2. Recognize the importance of patient privacy balanced with the need to involve family and support groups to improve functioning.
  3. Allow time for appropriate questions and concerns with emphasis on chronicity of the disease.

Problem-Based Learning

  1. Set learning goals in diagnosis and management of scleroderma.
  2. Integrate and apply information from the history and physical, laboratory and diagnostic testing to make informed decisions about patient care.
  3. Learn to incorporate formative evaluation and feedback into practice and management of these complex patients.
  4. Develop a willingness to learn from errors and use errors in a constructive way to learn and to improve the systems for patient care.
  5. Utilize web-based resources to enhance learning about scleroderma.

Systems Based Practice

  1. Effectively engage all medical providers and the health care system to manage this condition.
  2. Learn to incorporate considerations of cost awareness and risk benefit analysis in patient care.
  3. Demonstrate awareness of the impact of diagnostic and pharmacologic recommendations on the health care system, insurance companies and patient personal expenditures.
  4. Identify barriers to the delivery of optimal patient care for patients with scleroderma and offer improved ideas for delivering care.

References

Questions

(Answer questions 1 – 5 on a piece a paper. Find Answer Key at the bottom on the page.)

CASE 1

1) Which is the next best step in the management of this patient?

  1. Start cyclophosphamide
  2. Right heart catheterization
  3. Start Bosentan
  4. Right Ankle MRI
  5. Home blood pressure monitoring

2) Which of the following antibodies would be predictive of the development of hypertensive renal crisis in this patient?

  1. Anti-Centromere antibody
  2. Anti Jo-1 Ab
  3. Anti Mi-2 Ab
  4. Anti-SCL-70 antibody
  5. Anti- RNA polymerase 3 Ab

The patient returns 1 month after the intial visit because her home BP readings have been high. She continues to have active Raynauds phenomenon. On examination P 80 BP 160/90.

3) The next best step in the management would include:

  1. Continue Nifedipine, and add Enalapril
  2. Continue Nifedipine and add Atenolol
  3. Continue Nifedipine and add HCTZ
  4. Discontinue Nifedipine and add Verapamil
  5. Discontinue Nifedipine and add Clonidine

CASE 2

4) Which of the following antibodies would be most likely present in this patient?

  1. Anti-Centromere antibody
  2. Anti Jo-1 Ab
  3. Anti Mi-2 Ab
  4. Anti- RNA polymerase 3 Ab

5 years after the intitial evaluation the patient presents with increasing dyspnea on exertion for the past 4 months. Physical exam confirms stable findings of sclerodactyly, digital pitting scars, calcinosis over the elbows, and telangiectasias over the face and chest. Pulmonary examination is clear to auscultation. Cardiac exam reveals a regular rate and rhythm and a loud P2 component of S2. Pulmonary function tests reveal normal Lung volumes, and a DLCO of 40% of predicted.

5) The most likely cause for the dyspnea is?

  1. Anemia
  2. Congestive heart failure
  3. Interstitial lung disease
  4. Pulmonary HTN

Answers

CASE 1

1) The correct answer is E.

Home blood pressure is the correct answer and is a very important screening test in patients with early diffuse scleroderma to assure diagnosis of hypertension which could lead to hypertensive renal crisis. Cytoxan is used for treatment of active inflammatory pulmonary disease which has not been established in this patient. Right heart catheterization would be performed if there were additional signs and symptoms of pulmonary HTN including shortness of breath, Low DLCO on pulmonary function tests, or increased right sided pressures on echocardiogram.The patient denies shortness of breath, and has not yet had PFTs or echocardiogram. Bosentan is used for the treatment of pulmonary HTN which has not been established in this patient. Ankle MRI is not necessary, as a tendon friction rub is a clinical finding seen in patients with diffuse scleroderma, and does not need further evaluation.

2) The correct answer is E.

Anti RNA polymerase-3 is found in patients with diffuse scleroderm, and correlates with the development of hypertensive renal crisis and is the correct answer Anti centromere ab is see in the clinical subset of patients with with limited cutaneous disease as in this patient, Anti Jo1 is present in patients with antisynthetase syndrome a subset of the inflammatory myopathies Anti Mi-2 is found in a subset of patients with dermatomyositis. Anti SCL-70 is associated with diffuse scleroderma, and the presence of interstitial lung disease.

3) The correct answer is A.

This patient has hypertension in the setting diffuse scleroderma, and is at risk of developing renal crisis. Continue the Nifedipine and add Enalapril is the correct answer. Addition of the ACE inhibitor will help to prevent the development of hypertensive renal crisis, and is the drug category of choice. Discontinue the Nifedipine and add Verapamil would not protect the patient against hypertensive renal crisis. Continue the Nifedipine and add Atenolol would not protect the patient against hypertensive renal crisis. Discontinue Nifedipine and add CLonidine, again would not prevent renal crisis

CASE 2

4) The correct answer is A.

Anti centromere ab is seen in the clinical subset of patients with with limited cutaneous disease as in this patient, and is the correct answer Anti Jo1 is present in patients with antisynthetase syndrome a subset of the inflammatory myopathies. Anti Mi-2 is found in a subset of patients with dermatomyositis. Anti SCL-70 is associated with diffuse scleroderma, and the presence of interstitial lung disease. Anti RNA polymerase-3 is found in patients with diffuse scleroderma , and correlates with the development of hypertensive renal crisis.

5) The correct answer is D.

Pulmonary HTN is the correct answer, and is the likely diagnosis to explain dyspnea on exertion in a patient with long standing limited scleroderma. There are no physical exam features to suggest congestive heart failure, ie PND, LE edema, JVD, or rales Anemia can be seen in chronic disease, and can lead to dyspnes on exertion, but would not explain the abnormal P2 or DLcO. Interstitial lung disease would cause decreased lung volumes and a restrictive pattern on PFTs not seen in this patient.

Last updated February 2015.