Make the Diagnosis

Make the Diagnosis - July 2015

This case and photo were submitted by Charlotte E. LaSenna and Dr. Andrea Maderal of the University of Miami department of dermatology. Dr. Bilu Martin is in private practice at Premier Dermatology, MD in Aventura, Fla. To submit your case for possible publication, send an e-mail to [email protected] A 55-year-old woman with an 8-year history of previously diagnosed vitiligo presented with worsening pruritus and swelling of the hands and feet for several months. Her medical history included liver disease. Upon physical examination, she was ill-appearing, with notable salt-and-pepper diffuse depigmentation, as well as pitting edema of the bilateral hands and face. Laboratory studies showed a positive ANA >1:2,560 with a centromere pattern, negative Scl-70, and positive antimitochondrial antibody at 158.5. Renal function and urinalysis were normal. Liver function tests were abnormal with elevated alkaline phosphatase and bilirubin.

What’s your diagnosis?

Systemic sclerosis (scleroderma)


Mixed connective tissue disease

Diagnosis: Systemic sclerosis

Systemic sclerosis, or scleroderma, is a rare connective tissue disorder in which excessive collagen is deposited in the skin and internal organs. This disease predominantly affects women (3-6:1) between the ages of 20 and 60 years with no apparent racial predominance. Effective treatment is critical, as scleroderma carries a poor prognosis, with a mortality rate of up to 50% at 5 years in severe cases. The pathogenesis of systemic sclerosis is unknown, but three pathways are implicated, including immune deregulation, vascular abnormalities, and abnormal fibroblast activation.

Clinical presentation is variable because of the involvement of multiple organ systems. Common features include cutaneous pruritus, skin thickening, Raynaud's phenomenon, difficulty swallowing, shortness of breath, palpitations, nonproductive cough, and joint pain and swelling, as well as muscle pain and weakness. Laboratory findings may include elevated erythrocyte sedimentation rate, thrombocytopenia, hypergammaglobulinemia, increased urea and creatinine levels, and elevated C-reactive protein. Antinuclear antibodies are usually elevated, especially Scl-70, antimitochondrial, and anticentromere antibodies. Cardiac and pulmonary function should be assessed upon diagnosis. A Doppler echocardiogram may detect cardiac abnormalities, and chest x-ray or high-resolution CT is used to assess for pulmonary fibrosis.

Despite the severity of the disease, there are no Food and Drug Administration-approved disease-modifying agents for the treatment of scleroderma, and management often focuses on symptom relief. For example, patients with kidney involvement should be placed on an ACE inhibitor or angiotensin II inhibitor therapy, and patients with gastrointestinal tract involvement should use proton pump inhibitors and H2 blockers to control reflux. Bosentan and pentoxifylline, which target vascular abnormalities, also may help improve skin fibrosis. Steroids show benefits in the early stages of the disease, but carry a risk of scleroderma renal crisis with doses greater than 15 mg of prednisone daily. Mycophenolate mofetil and sirolimus have immunomodulatory and antifibrotic properties, which may be of benefit in this disease.

Cyclophosphamide is reserved for more severe cases. Other treatment modalities include rituximab, intravenous immunoglobulin, and autologous stem cell transplantation.

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