Board Review

A 31-year-old woman is evaluated during a routine physical examination. She feels well but notes skin changes on her legs that have been present for several years. The skin changes persist regardless of position or temperature. Medical history is unremarkable except for three episodes of first trimester spontaneous pregnancy loss. She takes no medications.

On physical examination, vital signs are normal. The general medical examination is normal. Skin findings are shown.

The skin changes are more prominent when she is sitting or standing, but persist while supine. They don't go away when she is warmed. There is no lower extremity edema.

Which of the following is the most likely diagnosis?

A) Amyloidosis

B) Antiphospholipid antibody syndrome

C) Autoimmune thyroid disease

D) Systemic sclerosis

Answer: B - Antiphospholipid antibody syndrome

Objective: Recognize livedo reticularis.

Key Point

Antiphospholipid antibody testing should be performed in persons with fixed livedo reticularis that persists despite position and temperature changes, or those with signs, symptoms, or history suggestive of thromboses.

The patient has livedo reticularis, and her clinical presentation is consistent with the antiphospholipid antibody syndrome. Livedo reticularis is a subtle, lacy network of faintly blue or purple vessels, usually seen on the lower legs, caused by the prominence of the vasculature under the skin. It is a very nonspecific finding and is most often seen in patients without an underlying condition. Livedo reticularis can sometimes be elicited by keeping a leg in the dependent position; if livedo resolves when the leg is straightened horizontally, it is likely not a pathologic process. However, it can also be a component of a variety of systemic diseases, typically those that cause a slow-flow or hypercoagulable state. Associated conditions include autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis), vasculitis (polyarteritis nodosa, giant cell arteritis), paraproteinemias (multiple myeloma, cryoglobulinemia), hematologic diseases (polycythemia vera, thrombocytosis), and infections. Livedo reticularis also has a strong association with the antiphospholipid antibody syndrome, and there is evidence that its presence suggests increased risk of cerebral or ocular ischemia. This patient's livedo reticularis and history of prior miscarriages are suggestive of antiphospholipid antibody syndrome. According to the revised Sapporo criterion, a diagnosis of antiphospholipid antibody syndrome requires at least one clinical criteria (vascular thrombosis excluding superficial venous thrombosis or pregnancy morbidity) and at least one laboratory criterion (the presence of antiphospholipid antibodies on two or more occasions at least 12 weeks apart).

Amyloidosis is an infiltrative disease that causes skin thickening and is more often associated with development of petechiae and ecchymoses than with changes consistent with livedo reticularis.

Autoimmune thyroid disease, particularly Graves disease, may uncommonly be associated with pretibial myxedema, an accumulation of glycosaminoglycans in the dermis, usually over the lower legs. This patient's clinical findings are not consistent with this diagnosis.

Systemic sclerosis involves excessive production of extracellular matrix with increased collagen production resulting in skin thickening. Livedo reticularis is not a common manifestation of this disorder.

Thornsberry LA, LoSicco KI, English JC 3rd. The skin and hypercoagulable states. J Am Acad Dermatol. 2013 Sep;69(3):450-62. Link Out