Patients with scleroderma, whether diffuse or limited, usually have acral sclerosis and sclerodactyly as well as history of Raynaud’s phenomenon. Other manifestations may include fingertip infarcts, telangiectasias, salt and pepper pigmentation especially over the upper back, and calcinosis. Some patients may have internal organ involvement, particularly the lungs and kidneys. Patients with generalized morphea should not be confused with scleroderma.

The primary manifestation of chronic GVHD is sclerodermoid skin changes akin to those of scleroderma. Without history of a bone marrow transplant, the two disorders may be difficult to differentiate. Features that may favor chronic GVHD include residual findings of subacute and rarely acute GVHD, that is, lichenoid papules and erythema. History of acute GVHD is almost universally elicited.

Patients with EF present either as acute–onset, painful, rapid induration of the skin of the extremities, especially the legs (reported in male runners in the initial report by Dr. Shulman), or as insidious progressive thickening of the skin diffusely, commonly with overlying peau de orange appearance of the skin surface that may be difficult to distinguish from subcutaneous morphea, also known as morphea profunda.