CHICAGO — Few rheumatologists would be fooled nowadays by gadolinium-induced nephrogenic systemic fibrosis, but there are other diseases that can masquerade as scleroderma.
The precise diagnosis of scleroderma-like illnesses is important because even though many of them are called scleroderma, they differ from systemic sclerosis in both treatment and outcome, Dr. Virginia Steen said at a symposium sponsored by the American College of Rheumatology.
The diagnosis is most often based on the distribution and clinical characteristics of skin findings, as biopsies don't always differentiate types of scleroderma. Rheumatologists would do well to keep in mind the following scleroderma mimics to avoid misdiagnosis:
▸ Lipodermatosclerosis is one condition that physicians often fail to think of as a scleroderma mimic. Also known as hypodermatitis sclerodermaformis, it refers to localized chronic inflammation and fibrosis of the skin and subcutaneous tissues of the lower leg. In the acute stage, the leg is inflamed and warm, the skin is very tight, and cellulitis may be present. The ankle and toes are not involved.
In its chronic stage, there is induration, contraction of the skin and subcutaneous tissues, and irregular depressions that can look almost identical to lower-leg scleroderma, she said. The leg eventually resembles an inverted champagne bottle, in which the upper half remains edematous and has a much greater circumference than does the lower sclerotic portion.
Lipodermatosclerosis is a sign of severe end-stage venous insufficiency, and should be differentiated from scleroderma, cellulitis, superficial thrombophlebitis, and erythema nodosum. The diagnosis is made from clinical observation, but direct immunofluorescence of early and late lesions has been used to show dermal pericapillary fibrin deposits.
If left untreated, lipodermatosclerosis can progress to ulceration, atrophy blanche, or shortening of the Achilles tendon. Treatment involves weight loss, controlling the underlying disease, and consistent wearing of support stockings that may need to be specially made, said Dr. Steen, professor of medicine and director of the rheumatology fellowship program at Georgetown University in Washington. Topical steroids are useful if the skin is inflamed, and antibiotics are recommended for cellulitis.
▸ Scleredema tends to target the upper body without affecting the lower extremities. Thickening occurs on the skin of the neck and face; severely affected patients are unable to wrinkle their foreheads or open their mouths. In most patients, the shawl sign is present, with skin involvement over the chest and arms, according to Dr. Steen.
Pathological features include swollen collagen with clear spaces and accumulation of hyaluronic acid and glycosaminoglycans. Although scleredema is commonly associated with diabetes, it can also occur after a viral illness. The treatment emphasis is on better diabetes control, but spontaneous resolution of symptoms is possible after infection.
▸ Eosinophilic fasciitis is a rare disorder characterized by symmetrical and painful inflammation and swelling of the extremities, leading to induration and the characteristic peau d'orange configuration. The palms may be involved, but typically the fingers and toes are spared. Contractures demonstrating the groove sign commonly evolve as a result of induration.
Eosinophilic fasciitis is slightly more common in middle-aged men, but can occur in women and children. It was initially distinguished from systemic sclerosis by the absence of Raynaud's phenomenon, autoantibodies, and visceral involvement, and—unlike systemic sclerosis—it responds to corticosteroids.
Histologically, there are marked eosinophilia and inflammatory infiltrates in the fascia. The extent of the histologic changes depends on the stage of the disease, and thus is not a consistent component of the disease. Aside from marked peripheral eosinophilia, other laboratory features to watch for include an increased erythrocyte sedimentation rate, increased gamma globulin, and an increased aldolase, with a normal creatinine phosphokinase.
Physical therapy is a key component of treatment, because this and most scleroderma mimics discussed here can cause joint contractures.
In eosinophilic fasciitis, low- to moderate-dose prednisone (20-30 mg)—and, if needed, methotrexate as a steroid-sparing agent—can be given. There is also some anecdotal evidence to suggest that rituximab (Rituxan), mycophenolate mofetil (CellCept), or tumor necrosis factor inhibitors may be useful, said Dr. Steen, who disclosed no conflicts of interest.