Clinical History:

A 55-year-old woman went to her local physician because she had difficulty swallowing. She had also noticed increasing difficulty in grasping objects along with stiffness of her fingers. Her blood pressure was markedly elevated. Laboratory testing revealed an antinuclear antibody (ANA) postive at 1:128 with a nucleolar pattern, normal serum complement levels, and a slightly elevated serum creatinine. She was referred to a nephrologist who performed a renal biopsy. A skin biopsy was also obtained.

Image 5.1:

The skin of the face and hands is shown here. The skin is taut and shiny, typical of sclerodactyly.

Image 5.2:

The antinuclear antibody test pattern is shown here. Note that the bright green fluoresence is localized to the nucleoli. This is a "nucleolar" pattern that suggests scleroderma (but is not specific for it).

Image 5.3:

The skin by light microscopy (H&E stain) shows dense collagenous fibrous thickening. There is virtually no inflammatory reaction visible.

Image 5.4:

The skin fibrosis is shown at higher power here. This is what produces the sclerodactyly.

Image 5.5:

A small renal arteriole (H&E stain) shows concentric, laminated thickening consistent with hyperplastic arteriolosclerosis.

Image 5.6:

This is a trichrome stain of the stomach (from another patient at autopsy with the same disease). What is wrong? There is marked diffuse fibrosis.

Questions:

1. What is the diagnosis? Are the pathologic findings specific? How do you arrive at a diagnosis in this case?

This is scleroderma (progressive systemic sclerosis). The pathologic findings are not specific until they reach a far advanced stage. This disease is mainly mediated by a type IV hypersensitivity response in which fibrosis (not inflammation) predominates. Dermal scarring can be seen in many disease processes. However, when the marked deformity and thickening of the skin of the fingers takes place, scleroderma is probable. The diagnosis of scleroderma is made by the finding of characteristic skin changes in the presence of serologic tests (ANA, ENA) specific for scleroderma, including autoantibodies to DNA topoisomerase I (more specific for diffuse scleroderma) and anticentromere antibody (for limited scleroderma, or CREST syndrome).

2. Does the immunofluorescence pattern help in making a diagnosis in this case?

Immunofluoresence tests are not very helpful in making the diagnosis of scleroderma. In the kidney, one finds the deposition of fibrin in arterioles typical of malignant hypertension.

3. What other symptoms might this patient have?

The patient might have gastrointestinal complaints, non-specific joint findings (arthralgias), and malignant hypertension.

4. What pathologic finding(s) might you expect in the gastrointestinal tract, particularly the esophagus?

The GI tract could show submucosal and muscular collagenous fibrosis, leading to motility problems (such as difficulty swallowing).