A Woman With Painful and Swollen Legs

A 46-year-old woman presented with a 2-month history of progressive fatigue, generalized edema, myalgia, and proximal muscle weakness. She had a 30-lb weight gain, diffuse large joint arthralgias, and morning stiffness; she also had an erythematous rash over her upper extremities, trunk, and back. She denied recent infections other than chronic sinusitis and had no fever, lymphadenopathy, dysphagia, or changes in bowel habits.

Examination revealed prominent limb edema and induration. There was a splotchy maculopapular rash on her proximal upper extremities, chest, and back. She had discomfort on range-of-motion testing but no warmth, inflammation, or joint infusions. Neurologic examination revealed tenderness on muscle palpation and a very mild proximal muscle weakness in the lower extremities, likely due to poor effort from pain. The examination was otherwise unremarkable.

Pertinent laboratory tests included a serum creatine kinase (CK) of 84 IU/L (normal, <200 IU/L); white blood count, 16 thou/mm ³ (normal, 5–10 thou/mm ³ ) with a differential significant for elevated eosinophils of 35%; hematocrit, 36% (normal, 37%–47%); and platelets, 436 mm ³ (normal, 150–400 mm ³ ). Alanine transaminase was 38 IU/L (normal, 0–30 IU/L); aspartate transaminase, 21 IU/L (normal, 0–30 mm ³ ); albumin, 2.3 g/dL; blood urea nitrogen, 33 mg/dL (normal, 6–20 mg/dL); the chemistry profile was otherwise normal, and the antinuclear antibody titer of 1:160 with a speckled pattern. Hepatitis B and C, HIV, antineutrophil cytoplasmic antibodies, and antichromatin antibodies were all negative.

What is the Most Likely Diagnosis?

Stiffness, erythema, and edema with eosinophilia are suggestive of an eosinophilic fasciitis. The absence of significant weakness and normal CK are against an inflammatory myopathy, which sometimes presents with subcutaneous edema. Amyloidosis and cysticercosis could also manifest with muscle swelling, but not with the skin changes seen in this case. It is also unlikely that she had myopathy with muscle enlargement, such as in the myotonias, as the swelling was not in the muscles and appeared to be subcutaneous. The absence of joint deformities argues against rheumatoid arthritis, although she did have joint pains. There were no systemic manifestations of lupus erythematosus. The prominent edema and the absence of sclerodactyly or systemic involvement argue against systemic sclerosis. However, systemic sclerosis and fasciitis may require biopsy and observation of therapeutic response to differentiate. Finally, fasciitis can occur secondary to toxic oil syndrome and in the eosinophilic syndrome secondary to contaminated tryptophan ingestion. This patient denied exposure to tryptophan. Systemic histiocytosis can sometimes manifest by fasciitis, but she had no evidence of a systemic disease.

What Should be Done Next?

A deltoid muscle and fascia biopsy were performed. This demonstrated normal muscle fibers without atrophy or necrosis. There were abundant mononuclear cells infiltrating the fascia and extending into the perimysium ( Fig. 103-1 ) but not into the endomysium ( Fig. 103-2 ). This infiltrate consisted mainly of macrophages and lymphocytes with very rare eosinophils. The macrophages stained very intensely with nonspecific esterase ( Fig. 103-3 ) and some with acid phosphatase ( Fig. 103-4 ) and NCL-MACRO 68 Ab. Most cells were CD45 positive. There were numerous CD8+ ( Fig. 103-5 ) and only a few CD4+ lymphocytes.