Why Has This Young Man Lost the Ability to Squat and Clench His Fists?

Why has this 31-year-old man gradually developed significant stiffness in his joints, which is now preventing him from clenching his fists or squatting? That's what Yafang Zhou, MD, PhD, of Xiangya Hospital in Hunan, China, and colleagues wanted to figure out.

As they reported in JAMA Neurology, the man's experience began about 6 months previously, when he found he could not press his palms into full contact with each other (the "prayer sign").

This continued to worsen, so that 4 months later he had become unable to clench his fists. When he presented to the clinic for an assessment, he explained that he was also no longer able to squat as of about 10 days earlier.

Neither his medical nor family history offered clues as to what might be causing the progressive joint stiffness. He had no symptoms that would suggest Raynaud's phenomenon, such as cold fingers or toes, or changes in skin color, pain, or numbness in response to cold or stress.

Physical examination revealed no superficial changes such as reddened or hardened areas of skin on his arms, legs, or trunk, or evidence of swelling. He had limited mobility of the joints in his hands, wrist, feet, and ankles. There was no evidence of muscular atrophy or sclerodactyly. Clinicians observed the "prayer sign" -- often due to diabetic cheiroarthropathy -- and a linear depression along the course of the superficial vein known as the "groove sign" when the patient's arm was elevated.

Blood test results indicated eosinophilia:

• Absolute eosinophil count: 1,300 μL; (reference <500 μL)

• Erythrocyte sedimentation rate (ESR): 31 mm/h (reference <15 mm/h)

• C-reactive protein (CRP): 3.01 mg/dL (reference <0.8 mg/dL)

Results of liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable.

Zhou and colleagues performed an electrocardiogram, an MRI of the cervical spine, and plain radiographs of the hands, wrists, feet, and ankles, as well as nerve conduction studies on all four limbs, with all returning normal findings.

Electromyography (EMG) showed spontaneous activities in the patient's limb muscles, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.

After the patient underwent a biopsy of the left calf muscle, analysis of the sample of skin, fascia, and muscle showed inflammatory cell infiltrate composed primarily of lymphocytes and eosinophils in the fascia and some subjacent endomysium and perimysium, although minimal in the skin. There were moderate variations in muscle fiber size; some muscle fibers had atrophied, and a few were necrotic.

Clinicians considered several differential diagnoses, including myotonic dystrophy, scleroderma, deep morphea (morphea profunda), and eosinophilic fasciitis.

Based on the clinical characteristics, laboratory findings, and biopsy results, clinicians diagnosed the patient with eosinophilic fasciitis.

Discussion

The authors presenting this case noted that neurologists rarely encounter patients with insidious onset of bilaterally limited joint mobility, and the rarity of eosinophilic fasciitis makes it especially challenging to diagnose.

Bilaterally limited mobility of joints, cutaneous manifestations (such as groove sign and orange peel appearance), and peripheral eosinophilia are all useful clues to the diagnosis, the team said.

EMG showed that the patient's muscles were unable to relax after use, which pointed to myotonic dystrophy as a possible diagnosis. However, there was no evidence of one particular effect typical of that condition -- unusually slow or delayed muscle relaxation after the muscles are contracted.

Another possible cause considered, the team related, was systemic sclerosis (scleroderma), based on the patient's reduced joint mobility and the prayer sign. However, given that his ANA test results were negative, that he was not affected by Raynaud's phenomenon, and that his internal organs were not involved, that diagnosis too was excluded.

According to proposed diagnostic criteria for eosinophilic fasciitis, which the case authors referenced, other features that help differentiate that condition from systemic sclerosis include the absence of "digital and facial skin sclerosis that are characteristic of systemic sclerosis, as well as nail fold capillary abnormalities, antinuclear antibodies, and disease-specific autoantibodies."

Given their patient's limited joint mobility, peripheral eosinophilia, and elevated ESR and CRP, Zhou and co-authors also considered a diagnosis of deep morphea, a rare subtype of morphea that mainly affects the deep dermis and subcutaneous tissue and may extend to involve the underlying fascia and muscle.

However, the patient's bilateral, symmetrical joint involvement, histology findings showing inflammatory cell infiltrate composed primarily of lymphocytes and eosinophils in the fascia, and the absence of sclerotic skin plaque suggested eosinophilic fasciitis.

"Eosinophilic fasciitis is a rare disorder characterized by the induration of fascia and skin, preceded by the abrupt onset of erythema and non-pitting edema, resulting in limited mobility of the underlying joints marked by hardening of the fascia and skin" and as in this patient's case, "the disease can have an insidious onset," Zhou and co-authors wrote.

Characteristic signs include orange peel appearance of the skin caused by skin induration, and the groove sign -- "probably due to the relative sparing of the epidermis and superficial dermis by the fibrotic process," the authors said.

Occasionally, the skin will remain unaffected; the fingers are usually spared, and Raynaud's phenomenon is usually absent. Results of laboratory tests include peripheral eosinophilia, increased levels of ESR and CRP, and polyclonal hypergammaglobulinemia; ANA test results are negative.

The case authors noted that the patient's EMG findings may be due to myositis, a common feature of eosinophilic fasciitis, and that myotonic discharges may be seen in a number of acquired myopathic disorders. In addition, certain drugs such as statins have been associated with myotonic discharges.

The cause and exact incidence of the disease remain unknown, the case authors noted, explaining that several possible causes or triggers have been proposed, including strenuous exercise or trauma.

According to the National Organization for Rare Disorders, "researchers have speculated that exposure to certain toxins, drugs such as simvastatin or phenytoin, or other environmental factors including infectious agents (Borrelia burgdorferi [Lyme disease] may [also] play a role in the development of eosinophilic fasciitis."

Zhou and co-authors noted that treatments for the disease have not been assessed to date in randomized trials, and that the typical current approach includes systemic glucocorticoids at doses equivalent to prednisone 0.5 to 1 mg/kg per day. An immunosuppressant such as methotrexate may also be used as concomitant initial therapy, or for patients not responding to steroid treatment.

In this case, the patient received prednisone and cyclophosphamide, which improved his joint mobility by follow-up 9 months later.

Conclusion

Summing up, the team concluded that diagnosing eosinophilic fasciitis is challenging because of its rarity, and that bilaterally limited mobility of joints, cutaneous manifestations such as groove sign and orange peel appearance, and peripheral eosinophilia are useful clues to help in the diagnosis.

Comment