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Rheumatology > Systemic Rheumatic Disease
Eosinophilic Fasciitis
Article Last Updated: Nov 7, 2006
AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: Sherif Nasef, MD, Consulting Staff, Department of Internal Medicine, Division of Rheumatology, Lake Havasu Regional Medical Center
Sherif Nasef is a member of the following medical societies: American College of Physicians, American College of Physicians-American Society of Internal Medicine, American College of Rheumatology, and American Medical Association
Coauthor(s):
Kristine M Lohr, MD, Associate Chief, Program Director, Professor, Department of Internal Medicine, Division of Rheumatology, University of Tennessee School of Medicine
Editors: John Varga, MD, Professor, Department of Internal Medicine, Division of Rheumatology, Northwestern University; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Lawrence H Brent, MD, Associate Professor of Medicine, Thomas Jefferson University; Chair, Program Director, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center; Alex J Mechaber, MD, FACP, Assistant Dean for Medical Curriculum, Associate Professor of Medicine, Division of General Internal Medicine, University of Miami Miller School of Medicine; Herbert S Diamond, MD, Professor of Medicine, Temple University School of Medicine; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital
Author and Editor Disclosure
Synonyms and related keywords:
eosinophilic fasciitis, EF, eosinophilia, scleroderma, elevated sedimentation rate, elevated ESR, hypergammaglobulinemia, fascial thickening, hematologic disease, Shulman syndrome, Shulman's syndrome, peripheral eosinophilia, fasciitis, Borrelia burgdorferi, B burgdorferi
Background
The early description of eosinophilic fasciitis (EF) by Shulman in 1975 was of a disorder characterized by peripheral eosinophilia and fasciitis, which could be differentiated from scleroderma by the distinctive pattern of skin involvement that spares the digits, involves fascia rather than dermis, and is not accompanied by Raynaud phenomenon.
In these early reports, the disorder was considered clinically and histopathologically localized to the fascia. Since 1974, more than 200 patients with eosinophilic fasciitis have been reported, and debates are still ongoing as to whether eosinophilic fasciitis represents a variant of scleroderma.
Several large reviews have generated a broader clinical image of the condition, but eosinophilia, elevated sedimentation rate, hypergammaglobulinemia, and fascial thickening are critical elements of the syndrome.
Visceral involvement in eosinophilic fasciitis is often mild and asymptomatic; however, an association with hematologic disease now is recognized and frequently carries a grave prognosis.
Pathophysiology
Although the etiology of eosinophilic fasciitis is unknown, recent studies have shed light on some of the mechanisms involved in its pathogenesis. Fibroblasts from lesional tissue of patients with eosinophilic fasciitis produce excess collagen in vitro and display elevated transforming growth factor-b (TGF-b) and type 1 collagen mRNA levels when examined via in situ hybridization with specific cDNA. Therefore, the pathogenesis appears to involve the concomitant increase in the expression of genes for TGF-b and extracellular matrix proteins in fibroblasts in the affected tissues. One study showed that the fascial inflammatory infiltrate is predominantly composed of CD8 T lymphocytes, macrophages, and fewer eosinophils, suggesting a possible cytotoxic immune reaction in response to a possible infectious or environmental agent. Recent reports indicate that Borrelia burgdorferi may be a possible etiologic agent in some cases. Other studies showed elevated levels of serum manganese superoxide dismutase and tissue metalloproteinase 1 (TIMP-1), which may serve as a marker of disease activity. Fasciitis may be a common manifestation of various pathophysiologic processes associated with eosinophilia. The existence of primary and secondary forms of fasciitis has recently been suggested. Understanding the mechanisms involved in the development of fascial inflammation and fibrosis in these conditions may yield insights into the pathogenesis of other fibrotic skin diseases. Some cases of eosinophilic fasciitis have been described as associated with ingestion of L-tryptophan (see Eosinophilia-Myalgia Syndrome [EMS] and Causes).
Frequency
United States
Eosinophilic fasciitis is very rare.
Mortality/Morbidity
No data are available on morbidity or mortality rates. Rarely, a fatal aplastic anemia may develop.
Race
Eosinophilic fasciitis affects whites more often than it affects blacks.
Sex
In adults, eosinophilic fasciitis predominantly affects women.
Age
The age range is 2-88 years, although most patients present during the third to sixth decades of life.
History
- The onset of illness is not accompanied by fever or other systemic symptoms and, in about half of patients, follows an episode of strenuous physical exercise or activity.
- Swelling and progressive induration of the skin associated with aching of the extremities and occasional morning stiffness develop over a period of weeks. The distribution is most often in the upper extremity, proximal and distal to the elbow, and in the lower extremity, proximal and distal to the knee. Onset may be acute following some sort of strenuous exercise, or it may be subacute.
- Paresthesias may develop in a distribution pattern consistent with carpal tunnel syndrome, which has been reported.
- Inflammatory arthritis affects mainly the hands and wrists. Contractures occur in 75% of patients, typically affecting elbows, wrists, ankles, knees, hands, and shoulders.
- Neither Raynaud phenomenon nor symptoms of respiratory, gastrointestinal, or cardiac involvement are present.
Physical
- Upon examination, cutaneous induration with venous furrowing and irregular coarse puckering or fine dimpling (peau d'orange) is found. Skin changes affect all extremities in most cases, but they may be limited to the arms or abdomen.
- Other cutaneous changes reported include erythema, urticaria, bullae, alopecia, lichen sclerosis et atrophicus, vitiligo, and hyperpigmentation.
- Although any area of the body may be affected, arms, legs, hands, and feet are involved most commonly.
- A clawlike deformity of the hands has been described.
- Tenosynovitis of the flexor tendon sheath at the wrist causes carpal tunnel syndrome in 20% of the cases.
- Frequently, the inflammation extends deep from the fascia into the underlying muscle. This may be difficult to detect clinically.
- Clinically significant visceral involvement is rare, but specific testing may demonstrate subtle abnormalities similar to those found in localized scleroderma (morphea).
- Esophageal dysmotility has been reported rarely.
- Fasciitis of the thorax may result in restrictive ventilatory defects.
- Although cardiac involvement in the form of a pericardial effusion is seldom noted, it has been reported.
- Interestingly, Sjögren syndrome and hepatic and splenic enlargement also have been reported.
- Inflammatory arthritis occurs in 40% of patients, and joint contractures of the elbows, wrists, ankles, knees, and shoulders may develop in 55-75% of patients.
- A concurrent localized lesion of morphea may be seen in 25% of patients.
Causes
The etiology of eosinophilic fasciitis is not known, but it may follow strenuous activity. Some cases of eosinophilic fasciitis have been described to occur simultaneously with the appearance of EMS associated with L-tryptophan ingestion.
Eosinophilia
Eosinophilia-Myalgia Syndrome
Scleroderma
Other Problems to be Considered
Eosinophilic fasciitis, EMS, and toxic oil syndrome (TOS) are a group of disorders that share common clinical and histopathological features. The latter 2 conditions appear to always be or nearly always be induced by a toxin.
In 1989, an epidemic of an eosinophilic connective-tissue disease recognized in the United States was termed EMS. Most of the affected patients were consuming L-tryptophan, an amino acid that was available as an over-the-counter nutritional supplement. Subsequent epidemiologic studies indicated that most individuals who developed EMS during the epidemic had consumed L-tryptophan. Diffuse induration of the integument affecting the extremities and occasionally the torso, but sparing the face, hands, and feet, developed in a large number of patients with EMS.
Eosinophilic fasciitis is a disorder that is clinically and histologically localized to the fascia, whereas EMS and TOS may be associated with fasciitis but also display other features (particularly neuromuscular and cardiopulmonary).
EMS and TOS are differentiated from eosinophilic fasciitis by cutaneous features (ie, urticaria, maculopapular rash, mucinosis, dermatographism, alopecia), neuromuscular features (ie, myalgia/myopathy, severe cramps, distal sensorimotor neuropathy, mononeuritis multiplex, cognitive symptoms), cardiopulmonary features (ie, pneumonitis, respiratory muscle dysfunction, pulmonary hypertension), and other features (ie, severe fatigue, sicca complex, gastrointestinal manifestations). Laboratory features include elevated serum aldolase and lactate dehydrogenase and abnormal levels of liver-associated enzymes.
Lab Studies
- Peripheral blood eosinophilia is present in 64% of patients. The degree of eosinophilia is variable over time, even in the absence of specific therapy.
- Aplastic anemia, although rare, is the most frequent serious hematological complication, but cases have been described with thrombocytopenia, hemolytic anemia, pernicious anemia, and leukemia.
- Immunofluorescence tests for antinuclear antibodies using a HEP-2 (ie, human epithelial) cell substrate are positive (titers >1:160) in 36% of patients.
- Hypergammaglobulinemia is characteristic, occurring in 75% of patients, and usually is due to a polyclonal increase in immunoglobulin G.
- Increase in the erythrocyte sedimentation rate (ESR) is found in 50-70% of cases.
- Serum creatine kinase and aldolase levels are normal.
- Rheumatoid factor (RF) and antinuclear antibodies are occasionally positive.
Imaging Studies
- MRI of the involved areas shows characteristic findings of fascial thickening, abnormal signal intensity, and contrast enhancement. MRI helps in making the diagnosis, locating the biopsy site, and monitoring the response to treatment.
- Contrast-enhanced radiographs of the GI tract demonstrated diminished peristaltic activity in the upper esophagus in one patient who had no symptoms of esophageal dysfunction.
Other Tests
- Electromyogram is the most sensitive test for myositis in eosinophilic fasciitis, and findings may be abnormal in the presence of normal serum muscle enzymes.
- Pulmonary function test (PFT) may show a restrictive pattern in patients with severe truncal involvement.
Procedures
- A full-thickness incisional biopsy specimen should be obtained, to include the skin, fat, fascia, and superficial muscle in continuity.
Histologic Findings
Inflammation, edema, thickening, and sclerosis of the fascia are hallmarks of eosinophilic fasciitis. The cellular infiltrate consists of lymphocytes, plasma cells, histiocytes, and eosinophils. Distribution of the eosinophils in the fascia may be focal, and a close relationship appears to exist between blood and tissue eosinophilia.
In the deeper portions of the panniculus, a similar infiltrate is found in the fibrous septa and at the periphery of the fat lobules. In advanced cases, dense sclerotic and hyalinized collagen bands run parallel to the fascia, with small foci of fat cells trapped between them. Often, vascular cuffing with lymphocytes and plasma cells is seen. Deep in the fascia, the inflammatory infiltrate extends into the epimysium, perimysium, and endomysium.
Medical Care
Treatment is with prednisone, in doses ranging from 20-60 mg/d.
- Response is considered satisfactory with reduction in edema, improvement in skin thickening, resolution of carpal tunnel syndrome, and gradual decrease in joint contracture.
- Eosinophilia resolves promptly after initiation of prednisone therapy.
Consultations
Dermatologists, rheumatologists, and surgeons (for the skin-muscle biopsy) are consulted most often.
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Drug Category: Corticosteroids
Have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.
| Drug Name | Prednisone (Deltasone, Orasone, Meticorten) |
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| Description | Useful in the treatment of inflammatory conditions by reversing increased capillary permeability and suppressing neutrophil activity. |
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| Adult Dose | 20-60 mg/d PO, usually undivided |
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| Pediatric Dose | 4-5 mg/m2/d PO |
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| Contraindications | No absolute contraindications; documented hypersensitivity; severe bacterial, viral, or fungal infection; active peptic ulcer disease; diabetes mellitus |
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| Interactions | Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics |
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| Pregnancy | B - Usually safe but benefits must outweigh the risks.
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| Precautions | Hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use; abrupt discontinuation of glucocorticoids may cause adrenal crisis |
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Further Outpatient Care
- Management of corticosteroid therapy should continue in the outpatient setting.
Prognosis
- Loss of edema usually is the first clinical sign of improvement and can occur within 4 weeks of commencing treatment. Concurrently, the skin becomes softer, but 3-6 months may elapse before maximal reduction in induration and contractures is achieved.
- While total resolution of the clinical signs can occur, some degree of induration remaining even after many months of prednisone therapy is not unusual.
- A direct correlation does not always exist between clinical disease activity and laboratory findings. The eosinophilia and ESR usually return to reference ranges within 6-8 weeks, although the ESR and hypergammaglobulinemia may remain abnormal for as long as 12 months.
- Eventually, corticosteroid therapy can be withdrawn in many of the patients, without relapse occurring.
- The development of aplastic anemia is a rare but grave complication.
Medical/Legal Pitfalls
- Failure to differentiate eosinophilic fasciitis from scleroderma (ie, misdiagnosis)
| Media file 1:
The arm of this patient demonstrates the puckered, so-called orange-peel or cobblestone skin that may occur in eosinophilic fasciitis. |
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Media type: Photo
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| Media file 2:
The skin of the patient's back appears shiny due to the stretched dermis overlying an inflamed fascia. Mild diffuse hyperpigmentation is present, along with a U-shaped area of hypopigmentation extending approximately from T10 to L4. |
 | View Full Size Image | |
Media type: Photo
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| Media file 3:
The skin of the abdomen and breasts is shiny and taut. The thigh reveals puckering or cobblestoning of the overlying dermis due to scattered retraction from scarred fascia. |
 | View Full Size Image | |
Media type: Photo
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| Media file 4:
Eosinophilic fasciitis. Top: In this gross specimen, the dermis (A), subcutaneous adipose tissue (B), and skeletal muscle do not appear unusual. However, the fascia (D) is markedly thickened. Bottom left: The gross findings are recapitulated in this low-power photomicrograph. The epidermis, dermis (A), and subcutaneous adipose tissue are not remarkable in this case. The fascia (D) is markedly thickened and focally infiltrated by inflammatory cells (E). The small amount of skeletal muscle (C) appears normal (hematoxylin and eosin stain at low power). Bottom right: A close-up photograph of a portion of the fascia showing mostly edematous cellular connective tissue (F). It is focally infiltrated by inflammatory cells, including lymphocytes, plasma cells, and histiocytes. The more intensely stained hypocellular pink bands across the top of the field (G) are part of an interstitial exudate of fibrin (hematoxylin and eosin stain at medium power). |
 | View Full Size Image | |
Media type: Photo
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Eosinophilic Fasciitis excerpt Article Last Updated: Nov 7, 2006
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