Ann Rheum Dis: first published as 10.1136/ard.42.1.103 on 1 February 1983. Downloaded from

Annals ofthe Rheumatic Diseases, 1983, 42, 103-105

Case report

Chronic progressive eosinophilic : report of a 20-year failure to attain remission RICHARD BERTKEN AND DAVID SHALLER From the Department ofMedicine, Veterans Administration Medical Center, Fresno, and University of California School ofMedicine, San Francisco, California, USA.

SUMMARY A retrospective diagnosis of eosinophilic fasciitis was made in a patient with disabling contractural disease of 20 years' duration. Chronic moderate-dose therapy had failed to halt either clinical or histological progression of the disease, but rapid worsening of skin thickening and followed withdrawal of . Muscle wasting was severe in spite of normal serum creatine kinase levels; urinary excretion of creatinine was consistently elevated.

Because eosinophilic fasciitis is in its infancy as a mm3 (0 35 x 109/1). He responded promptly to copyright. diagnostic entity, the long-term course of this disease chlorpheniramine. is uncertain. Considerable variability of the short- Twenty years ago he was admitted to hospital term outcome has been reported in about 75 patients because of aching pain in all extremities for 3 months since 1974.'-'3 Remission, usually steroid-induced, and recurrent urticaria for 3 weeks. All the muscles appears to be the rule. However, some patients in were tender, but their strength, motion, and mass clinical 'remission' had stable skin thickening and were normal. Several urticarial patches marked the .12 An occasional patient did not thorax and face as well as the limbs. The scrotum and improve, and at least one worsened in spite of steroid perianal region showed vitiligo. http://ard.bmj.com/ therapy.' 6-13 In some patients relapses occurred as The peripheral eosinophil count was 3200 per mm3 late as 7 years after the initial onset.4 12 However, all (3-2 x 109/l); the sedimentation rate 14 mm in 1 h; reported cases with as much as 15 years of follow-up the globulin fraction 3 2 gIdl (32 g/l); the albumin 3 3 had unequivocal remission of fasciitis."4 g/dl (33 g/l); rheumatoid factor and LE cell deter- This is a report of a patient with chronic progress- minations negative; and the SGOT 44 units (normal ive eosinophilic fasciitis over at least a 20-year 5-40 units). Muscle biopsy showed profound mono-

period. Serial myofascial biopsies and creatine excre- nuclear and eosinophilic infiltrate of the fascial and on September 29, 2021 by guest. Protected tion showed active disease over the entire span in subcutaneous layers. Muscular septa contained mod- spite of steroid therapy. The disease was uniquely est focal accumulations of eosinophils, more promi- extensive and the patient's functional outcome was nent in areas adjacent to the . Myonal necrosis poor. was absent. The epidermis was normal. The patho- logical diagnosis was 'anaphylactoid .' Case report The patient developed fevers, progressive weight loss, and stiff, swollen hands. Transient crops of Twenty-four years ago the patient, a white male then urticaria recurred. All these symptoms improved on 28 years old, was admitted to hospital for diffuse prednisone 5 mg t.i.d. and recurred when the steroid giant urticaria of 2 months' duration. He reported was tapered. He was discharged on prednisone 5 mg several previous episodes of urticaria associated with t.i.d. fever, and was being treated by atopic desensitisation Eighteen years ago he was readmitted to hospital without benefit. The eosinophil count was 350 per because of aching in both shoulders and difficulty Accepted for publication 6 January 1982. swallowing in spite of 20-30 mg prednisone daily. Correspondence to R. Bertken, MD, 2615 East Clinton Avenue, Muscle wasting and generalised thickening of the Fresno, California 93703, USA. skin was noted in the limbs. Motion of the shoulders, 103 Ann Rheum Dis: first published as 10.1136/ard.42.1.103 on 1 February 1983. Downloaded from

104 Bertken, Shaller elbows, and fingers was limited. Routine laboratory face; worsening of long-standing finger deformities investigations were normal. The urine creatine excre- was apparent, though hand films showed no bony tion was 140 mg in 24 hours (normal <50 mg). changes. Muscle biopsy revealed severe fasciitis with Barium swallow was normal. Repeat muscle biopsy substantially greater infiltrate than seen in previous showed greater fascial thickening with somewhat less biopsies. The was normal. The Westergren intense mononuclear infiltrate and occasional ESR was 12 mm/h, the globulins 3 7 g/dl (37 g/l). The eosinophils. He was discharged on prednisone 5 mg urinary excretion of creatine was 305 mg in 24 hours t.i.d. as a case of progressive systemic sclerosis. (urinary creatine:creatinine = 0.28). After 40 days Between 15 and 13 years ago, during a series of on 60 mg prednisone it increased to 402 mg (urinary hospital evaluations for flank pain and peptic ulcer creatine:creatinine = 0.36). disease, physicians noted thickening of nearly the Reinstitution of prednisone 40 mg. q.o.d. was entire cutis. Movement of the mouth, trunk, and attended by improved pain and objectively fingers became limited. Also noted were muscle wast- diminished skin tightening and contractures. Urinary ing and weight loss. Routine laboratory and extensive creatine excretion gradually declined over a 6-month radiographic examinations showed no abnormality period to 110 mg/24 hours. Nevertheless the patient, except for duodenal ulcer and sedimentation rates now 51, remains bound to a powered wheelchair and averaging 35 mm/h. Changes seen on a third muscle dependent on others for much of his care. biopsy resembled those on the previous biopsies. Prednisone was continued at 10-15 mg daily; para- Discussion amino benzoic acid 12 g daily was begun for a 2-year course terminated by gastrointestinal intolerance and Eosinophilic fasciitis of this extent and chronicity is with questionable effect. unprecedented in medical literature. Indeed, the sus- Nine years ago the patient developed causalgia of tained severity of this man's illness impeded the rec- the right leg 6 months after right iliofemoral bypass ognition of the correct diagnosis for several years graft. Symptoms improved following lumbar after eosinophilic fasciitis became widely known. The copyright. sympathectomy. Prednisone dosage was changed to eosinophilic nature of the onset was buried in 30 mg q.i.d. Attempts to withdraw this drug led to thousands of pages of medical charting, and the increased muscle pain, so that he was continued at this classic skin changes became prominent only when dosage for the next 6 years. prednisone was stopped. Between 8 and 3 years ago the patient was admit- This patient, as an extreme example of the disease ted to hospital many times, at several university- process, appears to confirm further the concept of affiliated government hospitals, because of intractable eosinophilic fasciitis as a disease chiefly of the body neuropathic pain in the feet. Extensive laboratory surface, with incidental involvement of muscles and http://ard.bmj.com/ and radiographic investigations aimed at clarifying joints. Only 10% of reported patients have associ- both his neurological and musculoskeletal symptoms ated disease outside these tissues.'° In this patient revealed no new abnormalities. Serum muscle pulmonary, cardiovascular, hepatic, renal, and intes- enzymes were repeatedly normal. The 24-hour tinal problems either did not occur or were clearly urinary excretion of creatine averaged 156 mg. attributable to intercurrent processes. Suppression of Sedimentation rates ranged between 15 and 57 haematopoiesis, reported by others in eosinophilic mm/h. Gammaglobulins showed a polyclonal rise of fasciitis, did not occur."5 The causalgia of the feet was on September 29, 2021 by guest. Protected 3 8 to 4 0 g/dl (38-40 g/l). Several electromyograms never clearly attributed, but may have been were normal. diseases-related by virtue of chronic peripheral nerve A fourth muscle biopsy again showed profound irritation in inflamed fascia. Another compressive inflammatory fascial thickening with mild, focal, neuropathy, the , occurred in non-necrotising myositis. The clinical diagnosis was one-third of one series of patients."3 No other clinical now . Skin changes were regarded as finding, no laboratory test, and no biopsy specimen insufficient for the diagnosis of . suggested . Three years ago prednisone was-slowly withdrawn. This case clearly makes the point that eosinophilic Enteric-coated aspirin was given in therapeutic dos- fasciitis can be extensive, chronic, and irreversibly age for . Contractures and muscle atrophy disabling. It also focuses attention on the difficulty of in all limbs and digits were evident, but the skin, while evaluating disease activity. We recognise 4 general taut to palpation, visually appeared normal. areas in the assessment of disease activity: acute One year ago the patient was admitted to the hos- phase (, elevated acute phase reactants, pital because of marked increase in skin thickening hypergammaglobulinaemia); skin thickening and and contractures. The skin ranged from woody to rock- contracture; muscle atrophy; and histological hard in consistency, with broad areas of lumpy sur- changes. Ann Rheum Dis: first published as 10.1136/ard.42.1.103 on 1 February 1983. Downloaded from

Chronic progressive eosinophilic fasciitis 105 Acute phase changes usually subside in the first progressive, 'stable' lesion. This observation suggests year or two of illness, whether or not the skin changes that biopsy is a sensitive method for detecting active resolve completely. In this patient eosinophilia dis- fasciitis. In the patient presented here, biopsy results appeared within 6 months of onset. The ESR varied did appear to parallel disease activity. Whether widely thereafter but was not clearly related to dis- biopsy information is unique and useful in therapeu- ease activity. It was normal at the onset of the disease tic decisions await a study of careful serial observa- and during most of the last 3 years of the case record, tions in patients with chronic eosinophilic fasciitis. times at which muscle biopsies showed marked fasciitis. Moderate polyclonal hypergamma- globulinaemia persisted throughout the illness, References almost as a fixed serological abnormality. Episodes of 1 Shulman L E. Diffuse fasciitis with eosinophilia: a new syn- depressed cryoglobulins and complement were drome? Trans Assoc Am Physicians 1975; 88: 70-86. absent. 2 Rodnan G P, Di Bartolomeo A G, Medsger T A, et al. Eosinophilic fasciitis. Report of seven cases of a newly- Fascial thickening is the hallmark of the disease, recognized scleroderma-like syndrome. Arthritis Rheum 1975; but no objective measurement of it has been pro- 18: 422-3. posed. The weight of 7 mm skin thickness cores, as is 3 Schumacher H R. A scleroderma-like syndrome with fasciitis, used to evaluate scleroderma, was increased in 5 of 8 myositis, and eosinophilia. Ann Intern Med 1976; 84: 49-50. 4 Caperton E M, Hathaway D E, Dehner L P. , fasciitis, patients with eosinophilic fasciitis in spite of the rela- and scleroderma with eosinophilia: a broad spectrum of disease. tive sparing of the dermis in the infiltrative process."6 Arthritis Rheum 1976; 19: 792-3. Serial skin determinations have not yet been 5 Bennett R M, Herron A, Keogh L. Eosinophilic fasciitis. Case reported. The thickening might also be indirectly report and review of the literature. Ann Rheum Dis 1977; 36: 354-9. followed by range of motion measurements, as is 6 Atherton D J, Wells R S. ? Scleroderma of Buschke? frequently done in scleroderma. Perhaps such eosinophilic fasciitis. Br J Dermatol 1976; 95 (suppl): 36-7. measurements would have detected the late intensifi- 7 Fleishmajer R, Jacotat A B, Shore S, et al. Scleroderma, of this disease following steroid with- eosinophilia, and diffuse fasciitis. Arch Dernatol 1978; 114: copyright. cation patient's 1320-5. drawal, but they were not recorded. 8 Weinstein D, Schwartz R A. Eosinophilic fasciitis. Arch Der- Muscle atrophy has not been emphasised in other matol 1978; 114: 1047-9. case reports. In this patient muscle atrophy was sub- 9 Fu T S, Soltani K, Sorensen L B, Levinson D, Lorincz A I. stantial within 5 years of the disease's onset. Over 20 Eosinophilic fasciitis. JAMA 1978; 204: 451-3. 10 Moore T L, Zuckner J. Eosinophilic fasciitis. Semin Arthritis years it became profound in spite of continuously Rheum 1980; 9: 228-35. normal muscle enzyme levels and evidence of modest 11 Moutsopoulos H M, Webber B L, Pavlidis N A, et al. Diffuse focal muscle involvement on biopsy. Urinary creatine fasciitis with eosinophilia: a clinicopathologic study. Am J Med

it 1980; 68: 701-9. http://ard.bmj.com/ excretion was increased on the several occasions 12 Michet C J, Doyle J A, Ginsburg W W. Eosinophilic fasciitis: was tested, but was not responsive to steroid therapy report of 15 cases. Mayo Clin Proc 1981; 56: 27-34. except over a course of many months. Unlike most 13 Barnes L. Rodnan G P, Medsger T A, Short D. Eosinophilic myositis patients, this patient's strength has.been fasciitis: a pathologic study of twenty cases. Am J Pathol 1979; been 96: 493-518. proportional to observed muscle mass. He has 14 Fernandez-Herihy L. Eosinophilic fasciitis: report of a 22-year more limited by contracture than by weakness, sug- follow-up study. Arthritis Rheum 1981; 24: 97-8. gesting the former might be responsible for the latter. 15 Hoffman R, Dainiak N, Sibrock L, et al. Antibody-mediated and diffuse fasciitis. N Engl J Med 1979; 300:

Repeat myofascial biopsies in 2 reported cases 18 on September 29, 2021 by guest. Protected 718-21. months after initiation of steroid therapy revealed 16 Rodnan G P, Lipinski E, Luksick J. Skin thickness and collagen persistent fasciitis." In both patients reduced skin content in progressive systemic sclerosis and localized thickening persisted as an apparently non- scleroderma. Arthritis Rheum 1979; 22: 130-40.