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Concurrent eosinophilic fasciitis and cutaneous T-cell lymphoma. Eosinophilic fasciitis as a paraneoplastic syndrome of T-cell malignant neoplasms?

Eosinophilic fasciitis has been reported to precede hematologic malignant neoplasms such as myelomonocytic leukemia, lymphocytic leukemia, and Hodgkin's lymphoma. In this case study, eosinophilic fasciitis occurred concurrently with cutaneous T-cell lymphoma (mycosis fungoides). The clinical diagnosis of eosinophilic fasciitis was based on painful sclerodermatous lesions on the extremities and trunk without acrosclerosis. There was histologic confirmation with edema and lymphocytic inflammation in the superficial muscular fascia and dermis. Deposition of immune reactants was found in the fascia and dermis. In addition, peripheral eosinophilia and circulating immune complexes were detected. The diagnosis of cutaneous T-cell lymphoma (mycosis fungoides) was based on extensive erythematous cutaneous plaques, dermal and epidermal lymphocytic atypia, loss of pan-T-cell immunologic markers, and a cutaneous lesional T-cell receptor beta-chain rearrangement by Southern blot analysis. Eosinophilic fasciitis may occur as a paraneoplastic syndrome associated with hematologic malignant neoplasms, including mycosis fungoides. Cytokines or lymphokines released by activated immunocytes, either malignant leukocytes or normal leukocytes reacting to malignant cells, may be responsible for the eosinophilia and sclerosis seen in these associated hematologic malignant neoplasms.

Aged

Tartrate-resistant acid phosphatase containing cells in nodular fasciitis, proliferative fasciitis, and proliferative myositis.

Five cases of nodular fasciitis, three cases of proliferative fasciitis, and one case of proliferative myositis were investigated by tartrate-resistant acid phosphatase (TRAP) histochemistry on conventional paraffin-embedded material. In all cases varying numbers of enzyme-positive cells were detected. Cytological investigations revealed the presence of small round cells, elongated spindle cells, medium-sized mono- or binucleated cells, and multinuclear giant cells, the latter resembling osteoclasts. However, the typical ganglion-like cells were TRAP-negative in almost all tests. The TRAP-pattern may help to differentiate nodular fasciitis and allied lesions from inflammatory pseudotumours or organising haematomas, as the latter do not contain TRAP-positive cells. As TRAP appears to be a marker for a special population of phagocytizing and non phagocytizing histiocytes, nodular fasciitis and its proliferative variants may be assumed to be fibrohistiocytic tumorous conditions.

Acid Phosphatase

Flow cytometric study of nodular fasciitis, proliferative fasciitis, and proliferative myositis.

DNA ploidy was assessed retrospectively, using flow cytometry, in 13 nodular fasciitis (NF) lesions, three proliferative myositis (PM) lesions, one proliferative fasciitis lesion, and 12 other benign fibrous lesions (BFLs). All were diploid. In view of the large amounts of cellular debris, cell cycle analysis was possible in only seven NF lesions, three PM lesions, and six BFLs. The mean percentage of S phase did not differ markedly between the combination of NF and PM lesions (6.6%) and BFLs (7.1%); the mean percentage of G2 + M phase (5.4%) of the NF/PM lesion combination was twice as large as that of the BFLs (2.5%). No correlation was detected between the cell cycle analysis and the mitotic count, the predominant histologic type in NF lesions, or the predominant stroma in PM lesions.

DNA

A histopathologic comparison of Shulman's syndrome (diffuse fasciitis with eosinophilia) and the fasciitis associated with the eosinophilia-myalgia syndrome.

A comparison of the histopathologic features of Shulman's syndrome (diffuse fasciitis with eosinophilia) and the fasciitis associated with the eosinophilia-myalgia syndrome is presented. The study population consisted of eight biopsy specimens of seven patients with Shulman's syndrome and 11 specimens from 10 patients with eosinophilia-myalgia syndrome. Both groups exhibited inflammatory changes in the subcutaneous fat, septa, and fascia; cutaneous changes were more prominent in cases of eosinophilia-myalgia syndrome. Eosinophils and plasma cells were not consistently present in either condition; mast cells and factor XIIIa-positive cells were consistently present in the inflammatory infiltrates. Although there was overlap in the histopathologic findings, Shulman's syndrome tends to involve the subcutis alone and the eosinophilia-myalgia syndrome tends to be a pancutaneous-subcutaneous process.

Eosinophilia

Proliferative fasciitis. A variant of nodular fasciitis.

The clinical and pathologic features of eight cases of proliferative fasciitis, a variant of nodular fasciitis, were described. The lesion affected adults older than 51 years of age. It involved various parts of the body and grew rapidly in most cases. Follow-up information, however, revealed that the patients took a benign clinical course after a local excision. Microscopically a diffuse proliferation of fibroblastic cells intermingled with a number of large basophilic cells resembling ganglion cells was characteristic, and was accompanied by slight lymphocytic infiltration and by slight fibrinous exudation and hemorrhage. The large basophilic cells seemed to be metamorphosed from cells of fibroblastic series.

Aged

Colitis and pericarditis in a patient with eosinophilic fasciitis. A contribution to the multisystem nature of eosinophilic fasciitis.

A case of eosinophilic fasciitis (EF), associated with monoclonal gammopathy, thyroglobulin antibodies, pericarditis and colitis, is described. The occurrence of EF in the framework of a multisystem disease is the outstanding feature, contrasting with the absence of visceral involvement or solitary organ involvement in the large majority of cases. The unusual histologic features of the colitis and beneficial effect of cimetidine on EF are discussed.

Aged

[Cranial fasciitis of childhood].

A rare case of cranial fasciitis in a 1-year-old boy arising in the temporoparietal bone has been described. In 1990, Lauer and Endinger first reported cranial fasciitis, which is a benign subcutaneous tumor of the head developing from the deep fascia or the cranial periosteum and showing a pathological finding characterized by proliferation of fibroblasts. They described this tumor as "cranial fasciitis of childhood" in view of a high incident in infants and child. Cranial fasciitis grows rapidly in the scalp without pain, but its mean size is 2.5-3cm. Cranial fasciitis is closely related a clinical course and pathological findings to nodular fasciitis, which is also a benign proliferative fibroblast tumor developing from the subcutaneous muscular layers of the trunk and extremities (especially, the forearms), which was reported by Konwaler in 1955. However, cranial fasciitis differs from nodular fasciitis in that it is associated with the skull bone and, in many cases, the tumor destroys the inner and outer table of the skull and adheres to the dura mater. Cranial fasciitis should be considered to be a variant of nodular fasciitis. Neurosurgeons should be aware of this entity in the differential diagnosis of a firm lesion of the scalp in children. A brief review of the literature disclosed only 17 cases in the world. This case report is the first one of cranial fasciitis in Japan.

Fasciitis

The fasciitis-morphea complex in children.

OBJECTIVE: To describe the clinical presentation and treatment of the combined syndrome of fasciitis and morphea in children. SETTING: The rheumatic disease clinic of a university children's hospital. PATIENTS: Six children who were referred for signs or symptoms of fasciitis were observed. SELECTION PROCEDURES: All children who were referred for fasciitis were included in the study. INTERVENTIONS: Therapy included prednisone initially and subsequent long-term treatment with penicillamine and alternate-day doses of prednisone. MEASUREMENTS AND RESULTS: Symptoms of morphea appeared 1 year before to 4 years after the first signs of fasciitis were observed. The fasciitis was characterized by usually symmetrical, centrifugal swelling, pain, and contracture formation. The morphea and fasciitis did not appear in the same areas of the body. CONCLUSIONS: The fasciitis and morphea are clearly linked manifestations. The fasciitis, but not the morphea, appears to respond to treatment with steroids. Treatment with penicillamine may ameliorate the sclerosis of the morphea but does not stop new lesions from appearing.

Adolescent

Eosinophilic fasciitis associated with use of L-tryptophan: a case-control study and comparison of clinical and histopathologic features.

We investigated the relationship between use of L-tryptophan and development of eosinophilic fasciitis by two methods: a retrospective patient survey and a case-control study of patients with eosinophilic fasciitis diagnosed at the Mayo Clinic between 1977 and 1989. Before 1986, no traceable patients with eosinophilic fasciitis had taken L-tryptophan. Between Jan. 1, 1986, and July 31, 1989, 8 of 34 patients had ingested L-tryptophan (P less than 0.001). In the case-control study, traceable patients with eosinophilic fasciitis were matched with patients who had systemic sclerosis or rheumatoid arthritis and healthy control subjects who had undergone a general medical examination. Of the 60 matched control subjects, 2 had used L-tryptophan. Thus, the odds ratio was 19, indicating a 19-fold greater likelihood of use of L-tryptophan in patients with eosinophilic fasciitis than in the control group. A retrospective assessment of clinical features, response to treatment, and blinded review of biopsy specimens of skin and fascia in patients who had eosinophilic fasciitis with or without exposure to L-tryptophan disclosed no significant differences in the two groups. This retrospective study confirms a strong association between consumption of L-tryptophan and development of eosinophilic fasciitis in some patients. No clinical or histopathologic features were detected that distinguished this disorder on the basis of previous exposure to L-tryptophan.

Adult

L-tryptophan ingestion associated with eosinophilic fasciitis but not progressive systemic sclerosis.

OBJECTIVE: To assess the use of L-tryptophan by patients with eosinophilic fasciitis and compare this with its use by patients with progressive systemic sclerosis (scleroderma). DESIGN: Retrospective and prospective analysis. Six patients with eosinophilic fasciitis were identified retrospectively and two prospectively. Retrospective identification of patients was done by questioning hospital-affiliated rheumatologists and dermatologists and by searching the hospital dermatopathology database. The patients with scleroderma or morphea were prospectively identified by questioning consecutive office patients with these established diagnoses. SETTING: University of Pennsylvania rheumatology and dermatology practices. PATIENTS: Eight patients with eosinophilic fasciitis; 40 consecutive patients with scleroderma (27 with diffuse cutaneous and 13, limited cutaneous disease); 3 patients with morphea. RESULTS OF DATA ANALYSIS: All eight patients with eosinophilic fasciitis had taken L-tryptophan before the onset of their disease. All had myalgias and high peripheral eosinophil counts (most greater than 5000 cells/mm3). Only 1 of 40 patients with scleroderma (no patients with morphea) had used L-tryptophan preceding illness (P less than 0.001 compared with eosinophilic fasciitis). Six patients with eosinophilic fasciitis had taken L-tryptophan for less than 8 months. One patient had taken it for 9 years before developing skin induration. Two patients were newly identified as having hypothyroidism; two developed neuropathy; and two had severe flexion contractures (several occurring in areas without skin induration). Five patients had low-titer antinuclear antibodies, indicating a possible autoimmune process. Most patients had only a partial response to systemic corticosteroid therapy. One patient has had important disease regression in response to isotretenoin therapy that was evident even while she continued to take L-tryptophan. CONCLUSIONS: L-Tryptophan use can lead to eosinophilic fasciitis whereas it does not appear to cause classic scleroderma. The disease process does not automatically remit after discontinuation of L-tryptophan-containing products.

Adult

Fasciitis, perimyositis, myositis, polymyositis, and eosinophilia.

Several groups of cases of fasciitis and myositis with eosinophilia are reported. The common features are inflammation into fascia and/or perimysium, and/or muscle fibers; eosinophilia in blood and/or in muscle biopsy. The following classification of 24 cases is suggested: at one end of the spectrum are fasciitis with eosinophilia: diffuse fasciitis (Shulman syndrome): 10 cases (3 with hematological complications); 2 cases of diffuse fasciitis with muscle atrophy; 3 cases of restricted fasciitis. Relapsing perimyositis with eosinophilia belong to the same spectrum, either diffuse (5 cases) with myalgias, or localized (2 cases). Other cases are focal myositis or multiple myositis, polymyositis with eosinophilia. The relationship among these cases is discussed. There is a continuum among the different groups. The pathophysiology remains unknown.

Adult

Frequency, levels, and significance of blood eosinophilia in systemic sclerosis, localized scleroderma, and eosinophilic fasciitis.

Blood eosinophilia is a common feature of eosinophilic fasciitis and is variably reported in systemic sclerosis and localized scleroderma. Since these diseases share cutaneous fibrosis as the final outcome and have other clinical and pathologic features that are difficult to differentiate, the presence of blood eosinophilia may be a further source of confusion. In this study, we examined the frequency and level of blood eosinophilia in 715 patients with systemic sclerosis, 72 patients with localized scleroderma, and 22 patients with clinically active eosinophilic fasciitis. When defined as greater than 400 cells/mm3, eosinophilia was present in 7% of patients with systemic sclerosis, 31% of patients with localized scleroderma, and 83% of patients with eosinophilic fasciitis. Greater than 1000 eosinophils/mm3 were present less frequently in systemic sclerosis (1%) and localized scleroderma (8%) than in eosinophilic fasciitis (61%). No difference in the frequency of eosinophilia was present in patients with the limited cutaneous CREST syndrome or the diffuse cutaneous variety of systemic sclerosis, and in these patients the presence of eosinophilia did not correlate with the extent of cutaneous or internal organ involvement or with other laboratory abnormalities. Among patients with localized scleroderma, eosinophilia was more common in those with linear scleroderma and generalized morphea than in those with morphea, and both the frequency and level of eosinophilia were greater in individuals with clinically active disease (p less than 0.02). Eosinophilia was a persistent feature in untreated patients with active eosinophilic fasciitis, even up to 30 months of disease duration.

Eosinophilia

Necrotizing fasciitis: a fatal outcome following minor trauma. Case report and literature review.

The death of a young healthy man, 11 days after he sustained minor trauma, illustrates the potential disaster of undiagnosed necrotizing fasciitis. Difficulty in early diagnosis often arises because the skin is initially spared and only later becomes secondarily involved. In this case, because of the lack of external manifestations, the diagnosis of necrotizing fasciitis was not considered until the postmortem examination. Necrotizing fasciitis should be considered a potentially serious problem that can follow minor trauma and eventually lead to death. The need for a high index of suspicion to make this diagnosis, along with the medicolegal implication of a diagnosis of necrotizing fasciitis, are both addressed in this report. Also of note is the fact that this patient was treated with nonsteroidal antiinflammatory drugs for pain and inflammation, which has recently been reported to be associated with an increased incidence of fulminant evolution of necrotizing fasciitis.

Adult

Proliferative fasciitis and myositis of childhood.

Eleven cases of proliferative fasciitis and myositis in children, ages 2.5 months to 13 years, are presented. Eight lesions averaging 2.3 cm in size occurred in the extremities, two in the head and neck region and one on the chest wall. Like proliferative fasciitis and myositis in adults, these lesions consisted of admixtures of large polygonal to spindled, ganglion-cell-like fibroblasts with vesicular nuclei and prominent inclusion-like nucleoli. Seven of 11 lesions were initially diagnosed as sarcomas, most commonly rhabdomyosarcoma. Four patients were treated by wide excision (three with regional lymphadenectomy), three received chemotherapy, and one was given radiation therapy. There were some histologic differences from adult-type proliferative fasciitis and myositis. The childhood lesions were generally well circumscribed, lobulated, extremely cellular with less collagen production, and often associated with acute inflammation and microscopic foci of necrosis. Immunohistochemical comparison with adult proliferative fasciitis and myositis showed similar immuneprofiles; the ganglion-like cells stained for vimentin and actin and focally with KP1, suggesting myofibroblastic and histiocytic features. None of the lesions stained for keratin, desmin, or S-100 protein. Ultrastructural examination of two cases revealed cells with a constellation of fibroblastic, myofibroblastic, and histiocytic features. Follow-up of seven patients, averaging 58 months from diagnosis, confirmed that all are alive and well. Recognition of this cellular variant of proliferative fasciitis and myositis is important to prevent misdiagnosis as a sarcoma and unnecessary, excessive therapy.

Actins

Plantar fasciitis: MR imaging.

The clinical presentation of plantar fasciitis may be mimicked by a number of other painful heel conditions. Thus, magnetic resonance (MR) imaging was used to develop objective morphologic criteria to establish a diagnosis of plantar fasciitis in eight patients. Sagittal T1-weighted and coronal intermediate and T2-weighted images of symptomatic and asymptomatic feet were obtained; additional sequences were used for symptomatic feet. Maximum thickness of the plantar fascia was significantly increased (P less than .0001) in patients with plantar fasciitis (sagittal, 7.40 mm +/- 1.17, and coronal, 7.56 mm +/- 1.01) compared with age- and sex-matched volunteers (sagittal, 3.22 mm +/- 0.44, and coronal, 3.44 mm +/- 0.53) and young male controls (sagittal, 3.00 mm +/- 0.8, and coronal, 3.00 mm +/- 0.0). Furthermore, nine of 10 feet with plantar fasciitis had areas of moderately increased signal intensity in the substance of the fascia. MR imaging may provide an objective assessment of the morphologic changes associated with plantar fasciitis, as well as assist in excluding other causes of heel pain.

Adult