Australasian Journal of Dermatology (2008) 49, 27–29
doi: 10.1111/j.1440-0960.2007.00415.x
CASE REPORT
Eosinophilic fasciitis as a paraneoplastic phenomenon associated with metastatic colorectal carcinoma Hamish Philpott,1 Pravin Hissaria,1 Lachlan Warrren,2 Nimit Singhal,3 Michael Brown,3 Susanna Proudman,4 Les Cleland4 and David Gillis1 Departments of 1Allergy and Immunology, 3Medical Oncology and 4Rheumatology, Royal Adelaide Hospital, Adelaide, and 2Norwood Skin Clinic, Norwood, South Australia, Australia
SUMMARY A 72-year-old man presented with erythema and induration of his calves and forearms. He had a past history of stage 1 colorectal carcinoma, treated with resection and primary anastamosis 4 years earlier. A diagnosis of eosinophilic fasciitis was made based on the characteristic clinical appearance, peripheral blood eosinophilia and a skin biopsy. There was no improvement in the condition following treatment with prednisolone or methotrexate. One year later, abnormal liver function studies were noted, and an abdominal computed tomography scan and subsequent needle biopsy of the liver confirmed a neoplastic lesion in the liver consistent with a metastatic colorectal carcinoma. Systemic chemotherapy with oxaliplatin, 5-fluorouracil and capecitabine was commenced, and resulted in partial remission of the colorectal carcinoma. Simultaneously, the indurations of the forearms and calves also improved, suggesting that the eosinophilic fasciitis was a paraneoplastic phenomenon. Keywords: fasciitis–panniculitis syndrome, malignancy, scleroderma-like conditions, treatment.
INTRODUCTION Eosinophilic fasciitis is a rare disorder of unknown aetiology, characterized clinically by symmetrical thickening and induration of the skin involving the proximal limbs and trunk, but notably sparing the hands and feet.1 Drugs, vigorous exercise, Borrelia infection and malignancy2 have been implicated in the pathogenesis of this condition;
Correspondence: Dr Pravin Hissaria, Department of Allergy and Immunology, Royal Adelaide Hospital, North Terrace, Adelaide, SA 5000, Australia. Email:
[email protected] Hamish Philpott, MRCP. Pravin Hissaria, FRCPA. Lachlan Warrren, FACD. Nimit Singhal, FRACP. Michael Brown, FRACP. Susanna Proudman, FRACP. Les Cleland, MD. David Gillis, FRCPA. Submitted 1 May 2007; accepted 13 September 2007.
however, most cases are idiopathic. Immunosuppressive medications have been used to treat this condition: partial improvement with corticosteroids is often noted.3 Cases associated with malignancy are often refractory to corticosteroids, but may respond to chemotherapy.4 We present a patient who developed eosinophilic fasciitis in association with metastatic colorectal carcinoma.
CASE REPORT A 72-year-old man presented with a 3-month history of erythema and thickening of the skin of his extremities. This was accompanied by anorexia and a weight loss of 10 kg in 3 months. He denied any history of Raynaud’s phenomenon, dysphagia, arthritis, muscle weakness, shortness of breath or fever. Four years earlier, he had been diagnosed with stage I colorectal carcinoma that was successfully resected with primary anastomosis. There was no clinical evidence of recurrence on regular follow up. He also had hypertension that was controlled with amlodipine 5 mg daily. On examination, there was skin thickening, induration and erythema affecting his legs and arms. There was neither skin thickening of the hands, feet or face, nor any digital ulcers or nail fold capillary changes. The rest of his physical examination was unremarkable. Investigations revealed a peripheral blood eosinophilia with mild elevation of liver enzymes (Table 1). Autoantibody tests were negative, in particular the antinuclear antibodies by indirect immunofluorescence and extractable nuclear antibodies. A CT scan of the chest and abdomen was unremarkable. A deep punch skin biopsy from the forearm showed a low-grade inflammatory infiltrate, including conspicuous eosinophils of the superficial and deep dermis extending into the subcutaneous fat space and fascia with some oedema and early fibrous thickening (Fig. 1), suggestive of eosinophilic fasciitis. A diagnosis of eosinophilic fasciitis
Abbreviation: CT
© 2008 The Authors Journal compilation © 2008 The Australasian College of Dermatologists
computed tomography
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Table 1
Routine investigations at presentation
Parameter
Values
Normal range
Haemoglobin (g/L) White cell count (n/L) Neutrophils (n/L) Lymphocycte count (n/L) Eosinophil count (n/L) Total bilirubin (mmol/L) Alanine aminotranferase (U/L) Aspartate aminotranferase (U/L) g-1-Glutamate transferase (U/L) Alkaline phosphatase (U/L) Antinuclear antibodies Extractable nuclear antigens
11.5 7 ¥ 109 2 ¥ 109 3.7 ¥ 109 1.1 ¥ 109 7 60 70 210 160 Undetectable Undetectable
135–175 4.0–11.0 ¥ 109 1.8–7.5 ¥ 109 1.0–3.5 ¥ 109 0.05–1 ¥ 109 6–24 0–45 0–55 0–60 30–110 Undetectable Undetectable
Bold type denotes abnormal values.
ments seven and eight of the liver associated with bile duct dilatation. Subsequent CT and positron emission tomography scans confirmed an isolated hepatic lesion suspicious of malignancy. The carcinoembryonic antigen level at this stage was 97 mg/L (NR < 10 mg/L). An ultrasound-guided liver biopsy of the lesion demonstrated adenocarcinoma, consistent with metastasis from his colorectal carcinoma. As this was considered to be inoperable, systemic chemotherapy consisting of six cycles of oxaliplatin, 5-fluorouracil and capecitabine was given. The methotrexate was stopped, and he continued on 7 mg daily of oral prednisolone. This resulted in partial reduction in the size of the liver lesion. Simultaneously, there was improvement in the skin thickening after two monthly cycles of chemotherapy and, by the end of six cycles (6 months), the skin had softened and was less erythematous. Six months after ceasing chemotherapy, the liver lesion had started to increase in size, but the skin remained unchanged.
DISCUSSION
Figure 1 Skin biopsy of right forearm showing mixed inflammatory infiltrate, including conspicuous eosinophils, in fascia and interlobular septa (H&E stain).
was made, given the clinical picture of proximal skin thickening, peripheral eosinophilia and a supportive skin biopsy. He was treated with oral prednisolone at a dose of 1 mg/kg daily. After 4 weeks, there was no improvement in the skin thickening, so oral methotrexate was started at a dose of 15 mg weekly as an additional anti-inflammatory agent. Prednisolone was subsequently tapered to a maintenance dose of 10 mg daily after 3 months. Over the next 1 year, the skin thickening and induration worsened with progressive truncal involvement despite increasing the dose of oral methotrexate to 25 mg weekly, and the addition of oral sulfasalazine 2 g daily. He lost an additional 5 kg in weight during this period. The CT scan now showed focal duct dilatation in segments seven and eight of the liver with no definite space-occupying lesion. Liver function tests were unchanged. The aetiology of this lesion was unclear, and it was not amenable to biopsy at this stage. An abdominal ultrasound performed after a further 3 months revealed a 7-cm, irregular calcified lesion in seg-
The coexistence of eosinophilic fasciitis and malignancy suggesting a paraneoplastic phenomenon is rare. In our case, the eosinophilic fasciitis preceded the detected metastases by 15 months, was unresponsive to corticosteroid therapy and improved following chemotherapy for the cancer. This is consistent with a paraneoplastic phenomenon.3 Eosinophilic fasciitis is sometimes categorized with fibrosing conditions or scleroderma-like diseases having similar histopathological features under the term ‘fasciitis– panniculitis syndromes’.4 The largest case series described 12 patients of whom eight were female and nine had haematological malignancy. The skin changes preceded the cancer diagnosis by a median of 1 year (range 0–3 years) and were unresponsive to prednisone therapy.5 There were three patients with solid malignancies: two breast and one prostate. The largest single centre experience of 52 patients from the Mayo Clinic, retrospectively describing patients with eosinophilic fasciitis, found only three cases associated with haematological malignancy and one with breast malignancy. Notably, there was complete resolution of eosinophilic fasciitis following mastectomy for breast cancer.6 A recent retrospective case series of 11 patients did not report any association with malignancy. However, one of the patients developed aplastic anaemia on follow up, which again underlines the association of this condition with haematological disorders.1 Treatment of cancer-associated eosinophilic fasciitis is usually difficult. Resistance to immunosuppressives, including corticosteroids, is common. Treatment of the underlying malignancy or the use of the H2-blocker cimetidine (given the elevations of plasma histamine in eosinophilic fasciitis) may result in cutaneous improvement.4 Surgical procedures, including fasciectomies, may be required in severe and resistant cases associated with marked functional impairment.7 We present a case of eosinophilic fasciitis with the previously undescribed association of colonic malignancy. The need to investigate a patient with eosinophilic fasciitis for
© 2008 The Authors Journal compilation © 2008 The Australasian College of Dermatologists
Paraneoplastic eosinophilic fasciitis an underlying malignancy (including a complete blood count and further investigations based on history and examination and for sex/age-appropriate malignancies), particularly when the condition is not responsive to corticosteroids, is illustrated.
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© 2008 The Authors Journal compilation © 2008 The Australasian College of Dermatologists
