Australasian Journal of Dermatology (2009) 50, 198–201
doi: 10.1111/j.1440-0960.2009.00538.x
CASE REPORT
Indurated reticulate palmar erythema as a sign of paraneoplastic palmar fasciitis and polyarthritis syndrome ajd_538
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Veronica A Preda,1 Peter Frederiksen2 and Steven Kossard1 1
Skin and Cancer Foundation Australia, Sydney, and 2Consultant Dermatologist, Hornsby, New South Wales, Australia
ABSTRACT A 62-year-old woman presented with a 6-month history of polyarthritis. She had also noted a 2-month history of indurated palmar erythema and increasing bilateral hand swelling and stiffness. A biopsy from the area of palmar erythema showed interstitial fibroplasia within the dermis and subcutis representing a palmar fibromatosis. This presentation appears to belong to the spectrum of palmar fasciitis and polyarthritis syndrome. Rheumatologists have recognised this syndrome as a paraneoplastic disorder and subsequent investigations in our patient revealed an elevated cancer antigen 125 and an inoperable ovarian carcinoma. Indurated palmar erythema is a sign that is not widely recognised by dermatologists as a clue for this paraneoplastic syndrome, and skin biopsy demonstrating dermal and subcutaneous fibroplasia may help in diagnosis in the absence of advanced signs of palmar fasciitis. Key words: ovarian carcinoma, palmar erythema, palmar fasciitis and polyarthritis syndrome, palmar fibromatosis, paraneoplastic.
INTRODUCTION Paraneoplastic syndromes are those cancer-associated syndromes that occur at a distance from the primary tumour or metastases and are induced by the malignancy through hormones, peptides autocrine and paracrine mediators, antibodies and cytotoxic lymphocytes.1 PFPA syndrome is widely recognised by rheumatologists and is most commonly asso-
Correspondence: Dr Veronica Preda, Skin & Cancer Foundation, 277 Bourke Street, Darlinghurst, NSW 2010, Australia. Email:
[email protected] Veronica A Preda, MB BS. Peter Frederiksen, FACD. Steven Kossard, FACD. Submitted 24 October 2008; accepted 4 November 2008.
ciated with malignancy as a paraneoplastic phenomenon, but has also been linked to other factors.2 It may precede, occur simultaneously or follow the diagnosis of malignancy.3 In this report, we present a patient with persisting polyarthritis and bilateral indurated palmar erythema demonstrating palmar fibromatosis on skin biopsy, which prompted further investigation for a malignant tumour.
CASE REPORT A 62-year-old Caucasian woman presented with a 2-month history of unusual bilateral reticulated palmar erythema extending over the fingers. She noted central palmar tenderness and induration but no evident contractures of the fingers or gross palmar nodules. These palmar changes developed on a background of a 6-month history of rheumatological symptoms, including generalized progressive musculoskeletal discomfort and a new-onset asymmetrical polyarthritis. The history was of tenderness, arthralgias of the shoulders, knees, hips, hands and feet, and progressive painful restriction in movement. She also reported a concurrent history of increasing fatigue. There was no history of prior rheumatological disease, Raynaud’s phenomenon or trauma. Despite a decreased appetite her weight had remained stable. There was no history of change in bowel habit, haematuria, per rectal or per vaginal bleeding, or cough. Her past medical history included hypothyroidism, for which she was taking thyroxine. A bone scan demonstrated widespread changes consistent with arthritis. She was initially prescribed meloxicam 15 mg p.o. daily and glucosamine sulfate 1.5 g p.o. daily for the polyarthritis, with no improvement. She was an ex-smoker and drank minimal alcohol. Regarding her family history, her mother died of metastatic carcinoma, presumed to be primary
Abbreviations: CA-125 PFPA
© 2009 The Authors Journal compilation © 2009 The Australasian College of Dermatologists
cancer antigen 125 palmar fasciitis and polyarthritis
Indurated reticulate palmar erythema
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Figure 1 Presenting feature of bilateral reticulated palmar erythema extending over the fingers.
kidney, and her father from metastatic carcinoma of the pancreas. Her brother has had carcinoma of the kidney and is well post-nephrectomy. Physical examination revealed infiltrated reticulate palmar erythema extending onto the fingers (Fig. 1). An initial punch biopsy of the palm showed interstitial fibrohistiocytes in the dermis and was diagnosed as a possible fibrous histiocytoma. After our clinical review a further biopsy to a depth of 5 mm was taken from the left palm (Fig. 2a,b). Skin sections showed an epidermis of normal thickness, under which there were increased numbers of fibroblasts and histiocytes that extended interstitially between the collagen bundles of the dermis (Fig. 2c). The fibrohistiocytes were also evident in the widened septa of the subcutis and extended to the full depth of the biopsy. The dermal vessels were dilated but there were only sparse lymphocytes and there was no liquefactive degeneration of the junctional zone. The biopsy was superficial and the underlying fascia was not sampled. Immunoperoxidase stains demonstrated strong positive stain of the fibroblasts with procollagen-1 (Fig. 3). There were increased numbers of factor XIIIa positive spindle cells but the cells were negative for CD34,CD1a, S100, CD10, panactin (HHF35) and nerve growth factor receptor (p75). CD68 highlighted scattered dendritic cells within the dermis. These findings supported a diagnosis of a palmar fibromatosis, as the spindle cells expressed principally procollagen-1. With the combined history of progressive polyarthritis, this presentation was linked to a group of patients described previously in the rheumatological literature as PFPA syndrome, which frequently has proved to be paraneoplastic.2 Subsequent oncological review revealed palpable lymphadenopathy in the axilla and left supraclavicular fossa.
Tumour markers were performed, yielding a moderately high CA-125 measuring 1516 (reference range 2–35 U/mL), and a computed tomography scan of the chest, abdomen and pelvis demonstrated heterogeneous soft-tissue masses within the pelvis and retroperitoneal region, in addition to left-sided axillary lymphadenopathy, suspicious of malignancy. Fine-needle aspirate biopsy of an axillary lymph gland revealed a metastatic adenocarcinoma with an immunoperoxidase pattern consistent with an ovarian carcinoma. Surgery for debulking of the pelvis followed by a standard intravenous chemotherapy regimen for ovarian cancer, with carboplatin (total dose mg = target area under curve ¥ (GFR + 25) ([mg/mL] ¥ minute) (target 6 mg/mL ¥ minute) and docetaxel 75 mg/m2, was administered. Our patient noted a significant reduction in her symptoms in the immediate post-operative period.
DISCUSSION PFPA syndrome is an uncommon disorder characterized by progressive flexion contractures of hands, inflammatory fasciitis, fibrosis and generalized inflammatory arthritis. This combination of signs was first described in the literature as a paraneoplastic phenomenon in association with ovarian cancer.4 Although often associated with malignancy, non-neoplastic presentations of PFPA have been described.5,6 Non-paraneoplastic PFPA syndrome has been seen in association with tuberculosis, thyroid disease, benign ovarian cyst and as an isolated finding.6 In paraneoplastic cases the most frequent associated malignancy is ovarian cancer,4 but other tumours reported include gastric cancer,7 colonic carcinoma,7 pancreatic carcinoma,8 nonsmall cell lung cancer,9 breast cancer,10 tubal carcinoma,11 cervical carcinoma3 and prostate cancer.5
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b
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Figure 2 (a) Biopsy from left palm showing extensive interstitial fibroblasts throughout dermis and within widened fat septa (H&E). (b) Biopsy from left palm showing upper dermis with increased interstitial fibroblasts and scattered mononuclear cells (H&E). (c) Biopsy from left palm showing detail of deeper dermis and widened septae with interstitial fibroblasts (H&E).
Figure 3 Biopsy from left palm. Immunoperoxidase stain demonstrating spindle cells that are strongly positive for procollagen-1, consistent with fibroblasts.
The underlying pathogenic pathway driving the fibroplasia and polyarthritis remains unknown. In the literature it has been quoted to be along the spectrum of a reflex sympathetic dystrophy; however, it is more rapidly progressive and there are no vasomotor or sudomotor disturbances in PFPA syndrome.7 Our patient presented with an unusual reticulate palmar erythema that was indurated and localized to the central palm. More commonly, non-indurated palmar erythema that is concentrated over the periphery of the palm is encountered clinically. Non-indurated palmar erythema, localized to the periphery, is associated with a variety of disorders, particularly liver disease, but also includes malignancy with tumours producing angiogenic mediators and oestrogens.12 Palmar biopsy in non-indurated palmar erythema shows non-diagnostic features and lacks the interstitial fibroplasia seen with palmar fibromatosis. In terms of treatment for the PFPA syndrome, curative therapy of the paraneoplastic illness is considered to involve removal of the underlying tumour.9 It is reported that if the ovarian carcinoma remits the PFPA symptoms abate, although contractures may remain.13 The relentless course of the indurated palmar erythema in the presence of progressive polyarthritis was an indicator for a paraneoplastic presentation of PFPA in our patient and prompted oncological review. Previous reports of PFPA indicate that the severity of the symptoms may be disproportionate to the clinical findings and that glucocorticoid or non-steroidal anti-inflammatory drugs are often ineffective in relieving the arthritic symptoms.3,14 In our own patient, initial non-steroidal and multivitamin therapy, as well as subsequent oral corticosteroids, were ineffectual in controlling the symptoms. The findings on palmar biopsy in our patient are shared by a variety of benign fibrohistiocytic conditions, ranging from fibrohistiocytic tumours to healing skin and scars. Although not present in our patient, vasculitis has been
© 2009 The Authors Journal compilation © 2009 The Australasian College of Dermatologists
Indurated reticulate palmar erythema rarely reported in association with the histopathology of this condition.15 The correct histopathological diagnosis of palmar fibromatosis ultimately required correlation with the clinical presentation, but formed an integral clue to recognising the PFPA syndrome and our search for occult malignancy. Indurated palmar erythema is a sign that is not widely recognised by dermatologists as a clue for this paraneoplastic syndrome, and skin biopsy demonstrating dermal and subcutaneous fibroplasia may help in diagnosis in the absence of advanced signs of palmar fasciitis.
The authors thank both Dr M Podogorski and Dr Josie Rutovitz for the oncological investigations of the patient reported here.
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ACKNOWLEDGEMENTS
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© 2009 The Authors Journal compilation © 2009 The Australasian College of Dermatologists
