Paraneoplastic fasciitis and polyarthritis syndrome as a manifestation of breast cancer recurrence in a BRCA1 gene-positive patient.

Abstract

Dear Editor, A 62-year-old woman presented to the rheumatology outpatients clinic with a 2-month history of symmetrical inflammatory polyarthritis affecting the metacarpophalangeal joints (MCPJs) and proximal interphalangeal joints (PIPJs). Other complaints included generalized fatigue and mild myalgia without weakness. There were no features of a connective tissue disorder. The patient had been started on prednisone by her family doctor with minimal relief of symptoms. The patient was known to be a carrier of the BRCA1 tumor suppressor gene and had undergone prophylactic oophorectomy 15 years prior. In 2013 a routine mammogram identified an early localized breast lump which was treated with a bilateral mastectomy. Histology confirmed estrogen and progesterone receptor (ER/PR) and (HER) Human epidermal growth factor receptor negativity so there was no role for tamoxifen or an aromatase inhibitor. Chemotherapy was felt to be of minimal benefit so was not administered. Past medical history was otherwise unremarkable. Examination revealed tenderness across multiple MCPJs and PIPJs with mild synovitis of a number of joints. An unusual feature was non-tender, purple erythematous nodularity of the palms without flexor tenosynovitis (Fig. 1). There was no sclerodactyl, nail bed changes or telangiectasia. General examination was unremarkable. Investigations included unremarkable inflammatory markers and negative rheumatoid factor (RF), anticyclic citrullinated peptide antibody (anti-CCP), antinuclear antibodies (ANA), extractable nuclear antigen (ENA) and double-stranded DNA. X-rays of the hands showed changes of early nodal osteoarthritis. The initial diagnosis was of a seronegative arthritis with atypical features. Methotrexate was started and prednisone was weaned. Over the following 6 weeks the patient developed rapidly progressive palmar fasciitis with marked fixed flexion deformities. She was unable to make a fist and had difficulty performing her job as a receptionist. An area of erythema developed on the reconstructed breast so a tissue biopsy was performed. This revealed recurrence of initial ER/PR/HER negative breast cancer within the dermal lymphatics. A diagnosis of paraneoplastic palmer fasciitis and polyarthritis syndrome was made. Methotrexate was stopped and ongoing symptoms were managed with anti-inflammatories. The patient was referred to the oncology service for further management. A re-staging computed tomography (CT) scan and nuclear medicine bone scan did not suggest metastatic disease. Adriamycin and cyclophosphamide chemotherapy was administered prior to further surgery. With chemotherapy the patient's palmar fasciitis and polyarthritis progression halted, although the palmar contractures have not at this stage resolved. Rheumatologists can be faced with a number of paraneoplastic syndromes such as palmar fasciitis with polyarthritis, remitting seronegative symmetrical synovitis with pitting edema (RS3PE), paraneoplastic polymyalgia rheumatica, hypertrophic osteoarthropathy, dermatomyositis and paraneoplastic vasculitis.1 Palmer fasciitis and polyarthritis was first identified as a rare paraneoplastic syndrome in 1982 by Medsger et al.2 The syndrome is most commonly described with ovarian cancer, although other malignancies including pancreatic, gastric, prostate, lung, breast and uterine have been reported.3-8 The paraneoplastic syndrome can precede the diagnosis of cancer, occur simultaneously or as in this case be a sign of disease recurrence. The condition is characterized by palmar fasciitis often with rapidly progressive flexion deformities and diffuse synovitis of the hands. Other joints are usually spared and plantar fasciitis rarely manifests. Indurated reticular palmar erythema and nodularity of the flexor tendons may be seen.9 Laboratory investigations including inflammatory markers and serology for autoantibodies are commonly unremarkable. X-rays may show periarticular demineralization without erosive changes3, 8 while ultrasound and magnetic resonance imaging have shown synovitis, tenosynovitis and soft tissue edema suggestive of nonspecific inflammation.8 Differentials could include systemic sclerosis, Dupuytren's disease, eosinophilic fasciitis or a complex regional pain syndrome (CRPS). The absence of Raynaud's phenomena, telangectasia, calcinosis or nailbed vasculitis with negative autoimmune serology would go against a diagnosis of systemic sclerosis. Dupuytren's disease would not be associated with an inflammatory polyarthritis and not commonly be as rapidly progressive. CRPS would typically be unilateral in nature, have associated vasomotor features and often occur following a localized insult. Eosinophilic fasciitis is often accompanied by blood eosinophilia and infrequently affects the hands. The underlying cause of palmar fasciitis and polyarthritis is not well understood. It has been proposed that the underlying mechanism is of fibrogenic growth factor production.3 Biopsies have revealed immunoglobulin deposition suggesting the cause involves an immune process.5 The syndrome typically responds poorly to anti-inflammatories and steroids. Anti-rheumatic drugs, including methotrexate, hydroxychloroquine, sulfasalazine and anti-tumor necrosis factor, have been used with disappointing results.3, 5, 8 Treatment of the underlying malignancy has been effective for the inflammatory symptoms, although the palmar contractures usually persist.4, 7 Atypical arthropathy, especially if accompanied by palmar fasciitis should raise the possibility of a paraneoplastic phenomenon such as palmar fasciitis and polyarthritis syndrome. This may allow earlier detection of the underlying malignancy and potentially improve treatment outcomes.