Rheumatology Advance Access originally published online on August 9, 2005
Rheumatology 2006 45(1):119-120; doi:10.1093/rheumatology/kei072
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LETTER TO THE EDITOR |
Systemic sclerosis, morphoea and breast cancer
Department of Rheumatology, Ysbyty Gwynedd, Bangor and University of Wales, Bangor and 1 Department of Rheumatology, Ysbyty Glan Clwyd, Bodelwyddan, UK
Correspondence to: P. Maddison, Department of Rheumatology, Ysbyty Gwynedd Hospital, Bangor LL57 2PW, UK. E-mail: peter.maddison{at}nww-tr.wales.nhs.uk
SIR, systemic sclerosis (SSc) and localized scleroderma (LS) are generally considered to be different entities. Raynaud's phenomenon, sclerodactyly, internal organ involvement and scleroderma-specific autoantibodies are usually not observed in LS. Nevertheless, there have been occasional reports of SSc and LS occurring together or LS evolving into SSc [1], suggesting a link between these disorders. We therefore describe a woman with SSc who developed typical lesions of generalized morphoea. A year later, invasive ductal carcinoma of breast was diagnosed. We discuss the rare coexistence of systemic sclerosis and morphoea, and the possible implications of breast cancer.
A 47-yr-old woman from North Wales presented in February 2003 with a 10-month history of Raynaud's phenomenon, arthralgia and mild heartburn. There was no other relevant past or family history, and no reported exposure to chemicals or toxins. On examination, the significant findings were sclerodactyly, a positive ‘prayer sign’ and abnormal nail fold capillaroscopy with capillary dropout. There was no clinical internal organ involvement; haematology, biochemistry, chest X-ray, pulmonary function tests and 2D echocardiogram results were normal. The ANA was positive at 1:160, in a nucleolar pattern. Limited cutaneous SSc was diagnosed.
In June 2003, she developed progressively enlarging intensely pruritic, hyperpigmented lesions on the back of both knees, the posterior aspect of both thighs and the outer aspect of the upper arms bilaterally. Examination showed extensive, confluent, hyperpigmented, indurated lesions with a violaceous, erythematous border typical of generalized morphoea. The surrounding skin was normal and there was no extension of sclerodactyly or any other clinical development. Methotrexate 15 mg once a week was started.
In June 2004, she reported a lump in the upper outer quadrant of left breast, present for 3 months. The patient had undergone pan-hysterectomy in 1994 and was on hormone replacement therapy (HRT). Histology confirmed an invasive ductal carcinoma of the breast. HRT was discontinued. Left mastectomy with axillary clearance surgery was followed by adjuvant chemotherapy with epirubicin for 3 months, then anastrozole 1 mg daily. By October 2004, there was a marked improvement in the morphoea. Induration of the skin and subcutaneous tissue had receded completely with only residual hyperpigmentation. Arthralgia and sclerodactyly remained unchanged. Methotrexate was continued.
Although considered to be rare, coexistence of SSc and LS has been reported in the past. Soma et al. [2] reported that 6.7% of 135 SSc patients at presentation had additional lesions of LS. Mizutani et al. [3] described recurrent morphoea lesions over 6 yr in a patient with SSc. Conversely, Rosenberg et al. [4] reported a positive ANA in 63% of children with LS. The scleroderma specific anticentromere antibody was detected in three of 25 patients with LS in another study [5]. Maricq [6] reported two of 27 LS patients with Raynaud's and fully established SSc.
SSc, but not LS, has been associated with approximately a two-fold increase in malignancy, the greatest risk being for lung cancer [7]. The results have been non-uniform and inconclusive for breast cancer. As reviewed in [7], a large population-based Australian study reported an insignificant increase whereas a Swedish study found no increase in breast cancer in SSc. Furthermore, a USA study reported no increase in breast or lung cancer but rather a non-significant decrease in risk of both. Although by itself not associated with increased risk of malignancy, LS may occur following radiotherapy for breast or other cancers.
The mechanisms explaining a relationship between SSc and cancer are unknown. A multitude of factors such as exposure to environmental agents, prior genetic damage, immunosuppressive therapy or paraneoplastic phenomenon have been implicated as potential common links between the two conditions [8]. Breast cancer in our patient developed within 2 yr of the onset of scleroderma. She had symptoms of breast cancer before methotrexate therapy was instituted and had never received radiotherapy. It is likely that the 10 yr of HRT was a contributing risk factor. HRT, however, is associated with an increased risk of lobular but not ductal carcinoma [9]. It remains unexplained why the morphoea improved dramatically within months of treating the breast cancer. While this may have been in response to cancer chemotherapy, another possibility was the eradication of the breast tumour per se since the morphoea in this setting was unusual and may have represented a paraneoplastic syndrome.
In summary, this case highlights the interesting association between SSc and LS. Such cases, although rare, might provide important clues to the pathogenesis of scleroderma. Development of breast cancer in such a rare clinical situation points to the possibility of common links between the three conditions.
The authors have declared no conflicts of interest.
References
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- Soma Y, Tamaki T, Kikuchi et al. Coexistence of morphea and systemic sclerosis. Dermatology 1993;186:103–5.[Medline]
- Mizutani H, Tanaka H, Okada H et al. Palindromic morphea: multiple recurrence of morphea lesions in a case of systemic sclerosis. J Dermatol 1992;19:298–301.[Medline]
- Rosenberg AM, Uziel Y, Krafchik BR et al. Antinuclear antibodies in children with localized scleroderma. J Rheumatol 1995;22:2337–43.[Web of Science][Medline]
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[Abstract/Free Full Text] - Pearson JE, Silman AJ. Risk of cancer in patients with scleroderma. Ann Rheum Dis 2003;62:697–9.
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- Li CI, Anderson BO, Daling JR, Moe RE. Trends in incidence rates of invasive lobular and ductal breast carcinoma. JAMA 2003;19:1421–4.
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