The Kennedy Institute of Rheumatology, 1 Aspenlea Road, Hammersmith, London W6 8LH and
1 Department of Rheumatology, Central Middlesex Hospital, Acton Lane, Park Royal, London NW10 7NS, UK
SIR, Four types of Kaposi's sarcoma (KS) are recognized: (i) classic KS, which is an indolent disease predominantly affecting the lower legs of eastern European Ashkenazi Jews; (ii) African endemic KS; (iii) HIV-related KS; and (iv) iatrogenic KS following immunosuppressive therapy.
We describe two patients who developed KS after low-dose corticosteroid treatment for underlying rheumatological disease in the absence of underlying immunosuppression.
Patient 1 was an 84-yr-old Polish immigrant of 40 years who was referred to the rheumatology clinic with a short history of stiffness and aching in the limb girdles. Abnormal investigations included the following: haemoglobin 10.2 g/dl; erythrocyte sedimentation rate (ESR) >100 mm/h; C-reactive protein (CRP) 179 mg/l. Autoantibodies and paraproteins were not detected. A clinical diagnosis of polymyalgia rheumatica was made and the patient was treated with prednisolone 20 mg/day for 6 weeks followed by gradual dose reduction to 10 mg over 12 weeks. There was a marked clinical improvement associated with a fall in her ESR to 20 mm/h. Four months after the start of treatment she developed a raised purpuric rash over her left shin extending onto the foot and toes (Fig. 1). Over the next month it extended up her leg with the development of lymphoedema. A skin biopsy showed spindle-shaped cells with large vascular spaces typical of KS, and serology demonstrated high-titre IgG antibody to human herpesvirus-8 (HHV-8).
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Iatrogenic KS was first described among post-transplant patients on high-dose immunosuppressive therapy. In one series [1], KS accounted for 3% of de novo neoplasms after organ transplantation. More recently, corticosteroids (CS) have been linked to the development of KS. In a series by Trattner et al. [2] from Israel, eight patients developed KS after a mean of 13.7 weeks of oral prednisolone treatment. Three patients were on low-dose corticosteroids (20 mg or less), and all of them had Jewish ancestry. Further cases include the development of KS in a rheumatoid arthritis patient after intra-articular injection of CS [3] and after topical application of CS for lichen planus [4]. In the majority of these cases withdrawal of CS led to resolution or improvement of the KS lesion.
In 1994 Chang et al. [5] described a novel herpesvirus from a KS lesion in an HIV-positive patient [5] which was named human herpesvirus-8 (HHV-8). It was subsequently isolated from all types of KS lesions, including corticosteroid-induced KS [6]. Prior infection with HHV-8 is a requisite for the development of disease and it is likely in each of our cases that infection was acquired (by a sexual or vertical route) whilst the patient was living in an endemic area before emigrating to the UK. Both patients were elderly and neither had significant lymphopenia. They had not been sexually active since arriving in the UK, making recent infection (with HHV-8 or HIV) extremely unlikely.
Whilst their advanced age may have contributed to the risk of KS, there is no evidence that either of these patients was significantly immunosuppressed by their disease or treatment. The question arises as to how steroid treatment alone can lead to the emergence of this malignancy. Recent in vitro evidence supports the hypothesis that glucocorticoids have a direct role in stimulating tumour development and growth. Guo et al. [7] have studied KS tumour cells from individuals with HIV and have shown that exogenous glucocorticoids stimulate their proliferation. They demonstrated that the glucocorticoid receptors are present at high levels on KS lesions and that receptors can be up-regulated by exogenous glucocorticoid and inflammatory cytokines [8]. Hudnall et al. [9] have reported increased viral replication and activation of the lytic cycle of HHV-8 after glucocorticoid administration in transfected cells. Thus the effects of glucocorticoids are two-fold: the up-regulation of Kaposi cell proliferation and the activation of HHV-8.
In north-western Europe, corticosteroid-induced KS may not be considered in a patient with rheumatic disease because HHV-8 infection is rare and KS is usually associated with high-dose immunosuppressive therapy or HIV. However, we have confirmed previous reports that modest doses of steroids can be causally linked to the malignancy in a susceptible patient, and that it can occur in routine rheumatological practice in a non-HHV-8-endemic area.
Notes
Correspondence to: T. Vincent, The Kennedy Institute of Rheumatology, 1 Aspenlea Road, Hammersmith, London W6 8LH, UK.
References