01 August 2012: Case Study
Disseminated cutaneous Kaposi sarcoma in a patient receiving triptolide/tripdiolide for rheumatoid arthritis
Alicja E. Grzegorzewska ABCDEFG , Dorota Frankiewicz ABD , Danuta Bręborowicz ABD , Irena Matławska BDFG , Wiesława Bylka BDF
DOI: 10.12659/MSM.883256
Med Sci Monit 2012; 18(8): CS67-71
Background
Our aim is to show a case of disseminated cutaneous Kaposi sarcoma (KS), occurring during a long-term usage of a powder containing triptolide/tripdiolide, for treatment of rheumatoid arthritis (RA). Triptolide and tripdiolide, compounds originally purified from
Case Report
AN ANALYSIS OF THE POWDER:
We have suspected that the powder could contain compounds of
Qualitative examination was done using Liquid Chromatography Electrospray Ionization Mass Spectrometry (LC/ESI-MS) system [13]. The presence of triptolide m/z=359 (M-H−) and tripdiolide m/z=375 (M-H−), 2 major active components of Trypterigium wilfordii Hook F, was confirmed. The content of triptolide in 1 g of the analyzed sample, determined by HPLC quantitative analysis, was 235 μg.
Discussion
A question arises how triptolide/tripdiolide, taken in the high daily dose [4] for years, could influence the patient’s health status.
Triptolide is a small molecule known to act as an anti-inflammatory [14] and anti-cancer [15] compound. Its anti-inflammatory and immunosuppressant activities are used in the treatment of RA [4]. AA amyloidosis, present in 4.44% of early RA patients [16], was shown to be inhibited in mice by experimental treatment with triptolide [17]. About 40 years had passes since diagnosis of RA in the examined patient. Joint surgery was never indicated. Amyloidosis was not detected, at least up to 62 year of age. Thus, progression of RA seemed to be slower than usually observed [18], independently of triptolide/tripdiolide administration. However, only while receiving triptolide/tripdiolide was she almost free from joint pain.
The most important point to determine is the possible association of KS with triptolide/tripdiolide medication. KS is a multifocal angioproliferative neoplasm of the skin (mainly affecting the skin of the limbs) and mucosa, frequently seen in immunosuppressed patients [19], also due to RA [12,20]. HHV8 is the infectious cause of this neoplasm. Over 95% of KS lesions, regardless of their source or clinical subtype, have been found to be infected with HHV8 [21]. HHV8 latent transcripts, such as latency-associated nuclear antigen, viral cyclin, viral FLIP and viral-encoded microRNAs, drive cell proliferation and prevent apoptosis, whereas HHV8 lytic proteins such as viral G protein-coupled receptor, K1 and virally encoded cytokines (viral interleukin-6 and viral chemokines) contribute to the angioproliferative and inflammatory KS lesions through a mechanism called paracrine neoplasia [22]. In patients infected with HIV, KS is associated with a low CD4 lymphocyte count [23–25]. Expression of the proliferative antigen Ki-67, shown in our patient in 20–30% of cell nuclei, does not correlate with skin and organ lesions [26] or early- and late-stage KS lesions [27], but is valuable in KS diagnosis. Triptolide has immunosuppressant activity [28]. Decreasing CD4 cells [29], triptolide could contribute to development of KS by reactivation of latent HHV8, permitted by triptolide-induced immunosuppression [5]. On the other hand, triptolide is an anti-cancer compound [15,30] and KS is not mentioned among the adverse effects of triptolide, ethyl acetate extracts or polyglycosides of the Chinese herbal remedy
Conclusions
Although we cannot definitively answer the question of whether triptolide/ tripdiolide contributed to development of KS in our patient, we also cannot exclude such a possibility. The case of our patient indicates an association between triptolide/tripdiolide chronic intake and development of HHV8 KS. Triptolide/ tripdiolide could contribute to development of KS by reactivation of latent HHV8, permitted by immunosuppression induced by triptolide. We believe that this case will help other physicians to be vigilant for a possible association between KS and medication with Chinese remedies containing triptolide.
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