Successful treatment of arthralgia with tamoxifen citrate in a patient with pachydermoperiostosis
H. Maeda,
K. Kumagai,
F. Konishi,
Y. Katayama,
K. Hiyama,
S. Ishioka and
M. Yamakido
Second Department of Internal Medicine, Hiroshima University School of Medicine, Hiroshima, Japan
SIR, Pachydermoperiostosis (PDP), a primary hypertrophic osteoarthropathy, is a rare disorder that is manifest clinically as digital clubbing, painful joints and cutis verticis gyrata [1]. We report a case of PDP whose painful joints were relieved with tamoxifen citrate, an antagonist of oestrogen.
A 24-yr-old man visited our hospital complaining of arthralgia in the finger, wrist and uncle joints, digital clubbing, and coarsening of facial features. He had been aware of the digital changes since the age of 14 yr. Chest examination, chest X-ray and ECG showed no abnormalities. Hand, foot and leg X-rays revealed thickening of soft tissues and periostosis of the long bones, including the tibiae, fibulae, metacarpals and metatarsals (Fig. 1
). Laboratory findings, including arterial blood gases, serum growth hormone, thyroid hormone, oestrone, oestradiol, and urinary oestrone, oestradiol and oestriol, showed no abnormalities except slightly elevated serum oestriol (10.2 pg/ml; normal range 05.0 pg/ml). Due to the absence of preceding disorders of secondary hypertrophic osteoarthropathy, he was diagnosed as having PDP. Although NSAIDs, including indomethacin and diclofenac sodium, were used for the vague arthralgia, the pain remained.

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FIG. 1. Hand, foot and leg X-rays showing thickening of soft tissues and periosteal new bone formation in long bones, including metacarpals (A), metatarsals (B) and tibiae and fibulae (C and D).
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Enhanced production and/or utilization of growth factors resulting from increased tissue sensitivity to circulating sex steroids has been related to the pathogenesis of various conditions, including benign prostatic hypertrophy [2] and uterine cell proliferation [3]. Regarding the pathogenic mechanisms of hypertrophic osteoarthropathy, an elevated number of cytosolic oestrogen receptors in the affected tissue of patient with PDP has been reported [4]. Thus, reducing the serum oestrogen level or tissue sensitivity to circulating sex steroids might become a therapeutic strategy for PDP. In our patient oral tamoxifen citrate at 20 mg daily was initiated with written informed consent regarding the nature of the treatment and the toxicity that might be expected [5]. A few days later, the pain began to improve. His arthralgia has been controlled successfully with daily oral tamoxifen for 5 consecutive months to date, without obvious adverse effects. The relief of arthralgia by anti-oestrogen therapy suggests the pathological involvement of sex steroids and target tissue reaction in PDP, which might provide a clue to new therapeutic strategies.
Notes
Correspondence to: H. Maeda, Second Department of Internal Medicine, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. 
References
- Martinez-Lavin M, Pineda C, Valdez T et al. Primary hypertrophic osteoarthropathy. Semin Arthritis Rheum1988;17:15662.[ISI][Medline]
- Levine AC, Ren M, Huber GK, Kirschenbaum A. The effect of androgen, estrogen, and growth factors on the proliferation of cultured fibroblasts derived from human fetal and adult prostates. Endocrinology1992;130:24139.[Abstract]
- Reynolds RK, Talavera F, Roberts JA, Hopkins MP, Menon KM. Regulation of epidermal growth factor and insulin-like growth factor I receptors by estradiol and progesterone in normal and neoplastic endometrial cell cultures. Gynecol Oncol1990;38:396406.[ISI][Medline]
- Bianchi L, Lubrano C, Carrozzo AM et al. Pachydermoperiostosis: study of epidermal growth factor and steroid receptors. Br J Dermatol1995;132:12833.[ISI][Medline]
- Anelli TF, Anelli A, Tran KN, Lebwohl DE, Borgen PI. Tamoxifen administration is associated with a high rate of treatment-limiting symptoms in male breast cancer patients. Cancer1994;74:747.[ISI][Medline]
Accepted 29 February 2000