HOLON, Israel—Estrogen is implicated in the higher rates of systemic lupus erythematosus (SLE) in women and appears to have induced a lupus-like syndrome in an otherwise nonpredisposed individual following male-to-female sex reassignment surgery. Gisele Zandman-Goddard, MD, head of the department of medicine at Wolfson Medical Center in Holon, Israel, reports this case in The Journal of Rheumatology.¹

"This is the first reported case of sex reassignment surgery and the subsequent development of cutaneous lupus. Although a genetic component was not sought, and SLE can appear in men, we present this first report to emphasize that environmental triggers including high doses of estrogens as part of sex reassignment surgery may lead to the development of lupus in a nonpredisposed individual," Dr. Zandman-Goddard notes of her patient's case.

Lupus skin, joint problems required hydroxychloroquine

Lupus erythematosus tumidus (LET) is a form of chronic cutaneous lupus erythematosus with urticarial plaque morphology. The 40-year-old patient had undergone male-to-female sex reassignment surgery and silicone augmentation mammoplasty in 2000. She subsequently developed a diffuse rash on the face, chest, and back and was diagnosed as having cutaneous lupus. This was followed by muscle weakness, symmetric joint pain in the knees and hands, chest pain exacerbated by deep inspiration, and mood swings.

The patient's medical history included treatment with estradiol ethinylestradiol, conjugated estrogens, and cyproterone acetate/ethinylestradiol (combination antiandrogen and estrogen); continuous estradiol valerate was initiated after surgery. The LET symptoms had previously been treated with monthly intramuscular betamethasone diproprionate.

Dr. Zandman-Goodard reports that on examination, her patient had female characteristics and "remarkable erythematous confluent papules on the presternal, shoulders, abdomen, and back without alopecia or oral ulcers." There was also tenderness of the wrists and metacarpophalangeal joints of the second and third digits but no swelling. The patient was treated with hydroxychloroquine 200 mg bid, which alleviated the cutaneous and joint problems.

Laboratory values were within normal limits. Serology (antinuclear antibodies and anti-DNA) was negative. "The hormonal profile (elevated follicle-stimulating hormone and luteinizing hormone, low testosterone) was compatible with menopausal women or Klinefelter's syndrome," Dr. Zandman-Goddard reports.
Skin biopsy showed mild interface vacuolar changes and dense perivascular lymphocytic inflitrates in the superficial and mid-dermis.

Dr. Zandman-Goddard explains that estrogens may act in conjunction with other factors to override immune tolerance to self-antigens. "The patient's hormonal profile at the development of lupus was equivalent to a woman during the menopausal period, with [an] elevated FSH level. The low testosterone level was probably a result of castration and feminizing hormone therapy. In addition, while maintaining female hormone therapy she had elevated levels of prolactin. Hyperprolactinemia has been reported in 20% to 30% of patients with lupus. Moreover, prolactin has a direct effect on B-cells enhancing autoimmunity. Importantly, cutaneous lupus developed in this case in a female hormonal milieu, one that is more optimal for B-cell dysregulation."

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