Anastrozole-Induced Subacute Cutaneous Lupus Erythematosus
Drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) has been associated with numerous drugs, but there are limited reports of its association with aromatase inhibitor anastrozole. We report the case of a patient undergoing treatment with anastrozole for breast cancer who presented with clinical, serological, and histological evidence consistent with DI-SCLE. Her condition quickly began to improve after the use of anastrozole was discontinued and hydroxychloroquine therapy was initiated. Cases such as ours as well as several others that implicate antiestrogen drugs in association with DI-SCLE seem to be contradictory to studies looking at the usefulness of treating systemic lupus erythematosus (SLE) with antiestrogen therapy. Further research on this relationship is warranted.
Practice Points
- There are numerous cases of drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) published in the literature; however, there are limited reports with anastrozole implicated as the causative agent.
- Cases of DI-SCLE are clinically and histologically indistinguishable from idiopathic cases. It is important to recognize and withdraw the offending agent.
Antiestrogen Drugs and SCLE
Anastrozole, the inciting agent in our case, is a third-generation, selective, nonsteroidal, aromatase inhibitor with no progestogenic, androgenic, or estrogenic activity. Anastrozole, when taken at its recommended dosage of 1 mg daily, will suppress estradiol. It is used as an adjuvant treatment of estrogen-sensitive breast cancer in postmenopausal women. In contrast to a prior case of DI-SCLE secondary to anastrozole in which the incubation period was approximately 1 month,8 our patient had an incubation period of approximately 16 months. Tamoxifen, another antiestrogen drug, also has been associated with DI-SCLE.9 In cases of tamoxifen-induced SCLE, the incubation period was several years, which is more similar to our patient.Although these drugs do not have the same mechanism of action, they both have antiestrogen properties.9 A systemic review of DI-SCLE reported that incubation periods between drug exposure and appearance of DI-SCLE varied greatly and were drug class dependent. It is possible that reactions associated with antiestrogen medications have a delayed presentation; however, given there are limited cases of anastrozole-induced DI-SCLE, we cannot make a clear statement on incubation periods.6
Reports of DI-SCLE caused by antiestrogen drugs are particularly interesting because sex hormones in relation to lupus disease activity have been the subject of debate for decades. Women are considerably more likely to develop autoimmune diseases than men, suggesting that steroid hormones, especially estrogen and progesterone, influence the immune system.16 Estrogen actions are proinflammatory, while the actions of progesterone, androgens, and glucocorticoids are anti-inflammatory.17 Studies in women with lupus revealed an increased rate of mild- to moderate-intensity disease flares associated with estrogen-containing hormone replace-ment therapy.18-20
,Over the years, several antiestrogen therapies have been used in murine models, which showed remarkable clinical improvement in the course of SLE. The precise mechanisms involved in disease immunomodulation by these therapies have not been elucidated.21-23 It is thought that estrogen plays a role in the synthesis and expression of Ro antigens on the surface of keratinocytes, increasing the fixation of anti-Ro antibodies in keratinocytes and provoking the appearance of a cutaneous eruption in patients with a susceptible HLA profile.6
Conclusion
We report a rare case of SCLE induced by anastrozole use. Cases such as ours and others that implicate antiestrogen drugs in association with DI-SCLE are particularly noteworthy, considering many studies are looking at the potential usefulness of antiestrogen therapy in the treatment of SLE. Further research on this relationship is warranted.
