Henoch-Schönlein purpura and aromatase inhibitors

ARTICLE

Auteur(s) : Federico Pellegrini, Valentina Rossi, Flavia Fassone, Enzo Castracane, Luca Persemoli, Claudio Altobelli, Paolo Astorre

Policlinico Militare di Roma “Celio”, Medical Oncology Department, P.zza Celimontana, 50 - 00184, Rome, Italy

The third-generation aromatase inhibitors (AIs) have only recently become standard care in the adjuvant treatment of postmenopausal women with endocrine-responsive breast cancer, according to internationally recognized guidelines. The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial has clearly demonstrated a statistically significant advantage of anastrozole, a reversible non-steroidal AI, over tamoxifen in disease-free survival (DFS) and time to recurrence (TTR) [1]. These results have led with time to the widespread use of anastrozole as initial therapy in the adjuvant setting of early breast cancer.

Side effects more commonly encountered during AI therapy are diffuse arthralgia and myalgia, bone loss and effects on the cardiovascular system and blood lipids. To our knowledge, only two cases of anastrozole-related Henoch Schönlein purpura (HSP) have been published so far in the literature [2, 3]. We report of a third case in a postmenopausal estrogen receptor-positive woman with early breast cancer.

A 55-year-old postmenopausal woman was referred to our department in June 2006 after undergoing a right breast lumpectomy and ipsilateral axillary node dissection for a 1.3 cm, HER-2 negative, node positive and hormone receptor-positive breast cancer. Postoperatively, she received four cycles of adjuvant chemotherapy followed by radiotherapy to the right breast and endocrine therapy with anastrozole. In July 2007 she presented with an episode of gross hematuria associated with abdominal pain followed, two days later, by the occurrence of several small palpable and burning purpuric lesions in both legs (figure 1A). The patient was then admitted to the hospital where a CBC, a serum chemistry panel including antinuclear antibody, hepatitis markers, cryoglobulin, p- and c-ANCA and coagulation studies were all within the normal range. A punch biopsy of the skin showed infiltration of dermal vessels by neutrophils, red blood cell extravasation and fibrinoid necrosis, consistent with a leucocytoclastic vasculitis (figure 1B). The immunofluorescent staining revealed IgA deposits in the dermal vessels suggestive of HSP. The cutaneous lesions resolved spontaneously about 2 weeks after anastrozole was withdrawn and the patient was then restarted on endocrine treatment with tamoxifen. Her subsequent skin examinations have been unremarkable.

Henoch-Schönlein purpura is an acute small vessel leucocytoclastic vasculitis which is prevalent in young children [4]. Adults may also be affected and often present with a more severe clinical picture. Although the cause is still controversial, IgA1 deposition in vessel walls and renal mesangium are responsible for the major clinical manifestations. Typically, patients present with a palpable purpuric rash, usually concentrated on the buttocks and lower extremities [5]. Painful arthritis, most often affecting the ankles and knees, may precede the onset of purpura in about one third of the cases. Gastrointestinal, renal, peripheral and central nervous system involvement may sometimes occur and be responsible for a delay in diagnosis. HSP has been linked to infectious agents as well as environmental factors, malignancy and various pharmacological agents. Tamoxifen, a selective estrogen receptor modulator (SERM), has also been reported to induce vasculitis but the underlying biological mechanism is still unclear. Paraneoplastic vasculitis always needs to be ruled out in a patient presenting with palpable purpura and history of cancer, though it usually parallels the course of the underlying malignancy [6]. In our case, somewhat similarly to the previous reports, prompt resolution of the skin changes after discontinuation of anastrozole and without a specific treatment with steroids or immunosuppressive agents, led us to exclude a paraneoplastic form.

In conclusion, anastrozole-related HSP may be a potential, though rare and completely reversible short-term adverse effect of aromatase inhibitor treatments and, as such, it needs to be recognized if a cutaneous vasculitis develops in patients on these medications.

Acknowledgments

References

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