[Orbital myositis associated with ipilimumab]. / Myosite orbitaire associée à un traitement par ipilimumab.

BACKGROUND: Ipilimumab is a monoclonal antibody targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) that allows increased survival and, occasionally, complete remission, in the treatment of metastatic melanoma. The most frequent adverse effects are attributed to dysimmunity. We report the case of a female patient who developed orbital myositis during treatment with ipilimumab. PATIENTS AND METHODS: A woman on ipilimumab for a heel melanoma with mediastinal metastases was referred for evaluation of painful diplopia and proptosis that began three days after the fourth infusion of ipilimumab. The clinical examination disclosed a left abductiondeficit associated with conjunctival hyperaemia and palpebral oedema. Orbital MRI disclosed enlargement of the left lateral rectus, enhancing after contrast. An extensive work-up did not find any evidence for thyroid-related eye disease, as well as other orbital inflammatory processes, orbital cellulitis or orbital metastases. Treatment with high-dose oral steroids resulted in complete clinical recovery within a few days. DISCUSSION: To our knowledge, this is the first clinical report of orbital myositis as an adverse event related to anti-CTLA-4 antibody treatment. Both timing and usual profile of adverse events support the hypothesis that orbital myositis has to be attributed there to ipilimumab. Several dysimmune toxicities were observed with ipilimumab. Ophtalmic toxicity has unusually been described. Most cases were uveitis. Whether immune-related adverse events correlate with clinical response to ipilimumab treatment remains to be determined.

Angio-oedema induced by oestrogen contraceptives is mediated by bradykinin and is frequently associated with urticaria.

BACKGROUND: Hereditary C1-inhibitor (C1-Inh) deficiency is associated with 'bradykinin-mediated angio-oedema' (BK-AO) and is believed not to be associated with urticaria. Acquired AO has been related to oestrogen contraceptives. OBJECTIVE: To demonstrate that AO precipitated by oestrogens and characterized by nonfunctional C1-Inh is mediated by BK and to evaluate the occurrence of urticaria in these patients. METHODS: A retrospective evaluation of patients referred for AO related to oestrogen was undertaken. Circulating C1-Inh, high molecular weight kininogen (HK) and enzymes involved in the metabolism of bradykinin were investigated. RESULTS: Fifteen patients were included. HK cleavage concurrent to oestrogen intake was demonstrated in 10 patients with available plasma. Eight patients reported recurrent or chronic urticaria. Discontinuation of the contraceptive resulted in a return to native C1-Inh and HK in all cases studied and to normal kininogenase activity in all but one. The clinical manifestations completely disappeared in 6 patients and improved in 7 after the withdrawal of oestrogen. CONCLUSION: Patients display extensive cleavage of HK in the plasma, which supports that AO precipitated by oestrogen contraception is BK-mediated. Recurrent urticaria may have been underestimated in this context. The presence of recurrent urticaria should not systematically rule out the diagnosis of BK-AO when the history is suggestive.

[Recurrences after conservative radiosurgical treatment of breast cancer]. / Les récidives mammaires après traitement conservateur radiochirurgical du cancer du sein.

From 1960 to 1989, 154 cases of recurrent breast cancer after conservative radiosurgery were treated at the Curie Institute. Relapse was discovered at clinical examination in 88% of the cases and mammography was only useful in 45%. In 18 cases (12%) an unpalpable tumour was discovered at mammography, especially for intragalactophoric tumors. Cytopuncture yielded a precise diagnosis in 83% of the cases. Overall survival rate after recurrence was 72% at 5 years (62% without metastasis). Survival rate was better for late recurrence, and poorer in cases with subclinical axillary invasion. Neither age nor type of treatment had any effect on survival. Indications for general associated treatment are based on: the invasive character of the recurrent tumour, axillary invasion, tumour size and delay to recurrence after initial surgery.