Opportunistic autoimmunity secondary to cancer immunotherapy (OASI): An emerging challenge.

With "checkpoint inhibitors" targeting PD1/PD-1-ligands or CTLA-4/CD28 pathways, immunotherapy has profoundly modified therapeutic strategies in oncology. First approved in refractory metastatic neoplasms (melanoma and lung adenocarcinoma), it is now being tested broadly in other cancers and/or as adjuvant treatment. For a significant proportion of patients, immunotherapy is responsible for "immunological" events, identified as Immune-Related Adverse Events (irAEs). Owing to the increasing number of prescriptions, identification and management of specific immunological side effects is crucial and requires close collaboration between oncologists and internists and/or other organ specialists. Within irAEs, we propose to individualize the induced autoimmunity by the term "Opportunistic Autoimmunity Secondary to Cancer Immunotherapy" (OASI). The aims of this article are (1) to present the different available checkpoint inhibitors and the OASIs reported with these treatments and (2) to propose practical recommendations for diagnosis, pre-therapeutic assessment and management of OASIs. The need for predictive biomarkers of OASIs occurrence will also be discussed.

Aetiologies of male osteoporosis: identification procedures.

Secondary causes and risk factors assume far greater importance in male osteoporosis than in female osteoporosis. The principal problem in dealing with male osteoporosis, above all in young men, is the difficulty to find a curable aetiology. Six groups of aetiologies can be drawn up: toxic causes or causes due to a change in the general state of health, drug-induced causes, renal causes, hormonal causes, exceptional causes and lastly the idiopathic form. The minimum number of investigations necessary so as to be quite sure not to overlook these various aetiologies is proposed.

Sex hormones in spondylarthropathies. A study in 57 patients.

Studies of the hormonal status of patients with spondylarthropathies are few in number, despite the predominantly male sex ratio characteristic of these diseases. Most suggested an elevation in androgen levels. We determined the following parameters in 57 men with spondylarthropathies: FSH, LH, prolactin, estradiol, total testosterone, free testosterone, delta-4-androstenedione, 17-OH-progesterone, estradiol over total testosterone ratio and estradiol over free testosterone ratio. Results were compared to those in a group of 100 healthy controls. Mean patient age was 41.9 years, and mean disease duration was one year. None of the patients were under corticosteroid therapy. The mean prolactin level was normal (8.4 +/- 4.5 ng/ml), whereas the mean 17-OH-progesterone level was significantly elevated (2.02 +/- 0.8 ng/ml). The estradiol over testosterone ratios were normal. This hormone profile is consistent with partial deficiency in the enzyme 21-hydroxylase, which is encoded by a gene located on chromosome 6 only 600 kb away from the HLA B locus. We suggest that some class I alleles may be associated with an alteration in 21-hydroxylase responsible for an increase in 17-OH-progesterone levels and for macrophage inhibition resulting in delayed elimination of antigens. This hypothesis is consistent with the possibility raised by others that macrophage inhibition may explain the increased prevalence of infections due to intracellular organisms in patients with spondylarthropathies.

Healing of Charcot's joint by pamidronate infusion.

Treatment of Charcot's joints remains difficult, and involves prolonged periods without weightbearing, immobilization, and surgical salvage procedures to avoid amputation. We describe the efficacy of pamidronate in treating a patient with Charcot's joint, due to hereditary sensory neuropathy, that caused loss of pain sensation. The bone and joint destruction in our patient's left foot was stopped by bisphosphonate treatment, and signs of a reconstructive healing process were observed on the control radiographs. The treatment was administered intravenously every 4 months for 2 years, without restriction on weightbearing, since the patient had refused a plaster cast and an orthotic device. This observation suggests that treatment with bisphosphonates should be used before, or in combination with, other treatment in such cases.