Risk of autoimmune diseases and human papilloma virus (HPV) vaccines: Six years of case-referent surveillance.

BACKGROUND: Safety of HPV vaccines is still in question due to reports of autoimmune diseases (ADs) following HPV immunization. OBJECTIVES: To assess the risk of ADs associated with HPV vaccination of female adolescents/young adults in France. METHODS: Systematic prospective case-referent study conducted to assess the risks associated with real-life use of HPV vaccines. Cases were female 11-25 years old with incident ADs [central demyelination/multiple sclerosis (CD/MS), connective tissue disease (CTD), Guillain-Barré syndrome (GBS), type-1 diabetes (T1D), autoimmune thyroiditis (AT), and idiopathic thrombocytopenic purpura (ITP)]. Cases were consecutively and prospectively identified at specialized centers across France (2008-2014) and individually matched by age and place of residence to referents recruited in general practice. Risk was computed using multivariate conditional logistic regression models adjusted for family history of ADs, living in France (north/south), co-medications and co-vaccinations. RESULTS: With a total of 478 definite cases matched to 1869 referents, all ADs combined were negatively associated to HPV vaccination with an adjusted odds ratio of 0.58 (95% confidence interval: 0.41-0.83). Similar results were obtained for CD/MS, AT, CT, and T1D, the last two not reaching statistical significance. No association was found for ITP and GBS. Sensitivity analyses combining definite and possible cases with secondary time window showed similar results. CONCLUSION: Exposure to HPV vaccines was not associated with an increased risk of ADs within the time period studied. Results were robust to case definitions and time windows of exposure. Continued active surveillance is needed to confirm this finding for individual ADs.

Sarcoidosis: clinical, hormonal, and magnetic resonance imaging (MRI) manifestations of hypothalamic-pituitary disease in 9 patients and review of the literature.

Hypothalamic-pituitary (HP) sarcoidosis has 2 main endocrine manifestations: diabetes insipidus and hyperprolactinemia. We conducted the current study to investigate pituitary dysfunction and perform imaging of the HP area in patients both immediately following diagnosis and after treatment. The study included 6 men and 3 women, with a mean age of 30 years at the onset of sarcoidosis. All patients had both hormonal and magnetic resonance imaging (MRI) HP disorders. All patients had anterior pituitary dysfunction, 7 of them with associated diabetes insipidus. Nine patients had gonadotropin deficiency and 3 had hyperprolactinemia. MRI revealed infundibulum involvement in 5 patients, pituitary stalk thickness abnormality in 5, and involvement of the pituitary gland in 2, associated with other parenchymal brain or spinal cord lesions in 6 patients. All patients had multiple localizations of sarcoidosis, and 5 had histologically confirmed sinonasal localizations. Mean follow-up of the HP disorder was 7.5 years. All patients received prednisone. There was no correlation between the number of hormonal dysfunctions and the area of the HP axis involved as assessed by MRI. Although corticoid treatment was associated with a reduction of radiologic lesions, only 2 patients had partial recovery of hormonal deficiency. In conclusion, hormonal deficiencies associated with HP sarcoidosis frequently include hypogonadism (all patients) and to a lesser degree diabetes insipidus (7 of 9 patients). MRI abnormalities improved or disappeared in 7 cases under corticosteroid treatment, but most endocrine defects were irreversible despite regression of the granulomatous process. Most cases presented with multivisceral localizations and an abnormally high proportion of sinonasal localizations.

Esophageal involvement as an initial manifestation of Churg-Strauss syndrome.

INTRODUCTION: Churg-Strauss syndrome (CSS) is a systemic disease characterized by asthma, blood and tissue eosinophilia, and necrotizing vasculitis with extravascular eosinophilic granulomas. CASES: We describe two cases of patients with CSS: a 56-year-old man, whose presentation was highly unusual because its initial predominant manifestation was odynophagia, and a 35-year-old man whose disease was diagnosed after a work-up because of nausea, vomiting and abdominal pain. In both cases, thoracic computerized tomography scans showed congestive esophagitis with a markedly thickened esophageal wall at diagnosis and at relapse. Both the vasculitis and the esophageal involvement improved with treatment. DISCUSSION: Gastrointestinal (GI) involvement is frequent in CSS patients and is one of the major causes of death associated with CSS. Nonetheless, eosinophilic vasculitis-related esophagitis is very rare.

Medical cure of plasma cell granuloma of the thyroid associated with Hashimoto's thyroiditis: a case report and review.

Plasma cell granuloma (PCG) is a rare, benign inflammatory tumor composed of myofibroblasts, abundant plasma cells, and lymphocytes combined with collagen. A thyroid localization of PCG is extremely rare, and surgical therapy is indicated. We report the case of a 35-yr-old woman with a thyroid PCG, associated with Hashimoto's thyroiditis, that was responsible for tracheal compression. Surgery was performed, but the thyroid could not be removed because of the fibrotic process. The patient was treated with corticosteroids and immunosuppressive therapy. Dyspnea and dysphagia improved within 1 month, whereas thyroid volume returned to normal within 3 yr. We also review other reports of thyroid PCG in the literature and discuss the differential diagnosis and treatment. Although the use of immunosuppressive therapy has never been reported for thyroid PCG until now, this treatment may represent a good alternative to surgery in life-threatening, unresectable PCG.

Idiopathic CD4 lymphocytopenia: clinical and immunologic characteristics and follow-up of 40 patients.

Idiopathic CD4 T lymphocytopenia (ICL) is a rare and severe condition with limited available data. We conducted a French multicenter study to analyze the clinical and immunologic characteristics of a cohort of patients with ICL according to the Centers for Disease Control criteria.We recruited 40 patients (24 female) of mean age 44.2 ± 12.2 (19-70) years. Patients underwent T-lymphocyte phenotyping and lymphoproliferation assay at diagnosis, and experiments related to thymic function and interferon (IFN)-γ release by natural killer (NK) cell were performed. Mean follow-up was 6.9 ± 6.7 (0.14-24.3) years. Infectious, autoimmune, and neoplastic events were recorded, as were outcomes of interleukin 2 therapy.In all, 25 patients had opportunistic infections (12 with human papillomavirus infection), 14 had autoimmune symptoms, 5 had malignancies, and 8 had mild or no symptoms. At the time of diagnosis, the mean cell counts were as follows: mean CD4 cell count: 127/mm (range, 4-294); mean CD8: 236/mm (range, 1-1293); mean CD19: 113/mm (range, 3-547); and mean NK cell count: 122/mm (range, 5-416). Most patients had deficiency in CD8, CD19, and/or NK cells. Cytotoxic function of NK cells was normal, and patients with infections had a significantly lower NK cell count than those without (p = 0.01). Patients with autoimmune manifestations had increased CD8 T-cell count. Proliferation of thymic precursors, as assessed by T-cell rearrangement excision circles, was increased. Six patients died (15%). CD4 T-cell count <150/mm and NK cell count <100/mm were predictors of death.In conclusion, ICL is a heterogeneous disorder often associated with deficiencies in CD8, CD19, and/or NK cells. Long-term prognosis may be related to initial CD4 and NK cell deficiency.