Clinical features and long-term outcomes of patients with systemic polyarteritis nodosa diagnosed since 2005: Data from 196 patients.

BACKGROUND: The landscape of polyarteritis nodosa (PAN) has substantially changed during the last decades. Recent data regarding causes, characteristics, and prognosis of systemic PAN in the modern era are lacking. METHODS: This retrospective study included patients with systemic PAN referred to the French Vasculitis Study Group between 2005 and 2019. Characteristics, associated conditions and outcomes were collected, and predictors of relapse and death were analyzed. RESULTS: 196 patients were included. Main clinical symptoms were constitutional (84%), neurological (59%), skin (58%) and musculoskeletal (58%) manifestations. Secondary PAN accounted for 55 (28%) patients, including myelodysplastic syndrome (9%), solid cancer (7%), lymphoma (4%) and autoinflammatory diseases (4%). No patient had active HBV infection. All treated patients (98.5%) received glucocorticoids (GCs), alone (41%) or in combination with immunosuppressants (59%), with remission achieved in 90%. Relapses were independently associated with age >65 years (HR 1.85; 95% CI1.12-3.08), gastrointestinal involvement (1.95; 95% CI1.09-3.52) and skin necrotic lesions (HR 1.95; 95%CI 1.24-3.05). One-, 5- and 10-year overall survival rates were 93%, 87% and 81%, respectively. In multivariate analyses, age >65 years (HR 2.80; 95%CI 1.23-6.37), necrotic purpura (HR 4.16; 95%CI 1.62-10.70), acute kidney injury (HR 4.89; 95% 1.71-13.99) and secondary PAN (HR 2.98; 95%CI 1.29-6.85) were independently associated with mortality. CONCLUSION: Landscape of PAN has changed during the last decades, with the disappearance of HBV-PAN and the emergence of secondary PAN. Relapse rate remains high, especially in aged patients with gastrointestinal and cutaneous necrosis, as well as mortality.

EVALUATION OF TUMOR NECROSIS FACTOR INHIBITOR THERAPY IN SUSAC SYNDROME.

PURPOSE: To evaluate the effect of tumor necrosis factor (TNF) inhibitor therapy on ocular relapses in patients with Susac syndrome. METHODS: Multicenter retrospective cohort study of patients diagnosed with Susac syndrome according to classical clinical criteria. We evaluated the disease activity before and after introduction of anti-TNF therapy and its value as a steroid-sparing agent. RESULTS: Five patients were included. All were initially treated with a combination of corticosteroids and classical immunosuppressive drugs. Infliximab was started in three patients, and adalimumab was started in two patients. Patients had on average 5 ocular relapses during a mean follow-up time of 2.59 years before introducing a TNF inhibitor, corresponding with on average 1.93 relapses per year. After the introduction of an anti-TNF agent, this number was reduced by factor 5.51 to an average of 0.35 relapses per year for a mean follow-up of 2.86 years (P = 0.10). Before anti-TNF introduction ocular relapses occurred at a mean daily dose of 34 mg of prednisone, whereas with anti-TNF treatment, corticosteroid administration could be completely stopped in four patients with one patient still needing 5 mg daily (P = 0.10). Infliximab and adalimumab generally were well tolerated, and no serious adverse events were reported. CONCLUSION: Although not statistically significant, our results suggest that anti-TNF therapy can be a valuable option for the treatment of ocular Susac syndrome and may especially be considered in those patients unresponsive to more conventional immunosuppressive treatment.

Gastrocnemius Myositis Associated with Behçet's Syndrome.

Behçet's syndrome is a complex vasculitis involving vessels of all sizes. The typical clinical presentation consists of recurrent oral ulcers associated with genital ulcers, and/or intra-ocular inflammation and/or cutaneous lesions. It may also involve the joints, central nervous system, cardiovascular system and gastrointestinal tract. Muscle involvement associated with Behçet's syndrome has been rarely described. We here report two cases of muscular manifestations in the setting of Behçet's syndrome with specific gastrocnemius muscle involvement. LEARNING POINTS: Behçet's syndrome (BS) is a vasculitis involving vessels of all sizes with multi-organ involvement.Myositis is a rare manifestation in the setting of BS.Musculoskeletal symptoms should be investigated in patients with BS.

Lysine 183 and glutamic acid 157 of the TSH receptor: two interacting residues with a key role in determining specificity toward TSH and human CG.

A naturally occurring mutation in the ectodomain of the TSH receptor (TSHr), K183R, has been described recently in a familial case of gestational hyperthyroidism. Hyperthyroidism was explained by the widening of the specificity of the mutant receptor toward human CG (hCG). In the present study, we attempted to understand in molecular terms the structure-phenotype relationships of this mutant in light of the available structural model of TSHr ectodomain established on the template of the atomic structure of the porcine ribonuclease inhibitor. To this aim, we studied by site-directed mutagenesis and functional assays in transfected COS cells the effects of substituting amino acids with different physicochemical properties for lysine 183. Unexpectedly, all TSHr mutants displayed widening of their specificity toward hCG. Molecular dynamics simulations suggested that the gain of function would be secondary to the release of a nearby glutamate residue (E157) from a salt bridge with K183. This hypothesis was supported by further site-directed mutagenesis experiments showing that the presence of an acidic residue in position 157, or in its vicinity, was required to observe the increase in sensitivity to hCG (an acidic residue in position 183 can partially fulfill the role of a free acidic residue in position 157 when tested on the background of a E157A mutant). Our results suggest also that additional natural mutations (especially K183M, N, or Q) in position 183 of TSHr are expected to be found in gestational hyperthyroidism.

Central retinal artery occlusion and Susac syndrome: a case report.

BACKGROUND: Susac syndrome is a rare disease attributed to microangiopathy involving the arterioles of the brain, retina, and cochlea. Understanding the pathogenesis is incomplete, but an immune-mediated process remains the leading hypothesis. METHODS: Report of a single case of a previously healthy 22-year-old female patient showing the complete clinical triad. RESULTS: Diagnosis of Susac syndrome in this patient was first questioned due to the atypical initial ophthalmologic presentation with central retinal artery occlusion. Multiple relapses occurred in the fellow eye during follow-up, showing the typical branch retinal artery occlusions, allowing definite diagnosis. CONCLUSION: Susac syndrome should be considered in the differential diagnosis when facing (young) patients with central retinal artery occlusion, especially in the presence of unexplained encephalopathy and/or sensorineural hearing loss.