Imbalance of TH17/TREG cells in Tunisian patients with systemic sclerosis.

Fibrosis is a pathological manifestation in which connective tissue replaces normal one. It can affect many tissues from the skin to internal organs such as the lungs. Manifestations of pulmonary involvement can be pulmonary arterial hypertension or pulmonary fibrosis. The latter one is currently the leading cause of death in various autoimmune diseases, including systemic sclerosis. Our study group consists of 50 patients with systemic sclerosis: 24 with limited cutaneous form and 26 with diffuse cutaneous form. This cohort was compared to 50 healthy controls (age and sex matched); our aim is to explore the distribution of TH17 cells (TH17) as well as regulatory T cells (TREG) and study their correlation with the disease's progress. Our results show an increase for IL17A in patients compared to controls and that this increase is correlated with a specific clinical involvement: Pulmonary fibrosis. This correlation suggests a crucial role of IL17A in fibrosis especially in systemic sclerosis. In addition, we have shown that the percentages of TH17 cells are higher in patients; however, the percentages of TREG cells are similar between patients and controls. A study of TREG cell activity showed that TREG lost suppressive activity by inactivating the FOXP3 transcription factor. This proves that despite their presence, TREG does not adequately carry out their regulatory activity. Finally, we analyzed the correlation between TH17/TREG and clinical damage; the results show a positive correlation with pulmonary involvement proving the role of TH17/TREG balance in induced fibrosis in systemic sclerosis. No significative difference was observed, for all the parameters, between the two different forms of the disease. In conclusion, the results associated with the TH17/TREG scale and their correlations with fibrosis in systemic sclerosis open a way for new tools to manage this autoimmune disease, which up to today has neither treatment nor accurate diagnosis.

Leg muscle involvement in polyarteritis nodosa (limited form)-A rare case report.

Polyarteritis nodosa is a necrotizing arteritis involving small and medium vessels. Polyarteritis nodosa can have variable presentations depending upon the organ involved. It can either present as a diffuse disease or a limited form confined to a particular organ. Isolated muscular involvement in this disease is rare, which may present as myalgia, nonspecific fever, weight loss or even as claudication. The imaging pattern on ultrasound and MRI can help diagnose this condition in the background of clinical history and muscle biopsy is confirmatory. We present a case of 15 years old boy who presented with fever, weight loss, myalgia in leg region. MRI and ultrasound examination showed perivascular inflammation in calf muscles with a characteristic "cotton wool" pattern of enhancement on contrast study.

Treatment response, risk of relapse and clinical characteristics of Taiwanese patients with neuromyelitis optica spectrum disorder.

BACKGROUND/PURPOSE: The long-term disease course and efficacy of maintenance therapies have rarely been investigated in Asian patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: Medical records of patients fulfilling the 2015 International Consensus Diagnostic Criteria for NMOSD at three medical centers in Taiwan were systematically analyzed. Linear regression analysis was performed to investigate factors related to annualized relapse rate (ARR); survival analysis was used to estimate the relapse-free intervals among therapies. RESULTS: A total of 557 relapses affecting 648 regions (202 optic neuritis, 352 acute myelitis, and 94 brain syndromes) in 204 patients were analyzed during a follow-up period of 69.5 months (range, 1-420). Up to 36.1% of myelitis-onset patients and 24.0% of optic neuritis-onset patients exhibited a limited form disease, defined as having one or more relapses confined to the same region. The median ARR was significantly lower in patients with limited form disease than those with relapses involving multiple regions (0.30 vs. 0.47, respectively). An older age at disease onset was associated with a lower ARR (p = 0.023). Kaplan-Meier analysis showed that the estimated time (months) to next relapse was longest in rituximab-treatment group (58.0 ± 13.2), followed by immunosuppressant (48.5 ± 4.8) or prednisone (29.6 ± 4.6) groups, and shortest in those without maintenance therapy (27.6 ± 4.2) (p = 8.1 × 10-7). CONCLUSION: Limited form disease and older age at disease onset are associated with a lower relapse rate in NMOSD. Compared to no maintenance therapy, rituximab and immunosuppressant significantly reduce the relapse risks.

Urethral involvement in granulomatosis with polyangiitis: a case-based review.

Granulomatosis with polyangiitis (GPA) commonly presents with glomerulonephritis and inflammation of upper and lower respiratory tracts. It can also involve other organs including those of the urinary tract. The involvement of the urethra is very rarely reported. We present a case of GPA in a patient who had recurrent urinary tract infections and an acute bladder outlet obstruction due to a urethral thickening by GPA. In this report, we discuss urethral involvement with GPA. The incidence of such involvement, as with other urinary tract organs, might be underestimated. It can affect both sexes, with male predominance, and can occur at any age. It responds to standard GPA medical treatment but may require surgical intervention. Rheumatologists should be aware of this limited form of GPA as early recognition and treatment can decrease the risk of complications.

Hypertrophic pachymeningitis: significance of myeloperoxidase anti-neutrophil cytoplasmic antibody.

The aim of this study was to elucidate the characteristics, pathogenesis and treatment strategy of hypertrophic pachymeningitis that is associated with myeloperoxidase anti-neutrophil cytoplasmic antibody (ANCA). We retrospectively investigated clinical, radiological, immunological and pathological profiles of 36 patients with immune-mediated or idiopathic hypertrophic pachymeningitis, including 17 patients with myeloperoxidase-ANCA, four patients with proteinase 3-ANCA, six patients with other immune-mediated disorders, and nine patients with 'idiopathic' variety. Myeloperoxidase-ANCA-positive hypertrophic pachymeningitis was characterized by: (i) an elderly female predominance; (ii) 82% of patients diagnosed with granulomatosis with polyangiitis (previously known as Wegener's granulomatosis) according to Watts' algorithm; (iii) a high frequency of patients with lesions limited to the dura mater and upper airways, developing headaches, chronic sinusitis, otitis media or mastoiditis; (iv) a low frequency of patients with the 'classical or generalized form' of granulomatosis with polyangiitis involving the entire upper and lower airways and kidney, or progressing to generalized disease, in contrast to proteinase 3-ANCA-positive hypertrophic pachymeningitis; (v) less severe neurological damage according to the modified Rankin Scale and low disease activity according to the Birmingham Vasculitis Activity Score compared with proteinase 3-ANCA-positive hypertrophic pachymeningitis; (vi) increased levels of CXCL10, CXCL8 and interleukin 6 in cerebrospinal fluids, and increased numbers of T cells, neutrophils, eosinophils, plasma cells and monocytes/macrophages in autopsied or biopsied dura mater with pachymeningitis, suggesting TH1-predominant granulomatous lesions in hypertrophic pachymeningitis, as previously reported in pulmonary or renal lesions of granulomatosis with polyangiitis; and (vii) greater efficacy of combination therapy with prednisolone and cyclophosphamide compared with monotherapy with prednisolone. Proteinase 3-ANCA may be considered a marker for more severe neurological damage, higher disease activity and a higher frequency of the generalized form compared with myeloperoxidase-ANCA-positive hypertrophic pachymeningitis. However, categorization into 'granulomatosis with polyangiitis' according to Watts' algorithm and immunological or pathological features were common in both proteinase 3- and myeloperoxidase-ANCA-positive hypertrophic pachymeningitis. These data indicate that most patients with myeloperoxidase-ANCA-positive hypertrophic pachymeningitis should be categorized as having the central nervous system-limited form of ANCA-associated vasculitis, consistent with the concept of ophthalmic-, pulmonary- or renal-limited vasculitis.

A Case of NK/T Cell Lymphoma Mimicking Limited Form of Wegener's Granulomatosis / 대한류마티스학회지

It is occasionally difficult to distinguish Wegener's granulomatosis (WG) from other diseases including malignancy, tuberculosis, and various types of vasculitis because of the overlapping symptoms and signs. We report on a patient with NK/T cell lymphoma who was treated with a limited form of WG. At his first visit, he presented with left foot drop and recurrent nasal swelling. Necrosis and massive infiltration of inflammatory cells were identified on a nasal tissue biopsy. Sural nerve biopsy findings also showed infiltration of inflammatory cells in both the endoneurium and perivascular area; thus, a diagnosis of a limited form of WG was made. After combination therapy with a glucocorticoid and oral cyclophosphamide was initiated, his condition completely recovered without recurrence for the next 2 years. However, he visited the hospital again for recurrence of nasal swelling. Repeated biopsy of nasal tissues, combined with an immunophenotypic analysis revealed NK/T cell lymphoma. The possibility of NK/T lymphoma should be considered when evaluating a limited type of WG, which shows atypical findings on biopsy as well as recurrent deterioration, as a suboptimal dose of immunosuppressive therapy may mask its expression and lead to a poor prognosis.