The impact of certolizumab pegol treatment on the incidence of anterior uveitis flares in patients with axial spondyloarthritis: 48-week interim results from C-VIEW.

BACKGROUND: Acute anterior uveitis (AAU) is the most common extra-articular manifestation in patients with axial spondyloarthritis (axSpA). C-VIEW investigates the impact of the Fc-free TNF inhibitor certolizumab pegol (CZP) on AAU flares in patients with active axSpA at high risk of recurrent AAU. METHODS: C-VIEW (NCT03020992) is a 96-week ongoing, multicentre, open-label, phase 4 study. Included patients had an axSpA diagnosis, a history of recurrent AAU (≥2 AAU flares, ≥1 flare in the year prior to study entry), HLA-B27 positivity, active disease, and failure of ≥2 non-steroidal anti-inflammatory drugs. Patients received CZP 400 mg at Weeks 0/2/4, then 200 mg every 2 weeks up to 96 weeks. This 48-week pre-planned interim analysis compares AAU flare incidence in the 48 weeks before and after initiation of CZP treatment, using Poisson regression to account for possible within-patient correlations. RESULTS: In total, 89 patients were included (male: 63%; radiographic/non-radiographic axSpA: 85%/15%; mean axSpA disease duration: 8.6 years). During 48 weeks' CZP treatment, 13 (15%) patients experienced 15 AAU flares, representing an 87% reduction in AAU incidence rate (146.6 per 100 patient-years (PY) in the 48 weeks pre-baseline to 18.7 per 100 PY during CZP treatment). Poisson regression analysis showed that the incidence rate of AAU per patient reduced from 1.5 to 0.2 (p<0.001). No new safety signals were identified. CONCLUSIONS: There was a significant reduction in the AAU flare rate during 48 weeks of CZP treatment, indicating that CZP is a suitable treatment option for patients with active axSpA and a history of recurrent AAU.

IFN-α kinoid in systemic lupus erythematosus: results from a phase IIb, randomised, placebo-controlled study.

OBJECTIVE: To evaluate the efficacy and safety of the immunotherapeutic vaccine interferon-α kinoid (IFN-K) in a 36-week (W) phase IIb, randomised, double-blind, placebo (PBO)-controlled trial in adults with active systemic lupus erythematosus (SLE) despite standard of care. METHODS: Patients with SLE (185) with moderate to severe disease activity and positive interferon (IFN) gene signature were randomised to receive IFN-K or PBO intramuscular injections (days 0, 7 and 28 and W12 and W24). Coprimary endpoints at W36 were neutralisation of IFN gene signature and the BILAG-Based Composite Lupus Assessment (BICLA) modified by mandatory corticosteroid (CS) tapering. RESULTS: IFN-K induced neutralising anti-IFN-α2b serum antibodies in 91% of treated patients and reduced the IFN gene signature (p<0.0001). Modified BICLA responses at W36 did not statistically differ between IFN-K (41%) and PBO (34%). Trends on Systemic Lupus Erythematosus Responder Index-4, including steroid tapering at W36, favoured the IFN-K and became significant (p<0.05) in analyses restricted to patients who developed neutralising anti-IFN-α2b antibodies. Attainment of lupus low disease activity state (LLDAS) at W36 discriminated the two groups in favour of IFN-K (53% vs 30%, p=0.0022). A significant CS sparing effect of IFN-K was observed from W28 onwards, with a 24% prednisone daily dose reduction at W36 in IFN-K compared with PBO (p=0.0097). The safety profile of IFN-K was acceptable. CONCLUSIONS: IFN-K induced neutralising anti-IFN-α2b antibodies and significantly reduced the IFN gene signature with an acceptable safety profile. Although the clinical coprimary endpoint was not met, relevant secondary endpoints were achieved in the IFN-K group, including attainment of LLDAS and steroid tapering. TRIAL REGISTRATION NUMBER: NCT02665364.

Immunohistochemical and ultrastructural analysis of sporadic inclusion body myositis: a case series.

Sporadic inclusion body myositis (s-IBM) is a progressive, skeletal muscle disease with poor prognosis. However, establishing the final diagnosis is difficult because of the lack of clear biomarkers in the blood serum and very slow development of clinical symptoms. Moreover, most other organs function normally without any disturbance. Here, in patients with this untreatable disease, we have underlined the importance of immunohistochemical and ultrastructural assessment of skeletal muscle in patients diagnosed with s-IBM. The goal of this study was to identify the distribution of specific antigens and to determine morphological features in order to localize pathological protein aggregates, rimmed vacuoles, and loss of myofibrils, which are key elements in the diagnosis of s-IBM. All studied patients were between 48 and 83 years of age and were hospitalized in the Department of Rheumatology and Internal Medicine between 2011 and 2016. Anamneses revealed an accelerated progression of muscle atrophy, weakness of limb muscles, and difficulties with climbing stairs. Based on histopathology and transmission electron microscopy examination, inflammatory infiltrations consisting of mononuclear cells, severe atrophy and focal necrosis of myofibers, splitting of myofilaments, myelinoid bodies and rimmed vacuoles were observed. Primary antibodies directed against CD3, CD8, CD68, cN1A, beta-amyloid, Tau protein and apolipoprotein B made it possible to identify types of cells within infiltrations as well as the protein deposits within myofibers. Using a combination of immunohistochemistry and electron microscopy methods, we were able to establish the correct final diagnosis and to implement a specific treatment to inhibit disease progression.

Challenges in diagnosis and treatment of sporadic inclusion-body myositis.

Sporadic inclusion body myositis (sIBM) is a rare yet increasingly prevalent disease and the most common cause of inflammatory myopathy in people over the age of 50. The exact cause of the disorder is unknown. In sIBM 2 processes, first autoimmune and the other degenerative, parallelly occur in the muscle cells. The inflammation aspect is characterized by the cloning of T cells that appear to be driven by specific antigens to invade muscle fibers. The degeneration aspect is characterized by the appearance of holes in the muscle cell vacuoles, deposits of abnormal proteins within the cells and in filamentous inclusions. The disease has a major impact on patients' motor functionality and their quality of life. The treatment of sIBM still remains a major challenge. Early diagnosis of sIBM (already at the histopathology stage), when one still cannot observe fully developed clinical symptoms, may stop help to the progression of the disease.

How to Distinguish Patients with pSS among Individuals with Dryness without Invasive Diagnostic Studies.

In the course of pSS, inflammatory cell infiltration consists mainly of lymphocytes infiltrating exocrine glands, which leads to their impaired function. The characteristic feature is generalized dryness. The aim of this study was to attempt to answer the question whether it is possible to distinguish between patients with pSS and individuals with dryness caused by other pathologies without applying invasive studies. The study included 68 patients with pSS and 43 healthy controls with dryness. FS ≥ 1 was observed in 90% of patients with pSS (with or without dryness), and only in 23% of the control group (only with xerostomia). In the pSS group, anaemia (p = 0.0085), lymphocytopenia (p = 0.0006), elevated ERS (p = 0.001), higher RF titer, and ANA antibodies were noted. Configuration of anti-SSA + SSB + Ro52 antibodies was characteristic for the pSS group. Considering the clinical symptoms, statistically significant differences were noted between pSS patients and the control group in frequency (p = 0.02) and severity (p = 0.042) of fatigue, lymphadenopathy, major salivary gland involvement, and photosensitivity to UV light. In conclusion, invasive methods are pivotal in pSS diagnosis in this salivary gland biopsy. Chronic fatigue syndrome is more common in pSS patients and can be subjective distinguishing factor in the group of people with dryness.

Analysis of peripheral nerve and autonomic nervous system function and the stage of microangiopathy in patients with secondary Raynaud's phenomenon in the course of connective tissue diseases.

BACKGROUND: The pathogenesis of secondary Raynaud's phenomenon (SRP) associated with connective tissue diseases (CTD) is not entirely understood. Nervous system dysfunction and microangiopathy are considered to be causes of this pathology. OBJECTIVES: Peripheral and autonomic nervous system function, the stage of microangiopathy, and the relationships between these in patients with SRP were analyzed. MATERIAL AND METHODS: In the study, 20 patients with CTD-related SRP and 30 healthy controls were subject to capillaroscopy, standard conduction velocity tests and conduction velocity distribution (CVD) tests in ulnar and peroneal nerves, heart rate variability (HRV), and sympathetic skin response (SSR) tests. RESULTS: There were no significant differences in the standard motor and sensory conduction velocity tests, or in CVD tests in the ulnar and peroneal nerves in SRP patients compared with the controls. The patients with SRP had a significantly lower SSR amplitude and longer latency in hands and feet. The patients with CTD-related SRP had a significantly lower mean HRV with higher low frequency (LF) values in the spectral analysis and expiration/inspiration ratio (E/I) during deep breathing. There was no correlation between the stage of microangiopathy and neurophysiological test results. CONCLUSIONS: Correct standard conduction velocity and CVD testing in patients with SPR suggest that vasomotor disturbances may occur in CTD regardless of peripheral neuropathy. The lack of relationship between SSR and microangiopathy could confirm that these 2 processes occur independently in patients with CTD-related SRP. Autonomic nervous system impairment together with normal peripheral nerve function suggest the central origin of CTD-related SRP.

The variety of clinical presentations in IgG4-related disease in Rheumatology.

IgG4-related disease (IgG4-RD) belongs to the group of rare diseases in which the identification of the characteristic histology and immunohistochemistry provides with the gold standard in the diagnosis. The variable organ dysfunction reflects the clinical presentation. The examples of different IgG4-RD presentations in the Rheumatology Unit were discussed in this article. The spectrum of IgG4-RD is wide-ranging and manifested in one or more organs synchronously or metachronously. In the presented article, we described five different cases of IgG4-RD. Four cases were reaffirmed in the histopathological assessment. The clinical and laboratory findings were analyzed and the assigned therapy was discussed. According to our experience, the diagnosis of IgG4-RD requires the careful clinicopathological correlation. The diagnosis relies on the coexistence of various clinical, laboratory, radiological, and histopathological findings, although none of them is pathognomonic itself. The time needed for the diagnosis and variety of clinical forms of IgG4-RD shows that there is need of the cooperation among many specialists for the better and earlier recognition of the disease.

Chest HRCT findings in patients with primary Sjögren's syndrome.

BACKGROUND: Pulmonary manifestations (PMs) in primary Sjögren's syndrome (pSS) are among the most frequent extraglandular complications, with reported prevalence varying widely (9-75%), depending on the methods of detection. OBJECTIVES: The aim of this study was to assess the incidence of PMs in pSS and to determine the factors predisposing to the occurrence of this complication. MATERIAL AND METHODS: The study group consisted of 68 patients with pSS. Among the patients who were possibly affected by PMs, chest High Resolution Computed Tomography (HRCT) was performed. RESULTS: In the group of all patients afflicted with pSS, 30 people indicated the need to expand medical imaging via chest HRCT scan. (The most frequent reason, in 80%, was persistent, dry cough periodically waking up patients at night). The chest HRCT scan revealed lung tissue changes in the course of 29% of all examined patients (of 68). No correlation was found between the occurrence of HRCT changes and the age of patients (p = 0.8), increased CRP > 5 mg/1 (p = 0.1) or ESR > 20 mm/h (p = 0.9), focus score (p = 0.8), leucopenia (p = 0.5), RF value (p = 0.3), gamma globulin value (p = 0.5), intensity of eye and oral cavity dryness (p = 0.6; 0.3) and smoking cigarettes. Additionally, no correlation was found between more frequent occurrences of antibodies anti-SSA, anti-SSB or anti-Ro52 and HRCT changes (p = 0.3; 0.07; 0.4). Pertaining to the clinical signs, HRCT changes occurred more often only in patients suffering from peripheral arthritis (p < 0.01). CONCLUSIONS: PM is a frequent symptom of pSS. A factor predisposing to the development of changes in the respiratory system was not found. Changes in HRCT occur more frequently in patients with peripheral arthritis.

Palpable mass of the neck in the course of Takayasu arteritis.

Takayasu arteritis is a rare, idiopathic inflammatory disease of the aorta and its major branches, usually affecting young women of Asian descent. In the course of the disease stenosis, occlusions as well as dilatations and aneurysms of vessels occur. Because of many possible localizations of pathological changes, the symptoms have a wide range, but the most common are a weak pulse or its absence on the brachial artery and a difference in systolic pressure above 10 mm Hg between the upper extremities. Here we present a case report of a young woman with Takayasu arteritis, who presented a palpable mass in the back of her neck, significantly diminished after treatment with glucocorticoids.

Inclusion body myositis associated with Sjögren's syndrome.

Inclusion body myositis (IBM) belongs to the group of idiopathic inflammatory myopathies. It is a poorly understood disease, which affects skeletal muscles. IBM usually occurs as an isolated condition, but in some cases, it may be associated with another autoimmune disorder, Sjögren's syndrome. We report a case of a 47-year-old woman with headaches, symptoms of trigeminal neuralgia, progressive weakness in muscles of the upper and lower extremities and symptoms of dry eyes and mouth. On admission, creatine kinase level was increased to 6,956 IU/mL and lactate dehydrogenase (LDH) to 1,011 U/L in the serum. The increase in inflammatory factor (CRP, ESR) levels was not found. The diagnosis of inclusion body myositis associated with Sjögren's syndrome was established on the basis of clinical picture and diagnostic tests. In this therapy, methotrexate and methylprednisolone were administered. The considerable improved muscle strength in the upper and lower extremities, improved speech and swallowing, disappearance of headache and reduction in CPK and LDH levels were found 8 months after establishing the diagnosis. Treatment with methotrexate and methylprednisolone improved the clinical symptoms and quality of life of this patient and may offer a therapeutic option for some patients with IBM and concomitant Sjögren's syndrome.

[Active psoriatic arthritis during pregnancy: challenges and limitations of pharmacotherapy]. / Aktywna postac Luszczycowego zapalenia stawów w ciazy--wyzwania i ograniczenia farmakoterapii.

Cases of psoriatic arthritis coexisting with pregnancy are sparse and therefore little is known about the fetal effect of medication in women with psoriatic arthritis. As a rule, drugs and dosages are minimized in these patients. Among disease-modifying antirheumatic drugs, cyclosporine and sulphasalazine are preferred. Methotrexate and leflunomide are strictly contraindicated and must be withdrawn 3 months or 2 years, respectively, before a pregnancy is planned. Psoriatic arthritis may be treated during pregnancy with glucocorticosteroids, especially with prednisone or prednisolone. We present the case ofa 40-year-old gravida with psoriatic arthritis which exacerbated during the first trimester of pregnancy. Therapeutic implications in such cases are discussed.

[A case of early recognized Wegener's granulomatosis with renal involvement. Insights for early diagnosis]. / Ziarniniak Wegenera--wczesnie rozpoznana postac z zajeciem nerek. Jak poprawic wczesna wykrywalnosc choroby?

Systemic necrotic and granulomatous vasculitis presents with vascular involvement in almost every organ, manifesting with stenosis, ischemia, infarction, or hemorrhage. The clinical picture depends on the kind and size of the involved vessels and on the activity of the inflammatory process. Wegener's granulomatosis is a necrotic, granulomatous inflammation of small vessels of the upper and lower airways and kidneys. We present the case of a 25-year-old male in whom the definitive diagnosis of Wegener's granulomatosis was achieved within five weeks from onset. Among the first symptoms were microinfarcts localized in the fingertips and the nail matrix; their nature was investigated with capillaroscopy.