Coexistence of IgG4-related disease and ANCA-associated vasculitis: case report and review of the literature.

IgG4-related disease (IgG4-RD) is a fibroinflammatory condition that is characterized by storiform fibrosis, infiltration of IgG4-positive lymphocytes, obliterative phlebitis, and high IgG4 levels. Since IgG4-RD affects a wide variety of organs, a differential diagnosis must include multiple conditions. IgG4-RD is also believed to coexist with certain diseases. In recent years, case reports and case series describing the co-occurrence of IgG4-RD and ANCA-associated vasculitis (AAV) have been published. We intended to evaluate patients with IgG4-RD and AAV overlap in the literature using a case similar to one that was diagnosed and monitored in our department. We searched the databases of Web of Science, Scopus, and Google Scholar as well as PubMed with the keywords ANCA, IgG4, IgG4-RD, granulomatosis with polyangiitis, Wegener's granulomatosis, microscopic polyangiitis, Eosinophilic granulomatosis with polyangiitis, and Churg-Strauss syndrome. Cases and Case series addressing the coexistence of IgG4-RD and AAV have been selected. Comprehensive diagnostic criteria are used to diagnose IgG4-RD. The Chapel Hill Consensus Conference nomenclature criteria were used for the inclusion of AAV. Out of a total of 910 publications, 20 articles, including 65 cases, were found to be eligible. Forty-seven cases with IgG4-RD were evaluated as definitive (71.2%), 10 cases as probable (15.1%), and 9 cases as possible IgG4-RD (13.6%). 26 patients were diagnosed with GPA, 1 patient with localized GPA, 23 patients with MPA, and 4 patients with EGPA. The aorta, lacrimal tissue, pancreas, and retroperitoneum are the sites of IgG4-RD rather than AAV. AAV and IgG4-RD might coexist in the same patient. IgG4-RD is mainly associated with GPA.

Evaluation of tocilizumab-induced hypofibrinogenemia in rheumatology practice: a retrospective, real-life, single-center experience.

Tocilizumab (TCZ) which is a humanized interleukin (IL)-6 receptor antibody has been increasingly widespread used in rheumatology practice. TCZ-related hypofibrinogenemia is a not well-described side effect, but awareness seems to be incresing as publications on this topic are also becoming more frequent. Our aim in this study was to determine the frequency, timing, and approach to TCZ-related hypofibrinogenemia in rheumatic diseases. We retrospectively screened our patients who received TCZ for inflammatory rheumatic diseases and studied serum fibrinogen at least once before and/or after drug administration. We recorded and analyzed demographic features (age, gender, diagnosis), comorbidities, laboratory parameters, management, and outcome data. 30 patients who received TCZ due to rheumatological diseases and had at least one fibrinogen level were included in this study. 73.3% were female and median age was found to be 65 (42-82) years, with median disease duration of 148 (36-500) months. 90% of the patients received TCZ for RA and 10% for GCA. We examined the fibrogen levels at an average of 24 months (min 1 max 108) following the start of TCZ treatment. The study group was divided into those with normal fibrinogen levels (normal fibrinogen group) and those with low fibrinogen levels (lowfibrinogen group). In total, hypofibrinogenemia was found in 14 (46.6%) patients. Median serum fibrinogen level in the low fibrinogen group after TCZ was calculated to be 151.5 mg/dl (min 92 max 171). Most patients were asymptomatic (71.4%). Ecchymoses were in seen 4 (28,6%) patients. No major bleeding were seen. TCZ was discontinued in 5 out of 14 patients (35.7%), while 9 out of 14 patients (64.3%) were closely followed. Outcomes regarding fibrinogen levels (11 out of 14) were as follows: increase in 4 and not checked in one after cessation of the drug, 3 spontaneous increases under the drug, and 3 persistently low levels on TCZ treatment. We found no difference in terms of gender (p = 0.417), platelets (p = 0.343), ESR (p = 0.448), and CRP (p = 0.660) at the time of TCZ initiation between groups. TCZ-related hypofibrinogenemia is more frequent than expected with occurence in both the early and late stages of treatment. Further research is required to determine whether to regularly measure fibrinogen levels in patients using TCZ and how to treat patients with hypofibrinogenemia.

Neurologic manifestations of Behçet disease: rheumatology experience.

OBJECTIVE: Neurologic involvement in Behçet disease (BD) is a rare manifestation. Herein, we aimed to evaluate the clinical features and treatment choices of neuro-Behçet (NB) patients. METHODS: There were records of 800 BD patients between 1998 and 2021. Fifty-five of the BD patients had NB and the files of these patients were retrospectively evaluated. Patients were grouped into three subgroups: 22 (40%) had non-parenchymal, 25 (45%) had parenchymal, and 8 (15%) had both parenchymal and non-parenchymal (mixed) involvement. RESULTS: Of the 55 patients, 32 were male. Twenty-six of the NB patients were diagnosed with BD simultaneously. The most common complaint was headache (n = 24, 44%). The most affected site was periventricular white matter (n = 21, 38%). All patients had received corticosteroids. Azathioprine (AZA; n = 39, 71%) was the most common immunosuppressive agent after corticosteroids, followed by cyclophosphamide (n = 16, 29%). CONCLUSION: Neurologic involvement is a rare complication of BD but is related to increased mortality and morbidity. Neurologic manifestations may be the initial symptom of BD, thus leading to diagnosis. Both neurology and rheumatology specialists should be aware of this rare condition.

Evaluation and Differential Diagnosis of Hypereosinophilia in Rheumatology Practice.

BACKGROUND: There has been no investigation so far on the prevalence or causes of hypereosinophilia during rheumatic diseases. OBJECTIVES: The study aimed to identify the prevalence and causes of hypereosinophilia among the patients followed in a rheumatology department. METHODS: The patients aged 18 years or over followed in our rheumatology department between January 2010 and December 2019 who had at least one AEC ≥1,500/µL measurement in their peripheral blood count were identified retrospectively. RESULTS: Over the 10 years, a total of 130,769 peripheral blood counts were performed, of which 3.9% showed eosinophilia and 0.065% showed hypereosinophilia. Hypereosinophilia was identified in 85 patients. The underlying rheumatic disease was determined in 89.4% (n = 76) of patients. Of these, the most frequent one was rheumatoid arthritis at a ratio of 40.8%, followed by eosinophilic granulomatosis with polyangiitis (EGPA) at a ratio of 10.5%. Hypereosinophilia was in primary form in 3.5% of the patients, whereas secondary to another condition in 91.8% (n = 78) of the cases and idiopathic in 4.7% (n = 4) of patients. The most common cause of secondary hypereosinophilia was drug induced, as detected in 61.2%, followed by allergic conditions in 11.5% and EGPA in 9.4%. In 15.2% (n = 13) of the cases, hypereosinophilia was associated with an underlying rheumatic disease. In the cases with drug-induced hypereosinophilia, most often (in 28.8%) methotrexate was the offending agent. CONCLUSIONS: Rheumatologists should be cognizant that hypereosinophilia concurrent to rheumatic diseases is usually not due to the underlying rheumatic disease, except for the conventional eosinophil-related rheumatic diseases.

Hypercalcemia in IgG4-related disease: coincidental or associated? Case based review.

Immunoglobulin (Ig) G4-related disease (IgG4RD) is a chronic autoimmune disorder characterized by dense lymphoplasmacytic infiltrations and fibrosis of storiform pattern. The most typical manifestations include major salivary or lacrimal gland involvement, autoimmune pancreatitis, and retroperitoneal fibrosis. While the increase in IgG4 is the typical feature of the disease, hypercalcemia has been rarely reported in IgG4RD so far, only one of these cases has been shown parathyroid gland involvement (isolated involvement). In this study, we present a 43-year-old female patient with weight loss, pancreatic mass, lymphadenopathy, nodular lesion in the lung, hypercalcemia, and also increased level of serum IgG4. Histopathological investigation following parathyroidectomy revealed a dense lymphoplasmacytic infiltrate with an IgG4 to IgG ratio of > 50% in the fat tissue surrounding the parathyroid gland, particularly at the perivascular areas. This is the first systemic IgG4RD case in combination with hypercalcemia in the literature who was detected to have parathyroid adenoma. Our aim in this review is to emphasize that, although rarely, IgG4RD may be accompanied by hypercalcemia and parathyroid gland may be one of its target sites.

The coexistence of IgA vasculitis and tuberculosis: a case-based review.

Immunoglobulin (Ig) A vasculitis (IgAV), formerly known as Henoch-Schonlein purpura (HSP), is a relatively uncommon form of vasculitis primarily targeting the skin, gastrointestinal system, and the kidneys. Although the pathogenesis has not yet been well identified, several triggering factors, such as infections, drugs, have been implicated in the development of IgAV. Tuberculosis (TB), albeit rare, may precipitate IgAV. Herein, we have presented a case manifested by purpuric skin rash and proteinuria 6 weeks following diagnosis of pulmonary tuberculosis while receiving anti-TB drugs. The case was diagnosed as having active tuberculosis and TB-related IgA vasculitis with multi-organ involvement. In this case-based review, we recruited cases with TB-related Ig A vasculitis from the literature and discussed the features of tuberculosis that mimic vasculitides and vice versa. We also discussed the difficulties in diagnosis and the therapeutic approach in the light of the literature.

Scoping beyond pulmonary artery involvement; pulmonary involvement in Behcet's disease; a retrospective analysis of 28 patients.

OBJECTIVES: Pulmonary involvement other than pulmonary artery involvement in Behcet's disease still remains an area of investigation. The aim of this study was to evaluate pulmonary involvement associated with Behcet's disease. METHOD: We retrospectively investigated all Behcet's disease patients in terms of pulmonary involvement. Twenty-eight patients, whose radiologic examinations were consistent with Behcet's disease-related involvement after excluding other possibilities, were included in this study. Data regarding demographic characteristics, other clinical components of Behcet's disease, treatment modalities, and types of pulmonary involvement were analyzed. RESULTS: Pulmonary involvement was seen more common in male (82.1% vs 17.9%). Mean age for Behcet's disease diagnosis was found 32 years (SD 10.9) and mean age for pulmonary involvement was calculated 37 years (SD 11.4). Deep vein thrombosis (DVT) was the most common associated vascular involvement (53.6%). In our study population, alveolar hemorrhage and/or ground glass appearance were seen in 46.4% (13/28) of BD patients with pulmonary involvement. Totally, pulmonary artery aneurysm (PAA), small-sized pulmonary vasculitis (sPV), and pulmonary thrombosis (PT) were seen in 7 (25%), 13 (46.3%), and 18 (64.4%) of patients, respectively. Intracardiac thrombosis (ICT) in the right ventricle was present in 5 patients. Cyclophosphamide (CYC) was the most common preferred agent (78%) followed by azathioprine (AZA) in the first line. Warfarin was used in 18 patients. Overall mortality was seen in 3 patients: 1 due to PAA bleeding and others with unknown causes. CONCLUSION: Despite the importance of pulmonary artery involvement and pulmonary thrombosis in Behcet's disease, small-sized pulmonary vasculitis in the form of small vessel involvement is generally overlooked. Our study findings have shown that alveolar hemorrhage and/or ground-glass appearance in the absence of pulmonary artery aneurysm and pulmonary thrombosis are seen commonly as well. Key Points • The characteristics of pulmonary small vasculature involvement in Behcet's disease which is still an area of investigation warrant further attention. • The clinician should bear in mind that the spectrum of pulmonary involvement in Behcet's disease may be variable, but an extensive work up is still of great importance especially in atypical cases.

Effect of aerobic exercise training on oxygen uptake and kinetics in patients with fibromyalgia.

The aim of this study is to investigate relation between cardiopulmonary performance and muscular microcirculation in patients with fibromyalgia syndrome (FMS). Twenty-one female sedentary patients who were diagnosed as FMS, and 15 sedentary females were enrolled in to the study. All participants underwent a modified Bruce multistage maximal treadmill protocol with metabolic measurements and Near-Infrared Spectroscopy measurements. Exercise sessions were performed 3 times a week for 8 weeks. The results of the study suggest that cardiopulmonary system in charge of delivering oxygen to whole body and muscular microcirculation may have dysfunction in patients with FMS.

Reduced tolerance of exercise in fibromyalgia may be a consequence of impaired microcirculation initiated by deficient action of nitric oxide.

Although the underlying mechanism responsible for muscular fatigue and exercise intolerance remains to be elucidated, it is reported two major mechanisms, central and peripheral hypothesis. As a peripheral mechanism, there are few reports on abnormalities of the microcirculation in patients with fibromyalgia. The key point to note is that ischemia associated with a modest decline in tissue oxygen causes muscle fatigue. It has been shown that have been found low muscle levels of phosphates and abnormalities in microcirculation in fibromyalgia. Based on several novel data, production abnormalities of nitric oxide level might lead to symptoms of fatigue as a long term effect. There a vicious cycle concerning impairment of microcirculation in FM. The cycle is firstly initiated decrease of production of nitric oxide in the endothelial level by some trigger factors. Changed level of nitric oxide may cause microcirculation abnormalities in the tissue levels, muscular region. At the end of these phases, muscular fatigue and exercise intolerance may progressively develop in the FM. It is possible that this theory appears to provide a physiopathological explanation for decreased exercise capacity in patients with fibromyalgia. This paper describes a plausible mechanism for the development of exercise intolerance on microcirculation abnormalities.

SPA therapy in fibromyalgia: a randomised controlled clinic study.

OBJECTIVE: The aim of the present study is to evaluate the effectiveness of spa therapy in the management of fibromyalgia. METHODS: Thirty women with fibromyalgia were randomly assigned to either a spa therapy group or a control group. The spa therapy group (n = 16) had spa treatment for 2 weeks in addition to their medical treatment. The control group (n = 14) continued to have their medical treatment and/or daily exercises. An investigator who was blinded for the intervention assessed all the patients for 9 months. Improvements in Fibromyalgia Impact Questionnaire (FIQ), pain and number of tender points were primary outcomes. Secondary outcome measures were improvement in sleep disturbance, fatigue, gastrointestinal symptoms, anxiety, Beck Depression Inventory and patient's global evaluation. RESULTS: the spa group was found to be superior to the control group at the end of intervention in terms of FIQ, pain, tender point count, fatigue and patients' global assessment. This superiority remained for 6 months in FIQ, 1 month in pain and tender point count. CONCLUSION: It was concluded that the addition of spa therapy to medical therapy has both short- and long-term beneficial effects in female patients with fibromyalgia.