Incidence and prevalence of large vessel vasculitis (giant cell arteritis and Takayasu arteritis) in northern Italy: A population-based study

ObjectivesTo investigate the epidemiology of the entire spectrum of large vessel vasculitis (LVV) in a well-defined population from a Northern Italian area.MethodsAll patients with incident giant cell arteritis (GCA) diagnosed from 2005 to 2016 and all patients with incident Takayasu arteritis (TAK) diagnosed from 1998 to 2016 living in the Reggio Emilia area were identified. Only patients satisfying the modified inclusion criteria of the GiACTA trial, and the 1990 ACR classification criteria for TAK were included. The epidemiology of cranial- and LV-GCA was separately evaluated.Results207 patients were diagnosed with GCA and 5 with TAK. 123 patients had cranial-GCA, 53 patients had LV-GCA, and the remaining 31 patients had overlapping features. The standardized annual incidence rate of GCA was 8.3 (95% CI 7.1, 9.4) per 100,000 population ages ≥50 years. The standardized annual incidence rate of cranial-GCA (6.1 [95% CI 5.1, 7.1] per 100,000 population ages ≥50 years) was double the rate of LV-GCA (3.4 [95% CI 2.7, 4.2]). The age-specific incidence rates were similar in the <70 and >90 years age groups, but they were higher in cranial-GCA than in LV-GCA in the age groups 70–79 and 80–89 years. The age- and sex-adjusted annual incidence rate of TAK was 0.5 (95% CI 0.1, 1.2) per 1,000,000 population.ConclusionIncidence of GCA is higher than previously reported by study evaluating only biopsy-proven or ACR classification criteria confirmed cases. Cranial-GCA and LV-GCA have epidemiological differences. TAK is an extremely rare disease also in Italy.     

Tocilizumab for the treatment of large‐vessel vasculitis (giant cell arteritis,Takayasu arteritis) and polymyalgia rheumatica

Objective

The interleukin‐6 pathway is up‐regulated in giant cell arteritis (GCA), Takayasu arteritis (TA), and polymyalgia rheumatica (PMR). We retrospectively assessed the outcomes of 10 patients with relapsing/refractory GCA, TA, or PMR treated with tocilizumab (TCZ).

Methods

Patients with GCA (n = 7), TA (n = 2), and PMR (n = 1) received TCZ. Seven subjects had failed at least 1 second‐line agent. The outcomes evaluated were symptoms of disease activity, inflammatory markers, ability to taper glucocorticoids, and cross‐sectional imaging when indicated clinically.

Results

The mean followup time of this cohort since diagnosis was 27 months (range 16–60 months). The patients were treated with TCZ for a mean period of 7.8 months (range 4–12 months). Before TCZ therapy, the patients experienced an average of 2.4 flares/year. All patients entered and maintained clinical remission during TCZ therapy. The mean daily prednisone dosages before and after TCZ initiation were 20.8 mg/day (range 7–34.3 mg/day) and 4.1 mg/day (range 0–10.7 mg/day), respectively (P = 0.0001). The mean erythrocyte sedimentation rate declined from 41.5 mm/hour (range 11–68 mm/hour) to 7 mm/hour (range 2.2–11.3 mm/hour; P = 0.0001). The adverse effects of TCZ included mild neutropenia (n = 4) and transaminitis (n = 4). One patient flared 2 months after TCZ discontinuation. An autopsy on 1 patient who died from a postoperative myocardial infarction following elective surgery revealed persistent vasculitis of large and medium‐sized arteries.

Conclusion

TCZ therapy led to clinical and serologic improvement in patients with refractory/relapsing GCA, TA, or PMR. The demonstration of persistent large‐vessel vasculitis at autopsy of 1 patient who had shown a substantial response requires close scrutiny in larger studies.     

A case of Takayasu arteritis complicated by Castleman's disease

We describe the first case of Takayasu Arteritis (TA) complicated by multicentric hyaline-vascular type of Castleman's disease (CD) which was diagnosed by the biopsy of mediastinal lymphnode 23 years after the diagnosis of TA. CD is classified as a lymphoid disorder of immune regulation characterized by a systemic, unregulated B cell proliferation, and there are some reports about the coincidence of CD and autoimmune diseases. This case has allowed us to gain some insight into a possible relation between the two disorders.     

Coexistence of 3q29 microdeletion syndrome and Takayasu arteritis: A case report

Takayasu arteritis (TAK) is a rare type of large and medial vessel systemic vasculitis. A variety of factors are thought to play a role in the occurrence and development of TAK such as human leukocyte antigen-B52, autoimmunity, inflammation and environmental factors. 3q29 microdeletion syndrome is also a very rare inherited disease, which includes intellectual disability, growth retardation and neuropsychiatric disorders. Here, we present a case with concomitant TAK and 3q29 microdeletion syndrome. A 22-year-old woman presented to the emergency department with sudden bilateral vision loss and severe headache. During physical examination, the patient was noted to have a difference in blood pressure between extremities. Computed tomography angiography revealed vascular wall inflammation in the abdominal aorta. Based on clinical and radiographical findings, a diagnosis of TAK was made. Concurrently, the patient was found to have short stature and intellectual disability. A possible genetic etiology was sought out. Chromosome analysis showed a 1.5 Mb heterozygous deletion on chromosome 3 and a diagnosis of 3q29 microdeletion was made. Additional imaging also revealed a split cord in medulla spinalis along with hemivertebrae and fusion anomalies, neither of which were reported in TAK or 3q29 microdeletion cases in the literature.     

Fever of unknown origin: large vessel vasculitis diagnosed by PET/CT

PET/CT is starting to play an important role in evaluating fever of unknown origin (FUO), due to its ability to localize and delineate areas of high metabolic activity, such as neoplastic proliferation and inflammation, including vasculitis. We present a case of giant cell arteritis (GCA) in a 72-year-old female patient admitted to our department with a 4-month history of FUO, weight loss and fatigue, without specific symptoms or signs. Laboratory investigations suggested acute phase response, with a pronounced erythrocyte sedimentation rate, high CRP level and microcytic anemia. A thorough diagnostic evaluation was performed to exclude an unknown primary tumor, which was initially suspected due to a positive family history of cancer. Surprisingly, PET/CT revealed large vessel vasculitis affecting the ascending, descending and abdominal aorta, as well as subclavian, proximal brachial and carotid arteries bilaterally. Biopsy of the superficial temporal artery confirmed the diagnosis of GCA. Treatment with methylprednisolone and azathioprine led to resolution of clinical symptoms and normalization of laboratory parameters. In addition to the use of PET/CT in the evaluation of FUO, its value as a method complementary to temporal artery biopsy is also discussed.     

Takayasu arteritis in China: A report of 530 cases

A total of 530 patients with Takayasu arteritis were studied. Among 346 patients who were diagnosed by aortography, the female to male ratio was 2.9 to 1, and the age of onset ranged from 5 to 45 years. Three hundred and eighteen (60%) patients with secondary hypertension, including renovascular hypertension in 281, and 197 (37.2%) with pulseless extremities were found in the series. All the patients were treated with medical or surgical procedures. Surgical treatment is preferred if clinical status of the patient permits. The patients were followed for 1–29 years (average 7.8 years). There were 55 deaths (10.4%) in this series. Cerebral hemorrhage was found as a common cause of death. Five-year and ten-year survival rates were 93.1% and 91.1%, respectively.     

A case of Takayasu arteritis complicated by Castleman’s disease

We describe the first case of Takayasu Arteritis (TA) complicated by multicentric hyaline-vascular type of Castleman’s disease (CD) which was diagnosed by the biopsy of mediastinal lymphnode 23 years after the diagnosis of TA. CD is classified as a lymphoid disorder of immune regulation characterized by a systemic, unregulated B cell proliferation, and there are some reports about the coincidence of CD and autoimmune diseases. This case has allowed us to gain some insight into a possible relation between the two disorders.     

Takayasu arteritis with acute interstitial pneumonia and coronary vasculitis: expanding the spectrum. report of a case

We describe the first reported case of Takayasu arteritis presenting as idiopathic adult respiratory distress syndrome, with a pathologic diagnosis of acute interstitial pneumonia. In the same patient, rarely occurring, diffuse coronary vasculitis developed. This case vividly illustrates the extensive, clinically significant vascular involvement that can occur in Takayasu arteritis, as well as the potential extravascular, multisystemic nature of the disease.     

Large vessel vasculitis without temporal artery involvement: Isolated form of giant cell arteritis?

Summary Diffuse arterial involvement in giant cell arteritis (GCA) is well recognized. By contrast, GCA clinically isolated to large vessels without cephalic, rheumatologic or systemic symptoms represents a much rarer manifestation of the disease.We report the cases of 4 elderly women presenting with a diffuse and symptomatic occlusive disease without the typical signs of temporal arteritis, in whom biological, angiographic or pathological findings were suggestive of GCA. Medium to high dose oral corticosteroids were given to the 4 patients, in combination with various revascularization procedures, allowing a fair clinical response. Large vessel arteritis should be considered in elderly women with diffuse non-atherosclerotic occlusive disease and elevated erythrocyte sedimentation rate, even if typical features of GCA are lacking. In those cases, a long-term treatment with corticosteroids is mandatory, but surgical or angioplastic revascularization is often required.     

Prevention of strongyloides hyperinfection syndrome: A rheumatological point of view

BackgroundStrongyloides stercoralis (S.stercoralis) is a parasite that infects humans and in conditions of immunodeficiency may disseminate, causing the potentially fatal strongyloides hyperinfection syndrome (SHS). The aim of this review was to investigate the literature evidence on the prophylaxis of SHS in immunosuppressed patients with rheumatological disorders.Material and methodsThe MEDLINE database (from 1966 to 2008) was searched using the following terms: “strongyloidiasis”, “disseminated strongyloidiasis”, “Strongyloides stercoralis”, “Strongyloides stercoralis dissemination”, “strongyloides hyperinfection syndrome”, “treatment”, “prophylaxis”, “prevention”, “immunocompromised”, “immunodepression”, “immunosuppressed”, “immunosuppression”, “corticosteroids”, “glucocorticoids”, “lupus erythematosus”, “rheumatoid arthritis”, “rheumatic diseases”. A search of the therapeutic studies using the same set of terms was carried out.ResultsNo study on the prophylaxis of SHS restricted to rheumatic immunosuppressed patients was identified. However, two articles have been published on the prophylaxis of strongyloidiasis in other immunosuppressed patients. Additionally, 13 studies dealing with different therapeutical options for strongyloidiasis were identified and presented.ConclusionsSince there is no evidence on the prophylaxis of SHS in immunosuppressed rheumatic patients, the suggested regimen for that prophylaxis may rely on the results obtained from therapeutical studies. Ivermectin has the best safety profile, lower cost and best efficacy and should be the drug of choice for the prophylaxis of SHS in such patients. Although a definitive prophylactic regimen has not been defined, the option for 200 µg/kg/day for 2 days, repeated within 2 weeks, seems to be a reasonable approach. Such regimen should be repeated every 6 months in case of persisting immunosuppression in permanent residents of endemic areas.     

Gemcitabine-induced large vessel vasculitis demonstrated by PET CT: a rare,important side effect

Gemcitabine is a nucleoside analogue used widely across haemato-oncology. Side effects are generally predictable, and typically consist of cytopenia, nausea, and infection. As the present case clearly demonstrates, gemcitabine is in rare cases associated with life-threatening large vessel vasculitis, which can involve the aorta. It is important to consider gemcitabine-induced vasculitis in non-specifically unwell patients with raised inflammatory markers and fever of unknown origin, with or without signs of vascular compromise. Early recognition, cessation of gemcitabine therapy, and high-dose steroids are critical for a good outcome. PET CT is valuable to diagnose large vessel vasculitis and monitor treatment response.     

Childhood-onset versus adult-onset Takayasu arteritis: A study of 141 patients from Turkey

AimTo compare childhood-onset (c-TAK) versus adult-onset Takayasu arteritis (a-TAK) patients for vascular involvement, disease activity, damage, and treatment.MethodsPatient charts from two tertiary-care centers of a pediatric and adult rheumatology clinic were reviewed. Adult patients diagnosed before the age of 18 years were included in the childhood-onset group. The activity was assessed with the physician's global assessment (PGA) and Indian Takayasu Clinical Activity Score (ITAS). The damage was evaluated with Takayasu Arteritis Damage Score (TADS) and Vasculitis Damage Index (VDI).ResultsTwenty-four c-TAK (follow-up duration: 53 months) and 117 a-TAK patients (follow-up duration: 68 months) were analyzed. Aorta involvement was more prevalent (79% vs. 33%), and the median PGA score was higher in the c-TAK group (9 vs. 7), whereas the mean Indian Takayasu Arteritis Score was similar (14 vs. 13) among both groups. Median VDI score was lower for c-TAK patients (4 vs. 5), whereas TADS was similar for children and adults (8 vs. 8). Higher incidence of glucocorticoid related side-effects, a longer time to diagnosis and upper extremity claudication seemed to account for higher VDI scores in adults.ConclusionAorta involvement was more common among children with TAK, whereas upper extremities were relatively spared. Biologic agents were used more commonly among children which may be explained by higher rates of aortic involvement. However, c-TAK patients did not have greater cumulative damage.     

Advances in the diagnosis of large vessel vasculitis: identification of biomarkers and imaging studies

Depending on the geographic area and the affected age group, large vessel vasculitis (LVV) are one of the most frequent types of systemic vasculitidies. Whereas giant cell arteritis (GCA) occurs exclusively in elderly individuals and is more frequent in countries with European ancestry, Takayasu?s arteritis (TA) mainly affects young women from eastern countries. The diagnosis of these disorders has been based on the characteristic clinical picture, together with the typical histopathological features in the temporal artery of patients with GCA, and the angiography results in TA patients. During the last few years, no new biomarkers have substituted the traditional ones (ESR and CRP) in the diagnosis and monitoring of disease activity in LVV. Only the levels of circulating IL-6 have demonstrated a higher sensitivity compared with the classic acute phase reactants, but its utility is limited due to its lack of inclusion as a routine technique. On the other hand, imaging techniques play a relevant role in the diagnosis and follow-up of patients with LVV. The use of new non-invasive techniques such as MRI, Doppler ultrasound, PET scan or CT has helped to improve the understanding of these disorders, although the sensitivity and specificity of these new imaging techniques compared with the classic temporal artery biopsy or angiography for diagnosis and follow-up remains to be established.     

Aortic dilatation in patients with large vessel vasculitis: A longitudinal case control study using PET/CT

ObjectiveTo evaluate aortic diameter and predictors of aortic dilatation using ¹⁸FDG-PET/CT in a longitudinally followed cohort of patients with large vessel vasculitis (LVV) compared with controls.MethodsAll consecutive patients with LVV who underwent at least 2 PET/CT scans between January 2008 and May 2015 were included. The first and last PET/CT study was evaluated by a radiologist and a nuclear medicine physician. Diameter and FDG uptake of the aorta was measured at 4 different levels: ascending, descending thoracic, suprarenal and infrarenal abdominal aorta. Twenty-nine age- and sex-matched patients with lymphoma who underwent at least 2 PET/CT scans in the same time interval were selected as controls.Results93 patients with LVV were included in the study. In the time interval between first and last PET/CT study (median time 31 months), the diameter of the ascending, descending thoracic and suprarenal abdominal aorta significantly increased in LVV patients but not in controls. At last PET/CT, patients with LVV compared with controls had higher diameter of ascending [35.41 (5.54) vs 32.97 (4.11) mm, p = 0.029], descending thoracic [28.42 (4.82) vs 25.72 (3.55) mm, p = 0.007] and suprarenal abdominal aorta, mean [25.34 (7.01) vs 22.16 (3.26) mm, p = 0.005] and more frequently had aortic dilatation [19% vs 3%, p = 0.023]. Significant predictors of aortic dilatation were male sex [OR 7.27, p = 0.001] and, only for GCA, hypertension [OR 6.30, p = 0.031]. Finally, GCA patients with aortic FDG uptake grade 3 at first PET/CT, compared to those with aortic FDG uptake ≤2, had significantly higher aortic diameter.ConclusionsPatients with LVV are at increased risk of aortic dilatation compared with age- and sex-matched controls. Significant predictors of aortic dilatation are male sex and, only for GCA, hypertension. GCA patients with aortic FDG uptake grade 3 are at increased risk of aortic dilatation.