Objective To determine the frequencies and types of ophthalmologic manifestations in patients with systemic necrotizing vasculitides (SNV), including polyarteritis nodosa (PAN) and ANCA-associated ...vasculitides (granulomatosis with polyangiitis (Wegener's, GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA); Churg–Strauss syndrome (CSS)) and review the literature on eye involvement in these diseases. Methods This retrospective analysis was conducted on the ophthalmologic manifestations of SNV patients entered into the French Vasculitis Study Group database between July 1955 and August 2008. Results Among the 1286 identified patients, 214 (16.6%) had ophthalmologic manifestations at diagnosis, significantly more often in GPA (117/343, 34.1%) than in EGPA (30/270, 11.1%; P = 0.0001), PAN (42/393, 10.7%; P = 0.0001) or MPA (25/280, 8.9%; P = 0.0001). The 3 most common recorded ophthalmologic manifestations were conjunctivitis (89, (7%)), episcleritis (56, (4%)), and/or blurred vision (44, (3%)), mainly caused by retinal vasculitis in 5, oculomotor nerve palsy in 4, uveitis in 4 and/or optic neuropathy in 3. Orbital inflammatory tumor, another common feature was rather specific to GPA (23/349, 6.6% ( P = 0.0001)) compared to other SNV. The literature on ophthalmologic manifestations of SNV is limited to case reports except for GPA, in which the eye involvement frequency ranged from 29% to 57%. Conclusions Eye manifestations were more common in GPA than MPA, PAN and EGPA, but can be sight-threatening in any SNV. Given the heterogeneity of ophthalmologic involvement in SNV, close collaboration between the ophthalmologists and internists is critical.
Scleroderma Renal Crisis Guillevin, Loïc; Mouthon, Luc
Rheumatic diseases clinics of North America,
08/2015, Volume:
41, Issue:
3
Journal Article
Peer reviewed
Scleroderma renal crisis is a rare complication of systemic sclerosis (SSc) that remains severe. Prompt recognition and initiation of therapy with an angiotensin-converting-enzyme inhibitor offer the ...best chance to achieve a good outcome. SSc prevalence is poorly known, with disparities among countries.
Heart involvement is the leading cause of death of patients with eosinophilic granulomatosis with polyangiitis (EGPA; formerly Churg-Strauss syndrome) and is more frequent in anti-neutrophil ...cytoplasm antibody (ANCA)-negative patients. Post-transplant outcome has only been reported once.
We conducted a retrospective international multicenter study. Patients satisfying the criteria of the American College of Rheumatology and/or revised Chapel Hill Consensus Conference Nomenclature were identified by collaborating vasculitis and transplant specialists, and the help of the Churg-Strauss Syndrome Association.
Nine ANCA(-) patients who received transplants between October 1987 and December 2009 were identified. The vasculitis and cardiomyopathy diagnoses were concomitant for 5 patients and separated by 12 to 288 months for the remaining 4 patients. Despite ongoing immunosuppression, histologic examination of 7 (78%) patients' explanted hearts showed histologic patterns suggestive of active vasculitis. The overall 5-year survival rate was low (57%), but rose to 80% when considering only the 6 patients transplanted during the last decade. After survival lasting 3 to 60 months, 4 (44%) patients died sudden deaths.
The search for EGPA-related cardiomyopathy is mandatory early in the course of this type of vasculitis. Indeed, prompt treatment with corticosteroids and cyclophosphamide may achieve restore cardiac function. Most patients in this series were undertreated. For patients with refractory EGPA, heart transplantation should be performed, which carries a fair prognosis. No optimal immunosuppressive strategy has yet been identified.
Summary The objective of the study was to investigate the role of endothelin-1 in the pathogenesis of scleroderma renal crisis in patients with systemic sclerosis. We used immunohistochemical ...analysis with anti–endothelin-1 and anti–von Willebrand factor antibodies in comparing kidney biopsies from patients with systemic sclerosis and scleroderma renal crisis (n = 14); from normal kidneys (n = 5); and from patients with typical hemolytic uremic syndrome and thrombotic microangiopathy (n = 5), antiphospholipid syndrome (n = 6), diabetic nephropathy (n = 5), minimal change disease with cyclosporine toxicity (n = 5), or nephroangiosclerosis (n = 5). Kidney biopsies from all systemic sclerosis patients presented specific lesions: glomerular lesions with thickened capillary walls (n = 6, 42.8%), mesangiolysis (n = 3, 21.4%), fibrin thrombi (n = 3, 21.4%), hypertrophy of juxtaglomerular apparatus (n = 5, 35.7%), arteriolar lesions showing mucinous intimal thickening and lumen mucoid occlusions (n = 13, 92.8%), proliferation of intimal cells (ie, “onion-skin” lesions; n = 13, 92.8%), fibrinoid necrosis (n = 3, 21.4%), and fibrin thrombosis (n = 4, 28.6%). Chronic lesions in large arteries showed modifications such as fibrous intimal thickening (n = 13, 92.8%). The pattern of endothelial staining for endothelin-1 in both glomeruli and arteriolar lesions appears to be specific for scleroderma renal crisis. Glomerular endothelin-1 staining without arteriolar staining was seen in hemolytic uremic syndrome; and isolated arteriolar staining (without glomerular staining) was seen in a number of conditions including antiphospholipid nephropathy, cyclosporine toxicity, and diabetic nephropathy. Endothelin-1 is overexpressed in glomeruli and arterioles of patients with scleroderma renal crisis, which suggests that endothelin-1 might be a therapeutic target in this condition.
Abstract Objectives To describe the prevalence, characteristics, and outcome of cutaneous ischemia, and whether it can occur in systemic necrotizing vasculitides (SNVs), i.e., polyarteritis nodosa, ...granulomatosis with polyangiitis, and eosinophilic granulomatosis with polyangiitis and microscopic polyangiitis. Methods We conducted a retrospective analysis of all patients with SNV who were included in the French Vasculitis Study Group cohort database between March 1963 and September 2007. We compared characteristics and outcomes for patients with and without cutaneous ischemia (digital necrosis and/or isolated necrotic cutaneous ulcers). Results Among the 1304 patients with a diagnosis of SNVs, 40 (3.1%) had digital necrosis and 25 (1.9%) had isolated necrotic cutaneous ulcers, with an equal distribution among SNVs. Presence of cutaneous ischemia was associated with past and/or current smoking odds ratio (OR), 1.73; 95% confidence interval (95% CI), 1.02–2.95 and history of coronary artery disease (2.40; 1.01–6.00), as well as with other cutaneous manifestations (6.54; 3.21–8.67), gastrointestinal tract perforations (4.29; 1.41–13.07), and arthralgias (1.84; 1.10–3.07) during diagnosis. Ten patients with digital necrosis underwent extremity amputation, but no patient with isolated necrotic cutaneous ulcers ( p = 0.007) underwent it. Smoking was the main risk factor of amputation (OR, 9.1; 1.7–48.9). At a mean follow-up of 10 years, cutaneous ischemia was identified as an independent predictor of vasculitis relapse (hazard ratio, 1.47; 95% CI, 1.05–2.05) and all-cause death (1.66; 1.01–2.74). Conclusions Cutaneous ischemia is a rare manifestation of SNVs but is associated with an increased risk of relapse and mortality. Tobacco use is associated with amputation, which emphasizes the importance of managing conventional cardiovascular risk factors in SNV patients.
Background Plasma exchange may be effective adjunctive treatment for renal vasculitis. We performed a systematic review and meta-analysis of randomized controlled trials of plasma exchange for renal ...vasculitis. Study Design Systematic review and meta-analysis of articles identified from electronic databases, bibliographies, and studies identified by experts. Data were abstracted in parallel by 2 reviewers. Setting & Population Adults with idiopathic renal vasculitis or rapidly progressive glomerulonephritis. Selection Criteria for Studies Randomized controlled trials that compared standard care with standard care plus adjuvant plasma exchange in adult patients with either renal vasculitis or idiopathic rapidly progressive glomerulonephritis. Intervention Adjuvant plasma exchange. Outcome Composite of end-stage renal disease or death. Results We identified 9 trials including 387 patients. In a fixed-effects model, the pooled RR for end-stage renal disease or death was 0.80 for patients treated with adjunctive plasma exchange compared with standard care alone (95% CI, 0.65-0.99; P = 0.04). No significant heterogeneity was detected ( P = 0.5; I2 = 0%). The effect of plasma exchange did not differ significantly across the range of baseline serum creatinine values ( P = 0.7) or number of plasma exchange treatments ( P = 0.8). The RR for end-stage renal disease was 0.64 (95% CI, 0.47-0.88; P = 0.006), whereas the RR for death alone was 1.01 (95% CI, 0.71-1.4; P = 0.9). Limitations Although the primary result was statistically significant, there is insufficient statistical information to reliably determine whether plasma exchange decreases the composite of end-stage renal disease or death. Conclusions Plasma exchange may decrease the composite end point of end-stage renal disease or death in patients with renal vasculitis. Additional trials are required given the limited data available.
Abstract Objective The association between vasculitis and large granular lymphocyte (LGL) leukemia has rarely been reported or investigated. Thus, we assessed the clinical and biological phenotypes ...of LGL leukemia associated with vasculitis. Results We studied a series of 11 patients displaying LGL leukemia associated with vasculitis (LAV). The mean age at diagnosis of LGL leukemia was 60.3 years; there were nine women and two men. The mean follow-up period was 45 months. The main LGL lineage was T-LGL (10 patients), and only one NK-LGL was identified. Clinical and biological features of T-LGL leukemia were compared with those from the 2009 French T-LGL registry. We did not find any relevant differences except that patients with LAV were predominantly female ( p < 0.05). The most frequently observed vasculitis was cryoglobulinemia ( n = 5). Three patients presented with cutaneous leukocytoclastic angiitis, two patients had ANCA-negative microscopic polyangiitis, and one patient had giant cell arteritis. The main clinical features involved the skin, e.g., purpura (91%), arthralgia (37%), peripheral neuritis (27%), and renal glomerulonephritis (18%). The most frequent histologic finding was leucocytoclastic vasculitis (54%). The rate of complete remission was high; i.e., 80%. A minority of patients had a vasculitis relapse (27%). Three patients (27%) died; one death was related to LGL leukemia (acute infection) and the two other deaths were related to vasculitis (both with heart failure). Conclusion We conclude that vasculitis is overrepresented in the population of LGL patients, LAV predominantly affects women, vasculitis preferentially affects the small vessels, and LAV has high rate of complete response.
Hypereosinophilia (>0.5 × 109 /L) is a common clinical finding that can be secondary to a large variety of diseases (helminth infections, allergic diseases, drug reactions, specific organ disease, ...malignancies, systemic diseases). When a complete evaluation of a chronic hypereosinophilia fails to reveal an underlying disease, the diagnosis of hypereosinophilic syndrome (HES) or Churg–Strauss syndrome (CSS) is suggested.
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