Vasculitis Highlights
Philip Seo, MD, MHS
- Abstract 2013: The Five-Factor Score (FFS) Revisited: a Tool to Assess the Prognoses of Polyarteritis Nodosa (PAN), Microscopic Polyangiitis (MPA), Churg-Strauss Syndrome (CSS) and Wegener’s Granulomatosis (WG) Based on 1108 Patients from the French Vasculitis Study Group (FVSG)
- Abstract 2014: Reversible Cerebral Vasoconstriction Syndromes
- Abstract 2016: Patient-Reported Outcome Assessment in Primary Systemic Vasculitis Provides a Unique Perspective
- Abstract 2015: Severe infections during Giant Cell Arteritis and Polymyalgia Rheumatica course: incidence and mortality. The prospective, multicenter cohort GRACG study
- Abstract 2076: Randomized Control Study (single blinded) of Rituximab versus Cytotoxic Combination Therapy in Severe Ocular Lesions of Behcet’s Disease: Pilot Study (ClinicalTrial.gov ID: NCT00664599)
- Abstract 2075: Mycophenolate Mofetil (MMF) for Remission Induction and Maintenance in Microscopic Polyangiitis (MPA) with Mild to Moderate Renal Dysfunction - Prospective Pilot Trial in 17 Patients
- Abstract 2074: Diagnostic marker for Takayasu’s arteritis
- Abstract 2073: Changes in Inflammatory-Mediators Induced by Glucocorticoids in Cultured Human Temporal Arteries from Patinets with Giant-Cell Arteritis (GCA)
Abstract 2013: The Five-Factor Score (FFS) Revisited: a Tool to Assess the Prognoses of Polyarteritis Nodosa (PAN), Microscopic Polyangiitis (MPA), Churg-Strauss Syndrome (CSS) and Wegener’s Granulomatosis (WG) Based on 1108 Patients from the French Vasculitis Study Group (FVSG)
Authors:
Loïc Guillevin, Christian Pagnoux, Alfred Mahr, Philippe Le Toumelin
Background:
In 1996, the French Vasculitis Study Group performed an analysis of participants in their clinical trials to determine which features at baseline predicted the worst outcomes. The resulting index, known as the Five Factor Score (FFS), has been widely used as a predictor of mortality among patients with polyarteritis nodosa, microscopic polyangiitis, and the Churg-Strauss syndrome, but the basis of the index has not been re-examined for over a decade. To address this, this group (under the stewardship of Loic Guillevin) analyzed clinical data relevant to 1108 patients with either ANCA-associated vasculitis or polyarteritis nodosa to reassess the utility of the FFS, and to extend their tool to include Wegener’s granulomatosis.
Methods:
The French Vasculitis Study Group analyzed data regarding the clinical presentation of 1108 patients with systemic vasculitis, including 349 patients with polyarteritis nodosa, 218 patients with microscopic polyangiitis, 230 patients with the Churg-Strauss syndrome, and 311 patients with Wegener’s granulomatosis. All cases of ANCA-associated vasculitis were confirmed by biopsy; polyarteritis nodosa was confirmed either by biopsy or the presence of characteristic findings on angiogram. All patients met the Chapel Hill Consensus Conference and American College of Rheumatology criteria for diagnosis. Log rank and Cox proportional hazards models were constructed to identify risk factors for mortality.
Results:
Overall, 1 out of every 5 patients enrolled in this cohort had died. The five-year mortality by diagnosis was as follows: Wegener’s granulomatosis: 15.2%; microscopic polyangiitis: 22.6%; polyarteritis nodosa: 19.7%; Churg-Strauss syndrome: 10.8%. Based on this analysis, age > 65 years (hazard ratio 1.1), cardiac symptoms (hazard ratio 1.8), gastrointestinal involvement (hazard ratio 1.7) and renal insufficiency, defined as a serum creatinine >1.7 mg/dL (hazard ratio 1.6) were all associated with an increase in mortality; otolaryngologic involvement (e.g., sinusitis) was associated with an improvement in mortality (hazard ratio 0.64). Using this revised FFS, a FFS=0 was associated with a 5-year mortality of 7.5%, a FFS=1 was associated with a 20% five-year mortality, and a FFS >1 was associated with a five-year mortality of 47%. Survival curves after 20 years of follow–up indicate that microscopic polyangiitis and polyarteritis nodosa are associated with greater mortality than the Churg-Strauss syndrome and Wegener’s granulomatosis.
Conclusions:
The Five Factor Score continues to be a useful instrument for assessing risk of mortality in patients with primary systemic vasculitis, and may also help clinicians identify patients who may merit more aggressive treatment.
Editorial:
The Five Factor Score captures observations that many of us recognize subconsciously—it is not difficult, for example, to convince yourself that patients with systemic vasculitis who develop acute renal failure or who are older at disease onset will have a worse prognosis. That said, it is interesting to note the rather modest hazard ratios associated with each of the factors—the most impressive (and new) finding is that sinus involvement seems to be protective, perhaps because if often precedes more serious organ involvement, and leads to earlier use of immunosuppression. It is also interesting to note what is not included in the FFS—neurologic involvement is no longer one of the “five factors”, and pulmonary hemorrhage was not determined to be an important risk factor for mortality, which is somewhat surprising. Finally, although this is described as an index for the primary systemic vasculitides, it is important to note that it has only been validated for the ANCA-associated vasculitides and polyarteritis nodosa—it probably has limited use for the evaluation of patients with large vessel vasculitis, such as Takayasu’s arteritis or giant cell arteritis.
Abstract 2014: Reversible Cerebral Vasoconstriction Syndromes
Authors:
Rula A. Hajj-Ali, Aneesh B. Singhal, Leonard H. Calabrese
Background:
In the early 1990s, benign angiopathy of the central nervous system was recognized as a separate disorder, distinct from primary angiitis of the central nervous system, which generally follows a much more fulminant course. Benign angiopathy of the central nervous system presents with an acute, severe headache with or without severe neurologic deficit. The headache is described as “thunderclap”, characterized by a rapid onset followed by gradual spontaneous resolution. Although angiographically, the syndrome is not distinguishable from primary angiitis of the central nervous system, analysis of the cerebrospinal fluid is typically normal, and the angiographic findings reverse spontaneously. Depending on the training of the clinician, this phenomenon might also be called post-partum angiopathy, migranous vasospasm, Call syndrome, and drug-induced vasospasm. Because of the confusing nomenclature in this field, in 2007, Calabrese proposed that this and similar syndromes should be known as the “reversible cerebral vasoconstriction syndromes.” This abstract represents a detailed look of a large population of patients from two referral centers diagnosed with this syndrome.
Methods:
Retrospective chart review of patients diagnosed with reversible cerebral vasoconstriction syndrome either at Massachusetts General Hospital (1997-2008) or the Cleveland Clinic Foundation (1990-2008) was performed. All patients met three of the following four criteria for diagnosis: imaging demonstrating multifocal segmental cerebral artery vasoconstriction; no evidence of aneurysm or subarachnoid hemorrhage, normal cerebrospinal fluid, and reversibility of changes in 12 weeks. Clinical, laboratory, pathologic, and neuroimaging data were collected and analyzed to characterize the clinical phenotype and outcomes associated with this syndrome.
Results:
A total of 120 patients with reversible cerebral vasoconstriction syndrome were identified (55 patients from the Cleveland Clinic and 65 patients from Massachusetts General Hospital). The mean age was 42.3 +/- 11 years, and 82.5% of patients with this syndrome were women. The most common risk factors were medications (including the selective serotonin and norepinephrine reuptake inhibitors and sympathomimetics), and the post-partum state, which was the only identified risk factor for 9% of patients. Interestingly, this syndrome occasionally occurred after carotid endarterectomy. Headache at time of syndrome onset was present in 94% of patients; 82% had the classic “thunderclap” headache. Recurrence was common, affecting 60.1% of patients. The most common neurologic symptoms were visual (43%), although weakness (35%) and seizures (34%) were also noted. Neuroimaging (either CT or MRI) was initially normal in half of patients. Although cerebrovascular imaging was almost invariably interpreted as “consistent” with vasculitis, reversibility was demonstrated in 98% of cases, and when available, none of the brain biopsies demonstrated evidence of vasculitis. Despite this, ischemic events and brain hemorrhage were not uncommon, despite the absence of active inflammation.
Conclusions:
Reversible cerebral vasoconstriction syndromes represent an important subset of diseases that can affect the central nervous system circulation. Unlike primary angiitis of the central nervous system, these syndromes are not inflammatory, and do not require immunosuppression, although neurologic sequelae are common.
Editorial:
One of the audience members at this abstract session called this syndrome “Prinzmetal’s angina of the brain,” which is an apt comparison. This work highlights the importance of careful clinical characterization when attempting to distinguish primary angiitis of the central nervous system from a reversible cerebral vasoconstriction syndrome. Crucially, this work also emphasizes the false comfort provided by angiograms that are deemed “classic” for vasculitis. Because of the substantial morbidity associated with chronic immunosuppression, brain biopsy remains an important adjunct to diagnosis.
Abstract 2016: Patient-Reported Outcome Assessment in Primary Systemic Vasculitis Provides a Unique Perspective
Authors:
Karen Herlyn, Philip Seo, Bernhard Hellmich, Jan Reimer, Peter A. Merkel
Background:
Clinical trials largely define success in terms of physician-defined outcomes, such as disease activity and disease damage; these outcomes faill to address the patient’s perspective on his or her disease. This work represents a first step towards defining a patient-reported outcome for use in clinical trials of systemic vasculitis.
Methods:
Patients with systemic vasculitis from both the United States and Europe participated in this exercise. The first part of the exercise listed 40 forms of chronic morbidity commonly associated with systemic vasculitis; patients were asked to rank each item on a five point Likert scale, where 0 indicated “no impact.” The second part of the exercise allowed patients to list the five forms of morbidity that were most important to them.
Results:
A total of 265 patients participated: 135 from the United States and an additional 130 patients from Europe. The majority of these patients had Wegener’s granulomatosis, although other diseases were represented. The highest ranked items were fatigue, loss of energy, weight gain, joint pain, and sinusitis. This was true regardless of whether the data were analyzed by country or in aggregate. Fatigue was also the most commonly mentioned form of morbidity in the second part of this exercise, followed by musculoskeletal pain, nasal discharge, and anxiety. Interestingly, patients ranked severe forms of damage, such as dialysis and oxygen dependency, at the lower end of the scale. Patients with active vasculitis reported fatigue, loss of energy, pain, and respiratory complaints as their most important concerns.
Conclusions:
These data effectively demonstrate that fatigue and loss of energy are the most important concerns of patients with systemic vasculitis. Together, these data represent an underappreciated dimension of disease assessment, and provide a first step towards a new instrument to assess patient-reported outcomes in clinical trials.
Editorial:
The basic concept behind this study—that we should ask patients how they are doing—seems so obvious that in some ways, it is surprising that a patient-reported outcome for vasculitis has not been developed previously. Clearly, if two treatments both induce remission, but one leaves the patient feeling miserable, the choice would be clear. Patient reported outcomes have been increasingly recognized as important to clinical trials, as demonstrated by the NIH-sponsored Patient-Reported Outcomes Measurement Information System (PROMIS) and the OMERACT-sponsored initiatives in this area. How to apply this sort of data is somewhat less clear; it is concerning to note that patients and physicians ranks are often disparate, and how to reconcile these differences is not immediately clear. Regarding this particular study, it is important to note that the majority of patients in this cohort had Wegener’s granulomatosis, which obviously influenced these findings to a degree, although one suspects that patients with giant cell arteritis and Takayasu’s arteritis would also list fatigue as their predominant concern.
Abstract 2015: Severe infections during Giant Cell Arteritis and Polymyalgia Rheumatica course: incidence and mortality. The prospective, multicenter cohort GRACG study
Authors:
Jean Schmidt, Pierre Duhaut, Amar Smail, Valéry Salle, Denis Chatelain, Sylvie Bosshard, Hélène Pellet, Jean-Charles Piette, Jean-Pierre Ducroix
Background:
Giant cell arteritis is the most common form of systemic vasculitis in the United States and in Europe. Fortunately, life threatening consequences of giant cell arteritis and polymyalgia rheumatic are rare. In theory, however, the side-effects of treatment with corticosteroids (including hypertension, diabetes, and infections) may lead to higher mortality among patients with these diseases. This study examined the incidence of severe infections in a prospective, multicenter cohort of patients with giant cell arteritis or polymyalgia rheumatica in France.
Methods:
Cases and controls were identified in 1991-2007 from 40 centers in France. All cases were recruited prior to institution of treatment, and met either American College of Rheumatology criteria for giant cell arteritis or Hunder’s criteria for polymyalgia rheumatica. Cases and controls were followed prospectively every six months over a 5 year period.
Results:
A total of 720 subjects with either polymyalgia rheumatica or giant cell arteritis were recruited, in addition to 695 control subjects. The mean age was 71 among women and 73 among men, with a gender ratio (M:F) of 3:2. Biopsy-proven giant-cell arteritis was found in 386 patients; an additional 149 patients had biopsy- negative giant cell arteritis, and 149 patients had isolated polymyalgia rheumatica. At 6 months, the relative risk for infection was 3.85 (P=0.00005). At 12 months, the relative risk of infection declined to 2.08 (P=0.007). The relative risk of infection at 24 months (or longer) was not statistically significant. Causes of early infection-related mortality included septic shock, bacterial pneumonia, infectious colitis, and tuberculosis.
Conclusions:
The overall mortality of patients with giant cell arteritis and polymyalgia rheumatica is similar to what was observed in control subjects, but infection related deaths and infection related hospitalizations were increased among patients with giant cell arteritis or polymyalgia rheumatica during the first 18 months after diagnosis (relative risk 2.36), but returned to normal after long-term follow up.
Editorial:
Giant cell arteritis and polymyalgia rheumatica are particularly frustrating diagnoses for the clinician because patients who develop these diagnoses are also the least likely to tolerate long courses of high-dose steroids. In addition to the more common untoward events, steroid psychosis, avascular necrosis, and acute glaucoma may all be seen with glucocorticoid therapy and lead to devastating consequences. It is reassuring to note that the risk of infection drops two years after diagnosis, likely reflecting the end of steroid treatment, but this study does not present any guidance regarding how to avoid serious infections in this patient population. Moreover, the design of this study does not allow one to determine the risk of infection among patients with giant cell arteritis versus isolated polymyalgia rheumatica; because the latter is treated with substantially lower doses of steroids, presumably the risk of infection during the first 18 months would also be substantially lower. Finally, it is interesting to note that Pneumocystis jiroveci was not found in any of these patients, confirming that PCP prophylaxis is not necessary in this patient population, despite treatment with high-dose steroids.
Abstract 2076: Randomized Control Study (single blinded) of Rituximab versus Cytotoxic Combination Therapy in Severe Ocular Lesions of Behcet’s Disease: Pilot Study (ClinicalTrial.gov ID: NCT00664599)
Authors:
Fereydoun Davatchi, Hormoz Shams, Mozhgan Rezaipoor, Bahar Sadeghi-Abdollahi, Farhad Shahram, Abdolhadi Nadji, Cheyda Chams-Davatchi, Massoomeh Akhlaghi, Tahereh Faezi, Nassim Naderi
Background:
Behcet’s disease commonly presents with ocular findings (including iritis, uveitis, and retinal vasculitis), which generally require treatment with cytotoxic agents such as cyclophosphamide. This open label study was an attempt to determine if rituximab might be a viable alternative for the treatment of this disease.
Methods:
Twenty patients with retinal vasculitis due to Behcet’s disease were randomized to receive treatment with rituximab or cyclophosphamide. Rituximab was dosed using a standard rheumatoid arthritis protocol (i.e.1000 mg intravenously on day 1 and day 14) and was supplemented with weekly methotrexate (15 mg). Cyclophosphamide was administered at 1000 mg intravenously per month for 6 months, and supplemented with azathioprine 2-3 mg/kg/day. Patients in both group were treated with prednisolone 0.5 mg/kg/day. The primary endpoint was assessed using the Total Adjusted Disease Activity Index (TADAI), which is based on visual acuity and evidence of ocular inflammation.
Results:
The TADAI improved significantly for patients treated with rituximab, but not for patients treated with cyclophosphamide combination therapy. Treatment with rituximab was also associated with improvement in visual acuity, posterior uveitis, ocular edema, and retinal vasculitis, although the last was not statistically significant.
Conclusions:
Rituximab appears to be more effective for the treatment of ocular lesions in Behcet’s disease than cyclophosphamide.
Editorial:
Enthusiasm for the use of rituximab for the treatment of systemic vasculitis continues to increase. Several case series indicate that rituximab is both safe and effective for the treatment of Wegener’s granulomatosis, microscopic polyangiitis, and cryoglobulinemic vasculitis; this study indicates that it may be a viable option for the ocular manifestations of Behcet’s disease as well. In this study, cyclophosphamide was dosed in a manner similar to what is used in the treatment of systemic lupus erythematosus (i.e., 375 mg/m2, which is around 750 mg monthly for many patients); it would have been interesting to know if daily oral cyclophosphamide (which is administered at 2 mg/kg/day) would have been more effective than this combination therapy, or if higher initial doses of glucocorticoids might have led to more favorable results. It is also important to note that this study does not address the efficacy of rituximab past 6 months, or the effects of retreatment. Finally, there was no comparison to infliximab, which has also been used with some success for the treatment of ocular Behcet’s disease.
Abstract 2075: Mycophenolate Mofetil (MMF) for Remission Induction and Maintenance in Microscopic Polyangiitis (MPA) with Mild to Moderate Renal Dysfunction - Prospective Pilot Trial in 17 Patients
Authors:
Francisco Silva, Ulrich Specks, Nelson Leung, Sanjay Kalra, Marie Hogan, Fernando Fervenza,
Background:
Microscopic polyangiitis is a pulmonary-renal hemorrhage syndrome caused by a small-vessel ANCA-associated vasculitis. Although cyclophosphamide is the standard treatment for this disorder, the toxicity associated with cytotoxic therapies has compelled a search for alternative treatments. Mycophenolate mofetil is a T-cell specific antimetabolite that has been used in renal transplantation and for the treatment of a variety of autoimmune disorders. This study examines the efficacy of mycophenolate mofetil for the treatment of microscopic polyangiitis with mild to moderate renal involvement.
Methods:
Eligibility was based on (1) clinical diagnosis of microscopic polyangiitis, (2) MPO-ANCA positivity, (3) and serum creatinine < 3.0 mg/dL. Patients were treated with mycophenolate mofetil 2000 mg/day for 18 months; glucocorticoids were tapered and discontinued by month 6. The primary endpoint was a Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis (BVAS/WG) of 0 and stable renal function at month 6.
Results:
Seventeen patients were deemed eligible for this trial. Approximately half of the patients in this trial had a new diagnosis of microscopic polyangiitis; the other half had been previously diagnosed, and were relapsing at the time of this trial. The average BVAS/WG score was 7, and renal involvement was documented by biopsy in 15 cases. By month 18, 12 patients had sustained remission (defined as a BVAS/WG=0); 4 patients suffered relapses, and one patient stopped taking the drug due to gastrointestinal side effects. There was a non-significant decline in serum creatinine, from 1.6 to 1.0.
Conclusions:
Mycophenolate mofetil may be a reasonable alternative for the treatment of microscopic polyangiitis with mild to moderate renal involvement.
Editorial:
Given the great success enjoyed by investigators using mycophenolate mofetil for the treatment of lupus nephritis, it is not surprising that there would be great interest in extending this to the treatment of other diseases. The sustained remission rate noted by the authors is comparable to the NIH experience using cyclophosphamide for the treatment of Wegener’s granulomatosis; one wonders if the remission rate might have been higher had the mycophenolate mofetil been titrated towards 3g/day. On the other hand, given the high relapse rate associated with methotrexate when used under similar circumstances, it will be interesting to note if patients treated initially with mycophenolate mofetil also experience a higher relapse rate than patients initially treated with cyclophosphamide, which might negate some of the ostensible benefits of this route. It is also important to note that the authors are not proposing mycophenolate mofetil as a replacement for cyclophosphamide for all patients with ANCA-associated vasculitis: patients with severe renal involvement, multisystem involvement, or PR3-ANCA positivity may still be better off with cyclophosphamide.
Abstract 2074: Diagnostic marker for Takayasu’s arteritis
Authors:
Rie Karasawa, Kazuo Yudoh, Mayumi Tamaki, Shoichi Ozaki, Kusuki Nishioka, Tomohiro Kato
Background:
Anti-endothelial cell antibodies (AECA) have been implicated in the pathogenesis of Takayasu’s arteritis. This study is an attempt to isolate the autoantigens that may be relevant to this disease.
Methods:
Proteins were derived from endothelial cells derived from human umbilical cord veins (HUVEC). Proteins were separated by 2-dimensional electrophoresis, and subjected to Western blotting using AECA derived from patients with systemic vasculitis. HUVEC-specific antigens were identified by eliminating antigens that were also present in a HeLa cell preparation. Mass spectroscopy was used to identify the candidate autoantigens.
Results:
A total of 153 proteins were identified using this technique; 63 of these proteins have been identified. One of these proteins is peroxiredoxin-2, an antioxidant enzyme that reduces hydrogen peroxide and is important to antioxidant defense and redox signaling. Autoantibodies against peroxiredoxin-2 were found in 61% of patients with systemic vasculitis and 88% of patients with Takayasu’s arteritis, but only 4% of normal healthy controls. A second protein that was identified is cyclophilin A, which binds cyclosporine and may function as a pro-inflammatory cytokine in endothelial cells. Antibodies to cyclophilin A were found in 86% of patients with Takayasu’s arteritis and 27% of patients with microscopic polyangiitis. Titers to both autoantigens correlated in part with disease activity.
Conclusions:
Autoantibodies against peroxiredoxin-2 and cyclophilin A may be useful diagnostic markers for Takayasu’s arteritis, especially when used in combination.
Editorial:
This interesting study is an extension of previous work performed by this group, and this short description belies the enormous amount of effort that underlies this work. A common criticism is that HUVEC may not be the appropriate substrate for this research, but the potential implications of these findings for Takayasu’s arteritis are exciting. At present, Takayasu’s arteritis is largely diagnosed based on symptoms, which occur only after substantial vascular damage has taken place. This work may provide the foundation for a diagnostic study that may allow the early identification of patients at high risk, raising the possibility of preventing the complications associated with this disease.
Abstract 2073: Changes in Inflammatory-Mediators Induced by Glucocorticoids in Cultured Human Temporal Arteries from Patinets with Giant-Cell Arteritis (GCA)
Authors:
Marc Corbera-Bellalta, Ester Lozano, Ana García-Martinez, Georgina Espígol-Frigolé, Sergio Prieto, Montserrat Butjosa, José Hernández-Rodríguez, Maria Cinta Cid.
Background:
Giant cell arteritis is generally treated with high-dose glucocorticoids, but the effect treatment on vascular inflammation has not been well defined. This study approaches this issue by examining the production of potential mediators of inflammation in the temporal artery, and the effect of high dose steroids on the inflammatory milieu.
Methods:
Temporal artery sections from two patients with biopsy-proven giant cell arteritis (prior to treatment) and two patients without disease were placed into culture. The supernatant and tissue samples were analyzed for the presence of 40 compounds (including cytokines, chemokines, adhesion molecules, metalloproteases, angiogenesis modulators, and fibrogenic factors) both before and after treatment with high dose steroids (dexamethasone 0.5 mcg/ml) for five days.
Results:
Normal temporal arteries produce several compounds associated with inflammation (IL-6), chemoattraction (IL-8, MCP-1), angiogenesis (IL-8, angiogenin), and extracellular matrix degredation (MMP-3, TIMP-1). Temporal arteries from patients with giant cell arteritis also produced chemokines (MIP-1α, CCL5), soluble IL-6R, soluble adhesion molecules (ICAM-1, VCAM-1), metalloproteases (MMP-2, MMP-9), angiogenesis modulators (VEGF, angiopoietin 1, angiopoietin 2, angiostatin), and fibrogenic factors (PDGF). Treatment with dexamethasone for five days led to downregulation of MIP-1α and MMP9 and upregulation of TIMP2 and angiopoeitin-2, but did not significantly alter the expression of the other factors elaborated by temporal artery specimens from patients with giant cell arteritis.
Conclusions:
Temporal arteries from patients with giant cell arteries produce multiple mediators associated with inflammation, chemotaxis, extracellular matrix modification, and angiogenesis. This pattern of expression is only minimally impacted by treatment with high doses of glucocorticoids.
Editorial:
Normal temporal arteries unexpectedly express several compounds associated with inflammation and angiogenesis. The significance of this finding is not clear, although it may, in part, be an artifact of this particular model. It would be interesting to see if other “normal” arteries also demonstrate similar expression patterns. It is fascinating to note the complex array of compounds associated with inflammation and vascular remodeling that are produced by temporal arteries in patients with giant cell arteritis. It is equally fascinating to note the underwhelming impact that high-dose glucocorticoids have on the synthesis of these compounds even after five days of therapy, which would generally be sufficient time to see a clinical response. Future iterations of this work may be able to identify baseline expression patterns or patterns of response that predict specific outcomes, such as cranial ischemic events or to relapse.
