Cancer in Biopsy-Proven Giant Cell Arteritis. A Population-Based Study

doi:10.1016/j.semarthrit.2007.03.006

Seminars in Arthritis and Rheumatism

Volume 37, Issue 3, December 2007, Pages 156-163

https://doi.org/10.1016/j.semarthrit.2007.03.006 Get rights and content

Objective

To investigate the potential association between giant cell arteritis (GCA) and cancer in a series of consecutive patients diagnosed with biopsy-proven GCA over a 25-year period at the single reference hospital for a well-defined population.

Methods

The case records of all patients diagnosed with biopsy-proven GCA at the Department of Medicine of the Hospital Xeral-Calde (Lugo, Northwest Spain) between January 1, 1981 and December 31, 2005 were reviewed. Information on cancer and cause of death over the extended follow-up was assessed. In all cases the presence of cancer was histologically confirmed.

Results

Cancer was found in 39 (15.3%) of the 255 GCA patients. Although 7 (18%) of the 39 patients had cancer either at the time or within the first 12 months after GCA diagnosis, the standardized mortality ratio (SMR) due to cancer in patients with biopsy-proven GCA showed no increase (overall SMR 1.06 [0.65-1.60]; men, 0.81; women, 1.50). The time interval between GCA diagnosis and cancer diagnosis was 5.2 ± 3.8 years (median 4.2 years; interquartile range: 3-7 years). When multivariate analysis adjusted by age and sex was performed, only the presence of dysphagia (adjusted hazards ratio (HR) = 3.90; P = 0.04), abnormal temporal artery on physical examination (adjusted HR = 4.61; P = 0.04), and anemia at the time of GCA diagnosis (adjusted HR = 3.39; P = 0.01) were associated with an increased risk of cancer over the extended follow-up.

Conclusion

The results from this series do not support an overall increase of mortality due to cancer in GCA.

Section snippets

Patients and Methods

The case records of all patients diagnosed with biopsy-proven GCA at the Department of Medicine of the Hospital Xeral-Calde (Lugo, Northwest Spain) between January 1, 1981 and December 31, 2005 were reviewed. As previously discussed, this hospital is the single reference center for a mixed rural and urban population of almost a quarter of a million people. Information about the characteristics of this white population has extensively been reported (18, 27, 28, 29). Patients were sent to the

Results

From 1981 to 2005, 255 Lugo residents were diagnosed with biopsy-proven GCA. All patients met the 1990 American College of Rheumatology criteria for the classification of GCA (42).

Discussion

The present study does not support an overall increase of cancer mortality in biopsy-proven GCA patients. Apart from a slight increase in the frequency of cancer within the first 12 months after GCA diagnosis and in accordance with previous studies from different regions of the world where incidence of GCA is high (9, 26), our study showed no significant association, supporting the notion that GCA is not a paraneoplastic condition. This is in agreement with an earlier epidemiological study that

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Risk of mortality in patients with giant cell arteritis: A systematic review and meta-analysis
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Stroke is a known complication of untreated GCA, yet there does not appear to be an increased risk of death in GCA patients due to cerebrovascular disease [15,20,24], which may be interpreted as a measure of treatment success. Similarly, there are no reports of an increased, cause-specific, risk of death in GCA patients due to malignancy [9,15,20,25,31]. While two studies reported no cause-specific increase in mortality in GCA patients due to infections, [15,25], a disproportionate contribution of infections to deaths in the first year has also been identified [29,30], which may possibly be attributable to immunosuppression following treatment initiation.
Previous studies of mortality associated with GCA have shown conflicting results. We conducted a systematic review and meta-analysis to determine the mortality risk in GCA patients compared to the general population.
We searched for published studies indexed in MEDLINE and EMBASE and the Cochrane database from inception to June 18, 2015 using the terms “giant cell arteritis” and “temporal arteritis” combined with the terms for death, mortality, and survival. A manual search of citations from retrieved articles was also performed. The inclusion criteria were as follows: (1) observational studies of mortality in GCA and (2) comparison of mortality to the general population. Studies published only in abstract form were excluded. Study eligibility and quality (Newcastle–Ottawa scale) were independently assessed by at least two investigators. Random effects meta-analysis of the mortality ratio (MR) was performed by the inverse variance method.
Out of 435 potentially relevant articles, 64 studies were reviewed, 19 studies were included in the review and 17 studies were included in the meta-analysis. Mortality was not increased in GCA patients ascertained from a population base (MR = 1.03, 95% CI: 0.96–1.10), but was increased in patients ascertained from a hospital setting (MR = 1.61, 95% CI: 1.19–2.19). There was no difference in MR by gender, and two studies provided evidence that mortality was increased in the early years following diagnosis.
At a population level, long-term mortality is not increased in GCA. However, mortality risk may be increased in some patients, and may vary over time.
Musculoskeletal Syndromes in Malignancy
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Giant cell arteritis: Diagnosis and treatment
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La arteritis de células gigantes es la vasculitis sistémica primaria más frecuente en el adulto. Es una arteritis granulomatosa de grandes y medianos vasos, que ocurre casi exclusivamente en mayores de 50 años. Este artículo revisa el diagnóstico y el tratamiento de esta entidad.
Giant cell arteritis is the most common primary systemic vasculitis in adults. The condition is granulomatous arteritis of large and medium vessels, which occurs almost exclusively in patients aged 50 years or more. This article reviews the diagnosis and treatment of the disease.
Risk of malignancy in patients with giant cell arteritis and polymyalgia rheumatica: A systematic review and meta-analysis
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Rest of the 29 articles underwent full-length article review. Of them, 20 were excluded since they were descriptive studies without a control group and three studies were excluded because they reported cancer–mortality ratios among patients with GCA/PMR but did not report incidence ratio [11–13]. Overall, six studies (five retrospective and one prospective cohort studies) with 39,808 patients with GCA/PMR met our eligibility criteria and were included in our data analyses [14–19].
To investigate the association between giant cell arteritis (GCA)/polymyalgia rheumatica (PMR) and malignancy risk.
We conducted a systematic review and meta-analysis of cohort studies that reported relative risk, hazard ratio, or standardized incidence ratio (SIRs) with 95% confidence comparing malignancy risk in patients with GCA/PMR versus non-GCA/PMR participants. Pooled risk ratios and 95% confidence intervals were calculated using a random-effect, generic inverse variance method.
A total of six studies were identified and included in our data analysis. The pooled risk ratio of malignancy in patients with GCA/PMR was 1.14 (95% CI: 1.05–1.22). The risk was higher in the first 6–12 months after diagnosis with the pooled risk ratio of 2.16 (95% CI: 1.85–2.53). However, when we performed a sensitivity analysis that excluded one study with a potential selection bias, the pooled risk ratio decreased and did not achieve statistical significance.
Our study demonstrated a low but statistically significant increased malignancy risk among patients with GCA/PMR. However, when we excluded one study with potential selection bias, the new pooled risk ratio did not achieve statistical significance.
Glucocorticoid-induced adverse events in patients with giant cell arteritis or polymyalgia rheumatica
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La maladie de Horton et la pseudopolyarthrite rhizomélique (PPR) sont des motifs fréquents de prescription d’une corticothérapie orale prolongée. Si l’efficacité de la corticothérapie chez ces patients est rapide et incontestable, elle est cependant souvent éclipsée par l’apparition d’effets indésirables plus ou moins précoces et plus ou moins sévères. Néanmoins, l’absence d’essais randomisés glucocorticoïdes contre placebo dans cette indication fait que l’imputabilité de la corticothérapie sur la survenue de certains symptômes ou pathologies pouvant également être mis sur le compte de la maladie elle-même (complications vasculaires par exemple) ou du terrain est impossible à préciser. Dans ce contexte, l’analyse de la morbi-mortalité « brute » des patients traités par glucocorticoïdes pour une maladie de Horton ou une PPR peut permettre d’anticiper les éventuels problèmes que rencontreront ces patients. Par ailleurs, la durée prolongée du traitement doit inciter les médecins à être particulièrement vigilants en ce qui concerne les effets indésirables peu symptomatiques mais au retentissement majeur à moyen et long termes.
Giant cell arteritis and polymyalgia rheumatica are common reasons for prescribing long-term glucocorticoid therapy. Glucocorticoids efficacy in these patients is rapid and undeniable, but it is often overshadowed by adverse events, appearing more or less early during treatment course. These adverse events are usually minor but some of them may be life threatening. Because of the absence of randomized, controlled trials comparing glucocorticoids to placebo in this indication and in this aged population, it is difficult to precise the role of corticosteroids in the occurrence of some complications that can also be precipitated by the disease itself (e.g., vascular complications) or related to aging. In this context, analysis of the crude morbidity and mortality can help in anticipating the potential problems that these patients will encounter. In addition, the long duration of glucocorticoid exposure should prompt physicians to be particularly vigilant regarding some adverse events that are minimally symptomatic on the short term but have a major long-term impact.
Giant cell arteritis: A review of classification, pathophysiology, geoepidemiology and treatment
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Others attributed excess early mortality to steroid-related complications, particularly infections [132,142,146]. The majority of studies indicate that patients with GCA do not face an increased risk of cancer overall or specific types of cancer, and mortality from cancer was not increased in a Spanish population-based study [147]. Importantly, patients who develop aortic dissection have a dramatically reduced life expectancy compared to patients without large artery complication (1.1 years vs. 10.9 years) [129].
Giant cell arteritis is a chronic vasculitis affecting large and medium-sized arteries, most commonly the temporal and other cranial arteries. Temporal artery biopsy has long been the gold standard for establishing the diagnosis of giant cell arteritis. There is growing evidence that simultaneous color Doppler and duplex ultrasonography of temporal arteries of GCA patients represents a valid alternative for this somewhat invasive procedure. Ultrasonography and other imaging modalities such as magnetic resonance imaging and positron emission tomography have also provided evidence that involvement of the aorta and its proximal branches is much more common in giant cell arteritis than previously appreciated; it will be important to clarify whether these patients need to be treated more aggressively. It has long been known that patients with giant cell arteritis face a markedly increased risk of developing aortic aneurysms and of dying from aortic dissection. This raises important questions as to whether patients should be screened regularly for extra-cranial large-vessel involvement and whether and how treatment of patients with positive screening results should be adjusted. In this review we discuss the pathophysiology of this disease and also the issues of epidemiology and sex differences.

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¹: Drs. Gonzalez-Gay and Llorca share senior authorship in this study.

View full text

Cancer in Biopsy-Proven Giant Cell Arteritis. A Population-Based Study

Objective

Methods

Results

Conclusion

Section snippets

Patients and Methods

Results

Discussion

Cancer-associated rheumatic disorders: clues to occult neoplasia

Semin Arthritis Rheum

Cutaneous vasculitis as a paraneoplastic syndrome in adults

Arthritis Rheum

Vasculitis associated with malignancyExperience with 13 patients and literature review

Medicine (Baltimore)

Temporal concurrence of vasculitis and cancer: a report of 12 cases

Arthritis Care Res

Giant cell arteritis

Curr Opin Rheumatol

Polymyalgia rheumatica and giant-cell arteritis

N Engl J Med

Epidemiology of the vasculitides

Rheum Dis Clin North Am

Epidemiology of biopsy proven giant cell arteritis in northwestern Spain: trend over an 18 year period

Ann Rheum Dis

Temporal arteritis: a 25-year epidemiologic, clinical, and pathologic study

Ann Intern Med

Temporal arteritis: a cough, toothache, and tongue infarction

JAMA

Systemic vasculitides

Best Pract Res Clin Rheumatol

Giant cell arteritis in IcelandAn epidemiologic and histopathologic analysis

Arthritis Rheum

Giant cell arteritis, temporal arteritis, and polymyalgia rheumatica in a Danish county

Arthritis Rheum

The incidence of polymyalgia rheumatica and temporal arteritis in the county of Aust Agder, south Norway: a prospective study 1987-94

J Rheumatol

Trends in incidence and clinical presentation of temporal arteritis in Olmsted County, Minnesota, 1950-1985

Arthritis Rheum

The incidence of giant cell arteritis in Olmsted County, Minnesota: apparent fluctuations in a cyclic pattern

Ann Intern Med

Approche épidémiologique de la maladie de Horton dans le département de Loire-Atlantique: 110 cas en 10 ans (1970-1979)

Rev Med Interne

Systemic vasculitis in adults in Northwestern Spain, 1988-1997: clinical and epidemiologic aspects

Medicine (Baltimore)

Giant cell arteritis in Northwestern Spain: a 25-year epidemiological study

Medicine (Baltimore)

Epidemiologic and immunogenetic aspects of polymyalgia rheumatica and giant cell arteritis in northern Italy

Arthritis Rheum

Giant cell arteritis in Jerusalem: a 12-year epidemiological study

Br J Rheumatol

“Polymyalgia arteritica” further clinical and histopathological studies with a report of six autopsy cases

Ann Rheum Dis

Temporal arteritis in a large necropsy series

Ann Rheum Dis

Concurrent temporal (giant cell) arteritis and malignancy: report of 20 patients with review of the literature

J Rheumatol

Cancer in association with polymyalgia rheumatica and temporal arteritis

J Rheumatol