Impaired Health-related Quality of Life in PatientsTreated for Wegener’s GranulomatosisMIKKEL FAURSCHOU, LENE SIGAARD, JAKOB BUE BJORNER, and BO BASLUND
ABSTRACT. Objective. To investigate whether patients with Wegener’s granulomatosis (WG) experience reduced
health-related quality of life (HRQOL) after accomplishment of remission, and to study the influ-
ence of WG-associated organ damage on HRQOL. Methods. Sixty-eight patients with inactive WG and 680 randomly selected, age- and sex-matched
controls of the Danish background population completed the Medical Outcomes Study Short-Form
36 (SF-36) survey for evaluation of HRQOL. Irreversible organ damage at ributable to WG and/or
its treatment was assessed using the Vasculitis Damage Index (VDI). Results. The median disease duration was 7.5 (range 1–26) years in the WG group, and the median
total VDI score was 2.0 (range 0–7). Compared to controls, WG patients reported impaired HRQOL
reflected by significantly lower SF-36 physical component summary scores (PCS) and mental com-
ponent summary scores (MCS) (p < 0.001) and by significantly lower scores in 7 out of 8 SF-36 sub-
scales (p ≤ 0.001). In the WG group, no statistical y significant correlations were found between the
different SF-36 scores and the total VDI score, number of organ systems affected by damage, dis-
ease duration, or number of WG relapses. Patients with organ failure or other major forms of dam-
age did not report significantly lower HRQOL than less severely affected patients. Conclusion. WG patients experience significantly reduced HRQOL even in phases with no appar-
ent vasculitis disease activity. Our data indicate that the level of HRQOL does not correlate wel with
the extent of vasculitis-associated organ damage in WG. (J Rheumatol First Release August 1 2010;
Wegener’s granulomatosis (WG) is a systemic inflammatory
forms of vasculitis-associated damage6,7,8. These scoring
disease of unknown etiology characterized by granuloma-
systems, however, do not provide information on the conse-
tous inflammation of the respiratory tract, necrotizing vas-
quences of WG as perceived by patients living with the dis-
culitis, glomerulonephritis, and the presence of antineu-
ease. To our knowledge, the influence of WG on patient-
trophil cytoplasmic autoantibodies (ANCA)1,2. The intro-
reported health-related quality of life (HRQOL) has been
duction of cyclophosphamide-based treatment regimens
systematical y investigated in only a few published studies.
improved the prognosis of patients with WG dramatic-
Further, data on the relationship between patient-perceived
al y1,3,4. Nevertheless, even with modern therapy, the dis-
health status and the extent of WG-associated organ damage
ease remains associated with significant morbidity. In large
are few. Studies based on patients with varied degrees of
WG studies, permanent organ damage at ributable to WG or
vasculitis disease activity have demonstrated a negative
its treatment affected the majority of patients during short-
effect of WG on HRQOL9,10,11,12. Comparable observations
and longterm fol owup1,5. The cumulative burden of such
were made in studies involving WG patients as wel as
inflammation- and treatment-induced irreversible tissue
patients with other ANCA-associated vasculitides13,14,15.
damage can be analyzed using the Vasculitis Damage Index
Seo and coworkers used the Medical Outcomes Study
(VDI) or related scoring systems, which quantify different
Short-Form 36 (SF-36) survey16,17,18 to evaluate HRQOL in
180 WG patients and found a statistical y significant,
From the Department of Rheumatology, Rigshospitalet, Copenhagen
inverse correlation between the SF-36 PCS and the VDI
University Hospital; and the National Research Centre for the Working
score in their cohort5. In contrast, Koutantji, et al did not
detect statistical y significant correlations between SF-36
M. Faurschou, MD, PhD; L. Sigaard, Study Nurse, Department of
scores and a modified VDI score among 51 patients with
Rheumatology, Rigshospitalet, Copenhagen University Hospital;J.B. Bjorner, MD, PhD, Professor, The National Research Centre for the
ANCA-associated vasculitides, including 31 WG patients19. Working Environment; B. Baslund, MD, PhD, Department of
We used the SF-36 survey to examine the self-reported
Rheumatology, Rigshospitalet, Copenhagen University Hospital.
health status of 68 Danish WG patients with inactive vas-
Address correspondence to Dr. B. Baslund, Department of Rheumatology,4242, Rigshospitalet, Copenhagen University Hospital, 9 Blegdamsvej,
culitis. The SF-36 scores of the patients were compared to
DK-2100 Copenhagen OE, Denmark. E-mail: baslund@rh.regionh.dk
SF-36 scores of 680 randomly selected, age- and sex-
Accepted for publication May 31, 2010.
matched controls of the Danish background population.
Personal non-commercial use only. The Journal of Rheumatology Copyright 2010. All rights reserved. Faurschou, et al. Quality of life in WG
Moreover, we analyzed the influence of vasculitis-associat-
Table 1. Descriptive data recorded at time of Medical Outcome Study
ed organ damage on HRQOL in the WG group.
Short-Form 36 survey for 68 Danish patients with inactive Wegener’s
MATERIALS AND METHODS Study subjects. The Department of Rheumatology at the Copenhagen
University Hospital, Rigshospitalet, provides treatment for patients with
systemic vasculitides in Eastern Denmark. Patients with inactive WG fol-
lowed at the department were invited to participate in the study. Patients
receiving treatment with cyclophosphamide, chlorambucil, and/or doses of
prednisolone > 10 mg/day were not considered eligible for the study. Out
of 75 invited WG patients, 68 (91%) accepted the invitation and completed
Median time since WG diagnosis, yrs (range)
the SF-36 questionnaire. No patient displayed clinical or laboratory signs
Immunosuppressive medication, % of patients
of active vasculitis at the time of SF-36 survey, corresponding to a
Methotrexate +/– prednisolone therapy (≤ 10 mg/day)
Birmingham Vasculitis Activity score (BVAS)20,21 of zero. Al patients met
Low-dose prednisolone monotherapy (≤ 10 mg/day)
the American Col ege of Rheumatology 1990 criteria for the classification
Other drugs* +/– prednisolone therapy (≤ 10 mg/day)
Irreversible organ damage at ributable to WG and/or its treatment was
evaluated at the time of the study, and the level of damage was scored using
Median Vasculitis Damage Index score (range)
the VDI data col ection form6,7. Further, we calculated a weighted damage
score, in which items of damage of the VDI were scored according to grade
of severity, and summed. In this scoring system, we adapted the median
damage severity ratings described by Seo, et al, who asked a group of
experts to score different forms of organ damage related to WG and micro-
scopic polyangi tis on a severity scale from 0 to 10, with 10 representing
For each WG patient, 10 age- and sex-matched control subjects were
randomly selected among participants in a Danish national health survey
conducted in 200524. The participants had been recruited at random from
the general population of Denmark by means of the Danish Central
Population Register, which holds key information on al citizens of the
country. The survey was the fourth of its kind conducted during the period
1987–2005. The purpose of the 4 surveys was to evaluate the health status
Median no. organ systems with damage** (range)
and analyze factors influencing health and morbidity among adult citizens
* Azathioprine (4 patients), mycophenolate mofetil (1 patient).
** Assessed by the Vasculitis Damage Index. Assessment of HRQOL. HRQOL was evaluated using a validated Danish
version of the SF-36 questionnaire25,26. The SF-36 questionnaire contains
36 items that assess HRQOL in 8 health dimensions: physical functioning
during the induction phase. The remaining 3 patients had
(PF); role physical (RP); bodily pain (BP); general health (GH); vitality
received corticosteroid monotherapy as the initial treatment
(VT); social functioning (SF); role emotional (RE); and mental health
for WG. At the time of the SF-36 survey, 28 patients were
(MH). In each dimension, item scores were coded and summed according
receiving immunosuppressive maintenance therapy as out-
to standard protocols16,17. Scores in the 8 SF-36 subscales range from 0 to
lined in Table 1, while 40 patients were fol owed without
100, zero indicating the worst and 100 indicating the best patient-reported
health status. Two summary scores, the PCS and the MCS, were derived
from the 8 subscale scores as described by Ware, et al18. These summary
Compared to controls, the WG patients reported impaired
scores were standardized based on US norms so that a score of 50 is the
HRQOL reflected by significantly reduced SF-36 PCS and
mean score of the US 1998 general population and higher scores indicate
MCS and by significantly lower scores in 7 out of 8 SF-36
subscales (Table 2). Patients < 58 years of age (the median
Statistical analyses. The Mann-Whitney rank-sum test was used for com-
patient age in the cohort) reported somewhat bet er HRQOL
parison of continuous data. Spearman’s rank correlation test was used in
correlation studies. In al analyses, p < 0.05 defined statistical significance.
than patients ≥ 58 years of age compared to controls. Thus,
Analyses were performed using SPSS version 9.0 for Windows (SPSS,
while patients ≥ 58 years presented with significantly lower
PCS and MCS than controls (p ≤ 0.001 in both compar-
isons), younger patients did not display significantly
reduced MCS compared with matched controls [mean PCS
Basic descriptive data for patients are summarized in Table
47.1 (SD 10.0) vs 53.9 (SD 7.6), respectively; p < 0.001;
1. Fifty-four patients had received oral therapy with
mean MCS 52.5 (SD 8.5) vs 54.3 (SD 8.3); p = 0.1].
cyclophosphamide (1–2 mg/kg/day) for induction of remis-
Within the WG group, no statistical y significant differ-
sion, 2 had been given intravenous cyclophosphamide (0.75
ences in SF-36 summary scores were found between men
g/m2 monthly), 6 cyclophosphamide-intolerant patients had
and women. Patients who were taking immunosuppressive
received oral chlorambucil (2–4 mg/day), and 3 patients had
maintenance therapy had significantly lower PCS than
been treated with oral azathioprine (1.5–2.0 mg/kg/day). Al
patients who were off immunosuppressive medication at the
these patients also received high-dose corticosteroid therapy
time of SF-36 survey [mean PCS 42.1 (SD 9.7) vs 46.6 (SD
Personal non-commercial use only. The Journal of Rheumatology Copyright 2010. All rights reserved. The Journal of Rheumatology 2010; 37:10; doi:10.3899/jrheum.100167Table 2. Medical Outcome Study Short-Form 36 survey scores for 68
on WG patients with varied degrees of vasculitis disease
Danish patients with inactive Wegener’s granulomatosis (WG) and 680
activity. In our study, we included only WG patients who
randomly selected age- and sex-matched controls of the Danish back-
were in remission at the time of quality of life assessment.
Our observations add to existing knowledge of HRQOL in
WG by showing that patients with the disorder experience
compromised self-perceived health status even in phases
with no apparent disease activity. Thus, our data substanti-
ate findings by Jayne, et al, who observed SF-36 scores
below UK norms during clinical remission in a large cohort
of patients with ANCA-associated vasculitides (WG or
In our cohort, patients ≥ 58 years of age presented with
lower SF-36 PCS and MCS than age- and sex-matched con-
trols. In contrast, younger patients did not display signifi-
Physical component summary score 44.9 (10.5)
Mental component summary score 51.5 (9.3)
cantly reduced MCS compared to controls. These observa-
tions suggest that the negative influence of WG on HRQOL
* SF-36 scores for patients and controls were compared using
may be particularly pronounced in elderly patients.
Moreover, we observed significantly lower SF-36 PCS for
patients who received immunosuppressive maintenance
10.5); p = 0.04]. These subgroups of patients did not differ
therapy than for patients who were fol owed without
significantly from each other with respect to age,
immunosuppressive medication. Since none of the study
male/female ratio, years since WG diagnosis, total VDI
subjects had active WG at the time of survey, this finding
seems to indicate that receiving immunosuppressive therapy
Correlation tests revealed no statistical y significant
per se may influence HRQOL negatively among patients
associations between SF-36 summary or subscale scores and
the number of WG relapses, years since WG diagnosis, the
Intriguingly, we did not detect significant correlations
total VDI score, the weighted damage score, or the number
between SF-36 summary or subscale scores and the total
of organ systems with damage as assessed by the VDI.
VDI score in our cohort. Statistical y significant, inverse
Statistical y significant, weak inverse correlations were
correlations were found between the VDI item score for pul-
found between 2 SF-36 subscale scores and the VDI item
monary damage and the PF and BP SF-36 subscale scores.
score for pulmonary damage (PF: rs = –0.292; p = 0.02. BP:
However, the observed correlations are weak, and the possi-
rs = –0.298; p = 0.01). We did not detect statistical y signif-
bility of chance findings related to multiple testing cannot
icant correlations between SF-36 scores and other organ-
be ruled out. Of note, our analyses did not reveal significant
specific VDI item scores. No significant differences in SF-
differences in SF-36 scores between patients presenting
36 scores were observed between patients with major forms
with major forms of damage and less severely affected
of damage, arbitrarily defined as items of damage of the
patients. Further, patients without permanent organ damage
VDI assigned a median severity rating of 7–10 by Seo, et
as assessed by the VDI did not present with bet er SF-36
al23 (n = 32), and other patients (n = 36). Further, patients
scores than other patients. It is interesting that comparable
with a VDI score of zero (n = 8) did not differ significantly
observations were made in a study from the UK19. Thus,
from patients with a VDI score ≥ 1 (n = 60) with respect to
Koutantji and coworkers did not detect statistical y signifi-
cant correlations between SF-36 scores and the number of
damaged organ systems as assessed by the VDI in a cohort
DISCUSSION
of patients with different ANCA-associated vasculitides.
Intense cytotoxic and immunosuppressive therapy has trans-
Together, these observations suggest that the level of
formed WG from a rapidly lethal disorder to a chronic dis-
patient-perceived quality of life does not correlate wel with
ease, during which prolonged periods of remission can be
either the extent or the severity of vasculitis-associated
obtained4,27. However, due to recurrent disease flares, grum-
organ damage in WG. It might therefore be speculated that
bling disease, and side-effects related to treatment, WG
the compromised HRQOL experienced by WG patients
remains associated with a substantial burden of physical
relates primarily to other consequences of living with the
morbidity1,5,28,29,30,31,32,33,34,35,36,37. Hoffman and cowork-
disease; e.g., development of fatigue and other constitution-
ers were the first to demonstrate that WG patients also suf-
al symptoms, reduced exercise capacity, social and occupa-
fer from impaired self-perceived health status9. This finding
tional disability, and fear of recurrent disease
was subsequently confirmed in European investiga-
flares9,10,11,15,19. Future HRQOL investigations should
tions10,11, which like the study by Hoffman, et al were based
at empt to elucidate the physical, social, and psychological
Personal non-commercial use only. The Journal of Rheumatology Copyright 2010. All rights reserved. Faurschou, et al. Quality of life in WG
factors that affect the self-perceived health status of patients
vasculitis associated with antineutrophil cytoplasmic
autoantibodies. N Engl J Med 2003;349:36-44.
Our study confirms that WG is associated with impaired
15. Newal C, Schinke S, Savage CO, Hil S, Harper L. Impairment of
HRQOL even in phases with no apparent vasculitis disease
lung function, health status and functional capacity in patients with
ANCA-associated vasculitis. Rheumatology 2005;44:623-8.
activity. We observed highly significant differences in SF-36
16. Ware JE, Sherbourne CD. The MOS 36-item Short-form Health
summary and subscale scores between WG patients with
Survey (SF-36). I. Conceptual framework and item selection. Med
inactive vasculitis and age- and sex-matched controls of the
general population. The negative impact of WG on HRQOL
17. Ware JE, Snow KK, Kosinski M, Gandek B. SF-36 health survey
should be recognized as an important aspect of the disease
manual and interpretation guide. Boston: New England Medical
18. Ware JE, Kosinski M, Bayliss MS, McHorney CA, Rogers WH,
Raczek A. Comparison of methods for the scoring and statistical
REFERENCES
analysis of SF-36 health profile and summary measures: summary
1. Hoffman GS, Kerr GS, Leavit RY, Hal ahan CW, Lebovics RS,
of results from the Medical Outcomes Study. Med Care 1995;33
Travis WD, et al. Wegener granulomatosis: an analysis of 158
patients. Ann Intern Med 1992;116:488-98.
19. Koutantji M, Harrold E, Lane SE, Pearce S, Wat s RA, Scot DG.
2. Jennet e JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL,
Investigation of quality of life, mood, pain, disability, and disease
et al. Nomenclature of systemic vasculitides. Proposal of an
status in primary systemic vasculitis. Arthritis Rheum
international consensus conference. Arthritis Rheum
20. Luqmani RA, Bacon PA, Moots RJ, Janssen BA, Pal A, Emery P,
3. Fauci AS, Haynes BF, Katz P, Wolff SM. Wegener’s
et al. Birmingham Vasculitis Activity Score (BVAS) in systemic
granulomatosis: prospective clinical and therapeutic experience
necrotizing vasculitis. QJM 1994;87:671-8.
with 85 patients for 21 years. Ann Intern Med 1983;98:76-85.
21. Flossmann O, Bacon P, de Groot K, Jayne D, Rasmussen N, Seo P,
4. Mukhtyar C, Flossmann O, Hel mich B, Bacon P, Cid M,
et al. Development of comprehensive disease assessment in
Cohen-Tervaert JW, et al. Outcomes from studies of antineutrophil
systemic vasculitis. Ann Rheum Dis 2007;66:283-92.
cytoplasm antibody associated vasculitis: a systematic review by
22. Leavit RY, Fauci AS, Bloch DA, Michel BA, Hunder GG, Arend
the European League Against Rheumatism systemic vasculitis task
WP, et al. The American Col ege of Rheumatology 1990 criteria for
force. Ann Rheum Dis 2008;67:1004-10.
the classification of Wegener’s granulomatosis. Arthritis Rheum
5. Seo P, Min YI, Holbrook JT, Hoffman GS, Merkel PA, Spiera R, et
al. Damage caused by Wegener’s granulomatosis and its treatment:
23. Seo P, Jayne D, Luqmani R, Merkel PA. Assessment of damage in
prospective data from the Wegener’s Granulomatosis Etanercept
vasculitis: expert ratings of damage. Rheumatology 2009;48:823-7.
Trial (WGET). Arthritis Rheum 2005;52:2168-78.
24. Ekholm O, Hesse U, Davidsen M, Kjol er M. The study design and
6. Exley AR, Bacon PA, Luqmani RA, Kitas GD, Gordon C, Savage
characteristics of the Danish national health interview surveys.
CO, et al. Development and initial validation of the Vasculitis
Scand J Public Health 2009;37:758-65.
Damage Index for the standardized clinical assessment of damage
25. Bjorner JB, Thunedborg K, Kristensen TS, Modvig J, Bech P. The
in the systemic vasculitides. Arthritis Rheum 1997;40:371-80.
Danish SF-36 Health Survey: translation and preliminary validity
7. Exley AR, Bacon PA, Luqmani RA, Kitas GD, Carruthers DM,
studies. J Clin Epidemiol 1998;51:991-9.
Moots R. Examination of disease severity in systemic vasculitis
26. Bjorner JB, Damsgaard MT, Wat T, Groenvold M. Tests of data
from the novel perspective of damage using the Vasculitis Damage
quality, scaling assumptions, and reliability of the Danish SF-36.
Index (VDI). Br J Rheumatol 1998;37:57-63.
27. Walton EW. Giant-cel granuloma of the respiratory tract
8. Seo P, Luqmani RA, Flossmann O, Hel mich B, Herlyn K, Hoffman
(Wegener’s granulomatosis). Br Med J 1958;2:265-70.
GS, et al. The future of damage assessment in vasculitis.
28. Koldingsnes W, Nossent H. Predictors of survival and organ
damage in Wegener’s granulomatosis. Rheumatology
9. Hoffman GS, Drucker Y, Cotch MF, Locker GA, Easley K, Kwoh
K. Wegener’s granulomatosis: patient-reported effects of disease on
29. Reinhold-Kel er E, Beuge N, Latza U, de Groot K, Rudert H, Nol e
health, function, and income. Arthritis Rheum 1998;41:2257-62.
B, et al. An interdisciplinary approach to the care of patients with
10. Boomsma MM, Bijl M, Stegeman CA, Kal enberg CG, Hoffman
Wegener’s granulomatosis: long-term outcome in 155 patients.
GS, Tervaert JW. Patients’ perceptions of the effects of systemic
lupus erythematosus on health, function, income, and interpersonal
30. Westman KW, Bygren PG, Olsson H, Ranstam J, Wieslander
relationships: a comparison with Wegener’s granulomatosis.
J. Relapse rate, renal survival, and cancer morbidity in patients with
Wegener’s granulomatosis or microscopic polyangi tis with renal
11. Reinhold-Kel er E, Herlyn K, Wagner-Bastmeyer R, Gutfleisch J,
involvement. J Am Soc Nephrol 1998;9:842-52.
Peter HH, Raspe HH, et al. Effect of Wegener’s granulomatosis on
31. Knight A, Askling J, Ekbom A. Cancer incidence in a
work disability, need for medical care, and quality of life in patients
population-based cohort of patients with Wegener’s granulomatosis.
younger than 40 years at diagnosis. Arthritis Rheum 2002;47:320-5.
12. Srouji IA, Andrews P, Edwards C, Lund VJ. General and
32. Talar-Wil iams C, Hijazi YM, Walther MM, Linehan WM, Hal ahan
rhinosinusitis-related quality of life in patients with Wegener’s
CW, Lubensky I, et al. Cyclophosphamide-induced cystitis and
granulomatosis. Laryngoscope 2006;116:1621-5.
bladder cancer in patients with Wegener granulomatosis. Ann Intern
13. Carpenter DM, Thorpe CT, Lewis M, Devel is RF, Hogan SL.
Health-related quality of life for patients with vasculitis and their
33. Faurschou M, Sorensen IJ, Mel emkjaer L, Loft AG, Thomsen BS,
spouses. Arthritis Rheum 2009;61:259-65.
Tvede N, et al. Malignancies in Wegener’s granulomatosis:
14. Jayne D, Rasmussen N, Andrassy K, Bacon P, Tervaert JW,
incidence and relation to cyclophosphamide therapy in a cohort of
Dadoniene J, et al. A randomized trial of maintenance therapy for
293 patients. J Rheumatol 2008;35:100-105.
Personal non-commercial use only. The Journal of Rheumatology Copyright 2010. All rights reserved. The Journal of Rheumatology 2010; 37:10; doi:10.3899/jrheum.100167
34. Faurschou M, Mel emkjaer L, Sorensen IJ, Svalgaard TB, Dreyer
36. Merkel PA, Lo GH, Holbrook JT, Tibbs AK, Al en NB, Davis JC Jr,
L, Baslund B. Increased morbidity from ischemic heart disease in
et al. Brief communication: high incidence of venous thrombotic
patients with Wegener’s granulomatosis. Arthritis Rheum
events among patients with Wegener granulomatosis: the Wegener’s
Clinical Occurrence of Thrombosis (WeCLOT) Study. Ann Intern
35. Morgan MD, Turnbul J, Selamet U, Kaur-Hayer M, Nightingale P,
Ferro CJ, et al. Increased incidence of cardiovascular events in
37. Stassen PM, Derks RP, Kal enberg CG, Stegeman CA. Venous
patients with antineutrophil cytoplasmic antibody-associated
thromboembolism in ANCA-associated vasculitis — incidence and
vasculitides: a matched-pair cohort study. Arthritis Rheum
risk factors. Rheumatology 2008;47:530-4.
Personal non-commercial use only. The Journal of Rheumatology Copyright 2010. All rights reserved. Faurschou, et al. Quality of life in WG
Aeromonas Infections 1 Aeromonas infections are caused by bacteria Some strains of Aeromonas are more virulent, which are present in the water all of the time. which means that they possess special properties Usually, when fish get sick with an Aeromonas which enable them to cause more serious disease infection, something has happened to make them outbreaks. If these more damaging strain
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