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La Presse Médicale
Volume 39, n° 5
pages e97-e102 (mai 2010)
Doi : 10.1016/j.lpm.2009.12.005
Received : 26 October 2009 ;  accepted : 17 December 2009
Articles originaux

Extraocular manifestations of birdshot chorioretinopathy in 118 French patients
Étude des manifestations extra-oculaires de 118 patients atteints de choriorétinopathie de birdshot

Christian Pagnoux 1, , Alfred Mahr 1, Achille Aouba 1, Alice Bérezné 1, Dominique Monnet 2, Pascal Cohen 1, Ralph D. Levinson 3, Antoine P. Brézin 2, Loïc Guillevin 1
1 Department of internal medicine, National referral center for “Systemic necrotizing vasculitides and systemic scleroderma”, hôpital Cochin, université Paris–Descartes, Assistance publique–Hôpitaux de Paris, 75879 Paris cedex 14, France 
2 Department of ophthalmology, hôpital Cochin, université Paris Descartes, Assistance publique–Hôpitaux de Paris, 75879 Paris cedex 14, France 
3 Ocular Inflammatory Disease Center, Jules Stein Eye Institute and the Department of Ophthalmology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, United States 

Christian Pagnoux, Pôle de médecine interne, hôpital Cochin, 27, rue du Faubourg-Saint-Jacques, 75879 Paris cedex 14, France.

Published studies on birdshot chorioretinopathy (BCR) did not provide definitive information on possibly associated extraocular manifestations.


Single-center cross-sectional analysis of extraocular manifestations in a cohort of patients with BCR.


Since 2002, 118 patients (45 men, 73 women) were enrolled. Their mean age was 51.5 years at diagnosis. The most common features of their medical histories were: hypertension (32 patients), drug allergy (19), sinusitis (17), thyroid disease (12), otitis media (11), asthma (11); diabetes (10); cancer (8); psoriasis (5); monoclonal gammopathies (3). At the time of disease onset, arthralgias were noted in 23, ENT manifestations in 26, Raynaud’s phenomenon in 6, headaches in 10, psoriasis in 3 others. Between diagnosis and cross-sectional evaluation visits, only the frequency of hypertension has increased significantly (11 additional patients).

Discussion and conclusions

No predominant extraocular manifestation of BCR was identified in our patients. Their ongoing follow-up may yet discern whether BCR is definitively eye-restricted.

The full text of this article is available in PDF format.

La choriorétinopathie de birdshot est une uvéite postérieure chronique associée à l’allèle A29 du CMH de classe I et fréquemment à une vascularite rétinienne angiographique, suggérant qu’il puisse s’agir d’une maladie auto-immune. Les séries déjà publiées, toutes rétrospectives, comportent peu de patients et n’ont pas permis d’étudier précisément la fréquence de toutes les éventuelles manifestations extra-oculaires.


Enquête clinique transversale d’une cohorte monocentrique de patients atteints de choriorétinopathie de birdshot . Les patients ont été vus et interrogés de manière systématique par des internistes. Les données ont été recueillies à l’aide d’un formulaire standardisé, déjà utilisé pour plusieurs études dans les vascularites systémiques.


Depuis 2002, 118 patients ont été inclus, âgés de 51,5±16 ans au diagnostic. Parmi leurs principaux antécédents, on notait une HTA (32 patients), des allergies médicamenteuses (n =19), des sinusites (n =17), des pathologies thyroïdiennes (n =12), des otites moyennes (n =11), un asthme (n =11), un diabète (n =10), un cancer (8), un psoriasis (5) et/ou une gammapathie monoclonale (3). Au début de la maladie, 23 patients avaient des arthralgies, 26 des manifestations ORL, notamment une baisse d’acuité auditive (n =8) et 6 un syndrome de Raynaud. Entre le diagnostic et la visite d’évaluation, 11 patients supplémentaires avaient une HTA, en majorité liée à la prise de ciclosporine.

Discussion et conclusions

La fréquence des manifestations extra-oculaires au cours de la choriorétinopathie de birdshot ne paraît pas plus importante que dans la population générale. Le suivi de cette cohorte permettra de confirmer s’il s’agit bien d’une pathologie ophtalmologique limitée.

What is already known

The cause of birdshot chorioretinopathy remains unknown.
Environmental factors, genetic and immunological predisposition might be involved.
Published studies on birdshot chorioretinopathy did not provide definitive information on possibly associated extraocular manifestations, that would suggest a more general immunological, and in particular auto-immune, disorder.

What this article adds

While exposure to tobacco, history of hypertension, psoriatic lesions and/or auditory manifestations, especially tinnitus and hearing loss, may appear intriguingly common in our patients, their exact frequencies do not strikingly differ from those reported in the French general population.
Hence, our results support that BCR is definitively an eye-restricted disease.

The full text of this article is available in PDF format.

Birdshot chorioretinopathy is a potentially blinding disease characterized by a chronic, bilateral, posterior uveitis, with distinctive hypopigmented choroidal lesions [1]. The disease is supposedly an eye-restricted disease. However, it is strongly associated with HLA A29 gene, that would suggest a more general immunological, and in particular auto-immune, disorder.

We therefore initiated a longitudinal cohort study of patients with birdshot chorioretinopathy to determine whether the disease is associated with some extraocular manifestations, like those encountered in systemic vasculitis. Baseline ophthalmological characteristics of the first 80 enrolled patients have already been published [2]. This paper reports the medical history and extraocular clinical characteristics of this population, which has now increased to a total of 118 patients.


Hundred and eighteen patients with birdshot chorioretinopathy were seen in the Department of ophthalmology, at Cochin Hospital, Paris, France between November 2002 and 2005 for the recruitment in the longitudinal cohort study (each patient will be seen yearly). All patients satisfied the diagnostic criteria for birdshot chorioretinopathy [3]. Although the presence of the HLA A29 allele was not required, all individuals diagnosed at Cochin Hospital had the HLA A29 allele. The local ethics committee approved the study, as well as the UCLA Human Subject Protection Committee. The study adhered to the tenets of the Declaration of Helsinki and fully informed consent was obtained from every patient.

All patients had a first standardized evaluation at a single visit. Evaluations included historical data collection (demography; detailed medical history) then ophthalmological examinations, as previously reported [2]. All the ophthalmological evaluations were made by trained ophthalmologists (DM, AB). Medical interviews were performed by 6 trained specialists in internal medicine (CP, AM, AA, AB, PC, LG). Data were recorded using a standardized form, which has already been used in clinical trials conducted by the French Vasculitis Study Group [4, 5, 6]. When available, we also recorded the results of C-reactive protein (CRP) levels and blood cell counts at disease onset and antineutrophil cytoplasm antibody (ANCA) testing.

Data were analyzed (Chi-square or Fisher exact tests) using statistical software SAS version 8.2 (SAS Institute Inc, Cary, North Carolina, USA).


Complete demographic characteristics of the 118 patients (45 men, 73 women; mean age at diagnosis, 51.5±15.9 years) are listed in Table I. All are whites, 2 originating from the Eastern part of Europe. Three patients are brothers.

Past medical history

The more common past medical features, as listed in Table I, were hypertension (27%), drug allergy (16%), sinusitis (14%), thyroid gland diseases (10%), otitis media, asthma (9% each) and diabetes (8%). The 12 patients with thyroid gland disease had hypothyroiditis (4 patients), benign nodules (7), or hyperthyroiditis (1). One patient had undergone surgery for hyperparathyroiditis. Among the 10 diabetics, 6 have type 2 diabetes, 3 have type 1 diabetes and 1 had gestational diabetes. One patient has antiphospholipid syndrome. Psoriasis was known prior to the first ocular signs in 5 patients (4%). Allergic manifestations were reported by 51 patients, but varied from minor allergic conjunctivitis to Quincke edema.

Six patients have been treated during childhood, or later, for latent tuberculosis, and 2 for lung tuberculosis. One patient was treated for Lyme disease 4 years before the diagnosis of birdshot disease. Eight patients had history of cancer (breast, 4; penile cutaneous carcinoma, 1; esophagus adenocarcinoma, 1; urinary bladder, 1; cervix, 1). Three patients had benign monoclonal gammapathy (2 with IgG lambda, 1 with IgM). Only 1 patient had history of myocardial infarction and 1 has atheromatous lower limb claudication. None of patients suffered from cerebral stroke prior to the diagnosis.

Extraocular manifestations reported at the onset of the first ocular signs and at diagnosis

Extraocular manifestations are given in Table II. Arthralgias were frequent but without arthritis. Three patients reported moderate fever, which disappeared under non steroidal anti-inflammatory drug in a few days. Ear, nose and throat manifestations were non specific, but with sudden unilateral hearing loss 5 months prior to the diagnosis in 1 patient, progressive hypoacousis just preceding ophthalmological signs in 7 and tinnitus in 5. Lung manifestations were transient, non-life incapacitating, and not related to any lung disease. Dyspnea sine materia was noted by 14 patients, graded 2 in the NYHA classification in 13 and grade 3 in one pre-obese female. One woman experienced 2 months prior to the ocular symptoms “cryptogenetic” pericarditis, which never reoccurred. Mild distal paresthesias were noted in 7 patients, transient, except when related to carpal tunnel syndrome (1 patient), diabetes neuropathy (1) or sequellar of surgery for esophagus cancer (1). None of the patients with known psoriasis had cutaneous flare, but 3 new patients developed psoriatic lesions within the 3 months close to the first ocular signs. Two of these patients were both HLA B27 and A29 positive, but none had extracutaneous psoriasis and ophthalmological examination was firmly consistent with the diagnosis of birdshot disease. No patient reported livedo.

All patients have been tested at least once for ANCA in their sera and none were positive. CRP levels and blood cell counts were available at disease onset for 16 and 19 patients only, respectively. Mean CRP was 2.9±2.5mg/L and neutrophil count was 4540±2161/mm3.

Subsequent extraocular manifestations

The mean duration between the first ophthalmological symptoms and this cross-sectional study was 75.7±84 months. Patients’ clinical characteristics did not change significantly from the time of diagnosis (Table II). Only hypertension has become significantly more frequent, with 11 more patients affected (10 of them taking cyclosporine A), among whom one also suffered from non-fatal myocardial infarction. One patient developed diabetes under corticosteroids, while 3 new cancers have been diagnosed (prostate 2, breast 1). No other systemic disease has occurred.


Because birdshot chorioretinopathy is a rare entity, detailed analyses of the patients’ clinical characteristics are difficult to obtain, particularly when focusing on extraocular manifestations. This study on 118 patients is the largest to date to have methodically analyzed this specific aspect in patients who all satisfy the diagnostic criteria of birdshot chorioretinopathy and were HLA-A29 positive. While these analyses did not reveal prominent extraocular features or comorbidities, several findings may deserve further attention. In particular, we found an overall high percentage of patients experiencing hearing loss concomitant with birdshot chorioretinopathy onset, hypertension and/or histories of allergy or psoriasis.

The potential limitations of our study are, the likelihood of potential recall bias, self-reported medical histories and, of course, the absence of a control population. Therefore, the results of this investigation must be viewed with its exploratory nature in mind. However, we think the use of a standardized form for this medical inquiry, conducted by physicians trained in systemic diseases and vasculitides, has provided interesting and confident data.

Indeed, the demographic data for our patients are in accordance with those published previously. In their compilation of all the published 692 birdshot chorioretinopathy patients, Shah et al. [7] found a slight female predominance (54%) and a mean age of 53 years at disease onset. Hypertension was reported with a rather high frequency (up to 46% of patients) [8]. Priem and Oosterhuis also found an association with a rather high rate of vascular accidents [9]. Hearing loss and cutaneous vitiligo have been reported in a few patients, whereas psoriasis has been mentioned in only one case report [10].

Notably, the frequencies of environmental exposures and extraocular manifestations in our patients did not differ strikingly from those observed in the French general population. Half of our patients were current or past regular smokers. However, in a study on the French adult population of the same-age conducted in 2004, current smokers represented 35% [11], with 47% men and 31% women having smoked >10 pack-years during their lifetimes [12]. Hypertension was common in our patients, with a rate rising to 41% when cases of hypertension possibly induced by treatment (i.e., corticosteroids or immunosuppressants, mainly cyclosporine A) were added. However, hypertension was observed in 36.6% of the individuals in the French middle-aged general population included in the DESIR cohort [13]. Similarly, while 4% of our patients reported psoriatic lesions, the prevalence of definitively diagnosed psoriasis is estimated at 1.5% to 3% in European countries [14, 15], with a maximum of 5% in 1 French study [16]. Nine percent of our patients had asthma, while the asthma rate in France is estimated between 7 and 9% of young adults [17].

Hence, it can be advanced with a certain degree of confidence that birdshot chorioretinopathy is an eye-restricted disease. Follow-up serial evaluations are planned that will give us the opportunity to detect any new extraocular manifestations or malignancy, along with the ophthalmological part of the project.

Conflicts of interest



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