Reumatología Clínica (English Edition) Reumatología Clínica (English Edition)
Reumatol Clin 2017;13:25-9 - Vol. 13 Num.1 DOI: 10.1016/j.reumae.2015.12.003
Brief Report
Diagnostic Categorization According to the First International Workshop on Ocular Sarcoidosis (FIWOS) Criteria in a Series of 11 Patients
Categorización diagnóstica según los criterios del First International Workshop on Ocular Sarcoidosis (FIWOS) en una serie de 11 pacientes
Carlos F. Menesesa,, , César A. Egüesa, Miren Uriartea, Nerea Errazquina, Alejandro Valero Jaimesa, Olga Maíza, Joaquín Belzuneguia, Ana Blancob
a Servicio de Reumatología, Hospital Universitario Donostia, San Sebastián, Guipúzcoa, Spain
b Servicio de Oftalmología, Hospital Universitario Donostia, San Sebastián, Guipúzcoa, Spain
Received 10 August 2015, Accepted 17 December 2015
Abstract
Objective

Categorization of patients diagnosed with ocular sarcoidosis during the period 2009–2014.

Methods

The medical records of patients with ocular sarcoidosis were reviewed and variables were collected to categorize the patients according to the criteria of the FIWOS.

Results

We found 11 patients, 7 women and 4 men, with sarcoid uveitis; the median age was 58 years. Bilateral panuveitis was the most common pattern (54.5%), followed by chronic anterior uveitis (27.2%). The diagnosis of sarcoidosis was definitive in 4 patients (36.3%), presumed in 5 (45.4%), probable in 1 (9%) and possible in 1 (9%).

Conclusions

Ocular sarcoidosis was diagnosed in more than half of the patients who had no confirmatory biopsy. Bilateral panuveitis and chronic anterior uveitis were the patterns most frequently observed.

Resumen
Objetivo

Categorizar a los pacientes con diagnóstico de sarcoidosis ocular en el período comprendido entre 2009 y 2014.

Métodos

Se revisaron las historias clínicas de los pacientes con sarcoidosis ocular y se recopilaron las variables para categorizar a los pacientes según los criterios del FIWOS.

Resultados

Se encontró a un total de 11 pacientes con uveítis sarcoidea, 7 mujeres y 4 hombres, con una mediana de edad de 58 años. El patrón de panuveítis bilateral crónica fue el más frecuente en un 54,5%, seguido de la uveítis anterior crónica unilateral, con 27,2%. El diagnóstico de sarcoidosis fue definitivo en 4 pacientes (36,3%), presunto en 5 pacientes (45,4%), probable en un paciente (9%) y posible en un paciente (9%).

Conclusiones

Más de la mitad de los pacientes sin biopsia confirmatoria fueron diagnosticados de sarcoidosis ocular. La panuveítis bilateral crónica y la uveítis anterior crónica fueron los patrones predominantes.

Keywords
Sarcoidosis, Uveitis, Sarcoid uveitis, Inflammatory uveitis, Panuveitis, Diagnostic criteria, First International Workshop on Ocular Sarcoidosis
Palabras clave
Sarcoidosis, Uveítis, Uveítis sarcoidea, Uveítis inflamatoria, Panuveítis, Criterios diagnósticos, First International Workshop on Ocular Sarcoidosis
Introduction

Sarcoidosis is a multisystem disorder of unknown cause, characterized by noncaseating granulomatous inflammation.1 It affects the parenchyma of almost any organ, and thoracic symptoms are those most frequently observed. Overall, 30%–60% of the patients have eye involvement. It is usually bilateral uveitis, although, uveitis can occasionally develop in the absence of systemic disease, or could be the predominant manifestation with no significant extraocular impact.2–4 In clinical practice, the diagnosis of systemic sarcoidosis is based on the combination of clinical, radiographic and histopathological findings. The diagnostic criteria proposed by the First International Workshop on Ocular Sarcoidosis (FIWOS) were recently validated.5 These criteria classify ocular sarcoidosis as definite (uveitis and positive biopsy), presumed (bilateral hilar lymphadenopathy and uveitis without biopsy), probable (3 ocular signs and 2 laboratory findings without biopsy or bilateral hilar lymphadenopathy) and possible (4 ocular signs and 2 laboratory findings with a negative biopsy), in accordance with specific ophthalmological and laboratory findings.6 The latter are especially useful when there is no biopsy or the biopsy is negative.

Objectives

The purpose was to categorize those patients with a diagnosis of ocular sarcoidosis from 2009 to 2014 in Hospital Universitario Donostia, in the province of Guipúzcoa in northern Spain, using the diagnostic and validated criteria of the FIWOS.

Material and Methods

We retrospectively reviewed the case reports of the patients diagnosed with ocular sarcoidosis. The diagnosis of sarcoidosis was based on a combination of the clinical, radiographic and histological criteria of the FIWOS, as well as the exclusion of other granulomatous diseases like tuberculosis.

The variables recorded were patient age and sex, presence of systemic manifestations, anatomical location of the inflammation, tuberculosis screening, positive test for angiotensin-converting enzyme, lymph node biopsy, chest radiographic findings and treatment. To classify uveitis we used the anatomical classification of the Standardization of Uveitis Nomenclature (SUN) Working Group7 (Table 1). We excluded patients who had a positive result on the Quantiferon® test. Using these findings, we categorized the patients according to the FIWOS.

Table 1.

Anatomical Classification of Uveitis (Sun Working Group, 2005).

Type  Primary site of inflammation  Includes 
Anterior uveitisAnterior chamberIritis 
Iridocyclitis 
Anterior cyclitis 
Intermediate uveitisVítreousPars planitis 
Posterior cyclitis 
Hyalitis 
Posterior uveitisRetina or choroidFocal, multifocal or diffuse choroiditis 
Chorioretinitis 
Retinochoroiditis 
Retinitis 
Neuroretinitis 
Panuveitis  Anterior chamber, vitreous and retina or choroid   
Results

We found a total of 11 patients with a diagnosis of sarcoid uveitis, 7 women (63.6%) and 4 men (36.3%). The median age±standard deviation was 58±20.5 years. In 7 patients (63.6%), the eye was the first organ to be affected: 5 of them later developed the systemic clinical signs and 2 had only ocular clinical features. Four patients (36.3%) began with extraocular systemic manifestations, which, in order of frequency, were: bilateral hilar lymphadenopathy in 81.8%, respiratory manifestations in 36.3%, peripheral lymphadenopathy in 18.1%, parotitis in 27.2% and erythema nodosum in 9%. The locations of inflammation most frequently observed were chronic bilateral panuveitis in 54.5%, unilateral chronic anterior uveitis in 27.2% and bilateral chronic anterior uveitis in 18.1%. When the patients were categorized, 4 (36.3%) had a definite diagnosis of sarcoidosis, 5 patients (45.4%) had a presumed diagnosis, 1 patient (9%) had a probable diagnosis and 1 patient (9%) had a possible diagnosis of sarcoidosis.

Table 2 shows the above-mentioned variables in the patients diagnosed with ocular sarcoidosis.

Table 2.

Demographic and Clinical Characteristics, Anatomical Location of Uveitis, Signs of Ocular Sarcoidosis, Ancillary Tests, Diagnosis and Treatment of the Series Presented.

ID  Age  Sex  Systemic clinical signs  Anatomical location of inflammation  Clinical signs of ocular sarcoidosis  Ancillary tests  Diagnosis of ocular sarcoidosis 
Initial signs of ocular sarcoidosis
77  Respiratory and neurological  Chronic bilateral
panuveitis 
BRV
Vitritis
Chorioretinitis
Periphlebitis 
Mantoux (−)
QTF (−)
Biopsy (+)
ACE (−)
AST and ALT (−)
Lysozyme (−)
X-ray with BHL 
Definite 
30  Parotitis  Chronic bilateral
panuveitis 
BRV
Chorioretinitis
Periphlebitis 
Mantoux (−)
QTF (−)
Biopsy (+)
ACE (+)
AST and ALT (−)
Lysozyme (−)
X-ray with BHL 
Definite 
Parotitis  Bilateral chronic anterior
uveitis 
KP
Vitritis
Iris nodules 
Mantoux (−)
QTF (−)
Biopsy (−)
ACE (+)
AST and ALT (−)
Lysozyme (−)
X-ray−no alterations 
Probable 
70  Parotitis  Bilateral chronic anterior
uveitis 
KP
Vitritis
Iris nodules 
Mantoux (-)
QTF (−)
Biopsy (−)
ACE (−)
AST and ALT (−)
Lysozyme (−)
X-ray with BHL 
Presumed 
49  Respiratory  Unilateral chronic anterior
uveitis 
KP
Vitritis
Iris nodules 
Mantoux (−)
QTF (−)
Biopsy (−)
ACE (−)
AST and ALT (−)
Lysozyme (−)
X-ray with BHL 
Presumed 
48  None  Chronic bilateral
panuveitis 
Vitritis
Chorioretinitis 
Mantoux (−)
QTF (−)
Biopsy (+)
ACE (+)
AST and ALT (−)
Lysozyme (−)
X-ray with BHL 
Definite 
69  None  Unilateral chronic anterior
uveitis 
Vitritis
Iris nodules 
Mantoux (−)
QTF (−)
Biopsy (+)
ACE (+)
AST and ALT (−)
Lysozyme (−)
X-ray with BHL 
Definite 
Inittial signs of systemic sarcoidosis
76  Respiratory  Chronic bilateral
panuveitis 
Vitritis
Chorioretinitis 
Mantoux (−)
QTF (−)
Biopsy (−)
ACE (−)
AST and ALT (−)
Lysozyme (−)
X-ray with BHL 
Presumed 
74  Respiratory
Peripheral lymphadenopathy 
Chronic bilateral
panuveitis 
Vitritis
Chorioretinitis
Periphlebitis 
Mantoux (−)
QTF (−)
Biopsy (−)
ACE (−)
AST and ALT (−)
Lysozyme (−)
X-ray with BHL 
Presumed 
10  57  Erythema nodosum  Unilateral chronic anterior
uveitis 
KP
Chorioretinitis 
Mantoux (−)
QTF (−)
Biopsy (−)
ACE (−)
AST and ALT (−)
Lysozyme (−)
X-ray with BHL 
Presumed 
11  58  Peripheral lymphadenopathy  Chronic bilateral
panuveitis 
KP
Vitritis
Iris nodules Chorioretinitis synechiae 
Mantoux (−)
QTF (−)
Biopsy (−)
ACE (+)
AST and ALT (−)
Lysozyme (−)
X-ray – no alterations 
Possible 

ACE, angiotensin-converting enzymes; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BHL, bilateral hilar lymphadenopathy; BRV, bilateral retinal vasculitis; ID, identification; KP, mutton fat keratic precipitates; M, man; QTF, Quantiferon®; X-ray, radiography; W, woman.

Discussion

The diagnosis of systemic sarcoidosis is presently based on a combination of clinical and radiographic findings, together with the histological confirmation and the exclusion of other granulomatous diseases, such as tuberculosis.8 In clinical practice, the determination of the angiotensin-converting enzyme level, serum calcium, plain chest X-ray, scintigraphy and screening tests, like Mantoux or Quantiferon®, initially indicate involvement of systemic sarcoid. Ocular involvement in sarcoidosis is presented by up to half of the patients and may even be the initial manifestation of the disease. Sarcoidosis can affect the lacrimal glands and cause keratoconjunctivitis sicca, involving the iris, as well, causing different forms of uveitis and even the development of optic neuritis when it affects the posterior pole. The anatomical location of inflammation in sarcoid uveitis mainly, and chronically, involves the posterior segment. It frequently consists of recurrent bilateral uveitis, and can even cause generalized involvement in the form of bilateral panuveitis associated with retinal vasculitis.9,10 The findings most frequently observed in uveitis associated with sarcoidosis include mutton fat keratic precipitates, iris nodules, tent-shaped peripheral anterior synechiae, vitreous opacities like “snowballs”, multiple peripheral chorioretinal lesions and nodular periphlebitis (Fig. 1). Moreover, there were other ocular signs that could indicate sarcoid involvement, especially if evaluated in the presence of ancillary tests that are positive for sarcoidosis11–14 (Table 3). The diagnostic criteria proposed by the FIWOS were validated in 2010. They include several ophthalmological signs indicative of sarcoidosis and comprise ancillary tests5 (Table 4). These criteria do not include invasive procedures and are useful, in clinical practice, when there is no confirmatory biopsy or when the biopsy is negative.

Fig. 1.
(0.11MB).

(A) Sequelae of anterior uveitis with tent-shaped peripheral anterior synechiae. (B) Multiple chorioretinal lesions in peripheral retina.

Table 3.

Involvement of the Eye and Its Neighboring Structures, Except for the Iris.

Location  Description 
Lacrimal glands  Keratoconjunctivitis sicca, lacrimal hypertrophy 
Orbit  Diffuse unilateral orbital inflammation 
Eyelid  Granuloma 
Conjunctiva  Granuloma, conjunctivitis 
Sclerotic  Scleritis, episcleritis 
Cornea  Interstitial keratitis 
Optic nerve  Optic neuropathy 
Table 4.

Diagnostic Criteria of the First International Workshop on Ocular Sarcoidosis (FIWOS).

Intraocular signs indicative of ocular sarcoidosis 
1. Mutton fat keratic precipitates and/or iris nodules (Koeppe/Bussaca) 
2. Trabecular meshwork nodules and/or tent-shaped peripheral anterior synechiae 
3. Vitreous opacities with “snowballs” or a string of pearls 
4. Multiple peripheral chorioretinal lesions (active and/or atrophic) 
5. Segmental and/or nodular periphlebitis and/or macroaneurysms in an inflamed eye 
6. Nodules or granulomas in the optic disc and/or solitary choroidal nodule 
7. Bilateral inflammation 
 
Ancillary tests suggestive of ocular sarcoidosis 
1. Negative tuberculin test in a BCG-vaccinated patient or in one who had a positive result on a previous Mantoux test 
2. Elevated angiotensin-converting enzyme and/or elevated lysozyme level 
3. Chest X-ray showing bilateral hilar lymphadenopathy 
4. Unexpected findings in liver enzyme tests 
5. Chest tomography in patients with a negative X-ray 

BCG, Bacillus Calmette-Guérin.

Ocular and systemic manifestations of sarcoidosis, as well as the ancillary tests, show a great variability, a fact that complicates the diagnosis. With our work, we have put into practice the FIWOS criteria, which enabled us to categorize the patients with systemic clinical signs indicative of sarcoidosis together with other ocular manifestations and positive ancillary tests. Because of the heterogeneity of this disease, not all the patients fulfilled the diagnostic criteria for sarcoidosis; for this reason, after the diagnostic categorization, we see that, after satisfying the clinical and ophthalmological criteria and that of the ancillary tests, the patients’ disorder was classified as sarcoidosis. Most of our patients, coinciding with the literature, were women (63.6%). Ocular problems were the initial symptom in 7 of the overall group and most of them had ocular manifestations indicative of sarcoid disease. Tuberculin tests were negative in all of the patients and only 3 patients had a compatible lymph node biopsy. Those who had not undergone a biopsy for the classification criteria, after categorization, had a “presumed” diagnosis of sarcoidosis. The ophthalmological data showed that the most common anatomical location was chronic bilateral panuveitis, affecting 54.5% of the patients. In second place, unilateral chronic anterior uveitis, with 27.2%, was the most frequent form. Most of the patients began with clinical manifestations of uveitis, developing the systemic clinical disease later on. After the categorization of the patients, the diagnosis of sarcoidosis was definite in 4 patients, presumed in 5, probable in 1 and possible in 1 other patient.

The present study is especially interesting for rheumatologists who work in collaboration with ophthalmologists in uveitis clinics, as sarcoidosis is an uncommon disease, it is best to standardize criteria for the correct diagnosis of this disorder. We should also point out that the use of these criteria enables the diagnosis without the need for a biopsy, which could be iatrogenic or difficult in certain patients.

These criteria categorize patients with data indicative of sarcoidosis and who, because of the variability in the clinical course and organic involvement, have not been categorized as patients with sarcoid disease. The sarcoid ocular involvement plays a very significant role for categorization and, for this reason, it is important to stress a detailed ophthalmological examination in search of ocular signs indicative of a granulomatous inflammatory disease.

Ethical DisclosuresProtection of human and animal subjects

The authors declare that no experiments were performed on humans or animals for this study.

Confidentiality of data

The authors declare that they have followed the protocols of their work center on the publication of patient data.

Right to privacy and informed consent

The authors declare that no patient data appear in this article.

Funding

None.

Conflicts of Interest

The authors declare they have no conflicts of interest.

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Please cite this article as: Meneses CF, Egües CA, Uriarte M, Errazquin N, Valero Jaimes A, Maíz O, et al. Categorización diagnóstica según los criterios del First International Workshop on Ocular Sarcoidosis (FIWOS) en una serie de 11 pacientes. Reumatol Clin. 2017;13:25–29.


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Reumatol Clin 2017;13:25-9 - Vol. 13 Num.1 DOI: 10.1016/j.reumae.2015.12.003