Original article
Kayser–Fleischer ring in Wilson's disease: A cohort study

https://doi.org/10.1016/j.ejim.2012.04.005Get rights and content

Abstract

Aims

To evaluate Wilson's disease (WD) features in Sardinian patients with Kayser–Fleischer (KF) ring and to evaluate correlations between modifications in KF and anti-copper therapy and systemic WD evolution.

Patients and methods

Sixty-seven WD patients (35 m/32 f; mean age 41 years) were retrospectively studied. At diagnosis and during follow up comprehensive ophthalmologic and neurologic examinations, brain RMN and ECD SPECT, detailed objective laboratory studies and hepatic histological examination were performed on all patients for analysis. All patients were given anti-copper therapy with d-Penicillamine in mono-therapy or in combination with Zinc Salts.

Results

At diagnosis, KF was observed in 27% of patients with equal distribution in all age groups. Significant correlations between KF at diagnosis, neuro-psychiatric manifestations and pathologic features in brain RMN and in brain ECD SPECT were found at diagnosis. During follow up, a decrease in, or regression of KF was seen in 14% of patients. Anti-copper therapy leads to KF regression and prevents the appearance of KF. No significant correlations were observed between KF regression and clinical neurological or neuro-imaging improvement nor between KF modifications and clinical hepatic improvement.

Conclusions

Our study highlights the peculiar features of Sardinian WD patients: low representation of KF, its equal distribution in all age groups, significant correlation between KF at diagnosis and clinical neurological manifestations, pathologic brain RMN and brain ECD-SPECT are highlighted by our study. Anti-copper therapy induces KF regression and prevents its onset. Therefore, KF ring does appear to be a predictive factor in the neurological and hepatic evolution of WD.

Introduction

Wilson's disease (WD) is a rare metabolic hereditary, autosomal recessive transmitted disorder, characterised by a hepatic bile copper excretion defect, leading to copper accumulation in different organ tissues, including the liver, nervous system, eyes and kidneys [1]. Average annual incidence is 12–29 cases per million individuals. Of those affected, 1/90 are heterozygotes. Geographically, incidence is highest in Costa Rica with 49 cases per million inhabitants [2]; and Japan with 30–35 cases [3]. In Europe, the highest frequency is seen in Sardinia [4] with 10–12 cases diagnosed per million inhabitants per year [5]. The Kayser–Fleischer ring (KF) is the most frequently observed ophthalmological manifestation.

The term KF refers to the golden-brown, golden-green, green-yellow, golden-yellow, bronze or reddish-brown colouring of the Descemet membrane in the limbic area of the cornea. KF is considered pathognomic of WD and represents a primary criteria in diagnosis of WD. It is an indicator of severe copper overload and appears correlated to the clinical presentation of the illness [6]. In fact, it is diagnosed in 90.4–100% of patients with neurological and psychological manifestations [7], [8], in 50–60% with non-neurological manifestations [9] and in only 10–40% of asymptomatic subjects [10]. A much less common ocular manifestation of WD is the so-called “sunflower cataract” [11].

In this cohort of 67 Sardinian WD patients, illness characteristics in relation to KF presence, ophthalmological picture modifications over the years, its correlation with the prescribed therapy and systemic evolution of the illness were evaluated respectively.

Section snippets

Materials and methods

A total of 67 Sardinian patients affected by Wilson's disease (WD) (35 male, 32 female), aged 13–62 years (average age ± SEM 40 ± 10 years) were enrolled and treated initially at the Istituto di Clinica Medica II and subsequently at the Department of Gastroenterology at the Policlinico Universitario in Cagliari, between 1980 and January 2011.

Following the exclusion of other known causes, diagnosis of WD in each patient was based on the presence of alterations of liver function tests and/or of the

Results

The clinical features of patients are summarised in Table 1.

Illness onset occurred between the ages of 4–12 years in 14/67 patients (21%), between 13 and 34 years in 37/67 (55%), and in 16/67 (24%) it occurred at > 35 years (late onset).

Evident neurological clinical picture was observed in 21/67 (31%) patients and psychiatric manifestations in 6/67 (9%).

Analysis revealed that 44/67 (66%) WD patients presented hepatic involvement only, 17/67 (25%) hepatic and neurological involvement, and 4/67 (6%)

Discussion

The term Kayser Fleischer ring (KF) refers to the golden-brown, brown-green, green-yellow, golden-yellow, bronze or reddish-brown colouring of the Descemet membrane in the limbic area of the cornea [20].

KF presence appears correlated to the clinical presentation of the illness [21]. It is in fact diagnosable in 90.4–100% of patients with neurological and psychiatric manifestations [8], [22], in 50–60% of patients without neurological signs and in only 10–40% of asymptomatic subjects [9], [23],

Learning points

Our study highlights the peculiar characteristics of WD in the Sardinian population:

  • low presence of KF

  • even distribution of KF in the different age groups

  • correlation between KF presence and clinical neurological manifestations of the illness and with neuro-radiological pictures studied from encephalic MRI and ECD-SPECT

  • no correlation between KF regression and improvement in the neurological picture, from both a clinical and neuro-imaging profile and the hepatic picture

  • KF ring regression with

Conflict of interest statement

I certify that there is no conflict of interest with any financial organisation regarding the material discussed in the manuscript.

Acknowledgements

We would like to thank Barry Mark Wheaton for his invaluable linguistic assistance.

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