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On-line version ISSN 1806-4841
An. Bras. Dermatol. vol.79 no.5 Rio de Janeiro Sept./Oct. 2004
CLINICAL, EPIDEMIOLOGICAL, LABORATORY AND THERAPEUTIC INVESTIGATION
Posterior subcapsular cataract in patients with pemphigus and pemphigoid using oral corticosteroid*
Viviane ReggianiI; Adriana Maria PorroII; Cristiane Ramos AlonsoIII; Adriana DiasIV; Fernando Augusto de AlmeidaV
IM.D., Dermatology Specialization
IIAssistant M.D. and Ph.D. candidate, head of the Bullous Dermatosis Outpatient Care Unit
IIIMaster's Degree and Ph.D. candidate
IVM.D., Dermatology specialization course (elective)
BACKGROUND: Oral corticosteroid is the
treatment most used for patients with chronic bullous dermatosis, often at high
dosages and over long periods of time. Arterial hypertension, diabetes, osteoporosis,
infections and hydro-electrolytic disturbances frequently occur as side effects
of this therapy. Posterior subcapsular cataract is rarely mentioned in the literature
as a side effect of corticosteroid in patients with bullous diseases.
OBJECTIVES: To evaluate the incidence of posterior subcapsular cataract as a side effect of oral corticosteroid.
METHODS: A retrospective study: 49 patients with chronic bullous diseases using a corticosteroid were followed-up from 1987 to 1997 at the Bullous Dermatosis Outpatient Care Unit of the Department of Dermatology, UNIFESP - EPM. The patients were regularly submitted to ophthalmologic evaluation in search for cortisone cataract. This evaluation was carried out at the beginning of the treatment and regularly during the use of the corticosteroid.
RESULTS: From 1987 to 1997, the incidence of posterior subcapsular cataract as a side effect of oral corticosteroid was 28.57% in these patients.
CONCLUSIONS: 1) among 49 patients, 14 (28.57%) presented with cortisone cataract. 2) the period of time of prednisone use up to the appearance of cataract varied from eight months to nine years and three months (average 45.71 months). 3) the maximum dose of oral corticosteroid required for the management of the clinical picture ranged from 60 to 120 mg daily (average of 78.57 mg daily).
Key words: cataract; Adrenal Cortex Hormones/therapeutic use; pemphigus; pemphigoid, bullous.
Bullous dermatoses are chronic diseases characterized by the appearance of chronic bullous dermatosis. By means of direct and indirect immunofluorescence, the participation of an autoimmune phenomenon can be observed. Among the most frequent are pemphigus (vulgaris and foliaceous) and bullous pemphigoid. Oral corticotherapy is used as treatment of these diseases, often in very high doses and for prolonged periods of time.
The side effects of corticosteroids are dose- and time-dependent. The toxicity of the corticosteroids is manifested mainly by hydroelectrolytic disturbances, musculoskeletal manifestations, cutaneous manifestations, gastrointestinal toxicity, neural complications, metabolic-endocrine toxicity, ophthalmic problems and effects on the immulogical system, with higher susceptibility to infections.
In a study by Lever and White,1 the main side effects in 46 patients with pemphigus were: hyperglycemia in 45%, mental alterations in 35% and fractured vertebrae in 26%. In a publication by Haim and Shafir,2 the main complication in 35 patients with pemphigus vulgaris was the development of cushingoid characteristics in 48% of them.
Ryan3 published an assessment of 70 patients with pemphigus, 44 of who had pemphigus vulgaris. All patients were treated with corticosteroids. Cushingoid characteristics were observed in 23% of them, diabetes in 23% and myopathy in 14%.
Rosemberg and collaborators4 published an observation of 107 pemphigus patients, 57% of whom showed cushingoid characteristics, 44% infection, 41% diabetes and 29% osteoporosis.
Cabrini and cols5 observed hyperglycemia in 44% of 16 pemphigoid patients undergoing corticotherapy.
Lapidoth and cols6 observed four cases of osteoporosis, three cases of diabetes, two of hypertension and one of cataract in 15 pemphigoid patients treated with corticosteroids
Mourellou and cols7 published an assessment of 48 patients with pemphigus vulgaris treated with corticosteroids. In patients who received a full dose of prednisone, i.e. above five grams, the authors observed five cases of diabetes, two of bronchopneumonia, two of congestive cardiac failure, one of lung embolia and one case of psychosis.
In Brazil, a doctoral dissertation written by one of the authors8 evaluated 40 patients with pemphigus vulgaris submitted to corticotherapy. The following side effects were observed: cushingoid characteristics (47.5%), arterial hypertension (32.5%), diabetes (20%) and acneiform eruption (10%).
Other complications referred to in the literature are: aseptic necrosis of femoral head,9 exacerbation of balantidiasis and strongyloidiasis,10,11 hemorrhage and perforation of the lower parts of the gastrointestinal tract12-15and pneumonia.16
The two main ophthalmologic complications in corticotherapy are posterior subcapsular cataract and glaucoma.17 There were no studies found in the literature assessing the ocular complications of prolonged corticotherapy in pemphigus and pemphigoid patients.
PATIENTS AND METHODS
The present survey is a retrospective study of 49 pemphigus and pemphigoid patients who used oral corticoids and were submitted to an ophthalmic evaluation. Diagnosis of the bullous disease was confirmed by anatomopathology.
The patients were registered at the Bullous Dermatosis Outpatient Care Unit of the Paulista Medical School, State University of Sao Paulo Dermatology Department (UNIFESP/EPM) from January 1987 to December 1997. All of the patients frequenting this outpatient care unit and using oral corticosteroids are regularly submitted to an ophthalmologic evaluation in a search for ocular complications resulting from the treatment. This evaluation is carried out at the beginning of treatment, and then regularly every six to 12 months, depending on the case.
The ophthalmologic evaluation in this survey consisted of a clinical examination, analysis of visual acuity and slit-lamp examination, with the objective of discovering cases of cataract induced by corticotherapy. A cataract was classified according to its intensity, which varied from 1+ (slight) to 4+ (maximum degree).
In the patients diagnosed with cataract induced by corticotherapy, its occurrence was related to variations in age, sex, ethnic group, dermatologic diagnosis, time of use and the corticosteroid used.
1) Among the 49 patients, 14 (28.57%) presented with cortisone cataract (posterior subcapsular).
2) Characteristics of patients with cataract as to sex, age, ethnic group, diagnosis, type and dose of corticosteroid used (Chart 1):
Chart 1 - Click to enlarge
Among the 14 patients with cortisone cataract, 11 were female and 3 male. The age of patients evaluated varied between 33 and 77 years (with an average of 55 years of age).
As for ethnic group, 12 patients were Caucasians, and two were Black.
As for the diagnosis, nine patients studied had pemphigus vulgaris, two foliaceous pemphigus, two bullous pemphigoid, and one pemphigus herpetiformis.
The oral corticosteroid used was prednisone. The maximum dosage necessary for control of the clinical condition varied from 60 to 120 mg daily (with an average of 78.57 mg daily).
3) Characteristics of cataract regarding its degree and the time of corticosteroid use up to its first appearance (Chart 2):
The time of prednisone use up to the appearance of cataract varied from eight months to nine years and three months (average of 45.71 months).
The degree of cataract was incipient (2+), and (4+) at the most. Ten patients presented with bilateral cataract and three with unilateral.
The most frequent side effects induced by oral corticotherapy to be described are hypertension, diabetes (23 to 45%), osteoporosis, infections (40%), hydroelectrolytic disturbances and cushingoid characteristics (23 to 57%).12
The relation between the chronic use of oral corticotherapy and the formation of posterior subcapsular cataract was originally put forward by Black and collaborators in 1960.18 That study proved to be of special interest in that posterior subcapsular cataract had not been observed in patients in treatment for less than a year, or in those treated for less than four years at low doses. Nonetheless, the dose and duration of treatment were considered directly proportional to the development of the cataract. Cortisone-type and senile cataracts differ insofar as the former is posterior subcapsular and the latter is nuclear.
Reduced vision is rare in patients with cataract induced by corticotherapy. The degree of sight impairment varies with the extension of the opacification. In most cases, visual alterations are absent,19,20 or minimal.21 Insignificant photophobia or visual disturbance in (bright) light might occur. So long as vision is affected by the posterior subcapsular cataract, one cannot expect complete resolution of the lenticular opacification, even by tapering the dose of corticotherapy, or interrupting it. In very few patients, a reduction of the opacification area was observed after tapering or interrupting the corticotherapy.18,23 In some cases, however, even after interrupting treatment, the cataract tends to progress.24,25
Several studies show that the effect of a corticosteroid on inducing cataract varies according to the patient's susceptibility.23,27 The total dosage of corticosteroid utilized, as well as the time of its use, is significantly important, but the influence of the patient's individual response to corticosteroid must be recalled.
Various factors seem to influence the induction of cataract by corticosteroid, among which are:
- inhibition of the Na-K ATPase pump: corticosteroids have been known to affect water transportation and increase the permeability of ocular lenses to cations. Clinically, hydration of the lenses is manifested either by generalized intumescence, or by generalized accumulation of fluid whose refraction index is different from the surrounding average, and is responsible in part for the dispersion of light and consequent reduction of its transmission by the lenses;28
- link of corticosteroids to lens proteins and consequent formation of lysine-ketosteroid adducts: induction of crystalline opacification by corticosteroids would occur in association with the formation of the crystalline's glucocorticosteroid protein covalent bond;29,30
- secondary oxidation of the SH-protein group of the lysine-ketosteroid adduct leading to crystalline aggregate formation:34 the glucocorticosteroids seem to cause cataract by penetrating the lens cells and reacting with specific crystalline amino groups, thereby inducing an alteration in the confirmation and exposure of protein disulfide groups. These groups are then released from their disulfide bond form, which subsequently leads to a protein aggregate formation and finally to the light-refracting complexes.
Cortisone cataract is rarely cited as a side effect from treating pemphigus and pemphigoid patients. At the UNIFESP/EPM Bullous Dermatosis Outpatient Care Unit, the authors observed that 14 (28.57%) of the 49 patients under corticotherapy showed posterior subcapsular cataract as a side effect of treatment, after an average period of 45.71 months.
As such, they emphasized the need to periodically carry out an ophthalmologic examination of patients with bullous dermatoses who are undergoing corticotherapy. The prevalence observed in the present survey was roughly 30%. Relatively young patients (33 years) and those who had not been under prolonged corticotherapy use (eight months) were found to be affected. The fact that patients usually showed slight alterations of visual acuity reinforces the need for an active search of cortisone cataract by means of regular ophthalmologic examinations.
In pemphigus and pemphigoid patients submitted to oral corticotherapy, the following could be observed:
1) the cataract was one among the important side effects manifested;
2) prevalence of the cataract was 28.57%;
3) the cortisone cataract might be unilateral or bilateral;
4) average time of treatment up to the appearance of the cataract was 45.71 months;
5) average maximal dose of corticosteroid utilized by patients was 78.57 mg daily.
The authors kindly thank the Cataract Section of the Paulista Medical School/UNIFESP Ophthalmology Department.
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Received on January 05, 2004.
Approved by the Consultive Council and accepted for publication on August 07, 2004.
* Work done at "Universidade Federal de São Paulo - Escola Paulista de Medicina" and "Departamento de Dermatologia - Ambulatório de Dermatoses Bolhosas".