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Inclusion and exclusion criteria, methodological flaw and ethical concepts for the treatment of patients with ocular Behçet disease

  • Author(s): Evereklioglu, Cem
  • et al.
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Inclusion and exclusion criteria, methodological flaw and ethical concepts for the treatment of patients with ocular Behçet disease
Cem Evereklioglu MD
Dermatology Online Journal 13: (3): 35

Department of Ophthalmology, Division of Uvea-Behçet Unit, Erciyes University Medical Faculty, Kayseri, Turkey

I read the case-comparative study of Al-Waiz et al. (Dermatology Online Journal 2005;11:3) with great interest titled "Colchicine and benzathine penicillin in the treatment of Behçet disease: A case comparative study". The authors performed an investigation to evaluate the efficacy of combined colchicine and benzathine penicillin in the treatment and prophylaxis of ocular and non-ocular Behçet disease and demonstrated that the clinical manifestation index was significantly reduced by this combination treatment. However, I have some important contributions and a few vital queries to the authors to be answered.

First; the authors stated that patients with neurological involvement were excluded from the study (see "patients and methods" section). However, they included the neurological manifestations in their clinical manifestation index in table 1 and scored them as intracranial hypertension (+2), multiple sclerosis–like syndrome (4+) and pyramidal or cerebellar involvement (+5). To rule out selection bias, the authors should first clarify this serious confusion and explain why they both scored neuro-Behçet patients for clinical manifestation index in table 1 and then stated that they excluded such patients from the study?

Second; although a full history was stated to be obtained from the patients regarding the first presenting feature, duration of symptoms, frequency of occurrence of symptoms, specific drug history with the determination of the size, duration, frequency and the number of the oral and genital ulcers, there are nothing in the text about the ophthalmic symptoms and signs. Moreover, there are nothing what kind of ocular examinations were made for their patients.

Third; the authors further reported that the patients were asked to stop any other treatment for one month before entering the study. What does it mean? How can a physician stop such medications. In the inclusion criteria, the authors stated that patients with mucocutaneous manifestations, eye and joint involvements were included in the study. It is clear that such patients have active lesions and active inflammation in the eye so that colchicine and/or benzathine penicillin can be started for them. What kind of, for instance, ocular complications developed in these active eyes during that one-month period? Ocular involvement, especially posterior segment disease, is a very serious organ involvement during the course of ocular Behçet disease and such patients need prompt and early topical and/or systemic intervention to prevent severe sight-threatening complications. Therefore, I would be very appreciated if the authors clarify this serious ethical and methodological flaws that necessitate extensive revisions and explanations.

And finally; it is clear that all of the patients, or at least some of them, included in the present study had ocular involvement as we understand from the authors' statement that discloses "Patients with the following manifestations were included in the study: mucocutaneous manifestations, eye involvement, joint involvement" in the "patients and methods" section. However, we cannot understand from the text whether they had anterior, intermediate, posterior or panuveitis. This point is very important because the treatment of anterior uveitis differ from that of posterior or panuveitis because colchicine is not effective in the management of posterior uveitis [1], although it may be effective in the anterior involvement, whereas some immunosuppresive agents are found to be effective in the posterior eye involvement [2]. Therefore, I would be very appreciated if the authors clarify this statement and express how many of Behçet cases were suffering from anterior or posterior uveitis, and to whom colchicine and/or Benzathine penicillin was started. Moreover, the patients were asked to stop any other treatment for one month before entering the study and, as I also stated above, such a blinding approach is clearly wrong that needs clear corrections. Why the patients with, for instance, anterior uveitis did not receive any steroid eyedrops and topical cycloplegic agents to prevent secondary severe complications such as posterior synechia formation as well to prevent photophobia. Neither colchicine nor Benzathine penicillin can act in that way. Similarly, neither colchicine nor Benzathine penicillin has been found to be effective for posterior segment involvement. How authors expected that they will treat their ocular Behçet patients with such medications. Did the visual acuities of the eye decreased or increased during that one-month of drug stopping?. How many of the eyes resulted in blind eye? Therefore, I would be very appreciated if the authors bring up their evidences to the scientific community and support their methodolical approach with references.

Therefore, I completely disagree with the authors about their final conclusion that such a multiple drug regimen with colchicine and benzathine penicillin is highly recommended in the treatment of Behçet patients. It should be remembered that one similar article about the effectiveness of benzathine penicillin on Behçet disease, previously published in the Lancet (2000;355:605-9) by Demiroglu et al. was retracted from the literature (Horton R. Lancet 2000;356:1292) from ethical reasons in the same year. People who know ophthalmic and systemic Behçet findings deeper and realize that severe sight-threatening complications occur fast enough when appropriate and sufficient ocular and systemic medications were not initiated to treat their patients by steroid eyedrops and topical cycloplegics with or without systemic steroids in the early period of the disease. So, all of the aforementioned methodological and ethical flaws should be clarified to make a definitive conclusion about the effectiveness of combined colchicine-benzathine penicillin therapy for such patients.

References

1. Evereklioglu C. Managing the symptoms of Behçet's disease. Expert Opin Pharmacother 2004; 5:317–28.

2. Evereklioglu C. Current concepts in the etiology and treatment of Behçet diseae. Surv Ophthalmol 2005; 50:277–350.

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