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• Reply to Dr Chan et al's comments on oral pilocarpine for ocular symptoms in Sjogren's syndrome
  Alexandros A Drosos
  Published on: 23 January 2004
• Comments on oral pilocarpine for ocular symptoms in Sjõgren’s syndrome
  Wai-Man Chan
  Published on: 18 December 2003

• Published on: 23 January 2004

  Reply to Dr Chan et al's comments on oral pilocarpine for ocular symptoms in Sjogren's syndrome

  • Alexandros A Drosos, Professor of Medicine/Rheumatology
  • Other Contributors:
    • Niki Tsifetaki, George Kitsos, Yannis Alamanos, Paraskevi V. Voulgari

  Dear Editor

  We thank Dr Chan and collaborators for their interest in our study and for their comments.[1] As concerns the patients’ selection, we excluded patients with serious medical problems such as heart, and lung diseases, as well as other ophthalmological disorders including glaucoma. Thus, none of our patients were treated with beta-blockers and none were on hormone replacement therapy which may exacerbate d...

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  Dear Editor

  We thank Dr Chan and collaborators for their interest in our study and for their comments.[1] As concerns the patients’ selection, we excluded patients with serious medical problems such as heart, and lung diseases, as well as other ophthalmological disorders including glaucoma. Thus, none of our patients were treated with beta-blockers and none were on hormone replacement therapy which may exacerbate dry eye symptoms. For postmenopausal osteoporosis some patients were treated with raloxifene and some others with biphosphonates. The type of artificial tears used by our patients was: natural tears free monodose and it was used according to their sicca complains, as they needed. The dose of oral pilocarpine was 5 mg at 08.00 in the morning and the same dose at 20.00 in the evening. Patients performed the Schirmer’s I test in the outpatient eye clinic between 09.00 and 11.00 in the morning, after receiving pilocarpine. Thus, we do not believe that the negative results of Schirmer’s I test are influenced by pilocarpine. We think that Schirmer’s I test is less sensitive than Rose Bengal test and is influenced from many factors like the body and room temperature, the status of hydradation, the climate, etc.[2] As regards the long-term safety of oral pilocarpine, this is exactly the reason for excluding patients with serious medical problems and of using small doses of pilocarpine. With 10 mg of oral pilocarpine daily we showed a substantial clinical response and improvement of Rose Bengal test in the majority of patients.[3] Of course local treatment for the dry eyes of Sjogren’s syndrome patients is essential.[4] However, not all patients responded to topical treatment. We have used cyclosporin A (since 1986) for the treatment of sicca syndrome in Sjogren’s patients,[5] but local cyclosporin A is not in use in many countries in Europe.

  References

  (1) Chan W-M et al. Comments on oral pilocarpine for ocular symptoms in Sjõgren’s syndrome [electronic response to Tsifetaki et al. Oral pilocarpine for the treatment of ocular symptoms in patients with Sjögren’s syndrome: a randomised 12 week controlled study] annrheumdis.com 2003http://ard.bmjjournals.com/cgi/eletters/62/12/1204#52

  (2) Talal N, Moutsopoulos HM, Kassan SS, ed. Sjogren’s syndrome: clinical and immunological aspects. Berlin: Springer, 1987.

  (3) Tsifetaki N, Kitsos G, Paschides CA, Alamanos Y, Eftaxias V, Voulgari PV, et al. Oral pilocarpine for the treatment of ocular symptoms in patients with Sjogren’s syndrome: a randomised 12 week controlled study. Ann Rheum Dis 2003;62:1204-7.

  (4) Bell M, Askari A, Bookman A, Frydrych S, Lamant J, McComp J et al. Sjogren’s syndrome: a critical review of clinical management. J Rheumatol 1999;26:2051-61

  (5) Drosos AA, Skopouli FN, Costopoulos JS, Papadimitriou CS, Moutsopoulos HM. Cyclosporin A (CyA) in primary Sjogren’s syndrome: a double blind study. Ann Rheum Dis 1986;45:732-5.

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  Conflict of Interest:
  None declared.

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• Published on: 18 December 2003

  Comments on oral pilocarpine for ocular symptoms in Sjõgren’s syndrome

  • Wai-Man Chan, Ophthalmologist
  • Other Contributors:
    • Carmen C. Chan, Dorothy S. Fan, Dennis S. Lam

  Dear Editor

  We read with great interest the study by Tsifetaki et al. on the efficacy and side effects of the use of oral pilocarpine for the treatment of ocular symptoms in Sjõgren’s syndrome.[1] In terms of patient selection, we noted the authors excluded patients with significant medical conditions, but we are not sure about the status of their concomitant medications. For women in their late 50s, suc...

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  Dear Editor

  We read with great interest the study by Tsifetaki et al. on the efficacy and side effects of the use of oral pilocarpine for the treatment of ocular symptoms in Sjõgren’s syndrome.[1] In terms of patient selection, we noted the authors excluded patients with significant medical conditions, but we are not sure about the status of their concomitant medications. For women in their late 50s, such as in the study population, drugs like beta blockers and hormone replacement therapy are commonly used, and it is well known that they may exacerbate dry eye symptoms.[2] The authors also did not specify the type and frequency of artificial tears used and whether the lubricants contained any preservatives, which could exacerbate the symptoms of keratoconjunctivitis sicca.[3] A standardization of the artificial tears across the groups seems necessary in testing the efficacy of oral pilocarpine on ocular symptoms.

  We are interested to know the timing of the Schirmer’s-I tests, with respect to the administration of the oral pilocarpine. In a study of salivary flow rates, the pilocarpine effect occurred within 30 minutes after the oral intake of the drug and it lasted for about 3 to 5 hours.[4] This might be the reason for the negative outcome of the Schirmer’s-I test in this study, especially when oral pilocarpine was taken twice a day rather than four times daily. The latter regime was established in a similar study on salivary secretion to be the optimal therapeutic regimen.[4]

  Another area of concern is about the safety of long-term systemic medication to treat a chronic local symptomatic problem. In this series, 4 out of 29 patients presented with headaches, sweating, nausea and vomiting, despite the fact that they were mild and tolerable. The parasympathomimetic effects of pilocarpine may cause potential problems in patients with history of asthma, chronic obstructive pulmonary disease, cardiac arrhythmia and uveitis.[4,5] These patients should be alerted for the possible complications from the drug.

  The lack of information about the use of oral pilocarpine in preventing serious ocular complications from sicca also undermines its clinical value. For symptomatic relief alone, we advocate local treatment for local symptoms with a balance of the efficacy and adverse effects of the drugs. Apart from maximum lubrication using artificial tears or ointments, topical cyclosporine or topical steroids have also been shown to be effective for dry eye symptoms in Sjõgren’s syndrome.[6] Other treatment strategies include partial or total occlusion of the upper puncta, in addition to the lower ones, may also be considered.[7] Systemic treatment may be reserved for patients who are resistant to local therapy or those with co-existent xerostomia symptoms.

  References

  (1) Tsifetaki N, Kitsos G, Paschides CA, Alamanos Y, Eftaxias V, Voulgari PV et al. Oral pilocarpine for the treatment of ocular symptoms in patients with Sjogren's syndrome: a randomised 12 week controlled study. Ann Rheum Dis 2003;62:1204-7.

  (2) Schaumberg DA, Buring JE, Sullivan DA, Dana MR. Hormone replacement therapy and dry eye syndrome. JAMA 2001;286:2114-9.

  (3) Albietz JM, Bruce AS. The conjunctival epithelium in dry eye subtypes: effect of preserved and non-preserved topical treatments. Curr.Eye Res 2001;22:8-18.

  (4) Vivino FB, Al-Hashimi I, Khan Z, LeVeque FG, Salisbury PL 3rd, Tran- Johnson TK, et al. Pilocarpine tablets for the treatment of dry mouth and dry eye symptoms in patients with Sjogren syndrome: a randomized, placebo -controlled, fixed-dose, multicenter trial. Arch Intern Med 1999;159:174- 81.

  (5) Greco JJ, Kelman CD. Systemic pilocarpine toxicity in the treatment of angle closure glaucoma. Ann Ophthalmol 1973;5:57-9.

  (6) Avunduk AM, Avunduk MC, Varnell ED, Kaufman HE. The comparison of efficacies of topical corticosteroids and nonsteroidal anti-inflammatory drops on dry eye patients: a clinical and immunocytochemical study. Am J Ophthalmol 2003;136:593-602.

  (7) Balaram M, Schaumberg DA, Dana MR. Efficacy and tolerability outcomes after punctal occlusion with silicone plugs in dry eye syndrome. Am.J Ophthalmol 2001;131:30-6.

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  Conflict of Interest:
  None declared.

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