- Email: [email protected]
Ophthalmic zoster
1527
(eg, pyoderma gangrenosum5 and respiratory distress6 for direct effects; thrombocytopeniaand increased risk of bacterial infections8 for indirect effects). Thus, rhGM-CSF, as well as cytokines already available or that will become available in the next few years, must be used with appropriate care in the patients most likely to benefit. B. DONATINI P. KRUPP T. JONES
Drug Monitoring Centre, Sandoz Pharma, CH-4400 Basel, Switzerland
1. Lieschke GJ, Maher D, Cebon J, et al. Effects of bacterially synthesized recombinant human granulocyte-macrophage colony-stimulating factor in patients with advanced malignancy. Ann Intern Med 1989; 110: 357-64 2. De Vries EGE, Willemse PHB, Biesma B, Stem AC, Limburg PC, Vellenga E. Flare-up of rheumatoid arthritis during GM-CSF treatment after chemotherapy.
Lancet 1991; 338: 517-18. 3. Hancock SL, Cox RS, McDougall IR. Thyroid diseases after treatment of Hodgkin’s disease. N Engl J Med 1991; 352: 599-605. 4. Atkins MB, Mier JW, Parkinson DR, Gould JA, Berkman EM, Kaplan MM. Hypothyroidism after treatment with interleukin-2 and lymphokine-activated killer cells. N Engl J Med 1988; 318: 1557-63. 5. Ross HJ, Moy LA, Kaplan R, Figlin RA. Bullous pyoderma gangrenosum after granulocyte colony-stimulating factor treatment. Cancer 1991; 68: 441-43. 6. Margolin KA, Rayner AA, Hawkins MJ, et al. Interleukin 2 and lymphokineactivated killer cell therapy of solid tumors: analysis of toxicity and management guidelines. J Clin Oncol 1989; 7: 486-98. 7. Mizushima Y, Morikage T, Kuwahara T, Yano S. Effects of granulocyte colonystimulating factor on hematopoietic injury induced by anticancer drugs in mice. J Biol Respir Med 1990; 9: 576-83. 8. Klemner MS, Noring R, Mier JW, Atkins MB. An acquired chemotactic defect in neutrophils from patients receiving interleukin-2 immunotherapy. N Engl J Med 1990; 322: 959-65.
Biliary colic on abrupt withdrawal of octreotide SIR,-Octreotide (’Sandostatin’, Sandoz) is highly effective in tumorous growth hormone secretion and resolves symptoms in most acromegalic patients.l Initial adverse effects include transient gastrointestinal disturbance with flatulence, loose motions, and mild steatorrhoea. Gallbladder paresis is also known
suppressing
to occur,
which may result in biliary
evacuation;4 (ii) giving octreotide injections between meats, thereby keeping to a minimum its paretic effect on postprandial biliary emptying; and (iii) co-administration of an oral bile salt (ursodeoxycholic acid) or aspirin to reduce the formation of biliary sludge during concurrent octreotide therapy. In line with the manufacturer’s recommendations all acromegalic patients should undergo routine biliary ultrasonography before and at 6-12 month intervals after the start of octreotide therapy. This identifies those patients in whom biliary sludging and/or calculi will develop, although as yet no firm recommendations have been proposed on how to deal with this problem. In patients who already have calculi, or who acquire them on treatment, dissolution therapy may have to be considered. More work is needed to identify those acromegalic patients who are potential stone formers on octreotide treatment and which prophylactic measures could most effectively be used to counteract this effect. Most important, abrupt withdrawal of octreotide in these patients, especially those with biliary sludge, should be avoided or undertaken with caution, and perhaps the data sheet should be amended accordingly. We thank Prof P. H. Baylis for allowing us to report on one of his patients.
Endocrine Unit, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, UK
1. Lamberts SWJ. The role of somatostatin in the regulation of anterior pituitary hormone secretion and the use of its analogues in the treatment of human pituitary tumours. Endocr Rev 1988; 9: 417-36. 2. van Liessum PA, Hopman WPM, Pieters GFFM, et al. Postprandial gallbladder motility during longterm treatment with the long-acting somatostatin analogues SMS 201-995 in acromegaly. J Clin Endocrinol Metab 1989; 69: 557-62. 3. McKnight JA, McCance DR, Crothers JG, Atkinson AB. Changes in glucose tolerance and development of gallstones during high dose treatment with octreotide in acromegaly. Br Med J 1989; 299: 604-05. 4. Rhodes M, James RA, Bird M, Clayton B, Kendall-Taylor P, Lennard TWJ. Gallbladder emptying in patients on long-term octreotide: evidence for rebound hypermotility after stopping treatment. Br J Surg 1991; 78: 1146.47.
sludging2 and predisposes to
gallstone formation in up to 30% of patients after medium to long term use ( > 3 months).3 Although biliary accretions and calculi can be detected on follow-up ultrasonography they seem to remain symptomless in most subjects. We report a previously unknown side-effect of abrupt withdrawal of octreotide in four acromegalic patients, which may have implications for long-term management on this drug. All patients were on long-term octreotide treatment. They had either discontinued their injections on instructions before reassessment or had inadvertently run out of drug. 12-16 hours after the last injection all patients reported similar symptoms of sudden, severe right hypochondrial pain, which lasted from 15 minutes to 3 hours and was followed by an episode of diarrhoea. By the next day all patients had fully recovered. One patient had identical symptoms on two separate occasions under similar circumstances of sudden drug withdrawal. ,
In all patients the attacks of biliary colic although severe were short lived with no apparent long-term sequelae. Calculi had developed in three patients after 1 year of octreotide; calculi did not develop in patient 2 until the third year of treatment:
These four cases of biliary colic point to a possible adverse effect of rebound gallbladder hypercontractility occurring about 12 hours after abrupt cessation of octreotide.4 Complications such as ascending cholangitis, biliary obstruction, and pancreatitis could be precipitated in this situation. Possible ways to avoid or ameliorate this effect could be: (i) frequent short-term withdrawal of octreotide from the start of treatment-ie, for one day a week-to prevent the development of biliary sludge by allowing regular gallbladder
R. A. JAMES M. RHODES P. ROSE P. KENDALL-TAYLOR
Ophthalmic zoster SIR,-Your editorial the
ophthalmic zoster (Nov 16, p 1244) importance of steroid use in inflammatory on
rightly emphasises complications and cautions about the side-effects and difficulties of withdrawal of the drug. However, confusion was introduced by mentioning epithelial keratitis and comeal ulceration without qualifications. This point deserves clarification because it does affect treatment. There are four main types of epithelial keratitis in zoster.1 The commonest is a microdendritic type that occurs right at the start of the disease and is transitory and self-limiting, requires no treatment, and yields varicella zoster virus on culture. The type known as pseudodendritic or mucous plaque keratitis is complex. No virus has been cultured from the lesions, there is a poor response to topical acyclovir, and steroids frequently have to be used because of underlying inflammation in the stroma and hypertensive iritis. In neuroparalytic keratitis steroids should be strenuously avoided. The fourth type is exposure keratitis, where steroids should be very sparingly used and there is no response to acyclovir. A true dendritic ulcer, like that occurring in herpes simplex, is not seen in zoster. In neuroparalytic ulcers steroids should be avoided; treatment is by inducing levator palsy with botulinum toxin or tarsorrhaphy to protect the cornea. In the very rare serpiginous ulcer3 (or marginal ulceration) there is an associated severe sclerokeratitis and topical steroids are usually required. Zoster Clinic, Moorfields Eye Hospital, London EC1V 2PG, UK
RONALD J. MARSH
RJ. Corneal epithelial lesions in herpes zoster. In: VIth Congress of the European Society of Ophthalmology: the cornea in health and disease (Int Congr Symp Ser no 40). London: Royal Society of Medicine, 1981, 791-95. Marsh RJ, Cooper M. Ophthalmic zoster: mucous plaque keratitis. Br J Ophthalmol
1. Marsh
2.
1987; 71: 690-93.
3. Liesegang TJ. Corneal complications from herpez Ophthalmology 1985; 92: 316-24.
zoster
ophthalmicus.
(eg, pyoderma gangrenosum5 and respiratory distress6 for direct effects; thrombocytopeniaand increased risk of bacterial infections8 for indirect effects). Thus, rhGM-CSF, as well as cytokines already available or that will become available in the next few years, must be used with appropriate care in the patients most likely to benefit. B. DONATINI P. KRUPP T. JONES
Drug Monitoring Centre, Sandoz Pharma, CH-4400 Basel, Switzerland
1. Lieschke GJ, Maher D, Cebon J, et al. Effects of bacterially synthesized recombinant human granulocyte-macrophage colony-stimulating factor in patients with advanced malignancy. Ann Intern Med 1989; 110: 357-64 2. De Vries EGE, Willemse PHB, Biesma B, Stem AC, Limburg PC, Vellenga E. Flare-up of rheumatoid arthritis during GM-CSF treatment after chemotherapy.
Lancet 1991; 338: 517-18. 3. Hancock SL, Cox RS, McDougall IR. Thyroid diseases after treatment of Hodgkin’s disease. N Engl J Med 1991; 352: 599-605. 4. Atkins MB, Mier JW, Parkinson DR, Gould JA, Berkman EM, Kaplan MM. Hypothyroidism after treatment with interleukin-2 and lymphokine-activated killer cells. N Engl J Med 1988; 318: 1557-63. 5. Ross HJ, Moy LA, Kaplan R, Figlin RA. Bullous pyoderma gangrenosum after granulocyte colony-stimulating factor treatment. Cancer 1991; 68: 441-43. 6. Margolin KA, Rayner AA, Hawkins MJ, et al. Interleukin 2 and lymphokineactivated killer cell therapy of solid tumors: analysis of toxicity and management guidelines. J Clin Oncol 1989; 7: 486-98. 7. Mizushima Y, Morikage T, Kuwahara T, Yano S. Effects of granulocyte colonystimulating factor on hematopoietic injury induced by anticancer drugs in mice. J Biol Respir Med 1990; 9: 576-83. 8. Klemner MS, Noring R, Mier JW, Atkins MB. An acquired chemotactic defect in neutrophils from patients receiving interleukin-2 immunotherapy. N Engl J Med 1990; 322: 959-65.
Biliary colic on abrupt withdrawal of octreotide SIR,-Octreotide (’Sandostatin’, Sandoz) is highly effective in tumorous growth hormone secretion and resolves symptoms in most acromegalic patients.l Initial adverse effects include transient gastrointestinal disturbance with flatulence, loose motions, and mild steatorrhoea. Gallbladder paresis is also known
suppressing
to occur,
which may result in biliary
evacuation;4 (ii) giving octreotide injections between meats, thereby keeping to a minimum its paretic effect on postprandial biliary emptying; and (iii) co-administration of an oral bile salt (ursodeoxycholic acid) or aspirin to reduce the formation of biliary sludge during concurrent octreotide therapy. In line with the manufacturer’s recommendations all acromegalic patients should undergo routine biliary ultrasonography before and at 6-12 month intervals after the start of octreotide therapy. This identifies those patients in whom biliary sludging and/or calculi will develop, although as yet no firm recommendations have been proposed on how to deal with this problem. In patients who already have calculi, or who acquire them on treatment, dissolution therapy may have to be considered. More work is needed to identify those acromegalic patients who are potential stone formers on octreotide treatment and which prophylactic measures could most effectively be used to counteract this effect. Most important, abrupt withdrawal of octreotide in these patients, especially those with biliary sludge, should be avoided or undertaken with caution, and perhaps the data sheet should be amended accordingly. We thank Prof P. H. Baylis for allowing us to report on one of his patients.
Endocrine Unit, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, UK
1. Lamberts SWJ. The role of somatostatin in the regulation of anterior pituitary hormone secretion and the use of its analogues in the treatment of human pituitary tumours. Endocr Rev 1988; 9: 417-36. 2. van Liessum PA, Hopman WPM, Pieters GFFM, et al. Postprandial gallbladder motility during longterm treatment with the long-acting somatostatin analogues SMS 201-995 in acromegaly. J Clin Endocrinol Metab 1989; 69: 557-62. 3. McKnight JA, McCance DR, Crothers JG, Atkinson AB. Changes in glucose tolerance and development of gallstones during high dose treatment with octreotide in acromegaly. Br Med J 1989; 299: 604-05. 4. Rhodes M, James RA, Bird M, Clayton B, Kendall-Taylor P, Lennard TWJ. Gallbladder emptying in patients on long-term octreotide: evidence for rebound hypermotility after stopping treatment. Br J Surg 1991; 78: 1146.47.
sludging2 and predisposes to
gallstone formation in up to 30% of patients after medium to long term use ( > 3 months).3 Although biliary accretions and calculi can be detected on follow-up ultrasonography they seem to remain symptomless in most subjects. We report a previously unknown side-effect of abrupt withdrawal of octreotide in four acromegalic patients, which may have implications for long-term management on this drug. All patients were on long-term octreotide treatment. They had either discontinued their injections on instructions before reassessment or had inadvertently run out of drug. 12-16 hours after the last injection all patients reported similar symptoms of sudden, severe right hypochondrial pain, which lasted from 15 minutes to 3 hours and was followed by an episode of diarrhoea. By the next day all patients had fully recovered. One patient had identical symptoms on two separate occasions under similar circumstances of sudden drug withdrawal. ,
In all patients the attacks of biliary colic although severe were short lived with no apparent long-term sequelae. Calculi had developed in three patients after 1 year of octreotide; calculi did not develop in patient 2 until the third year of treatment:
These four cases of biliary colic point to a possible adverse effect of rebound gallbladder hypercontractility occurring about 12 hours after abrupt cessation of octreotide.4 Complications such as ascending cholangitis, biliary obstruction, and pancreatitis could be precipitated in this situation. Possible ways to avoid or ameliorate this effect could be: (i) frequent short-term withdrawal of octreotide from the start of treatment-ie, for one day a week-to prevent the development of biliary sludge by allowing regular gallbladder
R. A. JAMES M. RHODES P. ROSE P. KENDALL-TAYLOR
Ophthalmic zoster SIR,-Your editorial the
ophthalmic zoster (Nov 16, p 1244) importance of steroid use in inflammatory on
rightly emphasises complications and cautions about the side-effects and difficulties of withdrawal of the drug. However, confusion was introduced by mentioning epithelial keratitis and comeal ulceration without qualifications. This point deserves clarification because it does affect treatment. There are four main types of epithelial keratitis in zoster.1 The commonest is a microdendritic type that occurs right at the start of the disease and is transitory and self-limiting, requires no treatment, and yields varicella zoster virus on culture. The type known as pseudodendritic or mucous plaque keratitis is complex. No virus has been cultured from the lesions, there is a poor response to topical acyclovir, and steroids frequently have to be used because of underlying inflammation in the stroma and hypertensive iritis. In neuroparalytic keratitis steroids should be strenuously avoided. The fourth type is exposure keratitis, where steroids should be very sparingly used and there is no response to acyclovir. A true dendritic ulcer, like that occurring in herpes simplex, is not seen in zoster. In neuroparalytic ulcers steroids should be avoided; treatment is by inducing levator palsy with botulinum toxin or tarsorrhaphy to protect the cornea. In the very rare serpiginous ulcer3 (or marginal ulceration) there is an associated severe sclerokeratitis and topical steroids are usually required. Zoster Clinic, Moorfields Eye Hospital, London EC1V 2PG, UK
RONALD J. MARSH
RJ. Corneal epithelial lesions in herpes zoster. In: VIth Congress of the European Society of Ophthalmology: the cornea in health and disease (Int Congr Symp Ser no 40). London: Royal Society of Medicine, 1981, 791-95. Marsh RJ, Cooper M. Ophthalmic zoster: mucous plaque keratitis. Br J Ophthalmol
1. Marsh
2.
1987; 71: 690-93.
3. Liesegang TJ. Corneal complications from herpez Ophthalmology 1985; 92: 316-24.
zoster
ophthalmicus.