443

doxylamine overdose is suspected, plasma creatine kinase should bemeasured.

Poison Control Centre (Adults),Reanimationszentrum,Klinikum Charlottenburg,Freie Universität Berlin,D-1000 Berlin 19, West Germany;and Poison Control Centre (Children),

Berlin

CLAUS KÖPPELKARLA IBEURSULA OBERDISSE

1. Steinhoff Kirschstein M, Castan H, Sack K. Akutes oligurisches Nierenversagennach Rhabdomyolyse durch Diphenhydramin. Dtsch Med Wschr 1985; 110: 2000.

2. Hampel G, Horstkotte K, Rumpf KW. Myoglobinuric renal failure due to

drug-induced rhabdomyolysis. Hum Toxicol 1983; 2: 197-201.3. Colombi A, Briner V, Truniger B. Rhabdomyolysis. Dtsch Med Wschr 1985; 110:

1461-63.

LYME ARTHRITIS

SIR,-Dr Muhlemann and Dr Wright (Jan 31, p 260) state thatarthritis has not been reported in European cases of Lyme disease.Not so: cases of Lyme arthritis have been published in France,1-3Sweden,’ Germany,5 Austria and Switzerland .7 Moreover, we andother colleagues have observed, in a three-month period, three casesof arthritis in Lyme disease (unpublished). The main features ofthese cases were: arthritis localised in that part of the leg whereneurological and cutaneous lesions had developed before theappearance of the arthritis, complete recovery of the arthritis after asingle course of intravenous penicillin therapy (20 megaunits perday for 10 days), and absence of cartilage erosions. These features fitin with most similar cases reported in Europe. The arthritis seems tobe less severe than that reported in the United States, perhapsbecause of quicker diagnosis and more rapid treatment withantibiotics. Some European cases not treated with antibiotics3 havehad prolonged, severe courses more closely resembling the patternseen in the USA. In our hospital, the three cases were recorded ineighteen patients with Lyme disease with neurologicalmanifestations, a frequency of 17 %.

Department of Rheumatology,St Luc University Hospital,B-1200 Brussels, Belgium

J. P. HUAUXC. NAGANT DE DEUXCHAISNES

1. Illouz G, Hewitt J. A propos de l’arthrite de Lyme. Polyarthrite inflammatoire aprèsun érythème annulaire migrant. Rev Rhum Mal Ostéoartic 1981; 48: 813-15.

2. Mallecourt J, Landureau M, Wirth AM. La maladie de Lyme: un cas clinique observéen Eure-et-Loir. Nouv Presse Méd 1982; 11: 39-41.

3 Dougados M, Kahan A, Vannier A, Amor B. Arthrite de Lyme: Deux nouveaux casfrançais. Rev Rhum Mal Ostéoartic 1983; 50: 299-302.

4. Stiernstedt G, Granstrom M. Ixodes ricinus spirochete infection as the cause ofpostinfectious arthritis in Sweden. Scand J Rheumatol 1985; 14: 336-42.

5 Ackermann R, Runne U, Klenk W, Dienst C. Erythema chronicum migrans mitArthritis. Dtsch Med Wschr 1980; 105: 1779-81.

6 Stanek G, Wewalka G, Groh V, Neumann R, Kristoferitsch W. Differences betweenLyme disease and European arthropod-borne borrelia infections. Lancet 1985; i:401.

7 Gerster JC, Guggi S. Lyme arthritis appearing outside the United States: a case reportfrom Switzerland. Br Med J 1981; 283: 951-52.

METHYSERGIDE AND RETROPERITONEALFIBROSIS

SIR,—Methysergide is used to prevent migraine headaches. Anuncommon side-effect is retroperitoneal fibrosis. Because of thisside-effect a one month drug "holiday" is recommended after sixmonths’ treatment.

Methysergide is the only ergot alkaloid reported to causeretroperitoneal fibrosis. For example, ergotamine and lysergide(LSD) lack this side-effect despite being structurally similar tomethysergide. This suggests that methysergide interacts with aspecific receptor to cause retroperitoneal fibrosis. Perhaps this drugacts as a growth factor agonist or as an agent that binds specificallyon or near a growth factor receptor so that a conformational changeto an active state is induced. Slight alterations in structure eliminatethe side-effect; retroperitoneal fibrosis is characterised by excessivefibroblast proliferation and connective tissue deposition, consistentwith growth factor stimulation of fibroblasts ; and discontinuation ofthe drug is followed by regression of the fibrosis, suggestingreversible interaction at receptor level. Idiopathic retroperitonealfibrosis, on the other hand, is irreversible, and may be due to adefective growth factor receptor which is permanently activated.Graham et all suggested that methysergide interacts with

serotonin (5-HT) receptors to cause retroperitoneal fibrosis, and

5-HT had been reported to cause fibrosis. However, methysergideis a 5-HT antagonist and should not have the same action as 5-HT if5-HT receptors are involved. Furthermore, cyproheptadine andpizotifen, 5-HT antagonists used prophylactically against migraine,interact with the same class of 5-HT receptor (5-HT-D) as doesmethysergide but have not been associated with retroperitonealfibrosis. Thus, an interaction at a 5-HT receptor seems unlikely.While the interaction of methysergide with growth factor

receptor is specific, the effect elicited is weak and cumulative;chronic methysergide use is required to produce retroperitonealfibrosis.

Department of Pathology,University of Arkansas for Medical Sciences,Little Rock, Arkansas 72205, USA ERIC REIMUND

1. Graham JR, Suby HI, LeCompte PR, Sadowsky NL. Fibrotic disorders associatedwith methysergide therapy for headache. N Engl J Med 1966; 274: 359-68.

PROGNOSIS OF DRUG-INDUCED PARKINSON’SDISEASE

SIR,-9% of patients referred to the university department ofgeriatric medicine in Edinburgh during 1982-84 had some

parkinsonian features and in half of those in whom the diagnosis wasconfirmed, the Parkinson’s disease was attributed to drugs.1 Sincestriatal dopamine receptors decline with age older people may bemore susceptible to the dopaminergic antagonist effects of

neuroleptic drugs. If old people with drug-induced Parkinson’s(DIP) have fewer remaining dopaminergic neurons they could beat increased risk of idiopathic Parkinson’s disease (IPD). Indeedthis had happened in 5 of 48 patients presenting to our unit withDIP, at follow-up after 18 months.

44 of the original 48 patients have now been followed up, 41months on average after diagnosis of DIP. These patients hadreceived neuroleptic therapy for 21 months before DIP wasdiagnosed.

20 patients remained alive. Survival was not related to age and themean age was 80 years. 78% of men but only 39% of women haddied. The mean length of survival from diagnosis of DIP was 20months. At follow-up, two-thirds of the patients were in hospital,residential accommodation, or a nursing home. The group as awhole had a high degree of dependency (table), and IPD haddeveloped in 8 of the original 44 patients (18%) and in 5 of thesurvivors (25 %). Information on drug treatment at follow-up wasobtained in 32 patients: 4 were receiving neuroleptics at follow-upor death but had no evidence of Parkinson’s disease and 4 remainedon the neuroleptic with persistence of DIP (all 4 died). The 5surviving cases with IPD following remission of DIP had fewerparkinsonian features than when they had DIP; 4 were onanti-parkinsonian treatment.Our main concern was how many patients with DIP would

subsequently have IPD. The high mortality observed is likely tohave led to an underestimate of IPD. When the patients with DIPwere followed up after 18 months, 12 % of those remaining alive andhaving remission of DIP had IPD.1 At 41 months, this figure was25 %. The development of more cases of IPD during the 41 monthsof follow-up suggests that age-related neuronal loss is veryimportant and adds weight to the hypothesis2,3 that an

environmental insult causes loss of dopamiriergic neurons that

FUNCTIONAL STATUS AT FOLLOW-UP OR JUST BEFORE DEATH