Eur Reeplr J 11192, 5, 283-285 CASE REPORT

Pleuropulmonary changes during treatment of Parkinson's disease with a long-acting ergot derivative, cabergollne

E. Frans*, A. Dom**, M. Demedts*

Pleuropulmonary changes during treatment of Parkinson's disease with a long­ • Pulmonary Division, Department of acting ergot derivative, cabergo/ine. E. Frans, R. Dom, M. Demedts. Medicine and • •Department of Neurol­ ABSTRACT: A patient with Parkinson's disease, Initially treated with ogy, University Hospitals, Catholic bromocrlptlne and subsequently with cabergolloe, developed progressive pleu­ University Leuven, Belgium. ropulmonary abnormalities during the latter therapy. These lesions even Correspondence: M. Demedts worsened for some weeks after Interruption of cabergollne, which may possi­ University Hospital bly be related to the prolonged action of this drug. Thus cabergollne may Wollgerveld 1 cause similar pleuropulmonary abnormalities to bromocrlptlne. B-3212 Pellenberg, Belgium. Eur Respir J., 1992, 5, 263-265. Received: 1une 11, 1991; accepted after revision October lS, 1991. Keywords: Cabergollne, Pleuropul­ monary change, Parkinson's disease.

In 1981, RINNE [1] reported the development of existed in that period. In August 1990, the patient pleuropulmonary changes during bromocriptine treat­ experienced an episode of adynamia, weight loss and ment of Parkinson's disease. This finding was later arthralgias, with no identifiable cause. A new chest confirmed by other authors [2-10]. The normal X-ray revealed a marked progression of the previously evolution on stopping bromocriptine is for pleuropul­ described abnormalities with occurrence of an interlo­ monary changes to regress. Similar abnormalities have bar pleural effusion at the right side. also been found with other derivatives with similar Cabergoline was discontinued in August 1990, and molecular structures, such as methysergide and the therapy was then changed to levodopa-benserazide ergotamine [11 ]. and trihexiphenidyl. In October 1990, the pleuropul­ In this case report, we describe a patient who monary abnormalities had progressed slightly (fig. 1), developed progressive pleuropulmonary abnormalities despite the withdrawal of cabergoline and the during treatment initially with bromocriptine and improvement of the patie nts' general condition. subsequently with cabergoline. The latter drug is a Computer tomographic (CT) scan showed right pleural new ergot derivative with a selective, potent and long­ thickening, with interstitial pulmonary markings and lasting dopaminergic agonistic activity [12, 13]. atelectasis, and also some shadowing in the left lung. (fig. 2).

Case report

A 57 year old man, nonsmoker, with no relevant medical history, worked as a carpenter in the manu­ facturing industry until retirement in 1988. He devel­ oped symptoms of Parkinson's disease in 1981. After a temporary treatment with biperiden, he received a therapy with levodopa-benserazide in combination with bromocriptine (mean dose 30 1 mg·day· ) until 1989. In October 1989, the therapy was changed to levo­ dopa-benserazide with cabergoline, in the framework of a clinical study with this new ergot derivative. Chest X-rays at that time already showed some pleuro­ pulmonary shadowing in the right basal lung field. The study medication was well-tolerated, with good clinical efficacy. After 2 months of treatment, how­ ever, erythrocyte sedimentation rate (ESR) increased to 1 95 mm·2b· for some weeks, and normalized sponta­ Fig. 1. - Pleuropulmonary abnormalities after two months of neously thereafter. No other signs or complaints interruption of carbergoline. 264 E. FRANS, R. DOM, M. DEMEDTS

There are several arguments for the causal relationship between cabergoline intake and these pleuropulmonary abnormalities. Firstly, the radiological pleuropulmo­ nary lesions are similar to those induced by bro­ mocriptine [1-10]. Secondly, we found an increased percentage of lymphocytes in BAL, and granulomatous histopathological features on transbronchial biopsies, which are consistent with a drug induced alveolitis. Finally, other causes for the pleuropulmonary abnor­ malities were excluded, e.g. tuberculosis, sarcoidosis, connective tissue diseases, other exposures. Although the type and progression of the pleuro­ pulmonary changes during cabergoline treatment, strongly suggest a causal relationship, this can only be proved by rechallenge. ToRNUNo et al. [7] described two patients with Parkinson's disease, intermittently treated with bromocriptine, in whom retrospective anal­ Fig. 2. - Computed tomographic (CT)-scan at the time of chest yses showed, an aggravation of the pleuropulmonary X-ray on figure 1 confirming pleuropulmonary abnormalities. disorders when bromocriptine was restarted. However, a prospective rechallenge study may be ethically non­ Laboratory results (with inclusion of ESR, liver acceptable because of the possible irreversible changes. function, complement, latex fixation test, immune In the reports on bromocriptine, a resolution or complexes, anti-nuclear factor, lupus erythematosus improvement of the clinical and radiographic signs has (LE)-cells, serum angiotensin converting enzyme) were been described shortly after reduction or withdrawal of within normal ranges. Tests for tuberculosis or other the medication. In the present case, the radiographic infectious diseases were negative. Pulmonary function abnormalities further progressed up to two months tests showed a slight restriction of vital capacity (3.161 after discontinuation of cabergoline. Cabergoline has = 77% pred), forced expiratory volume in one a more prolonged action than other dopaminergic ) second (FEV1 (2.58 I = 82% pred), total lung capac­ agonist ergot derivatives (bromocriptine, pergolide, ity ( 4.58 I = 72% pred) with a decreased diffusing Iisuride) (12, 13] which may explain our finding of a capacity (6.92 mmol·min·LkPa·1 = 76% pred) and a progression of the pleuropulmonary changes after reduced static lung compliance (1.53 l·kPa·1 at func­ withdrawal. tional residual capacity (FRC). On Gallium-67 lung scan, a slightly increased uptake in both lung fields (index 77/400) was seen, and on ventilation and References perfusion scintigraphy we noted a right/left ratio of 29/71 for both tests. Bronchoalveolar lavage fluid (BAL) examination revealed a lymphocytic alveolitis: 1. Rinne UK. - Pleuropulmonary changes during long­ 38% macrophages, 62% lymphocytes with a T4{f8 term bromocriptine treatment for Parkinson's disease. ratio of 3.3. Peripheral transbronchial lung biopsies Lancet, 1981; i: 44. 2. LeWitt PA, Calne DB. - Pleuropulmonary changes showed multifocal noncaseating granulomas with during long-term bromocriptine treatment for Parkinson's lymphocytic inflammatory infiltrates. disease. Lancet, 1981; i: 45. In March 1991 we noted a spontaneous, slight 3. Besser GM, Wass JAH. - Pleuropulmonary shadows improvement of the radiological pleuropulmonary on bromocriptine. Lancet, 1981; i: 323. abnormalities and of the diffusing disturbances (7.81 4. Dupont E, de Fine Olivarius B, Strong MJ. - mmol·min·1·kPa·1 = 86% pred). Bromocriptine induced collagenosis-like symptomatology in Based on the results of the investigations, on the Parkinson's disease. Lancet, 1982; i: 850-851. evolution, and on the exclusion of other aetiologies, 5. Vergeret J, Barat M, Taytard A, Bellevert P, Domblides the diagnosis was made of pleuropulmonary changes Ph, Douvier JJ, Fr6ovr P. - Fibrose pleuropulmonaire et initiated by bromocriptine and worsened during therapy bromocriptine. Sem Hop Paris, 1984; 60: 740-741. 6. Wiggins J, Skinner C. - Bromocriptine-induced with cabergoline. pleuropulmonary fibrosis. Thorax, 1986; 41: 328-330. 7. Tornling G, Unge G, Axelsson G, Noring L, Granerus Comment AK. - Pleuropulmonary reactions in patients on bromocriptine treatment. Eur J Respir Dis, 1986; 68: 35-38. Pleuropulmonary complications on bromocriptine 8. McElvany NG, Wilcox PG, Cburg AM, Fleetham JA. treatment have been described only in patients with - Pleuropulmonary disease during bromocriptine treatment Parkinson's disease, probably as a consequence of the of Parkinson's disease. Arch Intern Med, 1988; 148: higher dose (20-100 mg·day·1) compared with the 2231-2236. endocrinological indications. 9. Kinnunen E, Viljanen A. - Pleuropulmonary in­ Our patient developed pleuropulmonary abnormali­ volvement during bromocriptine treatment. Chest, 1988; 94: ties and systemic illness during cabergoline treatment. 1034-1036. PLEUROPULMONARY CHANOES WITH CABBROOLINB 265 10. Melmed S, Braunstein G. - Bromocriptine and pleu­ longterm treatment with cabergoline, a new long-lasting ropulmonary disease. Arch Intern Med, 1989; 149: 258-259. ergoline derivative, in hyperprolactinemic patients. J Clin 11. Taal BG, Spierings EL, Hilvering C. - Pleuropulmo­ Endocrinol Metab, 1989; 69: 725-728. nary changes with chronic and excessive intake of ergot­ 13. Ferrari C, Mattei A, Melis GB, et aL - Cabergoline: amine. Thorax, 1983; 38: 396-398. long-acting oral treatment of hyperprolactinemic dis­ 12. Ciccarelli E, Giusti M, Miola C, Sghedoni D, Camanni orders. J. Clin Endocrinol Metab, 1989; 68: 1201- F, Giordana G. - Effectiveness and tolerability of 1206.