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Topical cidofovir for severe molluscum contagiosum
Topical cidofovir for severe molluscum contagiosum E G Davies, A Thrasher, K Lacey, J Harper
Time-response curve for the positive subscore of PANSS (46 patients treated for 4 weeks) *p<0·01, †p<0·001.
(p<0·001, figure). The scores for six out of the seven items of the PANSS positive subscore (except item grandiosity) were significantly reduced. The MMS mean score did not change significantly in either group as well as the UPDRS mean motor score, which decreased by 3·5 and 3·0 points in the clozapine and placebo groups, respectively. The frequency of adverse events was similar in both groups and only somnolence and worsening of parkinsonism were significantly more frequently in the clozapine group. Seven patients in the clozapine group reported worsening of Parkinson’s disease, usually mild or transient, which was confirmed by an aggravation in the Schwab and England score by 10% to 20% in only three patients, and no patient discontinued the study for this reason. There was no case of agranulocytosis. We conclude that clozapine up to 50 mg daily is rapidly effective in psychosis associated with Parkinson’s disease. On the whole, parkinsonian symptoms and signs are not worsened though individual cases may exhibit transient or mild worsening without comprising treatment. Except for somnolence, clozapine is well tolerated in this group of elderly patients. Regular and long-term cell blood counts are mandatory.1 The French Clozapine Parkinson Study Group Steering committee—P Pollak, Hôpital Nord, Grenoble, Coordinator; A Destée, C.H.U. Lille; F Tison, Hôpital Sud Haut L’Evêque, Pessac; J J Péré. Novartis Pharma, Rueil Malmaison; I Bordeix, Novartis Pharma, Rueil Malmaison. Other members—Y Agid, Hopital Salpêtrière, Paris; H Allain, C.H.R.U. Rennes; M Borg, Hôpital Pasteur, Nice; E Broussolle, Hôpital Neurologique, Lyon; F Durif, Hôpital Gabriel Montpied, ClermontFerrand; C Geny, Centre Hospitalier Général, Pau; C Prunier-Levilon, C.H.U. Bretonneau, Tours; O Rascol, Hôpital Purpan, Toulouse; S Sangla, Hôpital Delafontaine, Paris; M Vérin, C.H.U., Rennes; F Viallet, Hôpital Général, Aix en Provence; C Tranchant, Hôpital Civil, Strasbourg. 1 2
3
4
5
Baldessarini RJ, Frankenburg FR. Drug therapy: clozapine—a novel antipsychotic agent. N Engl J Med 1991; 324: 746–54. Scholz E, Dichgans J. Treatment of drug-induced exogenous psychosis in parkinsonism with clozapine and fluperlapine. Eur Arch Psychiatry Neurol Sci 1985; 235: 60–64. The Parkinson Study Group. Low-dose clozapine for the treatment of drug-induced psychosis in Parkinson’s disease. N Engl J Med 1999; 340: 757–63. Kay SR, Opler LA, Lindenmayer JP. The Positive and Negative Syndrome Scale (PANSS): rationale and standardisation. Br J Psychiat 1989; 155: 59–65. Fahn S, Elton RL, and Members for the UPDRS development committee. Unified Parkinson’s Disease Rating Scale. In: Fahn S, Marsden CD, Calne D, Goldstein M, eds. Recent developments in Parkinson’s disease. Vol 2. Florham Park, NJ: MacMillan Healthcare Information, 1987: 153–63.
Service de Neurologie, Centre Hospitalier Universitaire de Grenoble, BP 217 X, 38043 Grenoble Cedex 9, France (P Pollak e-mail: [email protected])
2042
Molluscum contagiosum is a pox virus which commonly causes a self-limiting infection in children. However, in immunodeficient patients it can be severely disfiguring and intractable. Secondary bacterial infection is a common complication. There is no proven specific antiviral therapy and the efficacy of immunomodulatory therapies including alphaand beta-interferons has been limited. Cidofovir is an anti viral agent with a broad range of activity against the herpes group of viruses, pox viruses, and retroviruses.1 It has been reported to produce resolution of M contagiosum lesions in three patients with AIDS two of whom were being treated with the drug primarily for cytomegalovirus retinitis.2 In the third it was found to be of benefit when used topically—the advantage of this route of administration being the avoidance of potentially serious nephrotoxicity when the drug is given systemically. We report here the use of topical cidofovir in the treatment of intractable M contagiosum infection in a boy with Wiskott Aldrich syndrome. The boy had been diagnosed as suffering from this primary immunodeficiency syndrome in early infancy when he presented with eczema, bleeding due to thrombocytopenia, and recurrent bacterial infections. The diagnosis was confirmed by demonstration of the absence of the Wiskott Aldrich syndrome protein (WASP) in cells of haemopoietic lineage and the demonstration of a mutation in the WASP gene. His early childhood was complicated by frequent bleeding episodes which subsided after splenectomy, and a severe enteropathy associated with multiple food intolerances that required immunosuppressive treatment with steroids and cyclosporin. At age 11 years he developed sclerosing cholangitis. At the age of 12 he had skin lesions due to M contagiosum which spread rapidly affecting more than 75% of his skin surface. These became confluent in areas with very large lesions up to 2 cm in diameter. Secondary infection and cellulitis became a regular problem. Treatment with ␣ interferon followed by ␥ interferon was attempted but both were poorly tolerated and no benefit was seen. A trial of topical cidofovir (made up as a 1% preparation in unguentum merck) was started on one upper arm. At the same time the other arm was treated with topical lithium (Efalith), anecdotal reports suggesting that this preparation may be useful for the treatment of mollusca contagiosa. Within 2–3 weeks the lesions in the area treated with cidofovir showed acute inflammation which was followed by a dramatic resolution of all treated lesions. There were no changes observed in the lesions in non-treated areas nor in the area treated with lithium. Subsequently other skin areas have been treated with similar results. No systematic side effects were seen and no skin discolouration although scarring remains at the sites of some of the larger lesions. The treatment is continuing and recurrence of lesions has been minimal. To our knowledge this is the first use of this drug for severe M contagiosum infection in a patient with a primary immunodeficiency syndrome and, in view of the failure of other treatments to influence the disease, the results suggest that further studies of its use in similar patients are warranted. 1 2
De Clercq E. Acrylic nucleotide phosphonates in the chemotherapy of DNA virus and retrovirus infections. Intervirology 1997; 40: 295–303. Meadows KP, Tyring SK, Pavia AT, Rallis TM. Resolution of recalcitrant Molluscum Contagiosum virus lesions in human immunodeficiency virus-infected patients treated with Cidofovir. Arch Dermatol 1997; 133: 987–90.
Departments of Immunology and Dermatology, Great Ormond Street Hospital and Institute of Child Health, London WC1N 3JH (E G Davies) and Department of Paediatrics, Stepping Hill Hospital, Stockport
THE LANCET • Vol 353 • June 12, 1999
Time-response curve for the positive subscore of PANSS (46 patients treated for 4 weeks) *p<0·01, †p<0·001.
(p<0·001, figure). The scores for six out of the seven items of the PANSS positive subscore (except item grandiosity) were significantly reduced. The MMS mean score did not change significantly in either group as well as the UPDRS mean motor score, which decreased by 3·5 and 3·0 points in the clozapine and placebo groups, respectively. The frequency of adverse events was similar in both groups and only somnolence and worsening of parkinsonism were significantly more frequently in the clozapine group. Seven patients in the clozapine group reported worsening of Parkinson’s disease, usually mild or transient, which was confirmed by an aggravation in the Schwab and England score by 10% to 20% in only three patients, and no patient discontinued the study for this reason. There was no case of agranulocytosis. We conclude that clozapine up to 50 mg daily is rapidly effective in psychosis associated with Parkinson’s disease. On the whole, parkinsonian symptoms and signs are not worsened though individual cases may exhibit transient or mild worsening without comprising treatment. Except for somnolence, clozapine is well tolerated in this group of elderly patients. Regular and long-term cell blood counts are mandatory.1 The French Clozapine Parkinson Study Group Steering committee—P Pollak, Hôpital Nord, Grenoble, Coordinator; A Destée, C.H.U. Lille; F Tison, Hôpital Sud Haut L’Evêque, Pessac; J J Péré. Novartis Pharma, Rueil Malmaison; I Bordeix, Novartis Pharma, Rueil Malmaison. Other members—Y Agid, Hopital Salpêtrière, Paris; H Allain, C.H.R.U. Rennes; M Borg, Hôpital Pasteur, Nice; E Broussolle, Hôpital Neurologique, Lyon; F Durif, Hôpital Gabriel Montpied, ClermontFerrand; C Geny, Centre Hospitalier Général, Pau; C Prunier-Levilon, C.H.U. Bretonneau, Tours; O Rascol, Hôpital Purpan, Toulouse; S Sangla, Hôpital Delafontaine, Paris; M Vérin, C.H.U., Rennes; F Viallet, Hôpital Général, Aix en Provence; C Tranchant, Hôpital Civil, Strasbourg. 1 2
3
4
5
Baldessarini RJ, Frankenburg FR. Drug therapy: clozapine—a novel antipsychotic agent. N Engl J Med 1991; 324: 746–54. Scholz E, Dichgans J. Treatment of drug-induced exogenous psychosis in parkinsonism with clozapine and fluperlapine. Eur Arch Psychiatry Neurol Sci 1985; 235: 60–64. The Parkinson Study Group. Low-dose clozapine for the treatment of drug-induced psychosis in Parkinson’s disease. N Engl J Med 1999; 340: 757–63. Kay SR, Opler LA, Lindenmayer JP. The Positive and Negative Syndrome Scale (PANSS): rationale and standardisation. Br J Psychiat 1989; 155: 59–65. Fahn S, Elton RL, and Members for the UPDRS development committee. Unified Parkinson’s Disease Rating Scale. In: Fahn S, Marsden CD, Calne D, Goldstein M, eds. Recent developments in Parkinson’s disease. Vol 2. Florham Park, NJ: MacMillan Healthcare Information, 1987: 153–63.
Service de Neurologie, Centre Hospitalier Universitaire de Grenoble, BP 217 X, 38043 Grenoble Cedex 9, France (P Pollak e-mail: [email protected])
2042
Molluscum contagiosum is a pox virus which commonly causes a self-limiting infection in children. However, in immunodeficient patients it can be severely disfiguring and intractable. Secondary bacterial infection is a common complication. There is no proven specific antiviral therapy and the efficacy of immunomodulatory therapies including alphaand beta-interferons has been limited. Cidofovir is an anti viral agent with a broad range of activity against the herpes group of viruses, pox viruses, and retroviruses.1 It has been reported to produce resolution of M contagiosum lesions in three patients with AIDS two of whom were being treated with the drug primarily for cytomegalovirus retinitis.2 In the third it was found to be of benefit when used topically—the advantage of this route of administration being the avoidance of potentially serious nephrotoxicity when the drug is given systemically. We report here the use of topical cidofovir in the treatment of intractable M contagiosum infection in a boy with Wiskott Aldrich syndrome. The boy had been diagnosed as suffering from this primary immunodeficiency syndrome in early infancy when he presented with eczema, bleeding due to thrombocytopenia, and recurrent bacterial infections. The diagnosis was confirmed by demonstration of the absence of the Wiskott Aldrich syndrome protein (WASP) in cells of haemopoietic lineage and the demonstration of a mutation in the WASP gene. His early childhood was complicated by frequent bleeding episodes which subsided after splenectomy, and a severe enteropathy associated with multiple food intolerances that required immunosuppressive treatment with steroids and cyclosporin. At age 11 years he developed sclerosing cholangitis. At the age of 12 he had skin lesions due to M contagiosum which spread rapidly affecting more than 75% of his skin surface. These became confluent in areas with very large lesions up to 2 cm in diameter. Secondary infection and cellulitis became a regular problem. Treatment with ␣ interferon followed by ␥ interferon was attempted but both were poorly tolerated and no benefit was seen. A trial of topical cidofovir (made up as a 1% preparation in unguentum merck) was started on one upper arm. At the same time the other arm was treated with topical lithium (Efalith), anecdotal reports suggesting that this preparation may be useful for the treatment of mollusca contagiosa. Within 2–3 weeks the lesions in the area treated with cidofovir showed acute inflammation which was followed by a dramatic resolution of all treated lesions. There were no changes observed in the lesions in non-treated areas nor in the area treated with lithium. Subsequently other skin areas have been treated with similar results. No systematic side effects were seen and no skin discolouration although scarring remains at the sites of some of the larger lesions. The treatment is continuing and recurrence of lesions has been minimal. To our knowledge this is the first use of this drug for severe M contagiosum infection in a patient with a primary immunodeficiency syndrome and, in view of the failure of other treatments to influence the disease, the results suggest that further studies of its use in similar patients are warranted. 1 2
De Clercq E. Acrylic nucleotide phosphonates in the chemotherapy of DNA virus and retrovirus infections. Intervirology 1997; 40: 295–303. Meadows KP, Tyring SK, Pavia AT, Rallis TM. Resolution of recalcitrant Molluscum Contagiosum virus lesions in human immunodeficiency virus-infected patients treated with Cidofovir. Arch Dermatol 1997; 133: 987–90.
Departments of Immunology and Dermatology, Great Ormond Street Hospital and Institute of Child Health, London WC1N 3JH (E G Davies) and Department of Paediatrics, Stepping Hill Hospital, Stockport
THE LANCET • Vol 353 • June 12, 1999