668
of eczema. Onerecorded improvement in patients’ assessments of itch but the large difference in pre-trial scores between the groups makes interpretation difficult. Scotia Pharmaceuticals have given us details of two unpublished studies; neither shows a significant clinical difference between epogram and placebo. All the trials have been included in a meta-analysis,s originating from the Efamol Research Institute, which claimed very significant benefits for epogam in the treatment of eczema. The largest published trial was a double-blind crossover study completed by 123 patients with atopic eczema in which no significant effect of epogam was seen.6 The meta-analysis and the promotional literature reject these findings and suggest that placebo and epogam tablets were mixed, rendering the study void. Atopic eczema is a common and distressing condition, and the market for any potential treatment is huge. A safe oral treatment has obvious attractions. As for the evaluation of therapy in any chronic
relapsing disease, a double-blind, randomised, placebo-controlled parallel trial is the best study design. Such trials as have been done with epogam in atopic eczema do not show a significant advantage over placebo, and a meta-analysis is no more reliable than the data on which it is based. The claim of a "substantial and highly significant clinical improvement" is not substantiated. This should be considered before doctors put patients on a treatment for which even the manufacturers
to
recommend a treatment time of 8-12 weeks
achieve a benefit.
Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, UK
G. R. SHARPE P. M. FARR
Meigel W. Treatment of atopic dermatitis. Z Hautkr 1986; 61: 473-78. Wright S, Burton JL. Oral evening-primrose-seed oil improves atopic eczema. Lancet 1982; ii: 1220-22. 3. Schalin-Karrila M, Mattila L, Jansen CT, Uotila P. Evening primrose oil m the treatment of atopic eczema: effect on clinical status, plasma phospholipid fatty acids and circulating blood prostaglandins. Br J Dermatol 1987; 117: 11-19. 4. Bordoni A, Biagi PL, Masi M, et al. Evening primrose oil (Efamol) in the treatment of children with atopic eczema. Drugs Exp Clin Res 1987; 14: 291-97. 5. Morse PF, Horrobin DF, Manku MS, et al. Meta-analysis of placebo-controlled studies of the efficacy of Epogam in the treatment of atopic eczema: relationship between plasma essential fatty add changes and clinical response. Br J Dermatol 1989; 121: 75-90. 6. Bamford JTM, Gibson RW, Renier CM. Atopic eczema unresponsive to evening primrose oil (linoleic and &ggr;-linolenic acids). J Am Acad Dermatol 1985; 13: 959-65. 1.
2.
Pseudotumor cerebri associated with
leuprorelin acetate SIR,-Leuprorelin acetate is a synthetic nonapeptide analogue of naturally occurring gonadotropin releasing hormone (GnRH or LHRH) that is used in the treatment of sterility and advanced prostatic cancer. Its main side-effects include hot flushes, vaginal dryness, electrocardiographic changes, local wheal reactions, and peripheral oedema.1 We describe a patient in whom pseudotumor cerebri (benign increased intracranial pressure) developed during treatment with leuprorelin acetate agonist. A 33-year-old man with a long history of hypogonadism and azoospermia was admitted because of rheumatic fever. During the past 2 years, he had been placed on a pulsatile LHRH pump (’Lupron’) without improvement in his sterility. A year later, while still on leuprorelin acetate, the patient had severe constant headaches. On admission he had bilateral papilloedema. Neurological examination and computed tomography of brain were normal. The cerebrospinal fluid (CSF) was clear and acellular at a pressure of 429 mm H2O, within protein 17 mg/dl and glucose 51 mg/dl. Cultures for bacteria, viruses, and tuberculosis were negative. Visual field examination revealed slight bilateral nasal loss. No known
cause
of increased intracranial pressure
was
discontinuation of the drug. Transient frontal headaches have been frequently reported during treatment with another LHRH analogue.’ Pseudotumor cerebri is caused by several drugs, including tetracycline, steroids, vitamin A, nalidixic acid, nitrofurantoin, sulphur preparations, and phenytoin,
levothyroxine. Departments of Internal Medicine and Neurology, Beilinson Medical Centre, Petah Tiqva, Israel 49 100
N. ARBER R. FADILA J. PINKHAS
H. SHIRIN E. MELAMED Y. SIDI
GS, Coddington CC, Winkel CA, Shawker TH, Lonaux DL, Collins RL. Efficacy of a gonadotropin-releasing hormone agonist in the treatment of uterine leiomyomata. Fertil Steril 1989; 51: 951-56 2. Bowman MA. Pseudotumour cerebri. Am Fam Physician 1978; 35: 177-82. 3. Hoffman HJ. Pseudotumour cerebri. Surg Neurol 1987; 27: 405. 1 Letterie
Evidence for neoplasia in "pseudolymphoma" of lung SIR,-"Pseudolymphoma" is
a term
used
to
describe extranodal
tumour-like
lymphoid hyperplasia which is not clearly neoplastic histologically;’ its origin is uncertain. Our molecular genetic and cytogenetic studies in a case of pulmonary pseudolymphoma revealed the tumour to be neoplastic and of B-cell origin. A 43-year-old woman was admitted in December, 1988, for evaluation of slowly progressive lung disease which she had had for about 4 years. She had a history of left orbital tumour diagnosed histologically as a benign lymphoid hyperplasia in March, 1988. Chest X-rays revealed nodular shadows in the bilateral lower lung fields but there was no evidence of tumour involvement in other regions. She had autoimmune haemolytic anaemia (Hb 97 g/dl, haptoglobin 3-1 mg/dl, direct and indirect Coombs’ test positive); the gammaglobulin level was normal. In February, 1989, she underwent right lower lobectomy with removal of the tumour, which was histologically compatible with pseudolymphoma.1 Immunophenotypic findings on fresh excised tumour cells indicated polyclonal lymphoid hyperplasia. Studies of tumour DNA by Southern hybridisation with JH, JK, Cp, and Jyl probes revealed clonal rearrangements of Ig heavy-chain and kappa-chain genes (fig 1). Cytogenetic study after short-term culture of tumour cells without mitogens revealed, in the 11 metaphases studied, 7 normal diploid and 4 hyperdiploid patterns. +3, +7, lp+, and +mar2 were common constitutional abnormalities in 4 hyperdiploid metaphases (fig 2), that consisted of 49-50 chromosomes with minor karyotypic instabilities. Although some studies of extranodal lymphoid hyperplasias have revealed clonal Ig rearrangements2-4 this is not direct evidence of malignancy, and no cytogenetic study has been reported so far. The
found.
Leuprorelin acetate was discontinued. On follow-up the papilloedema resolved and headaches and visual-field defects subsided. Six months later, he had a normal CSF pressure of 180 H2O. Neurological and fundoscopic examinations were normal 30 months later. Headaches did not recur. We believe that leuprorelin acetate was responsible for the emergence of pseudotumor cerebri in our patient. There is no reported association between rheumatic fever and pseudotumor became normal Intracranial after cerebri.2,3 pressure
mm
Fig 1-Southern hybridisation analysis of DNA from tumour. - =germlme band position,
of eczema. Onerecorded improvement in patients’ assessments of itch but the large difference in pre-trial scores between the groups makes interpretation difficult. Scotia Pharmaceuticals have given us details of two unpublished studies; neither shows a significant clinical difference between epogram and placebo. All the trials have been included in a meta-analysis,s originating from the Efamol Research Institute, which claimed very significant benefits for epogam in the treatment of eczema. The largest published trial was a double-blind crossover study completed by 123 patients with atopic eczema in which no significant effect of epogam was seen.6 The meta-analysis and the promotional literature reject these findings and suggest that placebo and epogam tablets were mixed, rendering the study void. Atopic eczema is a common and distressing condition, and the market for any potential treatment is huge. A safe oral treatment has obvious attractions. As for the evaluation of therapy in any chronic
relapsing disease, a double-blind, randomised, placebo-controlled parallel trial is the best study design. Such trials as have been done with epogam in atopic eczema do not show a significant advantage over placebo, and a meta-analysis is no more reliable than the data on which it is based. The claim of a "substantial and highly significant clinical improvement" is not substantiated. This should be considered before doctors put patients on a treatment for which even the manufacturers
to
recommend a treatment time of 8-12 weeks
achieve a benefit.
Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, UK
G. R. SHARPE P. M. FARR
Meigel W. Treatment of atopic dermatitis. Z Hautkr 1986; 61: 473-78. Wright S, Burton JL. Oral evening-primrose-seed oil improves atopic eczema. Lancet 1982; ii: 1220-22. 3. Schalin-Karrila M, Mattila L, Jansen CT, Uotila P. Evening primrose oil m the treatment of atopic eczema: effect on clinical status, plasma phospholipid fatty acids and circulating blood prostaglandins. Br J Dermatol 1987; 117: 11-19. 4. Bordoni A, Biagi PL, Masi M, et al. Evening primrose oil (Efamol) in the treatment of children with atopic eczema. Drugs Exp Clin Res 1987; 14: 291-97. 5. Morse PF, Horrobin DF, Manku MS, et al. Meta-analysis of placebo-controlled studies of the efficacy of Epogam in the treatment of atopic eczema: relationship between plasma essential fatty add changes and clinical response. Br J Dermatol 1989; 121: 75-90. 6. Bamford JTM, Gibson RW, Renier CM. Atopic eczema unresponsive to evening primrose oil (linoleic and &ggr;-linolenic acids). J Am Acad Dermatol 1985; 13: 959-65. 1.
2.
Pseudotumor cerebri associated with
leuprorelin acetate SIR,-Leuprorelin acetate is a synthetic nonapeptide analogue of naturally occurring gonadotropin releasing hormone (GnRH or LHRH) that is used in the treatment of sterility and advanced prostatic cancer. Its main side-effects include hot flushes, vaginal dryness, electrocardiographic changes, local wheal reactions, and peripheral oedema.1 We describe a patient in whom pseudotumor cerebri (benign increased intracranial pressure) developed during treatment with leuprorelin acetate agonist. A 33-year-old man with a long history of hypogonadism and azoospermia was admitted because of rheumatic fever. During the past 2 years, he had been placed on a pulsatile LHRH pump (’Lupron’) without improvement in his sterility. A year later, while still on leuprorelin acetate, the patient had severe constant headaches. On admission he had bilateral papilloedema. Neurological examination and computed tomography of brain were normal. The cerebrospinal fluid (CSF) was clear and acellular at a pressure of 429 mm H2O, within protein 17 mg/dl and glucose 51 mg/dl. Cultures for bacteria, viruses, and tuberculosis were negative. Visual field examination revealed slight bilateral nasal loss. No known
cause
of increased intracranial pressure
was
discontinuation of the drug. Transient frontal headaches have been frequently reported during treatment with another LHRH analogue.’ Pseudotumor cerebri is caused by several drugs, including tetracycline, steroids, vitamin A, nalidixic acid, nitrofurantoin, sulphur preparations, and phenytoin,
levothyroxine. Departments of Internal Medicine and Neurology, Beilinson Medical Centre, Petah Tiqva, Israel 49 100
N. ARBER R. FADILA J. PINKHAS
H. SHIRIN E. MELAMED Y. SIDI
GS, Coddington CC, Winkel CA, Shawker TH, Lonaux DL, Collins RL. Efficacy of a gonadotropin-releasing hormone agonist in the treatment of uterine leiomyomata. Fertil Steril 1989; 51: 951-56 2. Bowman MA. Pseudotumour cerebri. Am Fam Physician 1978; 35: 177-82. 3. Hoffman HJ. Pseudotumour cerebri. Surg Neurol 1987; 27: 405. 1 Letterie
Evidence for neoplasia in "pseudolymphoma" of lung SIR,-"Pseudolymphoma" is
a term
used
to
describe extranodal
tumour-like
lymphoid hyperplasia which is not clearly neoplastic histologically;’ its origin is uncertain. Our molecular genetic and cytogenetic studies in a case of pulmonary pseudolymphoma revealed the tumour to be neoplastic and of B-cell origin. A 43-year-old woman was admitted in December, 1988, for evaluation of slowly progressive lung disease which she had had for about 4 years. She had a history of left orbital tumour diagnosed histologically as a benign lymphoid hyperplasia in March, 1988. Chest X-rays revealed nodular shadows in the bilateral lower lung fields but there was no evidence of tumour involvement in other regions. She had autoimmune haemolytic anaemia (Hb 97 g/dl, haptoglobin 3-1 mg/dl, direct and indirect Coombs’ test positive); the gammaglobulin level was normal. In February, 1989, she underwent right lower lobectomy with removal of the tumour, which was histologically compatible with pseudolymphoma.1 Immunophenotypic findings on fresh excised tumour cells indicated polyclonal lymphoid hyperplasia. Studies of tumour DNA by Southern hybridisation with JH, JK, Cp, and Jyl probes revealed clonal rearrangements of Ig heavy-chain and kappa-chain genes (fig 1). Cytogenetic study after short-term culture of tumour cells without mitogens revealed, in the 11 metaphases studied, 7 normal diploid and 4 hyperdiploid patterns. +3, +7, lp+, and +mar2 were common constitutional abnormalities in 4 hyperdiploid metaphases (fig 2), that consisted of 49-50 chromosomes with minor karyotypic instabilities. Although some studies of extranodal lymphoid hyperplasias have revealed clonal Ig rearrangements2-4 this is not direct evidence of malignancy, and no cytogenetic study has been reported so far. The
found.
Leuprorelin acetate was discontinued. On follow-up the papilloedema resolved and headaches and visual-field defects subsided. Six months later, he had a normal CSF pressure of 180 H2O. Neurological and fundoscopic examinations were normal 30 months later. Headaches did not recur. We believe that leuprorelin acetate was responsible for the emergence of pseudotumor cerebri in our patient. There is no reported association between rheumatic fever and pseudotumor became normal Intracranial after cerebri.2,3 pressure
mm
Fig 1-Southern hybridisation analysis of DNA from tumour. - =germlme band position,
