Syndrome Simulating Lymphosarcoma Induced by Diphenylhydantoin Sodium

Rosenfeld, Samuel S.; Swiller, A. Irving; Shenoy, Y. M. V.; Morrison, Alan N.

doi:10.1001/jama.1961.03040190013004

Cited by 43 publications

(7 citation statements)

References 3 publications

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“…How this could occur in conjunction with the metabolic alteration is questionable. It is of interest, however, that other known effects of DPH are consistent with a reduction in cortisol activity, namely, lymphoid hyperplasia (32,33), protein anabolism (34), dermal chemical response (35), and a suggestion of amelioration of Cushing's syndrome despite high levels of 17-OHCS in urine (36).…”

Section: Discussionmentioning

confidence: 99%

Effect of Diphenylhydantoin on Cortisol Metabolism in Man *

Werk¹,

MacGee²,

Sholiton³

1964

J. Clin. Invest.

165

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During a study of cortisol metabolism in advanced cancer and other disease states (1), we observed in patients receiving DPH 1 therapy for convulsive seizures an abnormal pattern of excretion of cortisol metabolites in urine. This abnormal pattern was characterized by increased urinary output of the polar unconjugated metabolite 6-OHF, suggesting an interference with extraadrenal metabolism of cortisol by DPH. We =5,5'-diphenylhydantoin; 6-hydroxycortisol (6 -OHF) = 6a (/3), 11,/, 17a, 21 -tetrahydroxy -4 -pregnene-3,20 -dione; 17-OHCS = 17-hydroxycorticosteroids; ACTH = adrenocorticotrophic hormone; methopyrapone (Metopirone, Ciba Pharmaceutical Co., Summit, N. J.) =2-methyl-1,2-di-(3-pyridyl)-1-propanone. Tetrahydro derivatives: THF (tetrahydrocortisol) = 3a,11,, 17a,21-tetrahydroxy-5/8-pregnan-20-one; allo-THF (allotetrahydrocortisol) = 3a,11/3,17a,21-tetrahydroxy-5a-?pregnan-20-one; THE (tetrahydrocortisone) = 3a,17a,21-trihydroxy-5p-pregnan-11,20-dione. Cortol = 3a,11,8,17a,20a (/3),21-pentahydroxy-5/3-pregnane; cortolone = 3a,17a,20a (/3) ,21-tetrahydroxy-5/8-pregnan-11-one; 17-KS = 17-ketosteroids; 1 1-hydroxyetiocholanolone = 3a,1j1/-dihydroxy-5,B-androstan-17-one; dehydroisoandrosterone = 3/3-hydroxy-5-androstene-17-one; TPNH = reduced triphosphopyridine nucleotide; o,p'DDD = 2,2-bis (2-chlorophenyl,4-chlorophenyl) 1,1-dichloroethane. since a) adrenal hypertrophy was observed in intact rats and b) in adrenalectomized rats treated with DPH a more profound decrease in brain excitability was demonstrated than in intact rats. Goncharov has observed that acute administration of DPH to dogs and guinea pigs increases adrenocortical output of cortisol (3). Reports by Staple (4) and Bonnycastle and Bradley (5) have, however, indicated an inhibition of pituitary-adrenal secretion after chronic DPH treatment of mice and rats.In humans also cortisol has been shown to enhance brain excitability (6). After chronic DPH therapy to patients, excretion of corticosteroids in urine is reported to decrease (7, 8) after an initial increase (7). These findings have led to the suggestion that the decrease in brain excitability induced by DPH might be mediated partially through adrenocortical suppression. However, levels of 17-OHCS in plasma from patients treated with DPH are usually normal (8, 9), as are responses to ACTH (8, 9) and rates of disappearance from plasma of infused cortisol (8). These observations detract from the possibility that direct adrenocortical suppression plays a significant role in therapeutic effectiveness of DPH. Recently, however, Krieger has demonstrated that control subjects treated with DPH manifest a reduced response in the methopyrapone test, which suggests an interference with ACTH release (10).2) The increased excretion of 6-OHF produced by DPH appears to be similar to that we have observed in patients with advanced cancer and certain terminal illnesses (1) as well as to that reported after estrogen therapy (11), during pregnancy (12), and in newborn infants (13).Thus we hoped that furthe...

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Section: Discussionmentioning

confidence: 99%

Effect of Diphenylhydantoin on Cortisol Metabolism in Man *

Werk¹,

MacGee²,

Sholiton³

1964

J. Clin. Invest.

165

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“…Glaser (1972) has listed at least 16 types of toxicity to hydantoins, one of which is the pseudolymphomatous reaction involving lymph nodes. These have been described by several authors (Merritt and Putnam, 1939;Coope and Burrows, 1940;Saltzstein and Ackerman, 1959;Bajoghli, 1961;Rosenfeld et al, 1961;Bjomberg and Holst, 1967). Others (Hyman and Sommers, 1966;Gams et al, 1968;Tashima and de los Santos, 1974) report the development of malignant lymphomas after hydantoin therapy, some of which did notregress onwithdrawal ofthe drug.…”

mentioning

confidence: 74%

“…Rosenfeld et al (1961) and Doyle and Hellstrom (1963) have each described patients with lymphadenopathy related to the hydantoins which histologically appeared to be lymphosarcoma and Hodgkin's disease, respectively.…”

Section: Discussionmentioning

confidence: 99%

A pseudolymphomatous reaction in soft tissue associated with phenytoin sodium.

Wilden¹,

Scott²

1978

J Clin Pathol

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A pseudolymphomatous reaction involving subcutaneous tissue and underlying skeletal muscle is described in a woman who was receiving phenytoin sodium and phenobarbitone. The histological appearance was of nodular, densely cellular tissue composed of histiocytes, plasma cells, lymphocytes, fibroblasts, and occasional polymorphonuclear cells. The significance of this finding is briefly considered in relation to the existing literature.

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“…The clinical picture of pseudolymphoma consists of generalized lymphadenopathy, malaise, fever and a skin rash, with the frequent association of pain and swelling in the joints as well as hepatosplenomegaly [1,2,[5][6][7][8][9]. In some cases diarrhea may be a part of this picture [10,11].…”

Section: Discussionmentioning

confidence: 99%

“…Since then many additional cases of what is now termed 'pseudolymphoma' have been reported in the literature [2][3][4][5]. This phenomenon has usually been found to be associated with skin disorders, including morbilliform or scarlatiniform rashes, urticaria, exfoliative dermatitis and abnormal pigmentation [1], It would appear, however, that in some cases this mimicking of a true lymphoma has its main expression in the skin lesions and not in the lymph nodes.…”

mentioning

confidence: 99%

Pseudolymphoma Syndrome

Halevy¹,

Feuerman²

1977

Dermatology

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A transient dermatologic abnormality which gave a histologic picture compatible with malignant lymphoma is described. The clinical manifestations included diarrhea, hepatosplenomegaly, moderate lymph node enlargement without histopathological changes and evidence of involvement of the reticulo-endothelial system. Both the dermatologic and gastrointestinal disorders appeared approximately 1 year after discontinuation of treatment with diphenylhydantoin, which the patient had taken for 2 years. The possible association between the transient abnormality and the previous diphenylhydantoin therapy justifies the classification of this case as ‘pseudolymphoma syndrome’.

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Syndrome Simulating Lymphosarcoma Induced by Diphenylhydantoin Sodium

Cited by 43 publications

References 3 publications

Effect of Diphenylhydantoin on Cortisol Metabolism in Man *

Effect of Diphenylhydantoin on Cortisol Metabolism in Man *

A pseudolymphomatous reaction in soft tissue associated with phenytoin sodium.

Pseudolymphoma Syndrome

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