Lupus Diathesis and the Hydralazine Syndrome

D, Alarcon Segovia; Jw, Worthington; Le, Ward; Kg, Wakim

doi:10.1056/nejm196503042720905

Cited by 53 publications

(6 citation statements)

References 23 publications

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“…Only two of these, procainamide and hydralazine, are considered as high risk for induction of the syndrome, with up to 8 and 20% frequency respectively, during 1 year of therapy at currently employed doses [ 64 , 65 ]. Hydralazine was introduced as an antihypertensive drug in 1952, and the first case of hydralazine-induced lupus was reported soon thereafter [ 66 ]. Prevalence of slow acetylators among patient populations at risk for developing lupus erythrematosus is obviously much greater than the disease prevalence.…”

Section: Reviewmentioning

confidence: 99%

Hydralazine target: From blood vessels to the epigenome

et al. 2006

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Hydralazine was one of the first orally active antihypertensive drugs developed. Currently, it is used principally to treat pregnancy-associated hypertension. Hydralazine causes two types of side effects. The first type is an extension of the pharmacologic effect of the drug and includes headache, nausea, flushing, hypotension, palpitation, tachycardia, dizziness, and salt retention. The second type of side effects is caused by immunologic reactions, of which the drug-induced lupus-like syndrome is the most common, and provides clues to underscoring hydralazine's DNA demethylating property in connection with studies demonstrating the participation of DNA methylation disorders in immune diseases. Abnormalities in DNA methylation have long been associated with cancer. Despite the fact that malignant tumors show global DNA hypomethylation, regional hypermethylation as a means to silence tumor suppressor gene expression has attracted the greatest attention. Reversibility of methylation-induced gene silencing by pharmacologic means, which in turns leads to antitumor effects in experimental and clinical scenarios, has directed efforts toward developing clinically useful demethylating agents. Among these, the most widely used comprise the nucleosides 5-azacytidine and 2'deoxy-5-azacytidine; however, these agents, like current cytotoxic chemotherapy, causes myelosuppression among other side effects that could limit exploitation of their demethylating properties. Among non-nucleoside DNA demethylating drugs currently under development, the oral drug hydralazine possess the ability to reactivate tumor suppressor gene expression, which is silenced by promoter hypermethylation in vitro and in vivo. Decades of extensive hydralazine use for hypertensive disorders that demonstrated hydralazine's clinical safety and tolerability supported its testing in a phase I trial in patients with cancer, confirming its DNA demethylating activity. Hydralazine is currently being evaluated, along with histone deacetylase inhibitors either alone or as adjuncts to chemotherapy and radiation, for hematologic and solid tumors in phase II studies.

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Section: Reviewmentioning

confidence: 99%

Hydralazine target: From blood vessels to the epigenome

et al. 2006

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“…This may represent a difference from the similar syndrome precipitated by hydrallazine, in which hypergammaglobulinaemia or antinuclear factor antibodies were found five years after discontinuation of the drug and disappearance of symptoms (Alargon-Segovia et al, 1965). Recrudescence has been found to follow reexposure to the drug, but it was not attempted in this case.…”

Section: Commentmentioning

confidence: 59%

“…Some authors Alargon-Segovia et al, 1965 ;Lee et al, 1966) feel that the drug unmasks a predisposition to develop lupus erythematosus. Studies in patients with the "hydrallazine syndrome" have shown that symptoms and signs possibly due to S.L.E.…”

Section: Commentmentioning

confidence: 99%

Hypoparathyroidism and malabsorption.

Russell¹

1967

BMJ

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“…Such immunosuppressive therapy could have blunted or masked any clinical deterioration induced by hydralazine. Administration of hydralazine has been reported to induce overt SLE in certain patients with an underlying lupus diathesis (8). Whether or not this drug alters the course of patients with established SLE remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Hydralazine therapy in hypertensive patients with idiopathic systemic lupus erythematosus

Reza¹,

Dornfeld²,

Goldberg³

1975

Arthritis & Rheumatism

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Seven hypertensive patients with idiopathic systemic lupus erythematosus were treated with hydralazine. They received a mean daily dose of 203 mg for a mean duration of 21 months. All were taking prednisone alone or in combination with azathioprine. During therapy with hydralazine, there were no new symptoms nor exacerbation of preexisting symptoms attributable to systemic lupus. Laboratory parameters, including antinuclear antibody titers and complement levels, either improved or remained stable. The results indicate that hydralazine can be safely used in hypertensive patients with systemic lupus who are receiving concomitant immunosuppressive therapy.

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Lupus Diathesis and the Hydralazine Syndrome

Cited by 53 publications

References 23 publications

Hydralazine target: From blood vessels to the epigenome

Hydralazine target: From blood vessels to the epigenome

Hypoparathyroidism and malabsorption.

Hydralazine therapy in hypertensive patients with idiopathic systemic lupus erythematosus

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