LETTER
Fatal All-Trans Retinoic Acid Pneumonitis
Kim Smith-Whitley and
Beverley Lange
15 March 1993 | Volume 118 Issue 6 | Pages 472-473
TO THE EDITOR:
In their article, Frankel and coworkers [1] describe a fulminant pneumonitis developing between days 2 and 21 in 9 of 35 adults treated with all-trans retinoic acid (TRA). Three of four patients responded to dexamethasone, 10 mg every 12 hours. We report a case of fatal TRA-associated pneumonitis that began on day 30 of TRA during tapering of high-dose dexamethasone for TRA-associated pseudotumor cerebri [2].
On 31 July 1992, a 4-year-old girl participating in the randomized intergroup trial for acute promyelocytic leukemia began induction therapy with TRA at 45 mg/m2 daily. At diagnosis, she had disseminated intravascular coagulation that persisted to day 21. Incapacitating headaches began on day 5. Evaluation was consistent with pseudotumor cerebri [3]. On day 10, her leukocyte count rose to 33.5 x 109/L. Hydroxyurea was added. On day 13, she developed sixth-nerve palsies and retinal hemorrhages. Magnetic resonance imaging showed normal ventricles, small bilateral subdural hematomas, and a sagittal sinus thrombosis. Dexamethasone, 1 mg/kg, was added. On day 17, her leukocyte count fell to 10 x 109/L. Her headaches persisted, necessitating therapeutic lumbar punctures, which relieved the pain transiently. A lumboperitoneal shunt on day 25 afforded some relief. On day 27, dexamethasone was tapered to 0.5 mg/kg. On day 29, she became febrile with clinical evidence of phlebitis. Broad-spectrum antibiotics were started. On day 30, she developed acute respiratory distress and hypoxia. Her leukocyte count rose to 24 x 109/L. Chest radiographs showed interstitial infiltrates. Within 6 hours, she required intubation, mechanical ventilation, and vasopressor support for hypotension, and within 24 hours, she died of respiratory failure. Cultures were negative. Autopsy showed a massive pulmonary exudate consisting of edema, fibrin, and myeloid precursors of all stages of maturation consistent with the retinoic acid syndrome. Marrow was not evaluable because of fixation artifacts or autolysis.
We conclude that the TRA syndrome can occur as late as day 30 and in the presence of moderately high-dose dexamethasone.
1. Frankel SR, Eardley A, Lauwers G, Weiss M, Warrell RP Jr. The "retinoic acid syndrome" in acute promyelocytic leukemia. Ann Intern Med. 1992; 117:292-6.
2. Warrell RP, Frankel SR, Miller WH, Scheinberg DA, Itri LM, Hittelman WN, et al. Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans retinoic acid). N Engl J Med. 1991; 324:1385-93.
3. Johnston I, Hawke S, Halmagyi M, Teo C. Disorders of cerebrospinal fluid circulation causing intracranial hypertension without ventriculomegaly. Arch Neurol. 1991; 48:740-7.
About Letters
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
Top
References
Article
