tretinoin and Intracranial-Hypertension

All-trans retinoic acid (ATRA) induces complete remission in 64-100 % of patients with acute promyelocytic leukemia (APL), and is considered to be a safe agent. Pseudotumor cerebri is a neurological side effect of ATRA reported in pediatric patients, and which is characterized by raised cerebrospinal fluid pressure in the absence of any intracranial pathology or secondary causes of intracranial hypertension. Involvement of cranial nerves other than II and VI is very uncommon in idiopathic intracranial hypertension (IIH); peripheral facial nerve palsy is exceptional and has rarely been described in the context of treatment with ATRA. We describe the case of a 15-year-old female patient with APL who developed an IIH and involvement of cranial nerves (bilateral papilledema, left facial and right sixth nerves) after receiving induction therapy including ATRA. Viral infections and other causes of secondary cranial nerve lesions were excluded. Symptoms completely subsided with the temporary withdrawal of ATRA and did not recur after reintroducing the drug. To date, the patient has managed to receive the treatment as per protocol. In conclusion, we report an atypical presentation of IIH that merits consideration, especially with respect to young patients with APL receiving ATRA; our most important observation is that the drug could be safely reintroduced once the symptoms had resolved.

Topics: Adolescent; Antineoplastic Agents; Cranial Nerve Diseases; Female; Humans; Intracranial Hypertension; Leukemia, Promyelocytic, Acute; Remission Induction; Treatment Outcome; Tretinoin

We report a case of benign intracranial hypertension (BIH) caused by all-trans retinoic acid (ATRA) in a patient with acute promyelocytic leukemia. A 21-year-old male was admitted to our hospital with pancytopenia. He was diagnosed as having acute promyelocytic leukemia due to increased promyelocytes, and PML-RAR alpha chimeric mRNA was detected. The administration of ATRA and idarubicin was started immediately. After 26 days of the chemotherapy, he complained of diplopia. Ophthalmologic examination revealed bilateral papilledema and hemorrhage. The cerebrospinal fluid showed an increase in pressure, but no other abnormalities. Computed tomography showed no intracranial abnormalities. The orbital MR imaging showed distension of the perioptic subarachnoid space and flattening of the posterior sclera. A diagnosis of BIH was made. After the discontinuation of ATRA, the symptoms improved and the MR abnormalities disappeared. As far as we know, there have been no reports illustrating MR abnormalities of BIH caused by ATRA, for the diagnosis and monitoring of which orbital MR imaging can provide important clues.

Topics: Adult; Humans; Intracranial Hypertension; Leukemia, Promyelocytic, Acute; Magnetic Resonance Imaging; Male; Tretinoin

With the recognition that vitamin A and isotretinoin may cause intracranial hypertension, the authors reviewed 331 case reports of ocular side effects associated with the three other marketed retinoids: tretinoin, acitretin, and etretinate. The reports were drawn from the National Registry of Drug-Induced Ocular Side Effects, the World Health Organization (WHO), the Food and Drug Administration, and medical journals between 1979 and 2003. There were 21 cases of intracranial hypertension associated with these three retinoids, leading to an inference that they are probably causally related to intracranial hypertension by WHO criteria. The lack of positive rechallenge data precludes the inference of a definite causal relationship to intracranial hypertension by WHO criteria. The inference of an independent causal role of these retinoids is further cautioned by the fact that six patients were concurrently using tetracycline or minocycline. Even so, the data suggest that all retinoids may, in rare instances, cause intracranial hypertension.

Topics: Acitretin; Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Child; Etretinate; Female; Humans; Intracranial Hypertension; Keratolytic Agents; Male; Registries; Tretinoin; United States; United States Food and Drug Administration; Vision Disorders; World Health Organization

Topics: Acetazolamide; Adolescent; Antineoplastic Agents; Carbonic Anhydrase Inhibitors; Female; Fundus Oculi; Humans; Intracranial Hypertension; Leukemia, Promyelocytic, Acute; Male; Papilledema; Treatment Outcome; Tretinoin

Sixty-three cases with acute promyelocytic leukemia (APL) were treated with all-trans retinoic acid (ATRA). The rates of hyperleukocytosis, intracranial hypertension, retinoic acid syndrome were 57.1%, 9.5%, and 3.2% respectively. Mortality of the treatment was 11.1%. Under ATRA treatment, hyperleukocytosis leading to leukostasis was the cause of death in patients with APL. We therefore suggest that the patients with such leukocyte levels (that is, 5.0 x 10(9).L-1 on the 6th day, 10.0 x 10(9).L-1 on the 10th day, 15.0 x 10(9).L-1 on the 15th day) can be used as guidelines for starting chemotherapy(homoharringtonine); before ATRA treatment, while leukocyte counts are > 10 x 10(9).L-1, the patients only receive homoharringtonine; when leukocyte counts are < or = 5.0 x 10(9).L-1, the patients receive a combination of homoharringtonine and ATRA. Retinoic acid syndrome is a distinctive complication of ATRA therapy in the patients with APL. While the syndrome occurs, the treatment of ATRA must be stopped and corticosteroids must be used.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Female; Harringtonines; Homoharringtonine; Humans; Intracranial Hypertension; Leukemia, Promyelocytic, Acute; Leukemoid Reaction; Male; Middle Aged; Tretinoin