Retinoic acid syndrome (RAS) is a potentially life-threatening complication observed in people with
acute promyelocytic leukemia
Acute promyelocytic leukemia (APML, APL) is a subtype of acute myeloid leukemia (AML), a cancer of the white blood cells. In APL, there is an abnormal accumulation of immature granulocytes called promyelocytes. The disease is characterized by ...
(APML) and first thought to be specifically associated with
all-''trans'' retinoic acid (ATRA) (also known as tretinoin) treatment.
Subsequently, so-called RAS was recognized in APML patients who had been treated with another highly efficacious drug,
arsenic trioxide
Arsenic trioxide is an inorganic compound with the formula . As an industrial chemical, its major uses include the manufacture of wood preservatives, pesticides, and glass. It is sold under the brand name Trisenox among others when used as a m ...
, and yet did not appear in patients treated with
tretinoin
Tretinoin, also known as all-''trans'' retinoic acid (ATRA), is a medication used for the treatment of acne and acute promyelocytic leukemia. For acne, it is applied to the skin as a cream, gel or ointment. For acute promyelocytic leukemia, ...
for other disorders. These facts and others support the notion that RAS depends on the presence of the malignant promyelocytes. This has led to the growing deprecation of the term 'retinoic acid syndrome' and to an increasing use of the term differentiation syndrome to signify this APML treatment complication.
Signs and symptoms
The syndrome is characterized by dyspnea, fever, weight gain, hypotension, and pulmonary infiltrates. This is effectively treated by giving
dexamethasone
Dexamethasone is a fluorinated glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive pulmonary disease (COPD), croup, brain swelling, eye pain following eye su ...
and withholding ATRA (or arsenic trioxide) in severe cases. An elevated white count is sometimes associated with this syndrome, but is not always pathognomonic.
Once RAS has resolved, pro-differentiation chemotherapy can be resumed.
Causes
The cause of RAS is not clear. Several causes have been speculated, including a
capillary leak syndrome from
cytokine
Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling.
Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
release from the differentiating myeloid cells. Alternatively, ATRA may cause the maturing myeloid cells to acquire the ability to infiltrate organs such as the lung.
Mediation by
cathepsin G has been suggested.
Diagnosis
Treatment
The treatment of RAS usually involves administering dexamethasone IV, with the dosage usually 10 mg twice a day for 10 days. It is important for patients to discontinue the use of tretinoin due to the elevation of white blood cells and possible low blood oxygen.
See also
*
Hypervitaminosis A
Hypervitaminosis A refers to the toxic effects of ingesting too much preformed vitamin A (retinyl esters, retinol, and retinal). Symptoms arise as a result of altered bone metabolism and altered metabolism of other fat-soluble vitamins. Hype ...
References
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Paraneoplastic syndromes