All trans retinoic acid syndrome
All trans retinoic acid (ATRA) syndrome (more recently known as differentiation syndrome (DS)8) is a condition that can occur with patients with acute promyelocytic leukemia who are on therapeutic all-trans-retinoic acid (ATRA).
It is characterized by fever, respiratory distress, pleural and pericardial effusion, weight gain, and pulmonary inﬁltrates noted on chest radiography.
All-trans-retinoic acid (ATRA) is a normal constituent of plasma. It is derived physiologically by intracellular oxidation of plasma retinol that has been absorbed from the intestines. ATRA is also used as an accepted therapy for acute promyelocytic leukemia. ATRA can differentiate acute promyelocytic leukemia blasts into mature granulocytes
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Will depend on the system involved although many of the features are described in relation to the lungs.
Although the chest radiograph features are not specific, in the context of an appropriate clinical history, they may aid in early recognition of the ATRA syndrome. Recognised chest radiographic features that can be part of the ATRA syndrome include
- increased cardiothoracic ratio
- increased vascular pedicle width
- ground-glass opacities
- peribronchial cufﬁng
- septal lines and
- pleural effusion(s)
In addition, chest radiography may show nodules and consolidation.
CT features may not be specific and the clinical context is extremely useful in image interpretation. According to one study, the most consistent CT findings were small, irregular peripheral nodules in the lungs along with pleural effusions 5.
Therapy and prognosis
Early intervention with high dose corticosteroids are thought to abort progression. While most patients do well the occurrence of ATRA syndrome was associated a lower event free survival.
History and etymology
It was first described in 1991 by Frankel et al 1-3,7.
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- 7. Nicolls MR, Terada LS, Tuder RM et-al. Diffuse alveolar hemorrhage with underlying pulmonary capillaritis in the retinoic acid syndrome. Am. J. Respir. Crit. Care Med. 1998;158 (4): 1302-5. doi:10.1164/ajrccm.158.4.9709085 - Pubmed citation
- 8. Montesinos P, Sanz MA. The differentiation syndrome in patients with acute promyelocytic leukemia: experience of the pethema group and review of the literature. Mediterr J Hematol Infect Dis. 2011;3 (1): e2011059. doi:10.4084/MJHID.2011.059 - Free text at pubmed - Pubmed citation