All-trans retinoic acid syndrome
Citation, DOI & article data
All-trans retinoic acid (ATRA) syndrome, more recently known as differentiation syndrome 8, is a condition that can occur with patients with acute promyelocytic leukemia who are on therapeutic all-trans-retinoic acid (ATRA).
All-trans retinoic acid (ATRA) is a normal constituent of plasma that 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.
It is characterized by fever, respiratory distress, pleural and pericardial effusion, weight gain, and pulmonary inﬁltrates noted on chest radiography.
Will depend on the system involved although many of the features are described in relation to the lungs.
Although the chest radiographic features are not specific, in the context of an appropriate clinical history, they may aid in early recognition of the ATRA syndrome. Recognized 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
- 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 chest findings were small, irregular peripheral nodules in the lungs along with pleural effusions 5.
Treatment and prognosis
Early intervention with high dose corticosteroids is thought to abort progression. While most patients do well the occurrence of ATRA syndrome was associated with lower event-free survival.
History and etymology
It was first described in 1991 by Frankel et al. 1-3,7.
- 1. Jung JI, Choi JE, Hahn ST et-al. Radiologic features of all-trans-retinoic acid syndrome. AJR Am J Roentgenol. 2002;178 (2): 475-80. AJR Am J Roentgenol (full text) - Pubmed citation
- 2. La fianza A, Bonfichi M, Gorone MS et-al. Unusual abdominal findings of all-trans-retinoic acid syndrome: role of diagnostic imaging. Clin Imaging. 31 (4): 276-8. doi:10.1016/j.clinimag.2006.11.004 - Pubmed citation
- 3. Frankel SR, Eardley A, Lauwers G et-al. The "retinoic acid syndrome" in acute promyelocytic leukemia. Ann. Intern. Med. 1992;117 (4): 292-6. - Pubmed citation
- 4. Amano Y, Tajika K, Mizuki T et-al. All-trans retinoic acid syndrome: chest CT assessment. Eur Radiol. 2001;11 (8): 1516-7. Eur Radiol (link) - Pubmed citation
- 5. Davis BA, Cervi P, Amin Z et-al. Retinoic acid syndrome: pulmonary computed tomography (CT) findings. Leuk. Lymphoma. 1996;23 (1-2): 113-7. doi:10.3109/10428199609054809 - Pubmed citation
- 6. De botton S, Dombret H, Sanz M et-al. Incidence, clinical features, and outcome of all trans-retinoic acid syndrome in 413 cases of newly diagnosed acute promyelocytic leukemia. The European APL Group. Blood. 1998;92 (8): 2712-8. Blood (link) - Pubmed citation
- 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
- 9. Miguel A. Sanz, Pau Montesinos. How we prevent and treat differentiation syndrome in patients with acute promyelocytic leukemia. (2014) Blood. 123 (18): 2777. doi:10.1182/blood-2013-10-512640 - Pubmed