Retinoic acid syndrome in a patient with psoriasis

ARTICLE

Auteur(s) : Dongxian Liu¹, Fei Cao², Xiaofeng Yan¹, Xingping Chen¹, Yingling Chen¹, Yating Tu³, Masutaka Furue⁴

¹Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
²Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
³Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
⁴Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashiku, Fukuoka, 812-8582, Japan

Retinoic acid syndrome (RAS), first described by Frankel et al. [1], is a potentially lethal complication associated with the use of all-trans-retinoic acid (ATRA) in the treatment of acute promyelocytic leukemia. This syndrome is characterized by leukocytosis, fever, hypotension, weight gain, respiratory distress, pleural and pericardial effusion, and pulmonary infiltrates on chest radiograph [2], occurring 2-21 days after the start of treatment with ATRA [1]. The incidence of RAS varied from 7% to 28% for lack of definitive criteria and mortality was about 1%. We would like to report the first case, as far as we know, of RAS in a patient with psoriasis.

A 32-year-old man presented with 10-year history of psoriasis. Vitamin D analogue, local retinoid and steroid therapy proved to be ineffective. This patient was then treated with acitretin 10 mg twice/day in June 2007. The improvement of lesions and a good tolerance of acitretin led to maintaining this treatment. Six months later, he turned to ATRA 50 mg twice/day because of lack of acitretin. After 6 days, the eruption developed and exacerbated rapidly, resulting in erythroderma covered by silvery white imbricated scales. He also had fever (> 39 °C) and severe edema, without arthralgia and pustules. The patient ceased taking ATRA and was hospitalized. The laboratory examination disclosed a marked leucocytosis (22,760/μL, baseline: 4,000-10,000/μL). Broad-spectrum antibiotics were administered, but the condition still progressed in an edematous form, with massive lamellar scales (figures 1A-C). Blood pressure decreased to 70/43 mmHg. He then presented respiratory distress and oxygen saturation decreased to 90%. On auscultation, bilateral moist crackles were present. Chest radiographs revealed bilateral patchy opacities. A high-resolution CT scan showed bilateral interstitial infiltrates with pleural and pericardial effusions. Blood culture showed no signs of bacterial or viral infection.

In view of the rapid development of tachypnea, hypotension, hypoxemia, and leucocytosis with chest abnormalities, RAS was suspected. Injection of methyl-prednisolone 80 mg i.v. for 5 consecutive days was started. With this therapy his respiratory distress resolved in a few hours, oxygen saturation rose to 98%. Blood pressure became 104/63 mmHg, bilateral moist crackles disappeared. Subsequently, his temperature and leucocyte counts became within normal ranges with the rapid disappearance of edema and scales (figures 1D-F). Chest radiographs showed complete resolution. Oral steroids were then tapered off over 2 months. With nearly one year of follow-up, this patient has experienced no recurrence of RAS, even when acitretin was reinstituted.

The pathophysiology of RAS is not completely understood, but the development of RAS in a patient with psoriasis is not unexpected, since RAS seems to be in part the result of an elevated release of cytokines, such as tumor necrosis factor (TNF)-α, interleukin(IL)-8 and intercellular adhesion molecule (ICAM)-1, by differentiating myeloid cells [3]. ATRA had been proved to induce IL-8 [4], TNF-α-induced ICAM-1 [5] expression in human keratinocytes, RAS may be caused by the massive release of these newly formed cytokines. Besides, ATRA can up-regulate vascular endothelial growth factor (VEGF) production in peripheral blood mononuclear cells [6], and VEGF promotes vascular permeability and induces angiogenesis. Induction of VEGF may therefore play a substantial role in the pathogenesis of RAS.

RAS is highly susceptible to administration of high-dose corticosteroids when treated early, as soon as the first symptoms occur [1]. Antihistamines and antibiotics are ineffective. In our case, a short course of high-dose corticosteroid therapy also resulted in prompt symptomatic improvement and full recovery. In addition, this patient did not present any of the conditions known to be associated with iatrogenic fluid overload, pneumonia, and sepsis, neglecting a possible involvement of other diseases.

In summary, RAS should be considered in patients using ATRA who present with leukocytosis, unexplained fever, hypotension, weight gain, respiratory distress, pleural and pericardial effusion. Early and rapid recognition of the symptoms and prompt administration with systemic corticosteroids may avoid potentially fatal complications of RAS.

Acknowledgements

References

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3 Hsu HC, Tsai WH, Chen PG, et al. In vitro effect of granulocyte-colony stimulating factor and all-trans retinoic acid on the expression of inflammatory cytokines and adhesion molecules in acute promyelocytic leukemic cells. Eur J Haematol 1999; 63: 11-8.

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6 Young HS, Summers AM, Read IR, et al. Interaction between genetic control of vascular endothelial growth factor production and retinoid responsiveness in psoriasis. J Invest Dermatol 2006; 126: 453-9.

* Equal contribution to this work.