Psoriasis Flare in a Liver Transplant Patient: A Case Report of a Successful Treatment With Apremilast : Transplantation

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Psoriasis Flare in a Liver Transplant Patient: A Case Report of a Successful Treatment With Apremilast

Rosi, Elia MD1; Fastame, Maria Thais MD1; Di Cesare, Antonella MD1; Prignano, Francesca MD, PhD1

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Transplantation 107(1):p e39-e40, January 2023. | DOI: 10.1097/TP.0000000000004376
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Psoriasis may be a pre-existing dermatologic condition in liver transplant recipients. The treatment of psoriasis flares in the posttransplant population is challenging.1,2 Apremilast is an orally administered small molecule that inhibits phosphodiesterase 4, an enzyme that hydrolyzes intracellular cAMP (cAMP), thus modulating production of inflammatory mediators. Its pharmacokinetics are not altered by moderate or severe hepatic impairment, it is not associated with hepatotoxic risk, and its use is associated with a decreased risk of serious infection when compared with methotrexate.3,4 Herein, we present a 72-y-old woman with a psoriasis flare following SARS-CoV-2 infection (Figure 1A–C). She was receiving immunosuppressive therapy with cyclosporine (50 mg BID) for a previous liver transplant in 2007 secondary to chronic hepatitis C virus infection. Hepatitis C virus eradication was confirmed after direct-acting antiviral therapy in the posttransplant period. The patient had a history of arterial hypertension, dyslipidemia, atrophic gastritis, autoimmune hemolytic anemia, and thalassemia trait. We started treatment with apremilast at 10 mg daily, increasing to a maintenance dose of 30 mg BID by day 6. After 8 wk of treatment, the patient’s lesions improved dramatically, and the Psoriasis Area and Severity Index was reduced by 75% (Figure 1D–F). Apremilast was well tolerated with no evidence of adverse events. The hepatic function panel revealed no abnormalities (glutamic-oxaloacetic transaminase 19 U/L, n.r. 10–35; glutamic-pyruvic transaminase 11 U/L, n.r. 10–35; gamma glutamyl transpeptidase 36 U/L, n.r. 6–42). Liver stiffness was not increased compared with baseline (7.0 kPa). She is still on treatment with apremilast at 30 mg BID.

F1
FIGURE 1.:
Erythematous scaly plaques on the scalp (A), left gluteal region (B), and right hand (C) at baseline. Scalp (D), left gluteal region (E), and right hand (F) after 8 wk of treatment with apremilast.

To the best of our knowledge, this is the first case describing the use of apremilast for the treatment of psoriasis in a liver transplant recipient in the setting of posttransplantation immunosuppressive therapy with cyclosporine. The cAMP signaling pathway plays a key role in hepatic stellate cells (HSCs) activation. The transdifferentiation of these activated cells into proliferative, contractile, and chemotactic myofibroblasts results in producing increasing amounts of extracellular matrix components leading to liver fibrosis. cAMP interacts with the protein kinase A (PKA) family of proteins and the exchange proteins activated by cAMP (EPACs), the most well-known downstream effector molecules. The activation of PKA results in the phosphorylation of the cAMP response element-binding protein (CREB), a transcription factor, which regulates gene transcription and protein synthesis. HSC activation was found to be correlated with reduced levels of phospho-CREB. The activation of the cAMP/PKA pathway may restore phospho-CREB levels, thus inhibiting proliferation of activated HSCs. The cAMP/EPAC pathway also plays a role in liver fibrosis. The administration of a cAMP activator may restore EPAC-1 levels, which were found to be decreased in fibrotic livers. EPAC-1 enhanced activity resulted in attenuation of proliferation and migration of HSCs.5 Considering the molecular mechanisms described earlier, it might be interesting to evaluate with further studies the effects of apremilast on fibrosis in this subset of patients.

This case shows that apremilast may be an effective and safe option for the treatment of psoriasis in liver transplant recipients in the setting of posttransplantation immunosuppressive treatment.

REFERENCES

1. Yadav DK, Bai XL, Liang T. Dermatological disorders following liver transplantation: an update. Can J Gastroenterol Hepatol. 2019;2019:9780952.
2. Prussick R, Wu JJ, Armstrong AW, et al. Psoriasis in solid organ transplant patients: best practice recommendations from The Medical Board of the National Psoriasis Foundation. J Dermatolog Treat. 2018;29:329–333.
3. Keating GM. Apremilast: a review in psoriasis and psoriatic arthritis. Drugs. 2017;77:459–472.
4. Dommasch ED, Kim SC, Lee MP, et al. Risk of serious infection in patients receiving systemic medications for the treatment of psoriasis. JAMA Dermatol. 2019;155:1142–1152.
5. Wahlang B, McClain C, Barve S, et al. Role of cAMP and phosphodiesterase signaling in liver health and disease. Cell Signal. 2018;49:105–115.
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