Use of interleukin 23 blocker in the treatment of psoriasis in a patient with schizoaffective disorder

Summary

Psoriasis is a disease characterized by specific skin lesions and is currently recognized as a systemic, chronic, immune-mediated, painful, disfiguring, and disabling inflammatory disease, which causes a significant negative impact on the individual's quality of life. Patients with psoriasis report emotional impairment comparable to that of heart disease, cancer, or diabetes, according to comparative studies. In addition, they _{= have a higher rate of suicide, depression, and alcohol consumption than the general population;} ¹,²,³ which is aggravated in those individuals who already have psychiatric disorders. The authors report the case of a 41-year-old patient with schizoaffective disorder who presented worsening of the psychiatric disease, leading him to attempt suicide, after worsening of the symptomatology of the dermatological disease. Treatment with interleukin 23 blocker allowed him to return to social life, significantly improve quality of life, as well as significant reversal of the psychiatric clinical condition.

Keywords: Psoriasis; Psychiatric illness; Interleukin blocker 23; Mental disorder; Depression

Introduction

Psoriasis is an inflammatory, polygenic, progressive and recurrent disease of chronic evolution, characterized by an accelerated evolutionary cycle of keratinocytes, associated with disordered immune activation and correlated systemic findings. It is characterized by inflammation and hyperproliferation of keratinocytes, manifesting as thick erythematous plaques covered by silvery scales, of varying sizes, distributed throughout the body.

The estimated worldwide prevalence of psoriasis is approximately 2% to 3%, although important regional variation has been observed. Psoriasis is often classified according to its severity as: mild, moderate to severe4. Different indices are used to assess disease severity, for example: Psoriasis area and severity index (PASI), Body surface area (BSA) and Dermatology Life Quality Index (DLQI).

In the pathophysiology of psoriasis, dendritic cells have the function of capturing antigens, processing them, and presenting them, within the context of MHC, to specific antigen T cells. In addition to the antigenic presentation, dendritic cells secrete high amounts of IL-12, which acts both on the innate immune response, activating natural killer cells, and on the acquired one, activating B and T lymphocytes. Although there is no consensus regarding the triggering factor of the disease, it is known that the development and maintenance of psoriasis plaques result from the participation of T lymphocytes (CD4 and CD8) and natural killer lymphocytes present in the epidermis and dermis. In recent decades, a considerable amount of experimental evidence has supported the concept that psoriasis is a dermatosis mediated by lymphocytes and cytokines that present the pattern of the TH1, TH17, and TH22 immune response; and, as a consequence of this discovery, the new medications aim to control the release of interleukins 23, 22 and 17 in addition to TNF; which are found at high levels in psoriasis plaques and are responsible for perpetuating the disease ⁵.

Case report

A 41-year-old male patient lived in the city of Piracicaba, state of São Paulo; with psoriasis for 19 years. The patient was undergoing psychiatric and psychological treatment for schizoaffective disorder, characterized by affective blunting, depressed mood and social anxiety; which was controlled with the use of the long-acting atypical antipsychotic (Invega Trinza) and lithium carbonate, however, he presented a worsening of the clinical picture of psoriasis, with a significant increase in skin lesions, disseminating to the whole body, including extensively affecting special areas such as the scalp and nails; leading him to a PASI = 18 and a DLQI = 26. In view of the worsening of the dermatological clinical picture, there was a deterioration of the psychiatric disease, with gradual loss of cognition and psychosocial functioning, with serious complications for his daily life, family and social relationships, leading him to much suffering, discrimination and affective blunting that culminated in a suicide attempt, generating great despair on the part of the family members.

The Brazilian Society of Dermatology (SBD) recommends, through the Brazilian Consensus for the Treatment of Psoriasis, that patients with the moderate to severe form of the disease be treated initially with phototherapy. If after twenty sessions there is no clinical improvement, or cases of intolerance or contraindications occur, methotrexate or acitretin should be used. The use of methotrexate associated with antipsychotics can induce the appearance of photosensitive dermatitis and increase the plasma concentration of lithium in the patient, increasing the risk of lithium poisoning; and, therefore, it was contraindicated in this patient. Phototherapy cannot be indicated because it is not available in the city of their residence. Treatment with INTERLEUKIN BLOCKER 23® (guseculmab) was then initiated, with 2 induction doses (100 mg subcutaneous) every 4 weeks, followed by treatment with a dose of 100 mg every 8 weeks. Soon after the 2 induction doses, the patient already showed significant clinical improvement, with a decrease in the thick plaques of psoriasis, regression of the clinical picture on the scalp and nails. The improvement was continuous, leading to total lightening of the lesions 24 weeks after the beginning of treatment. As the patient improved from the skin lesions, the psychiatric condition regressed precipitously, with the patient returning to social and family life.

 Before treatment:

After 10 weeks à PASI = 8:

After 24 weeks à , PASI = 90 and DLQI = 8:    

Discussion

Molecular and cellular understanding of the pathogenesis of psoriasis has evolved considerably over the past 30 years. The presence of the cytokine interleukin IL-12 in psoriatic lesions has led to the postulate that psoriasis is mediated by Th1 cells. Recent evidence has revealed a role for Th17 cells, and other immune cells, as regulators of psoriatic skin inflammation. IL-17A, the primary effector cytokine of Th17 cells, stimulates keratinocytes to produce chemokines, cytokines, and other pro-inflammatory mediators, thereby allowing IL-17A to bridge the gap between the innate and adaptive immune systems to sustain chronic inflammation. This model underlies the rationale for inhibiting IL-17A signaling as a potential therapeutic approach to disrupt the psoriatic inflammatory loop. A key breakthrough in our understanding of the immune system occurred in 2000 with the discovery of a new p19 protein and the finding that this protein pairs with the IL-12 p40 subunit to form a newly identified cytokine, IL-23. In 2003, IL-23 was shown to activate T cells that expressed a different cytokine profile than Th1 and Th2 cells including IL-17A expression. This distinct new lineage of CD4 cells was named Th17 cells and through its major effector cytokine, IL-17A, Th17 cells regulate tissue inflammation and autoimmune responses and psoriasis consolidates as a TH17/IL17-mediated disease; reducing the importance of the Th1 response in the pathogenesis of psoriasis ⁶.

In psoriatic skin, IL-23 is essential for stabilizing the phenotype of IL-17-producing lymphocytes, in addition to activating these cells and increasing cytokine production and pathogenicity by promoting IL-17 production by effector and memory T cells. IL-17 acts mainly synergistically with other cytokines, leading to massive activation of immune pathways and cytokines such as IL-22, IL-20, and IL-24, promoting epidermal changes ⁷.

Interleukin 23 blocker is a human immunoglobulin (Ig) monoclonal antibody (mAb) IgG1λ that selectively binds to the p19 subunit of IL-23 with high specificity and affinity, inhibiting its interaction with the IL-23 receptor 8,9.  IL-23 is a regulatory cytokine, affecting the differentiation, expansion, and survival of T cell subgroups (e.g., Th17 and Tc17) and innate immune cell subgroups, which represent sources of effector cytokines, including IL-17A, IL-17F, and IL-22, and which cause inflammatory disease ⁹. In humans, selective blockade of IL-23 has been shown to normalize the production of these cytokines ⁹.

Conclusion

Psoriasis is a chronic disease that causes serious social, psychological and financial damage to the patient and their families. In psychiatric patients, the dermatological disease aggravates the clinical picture; since diseases that affect the skin are stigmatizing, unsightly and often cause intense or prolonged symptoms that cause stress, irritability and self-rejection, which can lead the patient to commit suicide.

The most important effect of IL-23 on psoriatic lesions may be the stabilization of a cytokine-secreting pathogenic phenotype of Th17 cells and the promotion of IL-17 production by effector and memory T cells. Treatment of psoriasis using monoclonal antibodies that specifically inhibit IL-23 may directly reduce the production of psoriasis-relevant lymphocytic cytokines, such as IL-17, and, in the long term, reduce the number of pathogenic T cells in the skin by decreasing memory T lymphocytes, likely responsible for the reappearance of psoriatic plaques at the same sites.

The interleukin 23 blocker enabled the control of the disease, as well as the social rehabilitation of the patient, improving his work capacity and restoring him back to family and social life.

The immense suffering that the dermatological disease causes in the patient can be measured when upon returning to the doctor's office, the patient, with a smile on his face, looked face to face at the doctor and commented: "my eternal thanks to you! Now, I can look at myself in the mirror and recognize myself as a person".   

Bibliographic References

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2. Brazilian Consensus on Psoriasis 2012 – Evaluation and Treatment Guides. Brazilian Society of Dermatology. 2nd ed. Rio de Janeiro: INFOC nº ART_4300, 2012.

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6. Lynde, C. W., Poulin, Y., Vender, R., Bourcier, M., & Khalil, S. (2014). Interleukin 17A: Toward a new understanding of psoriasis pathogenesis. Journal of the American Academy of Dermatology, 71(1), 141–150. doi:10.1016/j.jaad.2013.12.036 

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8. Blauvelt A, Papp K, Griffiths CE, et al. Efficacy and safety of guselkumab, na anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients whitg moderate to severe psoriasis: Results from the phase III, double-blinded, placebo-and active comparator-controlled VOYAGE1 trial. J Am Acad Dermatol. 2017; 76:405:17.

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