Colchicine-Resistant Familial Mediterranean Fever With Depressive State Successfully Treated With Escitalopram

 

Abstract

Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease associated with the Mediterranean fever (MEFV) gene and is mainly characterized by periodic fever and serositis. Colchicine has been used to prevent FMF episodes and reduce the frequency of attacks. We report the case of a 64-year-old man who presented with depressive symptoms and was resistant to colchicine treatment. Adding escitalopram to the ongoing colchicine regimen dramatically improved his fever, abdominal pain, and depressive symptoms. The change in cytokines, ABCB1 effects, and increased serotonin were related to these mechanisms. This case suggested that adding escitalopram to colchicine is a viable treatment option for colchicine-resistant FMF.

Introduction

Familial Mediterranean fever (FMF) is characterized by recurrent acute fever, peritonitis, pleurisy, and arthritis with high inflammatory mediators. Acute attacks usually resolve within two to four days. However, even during the asymptomatic phase, these inflammatory mediators may be higher than normal, and the inflammation persists [1]. The Mediterranean fever gene (MEFV) was identified as a disease-associated gene, but the mechanism behind its pathogenesis remains unclear [2]. The protein encoded by the MEFV gene is called pyrin. Consisting of 781 amino acids, pyrin is expressed in granulocytes, eosinophils, activated monocytes, fibroblasts of the plasma, and synovial membranes [3]. Pyrin acts as an inhibitory molecule in inflammation by regulating IL-1β and NF-κB activation [4]. Dysfunction and disruption of pyrin mainly cause FMF. Colchicine has been used to prevent FMF episodes, and reduce the frequency and severity of attacks [5]. IL-1 receptor antagonists and anti-NTF-α have also been used in colchicine-refractory cases [6]. Selective serotonin reuptake inhibitors (SSRIs) were reportedly useful adjuncts in managing the FMF patients who continue to have attacks despite regular colchicine intake [7] because stress and emotional status can trigger FMF episodes. This sheds light on the role of cytokines in the pathogenesis of depression. We report the case of a patient with colchicine-resistant FMF and major depression secondary to a general medical condition. In this case, escitalopram significantly ameliorated the FMF attacks accompanied by depressive symptoms.

Case Presentation

A 65-year-old male with frequent episodes of abdominal pain and fever was referred to the University of Occupational and Environmental Hospital. Approximately seven years before the consult, the patient experienced abdominal pain and high-grade fever, lasting for a few days and spontaneously resolving without treatment. Similar attacks were noted once every two months, but he did not seek medical care because the symptoms were tolerable and spontaneously relieved within a few days. During the first visit, the patient presented with a fever of approximately 38°C, abdominal pain, watery diarrhea, and constipation. His blood test results revealed a white blood cell count of 11640/μL, serum C-reactive protein (CRP) level of 14.7 mg/dL, and erythrocyte sedimentation rate of 59 mm/h. These findings suggested ongoing inflammation. He was diagnosed with FMF based on the Livneh criteria [8]. Exon 10 mutations were not found, but P369S and R408Q were present. Subsequently, he was treated with colchicine (0.75 mg/day) for three years. However, the FMF attacks persisted. Thus, prednisolone (30 mg/day) was added to his treatment. The FMF attacks were slightly relieved, and the dose of prednisolone was gradually increased. However, the patient began exhibiting symptoms of depressed mood, anxiety, insomnia, fatigue, and decreased motivation. Prednisolone was tapered off due to prednisolone-induced depression. However, his depressive mood and restlessness worsened and were accompanied by agitation and suicidal thoughts. He attempted suicide via hanging, failed, and was admitted to the psychiatry ward at our university hospital. He was considered to be in a major depression secondary to a medical condition given in the Diagnostic and Statistical Manual of Mental Disorders 5th Edition. His 17-item version of the Hamilton Assessment Scale for Depression (HAM-D) score was 22 points on admission. Escitalopram (10 mg/day) was added to the colchicine regimen and increased to 20 mg/day. His psychiatric symptoms drastically improved, and the HAM-D score decreased to seven points three weeks after escitalopram treatment. In addition, he also tested negative for CRP, and the fever and abdominal pain attacks completely disappeared. Since then, his physical FMF symptoms and accompanying depressive symptoms have not relapsed with escitalopram and colchicine. Written informed consent was obtained from the patient for this case report (Figure 1).

Discussion

The present case showed that adding escitalopram to colchicine effectively mitigated FMF haps of pain, fever, and depression. This case was concordant with former cases showing that SSRIs, including paroxetine and fluoxetine, enriched the disorder exercise of colchicine-refractory FMF (7). Notwithstanding, the case was administered low medicinals of colchicine combined with escitalopram in this case.

Cases with FMF have dyed-in-the-wool physical symptoms

 that contribute to intellectual stress associated with the development of depressive symptoms. As a result, incendiary cytokines are elevated (8). A depressive state and FMF synergistically run the output of incendiary cytokines (9). SSRIs are fruitful against FMF because of their immunomodulatory movables. SSRIs, including escitalopram, alter the cytokine ranks in major depression (10). ABC transporter subfamily B member 1 (ABCB1) is responsible for the efflux of multihued medicines, including colchicine, out of the cell, and is associated with ABCB1 gene polymorphism and colchicine response in FMF cases (11). Escitalopram also influences ABCB1 and affects the medicinal necessitated to achieve forgiveness in major depression secondary to ABCB1 gene polymorphism (12). Hung on the findings in this case, the dealings between escitalopram and colchicine via ABCB1 likely contributed to their movables in a pharmacogenetic way. Notwithstanding, ABCB1 genotyping wasn't performed. Either, television and platelet serotonin ranks were reportedly involved in the disorder exercise of FMF. The television and platelet ranks of serotonin were reduced during the attack (13). Escitalopram increases the television and platelet serotonin ranks convinced by blocking serotonin transporters. In short, both pharmacokinetic mechanisms and pharmacodynamics of antidepressants might carry the response seen in the case. It has been reported that SSRIs haveanti-inflammatory and immunomodulatory parcels (14, 15). The detailed mechanisms of action of SSRIs with colchicine need another examination. Prednisolone was likely akin to the episode of depressive symptoms, but the depressive symptoms persisted despite reducing the cure of prednisolone. So, we can not rule out the possibility that tapering off prednisolone bettered depressive symptoms in this case.

Conclusions

This case suggested that a possibility of adding escitalopram to low- gelcap colchicine treatment significantly refined FMF attacks accompanied by depressive symptoms.

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