Successful use of Tofacitinib in Reactive Arthritis Refractory to Conventional Therapies – A Case Series

Reactive arthritis is an immune mediated aseptic arthritis resulting from either genitourinary or gastrointestinal tract in a genetically susceptible host. It commonly presents as oligoarthritis of the lower limbs with or without extra articular features such as urethritis and non-purulent conjunctivitis. Therapies include NSAIDs, conventional DMARDs and rarely biologics in severe cases. We report successful use of tofacitinib in four cases of reactive arthritis who failed to respond to conventional therapies.

A Case of Clinically Amyopathic Dermatomyositis that was Refractory to Intensive Immunosuppressive Therapy including Tofacitinib, but Successfully Treated with Plasma Exchange Therapy

ABSTRACT Clinically amyopathic dermatomyositis (CADM) patients often develop rapidly progressive interstitial lung disease (RP-ILD). A high level of anti-melanoma differentiation-associated gene 5 antibodies (anti-MDA5 Ab) before treatment is associated with RP-ILD development, a poor treatment response, and poor survival. The prognosis of CADM patients remains poor due to ILD even with combined intensive immunosuppressive therapy. Recently, several additional therapies, including tofacitinib (TOF) and plasma exchange (PE) therapy, have been reported to be effective. We herein report a case of CADM-ILD with a high level of anti-MDA5 Ab that was refractory to combined intensive immunosuppressive therapy including TOF, but successfully treated with PE. The following are possible reasons why TOF was ineffective: 1) cytokines that were not suppressed by TOF played an important role in RP-ILD; 2) TOF was administered later than previously reported; and 3) TOF did not suppress pathological substances such as antibodies. On the other hand, PE removes cytokines and various pathological substances. Therefore, PE may be a more reasonable additional therapy for intractable CADM-ILD.

A Three-Generation Muckle-Wells Syndrome Family: Detailed Family History, Physical Examination, and Inter-Departmental Collaboration

Cryopyrin-associated periodic syndrome (CAPS) is a rare inherited autoinflammatory disease caused by gain-of-function mutations in the NLRP3 gene, with a genotype-phenotype correlation. The clinical presentation of each mutation has been previously studied. However, very few studies have reported on the clinical characteristics and treatment effectiveness across different generations within a family with the same mutation. A detailed investigation of family members of patients with CAPS may help in the appropriate diagnosis and treatment of undiagnosed CAPS. Herein, we report a 2-year-old boy (proband), his father, and his grandmother who presented with several symptoms of CAPS, such as persistently positive inflammatory reactions and hearing impairment. All three patients had the same pathogenic mutation in the NLRP3 gene (c.1049C>T (p.Thr350Met) heterozygous mutation) and were diagnosed with CAPS. With canakinumab treatment, the laboratory data of all three patients improved, the proband and father’s skin rash disappeared, and his grandmother’s arthropathy improved. The proband’s hearing also showed slight improvement, but not in his father or grandmother. Among the various non-specific symptoms associated with CAPS, chronic ocular hyperemia is a finding that can be easily identified by non-ophthalmologists. Diagnosis of CAPS should be considered when eye symptoms are present in a combination of hyperinflammatory response, arthropathy, or skin symptoms. Thorough family history records, physical examinations, and close collaboration between pediatricians and adult rheumatologists are important for prompt diagnosis and appropriate treatment of inherited autoinflammatory diseases.

Epstein-Barr Virus Encephalitis in a Patient with Rheumatoid Arthritis

A 53-year-old woman with a 6-year history of rheumatoid arthritis (RA) presented with pharyngeal pain, fever, and altered mental status. The patient had been treated with methotrexate (MTX) 12 mg/week, baricitinib 4 mg/day, and tacrolimus 2 mg/day. Magnetic resonance imaging of the brain revealed diffuse high-intensity lesions in the cerebral white matter, basal ganglia, brainstem, and right cerebellar hemisphere. She was diagnosed with Epstein-Barr virus (EBV) encephalitis due to elevated levels of EBV-DNA in the cerebrospinal fluid and serum. Although MTX-associated lymphoproliferative disorders are well-known complications in patients with RA, EBV encephalitis requires careful attention for such patients undergoing treatment with multiple potent immunosuppressants.

A Rare Case of Atypical Cogan’s Syndrome Presenting as Encephalitis

Cogan’s syndrome (CS) is a rare autoimmune vasculitis of unknown aetiology characterised by non-syphilitic interstitial keratitis, audio-vestibular symptoms, sometimes systemic symptoms and multi-organ involvement. Atypical CS has other ocular features such as scleritis, episcelritis, retinitis and optic neuritis. Diagnosis of CS is purely clinical without a confirmatory test. Hereby, we report a case of atypical CS presenting with features of encephalitis who was treated successfully with intravenous pulse methylprednisolone with cyclophosphamide. It is important to consider Cogan’s syndrome in the differential diagnosis of encephalitis with ocular and vestibular symptoms in young patients, as high morbidity and mortality rates are effectively lowered by early immunosuppressive treatment.

Digital Gangrene and Pulmonary Consolidation in a Young Girl with Takayasu Arteritis

ABSTRACT Takayasu arteritis is a large-vessel vasculitis most commonly affecting women of childbearing age. The disease process is usually slow and smoldering, presenting over months to years. Digital gangrene is an uncommon manifestation of Takayasu arteritis because of the formation of good collateral circulation. Similarly, although pulmonary artery involvement is well described, pulmonary parenchymal involvement is very rare. We are reporting a case of a young girl with Takayasu arteritis presenting with digital gangrene and pulmonary consolidation, which was treated successfully with a combination of aggressive systemic immunosuppression and anti-coagulants. The possible mechanism for gangrene along with the confounding diagnostic possibility of co-existing tuberculosis have been discussed.

An Adult-Onset Still’s Disease During Pregnancy that Delivered a Neonate with Hemophagocytic Lymphohistiocytosis and Severe Liver Failure Requiring Liver Transplantation: A Case Report and Literature Review

Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology that is categorized as a non-hereditary disease. Neonatal hemophagocytic lymphohistiocytosis (HLH) is also a rare, but potentially fatal condition. Neonatal HLH is one of the causes of neonatal acute liver failure that often requires urgent liver transplantation. The relationship between AOSD during pregnancy and neonatal HLH currently remains unclear. We encountered a case of AOSD that developed during pregnancy, and an offspring was born with neonatal HLH resulting in severe liver failure. The mother with AOSD only presented with liver dysfunction during pregnancy; however, disease activity was exacerbated after delivery. The maternal clinical course was quite severe and refractory that she required biological therapy in addition to high-dose corticosteroids and immunosuppressants. Additionally, the severe condition of the neonate with HLH and acute liver failure required intensive care with the administration of steroids and intravenous immunoglobulin treatments, and ultimately liver transplantation. This is the first case that severe maternal AOSD associated with a neonatal HLH resulted in severe clinical courses. Physicians need to be aware of the risk of a mother with AOSD delivering an offspring with neonatal HLH with potentially acute liver failure.

Rituximab in Remission Induction and Maintenance Therapy for Microscopic Polyangiitis Associated with Gastric Cancer: A Case Report

We herein report a case of a patient with gastric cancer-associated microscopic polyangiitis (MPA) who was treated with combination glucocorticoids and rituximab (RTX) for remission induction and maintenance, and finally to discontinue glucocorticoids without recurrence of gastric cancer or MPA in a year. A 69-year-old man was suspected of having MPA because of fever, high C-reactive protein levels, neuritis, and a high titer of myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA). Upper gastrointestinal endoscopy indicated early-stage gastric cancer, for which he underwent surgery preceded by immunosuppressive therapy for vasculitis. Histopathological images showed vasculitis in the vicinity of the cancerous tissue, suggesting an association between gastric cancer and vasculitis. Postoperatively, fever and inflammatory response improved, but MPO-ANCA increased further and the patient developed alveolar hemorrhage. He resulted in remission with high-dose glucocorticoids and RTX, and he received maintenance therapy with RTX without additional immunosuppressive agents. After 1 year of treatment, he was able to discontinue glucocorticoids without recurrence of gastric cancer or vasculitis. There is no established treatment for malignancy-associated vasculitis other than glucocorticoids. Although more cases need to be accumulated in the future, RTX is expected to be useful in malignancy-associated vasculitis.

Tocilizumab for Juvenile Takayasu Arteritis Complicated with Acute Heart Failure at Onset

Chronic heart failure caused by aortic valve regurgitation is a common complication of Takayasu arteritis (TA). However, fewer patients develop acute heart failure (AHF), and no specific treatment for AHF in TA has been established. We encountered a 12-year-old girl with TA who developed AHF at onset. We successfully treated her with intravenous methylprednisolone and tocilizumab. She developed palpitations and shortness of breath three weeks before admission. Her symptoms exacerbated rapidly and she finally entered the intensive care unit due to respiratory distress and tachycardia. Blood pressure measurements on the left arm and bilateral legs were paradoxically lower than that on the right arm. Chest X-ray revealed a severely enlarged heart. Contrast computed tomography showed an expanded aorta, aortic aneurysm, meandering, and irregular diameter of the aorta. The left ventricular ejection fraction (LVEF) was 20% on cardiac ultrasound. Her medical condition was finally diagnosed as TA with AHF. Along with inotropes and diuretics, methylprednisolone pulse therapy was administered on hospital days 2-4 and hospital days 12-14, followed by oral prednisolone. However, cardiac function was not notably improved. As intravenous cyclophosphamide therapy requires hydration and may exacerbate AHF, we initiated weekly subcutaneous tocilizumab treatment (162 mg/week) from hospital day 20. Inotropes were discontinued on hospital day 51 and her LVEF had gradually improved to 37.5% at discharge (day 63). As AHF in TA is presumed to be due to inflammation of the myocardium, tocilizumab could be a treatment option for TA with AHF.

Acute Pancreatitis Coincided with Multiple Arteriolar Aneurysms in a Patient with Polyarteritis Nodosa

A 78-year-old man presented to our hospital with a history of 10kg weight loss within 6 months previously, and general fatigue and fever for 2 and 1 months, respectively. On hospitalization, the patient was diagnosed with polyarteritis nodosa after multiple microaneurysms were observed in the liver, kidney, pancreas, and mesenteries. He achieved remission with the administration of 1,000mg methylprednisolone for 3 days, followed by prednisolone (55mg/day). Steroids were successfully tapered with no re-elevation in inflammation. Two months after the administration of steroids, the patient complained of acute abdominal pain, and developed severe acute pancreatitis. During treatment for pancreatitis, the patient died due to septic shock and disseminated intravascular coagulation. An autopsy revealed necrotizing vasculitis in the intrapancreatic arteries and ischemia of the downstream arterioles resulting in acute pancreatitis.