Behçet’s disease associated with myelodysplastic syndrome with elevated levels of inflammatory cytokines

Abstract

We report the case of a 56-year-old Japanese woman with Behçet’s disease and myelodysplastic syndrome (MDS), who had a history of episodic high-grade fever, recurrent oral and genital ulcers, and erythema nodosum, during a 13-year period from 1989 to 2002. Bone marrow aspirates obtained in January 1995 showed refractory anemia with trisomy 8, a subtype of MDS. Her serum levels of soluble interleukin-2 receptor (IL-2R), interferon-γ, IL-1β, IL-6, IL-8, and granulocyte–macrophage colony stimulating factor in the active state were higher than those in the inactive state, whereas those of tumor necrosis factor-α and IL-10 did not increase even in the active state. In this case, it was speculated that a T-cell immune response might have been involved in the disease pathogenesis, and that the repeated febrile episodes might have been a manifestation of neutrophil hyperfunction induced by increased serum levels of inflammatory cytokines.     

Successful treatment of life-threatening intestinal ulcer in Behçet’s disease with infliximab: rapid healing of Behçet’s ulcer with infliximab

Behçet’s disease is a chronic, relapsing, multisystem inflammatory disorder characterized predominantly by recurrent orogenital ulcers, skin involvement, and uveitis. Recurrent mucocutaneous lesions may be the only symptom in mild cases, but ocular, gastrointestinal, and central nervous system involvement may occur in severe cases. We report in this study the successful treatment with infliximab of severe life-threatening GI bleeding caused by an ileal ulcer in a patient with Behçet’s disease. Antitumor necrosis factor (TNF) therapy could be an emergency therapeutic option in patients with massively bleeding Behçet’s disease and unstable patients or those with acute bleeding with other TNF-α-mediated autoimmune diseases. Another option for anti-TNF therapy could be as bridging management between conservative and surgical treatment.     

Successful treatment with stent angioplasty for Budd-Chiari syndrome in Behçet’s disease

Budd-Chiari syndrome (BCS) is a very rare vascular complication of Behçets disease (BD) which often leads to death as a result of portal hypertension and liver failure. We report a 45-year-old BD patient who presented with BCS. Diagnosis was confirmed with CT scan and contrast-enhanced MR angiography which showed ascites, short-segment stenosis of the inferior vena cava (IVC), and middle and left hepatic venous thrombosis. Percutaneous transluminal angioplasty (PTA) of the obstructed segment in the IVC was performed and resulted in dramatic reduction of portal venous pressure. Our experience indicates that PTA may be a safe and effective therapeutic modality for BCS in BD which is caused by short segmental obstruction of the IVC.     

BehÇet’s disease associated with myelodysplastic syndrome with elevated levels of inflammatory cytokines

We report the case of a 56-year-old Japanese woman with BehÇets disease and myelodysplastic syndrome (MDS), who had a history of episodic high-grade fever, recurrent oral and genital ulcers, and erythema nodosum, during a 13-year period from 1989 to 2002. Bone marrow aspirates obtained in January 1995 showed refractory anemia with trisomy 8, a subtype of MDS. Her serum levels of soluble interleukin-2 receptor (IL-2R), interferon-, IL-1, IL-6, IL-8, and granulocyte–macrophage colony stimulating factor in the active state were higher than those in the inactive state, whereas those of tumor necrosis factor- and IL-10 did not increase even in the active state. In this case, it was speculated that a T-cell immune response might have been involved in the disease pathogenesis, and that the repeated febrile episodes might have been a manifestation of neutrophil hyperfunction induced by increased serum levels of inflammatory cytokines.     

Neuro-Behçet’s disease with chorea after remission of intestinal Behçet’s disease

Neuro-Behçets disease shows various neuropsychiatric symptoms, but chorea has rarely been reported. We report a case of neuro-Behçets disease in a 67-year-old woman with depression and chorea that occurred 22 years after the onset of intestinal Behçets disease. Brain magnetic resonance imaging (MRI) using a fluid-attenuated inversion-recovery (FLAIR) sequence demonstrated lesions more clearly than did T₂-weighted MRI. Some of the lesions appeared as small ring-like foci, i.e. low-intensity spots rimmed with remarkable hyperintense signals, in the periventricular white matter and basal ganglia. A review of the literature revealed that the onset of chorea in cases of Behçets disease varied from the time of onset of Behçets disease to 31 years after onset of the disease. Psychiatric manifestations have often been associated with neuro-Behçets disease. In the present patient, treatment with prednisolone resolved the chorea, suggesting that the chorea was caused by an autoimmune mechanism. It seems likely that the long-term development of vasculitis in patients with Behçets disease results in the formation of these particular brain lesions on FLAIR MR images. Chorea should be taken into consideration as one of the manifestations of Behçets disease, even many years after remission of the disease.Abbreviations ANCA Antineutrophil cytoplasmic antibodies - FLAIR Fluid-attenuated inversion-recovery - MRI Magnetic resonance imaging     

Successful treatment of myelodysplastic syndrome (MDS)-related intestinal Behçet's disease by up-front cord blood transplantation

Beh?et's disease is a chronic, relapsing, inflammatory disease of unknown origin. The association of myelodysplastic syndrome and Beh?et's disease is rare, and recent reports have indicated that immunosuppressive agents alone are not sufficient to control Beh?et's disease associated with MDS and many patients die of infection or hemorrhage. We report a case of MDS with intestinal Beh?et's disease. We performed cord blood transplantation with a myeloablative regimen as the primary treatment. The patient achieved complete remission for both diseases, which continued for more than 16 months. Our experience suggests that CBT may provide a potent therapeutic option for the treatment of MDS-related Beh?et's disease.     

Myelodysplastic syndrome associated with intestinal tract-type Behçet disease characterized by an esophageal ulcer

A 55-year-old man with advanced myelodysplastic syndrome was hospitalized prior to undergoing an allogeneic bone marrow transplantation. Immediately before hospitalization, he had suffered from phlegmon in both lower extremities and right forearm as well as genital and oral ulcers. After admission, he developed an esophageal ulcer and was thus diagnosed as having intestinal tract-type Beh?et disease. HLA-B51 was not present. Within a month, he died of pulmonary hemorrhage associated with pneumonia, possibly because of a low platelet count, and vasculoendothelial damage related to Beh?et disease. This is a rare case of myelodysplastic syndrome that developed Beh?et disease with a severe esophageal ulcer.     

Diagnosis and management of intestinal Behçet’s disease

Behçet’s disease (BD) is a chronic relapsing disease with multiple organ system involvement characterized clinically by oral and genital aphthae, cutaneous lesions, and ophthalmological, neurological, and/or gastrointestinal manifestations. Little clinical evidence is available regarding the management of patients with intestinal BD, despite recognition that the presence of intestinal lesions is a poor prognostic factor, causing perforation and massive bleeding. Many recent case reports have suggested that anti-tumor necrosis factor alpha (TNF)α monoclonal antibodies (mAbs) are effective in patients with intestinal BD. Adalimumab, a fully human anti-TNFα mAb, has been approved in Japan for the treatment of intestinal BD. Here, we review the pathogenesis, diagnosis and management of intestinal BD, including evidence of the efficacy of anti-TNFα mAbs.     

Behçet’s disease associated with superior vena cava syndrome without thrombosis

Behçet’s disease is a multisystemic vasculitis of unknown etiology, which is characterized by recurrent urogenital ulceration, cutaneous eruptions, ocular manifestations, arthritis and vasculitis, and its diagnosis is based on clinical criteria. Superior vena cava (SVC) thrombosis is a rare but well-recognized manifestation of Behçet’s disease, whereas SVC syndrome due to vasculopathy, without evidence of thrombosis, has not yet been described in the literature. The authors report the case of a patient with Behçet’s disease, who presented SVC syndrome with reduction in the lumen of the SVC due to thickening of the vessel wall, without evidence of thrombosis upon computed tomography and magnetic angioresonance. The patient received early anticoagulant therapy, corticosteroid and monthly cyclophosphamide pulse therapy. Clinical control without recurrence was observed after 6 months of follow-up. Behçet’s disease should be suspected in young patients presenting with SVC syndrome, in the absence of thrombosis or of a hypercoagulable state.     

A case of Behçet’s disease associated with aortic regurgitation and nephrotic syndrome

Abstract

A 50-year-old housewife with chief complaint of dyspnea is reported. In 1975, the patient developed aphthous stomatitis, genital ulcers, uveitis and erythema nodosum, and was diagnosed as having Behçet’s disease at the Department of Dermatology of our hospital. Oral prednisolone was started in May 1985. Proteinuria was first detected in April 1987. The patient developed orthopnea in July 1992 and was admitted to our hospital in September of that year. Her past history revealed hyperlipidemia since January 1984 and a diagnosis of aortic regurgitation (AR) was made in 1984. Physical examination revealed a systolic/diastolic murmur in the chest and pretibial edema. Laboratory findings showed proteinuria (3.8 g/day) and hypoproteinemia. Microscopic findings of renal biopsy revealed mesangial proliferative glomerulonephritis and arteriosclerosis. Immunofluorescent studies demonstrated deposits of Apo B in the basement membrane and the mesangium. She was discharged from our hospital as proteinuria was decreased after combination treatment with camostat mesilate 600 mg/day and sairei-to 9.0 g/day. Hypertension and hyperlipidemia appeared to have acted as aggrevating factors for renal lesions caused by Behçet’s disease, so that our patient developed the nephrotic syndrome. We report a rare case of Behçet’s disease complicated by aortic regurgitation and the nephrotic syndrome.     

Etanercept therapy in Behçet’s disease

Study objective

The goal of the present study was to investigate patient outcome when using the TNF receptor fusion protein etanercept in addition to conventional immunosuppressive drugs in ameliorating disease intensity and reducing relapses in refractory Behçet’s disease (BD).

Patients and methods

A single center, prospective study was conducted over 1 year. A total of 15 patients with the established diagnosis of BS were enrolled (mean age: 36.5?±?6.75 years, mean disease duration: 3.86?±?1.30 years). Clinical features were classified as refractory if the patients failed to achieve the desired response within 6 months of immunosuppressive and oral glucocorticoid therapy or flare of lesions developed while on the maximum tolerable doses of these drugs. The study included 2 patients who were on previous infliximab therapy for refractory disease. Inflammatory biomarkers (ESR and CRP) were investigated.

Results

Baseline clinical features in the study prior to inclusion showed recurrent oro-genital ulcers were observed in 100?% of patients, the pathergy test was positive in 17.6?%, ocular involvement was observed in 86.7?%, and acne lesions were recorded in 73.3?%. The following values were also recorded: mean ESR 22?±?16.97 mm/h, mean CRP level 6.87?±?4.44 mg/l, mean visual analog score 5.46?±?1.55, and mean patient global score 5.13?±?1.30. At the beginning of the study, all patients were on oral prednisolone (mean dose: 20.16?±?11.81 mg/day), azathioprine (mean dose: 126.66?±?25.81 mg/day), and oral colchicine (mean dose: 1.08?±?0.10 mg/day), then etanercept was added at a regular weekly dose of 50 mg subcutaneously for 1 year. By 8 weeks, 100?% of the patients achieve the primary endpoint, which included clinical resolution of refractory mucocutaneous, joint, and active ocular lesions with normalization of the acute phase symptoms.

Conclusion

Patients with refractory BD who received a 12-month treatment with etanercept in addition to conventional immunosuppressive therapy achieved a good therapeutic response with successful reduction of oral prednisolone to a mean dose of 6.66?±?2.24 mg/day. No serious infections or drug-related adverse events reported.     

Essential thrombocythemia associated with incomplete type intestinal Behçet disease during hydroxyurea treatment

A 77-year-old man was diagnosed as having essential thrombocythemia in 1992. Treatment with hydroxyurea was started in 1997, which stabilized the platelet count. The patient then suffered from pharyngalgia and rhinitis with a high fever, immediately after which he developed tarry stools and anemia and was admitted to our hospital. The physical examination revealed splenomegaly, oral aphthous ulcers, genital ulcers and skin lesions on the lower limbs. His hematological and biochemical tests revealed anemia and increased level of C-reactive protein. He also had an HLA-B51 phenotype. The findings of gastro-intestinal and colon fiberoscopy showed a duodenal ulcer and multiple ulcers on ascending colon. He was thus diagnosed as having intestinal tract-type Beh?et disease. After withdrawal of the hydroxyurea administration, the intestinal ulcers, oral aphthous ulcers and genital ulcers improved.     

Risk factors of disease activity in patients with Behçet’s syndrome

Clinical Rheumatology - To investigate the clinical characteristics and laboratory data in Behçet’s syndrome (BS) patients in China and analyze the risk factors of disease activity. A...     

Successful treatment with adalimumab in a patient with coexisting Behçet’s disease and ankylosing spondylitis

The objective is to report a patient with concomitant ankylosing spondylitis (AS) and Behçet’s disease (BD) successfully treated with adalimumab. A 44-year-old male diagnosed as AS applied to our outpatient clinic with complaints of morning stiffness, pain and limitation of motion at spine, concurrence of oral and genital ulcerated lesions. He was on sulfasalazine together with different NSAIDs for the past 1 year. According to the criteria of International Study Group, he was diagnosed as BD. The patient was considered as refractory to current treatment and adalimumab treatment was started. During follow-up, not only AS was in remission, but also no new oral and genital ulcerations appeared. There were no complications related to the use of anti-TNFα therapy. In our case it was observed that anti-TNFα therapy, specifically adalimumab, was effective for symptoms of both AS and BD.     

Mortality associated with Behçet’s disease in France assessed by multiple-cause-of-death analysis

Clinical Rheumatology - To examine the mortality rates and causes of death among French decedents with Behçet’s disease (BD). Data collected between 1979 and 2016 by the French...     

Resolution of Behçet’s disease after HLA-mismatched unrelated cord blood transplantation for myelodysplastic syndrome

In 1991, a 27-year-old woman who presented with recurrent oral and genital ulcers, fever, and erythema nodosum was diagnosed with Behçets disease (BD). Her symptoms were refractory to conventional therapy. In 1999, pancytopenia was noticed in this patient for the first time, and in 2000, her white blood cell count decreased to 0.94×10⁹/l with 1% myeloblasts and 24% neutrophils. Bone marrow examination showed mild hypocellularity with 8% myeloblasts and 6% mature neutrophils with dysplastic features. A diagnosis of myelodysplastic syndrome (MDS)-refractory anemia with excess blasts was made. Despite marked neutropenia, the BD symptoms continued. Since her neutropenia worsened to 0.24×10⁹/l with 21% neutrophils, the patient underwent cord blood transplantation (CBT) from an unrelated donor in July 2001. Myeloid engraftment was documented on day 26. Grade I acute graft-versus-host disease occurred, but resolved spontaneously. Cyclosporin treatment was reduced gradually and discontinued 6 months after CBT. Twenty-three months after CBT, the patient is doing well and has no signs or symptoms of BD or MDS. These observations suggest that allogeneic hematopoietic stem cell transplantation, which encompasses CBT, may be an effective therapy in patients with high-risk aggressive BD.     

Successful treatment of recurrent intracardiac thrombus in Behçet's disease with immunosuppressive therapy

Beh?et's disease (BD) is a chronic multisystem inflammatory disorder characterized by recurrent oral and genital ulcers, skin eruptions and uveitis. Neurological, gastrointestinal, and musculoskeletal systems are also involved. Although venous and arterial vasculitis occur in up to one-third of patients, intracardiac thrombus is a very rare complication. We herein report the case of a 46-year-old man with BD who presented with a large right atrial thrombus. Within a month after surgical removal, the thrombus recurred and was successfully treated with immunosuppressants that included prednisolone and cyclophosphamide.     

Budd-Chiari syndrome associated with Behçet's disease

OBJECTIVES: Budd-Chiari syndrome is a rare and serious complication of Beh?et's disease, and is the result of occlusion of the major hepatic veins, the adjacent inferior vena cava, or both. The aim of this study was to determine the prevalence, clinical and laboratory findings, and treatment and clinical course of Budd-Chiari syndrome associated with Beh?et's disease. METHODS: We analyzed retrospectively the charts of 220 patients fulfilling the international diagnostic criteria of Beh?et's disease. From them, we selected those with Budd-Chiari syndrome, and analyzed their epidemiological and clinical imaging features and outcomes. RESULTS: Seven male patients, mean age 29 years and already diagnosed with Beh?et's disease, had Budd-Chiari syndrome. The clinical course was from subacute to chronic in all cases. Thrombosis of hepatic veins was associated with inferior vena cava thrombosis in six cases. Four patients had other venous thromboses (superior vena cava and lower limbs) and one also had pulmonary emboli. One patient was positive for anticardiolipin antibodies. All patients had anticoagulation therapy, and six had high-dose corticotherapy associated, in two cases, with monthly cyclophosphamid intravenous pulses. Clinical outcome was favourable in six cases, and one patient died of hepatic failure. CONCLUSION: The prevalence of Budd-Chiari syndrome in patients with Beh?et's disease is 3.2%, confirming that this syndrome is not uncommon in Beh?et's patients. The inferior vena cava is frequently involved in combination with hepatic veins and often associated with other venous thrombosis. The prognosis may be favorable with medical interventions, including anticoagulation, treatment of the vasculitis and the use of diuretics when required.