Evaluating the safety profile of calcineurin inhibitors: cancer risk in patients with systemic lupus erythematosus from the LUNA registry-a historical cohort study.

BACKGROUND: Previous studies have shown conflicting evidence regarding the incidence of cancer in patients with systemic lupus erythematosus (SLE) compared with that in healthy individuals. Calcineurin inhibitors (CNIs) such as cyclosporine and tacrolimus have been widely used to treat SLE; however, their effects on cancer risk remain unclear. We aimed to investigate the incidence of cancer in patients with SLE and determine the potential association between CNI use and cancer risk. METHODS: The standardized incidence ratio (SIR) of cancer among patients with lupus in the Lupus Registry of Nationwide Institutions (LUNA) was calculated based on the age-standardized incidence rate of cancer reported by Japan's Ministry of Health, Labour and Welfare. We also examined the association between CNI exposure and cancer risk, while considering potential confounding factors. The analysis accounted for confounding variables such as age, sex, smoking history, maximum glucocorticoid dose, treatment history with cyclophosphamide, ongoing hydroxychloroquine, Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index (SDI) value (excluding cancer occurrence), comorbidity of diabetes mellitus, and smoking history. RESULTS: The study included 704 patients with SLE (625 females; 88.8%) with a median age of 44 years [interquartile range (IQR) = 34-55] years. The median past maximum glucocorticoid dose was 40 mg/day [IQR = 30-60 mg/day], and the SDI at registration was 1 [IQR = 0-2]. Among the patients, 246 (35.1%) had smoking histories, and 38 (5.4%) experienced cancer complications. Gynecological malignancies accounted for 63.2% of all cancers. The SIR of cancer in the LUNA cohort was 1.08 (95% confidence interval [CI] = 0.74-1.43). No statistically significant risks of cancer were found in relation to CNI treatment history; the odds ratio using multiple logistic regression was 1.12 (95% CI = 0.42-3.00), the risk ratio using standardization was 1.18 (95% CI = 0.47-2.16), and the risk ratio using inverse probability weighting was 1.8 (95% CI = 0.41-4.66). CONCLUSIONS: The incidence of cancer in patients with SLE in the LUNA cohort did not significantly differ from that in the general population. These findings suggest that CNI treatment in this cohort did not pose a risk factor for cancer development.

Prediction of radiographic progression during a treat-to-target strategy by the sequential application of MRI-proven bone marrow oedema and power-Doppler grade ≥2 articular synovitis in rheumatoid arthritis: Retrospective observational study.

OBJECTIVES: To investigate the appropriate timing, useful findings and combination of magnetic resonance imaging (MRI) and ultrasound (US) for predicting the radiographic progression in early rheumatoid arthritis (RA). METHODS: Forty-four active RA patients, who examined by both of MRI and US in the symptomatic wrist and finger joints, were recruited in Nagasaki University Hospital from 2010 to 2017 and treated by the treat-to-target therapeutic strategy for 1 year. MRI was evaluated by RA MRI scoring and US by Outcomes Measures in Rheumatology Clinical Trial, respectively. Plain radiographs were assessed by the Genant-modified Sharp score for the symptomatic side in the same manner as MRI and US. Radiographic progression was defined as an annual increase ≥0.75 at 1 year. Factors associated with radiographic progression were analysed. Also, the optimal combination of MRI and US at each timepoint was considered. RESULTS: Logistic regression model revealed that MRI-proven bone marrow oedema at baseline and 6 months and joint counts of power-Doppler grade ≥2 articular synovitis at 3 or 6 months were significantly associated with radiographic progression at 1 year. CONCLUSION: This study may suggest the favourable timing and combination of MRI and US at each point to predict radiographic progression in patients with early-stage RA.

Real-world comparative effectiveness and safety of tofacitinib and baricitinib in patients with rheumatoid arthritis.

OBJECTIVE: To compare the efficacy and safety of tofacitinib and baricitinib in patients with RA in a real-world setting. METHODS: A total of 242 patients with RA who were treated with tofacitinib (n = 161) or baricitinib (n = 81) were enrolled. We evaluated efficacy and safety between tofacitinib and baricitinib using multivariable analyses to avoid confounding. Their clinical disease activity and AEs were evaluated for 24 weeks. RESULTS: The mean (SD) DAS28-ESR change from baseline to 24 weeks was 1.57 (1.55) (tofacitinib) and 1.46 (1.36) (baricitinib). There was no significant difference in the clinical response between the two groups (adjusted mean difference, 0.04; 95% CI, -0.35 to 0.28). The efficacy was not significantly changed in the patients without concomitant MTX use in both groups, but the concomitant MTX use showed better clinical efficacy in the cases of baricitinib treatment. In both groups, the most common AE was herpes zoster infection, and the AE rates were similar between the two groups. However, the predictive factors contributing to clinical response as revealed by a multivariable logistic analysis differed. The concomitant oral steroid use was independently associated with the achievement of DAS-low disease activity in the tofacitinib group, whereas in the baricitinib group, the number of biological and/or targeted synthetic DMARDs previously used was associated. CONCLUSIONS: Our findings indicate that tofacitinib and baricitinib had comparable continuing efficacies and safety profiles. However, there is a possibility that the influence of clinical characteristics on the treatment response differs. The comparison provides useful information to the optimal use of JAK inhibitors in real-world settings.

Effect of abatacept treatment on serum osteoclast-related biomarkers in patients with rheumatoid arthritis (RA): A multicenter RA ultrasound prospective cohort in Japan.

ABSTRACT: We evaluated the effect of abatacept treatment on osteoclast-related biomarkers and explored whether the biomarkers are associated with the therapeutic response in rheumatoid arthritis (RA) patients treated with abatacept.We enrolled 44 RA patients treated with abatacept from a multicenter prospective ultrasound cohort study of patients who received biologic or targeted synthetic disease-modifying antirheumatic drug therapy. We evaluated the disease activity score (DAS) 28-CRP (C-reactive protein), musculoskeletal ultrasound scores including the total grayscale score (GS)/power Doppler (PD) score and the serum concentrations of isoform 5b of tartrate-resistant acid phosphate (TRACP-5b) and soluble receptor activator of nuclear factor-κB ligand (sRANKL) at baseline and at 3 and 6 months of treatment. "PD responder" was defined as a patient whose Δtotal PD score over 6 months was greater than the median change of that.Abatacept significantly improved DAS28-CRP as well as the total GS/PD score over 6 months. Serum TRACP-5b was significantly elevated and serum sRANKL was significantly decreased at 6 months (P < .0001 and P < .01, respectively). At 6 months, serum sRANKL was significantly decreased in the patients who achieved DAS28-CRP remission and the PD responders but not in those who did not. However, serum TRACP-5b rose regardless of the therapeutic response.Among RA patients treated with abatacept, serum sRANKL decreased in the patients with a good therapeutic response, but serum TRACP-5b elevated paradoxically regardless of the therapeutic response.

Association between serum bone biomarker levels and therapeutic response to abatacept in patients with rheumatoid arthritis (RA): a multicenter, prospective, and observational RA ultrasound cohort study in Japan.

BACKGROUND: To evaluate the effect of treatment on serum bone biomarkers and explore whether serum bone biomarkers are associated with therapeutic response in rheumatoid arthritis (RA) patients treated with abatacept. METHODS: We enrolled 59 RA patients treated with abatacept from a multicenter, exploratory, short-term, prospective and observational ultrasound cohort study of patients who received biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) therapy. We evaluated the patients' clinical disease activity and musculoskeletal ultrasound (MSUS) scores. The serum concentrations of five bone biomarkers were evaluated (dickkopf-1 [Dkk-1], sclerostin [SOST], osteocalcin [OC], osteopontin [OPN], and osteoprotegerin [OPG]) by multiplex bead assays at baseline, 3, and 6 months: the change over 6 months was defined as the Δ value. 'Power Doppler (PD) responder' was defined as a patient whose Δtotal PD score over 6 months was greater than the median change. RESULTS: Abatacept significantly improved the clinical disease activity and MSUS score over 6 months. Serum OPG was significantly elevated at 6 months after the abatacept introduction (p = 0.016). The ΔSOST and ΔOPG were significantly greater in the PD responders versus the non-PD responders (p = 0.0041 and 0.0073, respectively). The serum Dkk-1 at baseline was significantly lower in the PD responders (n = 30) vs. the non-PD responders (n = 29) (p = 0.026). A multivariate logistic regression analysis showed that the serum Dkk-1 at baseline (odds ratio 0.50, 95% confidence interval [CI] 0.23-0.91, p = 0.043) was an independent predictor of PD responder status. CONCLUSION: Serum levels of bone biomarkers may be useful for predicting RA patients' therapeutic responses to abatacept. TRIAL REGISTRATION: Name of the registry: Assessment of therapeutic responsiveness by imaging of the joints in patients with rheumatoid arthritis; A observational cohort study Trial registration number: UMIN000012524 Date of registration: 12/9/2013 URL of trial registry record: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000014657.

Utility of a simplified ultrasonography scoring system among patients with rheumatoid arthritis: A multicenter cohort study.

ABSTRACT: We aimed to evaluate the utility of a simplified ultrasonography (US) scoring system, which is desired in daily clinical practice, among patients with rheumatoid arthritis (RA) receiving biological/targeted synthetic disease-modifying antirheumatic drugs (DMARDs).A total of 289 Japanese patients with RA who were started on tumor necrosis factor inhibitors, abatacept, tocilizumab, or Janus kinase inhibitors between June 2013 and April 2019 at one of the 15 participating rheumatology centers were reviewed. We performed US assessment of articular synovia over 22 joints among bilateral wrist and finger joints, and the 22-joint (22j)-GS and 22-joint (22j)-PD scores were evaluated as an indicator of US activity using the sum of the GS and PD scores, respectively.The top 6 most affected joints included the bilateral wrist and second/third metacarpophalangeal joints. Therefore, 6-joint (6j)-GS and -PD scores were defined as the sum of the GS and PD scores from the 6 synovial sites over the aforementioned 6 joints, respectively. Although the 22j- or 6j-US scores were significantly correlated with DAS28-ESR or -CRP scores, the correlations were weak. Conversely, 6j-US scores were significantly and strongly correlated with 22j-US scores not only at baseline but also after therapy initiation.Using a multicenter cohort data, our results indicated that a simplified US scoring system could be adequately tolerated during any disease course among patients with RA receiving biological/targeted synthetic DMARDs.

Comparison of the quantitative measurement of 18F-FDG PET/CT and histopathological findings in IgG4-related disease.

OBJECTIVES: To investigate the utility of 18F-FDG PET/CT in the diagnostic procedure of IgG4-related disease (IgG4-RD), we analysed the association between quantitative method of 18F-FDG PET/CT and histological findings. METHODS: Twenty-one patients with IgG4-RD in whom 18F-FDG PET/CT was performed at the time of diagnosis were enrolled. Tissue biopsy was performed at 24 sites in 21 patients. To perform quantitative analysis of 18F-FDG PET/CT imaging, the highest standardised uptake value (SUV) of the pixels (SUVmax) and the average SUV (SUVmean) within the biopsied lesion were measured. The SUVmean of the liver was also measured as a reference. RESULTS: The mean age at diagnosis was 64.6±11.9 years, and the median serum IgG4 level was 650 mg/dl. Histological findings were consistent with IgG4-RD (histopathology-positive) at 19 out of 24 sites. Although there was no significant difference in the values of SUVmax between histopathology-positive and histopathology-negative tissues, the values of SUVmean were significantly higher in the histopathology-positive tissue (4.98 and 3.54, respectively p<0.05). The values of SUVmean/liver were also higher in the histopathology-positive tissue (2.17 and 1.52, respectively p<0.05). To establish a cut-off value of SUVmean to determine which of multiple lesions should be biopsied, a ROC curve was constructed. ROC curve analysis indicated SUVmean=4.07 or SUVmean/liver=1.66 as a cut-off value. CONCLUSIONS: Our present study suggested that quantitative analysis of 18F-FDG-PET/CT imaging might be useful for selecting the biopsy site in IgG4-RD. The calculation of SUVmean, not of SUVmax, is important for evaluating IgG4-RD-related lesions in 18F-FDG PET/CT imaging.

Contributing factors of clinical outcomes at 1 year post-diagnosis in early rheumatoid arthritis patients with tightly controlled disease activity in clinical practice: a retrospective study.

OBJECTIVES: To determine whether specific parameters contribute to clinical outcomes at 1 year post-diagnosis in early rheumatoid arthritis (RA) patients under the 'treat-to-target' strategy in clinical practice. METHODS: We retrospectively analyzed 125 RA patients selected according to the following criteria; the patients' symptom duration was ≤6 months, and none had experience with DMARDs. We evaluated the patients' clinical disease activity at baseline and 1 year of treatment and the musculoskeletal ultrasound (MSUS)-detected synovitis activity at baseline. We performed an analysis to identify parameters that contribute to SDAI remission and the use of biologic/targeted synthetic (b/ts) DMARDs at 1 year post-diagnosis. RESULTS: Forty-seven patients received b/tsDMARDs therapy, and 58 patients achieved SDAI remission at 1 year post-diagnosis. Rheumatoid factor positivity, low patient's/evaluator's global assessment at baseline, and methotrexate use at 1 year post-diagnosis were associated with SDAI remission. The baseline clinical disease activity and MSUS scores were not associated with SDAI remission. Anti-cyclic citrullinated peptide antibody positivity/high titer and high swollen joint counts or the presence of severe synovial hypertrophy at baseline were associated with the use of b/tsDMARDs therapy. CONCLUSION: The value of the expected poor-prognosis factors may be diminished by intensive therapy within the 'windows of opportunity'.

Life prognosis and renal relapse after induction therapy in Japanese patients with proliferative and pure membranous lupus nephritis.

OBJECTIVE: We aimed to compare life prognosis and renal relapse after induction therapy in proliferative (PLN) and pure membranous LN (MLN). METHODS: We retrospectively analysed the cases of 140 of 172 patients with LN who underwent a renal biopsy at our hospital or community hospitals from 1993 to 2016. We determined the complete response (CR) rate at 12 months after the patients had started induction therapy, and we evaluated the predictive factors for CR, life prognosis and renal relapse in PLN and pure MLN. We defined PLN as International Society of Neurology and the Renal Pathology Society (ISN/RPS) Class III or IV and MLN as ISN/RPS Class V. RESULTS: The renal pathology of 99 (70.7%) patients was classified as PLN, and that of the other 41 (29.3%) patients as MLN. Fifty patients (50.5%) with PLN and 22 patients (53.7%) with MLN achieved a CR at 12 months. A multivariate analysis showed that a lower index of chronicity in PLN and a higher total haemolytic complement (CH50) level in MLN were predictive factors for achieving a CR at 12 months. A Kaplan-Meier analysis showed that the life prognosis (P = 0.93) and renal relapse (P = 0.52) were not significantly different between PLN and MLN. CONCLUSIONS: The predictive factors for a CR at 12 months post-induction therapy were index of chronicity in PLN and CH50 level in MLN. There were no significant differences in life prognosis or renal relapse between PLN and MLN in the achievement of a CR at 12 months post-induction therapy.

Non-TNF inhibitor switchers versus TNF inhibitor cyclers from multicentre rheumatoid arthritis ultrasonography prospective cohort in Japan.

To compare therapeutic efficacy of tumour necrosis factor inhibitor (TNFi) cyclers and non-TNFi switchers in patients with rheumatoid arthritis (RA) having inadequate response to previous TNFis (TNF-IR patients) using composite measures including imaging assessment with power Doppler ultrasonography (PDUS). Patients with RA who had inadequate response to one or more previous TNFi agents with moderate or higher disease activity were enrolled. The outcomes of 56 TNF-IR patients were analysed. Patients were divided into 19 TNFi cyclers and 37 non-TNFi switchers (16 abatacept [ABT] and 21 tocilizumab [TCZ] switchers). Retention ratio at 6 months was significantly higher in non-TNFi switchers than in TNFi cyclers (p < .05). Although there was no significant difference, non-TNFi switchers tended to have a larger decrease than TNFi cyclers in efficacy indicators based on clinical disease activity index and PDUS. Multivariate logistic regression analysis identified a following independent factor associated with both EULAR good response and retention of a biologic agent: non-TNFi switch (p < .05 for both). Non-TNFi switchers were shown to have significantly higher percentage of EULAR good response and higher retention than TNFi cyclers. A non-TNFi biologic agent may hence be a preferential next-line treatment for TNF-IR patients.

Reactive arthritis induced by active extra-articular tuberculosis: A case report.

RATIONALE: Rare cases of reactive arthritis induced by active extra-articular tuberculosis (Poncet disease) have been reported. Complete response to antitubercular treatment and evidence of active extra-articular tuberculosis are the most important clinical features of Poncet disease. We report the case of successfully treated a patient with reactive arthritis induced by active extra-articular tuberculosis with a TNF inhibitor after sufficient antitubercular treatment. PATIENT CONCERNS: A 56-year-old Japanese man was admitted to our department with polyarthralgia, low back pain, and high fever. The results of rheumatoid factor, anti-citrullinated protein antibody, human leukocyte antigen B27, and the assays for the detection of infections (with an exception of T-SPOT.TB) were all negative. Fluoro-deoxy-D-glucose-positron emission tomography with CT (PET/CT) showed moderate uptake in the right cervical, right supraclavicular, mediastinal, and abdominal lymph nodes. As magnetic resonance imaging and power Doppler ultrasonography showed peripheral inflammation (tendinitis, tenosynovitis, ligamentitis, and enthesitis in the limbs). DIAGNOSIS: A diagnosis of tuberculous lymphadenitis was eventually established on the basis of lymph node biopsy results. There was no evidence of a bacterial infection including acid-fast bacteria in his joints, and the symptoms of polyarthralgia and low back pain were improved but not completely resolved with NSAID therapy; in addition, a diagnosis of reactive arthritis induced by active extraarticular tuberculosis was made. INTERVENTIONS: The patient experienced persistent peripheral inflammation despite antitubercular treatment for more than nine months and was then successfully treated with a tumor necrosis factor inhibitor (adalimumab 40 mg every 2 weeks). OUTCOMES: Finally, the patient responded to the treatment and has been in remission for over 4 months as of this writing. LESSONS: In patients who present with symptoms associated with spondyloarthritis, it is important to distinguish between classic reactive arthritis and reactive arthritis induced by extra-articular tuberculosis infection. Introduction of biological agents should be carefully considered in settings where reactive arthritis induced by active extra-articular tuberculosis shows progression to chronicity despite sufficient antitubercular treatment.

Gastric mucormycosis complicated by a gastropleural fistula: A case report and review of the literature.

RATIONALE: Mucormycosis is a rare opportunistic fungal infection with poor prognosis. The incidence of mucormycosis has been increasing, and it is a threat to immunocompromised hosts. We present a case of gastric mucormycosis complicated by a gastropleural fistula during immunosuppressive treatment for adult-onset Still disease (AOSD). PATIENT CONCERNS: An 82-year-old woman diagnosed with AOSD who developed gastric ulcers during the administration of an immunosuppressive therapy with corticosteroids, cyclosporine, and tocilizumab complained of melena and epigastralgia. Esophagogastroduodenoscopy showed multiple ulcers covered with grayish or greenish exudates. DIAGNOSES: The patient diagnosed with mucormycosis based on culture and biopsy of the ulcers, which showed nonseptate hyphae branching at wide angles. Mucor indicus was identified using polymerase chain reaction. INTERVENTIONS AND OUTCOMES: Although liposomal amphotericin B was administered, gastric mucormycosis was found to be complicated by a gastropleural fistula. The patient died because of pneumonia due to cytomegalovirus infection, and autopsy revealed the presence of Mucorales around the fistula connecting the stomach and diaphragm. LESSONS: Gastric mucormycosis is refractory to treatment and fatal. Surgical resection, if possible, along with antifungal drugs can result in better outcomes.

Serial analysis of cytokine and chemokine profiles and viral load in severe fever with thrombocytopenia syndrome: Case report and review of literature.

RATIONALE: Severe fever with thrombocytopenia syndrome (SFTS) is a recently recognized fatal infectious disease caused by the SFTS virus, and severe cases are complicated by the presence of hemophagocytic lymphohistiocytosis (HLH) associated with a cytokine storm. Herein, we report on serial changes of serum cytokine levels and viral load in a severe case of SFTS. PATIENT CONCERNS: A 63-year-old Japanese woman presented with high-grade fever, abdominal pain, diarrhea, impaired consciousness, leukocytopenia, and thrombocytopenia. DIAGNOSIS: SFTS was diagnosed based on a positive serum test for SFTS virus RNA and electroencephalogram (EEG) findings of encephalopathy. INTERVENTIONS: The patient was treated with supportive therapy, including steroid pulse therapy (intravenous methylprednisolone 1 g/d for 3 days) for HLH and intravenous recombinant thrombomodulin 19200 U/d for 7 days for disseminated intravascular coagulation. OUTCOMES: Treatment for 7 days improved both symptoms and abnormal EEG findings, and SFTS virus RNA disappeared from the serum at day 10 from the onset of symptoms. The serum cytokines and chemokines analysis during the clinical course revealed 2 distinct phases: the acute phase and the recovery phase. The cytokines and chemokines elevated in the acute phase included interleukin (IL)-6, IL-10, interferon (IFN)-α2, IFN-γ, tumor necrosis factor-α, interferon-γ-induced protein-10, and fractalkine, while the IL-1ß, IL-12p40, IL-17, and vascular endothelial growth factor levels were higher in the recovery phase. CONCLUSION: These observations suggest that the cytokines and chemokines elevated in the acute phase may reflect the disease severity resulted in a cytokine storm, while those in the recovery phase may be attributed to T-cell activation and differentiation.

Rheumatoid Arthritis Complicated with Nasal Septum Perforation Due to Methotrexate-associated Lymphoproliferative Disorder.

A 44-year-old female with rheumatoid arthritis treated with methotrexate (MTX) and tocilizumab (TCZ) was admitted to our hospital with nasal pain. Nasal fiberscopy revealed septum perforation, while a membrane biopsy indicated granuloma and fibrinoid necrosis of the small artery. The patient was treated with prednisolone 30 mg/day after discontinuation of MTX and TCZ. Inguinal lymph node biopsy revealed diffuse infiltrations of atypical T-cells and Epstein-Barr virus-positive B cells. The patient was diagnosed with peripheral T-cell lymphoma due to MTX-associated lymphoproliferative disorder (MTX-LPD). We herein describe the case of a patient with nasal septum perforation due to MTX-LPD mimicking granulomatosis with polyangiitis.

Gastric Perforation due to Iatrogenic Immunodeficiency-associated Lymphoproliferative Disorder during the Treatment of Rheumatoid Arthritis.

A 71-year-old woman being treated with methotrexate (MTX) and tacrolimus (TAC) for rheumatoid arthritis (RA) was admitted to our hospital and underwent surgery for gastric perforation and peritonitis. An endoscopic examination six days post-surgery showed an extensive ulcer in the stomach, and a biopsy revealed diffused large B-cell lymphoma. We diagnosed her with immunodeficiency-associated lymphoproliferative disorder (LPD) and discontinued the MTX and TAC. She underwent gastrectomy due to stenosis approximately two months after the first operation, but the histopathological findings of lymphoma had disappeared. LPD should be considered as a potential cause of gastric perforation during RA treatment.

A case of neutrophilic dermatosis with MEFV gene variant and abnormal activation of peripheral blood monocytes: a case report.

A healthy 32-year-old man had a fever and elevated levels of white blood cells (WBC) and C-reactive protein (CRP). In addition, he presented with a skin rash on his forehead, around the neck, and from the anterior chest to the abdomen. His laboratory findings showed elevated levels of hepatic enzyme, CRP, and ferritin; therefore, he was suspected to have adult-onset Still's disease (AOSD) and referred to our department. We ruled out hematological malignancy and established diagnosis of AOSD according to Yamaguchi's criteria and treated with 20 mg/day prednisolone. His clinical condition did not improve, therefore, we increased the dosage of prednisolone to 40 mg/day; however, his rash gradually expanded with papules and plaques. A cervical skin biopsy revealed neutrophil dermatosis and analysis of the MEFV gene revealed a heterozygous variant in exon 2 (E148Q). We found an elevated percentage of CD86+CD14+CD16- classical monocytes in the peripheral blood using flow cytometry. We added oral potassium iodide as a treatment for neutrophil dermatosis. Despite this treatment, his eruption and fever did not subside, therefore, we changed potassium iodide to colchicine, this improved his clinical condition. This case suggests the importance of autoinflammation-related gene abnormalities and macrophage activation in the pathogenesis of neutrophil dermatosis.

Rheumatoid arthritis-like active synovitis with T-cell activation in a case of idiopathic multicentric Castleman disease: A case report.

RATIONALE: Idiopathic multicentric Castleman disease (iMCD) is a systemic disease with multiple regions of lymphadenopathy and systemic symptoms and associated with rheumatoid arthritis (RA) and collagen diseases. However, few reported have described the coexistence of iMCD and RA and the mechanisms by which iMCD induces arthritis remain elusive. We experienced a rare case of iMCD, wherein the patient exhibited symptoms of polyarthritis with high-grade fever. PATIENT CONCERNS: A 34-year-old woman was admitted to our hospital for further evaluation of a high fever with polyarthritis. The levels of both rheumatoid factor and anticitrullinated protein antibody were negative. F-fluorodeoxyglucose/positron emission tomography-computed tomography showed lymphadenopathy with increased fluoro-2-deoxy-D-glucose uptake. Magnetic resonance imaging and musculoskeletal ultrasonography revealed active synovitis in the hands which was consistent with RA. DIAGNOSES: We diagnosed iMCD based on human herpesvirus 8 negativity, HIV negativity, systemic lymphadenopathy, and pathologic findings of the lymph nodes. The patient did not satisfy the 2010 American College of Rheumatology and European League Against Rheumatism classification criteria for RA. Cytokine assay showed elevated serum levels of interleukin-17 and CXCL10, comparable to those in patients with RA. INTERVENTIONS: We administered 15 mg/d of predonisolone. OUTCOMES: After this treatment, the patient's symptoms showed improvement. As of this writing, we tapered the prednisolone to 7.5 mg/d, and the patient's remission has been maintained for >4 months. LESSONS: The present case suggests that RA-like active synovitis may coexist in iMCD, resulting from aberrant T-cell activation and histologic examination using lymph node biopsy may help enable early diagnosis of iMCD.

Atypical Familial Mediterranean Fever Complicated with Gastrointestinal Amyloidosis Diagnosed due to Paroxysmal Arthralgia and Intractable Diarrhea, Successfully Treated with Tocilizumab.

A 53-year-old man with recurrent episodes of large joint pain and a low-grade fever at irregular intervals for 16 years developed right knee and ankle arthralgia, watery diarrhea, and abdominal pain. Following an ileum and colon biopsy, he was diagnosed with gastrointestinal amyloidosis. We suspected familial Mediterranean fever (FMF) based on his history and administered colchicine; his symptoms subsequently improved. Thus, he was diagnosed with atypical FMF. After tocilizumab administration, the amyloid deposits disappeared. This case suggests that physicians should consider FMF even in cases with atypical symptoms in order to prevent the progression of amyloidosis and that amyloid deposits can be eliminated by interleukin (IL)-6 inhibition.