Apremilast is a potentially useful treatment for severe palmoplantar pustulosis with extra-palmoplantar symptoms.

Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disorder affecting the palms and soles. In rare cases, severe patients develop acute extra-palmoplantar lesions often accompanied by arthralgia. Such cases with extensive symptoms often necessitate systemic treatments with variable efficacy and potential side effects. Apremilast, known for its broad immune response modulation, presents promise as a therapeutic option for severe PPP with joint and extra-palmoplantar lesions. This case highlights apremilast as a potential systemic treatment for such cases with minimal side effects.

Successful treatment of lupus protein-losing enteropathy with belimumab: A case report.

Lupus protein-losing enteropathy (LUPLE) is a rare condition in patients with systemic lupus erythematosus (SLE). Since the causes and exact pathological mechanism have not been elucidated, appropriate treatment has not been determined. Here, we report the case of a 69-year-old woman with systemic lupus erythematosus who developed LUPLE which was successfully treated with belimumab without an increase in glucocorticoid dose. This case suggests that belimumab monotherapy may be a treatment option for LUPLE.

A Case of Successful Immunosuppressive Therapy for Interstitial Lung Disease Associated with Sjögren's Syndrome With Double-positive Anti-SS-A and Anti-centromere Antibodies.

Sjögren's syndrome (SS) can present with extraglandular organs, such as interstitial lung disease (ILD). Anti-SS-A antibody is frequently found in SS cases, whereas anti-centromere antibody (ACA) is detected in some SS cases. Notably, the anti-SS-A and ACA double-positive cases exhibited distinct features with a higher prevalence of ILD. However, there have so far been no reports on the treatment of ILD in anti-SS-A and ACA double-positive cases. We herein present a case of ILD with anti-SS-A and ACA double-positive SS that was successfully treated with immunosuppressive therapy. Our case suggests the potential efficacy of immunosuppressive therapy for this poorly understood condition.

Risk of disease flares after SARS-CoV-2 mRNA vaccination in patients with systemic lupus erythematosus.

This study aims to elucidate the effectiveness and safety of SARS-CoV-2 mRNA vaccination in patients with systemic lupus erythematosus (SLE). We enrolled uninfected SLE patients who received two vaccine doses (BNT162b2 or mRNA-1273) and historical unvaccinated patients. Neutralizing antibodies, adverse reactions, and disease flares were evaluated 4 weeks after the second vaccination. Ninety patients were enrolled in each group. Among the vaccinated patients, SLE Disease Activity Index (SLEDAI), and prednisolone doses before vaccination were 2, and 5 mg/d, respectively. After the second vaccination, 19 (21.1%) had no neutralizing antibodies. Adverse reactions occurred in 88.9% within 3 d. Negative antibodies were associated with anemia and mycophenolate mofetil administration. SLEDAI increased modestly but significantly after vaccination, with 13 (14.4%) experiencing flares and 4 (4.4%) severe flares (nephritis in three and vasculitis in one). The flare rate was higher in vaccinated patients than unvaccinated controls. The mean duration between the second vaccination and flares was 35 d, and flares occurred at least 8 days after vaccination. Multivariable analysis showed that high SLEDAI and anti-dsDNA antibodies were associated with flares. The vaccine type, neutralizing antibody titer, and adverse reaction frequency did not affect flares. Therefore, residual disease activity before vaccination increases flare risk.

Systemic lupus erythematosus mimicking retinal migraine: a case report.

BACKGROUND: Retinal migraine is a diagnosis of exclusion and is characterized by repeated episodes of transient monocular blindness associated with migraine. We report a case of systemic lupus erythematosus with acute episodes mimicking retinal migraines. CASE REPORT: A 46-year-old woman with a history of migraine with aura since her 20s and Evans syndrome presented with episodic transient monocular blindness. Retinal migraine was considered as the cause, and migraine prophylaxis initially reduced its frequency. After 5 months, the frequency increased, with chilblain-like lupus lesions on her extremities. Laboratory testing revealed lymphopenia and hypocomplementemia, fulfilling the diagnostic criteria for systemic lupus erythematosus, which may have caused Evans syndrome and transient monocular blindness, mimicking retinal migraines. After intravenous methylprednisolone and rituximab therapy, the transient monocular blindness episodes did not recur. CONCLUSION: Given the clinical presentation, systemic lupus erythematosus should be considered as a cause of transient monocular blindness and should be distinguished from retinal migraine.

Dissociating Autoantibody Responses against Ro52 Antigen in Patients with Anti-Synthetase or Anti-MDA5 Antibodies.

We aimed to dissociate the autoantibody response against the Ro52 protein in patients with anti-synthetase or anti-melanoma differentiation-associated gene 5 (MDA5) antibodies to explore the potential roles of different anti-Ro52 autoantibody responses in disease subclassification. This study used a single-center, prospective myositis cohort involving 122 consecutive patients with anti-synthetase antibodies identified by RNA immunoprecipitation (RNA-IP) and 34 patients with anti-MDA5 antibodies detected using enzyme immunoassay (EIA). Anti-Ro52 antibodies were measured using commercial EIA kits, while anti-Ro/SSA antibodies were identified using RNA-IP. Clinical features and outcomes were stratified according to two different patterns of autoantibody responses against Ro52, including "isolated anti-Ro52", defined by positive anti-Ro52 and negative anti-Ro/SSA antibodies, and "anti-SSA-Ro52", defined by positive anti-Ro52 and anti-Ro/SSA antibodies. Isolated anti-Ro52 positivity was the most prevalent autoantibody response in patients with both anti-synthetase (40/122; 32.8%) and anti-MDA5 antibodies (8/34; 23.5%). Isolated anti-Ro52 or anti-SSA-Ro52 positivity was associated with Gottron's sign in patients with anti-synthetase antibodies, while in patients with anti-MDA5 antibodies, isolated anti-Ro52 positivity was associated with respiratory insufficiency at initial presentation and poor overall survival. Isolated anti-Ro52 positivity could be a potential biomarker for patient stratification; however, the clinical significance of dissociating isolated anti-Ro52 positivity from overall anti-Ro52 positivity was not evident.

Re-emphasising the importance of catheter-based angiography to differentiate polyarteritis nodosa from cutaneous arteritis: Two case reports.

Polyarteritis nodosa (PAN) is a systemic necrotising vasculitis with a poor prognosis, characterised by inflammation and necrosis of medium-sized arteries. PAN patients can present with a wide range of systemic manifestations, whereas cutaneous arteritis (CA) is a restricted manifestation to skin of the disease with a more favourable prognosis. Thus, differentiation between PAN and CA is crucial. Here, we present two cases that were initially diagnosed as CA due to the limited presence of systemic symptoms, but were finally diagnosed as PAN through catheter-based angiography. Although contrast-enhanced computed tomography and computed tomographic angiography are increasingly used to diagnose PAN, neither case had any abnormal findings on these examinations. Our cases therefore underscore that catheter-based angiography is critical for differentiation between PAN and CA, even in cases with limited systemic symptoms.

Effectiveness and safety of rituximab in special types of rheumatoid arthritis.

OBJECTIVES: To elucidate the efficacy and safety of rituximab in special types of rheumatoid arthritis. METHODS: We retrospectively reviewed all patients with rheumatoid arthritis with lymphoproliferative disorder or vasculitis treated with rituximab between April 2010 and June 2022 at Keio University Hospital. We assessed the effectiveness of rituximab using the Disease Activity Score for 28 joints-erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease Activity Index (CDAI), and safety of rituximab during the disease course. We also assessed the glucocorticoid-sparing effects of rituximab. RESULTS: We included eight patients with a history of lymphoproliferative disorder and five patients with rheumatoid vasculitis. They were treated with rituximab without high-dose glucocorticoid. The mean DAS28-ESR and CDAI scores significantly improved 12 months after rituximab administration (DAS28-ESR, 4.7 vs. 2.7, p < .001; CDAI, 16.0 vs. 5.1, p = .006, respectively), and the dose of prednisolone was reduced from a mean of 7.4 mg/day to 4.0 mg/day at 12 months (p = .05) and 3.2 mg/day at the last visit (p = .04). During the mean follow-up period of 52 months, we recorded one recurrence of lymphoproliferative disorder (not B-cell type) in patients with a history of lymphoproliferative disorder and remarkable improvement of skin ulcers in patients with vasculitis. CONCLUSION: B-cell depletion by rituximab may be a useful treatment option for patients with lymphoproliferative disorder and rheumatoid vasculitis.

Sarcopenia in patients with rheumatic musculoskeletal diseases.

AIM: To investigate the impact of high-dose glucocorticoid therapy on sarcopenia in hospitalized patients with rheumatic musculoskeletal diseases (RMDs). METHODS: We included patients with RMDs who were hospitalized between 2020 and 2022 for remission induction treatment and collected information on skeletal mass index (SMI) before high-dose glucocorticoid therapy and 1 month later. We divided the patients into 2 groups according to the progression of sarcopenia, defined as a >10% decrease in SMI, and compared their clinical characteristics. RESULTS: Forty-nine patients were included in this analysis. The mean age was 53.3 years, 73.5% were female, and the mean SMI was 5.3 kg/m2 . Before treatment, 83.7% had already met the definition of sarcopenia, and 57.1% experienced further sarcopenia progression after 1 month of high-dose glucocorticoid treatment. Patients with sarcopenia progression were predominantly male (P = 0.025), had a higher body weight (P = 0.048), and showed a higher SMI than those without sarcopenia at baseline (P = 0.008). Multivariable analysis revealed that body weight increase from 0 to week 1 of high-dose glucocorticoid treatment was associated with sarcopenia progression (odds ratio: 0.22, 95% CI: 0.04-0.61, P = 0.007) with a cut-off of -1.8 kg. During a mean observation period of 30.2 days, the incidence of infection was significantly higher in patients with progressive sarcopenia (P = 0.042). CONCLUSIONS: One-month hospitalization with high-dose glucocorticoid therapy is associated with sarcopenia progression in patients with RMDs. An early decrease in body weight can be used to predict muscle volume loss.

Successful treatment of refractory enteritis and arthritis with combination of tumour necrosis factor and interleukin-6 inhibition in patients with ulcerative colitis.

An 18 year-old man with autoimmune hepatitis-primary sclerosing cholangitis-overlap syndrome and ulcerative colitis was admitted due to relapsed enteritis and polyarthritis after cessation of infliximab. Colonoscopy and articular ultrasonography revealed large ulcers in the colon with crypt abscess in the specimens and active enthesitis and synovitis, respectively. His intestinitis was improved with golimumab but arthritis was persistent. Golimumab was switched to secukinumab, which was effective for arthritis. However, colitis was flared resulting in total colorectal resection. One month after colectomy, polyarthritis was relapsed. Tocilizumab ameliorated arthritis but enteritis emerged again, and switching tocilizumab to adalimumab improved enteritis but arthritis exacerbated. Finally, we restarted tocilizumab for arthritis with continued adalimumab for enteritis. The dual cytokine blocking strategy, tumour necrosis factor-α and interleukin-6 inhibition, subsided both of his refractory enteritis and arthritis and maintained remission for more than 3 years without any serious adverse event. Our case suggests that enteritis and arthritis in inflammatory bowel disease may be different in pathophysiology and raises the possible usefulness of simultaneous inhibition of two inflammatory cytokines in such cases.

A severe cerebral infarction associated with giant cell arteritis, which developed during tocilizumab therapy and was successfully treated with intravenous cyclophosphamide.

Giant cell arteritis (GCA) is a large vessel vasculitis that primarily involves aorta and its major branches. Cerebral infarction is a serious complication that can occur secondary to GCA in up to 3% of patients with a mortality rate of over 50%. Due to the rarity of this severe complication, no therapeutic strategies are currently available. Furthermore, despite the recent progress in molecular-targeted therapy for GCA, it remains unknown whether tocilizumab is effective for severe ischemic complications such as cerebral infarction. The accumulation of individual cases in which this fatal complication could be treated is apparently required to build a better management of the disease. We present our case of GCA that developed severe cerebral infarction during high-dose glucocorticoid and tocilizumab therapy, and its symptoms and image findings were improved by switching to intravenous cyclophosphamide. Our case suggests that an intensive immunosuppressive therapy, including cyclophosphamide, may be necessary to stabilise this fatal complication of GCA.

Deep remission within 12 months prevents renal flare and damage accrual in lupus nephritis.

OBJECTIVES: To evaluate the significance of achieving deep remission by induction therapy in lupus nephritis (LN) patients. METHODS: We assessed consecutive patients undergoing induction therapy for active LN. Achievement of complete renal response (CR) was defined as a urine protein creatinine ratio (UPCR) ≤0.5 g/gCr, and deep remission (DR) was defined as a UPCR ≤0.15 g/gCr with stabilisation of serum creatinine levels assessed every 2-3 months. We compared renal flare and damage accrual rates among patients with CR, CR without DR, and DR at 3, 6, and 12 months and later. RESULTS: Fifty-nine Asian patients were enrolled, and the median observation period was 48.6 months. Of these, 55 patients achieved CR, and 33 achieved DR within 12 months of receiving induction therapy. The patients with DR within 12 months experienced a significantly lower rate of subsequent renal flare (p<0.001) and damage accrual (p=0.046) than those without CR, those with DR after 12 months, and those with no DR but CR within 12 months. In addition, younger age, shorter disease duration, lower urine protein at baseline, and earlier renal response were associated with DR within 12 months. CONCLUSIONS: Achievement of DR within 12 months after induction therapy should be a treatment target for active LN, as it has implications for preventing renal flare and damage accrual.

Differences in the strength of inhibition of interleukin-6 signalling by subcutaneous sarilumab and tocilizumab in rheumatoid arthritis patients.

OBJECTIVES: To assess differences in the strength of inhibition of IL-6/STAT3 signalling induced by subcutaneously (sc) administered tocilizumab (TCZ) and sarilumab (SAR). METHODS: Data were collected on patients with rheumatoid arthritis (RA) who achieved low disease activity (Clinical Disease Activity Index [CDAI]≤10) following treatment with weekly or bi-weekly administration of 162 mg sc of TCZ (TCZ qw group, n=8; TCZ q2w group, n=8), bi-weekly doses of 200 mg sc of SAR (SAR q2w group, n=7), or MTX (n=8) as a control. The clinical characteristics of each group were collected, and the serum concentrations of IL-6 and soluble IL-6 receptor (sIL-6R) were measured using ELISA. Whole blood samples from each group were stimulated with 100 ng/ml of IL-6. The proportion of phosphorylated (p)STAT3-positive CD4+ T cells was measured using phosflow cytometric analysis. RESULTS: The proportion of pSTAT3-positive CD4+ T cells following stimulation with 100 ng/ml of recombinant human IL-6 was significantly different among the groups (median 1.8% [0.9-3.0] vs. 7.7% [2.9-8.0] vs. 12.5% [11.4-16.6] vs. 71.5% [68.0-78.5] for the TCZ qw, SAR q2w, TCZ q2w, and MTX control groups, respectively; p<0.01 for all comparisons). CONCLUSIONS: SAR 200 mg q2w showed significantly stronger inhibition of IL-6/STAT3 signalling than TCZ sc q2w but weaker inhibition than TCZ sc qw. The results of this study may be useful for adjusting the IL-6 blockade treatment for patients with RA.

Clinical and immunological effects of hydroxychloroquine in patients with active rheumatoid arthritis despite antirheumatic treatment.

OBJECTIVE: To investigate the efficacy and safety of hydroxychloroquine (HCQ) in patients with rheumatoid arthritis (RA). METHODS: Patients with active RA, despite conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), were recruited. HCQ was administered for 24 weeks, in addition to prior treatment. The primary endpoint was the proportion of American College of Rheumatology (ACR) 20 achievement at week 24, compared to that of a propensity score matched historical control group. RESULTS: Sixty patients were enrolled and administered HCQ. We also identified 276 patients as candidates for the historical control group. Propensity score matching yielded 46 patients in each group. The proportion of ACR20 achievements at week 24 was significantly higher in the HCQ group than that in the control group (54.4% vs. 28.3%, P = 0.007). The proportion of ACR50 and ACR70 achievement at week 24 were also higher in the HCQ group than those in the control group (ACR50, 30.4% vs. 4.3%, P = 0.006; ACR70, 17.4% vs. 0%, P = 0.005). Neither hydroxychloroquine retinopathy nor any new safety signal was observed during the study. CONCLUSION: The addition of HCQ to csDMARDs was effective, with no new safety signal in patients with RA.

Decreased chronic kidney disease in rheumatoid arthritis in the era of biologic disease-modifying anti-rheumatic drugs.

Background: We investigated the incidence of chronic kidney disease (CKD) progression and its factors relevant to patients with stable rheumatoid arthritis (RA). Methods: We enrolled consecutive patients with RA who had initiated treatment with a biologic disease-modifying anti-rheumatic drug (bDMARD) at our institution and continued the same drug for >5 years between 2001 and 2016. Patients with CKD at bDMARD initiation were excluded. C-reactive protein (CRP) level, Clinical Disease Activity Index (CDAI) score and estimated glomerular filtration rate were measured every 6 months. Results: We included 423 patients, with 196 on tumour necrosis factor inhibitors, 190 on tocilizumab and 37 on abatacept. Among these patients, 34 (8.0%) progressed to CKD within 5 years. The mean CRP level and CDAI score over 5 years were significantly lower in patients without CKD progression than in those with CKD progression (P < .001 and P = .008, respectively). Multivariable analysis revealed that age at bDMARD initiation [odds ratio (OR) 1.05, P = .002], non-steroidal anti-inflammatory drug use (OR 3.47, P = .004) and mean CRP >0.14 mg/dL (OR 5.89, P = .015) were independently associated with CKD progression, while tocilizumab use was associated with a decreased risk of CKD progression (OR 0.31, P = .027). Conclusions: Controlling inflammation contributes to the inhibition of CKD progression in RA patients.

Presence and Implications of Anti-Angiotensin Converting Enzyme-2 Immunoglobulin M Antibodies in Anti-Melanoma-Differentiation-Associated 5 Dermatomyositis.

OBJECTIVE: Patients with anti-melanoma-differentiation-associated 5 (anti-MDA5)-positive dermatomyositis (DM) share several striking similarities to patients with SARS-CoV-2. Our objective was to assess the prevalence of anti-angiotensin converting enzyme-2 (ACE2) immunoglobulin M (IgM) antibodies, found in patients with severe SARS-CoV-2, in two independent anti-MDA5-positive DM cohorts. METHODS: Anti-ACE2 IgM antibodies were assayed by enzyme-linked immunosorbent assay (ELISA) in two anti-MDA5-positive DM cohorts: a predominantly outpatient North American cohort (n = 52) and a Japanese cohort enriched for new-onset disease (n = 32). Additionally, 118 patients with SARS-CoV-2 with a spectrum of clinical severity were tested for anti-MDA5 antibodies by ELISA. RESULTS: Five of fifty-two (9.6%) North American patients and five of thirty-two (15%) Japanese patients were positive for anti-ACE2 IgM. In the North American cohort, all five patients with anti-ACE2 IgM antibodies had proximal muscle weakness, had interstitial lung disease, were significantly more likely to receive pulse dose methylprednisolone (80% vs 30%, P = 0.043), and had worse forced vital capacity (median 59% predicted vs 78%, P = 0.056) compared with the anti-ACE2-IgM-negative group. In the Japanese cohort, all five anti-ACE2-IgM-positive patients also required pulse dose methylprednisolone, and three of five (60%) patients died. Japanese patients with anti-ACE2 IgM had significantly worse oxygenation, as defined by a lower partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio (233 vs 390, P = 0.021), and a higher alveolar-arterial oxygenation gradient (91 vs 23 mm Hg, P = 0.024) than the IgM-negative group. CONCLUSION: We describe anti-ACE2 IgM autoantibodies in two independent cohorts with anti-MDA5-positive DM. These autoantibodies may be biomarkers for severe disease and provide insight into disease pathogenesis.

Lupus low disease activity state within 12 months is associated with favourable outcomes in severely active systemic lupus erythematosus.

OBJECTIVES: To demonstrate the significance of the time to attain lupus low disease activity state (LLDAS) after remission induction therapy in patients with severely active SLE. METHODS: We enrolled 79 patients starting prednisolone ≥0.4 mg/kg/day for active lupus with a BILAG 2004 index of A ≥ 1 or B ≥ 2, or for severe flare based on the Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI). The time to LLDAS attainment was divided into ≤6, 6-12 and >12 months and non-LLDAS; associations between the timing of LLDAS and flares, damage accrual and ≥50% LLDAS attainment were examined. RESULTS: The mean SLEDAI was 17; median starting dose of prednisolone, 0.95 mg/kg/day; and mean observational period, 39.7 months. Six (7.6%) and 41 (51.9%) patients achieved LLDAS within 6 and 12 months. Patients with a shorter time to LLDAS achievement were more likely to spend ≥50% of the time in LLDAS and had a lower cumulative prednisolone dose; no differences were observed in damage accrual. Patients requiring longer than 12 months to achieve LLDAS had a higher prevalence of thrombocytopenia and those with non-LLDAS had lower renal function and a higher starting dose of prednisolone and steroid pulse therapy than those who achieved LLDAS within 12 months. CONCLUSION: Achieving LLDAS within 12 months of induction therapy may be favourable in patients with severely active SLE. The low frequency of LLDAS attainment in high-risk populations highlights the need for a new strategy for SLE treatment.