Prognosis and prognostic factors of lung cancer complications in patients with rheumatoid arthritis.

AIM: To clarify the prognosis and prognostic factors for lung cancer in patients with rheumatoid arthritis (RA). METHODS: In this retrospective longitudinal study, we investigated the medical records of patients with RA among 1422 patients diagnosed with lung cancer and registered in a hospital-based cancer registry between January 2013 and May 2022. The Kaplan-Meier method and Cox proportional hazards model were used to analyze survival and identify predictive factors. RESULTS: Of 26 patients with RA complicated with lung cancer (median age, 69 years), the 2-year overall survival rates for stages I-II were 90%-100%, and those for stages III-IV were 20%, respectively. Positivity of anti-citrullinated protein/peptide antibody, smoking history, interstitial lung disease, poorly controlled RA, stage III and IV lung cancer, histological types other than adenocarcinoma and squamous cell carcinoma, and RF ≧ 50 IU/mL were associated with increased mortality. After the surgical resection of stage I and II lung cancer, 5 of the 16 patients experienced cancer recurrence after resumption of RA treatment, and the histology of the recurrent cancers was mostly squamous cell carcinoma. CONCLUSIONS: Early detection of lung cancer is needed, especially in patients with RA who have a history of smoking, seropositivity, or interstitial lung disease. Even after surgical resection, it should be noted that squamous cell carcinoma is prone to recurrence.

IL-17A promotes vascular calcification in an ex vivo murine aorta culture.

BACKGROUND: Vascular calcification is characterized by mineral deposition in the vasculature, which is triggered by chronic systemic inflammation, including psoriasis. Psoriasis is an IL-17A-mediated inflammatory skin disease that is associated with exacerbated vascular calcification and high cardiovascular mortality. Although previous studies have shown that IL-17A induces vascular dysfunction in murine psoriasis models, it has not been clarified whether IL-17A induces vascular calcification. In this study, we investigated the potential vascular calcification-inducing effect of IL-17A in an ex vivo culture system. METHODS: Thoracic and abdominal aortas from mice were cultured in a medium supplemented with inorganic phosphate and were treated with inflammatory cytokines (IL-1ß, TNF-α, IL-6, and IL-17A). Vascular calcification was determined using micro-computed tomography (CT) and histological analyses. RESULTS: IL-1ß, TNF-α, and IL-6 did not significantly promote vascular calcification, whereas IL-17A significantly accelerated vascular calcification of the aorta, as indicated by the increased mineralized volume based on micro-CT analysis. Micro-CT and histological analyses also revealed that the promoting effect of IL-17A on vascular calcification was concentration dependent. CONCLUSIONS: IL-17A significantly promoted vascular calcification in ex vivo cultured aortas, which suggests that this mechanism is involved in the increased risk of cardiovascular events in IL-17A-mediated inflammatory diseases.

The "Ant-farm"-like Appearance of Restricted Lower Limb Vasculitis on Fluorodeoxyglucose-positron Emission Tomography.

Restricted lower limb vasculitis is a type of localized muscle vasculitis limited to the lower limbs. The usefulness of fluorodeoxyglucose-positron emission tomography (FDG-PET) for the diagnosis of this entity has not yet been reported. We herein report three patients with a fever and persistent lower limb pain. FDG-PET revealed linear and patchy FDG uptakes in their lower limbs. Combined with magnetic resonance imaging and histological findings, they were diagnosed with lower limb vasculitis. Linear and patchy FDG uptakes are considered to reflect the presence of muscle vasculitis. The characteristic "ant-farm"-like FDG-PET images can be a diagnostic clue for the currently overlooked vasculitis.

Barium-induced pneumatosis intestinalis in a patient with anti-synthetase syndrome.

Pneumatosis intestinalis is defined as the presence of gas in the bowel wall. The combination of the two risks, pre-existing connective tissue diseases and barium contrast examination, may trigger pneumatosis intestinalis, albeit at a low incidence. Clinicians should be aware of the condition for proper differential diagnosis.

Tattoo skin reaction as a skin manifestation of systemic sarcoidosis.

A 41-year-old man presented with itching of the skin surrounding his tattoos, blurred vision, fever, general fatigue, and arthralgia. Physical examination revealed skin bulges confined to the tattoo ink lines. Histological analyses of the skin revealed non-caseating granulomas surrounding the tattoo inks. Together with other clinical manifestations including uveitis, lymph nodes swelling, and elevated serum angiotensin-converting enzyme and lysozyme, he was diagnosed with systemic sarcoidosis. The administration of prednisolone alleviated the sarcoidosis-related symptoms, including skin changes. This case illustrates that skin changes on tattoos can be a presenting manifestation of systemic sarcoidosis and that skin biopsy is useful in early diagnosis.

Severe oral stomatitis due to reactivation of herpes simplex virus type 1 in a methotrexate-treated patient with dermatomyositis.

We herein report a case of a 79-year-old Japanese woman who developed severe oral stomatitis during methotrexate (MTX) treatment for dermatomyositis. She had been treated with MTX (12 mg/week) and prednisolone (5 mg/day) for dermatomyositis for 4 years. She developed painful stomatitis, fever, and pancytopenia. Initially, her symptoms were suspected to be caused by mucosal toxicity of MTX. Therefore, the drug was discontinued, and leucovorin was administered. However, oral stomatitis worsened in a few days, resulting in intolerance of oral ingestion due to severe pain. Polymerase chain reaction revealed the presence of herpes simplex virus type 1 (HSV-1) in oral erosive lesions, and blood examination was positive and negative for anti-HSV IgG and anti-HSV IgM, respectively. Therefore, HSV-1 reactivation-induced oral stomatitis was diagnosed, and acyclovir treatment was started, which promptly improved oral stomatitis. HSV-1 reactivation is usually asymptomatic or results in localized vesicular lesions at the mucocutaneous junction of the lips in immunocompetent individuals. Our case illustrates that HSV-1 reactivation induces severe stomatitis in patients treated with low-dose MTX for autoimmune diseases, not just in those with severe immunosuppressive conditions. Of note, HSV-1 reactivation-induced stomatitis is a diagnostic challenge, especially during MTX treatment.

Effect of Angiotensin II on Bone Erosion and Systemic Bone Loss in Mice with Tumor Necrosis Factor-Mediated Arthritis.

Angiotensin II (Ang II) is the main effector peptide of the renin-angiotensin system (RAS), which regulates the cardiovascular system. The RAS is reportedly also involved in bone metabolism. The upregulation of RAS components has been shown in arthritic synovial tissues, suggesting the potential involvement of Ang II in arthritis. Accordingly, in the present study, we investigated the role of Ang II in bone erosion and systemic bone loss in arthritis. Ang II was infused by osmotic pumps in tumor necrosis factor-transgenic (TNFtg) mice. Ang II infusion did not significantly affect the severity of clinical and histological inflammation, whereas bone erosion in the inflamed joints was significantly augmented. Ang II administration did not affect the bone mass of the tibia or vertebra. To suppress endogenous Ang II, Ang II type 1 receptor (AT1R)-deficient mice were crossed with TNFtg mice. Genetic deletion of AT1R did not significantly affect inflammation, bone erosion, or systemic bone loss. These results suggest that excessive systemic activation of the RAS can be a risk factor for progressive joint destruction. Our findings indicate an important implication for the pathogenesis of inflammatory bone destruction and for the clinical use of RAS inhibitors in patients with rheumatoid arthritis.

Tankyrase (PARP5) Inhibition Induces Bone Loss through Accumulation of Its Substrate SH3BP2.

There is considerable interest in tankyrase because of its potential use in cancer therapy. Tankyrase catalyzes the ADP-ribosylation of a variety of target proteins and regulates various cellular processes. The anti-cancer effects of tankyrase inhibitors are mainly due to their suppression of Wnt signaling and inhibition of telomerase activity, which are mediated by AXIN and TRF1 stabilization, respectively. In this review, we describe the underappreciated effects of another substrate, SH3 domain-binding protein 2 (SH3BP2). Specifically, SH3BP2 is an adaptor protein that regulates intracellular signaling pathways. Additionally, in the human genetic disorder cherubism, the gain-of-function mutations in SH3BP2 enhance osteoclastogenesis. The pharmacological inhibition of tankyrase in mice induces bone loss through the accumulation of SH3BP2 and the subsequent increase in osteoclast formation. These findings reveal the novel functions of tankyrase influencing bone homeostasis, and imply that tankyrase inhibitor treatments in a clinical setting may be associated with adverse effects on bone mass.

Bacteremia Possibly Caused by Helicobacter cinaedi and Associated with Painful Erythema in Rheumatoid Arthritis with Malignant Lymphoma.

We herein report the case of a 69-year-old woman with rheumatoid arthritis (RA) and malignant lymphoma who developed Helicobacter cinaedi bacteremia after starting rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. She had a recurrent fever and painful erythema for 13 months before the diagnosis was made. This delayed diagnosis was attributable to the underlying RA, which typically presents with various cutaneous manifestations and elevated C-reactive protein levels. The erythema on the thighs, abdomen, and left forearm improved following treatment with intravenous aminobenzyl penicillin; she received antibiotics for six weeks. This case emphasizes the importance of recognizing this opportunistic infection in immunocompromised patients.

Treatment of refractory rheumatoid pleural effusion with abatacept.

Rheumatoid pleural effusion is generally responsive to corticosteroids, but refractory cases require consideration of second-line therapy. Here we report the case of a 61-year-old man with rheumatoid arthritis (RA) who developed a large right-sided pleural effusion and was successfully treated with abatacept. Thoracocentesis showed a sterile exudate and an elevated adenosine deaminase level. The methotrexate and etanercept used to treat the RA were withheld initially while he underwent a trial of prednisolone 40 mg/day for the pleural effusion. However, the effusion did not respond to this therapy. Thoracoscopic biopsy of the right pleura revealed fibrotic changes with lymphocyte infiltration mainly composed of CD4+ T cells and B cells but no evidence of malignancy or infection. The patient was started on abatacept and resumed methotrexate. The treatment was effective in our case. Abatacept should be considered as a treatment option in patients with refractory rheumatoid pleural effusion.