The Pretreatment Gut Microbiome Is Associated With Lack of Response to Methotrexate in New-Onset Rheumatoid Arthritis.

OBJECTIVE: Although oral methotrexate (MTX) remains the anchor drug for rheumatoid arthritis (RA), up to 50% of patients do not achieve a clinically adequate outcome. In addition, there is a lack of prognostic tools for treatment response prior to drug initiation. This study was undertaken to investigate whether interindividual differences in the human gut microbiome can aid in the prediction of MTX efficacy in new-onset RA. METHODS: We performed 16S ribosomal RNA gene and shotgun metagenomic sequencing on the baseline gut microbiomes of drug-naive patients with new-onset RA (n = 26). Results were validated in an additional independent cohort (n = 21). To gain insight into potential microbial mechanisms, we conducted ex vivo experiments coupled with metabolomics analysis to evaluate the association between microbiome-driven MTX depletion and clinical response. RESULTS: Our analysis revealed significant associations of the abundance of gut bacterial taxa and their genes with future clinical response (q < 0.05), including orthologs related to purine and MTX metabolism. Machine learning techniques were applied to the metagenomic data, resulting in a microbiome-based model that predicted lack of response to MTX in an independent group of patients. Finally, MTX levels remaining after ex vivo incubation with distal gut samples from pretreatment RA patients significantly correlated with the magnitude of future clinical response, suggesting a possible direct effect of the gut microbiome on MTX metabolism and treatment outcomes. CONCLUSION: Taken together, these findings are the first step toward predicting lack of response to oral MTX in patients with new-onset RA and support the value of the gut microbiome as a possible prognostic tool and as a potential target in RA therapeutics.

Fatal Disseminated Aspergillosis in a Patient with Systemic Lupus Erythematosus.

Patients with systemic lupus erythematosus (SLE) are at increased risk for infection including opportunistic infections. Fungal infection in particular can be difficult to diagnose and treat and often can be life-threatening in the immunocompromised patient. We present a case in which a patient with SLE presented to the hospital with shortness of breath and cough. Throughout the hospital course, the patient's condition continued to decline leading to acute respiratory failure, and eventually, the patient expired. Postmortem autopsy revealed invasive fungal aspergillosis infection involving the heart, lungs, and brain. Earlier diagnosis and treatment with empiric antifungals may improve survival in these patients.

A Case of Multiple Myeloma Misdiagnosed as Seronegative Rheumatoid Arthritis and Review of Relevant Literature.

Multiple myeloma (MM) is a malignant plasma cell proliferation producing large numbers of monoclonal immunoglobulins. Typical MM symptoms include anemia, renal failure, hypercalcemia, and bone pain. Atypical symptoms have rarely been reported in the literature. We report a case of a 58-year-old male who presented with symmetrical inflammatory polyarthritis and was misdiagnosed with seronegative rheumatoid arthritis (RA). After failing many RA treatments and with further workup, the diagnosis of MM was made. This rare manifestation of MM carries a diagnostic challenge and causes a significant delay in treating such patients. Here, we report this unusual initial presentation with review of several cases in the English literature describing similar presentations.

Therapeutic effect of anti-IL-5 on eosinophilic myocarditis with large pericardial effusion.

Eosinophilic myocarditis (EM) is a rare myocardial disease that results from various eosinophilic diseases, such as idiopathic hypereosinophilic syndrome, helminth infection, medications and vasculitis. Patients with EM may present with different severities, ranging from mild symptoms to a life-threatening condition. Diagnosis of EM is a challenge and requires an extensive workup, including endomyocardial biopsy. Treatment options are limited because EM is rare and there is a lack of randomised controlled trials. We report a case of EM that presented as cardiac tamponade, which was initially treated with high-dose prednisone and immunosuppressant medications without significant improvement. Mepolizumab (anti-interleukin (IL)-5 antibody) was then applied, leading to an increased ejection fraction and stabilised cardiac function. This case report shows, for the first time, that mepolizumab has novel effects in treating EM. Our findings suggest that mepolizumab can be used as a steroid-sparing agent for treating EM.

Polyarteritis Nodosa Presenting as Digital Gangrene and Breast Lesion following Exposure to Silicone Breast Implants.

Polyarteritis nodosa (PAN) is a rare systemic necrotizing vasculitis of small and medium sized arteries. We report a case of a 49-year old woman who presented with PAN following exposure to silicone breast implants. Although the relationship between silicone implants and connective tissue diseases has been investigated in the literature, no prior reports were found documenting PAN after silicone mammoplasty. While the pathogenesis of idiopathic PAN is not known yet, responsiveness to immunosuppressive therapy may suggest an immunologic mechanism. More robust research is needed to understand the connection between silicone breast implants and autoimmunity.

Prolonged period of acute bronchitis with late progression to acute respiratory distress syndrome as possible result of influenza A (H1N1) virus infection.

Young adults with underlying medical conditions who are infected with the H1N1 virus are at risk of quickly progressing from mild upper airways infection to severe ARDS within 4 to 5 days after the onset of the illness. Here, we report the case of a 46-year-old morbidly obese and diabetic woman infected with the H1N1 virus who developed acute bronchitis that lasted for 4 weeks and then progressed to ARDS. We discuss the month-long persistence of the H1N1 viral bronchitis and its late progression to ARDS which may reflect prolonged viral activity. Such a prolonged, rather than quick, course of deterioration can cause clinicians to misdiagnose the etiology of the ARDS and may cause the patient to receive a prolonged treatment with steroids to treat bronchitis symptoms. These steroids may cause increased viral replication and promote parenchymal involvement and the development of ARDS.

Clinical pathological characteristics and management of acute respiratory distress syndrome resulting from influenza A (H1N1) virus.

Young adults, especially pregnant woman and patients with pre-existing medical conditions, appear to be at risk for the development of severe acute respiratory distress syndrome (ARDS) from influenza A (H1N1) infection, leading to critical hypoxemia. This may require high ventilator settings, the use of nonconventional modes, and extracorporeal membrane oxygenation in some cases. This severe ARDS may be related to prolonged and virulent viral infection, inducing ongoing aberrant immune responses and leading to extensive lung damage. Duration of antiviral therapy, the timing of steroid introduction, and moving away from standard ventilation techniques in ARDS may be key points in disease management.

Diffuse large B-cell lymphoma with lung involvement in a psoriatic arthritis patient treated with methotrexate.

Non-Hodgkin lymphoma (NHL) occurs in the setting of methotrexate (MTX) therapy for rheumatoid arthritis. However, it has been very rarely reported in subjects with psoriatic arthritis treated with MTX. We report here a case of a 70-year-old woman with psoriatic arthritis who presented with bilateral lung infiltrates, pleural effusion, splenomegaly, and inguinal lymphadenopathy during treatment with MTX. The diagnosis of diffuse large B-cell lymphoma was made by analysis of the pleural fluid via thoracentesis and biopsy of an enlarged inguinal lymph node. Clinicians should consider the possibility of a NHL complicating psoriasis and with MTX therapy in order to prevent treatment delays.

Squamous cell lung cancer presenting with pulmonary lymphangitic carcinomatosis.

Pulmonary lymphangitic carcinomatosis (PLC) refers to the infiltration of lung lymphatic channels with metastatic carcinoma and is associated with a dismal prognosis. PLC accompanies circa 7% of all pulmonary metastases and is most commonly caused by various metastatic adenocarcinomas. Only two cases of PLC due to squamous cell lung carcinoma have been reported to date in the English literature. We report herein a unique case of squamous cell lung carcinoma with lymphangitic spread, displaying bilateral and diffuse bronchial tree involvement that might have been a result of invasion from the pulmonary lymphatics into the bronchial lumen.