Pulmonary arterial hypertension in systemic sclerosis: a national inpatient analysis.

OBJECTIVES: We aim to study the prevalence and epidemiology of pulmonary arterial hypertension in SS, and the impact of PAH on SSc hospitalizations in the United States population. METHODS: We utilized the National Inpatient Sample (NIS) from 2016-2019 to obtain adult hospitalizations with the primary/secondary diagnosis of SSc and coexistent PAH (SSc-PAH). Epidemiological variables, mortality rates, and secondary outcomes were studied including pulmonary embolism, atrial flutter, atrial and ventricular fibrillation, pneumonia, sepsis, cardiac arrest and cardiac & renal failure, and ventilator requirement. Healthcare burden was estimated from total hospital charges (THC) and length of stay (LOS). Statistical analysis was performed on STATA 16.1, using linear and logistic regression analyses. RESULTS: Out of 126,685 adult systemic sclerosis hospitalizations, 16.89% had PAH (SSc-PAH). The SSc-PAH group had significantly more females (85.4 % vs. 83.8%) and higher mean age (64.85±13.29 vs. 62.56±14.51). More African Americans were in this group than in the control group (19.5% vs. 14.6, p-value<0.001) while Whites (61.3% vs. 65.6%, p<0.001) and Asians (18.0 % vs. 2.8%, p<0.001) were less common. Charlson comorbidity index was higher for the SSc-PAH population (3.42 vs. 2.94, p-value<0.001). SSc-PAH group had a higher adjusted odds ratio (aOR) for mortality (aOR: 1.39, p<0.001), increased LOS (6.64 vs. 6.0 days, p<0.001) increased THC ($83,813 vs. $71,016, p <0.001). For the SSc-PAH group, there were also significantly higher odds of cardiac failure (aOR 3.13), ventilator requirement (aOR 2.15), cardiac arrest (aOR 1.39), kidney failure (aOR 1.63), pulmonary embolism (aOR 1.84), atrial flutter (aOR 1.86) atrial fibrillation (aOR1.56) and pneumonia (aOR 1.22). No significant difference in ventricular fibrillation, sepsis, or respiratory failure was noted. CONCLUSION: Pulmonary arterial hypertension in SSc is associated with worse outcomes in terms of mortality and morbidity, and higher healthcare burden compared to SSc without PAH. Also, PAH disproportionately affects White, African American & Asian populations. There remains a pressing need to continue efforts for early diagnosis and management of PAH in SSc patients.

Nationwide Analysis of Adult-Onset Still Disease With and Without Hemophagocytic Lymphohistiocytosis.

INTRODUCTION: Adult-onset Still disease (AOSD) is a rare inflammatory condition with a monophasic, intermittent, or chronic clinical course, and a subset may experience life-threatening complications such as hemophagocytic lymphohistiocytosis (HLH). This study aims to characterize concurrent AOSD and HLH and identify variables independently associated with in-hospital death. METHODS: We performed a medical records review of AOSD with and without HLH from the 2016-2019 National Inpatient Sample database. We performed a multivariable logistic regression analysis for in-hospital death. Results were reported as adjusted odds ratios (ORadj). RESULTS: There were 5495 hospitalizations with AOSD, of which 340 (6.2%) had HLH. Thirty (9.0%) of the combined AOSD and HLH group died in the hospital compared with 75 (1.5%) of those without HLH. Multivariable analysis in AOSD inpatients showed that disseminated intravascular coagulation (ORadj 6.13), hepatic failure (ORadj 7.16), infection (ORadj 3.72), respiratory failure (ORadj 6.89), and thrombotic microangiopathy (ORadj 14.05) were associated with higher odds of death. However, HLH itself was not an independent predictor of mortality in AOSD population. CONCLUSIONS: HLH occurred in a small minority of inpatients with AOSD. HLH itself was not an independent risk factor for in-hospital death. Disseminated intravascular coagulation, hepatic failure, infection, respiratory failure, and thrombotic microangiopathy were associated with higher odds of in-hospital death in AOSD. Better awareness of these life-threatening complications may improve hospital outcomes.

A Severe Case of Overlap of Morphea and Eosinophilic Fasciitis after Burn Injuries.

Background: Generalized morphea is a rare fibrosing skin illness that progresses from erythematous, violet-colored skin patches to sclerotic plaques. Another uncommon immune-mediated connective tissue disease called eosinophilic fasciitis (EF) evolves to cause sclerosis and woody skin induration. The coexistence of the two is extremely rare and has a poorer prognosis. Our case report is one of the first to report burn injuries as a trigger factor for EF and generalized morphea overlap. Case Presentation. A 36-year-old man presented with acute onset of rapidly progressing skin thickening, tender edema, and skin contractures involving all extremities, shortly after enduring burn injuries from a gasoline explosion. Workup was remarkable for peripheral eosinophilia, hypergammaglobulinemia, and elevated C-reactive protein. Skin biopsy demonstrated sclerodermoid changes and sclerotic thickening of subcutaneous fibrous septa associated with stromal mucin, dermal perivascular, diffuse lymphoplasmacytic infiltrate with eosinophils, decreased CD34 expression, and increased factor XIIIa. He was subsequently diagnosed with an overlap of generalized morphea and eosinophilic fasciitis. The patient had only limited improvement with steroids, methotrexate, mycophenolate mofetil, and intralesional triamcinolone acetonide injections. Conclusion: Generalized morphea with concomitant EF indicates some degree of therapeutic resistance and poor prognosis with a low quality of life. Burn injuries can be a trigger factor for this overlap syndrome. Prompt identification of at-risk individuals and initiating aggressive management are necessary.

Acetaminophen overdose: analysis of 2018 US nationwide emergency database.

INTRODUCTION: Recognized risk factors for acetaminophen overdose include alcohol, opioids, and mood disorders. The aim of this study is to assess additional risk factors for acetaminophen overdose evaluated in the emergency department (ED). METHODS: A retrospective study was performed using the 2018 US Nationwide Emergency Department Sample (NEDS). All adult ED visits for acetaminophen overdose were included in the study group and those without it were taken as control. STATA, 16.1 was used to perform multivariable logistic regression analysis and adjusted odds ratios (ORadj) were reported. RESULTS: We identified 27,792 ED visits for acetaminophen overdose. Relative to non-acetaminophen ED visits, this group was younger (median age 32 vs 47 years; p < 0.0001), more often female (66.1% vs 57.0%; p < 0.0001), had higher ED charges ($3,506 vs $2,714; p < 0.0001), higher proportion of alcohol-related disorders (15.8% vs 3.5%; p < 0.0001), anxiety disorders (30.2% vs 8.3%; p < 0.0001), cannabis use (8.7% vs 1.4%; p < 0.0001), hematology/oncology diagnoses (13.3% vs 10.9%; p < 0.0001), mood disorders (52.4% vs 7.9%; p < 0.0001), opioid-related disorders (4.1% vs 1.0%; p < 0.0001), and suicide attempt/ideation (12.2% vs 1.1%; p < 0.0001). Multivariable analysis showed alcohol-related disorders (ORadj 2.67), anxiety disorders (ORadj 1.24), cannabis (ORadj 1.63), females (ORadj 1.45), Income Q3 (ORadj 1.09), hematology/oncology diagnoses (ORadj 1.40), mood disorders (ORadj 10.07), opioid-related disorders (ORadj 1.20), and suicide attempt/ideation (ORadj 1.68) were associated with acetaminophen overdose. CONCLUSION: In addition to previously recognized risks, our study demonstrated that cannabis use and hematologic/oncologic comorbidities were more common among acetaminophen-overdose ED visits. These new findings are concerning because of rapid legalization of cannabis and the increasing incidence of cancer worldwide. Additional investigation into these risks should be a priority for clinicians, policymakers, and researchers.

Nationwide analysis of neuromyelitis optica in systemic lupus erythematosus and Sjogren's syndrome.

OBJECTIVE: Neuromyelitis optica (NMO), also known as Devic's disease, is a rare inflammatory demyelinating disorder causing myelitis and optic neuritis. While there have been reports of systemic lupus erythematosus (SLE) and primary Sjogren's syndrome (SS) occurring with NMO, a formal association is not established. We aimed to investigate the occurrence of NMO in SLE and SS patients and study the clinical characteristics and outcomes of NMO and SLE/SS hospitalizations utilizing the national inpatient sample (NIS) database. METHODS: The NIS database from 2016 to 2019 was used to extract data. Adult hospitalizations with the principal or secondary diagnosis of NMO were included. We classified NMO patients with and without concomitant diagnosis of SLE or Sjogren's syndrome. We evaluated and compared the clinical characteristics and outcomes of NMO hospitalizations with and without SLE or Sjogren's syndrome. STATA17 was used for data analysis. We also calculated the odds ratio of NMO in SLE and Sjogren's syndrome. RESULTS: There were a total of 16,360 adult hospitalizations with the principal or secondary discharge diagnosis of NMO. Among all NMO hospitalizations, 1425 (8.71%) had the primary or secondary diagnosis of SLE or SS. The odds of NMO in SLE and Sjogren's syndrome were noted to be 12.29 and 5.56, respectively. NMO with SLE/SS group had higher proportion of females (89.82% vs 79%, P value < 0.001), African Americans (56.63% vs 38.28, P value < 0.001), and Asians (5.73% vs 3.25, P value 0.04). The Charlson comorbidity index was higher for NMO-SLE/SS overlap (2.44 vs 1.28, P value < 0.001). There was no significant difference in overall mortality rates of both groups (2.11% vs 1.2%, P value 0.197). There were significantly higher reported seizures (14.73% vs 6.05, P value < 0.001) and paraplegia (21.75% vs 13.93%, P value < 0.001) in NMO-SLE/SS patients. These patients also had a longer length of stay in comparison to the reference group (7 vs 5 days, P value < 0.001) as well as higher total charges. CONCLUSIONS: NMO patients had a 12-fold higher risk of SLE and 5-fold higher risk of Sjogren's disease when compared to general population. Patients with overlap of NMO and SLE or Sjogren's were predominantly women and were more likely to be African-American. Co-existence of these autoimmune disorders was associated with poor prognosis in terms of higher morbidity for patients and increased health care burden. Key Points • NMO is a rare autoimmune disease seen predominantly in women in the middle age group with low overall mortality. • SLE and Sjogren's have increased odds of NMO in comparison to general population. • NMO patients have high rates of several complications such as paraplegia, quadriplegia, seizures, blindness, sepsis, and respiratory failure with even higher rates of seizures and paraplegia in those with concomitant SLE or Sjogren's.

Familial Association of Granulomatosis With Polyangiitis: A Case-Based Review of Literature.

Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a class of small vessel vasculitis that includes granulomatosis with polyangiitis (GPA), eosinophilic GPA (EGPA), and microscopic polyangiitis (MPA). Despite extensive research, the mechanisms behind AAV etiology remain obscure. The genetics of AAV is a complex area of investigation because of the rarity of familial cases. However, recent multi-center genome-wide association studies (GWAS) have greatly contributed to our understanding of the genetic basis of AAV. In this study, we report a rare occurrence of GPA in two Caucasian family members who presented with similar clinical symptoms and performed a comprehensive review to study the present literature available regarding the heritability of this disease.

IgG4-related disease and isolated retroperitoneal fibrosis: A narrative review.

Retroperitoneal fibrosis (RPF) can occur due to many etiologies and is categorized into idiopathic and secondary. Etiologies of secondary RPF include medications, autoimmune disease, malignancy, and IgG4-related disease (IgG4-RD). Although IgG4-RD usually involves multiple systems synchronically including the pancreas, aorta, and kidneys, it can present with isolated RPF without involvement of other organ systems. Caution must be exercised in these instances as the diagnosis should be confirmed based on specific clinical, radiographic, and histopathologic criteria. Such confirmation can affect the work-up and therapeutic approach as treatment with corticosteroids can lead to remission, both clinically and radiographically.

Hemorrhagic Cardiac Tamponade as a Complication of Limited Cutaneous Systemic Sclerosis.

Cardiac tamponade is an uncommon complication of systemic sclerosis (SSc) with a high mortality rate. Here, we report a case of a 58-year-old patient with limited cutaneous systemic sclerosis (lcSSc), gastroesophageal reflux disease (GERD), diabetes mellitus, pulmonary hypertension (PHTN), and COVID-19 infection, which occurred one month ago, presenting with a large hemorrhagic pericardial effusion and early cardiac tamponade. The patient had an acute onset of progressive dyspnea and anasarca. On examination, she was tachypneic, tachycardic, desaturating on room air, and hypotensive. Pitting edema up to thighs and bilateral basilar crackles were also appreciated. Labs were remarkable for negative troponin, chest X-ray with pulmonary congestion, D-dimer at 6.01, CT angiogram negative, brain natriuretic peptide level at 73 pg/mL, C-reactive protein level at 7.64 mg/dL, normal complement levels, and negative COVID-19 test results. Echocardiography showed early tamponade and a large circumferential effusion with chamber collapse. Right heart catheterization was performed finding PHTN at 54 mmHg. Pericardiocentesis drained 500 mL of the hemorrhagic effusion. Fluid analysis showed RBC at 220,000/uL, WBC at 5000/uL, protein 4.8 g/dL, lactate dehydrogenase level of 1275 U/L, and negative cytology. The patient was treated for serositis from lcSSc flare with mycophenolate mofetil and steroids, and responded very well. Hemorrhagic cardiac tamponade is a very rare phenomenon in limited scleroderma. A recent COVID-19 infection could have served as a trigger factor for our patient's lcSSc in long remission to flare up. Clinicians should maintain a high index of suspicion and a low threshold for intervention when lcSSc patients have an acute onset of cardiac compromise, especially with a history of a recent COVID-19 infection.

Rare Presentation of Disseminated Gout Nodulosis and Chronic Inflammatory Arthritis.

Background: Gout is an inflammatory arthritis caused by monosodium urate (MSU) deposition. Acute gout is a dramatic painful swelling of the joint; however, MSU can deposit in other tissues as well, including skin, gastrointestinal tract, and bones over time. Disseminated tophi in the skin are a rare presentation of gout known as gout nodulosis. We present a case of gout nodulosis with subcutaneous diffuse miliary nodules in nonarticular areas with concurrent findings suggestive of chronic inflammatory arthritis. Case Presentation. A 39-year-old patient presented with intermittent painful swelling in multiple joints with prolonged morning stiffness. On exam, synovitis was present in multiple proximal interphalangeal joints, wrists, elbows, and knees. Chronic raised pearly nodular rash and swellings on extensor aspects of arms, legs, and anterior abdomen were noticeable. He had negative rheumatoid factor and anti-CCP antibody, C-reactive protein of 0.23 mg/dL, erythrocyte sedimentation rate of 37 mm/hr, and uric acid of 10.6 mg/dL. Hand X-rays revealed severe periarticular osteopenia and joint space narrowing in several joints. Musculoskeletal ultrasound showed a double contour sign at multiple joints and a tophaceous deposit over the olecranon fossa. The biopsy of the nodular rash was consistent with tophi. He was diagnosed with chronic tophaceous gout with skin nodulosis and possible overlap of seronegative rheumatoid arthritis given his X-ray findings. Conclusion: This case discusses one of the rare presentations of gout with disseminated gouty tophi in the skin to raise clinical awareness. The clinical dilemma of the overlap of gout and rheumatoid arthritis posing a diagnostic challenge for clinicians is also highlighted.

Nationwide analysis of adult hospitalizations with hematologic malignancies and systemic sclerosis.

Introduction Systemic sclerosis (SSc) is a connective tissue disease with multi-system involvement and it has an increased risk of developing hematologic malignancies. This study aims to report the association between hematologic malignancies with SSc and to characterize in-hospital demographics and outcomes in patients with hematologic malignancies with and without SSc. Methods We performed a retrospective review of pooled data from the National Inpatient Sample (NIS) database from 2016 to 2020. Crude prevalence of hematologic malignancies among hospitalized patients with and without SSc was calculated. Logistic regression was used for statistical significance of differences in prevalence while adjusting for confounders. Demographic characteristics and outcomes of patients with hematologic malignancies with and without SSc was compared. Statistical analysis was done using chi-square and multivariate logistic regression. Results Among all adult hospitalizations, the prevalence of hematologic malignancy was 1.87% compared to 2.66% among patients with SSc (adjusted odds ratio (aOR) 1.52, p <0.01). Relative to the non-SSc group, the SSc group had higher odds of in-patient mortality (OR 1.43; 95% confidence interval (CI) 1.11 - 1.87; p<0.01). The prevalence of lymphoma was 0.71% compared to 1.04% among patients with SSc (aOR 1.6, p < 0.01). Relative to the non-SSc group, the lymphoma-SSc group had similar odds of in-patient mortality (OR 0.93; 95% CI 0.55 - 1.59; p=0.80). The prevalence of leukemia was 0.79% compared to 1.28% among patients with SSc (aOR 1.74, p < 0.01). The leukemia-SSc group had higher odds of in-patient mortality (OR 1.78; 95% CI 1.29 - 2.46; p<0.01). For myeloma, there was no difference in the prevalence in adults with and without SSc (0.4 vs. 0.38%, aOR 0.96, p=0.64) and there was no difference of in-hospital mortality. Conclusions There is a positive significant association between hematologic malignancies including lymphoma and leukemia, and SSc. This association was not seen between myeloma and SSc. There is increased in-hospital mortality of patients with leukemia and SSc.

Angioedema as a Rare Presentation of Systemic Lupus Erythematosus.

Angioedema (AE) is an immune-mediated tissue swelling that can be life-threatening if it compromises the airway. This makes prompt diagnosis and management of the condition excruciatingly important. It can be hereditary or associated with infections, malignancies, and autoimmune diseases. There have been reported cases in the literature where Systemic lupus erythematosus (SLE) patients developed acquired angioedema raising suspicion of a possible association between the two conditions. We describe a case of a patient with no known medical issues, presenting with acute onset of her first episode of angioedema with airway compromise. Because of the rarity of awareness of the possible association of our conditions of interest, there was an inevitable delay in diagnosis and the patient was eventually diagnosed to have SLE and associated acquired angioedema as its first presentation.  This case report highlights the importance of maintaining high suspicion for SLE in patients with an isolated first episode of AE and discusses mechanisms involved in the disease process to shed light on available treatment modalities.

Crystalline Nephropathy With High-Dose Methotrexate in a Patient With Primary CNS Lymphoma: A Case Report.

Methotrexate (MTX) is a folate antimetabolite used in the treatment of several malignancies and rheumatologic diseases. It is metabolized in the liver and excreted via the kidneys. Several adverse effects of MTX have been noted, including bone marrow suppression, mucositis, and hepatic and renal dysfunction. Close monitoring of drug levels, concurrent leucovorin administration, and urinary alkalization with aggressive hydration are some steps taken to prevent these unfavorable outcomes. We describe a case of a patient with primary CNS lymphoma undergoing chemotherapy with high-dose methotrexate (HD-MTX) who developed methotrexate-induced crystalline nephropathy despite preventative measures. Birefringent needle-shaped crystals were demonstrated under polarized light in the urine sample in the setting of acute kidney injury (AKI). The slow decay curve of MTX causing renal and hepatic dysfunction was an indication to start glucarpidase, and a subsequent rapid decline in MTX levels with improvement in AKI was observed. Methotrexate-induced crystalline nephropathy results from damage to the renal tubules, which in most cases is reversible. Patients with a slow decline in MTX levels may be candidates for treatment with glucarpidase, a recombinant form of carboxypeptidase G2, to allow for rapid MTX breakdown and clearance. Hemodialysis is another available treatment option for patients who develop these adverse effects.