Epidemiology, characteristics, and outcomes of adult haemophagocytic lymphohistiocytosis in the USA, 2006-19: a national, retrospective cohort study.

Background: Haemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening syndrome characterized by an excessive inflammatory response. Limited data exist on adult HLH. Methods: In this national, retrospective cohort study, we analysed data from the US National Inpatient Sample database collected between October 1, 2006 and December 31, 2019. Using the International Classification of Diseases (ICD) codes, we identified all adult patients who were admitted non-electively with the diagnosis of HLH. We described demographic characteristics, triggers, and associated conditions. Trends of diagnosis, treatment, and in-hospital mortality were analysed using joinpoint models. In-hospital mortality rates were compared using multivariable logistic regression models that adjusted for demographic characteristics and associated conditions. Finally, we described resource utilization outcomes including cost of hospitalization and length of stay. Findings: We identified 16,136 non-elective adult HLH admissions. The population pyramid showed a bimodal distribution, with peaks in young adults (16-30 years) and older adults (56-70 years). Joinpoint regression analysis revealed a significant increase in HLH incidence per 100,000 admissions over the study period (Average Annual Percent Change [APC] = 25.3%, p < 0.0001), and no significant change in rates of in-hospital mortality (slope = -0.01; p = 0.95) or administration of in-hospital HLH treatment (slope = 0.46, p = 0.20). The most common associated conditions were malignancy (4953 admissions [30.7%]), infections (3913 admissions [24.3%]), autoimmune conditions (3362 admissions [20.8%]), organ transplant status (639 admissions [4%]), and congenital immunodeficiency syndromes (399 admissions [2.5%]). In-hospital mortality was higher in older adults and males. Furthermore, Congenital immunodeficiency syndromes had the worst in-hospital mortality rate (mortality rate 31.1%, adjusted OR 2.36 [1.56-3.59]), followed by malignancies (mortality rate 28.4%, adjusted OR 1.80 [1.46-2.22]), infections (mortality rate 21.4%, adjusted OR 1.33 [1.10-1.62]), other/no trigger (mortality rate 13.6%, adjusted OR 0.73 [0.58-0.92]), autoimmune (mortality rate 13%, adjusted OR 0.72 [0.57-0.92]), and post-organ transplant status (mortality rate 14.1%, adjusted OR 0.64 [0.43-0.97]). The overall mean length of stay was 14.3 ± 13.9 days, and the mean cost of hospitalization was $54,900 ± 59,800. Interpretation: We provide insight into the burden of adult HLH in the USA. The incidence has been increasing and the outcomes remain dismal. This signifies the growing need for the development of updated diagnosis and treatment protocols that are specific to adult HLH. Funding: None.

Bullous herpes zoster masquerading as a bullous pemphigoid flare: A case report.

Herpes zoster (HZ) results from the reactivation of dormant varicella zoster virus (VZV) in the posterior dorsal root ganglia manifesting as painful vesicles along the dermatomal distribution as shingles. The risk of reactivation is higher in immunocompromised patients. Herpes zoster lesions can have varied presentations including bullous forms, may induce BP flare, may co-exist in the same lesions, and should be included in the list of differentials for BP flares not responding to the standard of care. Here, we describe a case of a 74-year-old female with a history of recurrent bullous pemphigoid (BP) flares, who was on mycophenolate mofetil, and presented with skin lesions on her right thigh which were typical for her BP flares. Unlike prior flares, the lesions did not respond to prednisone therapy. Her hospitalization course was complicated by encephalopathy. Intravenous acyclovir was started empirically. Viral cultures and polymerase chain reaction from the lesions came back positive for VZV, but the patient succumbed to her illness shortly afterward.

Trends of chronic lymphocytic leukemia incidence and mortality in the United States: a population-based study over the last four decades.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults, and its incidence is higher in elderly individuals. This study aims to examine the burden of CLL in the United States (US) by exploring the incidence-based rates (IBR) and incidence-based mortality (IBMR) across four decades. RESEARCH DESIGN AND METHODS: CLL incidence data were obtained from the SEER-8 registry, covering 8.3% of the US population. Cases were identified using specific diagnostic codes and excluded if diagnosed on autopsy or death certificate. Age-standardized IBR and IBMR were calculated based on age, sex, and ethnicity/race. Joinpoint Regression Program was used to analyze changing trends in incidence and mortality. RESULTS: Since 2011, males' and females' IBRs declined by -1.72%/year (p = 0.028) and -1.07%/year (p = 0.222), respectively. IBR of patients > 75 years increased by 4.01%/year (p < 0.001) form 1998-2010, then declined by 2.02%/year (p = 0.011). IBR of Blacks increased by 0.96%/year (p < 0.001) throughout the study period. CLL IBMR stabilized at -0.38%/year (p = 0.457) since 2012. Whites' IBMR plateaued at a rate of -0.10%/year (p = 0.857) form 2012-2019, while blacks' IBMR increased by 1.40%/year (p = 0.056) between 2000-2019. CONCLUSIONS: The analysis revealed a decline in CLL incidence since 2013, with stable mortality rates since 2012, indicating advancements in CLL management.

Outcomes of therapeutic plasma exchange in severe autoimmune hemolytic anemia hospitalizations: An analysis of the National Inpatient Sample.

BACKGROUND: Autoimmune hemolytic anemia (AIHA) is characterized by humoral and/or cellular immune-mediated hemolysis of red blood cells. The role of therapeutic plasma exchange (TPE) in AIHA is unclear. STUDY DESIGN AND METHODS: We queried the National Inpatient Sample (NIS) for 2002-2019 to identify hospitalizations with the primary diagnosis of AIHA. We included hospitalizations with the highest severity subclass identified by All Patient Refined Disease Related Group (APR-DRG). We used multivariate regression analysis to compare in-hospital mortality and other relevant in-hospital outcomes between hospitalizations that received TPE and those that did not. RESULTS: We identified 255 weighted hospitalizations in the TPE group and 4973 in the control group. Those in the control group were older (median age 67 vs. 48 years, p < .001) and had a higher prevalence of most comorbidities. The TPE group had higher odds of all-cause in-hospital mortality (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.19-2.11). They also had higher rates of many secondary outcomes, including requiring mechanical ventilation, developing circulatory shock, acute stroke, urinary tract infections, intracranial hemorrhage, acute kidney injury, and requiring new hemodialysis. No significant differences were noted in the rates of acute myocardial infarctions, bacterial pneumonia, sepsis/septicemia, thromboembolic events, and other bleeding events. Furthermore, the TPE group had a higher median length of hospital stay (19 vs. 9 days, p < .001). CONCLUSION: Hospitalizations with severe AIHA that received TPE had higher rates of adverse in-hospital outcomes.

Atypical Peutz-Jeghers Syndrome Presenting With a Huge Jejunojejunal Intussusception in a Young Male: A Case Report.

Intussusception is considered one of the rare causes of intestinal obstruction in adults compared to pediatric patients. It usually presents with non-specific clinical manifestations ranging from mild recurrent abdominal pain to severe acute abdominal pain. The non-specificity of its symptoms makes it difficult to diagnose preoperatively. As 90% of adult intussusceptions are due to a pathological lead point, this prompts the underlying medical condition to be identified. We herein report a rare case of a 21-year-old male with atypical clinical features of Peutz-Jegher syndrome (PJS), presenting with jejunojejunal intussusception as a result of a hamartomatous intestinal polyp. A preliminary diagnosis of intussusception was made after an abdominal computed tomography (CT) scan and was confirmed intraoperatively. Postoperatively, the patient's condition improved steadily, and he was discharged with a referral to the gastroenterologist for further assessment.

Hemophagocytic lymphohistiocytosis in inflammatory bowel disease: a nationwide analysis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening immune dysregulation disease. Patients with inflammatory bowel disease (IBD) can become profoundly immunocompromised due to immunosuppressive therapy, hence increasing the risk of viral infections that can trigger HLH. However, data on the association between IBD and HLH remains limited. We used data from the National Inpatient Sample (2012-2019) utilizing International Classification of Diseases (ICD)-9 or ICD-10 codes to identify individuals with IBD, either Crohn's disease (CD) or ulcerative colitis (UC), and HLH. The primary outcome was to compare the prevalence of HLH among patients with IBD with those without IBD. Secondary outcomes included in-hospital mortality, mean hospital length of stay, and description of HLH-associated triggers in IBD patients. A total of 513,322 hospitalizations included a diagnosis of IBD, 188,297 had UC and 325,025 had CD. Compared to the general population, patients with IBD were older (median age of 52 vs. 49 years, p < 0.05), more likely to be male, and of Asian/Pacific Islander descent, and had a higher median household income. There was also a higher prevalence of liver disease, autoimmune diseases, tobacco abuse, and hypothyroidism (all had p-value of < 0.001) in IBD patients. There were 94 hospitalizations identified with a diagnosis of HLH in IBD patients. Compared to patients without IBD, patients with IBD had increased odds of developing HLH (0.02% vs 0.01%, p-value < 0.001). After adjusting for various demographic characteristics, co-morbidities, and HLH-related conditions, IBD was an independent predictor for developing HLH (adjusted OR, 2.3; 95% CI, 1.847-2.866, p-value of < 0.001). There was no statistical difference between CD and UC in the odds of developing HLH. Compared to IBD patients without HLH, patients with IBD and HLH had a lower mean age at diagnosis (38 vs 52, p-value of < 0.001), higher in-hospital mortality (14.9% vs 1.5%, p-value of < 0.001), and longer mean hospital length of stay (days) (17 vs 5.4, p-value of < 0.001). Prevalence of different HLH-associated illnesses was identified in HLH patient's discharge data. Lymphoma was the most common associated malignancy (18.1%) and cytomegalovirus infection was the most common associated infection (16.0%). Our population-based study suggests that IBD is independently associated with developing HLH. Early recognition of IBD patients presenting with features suggestive of HLH is warranted to aide early diagnosis and aggressive treatment.

Acute venous thromboembolic events in patients with monoclonal gammopathy of undetermined significance: An analysis of the National Inpatient Sample.

BACKGROUND: Monoclonal Gammopathy of Undetermined Significance (MGUS) is a premalignant plasma cell disorder which despite being clinically silent carries an increased risk of venous thromboembolism (VTE). We conducted a population-based study to investigate the risk of VTE in these patients. METHODS: We utilized the National Inpatient Sample (NIS) for the year 2016 to compare the incidence of acute VTE between patients who carry the diagnosis of MGUS and those who don't. We excluded hospitalizations with age < 18 years and those that had a diagnosed lymphoma, leukemia, solid malignancy, or other plasma cell dyscrasia. We utilized the ICD-10-CM coding system to search the database for codes of VTE, MGUS, and other comorbid conditions. Multivariate logistic regression models were used for comparative analysis adjusting for demographic characteristics and comorbidities. Baseline comorbidities were described as frequencies and proportions for categorical variables and as medians with interquartile ranges for continuous variables. RESULTS: A total of 33,115 weighted hospitalizations were included in the MGUS group. These were compared to 27,418,403 weighted hospitalizations without the diagnosis of MGUS. The MGUS group had higher odds of composite venous thromboembolism (adjusted OR 1.33, 95 % CI 1.22-1.44), deep vein thrombosis (adjusted OR 1.46, 95 % CI 1.29-1.65), and pulmonary embolism (adjusted OR 1.22, 95 % CI 1.09-1.37). CONCLUSION: Patients with MGUS had increased odds of developing acute venous thromboembolism compared to patients with no history of MGUS.

Isolated Tuberculosis of the Cervical Vertebrae.

Tuberculosis (TB) is a highly infectious disease that primarily affects the lungs, but extrapulmonary affection can occur with lymphatic or hematogenous spread. Skeletal affection commonly involves the spine, but cervical vertebral affection is rare. We report a 23-year-old female patient who presented to the hospital with diffuse limb weakness and neck pain as the only complaints. MRI of the cervical spine revealed a peripherally enhancing lesion arising from the posterior aspects of the cervical vertebrae with compressive myelopathy. She underwent surgical decompression and was noted to have caseous drainage during the procedure. She was started promptly on anti-tuberculous therapy after she had a positive interferon-gamma release assay. Late culture results confirmed isolated cervical TB of the vertebrae as the diagnosis. Prompt awareness and initiation of treatment for vertebral TB are necessary as clinical presentation can mimic other infectious and malignant etiologies.

Relapsed chronic lymphocytic leukemia with a cardiac mass: A case report.

Chronic lymphocytic leukemia (CLL) is the most common hematological malignancy in the USA. Extra-medullary disease is very rare and is not well characterized. In practice, clinically significant cardiac or pericardial involvement by CLL is extremely rare with only a few case reports in literature. We report a 51-year-old male patient with a past medical history of CLL in remission, who presented with fatigue, dyspnea on exertion, night sweats and left supraclavicular lymphadenopathy. Laboratory investigations were notable for leukopenia and thrombocytopenia. Due to high suspicion of an underlying malignant process, a full body computerized tomography (CT) scan was obtained and showed an 8.8 cm soft tissue mass-like lesion occupying the majority of the right atrium and extending into the right ventricle, with probable pericardial involvement. Enlarged left supraclavicular and mediastinal lymph nodes were also present and had a mild mass effect on the traversing left internal thoracic artery and left pulmonary artery. A transesophageal echocardiogram and cardiac magnetic resonance imaging (MRI) were done to better characterize the cardiac mass. They confirmed a large infiltrating mass (measuring 10 × 7.4 cm) in the right atrium and ventricle, extending into the inferior vena cava inferiorly and coronary sinus posteriorly. A left supraclavicular excisional lymph node biopsy was performed and histopathology was consistent with Small Lymphocytic Lymphoma (SLL)/CLL. This case represents one of the few known cases of cardiac extramedullary-CLL presenting with an isolated cardiac mass. Further studies are needed to characterize the course of the disease, prognosis and optimum management along with the role of surgery.

Pheochromocytoma with fever and iron deficiency anemia.

Pheochromocytoma is a rare neuroendocrine tumor of the adrenal gland. With its heterogeneous clinical presentation, its diagnosis is frequently elusive. This case focuses on an unusual presentation of pheochromocytoma without the typical picture of hypertension, palpitations, and headaches. A few similar reports suggest a role of interleukin-6 production by the tumor in this presentation, indicating that not all symptoms and signs of the disease are due to catecholamine secretion.

Caplacizumab in the successful management of cardiac involvement in thrombotic thrombocytopenic purpura.

Cardiac involvement is well documented in thrombotic thrombocytopenic purpura (TTP). Management remains challenging due to thrombocytopenia. Caplacizumab is a novel medication in TTP, but questions remain on its overall benefit in TTP patients. We report a 76-year-old woman who was admitted for non-ST segment elevation myocardial infarction, left systolic ventricular dysfunction, severe hemolytic anemia, and thrombocytopenia suggestive of TTP (PLASMIC score 7). Therapeutic plasma exchange (TPE) and caplacizumab were started alongside an immunosuppressive regimen. After 3 days of treatment, repeat echocardiography showed complete resolution of left ventricular dysfunction. We were able to stop TPE and start aspirin on the fourth day after normalization of platelet count. Our report outlines the potential benefits of caplacizumab for the time-sensitive management of acute coronary syndrome and the compromised volume status of heart failure patients, with early platelet recovery and lower duration of TPE.

Prognostic significance of serum progranulin level in de novo adult acute lymphoblastic leukemia patients.

Increased expression of progranulin (PGRN) has been reported in some hematological cancers, but limited information regarding its significance in acute lymphoblastic leukemia (ALL) is available. This study involved 60 subjects (40 de novo adult ALL patients and 20 controls). Serum PGRN level was measured by enzyme-linked immunosorbent assay and was correlated with patient outcome. Serum PGRN level was significantly higher in patients than controls. Serum PGRN level did not correlate with age, total leukocytic count, hemoglobin, platelets, absolute blast count in peripheral blood, lactate dehydrogenase, percent of blasts in bone marrow, gender, comorbidities, the presence of central nervous system infiltration, ALL phenotype, cytogenetics and risk of the disease. High serum PGRN level was not associated with inferior overall survival (OS) on univariate analysis. Regarding cumulative incidence of relapse (CIR) and disease-free survival (DFS), high PGRN level was associated with poor results on univariate analysis. Moreover, it tended to be independent risk factor on multivariate analysis for CIR but was not an independent predictor of inferior DFS. Serum PGRN level is significantly elevated in de novo adult ALL patients and may be used as a predictor of increased relapse risk.