BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease, which is mainly characterized by joint swelling, pressure pain and joint destruction. Some patients may suffer from a variety of serious complications, which require prompt diagnosis and treatment. Otherwise, the patient condition may deteriorate rapidly, leading to premature death.
OBJECTIVE: We reported a case of RA combined with hyperferritinemic syndrome and capillary leak syndrome (CLS) that was successfully treated with tocilizumab (TCZ), with the aim of improving diagnostic ideas for clinicians and consequently improving the diagnosis and treatment of the hyperferritinemic syndrome and CLS.
METHODS: A 55-year-old female patient was admitted to the Department of Infectious Diseases of our hospital due to \"recurrent fever for more than 1 month and aggravation for 3 days.\" The patient was diagnosed with fever of unknown origin (lung infection?) and received anti-infective therapy with large encirclement of anti-bacterial, antifungal and empirical anti-tuberculosis successively during hospitalization in the Department of Infectious Diseases. Yet her condition continues to progress. The patient was eventually diagnosed with RA combined with hyperferritinemic syndrome and CLS. Then she received glucocorticoids (GC) (160 mg qd) combined with intravenous immunoglobulin (IVIG, 20 g/d, for 3 days). We considered that the patient also had an overwhelming proinflammatory cytokine storm, so she received a strong anti-inflammatory treatment with TCZ (400 mg qm). The patient symptoms and follow-up chest CT showed significant improvement following treatment.
CONCLUSIONS: TCZ has good efficacy in the treatment of RA combined with hyperferritinemic syndrome and CLS and is expected to be a promising treatment.

UNASSIGNED: Upon re-examination of our human history, evolutionary perspectives, and genetics, a prevailing iron deficiency phenotype appears to have evolved to protect the human race from extinction.
UNASSIGNED: In this review, we summarize the evolutionary and genetic perspectives pointing towards the hypothesis that low iron mitigates infection. The presence of infection promotes the generation of resistance alleles, and there are some evolutionary and genetic clues that suggest the presence of an iron deficiency phenotype that may have developed to protect against infection. Examples include the relative paucity of iron overload genes given the essential role of iron, as well as the persistence of iron deficiency among populations in spite of public health efforts to treat it. Additional examination of geographic areas with severe iron deficiency in the setting of pandemics including H1N1, SARS, and COVID-19 reveals that areas with higher prevalence of iron deficiency are less affected. RNA viruses have several evolutionary adaptations which suggest their absolute need for iron, and this dependency may be exploited during treatment.
UNASSIGNED: RNA viruses pose a unique challenge to modern healthcare, with an average of 2-3 new pathogens being discovered yearly. Their overarching requirements for iron, along with human evolutionary and genetic adaptations which favored an iron deficiency phenotype, ultimately suggest the potential need for iron control in these infections.

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Generalized pruritus can be the manifestation of many dermatologic and systemic diseases. However, it has been reported infrequently in the literature as a consequence of hyperferritinemia. We report the case of a 70-year-old male presenting to dermatology due to generalized pruritus in the absence of a rash, who was subsequently found to have a significantly elevated serum ferritin and transferrin saturation with otherwise normal iron studies. Hereditary hemochromatosis was ruled out on genetic testing; however, etiologies of secondary iron overload including alcohol use disorder and non-alcoholic fatty liver disease were present. The patient had minimal relief of his pruritus with topical corticosteroids, oral prednisone, and moisturizers. The only successful treatment was phlebotomy which resulted in complete resolution of his long-standing pruritus. We present the fifth case of generalized pruritus associated with hyperferritinemia, treated successfully with phlebotomy.

This scoping review aimed to elucidate and summarize the predictive role of serum ferritin in critical pediatric illness. The Preferred Reporting Items for Systematic reviews and Meta-Analyses methodology was employed to conduct a scoping review of 5 databases (MEDLINE, CENTRAL, ProQuest, ScienceDirect, and Epistemonikos) from the date of inception through January 24, 2022. Primary research studies involving subjects aged <18 years and serum ferritin levels were screened and reviewed independently following an a priori defined protocol. Of the 1,580 retrieved studies, 66 were analyzed. Summary statistics of serum ferritin levels for overall and condition-specific studies were reported in 30 (45.4%) and 47 studies (71.2%), respectively. The normal range was defined in 16 studies (24.2%), whereas the threshold was determined in 43 studies (65.1%). A value of <500 ng/mL was most often the upper limit of the normal range. Serum ferritin as a numerical variable (78.9%) was usually significantly higher (80.8%) in the predicted condition than in controls, while as a categorical variable with preset thresholds, ferritin was a significant predictor in 84.6% of studies. A total of 22 predictive thresholds predicted mortality (12 of 46 [26.1%]), morbidity (18 of 46 [39.1%]), and specific (16 of 46 [34.8%]) outcomes in 15 unique conditions. Increased precision in serum ferritin measures followed by close attention to the threshold modeling strategy and reporting can accelerate the translation from evidence to clinical practice.

BACKGROUND: Macrophage activation syndrome (MAS) is a severe and under-recognized complication of rheumatologic diseases. We describe a patient who presented with rapidly progressive, refractory MAS found to have anti-MDA5 antibody Juvenile Dermatomyositis (JDM) as her underlying rheumatologic diagnosis.
METHODS: We describe a 14-year-old female who at the time of admission had a history of daily fevers for 6 weeks and an unintentional sixteen-pound weight loss. Review of systems was significant for cough, shortness of breath, chest pain, headaches, sore throat, muscle aches, rash, nausea, and loss of appetite. An extensive initial workup revealed findings consistent with an autoimmune process. While awaiting results of her workup she had clinical decompensation with multi-organ system involvement including pancytopenias, interstitial lung disease, hepatitis, cardiac involvement, gastrointestinal distension and pain, feeding intolerance, extensive mucocutaneous candidiasis, and neuropsychiatric decline. Due to her decompensation, significant interstitial lung disease, and likely underlying rheumatologic condition she was started on high dose pulse steroids and mycophenolate. An MRI was performed due to her transaminitis and shoulder pain revealing significant myositis. Intravenous immunoglobulin was then initiated. The myositis antibody panel sent early in her workup was significant for anti-MDA5 and anti-SSA-52 antibodies. Despite high dose pulse steroids, mycophenolate, and IVIG, her disease progressed requiring escalating therapies. Ultimately, she responded with resolution of her MAS as well as significant and steady improvement in her feeding intolerance, interstitial lung disease, cardiac dysfunction, myositis, arthritis, and cutaneous findings.
CONCLUSIONS: JDM in the pediatric patient is rare, as is MAS. In patients with complex rheumatologic conditions and lack of response to treatment, it is important to continually assess the patient\'s clinical status with MAS in mind, as this may change the treatment approach. Without proper recognition of this complication, patients can have a significant delay in diagnosis leading to life-threatening consequences.

Hemophagocytic lymphohistiocytosis (HLH) is an uncommon fatal disease of otherwise normal but hyperactive lymphocytes and histocytes. HLH could be primary (hereditary) or secondary (acquired). Fever, hepatosplenomegaly, lymphadenopathy, and neurologic dysfunction are among the common symptoms of HLH. The diagnosis of HLH is based on clinical and biochemical findings. We report here a case of a patient infected with the dengue virus who developed HLH during hospitalization. A 63-year-old female known case of asthma on inhalers, chronic hepatitis B virus, gastritis on proton pump inhibitors, and hemoglobin H disease presented to the emergency department (ED) with a history of high-grade fever (highest recorded temperature 40° C/ 104° F), which was relieved partially by antipyretics, generalized fatigability, body aches, headache and mosquito bites for four days. The physical examination was significant for hepatomegaly of 4 cm below the right costal margin. Investigations revealed pancytopenia with elevated ferritin levels (> 40000 µg/L). Viral serology was positive for dengue NS1 antigen. After hematology consultation, a bone marrow biopsy was done, which showed trilineage hematopoiesis with increased histiocytes and occasional hemophagocytosis. Given that the patient was clinically stable and there was a clear triggering condition, we opted for supportive measures rather than HLH-specific therapy. The patient was given 2 units packed red blood cells for anemia. On the following days, the patient has no recurrence of fever, with marked improvement in the biochemical profile including ferritin level (1165 µg/L). HLH is a deleterious disease with a high fatality rate, which requires the clinician to have a low threshold for suspicion in the differentials of children and adults with symptoms of persistent fever, hepatosplenomegaly, and cytopenia. Dengue-associated HLH diagnosis is challenging, but it is very important to be recognized, as early recognition is associated with better outcomes. Physicians must work in collaboration with pathologists and microbiologists for the proper diagnosis.

BACKGROUND: Adult onset Still\'s disease (AOSD) is a rare inflammatory disorder that classically presents with high spiking fevers, evanescent rash, and arthritis. The diagnosis is one of exclusion and can be further complicated by atypical presentations, particularly in elderly patients in whom AOSD is very rare.
METHODS: A case of AOSD in a 73-year-old woman with a non-classic presentation, leading to delayed diagnosis and management, is presented along with a review of the English literature for AOSD cases in elderly people over 70 years of age. Thirty nine case reports and series were identified and the current case was added, totaling 42 individual cases. Significant findings included a four-times higher prevalence in females, a higher prevalence of macrophage activation syndrome despite lower mortality, the presence of pruritic rash in almost one fifth of the cases, and high prevalence of delayed diagnosis.
CONCLUSIONS: AOSD in the elderly may vary from the classic criteria described in the medical literature and may lead to delayed diagnosis and management. Further evaluation and better characterization of AOSD in the elderly remains an area of interest.

Aboriginal and Torres Strait Islander Australians (Indigenous Australians) suffer some of the highest rates of chronic kidney disease (CKD) in the world. Among Indigenous Australians in remote areas of the Northern Territory, prevalence rates for renal replacement therapy (RRT) are up to 30 times higher than national prevalence. Anemia among patients with CKD is a common complication. Iron deficiency is one of the major causes. Iron deficiency is also one of the key causes of poor response to the mainstay of anemia therapy with erythropoiesis-stimulating agents (ESAs). Therefore, the effective management of anemia in people with CKD is largely dependent on effective identification and correction of iron deficiency. The current identification of iron deficiency in routine clinical practice is dependent on 2 surrogate markers of iron status: serum ferritin concentration and transferrin saturation (TSAT). However, questions exist regarding the use of serum ferritin concentration in people with CKD because it is an acute-phase reactant that can be raised in the context of acute and chronic inflammation. Serum ferritin concentration among Indigenous Australians receiving RRT is often markedly elevated and falls outside reference ranges within most national and international guidelines for iron therapy for people with CKD. This review explores published data on the challenges of managing anemia in Indigenous people with CKD and the need for future research on the efficacy and safety of treatment of anemia of CKD in patients with high ferritin and evidence iron deficiency.

Several reports have determined that changes in white blood cell counts and inflammatory biomarkers are related to disease outcome of coronavirus disease 2019 (COVID-19) and they can be utilized as prognostic biomarkers. For introducing a factor as a diagnostic/prognostic biomarker, diagnostic test accuracy (DTA) systematic review and meta-analysis are recommended. For the first time, we aimed to determine the accuracies of white blood cell counts and inflammatory biomarkers for prognosis of COVID-19 patient\'s outcome by a DTA meta-analysis. Until August24, 2020, we searched Web of Sciences, Scopus, and MEDLINE/PubMed databases to achieve related papers. Summary points and lines of included studies were calculated from 2×2 tables by bivariate/hierarchical models. Critical condition and mortality were considered as outcomes. A total of 13387 patients from 28 studies were included in this study. Six biomarkers containing leukocytosis, neutrophilia, lymphopenia, increased level of C-reactive protein, procalcitonin (PCT), and ferritin met the inclusion criteria. Analysis of the area under the curve (AUCHSROC) indicated that the PCT was the only applicable prognostic biomarker for critical condition and mortality (AUCHSROC=0.80 for both conditions). Pooled-diagnostic odds ratios were 6.78 (95% CI, 3.65-12.61) for prognosis of critical condition and 13.21 (95% CI, 3.95-44.19) for mortality. Other biomarkers had insufficient accuracies for both conditions (AUCHSROC< 0.80). Among evaluated biomarkers, only PCT has good accuracy for the prognosis of both critical condition and mortality in COVID-19 and it can be considered as a single prognostic biomarker for poor outcomes. Also, PCT has more accuracy for the prognosis of mortality in comparison to critical condition.