Fiebre de origen desconocido como forma de presentación de la enfermedad de Still del adulto / Fever of unknown origin as a form of presentation of an adult-onset Still's disease

Introducción: La enfermedad de Still del adulto es una enfermedad reumática, inflamatoria, sistémica y crónica cuya prevalencia en la población caucásica se estima en 1 caso por cada 100 000 adultos Objetivo: Presentar un paciente adulto joven, con una fiebre de origen desconocido como forma de presentación de la enfermedad de Still del adulto. Caso clínico: Paciente de 29 años de edad con antecedente de fiebre reumática, con un ingreso hospitalario anterior; que presentó un cuadro febril no infeccioso, de 50 días de duración, al cual no se le determinó la causa. Un año después reapareció la fiebre, de similares características, asociada a poliartralgia, hepatoesplenomegalia, anemia, hiperferritinemia, neutrofilia, factor reumatoideo negativo y se constató un cuadro de pericarditis durante el ingreso. Se realizó el diagnóstico de enfermedad de Still del adulto, por exclusión. Se inició tratamiento con esteroides, desapareció la fiebre en las primeras 24 horas y el paciente tuvo una evolución favorable. Conclusiones: La enfermedad de Still del adulto puede presentarse como una fiebre de origen desconocido y se diagnostica por exclusión, ya que no existen manifestaciones clínicas ni pruebas de laboratorio, patognomónicas. La hiperferritinemia es útil para la sospecha diagnóstica(AU)

Introduction: Adult Still's disease is a rheumatic, inflammatory, systemic and chronic disease whose prevalence in the Caucasian population is estimated at 1 case per 100,000 adults. Objective: To present a young adult patient with a fever of unknown origin as the presentation of adult Still's disease. Clinical case: 29-year-old patient with a history of rheumatic fever, with a previous hospital admission; who presented a non-infectious febrile illness lasting 50 days, for which the cause was not determined. A year later, the fever reappeared, with similar characteristics, associated with polyarthralgia, hepatosplenomegaly, anemia, hyperferritinemia, neutrophilia, negative rheumatoid factor, and pericarditis was noted during admission. The diagnosis of adult Still's disease was made by exclusion. Treatment with steroids was started, the fever disappeared in the first 24 hours and the patient had a favorable evolution. Conclusions: Adult Still's disease can present as a fever of unknown origin and is diagnosed by exclusion, since there are no pathognomonic clinical manifestations or laboratory tests. Hyperferritinemia is useful for diagnostic suspicion(AU)

Hiperferritinemia: Experiencia de un Centro Universitario en Chile / Hyperferritinemia in a Chilean Academic Healthcare Network: A Retrospective Study

INTRODUCTION: The distribution of causes of hyperferritinemia in international series is heterogeneous. Also, the association between ferritin and prognosis is controversial. This study aims to describe the diagnosis associated with hyperferritinemia in a retrospective cohort at an academic healthcare network in Chile. METHODS: A retrospective review of adult patients admitted to our academic medical center from June 2014 to February 2017 with ferritin ≥3,000 ng/mL. All patients were classified into nine diagnostic categories. Then, the association between ferritin level and disease category, as well as mortality, was evaluated. RESULTS: Ninety-nine patients were identified. The mean age was 50.8 ± 19.9 years, 54.5% were men. The most frequent categories were "inflammatory and autoimmune diseases" (21.2%) and "hematological malignancies" (19.2%). The average ferritin was 10,539 ± 13,016.9 ng/mL, while the higher mean was 16,707 ng/mL in the "inflammatory and autoimmune diseases" category. There was a statistically significant association between the ferritin value and age but not between ferritin and diagnostic categories. In the group over 50, hematologic neoplasms (19%) and infections (19%) were more frequent. In those under 50, inflammatory and autoimmune diseases were more frequent (26.8%). There was no association between the ferritin level and mortality at 1, 3, and 12 months. CONCLUSIONS: The most frequent categories were "inflammatory and autoimmune diseases" and "hematological malignancies", but ferritin level was similar in both. Further research could validate a prognostic role.

Hiperferritinemia y sospecha de sobrecarga de hierro en pacientes del Hospital Pablo Tobón Uribe, entre los años 2010 a 2020 / Hyperferritinemia and suspected iron overload in patients at the Pablo Tobón Uribe Hospital, between 2010 and 2020

Introducción. El objetivo de esta investigación fue comparar el perfil bioquímico y clínico de los pacientes con hiperferritinemia secundaria a hemocromatosis hereditaria (HH), frente a aquellos con hiperferritinemia por causas sospechosas de sobrecarga de hierro (Fe) diferentes a la HH. Metodología. Se estudiaron 92 pacientes (61 hombres y 31 mujeres), remitidos tras la detección de valores de ferritina >300 µg/L en hombres y >200 µg/L en mujeres. En todos se analizaron datos demográficos generales, comorbilidades, motivo de remisión para estudios de hiperferritinemia, manifestaciones clínicas, antecedente familiar de HH y tratamiento reci-bido. Los resultados de las pruebas de laboratorio, imagenología, hallazgos histopatológicos y estudios genéticos, se describieron según la disponibilidad. Resultados. El 96,74 % de los pacientes fueron evaluados en consulta externa, 86,96 % procedían de Medellín o de otros municipios de Antioquia, Colombia. La edad promedio de los participantes fue de 52 años, la principal razón para ser derivados para estudios fue la elevación de los marcadores de Fe sérico, la causa más frecuente de hiperferritinemia fueron los diagnósticos diferentes a la HH (64,13 %) y entre quienes no tenían HH, la etiología metabólica fue la más común (59,32 %). Los pacientes con HH tuvieron niveles más elevados de ferritina y Fe sérico, mientras que en el grupo sin HH se presentaron mayores elevaciones en la saturación de transferrina, transfe-rrina y transaminasas. En pacientes con sobrecarga de Fe, la mutación más frecuentemente encontrada fue la homocigota H63D (36,67 %). Finalmente, 93,94 % de los pacientes con HH recibieron tratamiento con flebotomías, mientras que los cambios en el estilo de vida fueron indicados en el 55,93 % de los pacientes sin HH. Conclusiones. La hiperferritinemia es una presentación clínica frecuente y es importante hacer un abordaje sistemático para identificar sus causas. Aunque la HH es una causa importante de elevación persistente de ferritina, en el enfoque de los pacientes con esta condición, se deben descartar etiologías más frecuentes como la hiperferritinemia de etiología metabólica.

Introduction. The aim of this investigation was to compare the biochemical and clinical profile of patients with secondary hyperferritinemia caused by hereditary hemochromatosis (HH), versus those with hyperferritinemia due to suspected causes of iron (Fe) overload other than HH. Methodology. A total of 92 patients (61 men and 31 women) referred after the detection of ferritin values >300 µg/L in men and >200 µg/L in women were studied. General demographic data, comorbidities, referral reasons for hyperferritinemia studies, clinical manifestations, family history of HH, and treatment received were analyzed in all patients. The results of laboratory tests, medical imaging, histopatho-logical findings, and genetic studies were described based on availability. Results. Of all patients, 96.74% were evaluated as outpatients, 86,96% from the municipality of Medellin in Antioquia, Colombia. The average age of the participants was 52 years, the main reason for being referred for studies was the elevation of serum Fe markers, the most frequent cause of hyperferritinemia in the population studied were conditions other than HH (64.13%), and among those who did not have HH, the metabolic etiology was the most common cause (60%). Patients with HH had higher levels of ferritin and serum Fe, while in the group without HH there were greater elevations of transferrin saturation, transferrin and transaminases. In patients with iron overload, the most frequently found mutation was the homozygous H63D (36.67%). Finally, 93.94% of the patients with HH received phlebotomy treatment, while changes in lifestyle were indicated in 55.93% of patients without HH. Conclusions. Hyperferritinemia is a frequent clinical presentation and it is important to make a systematic approach to identify its causes. Although HH is an important cause of persistent ferritin elevation, in the approach to patients with this condition, more frequent etiologies such as hyperfe-rritinemia of metabolic etiology should be ruled out.

Hemophagocytic lymphohistiocytosis: presentation and outcome of twenty-one patients at a single institution

ABSTRACT Introduction: Hemophagocytic lymphohistiocytosis comprises a systemic hyperactivation of macrophages that requires prompt recognition of symptoms and early treatment. Objective and Method: In this context, we described clinical and laboratory characteristics, therapeutic modality and outcome of 21 patients with HLH treated at a pediatric oncology hospital between January 2000 and February 2019. Results: HLH mainly affected females, fever was the most frequent clinical sign and hyperferritinemia was the most prevalent laboratory abnormality. All patients were admitted to the intensive care unit (ICU) at some point. Fifteen (71.4%) patients presented resolution criteria and eight (53.3%) of them presented reactivation. The mortality rate was 57.1% and the mean time between diagnosis and death was 9.98 months. The 5-year overall survival (OS) was 36.7%. We observed a significant difference in prognosis associated with reactivation of HLH. These patients demonstrated an estimated 5-year OS of 25%, while all patients that did not reactivate were alive until the end of the follow-up. Conclusion: In conclusion, HLH is a rare disease with a high mortality rate, especially in patients with disease reactivation and those with familial- or immunodeficiency-associated forms, which makes early recognition and genetic testing crucial for appropriate management and prompt SCT indication.

Perfil dos pacientes com hiperferritinemia em acompanhamento ambulatorial em um serviço no sul do Brasil / Profile of patients with hyperferritinemia in ambulatorial follow-up in southern Brazil

O achado de hiperferritinemia é comum na prática clínica. Além de representar os estoques de ferro no organismo, a ferritina se mostra como proteína de fase inflamatória, podendo elevar-se em comorbidades inflamatórias agudas ou crônicas e se associar com a chamada síndrome plurimetabólica. Objetivo: Avaliar as características clínicas de pacientes com hiperferritinemia em acompanhamento ambulatorial no período de janeiro de 2013 a novembro de 2016. Métodos: Estudo observacional transversal, desenvolvido em um serviço de Hematologia na cidade de Tubarão, Santa Catarina. Coletaram-se dados de 136 pacientes com o diagnóstico de hiperferritinemia através de prontuários digitais. Foram realizadas análises descritivas e associações com os testes qui-quadrado e t Student, quando apropriado. Resultados: Houve um predomínio do sexo masculino (83,50%) com idade média de 56,62 anos, a média de ferritina de 693,45mcg/L e de ferro sérico 121,52mcg/dL, sendo as causas secundárias de hiperferritinemia as predominantes. Ao se estratificar os valores de ferritina constatou-se que os pacientes com ferritina >1000mcg/L tiveram um risco 50% maior de possuir alterações ao ultrassom, 70% maior prevalência de HDL<40 e 40% maior prevalência de hipertrigliceridemia. Os pacientes com ferritina >400mcg/L tiveram duas vezes maior chance de apresentar resistência à insulina. Conclusão: As principais causas de hiperferritinemia foram secundárias a doenças crônicas metabólicas

Hyperferritinemia is common in the clinical practice. In aside from representing the stocks of iron in the organism, ferritin is also a inflammatory phase protein, witch can be elevated in chronic or acute inflammatory comorbidities and be associated with plurimetabolic syndrome. This study aims the evaluation of the clinical characteristics of ambulatory patients with hyperferritinemia between January-2013 and November-2016. Methods: It is a cross-sectional, descriptive study, developed in the hematology center of the medical specialities clinic in Tubarão ­ Santa Catarina. Data from 136 patients have been collected and then transferred to an Excel spreadsheet, imported to Epiiinfo 7 and the expressed into absolute and relative numbers, graphics and figures. Results: It was found a predominance of males (83,50%) with a mean age of 56,62 years, a mean ferritin level of 693,45mcg/L and seric iron of 121,52mcg/dL being the secondary causes of hyperferritinemia the most predominant. When stratified the ferritin levels, it was verified that patients with a ferritin >1000mcg/L had 50% more risk of having ultrasound alterations, 70% more prevalence of HDL<40 and 40% more prevalence of having hypertriglyceridemia. Patients with a ferrintin >400mcg/L had twice as many chances of having insulin resistance. Conclusion: The main causes of hyperferritinemia were secondary to chronic metabolic diseases

Relationship between marked hyperferritinemia and hemophagocytic lymphohistiocytosis / 北京大学学报(医学版)

OBJECTIVE@#To investigate the relationship between marked hyperferritinemia (MHF) and hemophagocytic lymphohistiocytosis(HLH).@*METHODS@#The clinical data of 123 patients with MHF admitted to Peking University People's Hospital from January 2017 to September 2018 were collected, including demographics, baseline characteristics, signs and symptoms, blood routine, blood biochemistry, coagulation function parameters, such as prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib), d-dimer (D-D), fibrin degradation product (FDP), blood ferritin, natural killer (NK) cell activity, soluble interleukin (IL)-2 receptor and bone marrow examination. According to the diagnosis of HLH, the patients were divided into HLH group and non HLH group. The patients were divided into death group and survival group according to the 3-month follow-up results. The groups were compared and statistically analyzed.@*RESULTS@#In the 123 patients with MHF, the average age was (44.2±17.4) years with a male/female ratio of 1.3 ∶1. The most common causes were hematolo-gic malignancies, rheumatologic and inflammatory disorders, iron overload, and HLH. HLH was enriched as the ferritin increased, and the HLH ratios were 28.8%, 40.0%, 54.5%, 50.0%, 50.0% in ferritin value of 10 000-19 999, 20 000-29 999, 30 000-39 999, 40 000-49 999 μg/L, more than 50 000 μg/L respectively. There were 46 cases of HLH, among which 15 cases were secondary to malignancies, 14 cases secondary to rheumatologic disorders, 2 cases secondary to infection, and 15 cases with no clear precipitating cause. There were significant differences between the HLH group and non-HLH group in hepatomegaly, splenomegaly, lymphadenectasis, albumin (ALB), fibrinogen(Fib), P < 0.05, and no significant differences in age, gender, fever, disturbance of consciousness, ferritin level on presentation, maximum ferritin level, cytopenia in 2 or more cell lines, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), triglyceride (TG), coagulation parameters (PT, APTT, D-D, FDP, exception of Fib), and mortality rate (P > 0.05). There were significant differences between the death group and survival group in disturbance of consciousness, platelet count, PT, TBIL, and DBIL (P < 0.05), but no significant differences in age, gender, fever, hepatomegaly, splenomegaly, lymphadenectasis, ferritin level on presentation, maximum ferritin level, neutrophils, hemoglobin, ALT, AST, ALB, TG, coagulation parameters (Fib, APTT, D-D, FDP, exception of PT) and the HLH ratio (P > 0.05).@*CONCLUSION@#HLH was enriched as the ferritin increased, but marked hyperferritinemia was not specific for HLH in adults.

Hemophagocytic lymphohistiocytosis presenting as acute coronary syndrome

Acquired Hemophagocytic Lymphohistiocytosis is a rare and deadly syndrome resulting from an overactive immune system, with uncontrolled activation of macrophages and lymphocytes, hypercytokinemia, and systemic inflammatory response. A 75-year-old male presented with typical anginal pain and was diagnosed with the acute coronary syndrome, which required a percutaneous transluminal coronary angioplasty. Instead of resolving the symptoms, the patient began to exhibit pyrexia and worsening altered sensorium with progressing renal failure, anemia, thrombocytopenia and respiratory failure. This constellation of symptoms caused the patient to require mechanical ventilation and hemodialysis. Upon laboratory analysis, hyperferritinemia provided an indication to the diagnosis of acquired hemophagocytic lymphohistiocytosis. After the initiation of dexamethasone, the patient made a significant recovery and was discharged from the hospital.

Doença de Still do adulto: um desafio diagnóstico / Adult-onset Still's disease: a diagnostic challenge

A doença de Still do adulto é uma rara condição inflamatória, cujo diagnóstico é um desafio, por se tratar de diagnóstico de exclusão, após vasta investigação. Manifesta-se com febre alta diária, amigdalite não supurativa, artrite, rash evanescente, leucocitose e hiperferritinemia. O presente caso demonstra a doença de Still do adulto e sua vasta investigação, motivando a realização de revisão bibliográfica sobre inovações na fisiopatologia, no diagnóstico e no tratamento.

Adult onset Still's disease is a rare inflammatory condition, the diagnosis of which is a challenge, because it is a diagnosis of exclusion, and demands extensive investigation. It manifests with high daily fever, nonsuppurative tonsillitis, arthritis, evanescent rash, leukocytosis, and hyperferritinemia. The present case de­monstrates adult-onset Still's disease and its extensive inves­tigation, motivating literature review on innovations of its pathophysiology, diagnosis, and treatment.