BACKGROUND: Protracted febrile myalgia syndrome (PFMS) is a rare manifestation of familial Mediterranean fever (FMF), characterized by myalgia, fever and elevated inflammatory markers lasting several weeks. As the hallmark of FMF are short episodes of disease symptoms, the long duration of PFMS may lead to a delayed diagnosis and treatment.
OBJECTIVE: 1. To perform a review of literature and rheumatology textbooks focused on clinical features and treatment of PFMS in children. 2. To present our own case.
METHODS: All articles in Pub Med generated using the keywords \"protracted febrile myalgia\" and information on PFMS in seven rheumatology textbooks were collected. The systematic review was supplemented with our own case presentation.
RESULTS: In total, 18 articles with 78 pediatric patients (including our own) were retrieved. More than half of the patients presented with PFMS as the first manifestation of FMF. All complained of myalgia, 65% of abdominal pain and 26% had a rash. Corticosteroids (CS) were effective in 77%. In all CS-refractory cases, anakinra was shown efficient. MRI was used in 5 patients and showed myositis in all of them. The scrutiny of seven rheumatology textbooks showed that PFMS presenting with myalgia was mentioned in six. Possible accompanying symptoms were described only once, the long duration of symptoms twice, the efficacy of corticosteroids three times and anakinra only once. The presented 6 year old patient manifested with fever, myalgia, abdominal pain and petechial rash lasting 6 weeks. She had undergone multiple diagnostic procedures before her parents mentioned a positive family history for FMF. The subsequent genetic testing confirmed a homozygosity for M694V pathogenic variant in the MEFV gene.
CONCLUSIONS: The long duration of PFMS may be misleading to clinicians especially if PFMS occurs at manifestation of FMF. The fact that more than half of the reported patients experienced PFMS as the presenting symptom of FMF is one of the key findings of our study. Our case presentation demonstrates the importance of genetic testing early in suspected autoinflammatory diseases. Furthermore, MRI may be an important diagnostic tool showing myositis in PFMS.

BACKGROUND: Understanding the epidemiological patterns of febrile infants can offer valuable insights for optimising management strategies and developing quality improvement initiatives, aiming to improve healthcare delivery in high-volume, low-resource emergency departments (EDs).
OBJECTIVE: To characterise the epidemiology of febrile infants presenting to the paediatric ED of a tertiary care hospital.
METHODS: A retrospective chart review of medical records was performed for febrile infants ≤1 year old, at paediatric ED, Indus Hospital and Health Network (IHHN), Karachi, Pakistan (1 January 2020-31 December 2020).
RESULTS: There were a total of 2311 patients in the study, with a male-to-female ratio of 1.4:1. The mean age of presentation was 4.9±2.7 months. Cough (n=1002, 43.2%) was the most frequent presenting symptom. The most common provisional ED diagnosis in ≤1 month of age was sepsis (n=98, 51%), bronchopneumonia (n=138, 28.6%) in 1.1-3 and 3.1-6 months (n=176, 36.45%); and upper respiratory tract illness (n=206, 47.4%) in 6.1-12 months of age. Age was significantly associated with provisional ED diagnosis and outcomes (p<0.001). Of 175 ED admissions (n=47, 26.8%), patients were discharged with a hospital diagnosis of bronchopneumonia and (n=27, 15.4) of sepsis. The infant mortality rate was 3/1000 live births.
CONCLUSIONS: This study is the first of its kind to explore the epidemiology of febrile infants in Pakistan, highlighting the burden and severity of respiratory illnesses and sepsis. It underscores the challenges of resource-limited settings, failing to meet the need for admission of febrile infants presenting to ED, IHHN. Moreover, it has highlighted the necessity to optimise the existing triage systems to effectively allocate resources and manage high patient volumes in low-resource EDs.

BACKGROUND: Rapid point-of-care tests for malaria are now widely used in many countries to guide the initial clinical management of patients presenting with febrile illness. With China having recently achieved malaria elimination, better understanding regarding the identity and distribution of major non-malarial causes of febrile illnesses is of particular importance to inform evidence-based empirical treatment policy.
METHODS: A systematic review of published literature was undertaken to characterise the spectrum of pathogens causing non-malaria febrile illness in China (1980-2015). Literature searches were conducted in English and Chinese languages in six databases: Ovid MEDLINE, Global Health, EMBASE, Web of Science™ - Chinese Science Citation Database SM, The China National Knowledge Infrastructure (CNKI), and WanFang Med Online. Selection criteria included reporting on an infection or infections with a confirmed diagnosis, defined as pathogens detected in or cultured from samples from normally sterile sites, or serological evidence of current or past infection. The number of published articles, reporting a given pathogen were presented, rather than incidence or prevalence of infection.
RESULTS: A total of 57,181 records from 13 provinces of China where malaria used to be endemic were screened, of which 392 met selection criteria and were included in this review. The review includes 60 (15.3%) records published from 1980 to 2000, 211 (53.8%) from 2001 to 2010 and 121 (30.9%) from 2011 to 2015;. Of the 392 records, 166 (42.3%) were from the eastern region of China, 120 (30.6%) were from the south-west, 102 (26.0%) from south-central, and four (1.0%) were multi-regional studies. Bacterial infections were reported in 154 (39.3%) records, viral infections in 219 (55.9%), parasitic infections in four (1.0%), fungal infections in one (0.3%), and 14 (3.6%) publications reported more than one pathogen group. Participants of all ages were included in 136 (34.7%) studies, only adults in 75 (19.1%), only children in 17 (4.3%), only neonates in two (0.5%) and the age distribution was not specified in 162 (41.3%) records. The most commonly reported bacterial pathogens included Typhoidal Salmonella (n = 30), Orientia/ Rickettsia tsutsugamushi (n = 31), Coxiella burnetii (n = 17), Leptospira spp. (n = 15) and Brucella spp. (n = 15). The most commonly reported viral pathogens included Hantavirus/Hantaan virus (n = 89), dengue virus (DENV) (n = 76 including those with unknown serovars), Japanese encephalitis virus (n = 21), and measles virus (n = 15). The relative lack of data in the western region of the country, as well as in in neonates and children, represented major gaps in the understanding of the aetiology of fever in China.
CONCLUSIONS: This review presents a landscape of non-malaria pathogens causing febrile illness in China over 36 years as the country progressed toward malaria elimination. These findings can inform guidelines for clinical management of fever cases and infection surveillance and prevention, and highlight the need to standardize operational and reporting protocols for better understanding of fever aetiology in the country.

BACKGROUND: Clozapine-induced inflammation, such as myocarditis and pneumonia, can occur during initial titration and can be fatal. Fever is often the first sign of severe inflammation, and early detection and prevention are essential. Few studies have investigated the effects of clozapine titration speed and concomitant medication use on the risk of clozapine-induced inflammation.
OBJECTIVE: We evaluated the risk factors for clozapine-associated fever, including titration speed, concomitant medication use, gender and obesity, and their impact on the risk of fever and the fever onset date.
METHODS: We conducted a case-control study. The medical records of 539 Japanese participants with treatment-resistant schizophrenia at 21 hospitals in Japan who received clozapine for the first time between 2010 and 2022 were retrospectively investigated. Of these, 512 individuals were included in the analysis. Individuals were divided into three groups according to the titration rate recommended by international guidelines for East Asians: the faster titration group, the slower titration group and the ultra-slower titration group. The use of concomitant medications (such as antipsychotics, mood stabilisers, hypnotics and anxiolytics) at clozapine initiation was comprehensively investigated. Logistic regression analysis was performed to identify the explanatory variables for the risk of a fever of 37.5°C or higher lasting at least 2 days.
RESULTS: Fever risk significantly increased with faster titration, male gender and concomitant use of valproic acid or quetiapine. No increased fever risk was detected with the use of other concomitant drugs, such as olanzapine, lithium or orexin receptor antagonists. Fever onset occurred significantly earlier with faster titration. Multivariate analysis identified obesity as being a factor that accelerated fever onset.
CONCLUSIONS: A faster titration speed and concomitant treatment with valproic acid and quetiapine at clozapine initiation increased the risk of clozapine-associated fever. Clinicians should titrate clozapine with caution and consider both the titration speed and concomitant medications.

BACKGROUND: Criteria classifying fever of unknown origin (FUO) patients remains subject to discrepancies. A minimal standardized set of investigative tests serves as the foundation for the qualitative criteria, whereas quantitative incorporates the length of evaluation (7 or 3 days). A systematic review of studies would help physicians anticipate the frequency of illness types that could influence management.
METHODS: Prospective studies published in Medline (PubMed), Embase, Scopus, and Web of Science databases from January 1, 1997, to July 31, 2022, were included. A meta-analysis estimated associated pooled proportions between these criteria and diagnostic outcomes adjusted to the International Classification of Diseases, 10th edition (ICD-10) definitions.
RESULTS: Five qualitative studies corresponded to an increase of 15.3% (95% CI: 2.3-28.3%, p=0.021) in undiagnosed FUO proportions compared to eleven quantitative studies. Quantitative studies had 19.7% (95% CI: 6.0-33.4%, p=0.005) more in adjusted infectious disease proportions than qualitative studies. No significant differences in proportions between FUO defining criteria were noted for adjusted noninfectious inflammatory disorders (p=0.318), oncology (p=0.901), non-inflammatory miscellaneous disorders (p=0.321), diagnostic evaluation process, gross national income (GNI), or World Health Organization (WHO) geographic region.
CONCLUSIONS: Use of either qualitative or quantitative FUO criteria was associated with a statistically significant risk of over- or under-estimating infectious diseases and undiagnosed illnesses when using an ICD-10 adjusted FUO five-category system. Clinicians should anticipate differences depending on which criteria are used. While further research is warranted, qualitative criteria provide the best framework for study comparisons.

Clostridial myonecrosis, commonly known as gas gangrene (GG), is a rapidly progressing and potentially fatal bacterial infection that primarily affects muscle and soft tissue. In the United States, the incidence of GG is roughly 1000 cases per year, while, in developing countries, the incidence is higher. This condition is most often caused by Clostridium perfringens, a Gram-positive, spore-forming anaerobic bacterium widely distributed in the environment, although other Clostridium species have also been reported to cause GG. The CP genome contains over 200 transport-related genes, including ABC transporters, which facilitate the uptake of sugars, amino acids, nucleotides, and ions from the host environment. There are two main subtypes of GG: traumatic GG, resulting from injuries that introduce Clostridium spores into deep tissue, where anaerobic conditions allow for bacterial growth and toxin production, and spontaneous GG, which is rarer and often occurs in immunocompromised patients. Clostridium species produce various toxins (e.g., alpha, theta, beta) that induce specific downstream signaling changes in cellular pathways, causing apoptosis or severe, fatal immunological conditions. For example, the Clostridium perfringens alpha toxin (CPA) targets the host cell\'s plasma membrane, hydrolyzing sphingomyelin and phosphatidylcholine, which triggers necrosis and apoptosis. The clinical manifestations of clostridial myonecrosis vary. Some patients experience the sudden onset of severe pain, swelling, and muscle tenderness, with the infection progressing rapidly to widespread tissue necrosis, systemic toxicity, and, if untreated, death. Other patients present with discharge, pain, and features of cellulitis. The diagnosis of GG primarily involves clinical evaluation, imaging studies such as X-rays, computer tomography (CT) scans, and culture. The treatment of GG involves surgical exploration, broad-spectrum antibiotics, antitoxin, and hyperbaric oxygen therapy, which is considered an adjunctive treatment to inhibit anaerobic bacterial growth and enhance the antibiotic efficacy. Early recognition and prompt, comprehensive treatment are critical to improving the outcomes for patients affected by this severe and life-threatening condition.

暂无摘要。

Febrile ulceronecrotic Mucha-Habermann disease is a rare and severe variant of pityriasis lichenoides, characterized by sudden onset of generalized ulceronecrotic papules that rapidly coalesce into ulcers associated with high fever. Systemic manifestations such as intravascular disseminated coagulation and pulmonary, cardiac, gastrointestinal, and central nervous system involvement are common. Treatment is based on oral corticosteroids, immunosuppressive drugs such as methotrexate, and general supportive treatment. The present case describes a stepwise approach to a patient with Mucha-Habermann disease with insufficient response to methotrexate.

BACKGROUND: Febrile illnesses that persist despite initial treatment are common clinical challenges in (sub)tropical low-resource settings. Our aim is to review infectious etiologies of \"prolonged fevers\" (persistent febrile illnesses, PFI) and to quantify relative contributions of selected neglected target diseases with limited diagnostic options, often overlooked, causing inadequate antibiotic prescriptions, or requiring prolonged and potentially toxic treatments.
METHODS: We performed a systematic review of articles addressing the infectious etiologies of PFI in adults and children in sub-/tropical low- and middle-income countries (LMICs) using the PRISMA guidelines. A list of target diseases, including neglected parasites and zoonotic bacteria (e.g., Leishmania and Brucella), were identified by infectious diseases and tropical medicine specialists and prioritized in the search. Malaria and tuberculosis (TB) were not included as target diseases due to well-established epidemiology and diagnostic options. Four co-investigators independently extracted data from the identified articles while assessing for risk of bias.
RESULTS: 196 articles from 52 countries were included, 117 from Africa (33 countries), 71 from Asia (16 countries), and 8 from Central and -South America (3 countries). Target diseases were reported as the cause of PFI in almost half of the articles, most frequently rickettsioses (including scrub typhus), relapsing fever borreliosis (RF-borreliosis), brucellosis, enteric fever, leptospirosis, Q fever and leishmaniasis. Among those, RF-borreliosis was by far the most frequently reported disease in Africa, particularly in Eastern Africa. Rickettsioses (including scrub typhus) were often described in both Africa and Asia. Leishmaniasis, toxoplasmosis and amoebiasis were the most frequent parasitic etiologies. Non-target diseases and non-tropical organisms (Streptococcus pneumoniae, Escherichia coli, and non-typhoidal Salmonella spp) were documented in a fifth of articles.
CONCLUSIONS: Clinicians faced with PFI in sub-/tropical LMICs should consider a wide differential diagnosis including enteric fever and zoonotic bacterial diseases (e.g., rickettsiosis, RF-borreliosis and brucellosis), or parasite infections (e.g., leishmaniasis) depending on geography and syndromes. In the absence of adequate diagnostic capacity, a trial of antibiotics targeting relevant intra-cellular bacteria, such as doxycycline or azithromycin, may be considered.

BACKGROUND: Chikungunya is a viral disease caused by a mosquito-borne alphavirus. The acute phase of the disease includes symptoms such as fever and arthralgia and lasts 7-10 days. However, debilitating symptoms can persist for months or years. Despite the substantial impact of this disease, a comprehensive assessment of its clinical picture is currently lacking.
METHODS: We conducted a systematic literature review on the clinical manifestations of chikungunya, their prevalence and duration, and related hospitalization. Embase and MEDLINE were searched with no time restrictions. Subsequently, meta-analyses were conducted to quantify pooled estimates on clinical outcomes, the symptomatic rate, the mortality rate, and the hospitalization rate. The pooling of effects was conducted using the inverse-variance weighting methods and generalized linear mixed effects models, with measures of heterogeneity reported.
RESULTS: The systematic literature review identified 316 articles. Out of the 28 outcomes of interest, we were able to conduct 11 meta-analyses. The most prevalent symptoms during the acute phase included arthralgia in 90% of cases (95% CI: 83-94%), and fever in 88% of cases (95% CI: 85-90%). Upon employing broader inclusion criteria, the overall symptomatic rate was 75% (95% CI: 63-84%), the chronicity rate was 44% (95% CI: 31-57%), and the mortality rate was 0.3% (95% CI: 0.1-0.7%). The heterogeneity between subpopulations was more than 92% for most outcomes. We were not able to estimate all predefined outcomes, highlighting the existing data gap.
CONCLUSIONS: Chikungunya is an emerging public health concern. Consequently, a thorough understanding of the clinical burden of this disease is necessary. Our study highlighted the substantial clinical burden of chikungunya in the acute phase and a potentially long-lasting chronic phase. Understanding this enables health authorities and healthcare professionals to effectively recognize and address the associated symptoms and raise awareness in society.