Recurrent Fever Research Articles

Bladder stone in a 1-year infant with recurrent urinary tract infections: a rare case report

Background: Bladder stone is a rare disease accounting for 5% of all urinary calculi. It is more common in middle- and low-income countries due to nutritional obstacles, water sanitation, and warm climates. Primary bladder calculi are most common in children younger than 10 years old, with a peak incidence at 2 to 4 years. There have been no reports of bladder stones in children under 2 years of age. This case study aims to evaluate the bladder stone in a 1-year infant with recurrent urinary tract infections. Case Presentation: An infant boy 1 year and 2 months presented with a 6-month history of complaints of pain on micturition presented with pulling the penis, cloudy urine, and recurrent fever in our clinic. During the 6 months before admission, he visited several pediatric clinics and was diagnosed with and treated for UTI. On ultrasonography, we found a bladder stone 1,9 x 1,3 cm in size. Then we performed open cystolithotomy under general anesthesia. One day after surgery, the patient was discharged from the hospital. Conclusion: Children who live in endemic areas are more likely to develop bladder stones due to dietary issues. Preventing dehydration, treating urinary tract infections effectively, and securing metabolic abnormalities are the methods for reducing the prevalence of pediatric bladder stones. Pediatric bladder stones must be diagnosed and treated to avoid the stones' recurrence and improve quality of life.

Successful transabdominal treatment of a chronic splenic abscess caused byClostridium perfringensafter penetrating external trauma in a horse

SummaryThis report describes the successful treatment of a traumatic splenic abscess by transabdominal drainage under ultrasonographic guidance. The gelding presented for investigation of recurrent pyrexia, mild abdominal pain and weight loss after a penetrating trauma to the caudolateral abdomen 5 weeks previously. At this stage, the abdominal wall had healed and a splenic abscess was diagnosed. Before treatment, mature adhesions between the abdominal wall and the spleen were confirmed by diagnostic laparoscopy in the standing horse. Transabdominal ultrasound‐guided drainage was performed, followed by intralesional placement of a balloon catheter for 2 weeks and a silicone drain for an additional week. Postoperatively, the horse was treated with intralesional and systemic antibiotics. The healing process was unremarkable and the horse was discharged 4 weeks postoperatively. At 10 months post‐surgery, after the body condition score had normalised, the horse returned to its previous level of performance.

A nagy imitátorok – Szifilisz és szisztémás lupus erythematosus differenciáldiagnosztikája egy eset kapcsán

The authors report the case of a 29-year-old male patient presenting with erythematous maculopapular rash, painful oral and genital erosions, dysuria, scleroconjunctivitis, painful palmoplantar hyperkeratotic papules, asymmetric, migratory oligoarthritis, recurrent fever and alopecia parvimaculata. Based on the clinical symptoms the first suspected diagnoses were secondary syphilis and reactive arthritis, however the performed laboratory tests did not confirmed the diagnoses. The autoimmune serology tests, the clinical symptoms, and the results of further investigations established the diagnosis of systemic lupus erythematosus (SLE). By presenting this case the authors highlight the differential diagnostic challanges of secondary syphilis and SLE.

Fulminant Hepatic Failure as the Initial Presentation of Hodgkin Lymphoma in 4 Patients With Human Immunodeficiency Virus

Abstract In the era of antiretroviral therapy (ART), Hodgkin Lymphoma (HL) is a common non-AIDS-defining cancer with increasing incidence in people with human immunodeficiency virus (PWH). Through review of these cases, we identify clinical patterns such as declining CD4 count despite ART, hyperbilirubinemia and recurrent fever, which preceded diagnosis. Identifying these important signs and symptoms may lead to earlier diagnosis and initiation of therapy. Fulminant hepatic failure limits the ability to give standard of care chemotherapy, likely jeopardizing outcomes in this patient population. Alternative bridging therapies should be considered until hepatic function improves.

Shear wave elastography evaluation of kidneys in children with familial mediterranean fever.

Familial Mediterranean fever (FMF) is an autosomal recessive disorder. Typical clinical manifestations are self-limiting attacks of recurrent fever, abdominal pain, arthralgia, and chest pain due to aseptic polyserositis. Renal involvement is common in FMF patients. Shear wave elastography (SWE) is a noninvasive method that provides the measurement of tissue stiffness. In this study, we aimed to show that SWE can be used as an adjunctive method for evaluating renal involvement in children with FMF. Our study group consists of 79 pediatric FMF patients and 79 control individuals. The study was planned prospectively. The variables, such as age, height, weight, and body mass index (BMI) of the patient and control groups, were kept in a similar way in order not to be affected by the differences. The right and left kidney sizes, parenchymal thicknesses, and SWE values in both groups were compared. The parenchymal stiffness degrees of the kidneys were quantified by shear modulus values in kilopascals. In our study, no statistically significant difference was found between the control and patient groups in terms of the right and left kidney longitudinal dimensions, transverse dimensions, and parenchymal thicknesses. When the kidneys were evaluated in terms of the right and left kidney stiffness values, the stiffness values in the patient group were significantly higher in both kidneys compared with those in the control group (P < 0.001). SWE can be a noninvasive quantitative imaging method that can be used to evaluate kidney involvement by detecting changes in kidney stiffness in children with FMF.

Not easy-peasy to diagnose: familial Mediterranean fever unaccompanied by fever.

Classical attacks of familial Mediterranean fever (FMF) are often accompanied by fever, but some of the patients have attacks without fever. This study aimed to compare the characteristics of FMF patients with and without fever during their attacks and draw attention to the different clinical presentations of FMF in children.Medical files of patients aged 0-18years who were followed up with the diagnosis of FMF in two reference pediatric rheumatology centers were reviewed retrospectively. The patients were divided into two groups: children who had had no fever in any of their attacks were assigned as group 1, and those who had fever during their attacks were classified as group 2.Out of 2003 patients evaluated, 191 (9.53%) patients had attacks not accompanied by fever and their median age at onset of symptoms (7.0 vs. 4.0years, p < 0.001) and the median age at diagnosis (8.6 vs. 6.0years, p < 0.001) were significantly higher; however, group 2 had a delay in diagnosis. The annual number of attacks and abdominal attacks were more common in group 2; arthritis, arthralgia, erysipelas-like rash, exercise-induced leg pain, and myalgia were more common in group 1. Conclusion: The data from the assessment of children with FMF attacks not accompanied with fever were presented for the first time. Children with late age onset of FMF and dominance of musculoskeletal features may display attacks not accompanied with fever. What is Known: • Familial Mediterranean fever (FMF) is the most common inherited auto-inflammatory disease, characterized by recurrent attacks of fever, serositis, and musculoskeletal symptoms. •Although fever is the most common symptom, few studies have reported attacks without fever. What is New: • The aim of this study was to identify patients with FMF but without fever during attacks and to demonstrate their distinctive presentations. • We found that 7% of our patients had afebrile attacks with predominant musculoskeletal symptoms and were diagnosed earlier than patients with febrile attacks, probably due to early referral to pediatric rheumatology clinics.

A Case Report of Hyper-IgM Syndrome Patient with Normal Serum IgA Level

Hyper IgM syndromes are a group of disorders characterized by defective T and B cell interactions resulting in the lack of Immunoglobulin class switching. The most common hyper IgM syndrome is CD40 ligand (CD40L) deficiency. Patients with CD40L deficiency present with recurrent infection, neutropenia, and autoimmunity. These patients typically have absent serum IgA and IgG due to the class switch defect. Here we present a case of CD40L deficiency who presented with oral ulcers, failure to thrive, and recurrent fever. His laboratory evaluation was notable for intermittent neutropenia, elevated IgM (397mg/dl), normal IgA (78mg/dl) and low IgG (51mg/dl). Antibody responses to tetanus and measles were undetectable despite full vaccination. Whole exome sequencing showed a likely pathologic variant in CD40LG (c.674 T&gt;C, p.L225S). This case highlights the importance of considering the diagnosis of hyper IgM syndrome in the appropriate clinical setting, even if the patient has a normal serum IgA level.

The phenotype and genotype of Chinese adult patients with NLRP3-associated autoinflammatory disease.

NLRP3-associated autoinflammatory disease (NLRP3-AID) is a spectrum of autosomal dominant inherited diseases associated with NLRP3 gene mutations. Reports of Chinese NLRP3-AID cases are limited to date. In the present study, we aim to describe the phenotype and genotype of a cohort of Chinese adult NLRP3-AID patients METHODS: This single-center study included sixteen adult patients diagnosed with NLRP3-AID at Department of Rheumatology, Peking Union Medical College Hospital from April 2015 to September 2021. Whole-exome sequencing using next-generation sequencing was performed in each patient. Clinical data and mutational information were compared with a European cohort. The median age of disease onset was 16 (0-46) years old, and adult-onset was observed in 4 patients (25%). The median time of diagnosis delay was 20 (0-39) years. Five patients (31.3%) had family history of similar symptoms. The most common clinical manifestations were recurrent fever (93.8%), arthralgia/arthritis (81.3%), skin rash (75%), myalgia (62.5%), and central nervous system manifestations (50%). Heterozygous NLRP3 variants detected in these patients were p.T348M (n = 4, 25%), Q703K, V70M, K129R, M116I, P38S, V442I, D303G, G326E, A439V, K829T, L632F and V198M (n = 1, separately). All the variants were missense mutations. We reported the largest case series of Chinese adult NLRP3-AID patients. The distinct symptoms of NLRP3-AID patients suggest the heterogeneity of disease. P38S, M116I, K129R, V442I and K829T were identified as novel NLRP3 variants. These data expand the clinical phenotypic and genotypic profiles of NLRP3-AID. Key Points • We characterized the clinical and genetic features of sixteen Chinese adult NLRP3-AID patients. • Thirteen NLRP3 gene variants were confirmed in this cohort, and P38S, M116I, K129R, V442I and K829T were identified as novel variants. • Clinical data and mutation information were compared with a European cohort. • We hope these data would expand the phenotypic and genotypic profile of NLRP3-AID and raise the awareness of early diagnosis and accurate treatment among rheumatologists.

Absolute Monocyte Count as Early and Safe Marker for Antibiotic Cessation in Febrile Neutropenia Without Etiology in Pediatric Oncology Patients.

There is no practice standard regarding antibiotic duration in children with cancer and unexplained febrile neutropenia (FN). We hypothesized that absolute monocyte count (AMC) and absolute phagocyte count (APC= ANC + AMC + bands) are more sensitive, earlier, and safe markers of antibiotic cessation compared with absolute neutrophil count (ANC). A retrospective review of FN episodes (FNEs) in pediatric oncology patients was conducted between 2009 and 2016. Included patients were afebrile for 24 hours and without an identified infectious source at antibiotic cessation. Primary endpoints, including recurrent fever, readmission, bloodstream infection, microbiologically documented infection, and adverse outcomes, were assessed 10 days after antibiotic cessation and compared among different bone marrow recovery parameters (ANC, AMC, APC). Secondary endpoints included length of FN stay, antibiotic-free days, and cost. Three hundred ninety-one FNEs in 235 patients were included. Three groups were compared based on ANC (cells/μL) at the time of antibiotic cessation: < 200 in 102 (26%), 200 to 500 in 111 (28%), and >500 in 178 (46%). No statistically significant differences in primary endpoints were identified among the 3 ANC groups; however, a trend toward unfavorable outcomes in the ANC ≤200 cells/μL group compared with the ANC >200 cells/μL was observed. Primary endpoints based on AMC >100 cells/μL at the time of antibiotic cessation showed statistically significant favorable outcomes compared AMC ≤100 cells/μL (80%, 88%, 90%, 89%, and 93% risk reduction in recurrent fever, readmission, new bloodstream infection, new microbiologically documented infection, and adverse events, respectively). Similar favorable results were seen when APC >300 cells/μL was used as a threshold for antibiotic cessation. The median length of stay for FN if discharged when AMC >100 cells/μL was 3 days shorter and associated with fewer unfavorable outcomes, thus resulting in fewer hospital days, fewer antibiotic days, and decreased cost. Our results suggest that AMC >100 cells/μL (regardless of ANC) or APC >300 cells/μL may be safe thresholds for empiric antibiotic cessation and result in reduced unfavorable clinical outcomes within 10 days postdischarge, reduced antibiotic days of therapy and reduced health care costs. Further prospective studies are needed to validate AMC as an accurate surrogate marker for antibiotic cessation in FNEs in children with cancer.

Phosphomevalonate kinase deficiency expands the genetic spectrum of systemic autoinflammatory diseases

In the isoprenoid biosynthesis pathway, mevalonate is phosphorylated in two subsequent enzyme steps by mevalonate kinase (MVK) and phosphomevalonate kinase (PMVK) to generate mevalonate pyrophosphate that is further metabolized to produce sterol and non-sterol isoprenoids. Biallelic pathogenic variants in the MVK gene result in the autoinflammatory metabolic disorder MVK Deficiency (MKD). So far, however, no patients with proven PMVK deficiency due to biallelic pathogenic variants in the PMVK gene have been reported. This study aims to report the first patient with functionally confirmed PMVK deficiency, including the clinical, biochemical and immunological consequences of a homozygous missense variant in the PMVK gene. We performed whole-exome sequencing and functional studies in cells from a patient who, upon clinical and immunological evaluation, was suspected of an autoinflammatory disease. We identified a homozygous PMVK p.Val131Ala (NM_006556.4: c.392T>C,) missense variant in our patient. Pathogenicity was supported by genetic algorithms and modeling analysis and confirmed in patient cells that revealed a markedly reduced PMVK enzyme activity due to a virtually complete absence of PMVK protein. Clinically, the patient showed various similarities, but also distinct features compared to MKD patients, and responded well to therapeutic IL-1 inhibition. In this study we report the first patient with proven PMVK deficiency due to a homozygous missense variant in PMVK leading to an autoinflammatory disease. PMVK deficiency expands the genetic spectrum of systemic autoinflammatory diseases (SAID), characterized by recurrent fevers, arthritis and cytopenia and thus should be included in the differential diagnosis and genetic testing for SAIDs.

PERIODIC FEVER, APHTHOUS STOMATITIS, PHARYNGITIS, (PFAPA) SYNDROME AND NLRP3 GENE ASSOCIATION

PFAPA syndrome, which also includes aphthous stomatitis, pharyngitis, and adenitis, is the most common type of recurrent fever in children. Usually happens before the age of five. This syndrome is characterized by attacks lasting 3-7 days, recurring every 2-8 weeks with high fever (39 C and above) accompanied by at least one of the signs of aphthous stomatitis, pharyngitis, and/or cervical adenitis. Between attacks, the child is completely healthy.PFAPA is a benign disease that regresses with age. Steroids are used in the treatment of attacks. Colchicine is often preferred in prophylactic treatment. However, if there is no response to medical treatment, surgery (tonsillectomy) can be performed. Genetic and environmental factors are considered in the etiology. Genetic susceptibility concentrated on the genes for Familiar Mediterranean Fever (FMF, MEFV), TNF-Receptor-Associated Periodic Syndrome (TRAPS, gene TNFRF1A), HyperIgDSyndrome (HIDS, gene MVK), and Cryopyrin-Associated Periodic Syndrome (CAPS, gene NLRP3). But its etiology is still unknown.

Group B Streptococcus infection-induced ovarian vein thrombosis identified during cesarean section: A case report and a literature review.

Ovarian vein thrombosis (OVT) is a rare yet potentially life-threatening condition associated with thromboembolic events. Group B Streptococcus (GBS) is a type of β-hemolytic Gram-positive bacterium known for asymptomatic colonization in the lower genital and gastrointestinal tracts. Here we reported a 35-year-old multiparous woman with gestational diabetes who suffered from placental abruption, stillbirth, OVT, septic shock, and renal failure due to severe GBS infection. A 35-year-old woman with gestational diabetes presented with acute and sustained lower abdominal cramping, vaginal bleeding, and fever at 35 gestational weeks. Based on preoperative ultrasound and intraoperative findings, the patient was diagnosed with placental abruption, intrauterine fetal demise, and right OVT. GBS was cultured from the amniotic fluid obtained during cesarean section. The patient underwent a right adnexectomy during a cesarean section and received intravenous antibiotics. Subsequently, an ultrasound-guided uterine curettage was performed due to recurrent fever. After a prolonged course of intravenous antibiotics for over a month, the patient recovered and was discharged from the hospital. This case underscores the need for early initiation of anticoagulant protocols in cases of OVT, particularly when GBS infection is identified as a predisposing factor. Further research and awareness are warranted to better understand the relationship between GBS infection and OVT and to optimize management strategies in such cases.

Exertional leg pain represents a severe disease phenotype in childhood familial Mediterranean fever

ABSTRACT Objectives Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease. Recurrent fever, serositis, and arthritis are common findings of the disease. In addition, musculoskeletal complaints such as exertional leg pain can be overlooked, although they are common and affect patients’ quality of life. The aim of this study was to evaluate the frequency of exertional leg pain in pediatric FMF patients and to analyze the association of this finding with other characteristics of FMF Methods The files of FMF patients were retrospectively evaluated. The clinical characteristics and disease severity of the patients with exertional leg pain were compared with the patients without exertional leg pain. International severity scoring system for FMF (ISSF) and Mor severity score were used for assessment. Results The study included 541 FMF patients (287 females), 149 (27.5%) with exertional leg pain. The median colchicine dosage was significantly higher in patients with exertional leg pain (p = 0.02), arthritis (p = 0.001) and arthralgia (p˂0.001) were encountered more frequently in the attacks of these patients. The median disease severity scores calculated by both Mor severity scale and ISSF were significantly higher in patients with exertional leg pain compared to those without (p˂0.001). In the group of patients with exertional leg pain, the M694V mutation, either in one allele or in two alleles, was found to be significantly more common (p = 0.006 and p˂0.001, respectively). Conclusions Exertional leg pain in pediatric FMF patients is the component of moderate-to-severe disease course, and this may be considerably associated with the presence of M694V mutation.

Identification by Exome Sequencing of Predisposing Variants in Familial Cases of Autoinflammatory Recurrent Fevers.

Periodic fever syndromes include autoinflammatory disorders (AID) that involve innate immunity. These disorders are characterized by recurrent fevers and aberrant multi-organ inflammation, without any involvement of T or B cells or the presence of autoantibodies. A complex genetic architecture has been recognized for many AID. However, this complexity has only been partially uncovered for familial Mediterranean fever and other conditions that have a classical monogenic origin and Mendelian transmission. Several gene panels are currently available for molecular diagnosis in patients suspected of having AID. However, even when an extensive number of genes (up to 50-100) are tested in a cohort of clinically selected patients, the diagnostic yield of AID ranges between 15% and 25%, depending on the clinical criteria used for patient selection. In the remaining 75-85% of cases, it is conceivable that the causative gene or genes responsible for a specific condition are still elusive. In these cases, the disease could be explained by variants, either recessive or dominant, that have a major effect on unknown genes, or by the cumulative impact of different variants in more than one gene, each with minor additive effects. In this study, we focused our attention on five familial cases of AID presenting with classical autosomal dominant transmission. To identify the probable monogenic cause, we performed exome sequencing. Through prioritization, filtering, and segregation analysis, we identified a few variants for each family. Subsequent bioinformatics evaluation and pathway analysis helped to narrow down the best candidate genes for each family to FCRL6, PKN1, STAB1, PTDGR, and VCAM1. Future studies on larger cohorts of familial cases will help confirm the pathogenic role of these genes in the pathogenesis of these complex disorders.

Bsymptoms in unexplained mediastinal lymphadenopathy : Case report of a72-year-old male patient with VEXAS syndrome

The case of a72-year-old male patient who presented to our centre for rare diseases with recurrent fever, night sweats and weight loss with initially confirmed mediastinal lymphadenopathy is reported. Investigation of lymph node material was unrevealing. As an additional finding, the patient had amyelodysplastic syndrome. VEXAS syndrome (vacuoles, E1 enzyme, X‑linked, autoinflammatory, somatic) could be confirmed on the basis of abone marrow biopsy and genetic testing.

Characteristics of persistent arthritis with refractory Kawasaki disease: a single-center retrospective study

Arthritis is one complication of Kawasaki disease (KD); however, the clinical features of arthritis in KD have not been well clarified. We retrospectively investigated the characteristics of persistent arthritis beyond the subacute phase of KD. In this cohort, 49 of 243 patients (20%) developed arthritis, with 33 patients (14%) experiencing persistent arthritis. Among these 33 patients, 31 (94%) had complete KD. Thirty (91%) were resistant to first intravenous immunoglobulin, and 15 (45%) required additional infliximab. Five patients (15%) developed coronary artery lesions, and 24 (73%) had oligoarthritis, mainly in large lower-extremity joints. Twenty-four patients (73%) complained of arthralgia. At arthritis onset, 16 patients (48%) presented with fever, including recurrent fever in 10 patients. Serum C-reactive protein concentration in patients with active arthritis significantly increased compared with after acute KD treatment (2.4 vs. 0.7 mg/dL, p < 0.001). Serum matrix metalloproteinase-3, a biomarker of arthritis, was significantly higher in patients with active arthritis than in remission (93.7 vs. 20.3 ng/mL, p < 0.001). Thirty (91%) and 14 (42%) patients, respectively, were treated with non-steroidal anti-inflammatory drugs and prednisolone, and they completely recovered. To summarize, persistent arthritis is a common complication in refractory KD, and adequate diagnosis and treatment are necessary.

A patient-driven registry on Behçet's disease: the AIDA for patients pilot project.

This paper describes the creation and preliminary results of a patient-driven registry for the collection of patient-reported outcomes (PROs) and patient-reported experiences (PREs) in Behçet's disease (BD). The project was coordinated by the University of Siena and the Italian patient advocacy organization SIMBA (Associazione Italiana Sindrome e Malattia di Behçet), in the context of the AIDA (AutoInflammatory Diseases Alliance) Network programme. Quality of life, fatigue, socioeconomic impact of the disease and therapeutic adherence were selected as core domains to include in the registry. Respondents were reached via SIMBA communication channels in 167 cases (83.5%) and the AIDA Network affiliated clinical centers in 33 cases (16.5%). The median value of the Behçet's Disease Quality of Life (BDQoL) score was 14 (IQR 11, range 0-30), indicating a medium quality of life, and the median Global Fatigue Index (GFI) was 38.7 (IQR 10.9, range 1-50), expressing a significant level of fatigue. The mean Beliefs about Medicines Questionnaire (BMQ) necessity-concern differential was 0.9 ± 1.1 (range - 1.8-4), showing that the registry participants prioritized necessity belief over concerns to a limited extent. As for the socioeconomic impact of BD, in 104 out of 187 cases (55.6%), patients had to pay from their own pocket for medical exams required to reach the diagnosis. The low family socioeconomic status (p < 0.001), the presence of any major organ involvement (p < 0.031), the presence of gastro-intestinal (p < 0.001), neurological (p = 0.012) and musculoskeletal (p = 0.022) symptoms, recurrent fever (p = 0.002), and headache (p < 0.001) were associated to a higher number of accesses to the healthcare system. Multiple linear regression showed that the BDQoL score could significantly predict the global socioeconomic impact of BD (F = 14.519, OR 1.162 [CI 0.557-1.766], p < 0.001). Preliminary results from the AIDA for Patients BD registry were consistent with data available in the literature, confirming that PROs and PREs could be easily provided by the patient remotely to integrate physician-driven registries with complementary and reliable information.

Infective Endocarditis Due to Haemophilus parainfluenzae: A Case Report and Review of the Literature

We present a 20-year-old male who was admitted with recurrent fevers. He was diagnosed with Haemophilus parainfluenzae mitral valve endocarditis with severe regurgitation and perforated leaflet. H. parainfluenzae was resistant to ceftriaxone but repeated sensitivities showed a sensitive organism. Despite endocarditis caused by H. parainfluenzae is rare, physicians should be vigilant of such diagnosis. Antibiotics sensitivity may be questioned if shows a resistant organism.

Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis Syndrome and Syndrome of Unexplained Recurrent Fevers in Children and Adults.

Children and adults with autoinflammatory disorders, who often experience recurrent fevers, rashes, cold-induced symptoms, conjunctivitis, lymphadenopathy, recurrent infections, aphthous stomatitis, and abnormal blood cell counts, may present to the allergist/immunologist because the symptoms mimic allergies and disorders of immunity. In recent years, there has been increased recognition of non-monogenic autoinflammatory disorders, including periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome and syndrome of undifferentiated recurrent fevers. For many clinical practitioners, the natural history, diagnostic criteria, differential diagnoses, and preferred therapies remain challenging because of the presumed rarity of patients and the evolving field of autoinflammation. Here, we aim to provide a practical framework for the clinical allergist/immunologist to evaluate and treat this patient population.

Axial spondyloarthritis in patients with recurrent fever attacks: data from the AIDA network registry for undifferentiated autoInflammatory diseases (USAIDs).

Despite the recent advances in the field of autoinflammatory diseases, most patients with recurrent fever episodes do not have any defined diagnosis. The present study aims at describing a cohort of patients suffering from apparently unexplained recurrent fever, in whom non-radiographic axial spondylarthritis (SpA) represented the unique diagnosis identified after a complete clinical and radiologic assessment. Patients' data were obtained from the international registry on Undifferentiated Systemic AutoInflammatory Diseases (USAIDs) developed by the AutoInflammatory Disease Alliance (AIDA) network. A total of 54 patients with recurrent fever episodes were also affected by non-radiographic axial SpA according to the international classification criteria. SpA was diagnosed after the start of fever episodes in all cases; the mean age at the diagnosis of axial SpA was 39.9 ± 14.8 years with a diagnostic delay of 9.3 years. The highest body temperature reached during flares was 42°C, with a mean temperature of 38.8 ± 1.1°C. The most frequent manifestations associated to fever were: arthralgia in 33 (61.1%) cases, myalgia in 24 (44.4%) cases, arthritis in 22 (40.7%) cases, headache in 15 (27.8%) cases, diarrhea in 14 (25.9%) cases, abdominal pain in 13 (24.1%) cases, and skin rash in 12 (22.1%) cases. Twenty-four (44.4%) patients have taken daily or on-demand non-steroidal anti-inflammatory drugs (NSAIDs) and 31 (57.4%) patients have been treated with daily or on demand oral glucocorticoids. Colchicine was used in 28 (51.8%) patients, while other conventional disease modifying anti-rheumatic drugs (cDMARDs) were employed in 28 (51.8%) patients. Forty (74.1%) patients underwent anti-tumor necrosis factor (TNF) agents and 11 (20.4%) were treated with interleukin (IL)-1 inhibitors. The response to TNF inhibitors on recurrent fever episodes appeared more effective than that observed with anti-IL-1 agents; colchicine and other cDMARDs were more useful when combined with biotechnological agents. Signs and symptoms referring to axial SpA should be inquired in patients with apparently unexplained recurrent fever episodes. The specific treatment for axial SpA may lead to a remarkable improvement in the severity and/or frequency of fever episodes in patients with unexplained fevers and concomitant axial SpA.