Elevated Acute Phase Reactants Research Articles

Familial Mediterranean Fever: Recent Developments in Pathogenesis and New Recommendations for Management.

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease (AID) affecting mainly the ethnic groups originating from Mediterranean basin. The disease is characterized by self-limited inflammatory attacks of fever and polyserositis along with elevated acute phase reactants. FMF is inherited autosomal recessively; however, a significant proportion of heterozygotes also express the phenotype. FMF is caused by mutations in the MEFV gene coding for pyrin, which is a component of inflammasome functioning in inflammatory response and production of interleukin-1β (IL-1β). Recent studies have shown that pyrin recognizes bacterial modifications in Rho GTPases, which results in inflammasome activation and increase in IL-1β. Pyrin does not directly recognize Rho modification but probably affected by Rho effector kinase, which is a downstream event in the actin cytoskeleton pathway. Recently, an international group of experts has published the recommendations for the management of FMF. Colchicine is the mainstay of FMF treatment, and its regular use prevents attacks and controls subclinical inflammation in the majority of patients. Furthermore, it decreases the long-term risk of amyloidosis. However, a minority of FMF patients fail to response or tolerate colchicine treatment. Anti-interleukin-1 drugs could be considered in these patients. One should keep in mind the possibility of non-compliance in colchicine-non-responders. Although FMF is a relatively well-described AID and almost 20 years has passed since the discovery of the MEFV gene, there are still a number of unsolved problems about it such as the exact mechanism of the disease, symptomatic heterozygotes and their treatment, and the optimal management of colchicine resistance.

Cord Blood Acute Phase Reactants Predict Early Onset Neonatal Sepsis in Preterm Infants.

BackgroundEarly onset sepsis (EOS) is a major cause of morbidity and mortality in preterm infants, yet diagnosis remains inadequate resulting in missed cases or prolonged empiric antibiotics with adverse consequences. Evaluation of acute phase reactant (APR) biomarkers in umbilical cord blood at birth may improve EOS detection in preterm infants with intrauterine infection.MethodsIn this nested case-control study, infants (29.7 weeks gestation, IQR: 27.7–32.2) were identified from a longitudinal cohort with archived cord blood and placental histopathology. Patients were categorized using culture, laboratory, clinical, and antibiotic treatment data into sepsis groups: confirmed sepsis (cEOS, n = 12); presumed sepsis (PS, n = 30); and no sepsis (controls, n = 30). Nine APRs were measured in duplicate from cord blood using commercially available multiplex immunoassays (Bio-Plex Pro™). In addition, placental histopathologic data were linked to biomarker results.ResultscEOS organisms were Escherichia coli, Streptococcus agalactiae, Proteus mirabilis, Haemophilus influenzae and Listeria monocytogenes. C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp), serum amyloid P and ferritin were significantly elevated in cEOS compared to controls (p<0.01). SAA, CRP, and Hp were elevated in cEOS but not in PS (p<0.01) and had AUCs of 99%, 96%, and 95% respectively in predicting cEOS. Regression analysis revealed robust associations of SAA, CRP, and Hp with EOS after adjustment for covariates. Procalcitonin, fibrinogen, α-2-macroglobulin and tissue plasminogen activator were not significantly different across groups. Placental acute inflammation was associated with APR elevation and was present in all cEOS, 9 PS, and 17 control infants.ConclusionThis study shows that certain APRs are elevated in cord blood of premature infants with EOS of intrauterine origin. SAA, CRP, and Hp at birth have potential diagnostic utility for risk stratification and identification of infants with EOS.

Carotid Artery Atherosclerosis in Patients with Active Rheumatoid Arthritis: Predictors of Plaque Occurrence and Progression Over 24 Weeks.

Introduction:This study evaluated the prevalence and progression of subclinical carotid artery atherosclerosis in active rheumatoid arthritis (RA).Methods:Carotid arteries of RA patients were scanned using 3D ultrasound at baseline and 24 weeks for total plaque area, vessel wall volume, and intima-media thickness (IMT), as well as arterial stiffness measured using pulse wave velocity. Variables related to inflammation, lipids and cardiovascular (CV) risk were assessed for associations with plaque progression. Of 195 screened patients, 31 met inclusion criteria (66 Swollen joint count (SJC) plus 68 Tender joint count (TJC)≥8 OR SJC plus TJC≥4 with elevated acute phase reactants) and were enrolled (27 female; mean age 59.3±9.8years). Patients using lipid lowering drugs and uncontrolled comorbidities were excluded.Results:Atherosclerotic plaque occurred in 35% and arterial wall hypertrophy (IMT≥0.6mm) in 86% of patients. Most (68%) had an abnormal lipid profile characterized by reduced HDL and/or increased total cholesterol/HDL index, which was adversely affected by disease activity. Stepwise binary logistic regression analysis showed that Framingham risk score (OR=1.155, 95%CI:1.002-1.332, p=0.046) and ESR (OR=1.148, 95%CI:1.015-1.299, p=0.028) predicted plaque burden most strongly. Plaque progression was significantly associated with baseline higher hsCRP, ESR, and heavy smoking, but only hsCRP predicted plaque growth in multivariate regression analysis (p=0.004); and hsCRP was related to higher disease activity (r=0.443, p=0.016), LDL (r=0.544, p=0.007), and smoking (r=0.384, p=0.04).Conclusion:RA-related inflammation contributed to augmented CV burden in RA and might mediate its effect on atherosclerosis through hsCRP and modulation of the traditional CV risk factors, such as dyslipidemia.

Monogenic polyarteritis: the lesson of ADA2 deficiency

The deficiency of Adenosine Deaminase 2 (DADA2) is a new autoinflammatory disease characterised by an early onset vasculopathy with livedoid skin rash associated with systemic manifestations, CNS involvement and mild immunodeficiency.This condition is secondary to autosomal recessive mutations of CECR1 (Cat Eye Syndrome Chromosome Region 1) gene, mapped to chromosome 22q11.1, that encodes for the enzymatic protein adenosine deaminase 2 (ADA2). By now 19 different mutations in CECR1 gene have been detected.The pathogenetic mechanism of DADA2 is still unclear. ADA2 in a secreted protein mainly expressed by cells of the myeloid lineage; its enzymatic activity is higher in conditions of hypoxia, inflammation and oncogenesis. Moreover ADA2 is able to induce macrophages proliferation and differentiation; it’s deficiency is in fact associated with a reduction of anti-inflammatory macrophages (M2). The deficiency of ADA2 is also associated with an up-regulation of neutrophils-expressed genes and an increased secretion of pro-inflammatory cytokines. The mild immunodeficiency detected in many DADA2 patients suggests a role of this protein in the adaptive immune response; an increased mortality of B cells and a reduction in the number of memory B cells, terminally differentiated B cells and plasmacells has been described in many patients. The lack of the protein is associated with endothelium damage; however the function of this protein in the endothelial homeostasis is still unknown.From the clinical point of view, this disease is characterized by a wide spectrum of severity. Chronic or recurrent systemic inflammation with fever, elevation of acute phase reactants and skin manifestations (mainly represented by livedo reticularis) is the typical clinical picture. While in some patients the disease is mild and skin-limited, others present a severe, even lethal, disease with multi-organ involvement; the CNS involvement is rather common with ischemic or hemorrhagic strokes. In many patients not only the clinical picture but also the histopathologic features are undistinguishable from those of systemic polyarteritis nodosa (PAN). Of note, patients with an unusual phenotype, mainly dominated by clinical manifestations suggestive for an immune-disrective condition, have been described.Due to its rarity, the response to treatment of DADA2 is still anecdotal. While steroids can control the disease’s manifestations at high dosage, none of the common immunosuppressive drugs turned out to be effective. Biologic drugs have been used only in few patients, without a clear effectiveness; anti-TNF drugs are those associated to a better clinical response. Hematopoietic stem cells transplantation was effective in patients with a severe phenotype.

Identification of Pasteurella canis in a Soft Tissue Infection Caused by a Dog Bite: The First Report in Korea

Dear Editor, Pasteurella canis is a small, gram-negative coccobacillus that is a part of the normal flora of healthy domestic animals, especially dogs [1]. Although P. canis is a well-known major pathogen of infections caused by dog bites, only few cases of human infections with P. canis have been reported [2-5]. We report a case of soft tissue infection caused by P. canis. A 54-yr-old woman without underlying diseases visited the emergency department with multiple lacerations caused by a dog bite incurred two days prior. She had received immediate treatment with wound dressing, antibiotics (amoxicillin/clavulanic acid), and tetanus immunoglobulin at another hospital on the day she was bitten. However, the wound was worsening. The initial vital signs were as follows: temperature, 37.7°C; pulse rate, 88/min; respiratory rate, 20/min; blood pressure 108/73 mmHg. The wounds were located on the right distal arm (3 cm in the anteromedial area, 3 cm in the anterolateral area, and 4 cm in the posterior area with muscle exposure). Abnormalities such as fracture were absent on plain radiographs. The initial blood counts were as follows: white blood cells (WBCs), 10.4×10/L (neutrophils, 80.5%); hemoglobin, 12.4 g/ dL; and platelets 173×10/L. No prominent abnormalities in blood chemistry were observed on routine tests except for mildly elevated acute phase reactants (C-reactive protein [CRP], 5.82 mg/dL; erythrocyte sedimentation rate [ESR], 52 mm/hr). The patient was admitted, and amoxicillin/clavulanic acid were administered immediately and maintained throughout the hospitalization period. Tetanus and rabies vaccines were also given to prevent potential infections. Microbiological examination of the wounds was performed. A specimen was collected for Gram staining and culture. Gram-negative coccobacilli were observed on a direct gram-stained smear from the wound specimens (Fig. 1A). Pus specimens were inoculated on 5% sheep blood agar, chocolate agar, and MacConkey agar. After 24 hr, the growth of smooth, grayish-white colonies was observed on the blood agar and chocolate agar but not on the MacConkey agar (Fig. 1B). The colonies were positive for catalase and oxidase reactions. All isolates were identified with MicroScan Walkaway (Beckman Coulter, Brea, CA, USA) and Vitek automated bacterial identification systems 2 (bioMerieux, Marcy-l’Etoile, France) and a VITEK MS matrix-assisted laser desorption ionization mass spectrometry (MALDI-TOF MS) system (bioMerieux). For further identification of bacterial species, 16S ribosomal RNA (rRNA) gene sequencing was carried out. The universal primers 8F (5 -TTGGAGAGTTTGATCCTGGCTC-3 ) and 801R (5 -GGCGTGGACTTCCAGGGTATCT-3 ) were used to amplify

¿La enfermedad de Kawasaki ha perdido su afectación articular?

ObjectiveKawasaki disease (KD) is an acute systemic vasculitis affecting medium-sized arteries, particularly the coronary arteries. Classic diagnosis is based in prolonged fever and different clinical features, including acute arthritis. Our objective is to determine the prevalence of arthritis at the moment of the diagnosis, the response to intravenous immunoglobulin infusion and the relation with cardiac findings. Material and MethodsRetrospective study through review of medical records of 42 patients with KD from 1988 to 2013. Demographic, clinical, laboratory variables and treatment were reviewed. ResultsMale sex was predominant (57%). Fever (100%), exanthema (92,9%), conjunctivitis (78,6%), oropharingeal changes (76,2%), cervical lymphadenopathy (71,4%), edema (52,4%) and peripheral desquamation (46,3%) were reported. Eight patients presented ecocardiography alterations (ectasia and aneurism). Acute articular involvement was reported in 7 (16%) patients, including oligoarticular (57%), monoarticular (29%) and polyarticular (14%) patterns. All patients had elevation of acute phase reactants with neutrophilia (57%) and hypoalbuminemia (71,5%), but showed a good therapeutic response to intravenous immunoglobulin, without sequelaes. Sixteen patients had incomplete KD nine males, with 100% of fever exanthema (75%), conjunctivitis (56%) and 50% of cervical lymphadenopathy. Whereas oropharingeal changes and edemas was described in 44% and 25% of them. Four patients with incomplete KD had coronary artery abnormalities. ConclusionsAcute arthritis was an uncommon finding (16%) and resulted in no sequelae. Maybe the treatment with intravenous immunoglobulin and aspirin prevents the development of articular abnormalities and then leading to a decrease in its follow-up requierement by reumathologist. The cardiovascular sequelae, mainly incomplete KD, remains determining its prognosis. The presence of articular involvement seems not to have influence over cardiac involvement.

Pediatric Kawasaki Disease and Adult Human Immunodeficiency Virus Kawasaki-Like Syndrome Are Likely the Same Malady.

Background. Pediatric Kawasaki disease (KD) and human immunodeficiency virus (HIV)+ adult Kawasaki-like syndrome (KLS) are dramatic vasculitides with similar physical findings. Both syndromes include unusual arterial histopathology with immunoglobulin (Ig)A+ plasma cells, and both impressively respond to pooled Ig therapy. Their distinctive presentations, histopathology, and therapeutic response suggest a common etiology. Because blood is in immediate contact with inflamed arteries, we investigated whether KD and KLS share an inflammatory signature in serum.Methods. A custom multiplex enzyme-linked immunosorbent assay (ELISA) defined the serum cytokine milieu in 2 adults with KLS during acute and convalescent phases, with asymptomatic HIV+ subjects not taking antiretroviral therapy serving as controls. We then prospectively collected serum and plasma samples from children hospitalized with KD, unrelated febrile illnesses, and noninfectious conditions, analyzing them with a custom multiplex ELISA based on the KLS data.Results. Patients with KLS and KD subjects shared an inflammatory signature including acute-phase reactants reflecting tumor necrosis factor (TNF)-α biologic activity (soluble TNF receptor I/II) and endothelial/smooth muscle chemokines Ccl1 (Th2), Ccl2 (vascular inflammation), and Cxcl11 (plasma cell recruitment). Ccl1 was specifically elevated in KD versus febrile controls, suggesting a unique relationship between Ccl1 and KD/KLS pathogenesis.Conclusions. This study defines a KD/KLS inflammatory signature mirroring a dysfunctional response likely to a common etiologic agent. The KD/KLS inflammatory signature based on elevated acute-phase reactants and specific endothelial/smooth muscle chemokines was able to identify KD subjects versus febrile controls, and it may serve as a practicable diagnostic test for KD.

Abstract TP353: Glucose on Admission Associated With Post-stroke Outcome

Introduction: Studies suggest that an elevated inflammatory profile is associated with increased stroke incidence and worse post-stroke outcome. It is unclear if an elevated inflammatory profile on admission is a useful prognostic marker of poor outcome after stroke, a reflection of a more severe stroke, or a marker of infection or the comorbidities that caused the stroke. Hypothesis: We hypothesized that elevated acute phase reactants (APRs) are associated with poor outcome post-stroke, independent of stroke severity and infection. Methods: The study used a prospectively collected clinical database of 755 patients admitted for ischemic or hemorrhagic stroke. APRs studied included erythrocyte sedimentation rate (ESR), glucose, platelets, and white blood cell count. Outcome was assessed at discharge using a dichotomous modified Rankin Scale (mRS) score of 3-6 (poor outcome) vs. 0-2 (good outcome), and was evaluated in multivariate logistic regression. Analyses were adjusted for NIHSS, age, sex, race, hypertension, diabetes, and use of antithrombotic medication, and were further stratified by presence/ absence of diabetes, infection (via urinalysis), and by race. Results: Elevated ESR (OR: 1.16, 95% CI: 1.00-1.33) and glucose (OR: 1.04 per 10 mg/dL, 95% CI: 1.00-1.09), were each associated with poor outcome, independent of stroke severity (NIHSS). Even in non-diabetics, elevated glucose was associated with 15% non-significantly higher odds of poor outcome per 10 mg/dL (95% CI: 0.998-1.34). However, subgroup analysis of those without infection showed no association between APRs and poor outcome. In race-stratified models, glucose level was significantly associated with poor outcome in African Americans (OR: 1.13, 95% CI: 1.01-1.26), but not in other races. Conclusion: Our study shows that ESR is associated with poor outcome after stroke, independently of stroke severity, and that elevated glucose may be associated with increased odds of poor outcome in non-diabetic or African American ischemic stroke patients. Glucose and ESR may play a role in determining prognosis of stroke patients, and therefore point to a potential target for improving outcome of stroke patients.

Assessment of the New 2012 EULAR/ACR Clinical Classification Criteria for Polymyalgia Rheumatica: A Prospective Multicenter Study.

To assess the performance of the new 2012 provisional European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) polymyalgia rheumatica (PMR) clinical classification criteria in discriminating PMR from other mimicking conditions compared with the previous 5 diagnostic criteria in a multicenter prospective study. Patients older than 50 years, presenting with new-onset bilateral shoulder pain with elevated acute-phase reactants (APR), were assessed for the fulfillment of the new and old classification/diagnostic criteria sets for PMR. At the end of the 1-year followup, 133 patients were diagnosed with PMR (expert opinion) and 142 with non-PMR conditions [69 rheumatoid arthritis (RA)]. Discriminating capacity, sensitivity, and specificity of the criteria sets were estimated. Discriminating capacity of the new clinical criteria for PMR from non-PMR conditions and RA as estimated by area under the curve (AUC) were good with AUC of 0.736 and 0.781, respectively. The new criteria had a sensitivity of 89.5% and a specificity of 57.7% when tested against all non-PMR cases. When tested against all RA, seropositive RA, seronegative RA, and non-RA control patients, specificity changed to 66.7%, 100%, 20.7%, and 49.3%, respectively. Except for the Bird criteria, the 4 previous criteria had lower sensitivity and higher specificity (ranging from 83%-93%) compared with the new clinical criteria in discriminating PMR from all other controls. The new 2012 EULAR/ACR clinical classification criteria for PMR is highly sensitive; however, its ability to discriminate PMR from other inflammatory/noninflammatory shoulder conditions, especially from seronegative RA, is not adequate. Imaging and other modifications such as cutoff values for APR might increase the specificity of the criteria.

How do general practitioners identify inflammatory arthritis? A cohort analysis of Dutch general practitioner electronic medical records.

To examine the symptoms, signs and additional investigations that general practitioners (GPs) used in the process of diagnosing recent-onset inflammatory arthritis. Here, we assumed that the recorded information was crucial in the diagnostic process of arthritis. A database including electronic medical records of 16 Dutch general practices with 44,350 patients was studied. Patients with an episode of RA and allied conditions according to the International Classification of Primary Care-1 code L88 (here summarized as inflammatory arthritis) in the period 2009-2013 were selected. Frequencies of symptoms, signs and performed additional investigations were evaluated and compared between referred and non-referred patients. A total of 126 patients were diagnosed with inflammatory arthritis. Information on symptom duration, symptom location, swelling, loss of function, redness and warmth were recorded in, respectively, 64, 90, 80, 52, 48 and 41% of patients. Information on morning stiffness, family history or the squeeze-test was provided in 20, 18 and 17% of patients. Symmetry, inflammatory type arthralgia and fist closure were not recorded. Acute phase reactants and auto-antibody tests were performed in 40-46% and 8-11%, respectively. Eighty-four patients (67%) were referred to secondary care. Symptoms located in the foot, morning stiffness, family history, myalgia, absence of redness and elevated acute phase reactants were associated with referral (all P < 0.05). GPs mainly used classical signs of inflammation to diagnose inflammatory arthritis. Other items that are regularly assessed in secondary care (morning stiffness, squeeze-test, family history) were infrequently recorded by GPs.

Is Acute Coronary Syndrome Secondary to Coronary Vasculitis Underestimated in Daily Cardiology Practice?

Acute coronary syndrome (ACS) is an increasing clinical diagnosis in daily practice. ACS is a life-threatening condition with high mortality rate if left untreated. The better-known risk factors for ACS are dyslipidemia, diabetes mellitus, hypertension2 and coronary vasospasm. Coronary vasculitis is the least appreciated cause of ACS that is subject to neglect among clinicians. Coronary vasculitis (CV) may occur as a single organ vasculitis (SOV) or in the context of specific systemic vasculitides. CV may be the initial presentation of specific systemic vasculitis. Current concept indicates the “worse prognosis” in myocardial infarction associated with elevated acute phase reactants, while these could be the critical point in missed-diagnosis of occult coronary vasculitis as classic cases with atherosclerosis of coronary vessels as the culprit mechanism. We suppose that if elevated CRP/ ESR be due to inflammatory process within the vessel wall, then a classic approach of anticoagulants, thrombolytic therapy or primary coronary angioplasty paradoxically could be dangerous13 and, vice versa, different look with using glucocorticoids could be lifesaving, the medication that later on proved that can improve prognosis in ACS and MI. So, with increasing prevalence of acute coronary syndromes in younger people, the possibility of underestimating coronary vasculitis is potentiated and emphasizing only on classic and common risk factors of ACS is not prudent.

Chest Pain: The Need to Consider Less Frequent Diagnosis

Chest pain is one of the most frequent patient's complaints. The commonest underlying causes are well known, but, sometimes, in some clinical scenarios, it is necessary to consider other diagnoses. We report a case of a 68-year-old Caucasian male, chronically hypertensive, who complained of recurrent episodes of chest pain and fever with elevated acute phase reactants. The first investigation was negative for some of the most likely diagnosis and he quickly improved with anti-inflammatory drugs. Over a few months, his symptoms continued to recur periodically, his hypertension was aggravated, and he developed headaches and lower limbs claudication. After a temporal artery biopsy that was negative for vasculitis, he underwent a positron emission tomography suggestive of Takayasu Arteritis. Takayasu Arteritis is a rare chronic granulomatous vasculitis of the aorta and its first-order branches affecting mostly females up to 50 years old. Chest pain is experienced by >40% of the patients and results from the inflammation of the aorta, pulmonary artery, or coronaries.

Parenchymal Pulmonary Disease in Systemic Idiopathic Juvenile Arthritis: A Case Report

Parenchymal pulmonary disease is a rare and poorly described manifestation of systemic juvenile idiopathic arthritis (sJIA). We report the case of a girl, 6.5 years-old, admitted due to an alleged infectious pneumonia in the context of 14 days of fever, pulmonary consolidation and pleural effusion unresponsive to antibiotics. The latter association of hip and cervical arthritis, hepatosplenomegaly and persistent elevated acute phase reactants evoked the diagnosis of sJIA, which promptly improved with oral prednisolone and oral methotrexate. This case illustrates parenchymal pulmonary involvement as the main manifestation of sJIA.

Coronary aneurysms and coronary arterial bypass graft disease as initial presentation of Takayasu's arteritis, induced by hepatitis B infection

A 51-year-old Indian gentleman, after CABG surgery, developed blood transfusion induced acute hepatitis B infection, which recovered completely with symptomatic treatment. Subsequently, he developed recurrent angina, dyspnoea along with musculoskeletal symptoms with elevated acute phase reactants. A CT angiography showed thickening of bilateral subclavian arteries and left renal artery stenosis. His RIMA graft was totally occluded at the origin and the LIMA graft showed an aneurysm at the anastomotic site with the left anterior descending artery (LAD). FDG-PET scan showed active inflammation of the ascending and descending thoracic aorta. He was diagnosed as Takayasu's arteritis. He responded to steroids and immunosuppressants. One month later he developed acute coronary syndrome and a coronary angiography showed severe left main stenosis with a left main aneurysm and a significant ostial LCx lesion. His LAD had an aneurysm at the anastomotic site with the patent LIMA graft. His RCA also had an aneurysm followed by a total occlusion. His LIMA graft also showed a significant lesion and his RIMA graft was occluded. He underwent angioplasty and stenting with DES to the LAD at the anastomotic site and to the left main-LCx. DiscussionThe case highlights the diverse modes of presentation of Takayasu's arteritis. Our case presented as acute coronary syndrome with multiple coronary aneurysms and bypass graft disease, which was successfully treated with angioplasty and stenting. The case also highlights the importance of viral infections and vaccinations in the pathogenesis of Takayasu's arteritis.

Prevalence of CECR1 mutations in pediatric patients with polyarteritis nodosa, livedo reticularis and/or stroke

Methods Pediatric patients of Caucasian Italian origin with the following diseases/manifestations were included in the study: i) histologically confirmed polyartiritis nodosa (PAN) or cutaneous polyartiritis nodosa (cPAN), ii) persistent livedo reticularis with elevation of acute phase reactants, iii) ischemic or hemorrhagic strokes with systemic inflammation. Direct sequencing of CECR1 gene (exons 1-9) was performed with Sanger analysis.

Deficiency of Interleukin-1 Receptor Antagonist (DIRA): Report of the First Indian Patient and a Novel Deletion Affecting IL1RN

Purpose Deficiency of interleukin-1 receptor antagonist (DIRA) is a rare life-threatening autoinflammatory disease caused by autosomal recessive mutations in IL1RN. DIRA presents clinically with early onset generalized pustulosis, multifocal osteomyelitis, and elevation of acute phase reactants. We evaluated and treated an antibiotic-unresponsive patient with presumed DIRA with recombinant IL-1Ra (anakinra). The patient developed anaphylaxis to anakinra and was subsequently desensitized.

Underlying causes of persistently elevated acute phase reactants in patiens with Familial Mediterranean Fever

Background Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are most commonly employed acute phase reactants in follow up of patients with Familial Mediterranean Fever (FMF). As a rule CRP increases during FMF attacks but it returns to normal values in attack free periods. Persistently elevated acute phase reactants in attack free periods can be occasionally observed in patients with FMF and is suggested to be a risk for the development of amyloidosis. Some authors suggested the use of IL-1 antagonists in such patients to prevent from amyloidosis. However there is no data regarding causes of elevated acute phase reactants in patients with FMF.

Typhus Fever—A Diagnostic Dilemma

Five cases with prolonged fever, marked toxemia, generalized lymphadenopathy, and abdominal distension presented to us at the Institute of Child Health, Kolkata, India. The clinical pictures mimicked enteric fever in that all of the cases had continuous fever, toxemia, apathy, and significant abdominal distension. A clinician encountering the cases would have thought of enteric fever except for the presence of generalized lymphadenopathy. Investigations revealed leukocytosis, elevated acute phase reactants (ESR and CRP), and negative blood cultures. The Weil–Felix reaction was positive in all the cases. Our case series is an important reminder to clinicians in developing countries that typhus fever, which is a reemerging disease, can closely mimic enteric fever. All the children made a full recovery after treatment with oral doxycycline or azithromycin.

Considerations on treatment recommendations for rheumatoid arthritis

Given the polyarticular, chronic, progressive, incapacitating, invalidating effects that shorten survival in patients with rheumatoid arthritis (AR), achieving a state of remission, or at least minimal activity, is imperative. In this quest, several guidelines have been published to reach this outcome. Some recommendations, however, may awaken a certain degree of dissent or provide food for thought, while yet other points of interest merit inclusion in these guidelines. Periodical guideline evaluations have produced clarifications, such as, “monitoring should be frequent in active disease (every 1–3 months); if there is no improvement by at most 3 months after treatment start or the target has not been reached by 6 months, therapy should be adjusted.”1 It is reasonable that adjustments in treatment may be done one month after treatment for those patients with poor prognostic factors,2,3 those with high disease activity score with triple therapy, and in cases of persistent or increased activity (number of painful and inflamed joints, elevated acute-phase reactants, positive serology, early radiological changes, extra-articular manifestations). Rheumatologists should make therapeutic modifications without waiting to reach wideranging limits to modify treatment, which is also applicable when there is expression of toxicity. Several studies have emphasized the advantages of achieving early remission, even for longer survival.4 Despite this, most controlled studies have evaluations for decisionmaking some 3 months or more after the start of treatment, even with small-molecules and biological therapy, which are treatments that show a response in days or weeks. Methotrexate is the cornerstone of initial treatment; it is accessible and provides adequate effectiveness and tolerability. The ACR guidelines, which are to be published in 2015, are based on

ACPA-positive primary Sjögren's syndrome: true primary or rheumatoid arthritis-associated Sjögren's syndrome?

ObjectivesAnticyclic citrullinated protein antibodies (ACPA) are highly specific of rheumatoid arthritis (RA). However, they have also been detected in 5–10% of primary Sjögren's syndrome (pSS). We compared ACPA-positive and negative...