Elevated Acute Phase Reactants Research Articles

A case of bilateral suppurative arthritis of hip joint with concomitant pyomyositis.

A case of bilateral suppurative arthritis of hip joint with concomitant pyomyositis.

Factors associated to temporal artery biopsy result in suspects of giant cell arteritis: a retrospective, multicenter, case-control study

To evaluate the positivity rate of temporal artery biopsies (TAB) performed in suspects of giant cell arteritis (GCA) and to study the epidemiological and clinical factors associated to the biopsy result. A retrospective, multicenter, case-control study was performed, including three hundred and thirty-five patients who underwent TAB for a suspicion of GCA from 2001 to 2010. Clinical, epidemiological and pathology data were recovered from the patients' clinical records. Histologic diagnosis of GCA was made when active inflammation or giant cells were found in the arterial wall. Eighty-one biopsies (24.2%) were considered positive for GCA. Clinical factors independently associated to TAB result in a logistic regression analysis were temporal cutaneous hyperalgesia (OR = 10.8; p < 0.001), jaw claudication (OR = 4.6; p = 0.001), recent-onset headache (OR = 4.4; p = 0.001), decreased temporal pulse (OR = 2.8; p = 0.02), pain and stiffness in neck and shoulders (OR = 2.3; p = 0.05), unintentional weight loss (OR = 1.33; p = 0.003) and age (OR = 1.085; p = 0.004). Other factors such as length of the surgical specimen (OR = 1.079; p = 0.028) and erythrocyte sedimentation rate (OR = 1.042; p < 0.001) were also statistically significant. The model was accurate (C-index = 0.921), reliable (pHosmer-Lemeshow = 0.733) and consistent in the bootstrap sensitivity analysis. No significant association was detected between TAB result and number of days of previous systemic corticosteroid treatment (p = 0.146). However, an association was observed between TAB result and the total accumulated dose of previous systemic corticotherapy (p = 0.043). Exhaustive anamnesis and clinical examination remain of paramount importance in the diagnosis of GCA. To improve the yield of TAB, it should be performed specially in older patients with GCA-compatible clinic. TAB could be avoided in patients with an isolated elevation of acute phase reactants, without GCA-compatible clinic.

Radiographic progression in ankylosing spondylitis/axial spondyloarthritis

Radiographic progression in the axial skeleton is considered as an important outcome in ankylosing spondylitis (AS) and in the whole group of axial spondyloarthritis (SpA). Recently new data on the rates and predictors of radiographic progression from observational cohorts have become available. Here we summarize recent data and discuss their clinical relevance and directions for further investigations. Nonradiographic axial SpA progresses to AS with a rate of about 12% over 2 years; elevated C-reactive protein (CRP) is an important predictor of such a progression. The rate of radiographic progression in the spine is strongly dependent on the presence of the following risk factors: syndesmophytes at baseline, elevated acute phase reactants (CRP and/or erythrocyte sedimentation rate) and smoking. The presence of radiographic damage in the spine has a strong impact on spinal mobility and functional status, although the association of radiographic sacroiliitis progression with the functional status remains unclear. Radiographic progression in the spine and, to a lesser extent, in the sacroiliac joint represents a clinically relevant clinical outcome and treatment target in AS/axial SpA.

Diagnose und Therapie der axialen Spondyloarthritis einschließlich des Morbus Bechterew

The term axial spondyloarthritis covers patients with established structural changes visible on x-ray in sacroiliac joints and/or in the spine (classical ankylosing spondylitis) but also patients with non-radiographic axial spondyloarthritis in whom early inflammatory signs of the disease can only be visualized with magnetic resonance imaging (MRI). The MRI technique plays an important role in the diagnosis of this disease and an early diagnosis is normally based on a combination of clinical, laboratory and imaging parameters. Only non-steroidal anti-inflammatory drugs and TNF-α blockers are effective in the treatment of axial spondyloarthritis. Patients with short disease duration and elevated acute phase reactant levels demonstrate best therapy response and, therefore, should be closely followed-up and consistently treated.

Pseudocoarctation of the Aorta Secondary to Aortic Intimal Sarcoma

We describe a case of a 66-year-old woman who presented with upper extremity hypertension and a pseudocoarctation-like picture secondary to an aortic arch intimal sarcoma.

The autoinflammatory diseases

The monogenic autoinflammatory syndromes are conditions caused by mutations of genes coding for proteins that play a pivotal role in the regulation of the inflammatory response. Due to their genetic nature, most of these disorders have an early onset. Clinically they are characterised by recurrent flares of systemic inflammation presenting most of the time as sudden fever episodes associated with elevation of acute phase reactants and with a number of clinical manifestations such as rash, serositis, lymphadenopathy and arthritis. Symptom-free intervals are characterised by complete wellbeing, normal growth and complete normalisation of acute phase reactants. Familial Mediterranean fever (FMF), mevalonate-kinase deficiency (MKD) and tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) are the three monogenic disorders subsumed under the term periodic fevers, while a systemic inflammation dominated by a characteristic urticarial rash associated with a number of other clinical manifestations is typical of familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and chronic infantile neurological cutaneous and articular syndrome (CINCA). These diseases represent the clinical spectrum of different mutations of a gene named cold-induced autoinflammatory syndrome 1 (CIAS-1, or NLRP3) coding for a protein called cryopyrin. Hence these disorders are also known as cryopyrin-associated periodic syndromes (CAPS). Other conditions are characterised by typical granulomatous formations (granulomatous disorders). Blau's syndrome (familial juvenile systemic granulomatosis) presents with non-caseating granulomatous inflammation affecting the joint, skin, and uveal tract (the triad of arthritis, dermatitis and uveitis) and is associated with mutations of the NACHT domain of the gene CARD15 (or NOD2).

Monocular Vision Loss and Headache in a 60-Year-Old Liver Transplant Patient

Monocular Vision Loss and Headache in a 60-Year-Old Liver Transplant Patient

The prevalence of clinical remission in RA patients treated with anti-TNF: results from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry

To evaluate the prevalence of clinical remission and minimal disease activity according to the ACR/European League Against Rheumatism (EULAR) remission, DAS-28 <2.6 and minimal disease activity (MDA) criteria, and to compare the extent of residual disease activity with disability in RA patients after 6 months of treatment with anti-TNF. In the Dutch Rheumatoid Arthritis Monitoring (DREAM) biologic registry the prevalence of DAS-28 <2.6, MDA and ACR/EULAR remission criteria was assessed. Residual disease activity during MDA or remission was assessed as the percentage of patients with swollen and tender joints, elevated acute-phase reactants and general health on a visual analogue scale (VAS). Disability was evaluated with the HAQ score. Prevalence of DAS-28 <2.6 was 27%, prevalence of MDA was 34% and ACR/EULAR remission was reached by 6% of patients. Residual disease activity was present mostly in the most lenient criteria and occurred most frequently on the level of swollen joint count and VAS score: at least one swollen joint in DAS-28 <2.6, MDA and ACR/EULAR remission was present in, respectively, 51, 54 and 34% of the patients. VAS >1 occurred in, respectively, 67, 69 and 0% of the patients. Modification of the cut-point of the patient-reported outcome increased the prevalence of ACR/EULAR remission, but also the level of disability. MDA and DAS-28 <2.6 are reachable treatment targets in RA with anti-TNF, although residual disease activity might still be present. In turn, ACR/EULAR remission criteria leave little residual disease activity, but might be too stringent for use in daily clinical practice due to the strict cut-point in the patient-reported outcome.

Continuous NSAID use reverts the effects of inflammation on radiographic progression in patients with ankylosing spondylitis

ObjectivesThe aim was to compare continuous and on-demand NSAID treatment with respect to their ability to suppress radiographic progression in subgroups of patients with high/elevated CRP-levels, ESR, ASDAS-levels or BASDAI-levels...

DIRA, DITRA, and New Insights Into Pathways of Skin Inflammation

Dermatology has a long-standing affinity for acronyms. From AGEP (acute generalized exanthematous pustulosis) to XP (xeroderma pigmentosum), acronyms have become a part of our dermatology lexicon, perhaps occasionally to the consternation of our colleagues in other specialties. In this issue, Brau-Javier et al1 describe a patient with a severe pustular skin disease called “DIRA”—an acronym for “deficiency of the interleukin 1 (IL-1) receptor antagonist,” which we first described in 9 pediatric patients in 2009.2 As its name suggests, DIRA is a new autoinflammatory disease linked to activation of the IL-1 pathway (Figure), joining the ranks of other IL-1–associated conditions with a prominent dermatologic component, foremost the cryopyrin-associated periodic fever syndromes (CAPS)—familial cold–induced autoinflammatory syndrome (FCAS), Muckle-Wells syndrome, and neonatal-onset multisystem inflammatory disease (NOMID).3 Figure The pathogenesis of DIRA (deficiency of the interleukin 1 [IL-1] receptor [IL-1R] antagonist) and DITRA (deficiency of the IL-36 receptor [IL-36R] antagonist). Loss of the IL-1R antagonist leads to unopposed proinflammatory signaling by IL-1α ... CAPS is caused by gain of function mutations that lead to oversecretion of the well-established fever causing cytokine IL-1Β, and all 3 disorders manifest in the skin as neutrophilic urticaria. In contrast, DIRA presents in the neonatal period with a severe neutrophilic “pustular” skin eruption, skin pathergy, and nail dystrophy, as well as elevated acute-phase reactants, sterile osteomyelitis, and periostitis. DIRA is caused by loss of function of the IL-1 receptor (IL-1R) antagonist, the first endogenous cytokine receptor antagonist identified that blocks IL-1 signaling (Figure). Absence of the IL-1R antagonist results in unopposed proinflammatory signaling via the cytokines IL-1α and IL-1β on the IL-1R type I (IL-1R1). DIRA is a rare condition that you may never encounter in your practice, so why bother filing away another acronym in the deep recesses of your dermatologic cortex? First, as Brau-Javier et al1 demonstrate, just as with CAPS, DIRA is exquisitely responsive to IL-1 blockade. Responses are similar to those seen following anti–IL-1 treatment for NOMID, the most severe form of CAPS; children who have been ill since infancy now feel well for the first time; others confined to wheelchairs because of disabling joint pain are able to walk; and growth curves begin to arc upward again for the first time in years. Interleukin 1–blocking therapy is now the standard of care for CAPS, and 3 Food and Drug Administration–approved agents, anakinra, rilonacept, and canakinumab, are currently available that provide targeted inhibition of IL-1 signaling.4 Second, understanding DIRA may yield new insights into the mechanism of other challenging pustular skin conditions. The cutaneous and systemic features of DIRA bear similarity to features seen in pustular psoriasis and SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis), suggesting that IL-1 signaling may play a role in these conditions as well.

A Case of Macrophagic Myofasciitis Initially Thought to Be a Metastatic Infection

Macrophagic myofasciitis (MMF) is a rare disease, often associated with the pathological persistence of aluminum hydroxide used in some vaccines, and is characterized by macrophage infiltration of the muscle. We report a case of MMF, initially thought to be a metastatic infection. A 38-year-old woman presented with fever, as well as pain and weakness in both thighs. On physical examination both thighs were swollen and lower-extremity motor-power was decreased to grade III. Laboratory tests showed leukocytosis and elevation of acute phase reactants, but all muscle enzymes except lactate dehydrogenase (LDH) were within normal range. Initially metastatic infection was suspected but she was diagnosed with MMF by muscle biopsy showing heavy CD68 positive macrophage infiltration. Her myalgia and muscle weakness improved after systemic steroid treatment. This case suggests that MMF might be considered for a patient with unexplained inflammatory myopathy with or without a history of vaccination.

The First Case of Familial Mediterranean Fever Associated with Renal Amyloidosis in Korea

Familial Mediterranean fever (FMF) is an auto-inflammatory disease characterized by periodic episodes of fever and recurrent polyserositis. It is caused by a dysfunction of pyrin (or marenostrin) as a result of a mutation within the MEFV gene. It occurs mostly in individuals of Mediterranean origin; however, it has also been reported in non-Mediterranean populations. In this report, we describe the first case of FMF in a Korean child. As eight-year-old boy presented recurrent febrile attacks from an unknown cause, an acute scrotum and renal amyloidosis. He also showed splenomegaly, lymphadenopathy, pleural effusion, ascites and elevated acute phase reactants. After MEFV gene analysis, he was diagnosed as FMF combined with amyloidosis.

Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is the prototypical autoimmune disease, associated with autoantibody production and evidence for immune complex deposition among the many aspects of its pathophysiology. SLE occurs most commonly in women during their reproductive years. The disease is approximately nine times more common among women than men. Virtually any organ can be affected by SLE. However, constitutional symptoms, mucocutaneous features, mus-culoskeletal involvement, and renal and central nervous system disease are the most common manifestations. Many aspects of SLE appear to be triggered by classic inflammatory mechanisms, accompanied by elevated acute phase reactants, and responsive to immunosuppres-sive therapies. Other aspects, such as those associated with antiphospholipid antibodies (aPL), are associated with hypercoagulability. Although inflammation contributes to these aspects as well, the approach to the treatment of aPL-mediated disease manifestations is usually centered on anticoagulation. Autoantibodies can occur in the absence of clinical features of SLE, but strong evidence implicates certain autoantibodies in the mediation of tissue damage in the kidney and other organs. Genetics plays a significant role in SLE, but the disease is clearly polygenic, with multiple genetic risk factors contributing incrementally to the overall genetic risk. Environmental risk factors are also critical. Established environmental risk factors for the disease include hormones, ultraviolet light, the exposure to certain medications, and possibly dietary exposures and infectious agents.

Is IL-6 an appropriate target to treat spondyloarthritis patients refractory to anti-TNF therapy? A multicentre retrospective observational study.

IntroductionThe aim of this study was to evaluate, under real-life conditions, the safety and efficacy of tocilizumab in patients having failed anti-TNFα therapy for spondyloarthritis.MethodsFrench rheumatologists and internal-medicine practitioners registered on the Club Rhumatismes et Inflammations website were asked to report on patients given tocilizumab (4 or 8 mg/kg) to treat active disease meeting Assessment of SpondyloArthritis International Society (ASAS) criteria for axial or peripheral spondyloarthritis, after anti-TNFα treatment failure. Safety and efficacy after 3 and 6 months were assessed retrospectively using standardised questionnaires.ResultsData were obtained for 21 patients, 13 with axial spondyloarthritis (46% men; median age, 42 years; disease duration, 11 years; HLA-B27-positive, 92.3%) and eight with peripheral spondyloarthritis (25% men; median age, 40 years; disease duration, 10 years; HLA-B27-positive, 62.5%). No patients with axial disease had at least a 20 mm decrease in the BASDAI, nor a BASDAI50 response or major ASAS-endorsed disease activity score improvements after 3 or 6 months; an ASAS-endorsed disease activity score clinically important improvement was noted at month 3 in five of 13 patients and at month 6 in one of four patients. A good DAS28 response was achieved in four patients with peripheral disease, including one in EULAR remission at month 3. Four patients were still taking tocilizumab at month 6, including one in EULAR remission and one with a good DAS28 response. Tocilizumab was well tolerated, with no serious adverse events. Initially elevated acute-phase reactants declined during tocilizumab therapy.ConclusionIn patients having failed anti-TNFα therapy, tocilizumab decreased acute-phase reactants but failed to substantially improve axial spondyloarthritis and was inconsistently effective in peripheral spondyloarthritis.

Primary Pyomyositis of the Pelvis in Children: A Retrospective Review of 8 Cases

Primary pyomyositis of the pelvic musculature is a condition rarely seen in temperate climates, although its frequency has been increasing in the United States. The condition should be considered in the initial differential diagnosis of an adolescent presenting with fever, difficulty ambulating, and hip pain. This is a retrospective review of 8 cases of primary pelvic pyomyositis in patients aged 18 years or younger who were treated at the Children's Medical Center in Augusta, Georgia. The site of infection was the obturator internus in the majority of the cases (5). The site was the gluteus, iliopsoas, and iliacus in 1 case each. Four patients who were diagnosed early responded to intravenous antibiotics with no need for further intervention. Two patients required incision and drainage of an abscess combined with antibiotics. Two patients had prolonged hospital courses requiring intensive unit care and mechanical ventilation. Blood cultures were positive in 87.5% of patients, and all patients presented with elevated acute phase reactants. One of the most difficult diagnostic aspects of presentation is an inconclusive symptom profile. It is noteworthy that patients with pelvic pyomyositis may present with limited range of motion in a specific plane (the motion placing the infected muscle on stretch) vs global limited range of motion of the joint as is commonly seen in septic arthritis. Early diagnosis is essential to prevent systemic illness and complications associated with this condition. Magnetic resonance imaging with gadolinium is helpful to diagnose and guide treatment.

Takayasu Arteritis Presenting as Severe Ascending Aortic Arch Dilation and Aortic Regurgitation in a 10-Year-Old Female

Takayasu arteritis (TA) is a large-vessel arteritis affecting the aorta and its major branches. It is a rare disease in children less than 10 years old, and its diagnosis is frequently delayed, likely because of TA's rarity and nonspecific symptoms early in the disease. Females are affected disproportionately, with a female to male ratio of 8.5 to 1. Recently, the European League against Rheumatism published an international consensus statement for making the diagnosis of childhood TA. Criteria include angiographic abnormalities of the aorta and/or its branches, pulse deficit or claudication, blood pressure discrepancy, bruits, hypertension, and elevated acute phase reactants. We described a 10-year-old female with severe TA of the ascending aorta and who presented with classic signs and symptoms of this rare disease.

COMPLETE HEART BLOCK COMPLICATING ACUTE RHEUMATIC FEVER

5 December 2010 Dear Editor, One of the common manifestations included in the Jones Criteria for diagnosis of Acute Rheumatic Fever (ARF) is first-degree heart block. Higher grades of heart block, including complete heart block, are described infrequently in the literature, but have the potential to cause severe symptoms, especially in isolated regions where this disease remains relatively common. An 8-and-a-half year old indigenous boy was referred with complete heart block in the setting of ARF. He had previously been entirely well, with no previous episode of ARF and no previous cardiac symptoms. He presented with a 1-week history of fever and migratory arthritis of his left knee and ankle. Initial examination did not reveal a cardiac murmur. His left knee was mildly swollen with tenderness to palpation and with reduced movement. ECG demonstrated complete heart block with a junctional escape rhythm at 60–70 beats per minute (Fig. 1a). Blood tests revealed elevated acute phase reactants (ESR 56; CRP 154; WCC 15.1; neutrophils 10.08; platelets 421), ASOT 1520 (<200), Anti-Dnase B 1080. Other relevant results included CK 221 (31–152) and cTnI 0.2 (<0.04). (a) Complete Heart block with narrow complex junctional escape rhythm in haemodynamically stable child. (b) Recovery phase demonstrating second-degree AV-block in same child. Echocardiography revealed a structurally normal heart with physiologic mitral regurgitation. There was no evidence of valvular heart disease and cardiac function and chamber size was normal. There was no pericardial effusion. The child commenced aspirin at anti-inflammatory doses and showed rapid improvement in symptoms of arthritis. Prednisone 1 mg/kg daily was also commenced and he was placed on telemetry to observe the progress of his heart block. He received intramuscular benzathine penicillin and commenced a course of monthly penicillin prophylaxis against further episodes of ARF. Blood and throat cultures were negative for Group-A streptococci. Over several days observation, the complete heart block showed complete recovery, progressing through second degree heart block (Fig. 1b) to sinus rhythm and first-degree heart block upon discharge. No active treatment was required for heart block during his admission. Complete heart block is rarely reported in association with acute rheumatic fever.1–3 In 508 patients seen with ARF in Toronto from 1948–1971, 3 had ECG evidence of complete heart block.4 The natural history tending to spontaneous resolution in this case is similar to other reports in the literature. This patient remained haemodynamically stable throughout, and did not require any pharmacologic treatment or pacing. Temporary pacing, via trans-venous electrode may be instituted for complete heart block associated with haemodynamic compromise. Indeed, two case reports exist documenting in-hospital cardiac arrest as a result of complete heart block during admission for ARF in a 12–year-old boy from Hobart and a 13-year-old boy in Pittsburgh.5,6 This instructive case highlights a potential cause of sudden cardiac death in ARF, and encourages wider awareness of this rare but serious complication.

Significance of I313V mutation of NLPR3 gene in two pediatric patients

Results Both case #1 (M.T) and #2 (V.C) displayed a mild clinical phenotype (episodes of urticarial rash and arthralgia associated with elevation of acute phase reactants), compatible with FCAS and Muckle-Wells syndrome, respectively. Both patients displayed good response to NSAID and/or steroid on demand. Compared to HD controls, patients displayed enhanced and delayed IL1b secretion. This was accompanied by higher levels of lL1Ra and IL-6 without any significant differences in IL-8. Interestingly, parents carrying the mutation also displayed higher levels of secreted IL-1b compared to HD control group. Conclusion The I313V mutation is associated with a mild CAPS phenotype and with an increased IL-1b secretion.

Canakinumab in the routinary clinical practice in cryopyrin-associated periodic syndromes (CAPS): one year of follow-up

Results At baseline, 7 patients were treated with the initial dosage of 2 mg/kg (or 150 mg, if > 40 Kg) every 8 weeks. In 5 patients (2 MWS/CINCA overlap, 5 CINCA) the dosage was 4 mg/kg (or 300 mg) every 8 weeks. During the following 12 months modification of dosage of frequency was performed in 7/12 patients. The 5 patients at higher dosage during the CACZ885D2306 study needed to increase the frequency of administration with a mean frequency of 6 weeks (range 4-8). The mean reason was the presence of mild clinical manifestation and/or persistent elevation of acute phase reactants. In one of these patients the therapy was subsequently discontinued due to persistent disease activity. An increased frequency (6 and 7 weeks) was also performed in 1 MWS and 1 CINCA patient, respectively. In 5 patients the treatment was not modified being effective in the control of the disease.

Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated Temperature Syndrome: A Case Report

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome is a recently described chronic inflammatory syndrome consisting of widespread annular violaceous skin lesions and multisystemic inflammatory manifestations. We report a 12½-year-old boy with a young-age onset of recurrent fevers, annular violaceous plaques, alopecia areata, lipodystrophy, low weight and height, deformed fingers, wide-spaced nipples, chronic anemia, and elevated acute phase reactants. An abdominal punch biopsy demonstrated dense perivascular and interstitial infiltrates in the dermis, composed mainly of mononuclear cells. This syndrome may represent a new autosomal recessive auto-inflammatory genodermatosis. Increased awareness may lead to the discovery of more cases, and clarify its pathogenesis.