Chronic Arthralgia Research Articles

Prolonged Myalgia in Sindbis Virus Infection: Case Description and In Vitro Infection of Myotubes and Myoblasts

Sindbis virus (SINV) is a mosquito-borne alphavirus found in Eurasia, Africa, and Oceania. Clinical SINV infection is characterized by febrile rash and arthritis and sometimes prolonged arthralgia and myalgia. The pathophysiological mechanisms of musculoskeletal and rheumatic disease caused by SINV are inadequately understood. We studied the muscle pathology of SINV infection ex vivo by examining a unique muscle biopsy obtained from a patient with chronic myalgia and arthralgia 6 months after acute SINV infection and assessed potential genetic predisposing factors by determining the human leukocyte antigen (HLA) and complement factor C4 genes and proteins. In addition, we performed in vitro SINV infections of primary human myoblasts and myotubes. In the muscle biopsy we found evidence of muscle regeneration due to previous necrotic lesions likely caused by earlier SINV infection. We showed that human myoblasts and myotubes were susceptible in vitro for SINV infection as the cells became immunoreactive for viral antigens and cytopathic effect was observed. The patient was homozygous for HLA-B*35 alleles and heterozygous for HLA-DRB1*01 and HLA-DRB1*03 alleles and had total deficiency of C4B protein. This study provides new insights concerning pathological processes leading to chronic symptoms in SINV infection and demonstrates for the first time the susceptibility of human myogenic cells to SINV infection.

Chikungunya Disease: Infection-Associated Markers from the Acute to the Chronic Phase of Arbovirus-Induced Arthralgia

At the end of 2005, an outbreak of fever associated with joint pain occurred in La Réunion. The causal agent, chikungunya virus (CHIKV), has been known for 50 years and could thus be readily identified. This arbovirus is present worldwide, particularly in India, but also in Europe, with new variants returning to Africa. In humans, it causes a disease characterized by a typical acute infection, sometimes followed by persistent arthralgia and myalgia lasting months or years. Investigations in the La Réunion cohort and studies in a macaque model of chikungunya implicated monocytes-macrophages in viral persistence. In this Review, we consider the relationship between CHIKV and the immune response and discuss predictive factors for chronic arthralgia and myalgia by providing an overview of current knowledge on chikungunya pathogenesis. Comparisons of data from animal models of the acute and chronic phases of infection, and data from clinical series, provide information about the mechanisms of CHIKV infection–associated inflammation, viral persistence in monocytes-macrophages, and their link to chronic signs.

Pulmonary Arterial Hypertension in Adult-Onset Still’s Disease: Rapid Response to Anakinra

Adult-onset Still's disease (AOSD) is a rare inflammatory condition characterized by spiking quotidian fever, rash, chronic arthralgia, leukocytosis, and occasional pulmonary involvement such as pleural effusion and transient pulmonary infiltrates. Pulmonary arterial hypertension (PAH) is a rare pulmonary complication of AOSD, and we are aware of only 5 cases reported in the literature. We report the case of a 27-year-old woman of Middle Eastern descent, with a 7-year history of AOSD, who developed severe pulmonary arterial hypertension (PAH). After unsuccessful exposure to various immunosuppressive regimens, shortly following the initiation of anakinra, an interleukin-1 (IL-1) receptor antagonist, her disease became quiescent and the PAH resolved. With this case report, we hope to show that anakinra, either by virtue of controlling the overall inflammation in AOSD, or by direct effect on the pulmonary microangiopathy, can improve severe PAH.

Hemolytic Crisis as the Initial Presentation of Hereditary Spherocytosis Induced by Parvovirus B19 and Herpes Virus Infection in a Patient with the Thalassemia Trait: A Case Report

To the Editor, Human parvovirus B19 (PV-B19) causes erythema infectiosum, hydrops fetalis, and transient aplastic crisis in immunocompromised patients with chronic hemolytic anemia, arthralgia, and chronic pure red cell aplasia [1]. It may also cause autoimmune hemolytic anemia [2] (which presents as aplastic crisis with reticulocytopenia or increased erythropoiesis with reticulocytosis) [3], autoimmune thrombocytopenia/neutropenia, myelodysplastic syndrome, leukoerythroblastosis, hemophagocytic lymphohistiocytosis, and leukemia [1]. Transient aplastic crisis manifests as sudden exacerbation of anemia in patients with chronic hemolytic anemia, with severe reticulocytopenia lasting 7-10 days in the absence of erythroid precursors due to lysis of the precursors by PV-B19 [4]—the hallmark of which is giant pronormoblasts in the bone marrow [5]. Hemolytic crisis in hereditary spherocytosis (HS) is characterized by more pronounced jaundice than that in stable state of HS due to accelerated hemolysis and probable viral infection [6]. Herein we describe a patient that presented with hemolytic crisis as the initial manifestation of HS during PV-B19 infection—in contrast to the expectation of transient aplastic crisis [7]. This condition was attributed to coexistent herpes virus infection. The patient had a low mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) due to the thalassemia trait, which masked spherocytosis. A 15-year-old female was presented for evaluation of anemia. She had a 4-month history of progressive pallor, fatigue, scleral icterus, and dark urine. She has had intractable pallor since nearly 3 years of age Icterus was not noted until four months prior to her presentation to our hospital. Her brother also had pallor without icterus. Physical examination showed pallor, scleral icterus, and hepatosplenomegaly (spleen and liver extended the costal margins by 4 cm and 3 cm, respectively). Laboratory findings were as follows: hemoglobin level: 75 g/L; hematocrit: 24.1%; red blood cell count (RBC):4.11x1012/dL; platelet count: 279 x 109/L; white blood cell count: 7.3 x 109/L: mean corpuscular volume (MCV): 59.5 fL: mean corpuscular hemoglobin concentration MCHC 31.5 g/dl (N: 32.7-35.6 g/dl); mean corpuscular hemoglobin (MCH): 18.5 pg (normal range: 27.2-33.5 pg); red blood cell distribution width: 21% (normal range: 11.8%-14.3%); reticulocyte count: 2.2% (normal range: 0.6%-2.6%). Peripheral blood smear showed anisocytosis, poikilocytosis, hypochromia, and spherocytes. Direct and indirect Coombs tests were negative, and total/indirect bilirubin was 1.68/1.33 mg/dL, haptoglobin was <5.83 mg/dL (normal range: 36-195mg/dL), plasma hemoglobin was 7% (normal: <3), serum lactate dehydrogenase was 254 IU/L, and Hb A2 was 4.37%. Bone marrow aspiration showed erythroid hyperplasia, glucose-6-phosphate dehydrogenase, pyrimidine 5’ nucleotidase, pyruvate kinase, CD 55, and CD 59 evaluation of CD 55, and CD 59 on granulocytes by flow cytometry were normal. Collagen tissue disease markers were negative. Abdominal ultrasonography showed splenomegaly and elevated osmotic fragility. Herpes simplex virus HSV type 1-2 IgM was positive. PV-B19 PCR was 75.3 copies/mL in plasma, based on real-time PCR (normal: negative). The patient was diagnosed as hereditary spherocytosis and thalassemia trait, with coexistent PV-B19 and herpes virus infections.The hemoglobin level was found to have increased spontaneously to 88 g/L and her pallor and scleral icterus were found resolved at the end of in her evaluation made on 46th day of admission At this time blood smear findings and mild indirect hyperbilirubinemia persisted and PV-B19 DNA showed 13 copies and HSV type 1-2 IgM was still positive. Viral serological tests may cross react with each other and we couldn’t perform HSV PCR. But HSV IgG was found to have increased from 6.15 to 113.2 RU/mL on the 46th day of admission and this confirmed that PV-B19 and HSV infected the patient coexistently., The presented patient had mild HS, which manifested first as hemolytic crisis due to herpes virus infection, although infection by other viruses we didn’t test for could not be excluded. Her RBC count was within the lower limits of normal, which is unexpected in a patient with hemolytic anemia and the thalassemia trait. We think the normal RBC and reticulocyte counts, despite erythroid hyperplasia of the bone marrow, were indicative of repressed erythropoiesis due to PV-B19 infection. The presented case highlights the fact that, in the setting of chronic mild hemolytic anemia, patients in hemolytic crisis that have normal reticulocyte and RBC counts should be tested for PV-B19 infection and accompanying other viral infections . Clinicians should be aware that MCH and MCHC are not elevated in HS patients with thalassemia trait. Conflict of Interest Statement None of the authors have any conflicts of interest, including specific financial interests, relationships, and/or affiliations, relevant to the subject matter or materials included.

Risk Factors for Zaireebolavirus–Specific IgG in Rural Gabonese Populations

In Gabon, several Ebolavirus outbreaks have occurred exclusively in the northeastern region. We conducted a large serosurvey to identify areas and populations at risk and potential demographic, clinical, and behavioral risk factors. Blood samples and clinical and sociodemographic data were collected from 4349 adults and 362 children in a random sample of 220 villages in the 9 provinces of Gabon. An enzyme-linked immunosorbent assay was used to detect Zaire ebolavirus (ZEBOV)-specific IgG, and thin blood smears were used to detect parasites. Logistic regression was implemented using Stata software (Stata), and a probability level of <.05 was considered to be statistically significant. The prevalence of ZEBOV-specific IgG was 15.3% overall, increasing to 32.4% (P< .001) in forest areas. No sociodemographic risk factors were found, but the antibody prevalence increased linearly up to 20 years of age. Chronic arthralgia and amicrofilaremia were the only factors associated with ZEBOV seropositivity. These findings confirm the endemicity of ZEBOV in Gabon and its link to the ecosystem. Human antibody positivity would appear to be to the result of exposure to contaminated fruits.

Manifestations ostéoarticulaires des amyloses

Amyloidosis is defined by the extracellular deposit of proteins which share common tinctorial affinities, a fibril aspect under electron microscopy and spatial conformation called beta pleated. Significant progress has been made in gaining an insight into the clinical, biochemical and genetic characteristics of amyloidosis. Once regarded a mere overload disease, it is currently considered as a disease of misfolded proteins. Indeed it is certain that abnormalities of spatial pattern play an essential role in the responsibility for the pathology of many proteins whose amyloid fiber is the final common way. The mechanisms of fibril formation remain poorly understood. They involve both changes in the conformation of proteins and other major in vivo interactions between amyloid protein and the extracellular matrix. In most cases amyloidosis represents the bulk of histopathological lesions and its pathogenic role is certain. In other cases it is only one elementary lesion of the disease and its role is controversial. The amyloidosis responsible for osteoarticular manifestations are the AL immunoglobulin amyloidosis, the beta2-microglobulin amyloidosis in patients under haemodialysis and finally the amyloidosis of transthyretin in its genetic and senile forms. Rheumatological manifestations of immunoglobulin amyloidosis are numerous and important to know because often indicative of the disease. Deposits affect joint and periarticular structures. The most common sign and symptom that should raise questions is a progressively developing bilateral symmetric polyarthritis with negative immunology and absent specific structural abnormalities. Carpal tunnel syndrome is also very common and should suggest the etiology. Other clinical representations are rarer and can be expressed by an isolated bone tumour (amyloidoma) or integrating in a form of systemic AL amyloidosis. The beta2-microglobulin amyloidosis occurs in patients treated by chronic haemodialysis. It is responsible for carpal tunnel syndrome, chronic arthralgia, and above all a specific destructive spondyloarthropathy. Finally the transthyretin amyloidosis can also cause carpal tunnel syndrome.

Chikungunya physiopathology: Infection data from acute to chronic phase

During the 2005-2006 austral summer, an outbreak of fever associated with joint pain hit the Reunion Island inhabitants. Chikungunya virus (CHIKV), the agent involved in this epidemic, was known since 50 years and was thus brought to general attention together with the risk of emergence or re-emergence of arboviral infections. This arbovirus rapidly spread worldwide, specifically in India with millions of cases, but also in Europe through imported cases (>2,000) and fewautochthonous cases in Italy and in France. Human pathology is characterized by arthralgia and myalgia, which persist for months or years. Development of macaque model of CHIKV disease evidenced the key role of monocytesmacrophages in viral persistence.We are reporting herein the present knowledge about physiopathology of the virus and the CHIKV disease. Comparison of animal model data in chronic phase of infection and data acquired in follow-up of patients allows us to propose explanation of mechanisms of inflammation associated with viral infection. This review is aimed at opening discussion about the relationship between the CHIKV, the immune response and the development of virus-induced chronic arthralgia and myalgia.

Novel Chikungunya Vaccine Candidate with an IRES-Based Attenuation and Host Range Alteration Mechanism

Chikungunya virus (CHIKV) is a reemerging mosquito-borne pathogen that has recently caused devastating urban epidemics of severe and sometimes chronic arthralgia. As with most other mosquito-borne viral diseases, control relies on reducing mosquito populations and their contact with people, which has been ineffective in most locations. Therefore, vaccines remain the best strategy to prevent most vector-borne diseases. Ideally, vaccines for diseases of resource-limited countries should combine low cost and single dose efficacy, yet induce rapid and long-lived immunity with negligible risk of serious adverse reactions. To develop such a vaccine to protect against chikungunya fever, we employed a rational attenuation mechanism that also prevents the infection of mosquito vectors. The internal ribosome entry site (IRES) from encephalomyocarditis virus replaced the subgenomic promoter in a cDNA CHIKV clone, thus altering the levels and host-specific mechanism of structural protein gene expression. Testing in both normal outbred and interferon response-defective mice indicated that the new vaccine candidate is highly attenuated, immunogenic and efficacious after a single dose. Furthermore, it is incapable of replicating in mosquito cells or infecting mosquitoes in vivo. This IRES-based attenuation platform technology may be useful for the predictable attenuation of any alphavirus.

Applications of Animal Models of Infectious Arthritis in Drug Discovery:A focus on Alphaviral Disease

Animal models, which mimic human disease, are invaluable tools for understanding the mechanisms of disease pathogenesis and development of treatment strategies. In particular, animal models play important roles in the area of infectious arthritis. Alphaviruses, including Ross River virus (RRV), o'nyong-nyong virus, chikungunya virus (CHIKV), mayaro virus, Semliki Forest virus and sindbis virus, are globally distributed and cause transient illness characterized by fever, rash, myalgia, arthralgia and arthritis in humans. Severe forms of the disease result in chronic incapacitating arthralgia and arthritis. The mechanisms of how these viruses cause musculoskeletal disease are ill defined. In recent years, the use of a mouse model for RRV-induced disease has assisted in unraveling the pathobiology of infection and in discovering novel drugs to ameliorate disease. RRV as an infection model has the potential to provide key insights into such disease processes, particularly as many viruses, other than alphaviruses, are known to cause infectious arthritides. The emergence and outbreak of CHIKV in many parts of the world has necessitated the need to develop animal models of CHIKV disease. The development of non-human primate models of CHIKV disease has given insights into viral tropism and disease pathogenesis and facilitated the development of new treatment strategies. This review highlights the application of animal models of alphaviral diseases in the fundamental understanding of the mechanisms that contribute to disease and for defining the role that the immune response may have on disease pathogenesis, with the view of providing the foundation for new treatments.

Chikungunya Fever: Focus on Peripheral Markers of Pathogenesis

Chikungunya Fever: Focus on Peripheral Markers of Pathogenesis

Antibody to parvovirus B19 nonstructural protein is associated with chronic arthralgia in patients with chronic fatigue syndrome/myalgic encephalomyelitis

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a neuro-immune disease of uncertain pathogenesis. Human parvovirus B19 infection has been shown to occur just prior to development of the onset of CFS/ME in several cases, although B19 seroprevalence studies do not show any significant differences between CFS/ME and controls. In this study, we analysed parvovirus B19 markers in CFS/ME patients (n=200), diagnosed according to Fukuda CDC criteria, and normal blood donors (n=200). Serum from each subject was tested for anti-B19 VP2 IgM and IgG (by Biotrin ELISA), anti-B19 NS1 IgM and IgG (by immunofluorescence), and B19 DNA (by real-time PCR). CFS/ME patients and normal blood donors had a similar B19 seroprevalence (75 % versus 78 %, respectively). Eighty-three CFS patients (41.5 %) as compared with fourteen (7 %) normal blood donors tested positive for anti-B19 NS1 IgG (chi(2)=64.8; P<0.0001; odds ratio=9.42, CI 5.11-17.38). Of these 83 patients, 61 complained of chronic joint pain, while 22 did not. Parvovirus B19 DNA was detected in serum of 11 CFS patients and none of the controls by Taqman real-time PCR (chi(2)=9.35, P<0.002). Positivity for anti-B19 NS1 IgG was associated with higher expression levels of the human CFS-associated genes NHLH1 and GABPA. As NS1 antibodies are thought to indicate chronic or severe courses of B19 infection, these findings suggest that although the seroprevalence of B19 in CFS patients is similar to controls, the immune control of the virus in these patients may not be efficient.

Free circulating interleukin-18 is increased in Schnitzler syndrome: a new autoinflammatory disease?

Schnitzler syndrome is a rare disease characterised by chronic urticaria and arthralgia. The recent evidence that the IL-1 receptor antagonist IL-1Ra could induce rapid and complete remission of Schnitzler symptoms has pointed to IL-1 as a major pathological factor in this disease. To examine the possibility that Schnitzler syndrome may be considered to be an autoinflammatory disease, in this study we measured the serum levels of IL-18, another cytokine of the IL-1 family that is cleaved by caspase-1, in two recently diagnosed Schnitzler patients before and after treatment with IL-1Ra. In parallel, mRNA expression of IL-1 family cytokines and caspase-1 were assessed in isolated blood monocytes. Treatment with IL-1Ra significantly inhibited IL-1beta gene expression, indicating that IL-1beta activity in Schnitzler syndrome is central to IL-1beta gene upregulation in a type of auto-amplification loop. While no IL-1beta was detected in serum, free circulating IL-18 was increased in patients with Schnitzler syndrome, despite low IL-18 gene expression in monocytes. This suggests constitutive activation of the IL-1beta/IL-18-producing inflammasome, and supports the hypothesis that Schnitzler's syndrome is a new autoinflammatory disease.

Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome and acne fulminans: are they part of the same disease spectrum?

Conflict of interest: none declared. Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome describes a clinical condition with both cutaneous and osteoarticular features. Skin features include severe acne, palmoplantar pustulosis, hidradenitis suppurativa and psoriasis. This condition has been described in both adults and children.1 We would like to illustrate the broad spectrum of this syndrome with two cases, which encompass the diagnosis of acne fulminans and highlight the inflammatory osteitis, a fundamental component of this condition that is present in both cases. Patient 1 was a 25‐year‐old man who presented with extensive crusted nodular and pustular lesions on his scalp (Fig. 1a), face and trunk (Fig. 1b), which had been present since the age of 13 years. Treatment with oral antibiotics including tetracyclines, macrolides, flucoxacillin and isotretinoin (1 mg/kg daily for > 1 year) resulted in temporary but unsustained improvement in his skin condition. He has severe scarring and alopecia. He was investigated by the rheumatologists for chronic arthralgia. Bone scintigraphy revealed multiple areas of increased tracer uptake on the midline of the skull, both mandibles, right maxilla, both calcanei and right mid‐foot. Corresponding radiographs showed a lytic lesion on the skull (Fig. 2), and erosive arthropathy at the right first metatarsophalangeal joint. Intravenous pamidronate has not helped to diminish the arthralgia. Methotrexate is being considered by the rheumatologists as a disease‐modifying agent.

The Prevalence and Clinical Features of Musculoskeletal Diseases in Incheon: Results from Chronic Disease Management Surveys

Objective: To estimate the prevalence of musculoskeletal diseases in Incheon. Methods: This study was based on data from chronic disease management surveys of Incheon. The surveys were conducted from 12 Sept 2005 to 7 Oct 2005 on 5,144 households using proportional stratified sampling methods. Three questionnaires were performed on all study subjects. All analyses were done using SPSS version 11.5. Results: Out of 16,623 subjects, the mean age was 34.5±20.2 (years, ±SD). The crude prevalence rate of musculoskeletal diseases were as follows: osteoarthritis 3.2%, rheumatoid arthritis 1.1%, spondyloarthropathy 0.3%, gouty arthritis 0.1%, Behcet’s disease 0.04%, herniated disc 1.1%, and osteoporosis 0.8%. Age-standardized prevalence of rheumatoid arthritis was 1.6%, and osteoarthritis 5.2%. The prevalence of rheumatoid arthritis and osteoarthritis tended to be higher among older age groups, low socioeconomic/education state, and homemakers. The age-standardized prevalence of arthritis was higher in rural than in urban area. There were more concurrent chronic diseases such as hypertension or diabetes mellitus in the arthritis group than in the whole population. Questionnaires were performed on subjects with musculoskeletal disease. It revealed chronic arthralgia at 3%, spine arthralgia 2.5%, and chronic myalgia 2.8%.

A rare cause of a common symptom, Anakinra is effective in the urticaria of Schnitzler Syndrome: a case report

IntroductionSchnitzler Syndrome is an uncommon, inflammatory condition that presents with a constellation of chronic unremitting urticaria, fever, bone pain, arthralgia or arthritis, and a monoclonal IgM gammopathy. There is usually neutrophilia and raised inflammatory markers. Delayed diagnosis is common and treatment often unsuccessful.Case presentationWe report the case of a 43-year-old caucasian man who presented with urticaria unresponsive to conventional therapy. There was considerable delay in recognition of this as Schnitzler Syndrome, and symptoms were unresponsive to conventional immunosuppressive therapy.Commencement of anakinra was associated with a rapid and sustained clinical response.ConclusionSchnitzler Syndrome is a rare disorder that mimics chronic idiopathic urticaria. This diagnosis should be considered in patients with urticaria unresponsive to antihistamines and conventional immunosuppressive therapy. Anakinra is an effective treatment although further studies are required, to determine long term therapeutic requirements and assess any potential adverse effects.

Joint hypermobility and skin elasticity: the hereditary disorders of connective tissue

The hereditary disorders of connective tissues (HDCTs) encompass a spectrum of conditions linked pathophysiologically by abnormalities of collagen, fibrillin, and matrix proteins. The clinical picture ranges from morbidity because of musculoskeletal, skin, ocular and visceral pathologies to mortality from acute vascular collapse. For many of the conditions, there is a considerable overlap in clinical features, although severity varies; appreciating the subtle differences in presentation is vital to the clinician in determining the diagnosis. Though conditions associated with severe vascular pathology are rare, other hereditary disorders of connective tissues such as the joint hypermobility syndrome and Stickler's disease are common and probably underrecognized. Abnormal skin elasticity and scaring, joint hypermobility, and chronic arthralgia are important clues that should trigger the clinician to search for underlying hereditary disorders of connective tissues. In this article, we discuss the spectrum of clinical findings, management, and genetic screening of the more common hereditary disorders of connective tissues, highlighting their diagnostic criteria and their differences.

The burden of rheumatic disease

Abstract Musculoskeletal conditions are a major burden to the individual, society and the health service. Most new musculoskeletal GP consultations are for self-limiting conditions such as soft tissue rheumatism, chronic widespread pain and arthralgia. Incident cases of osteoarthritis are ten times more common compared to rheumatoid arthritis. The prevalence of musculoskeletal conditions is more common in women and tends to rise with age. Approximately one tenth of GP consultations are for diseases of the musculoskeletal system. It is likely that prevalence rates will continue to rise as life expectancy increases. This will in turn lead to an increase in health professional workloads and a further burden on healthcare services. Costs for musculoskeletal conditions include those to healthcare services, to society and indirect costs. A fifth of all incapacity claims in Great Britain are for diseases of the musculoskeletal system. Combined costs for rheumatoid arthritis patients amount to £7000 per person affected per year, while each hip and knee replacement costs on average £5000. Risk factors for musculoskeletal conditions include age and gender. The prevalence of certain musculoskeletal conditions can vary depending on ethnicity, lifestyle factors and genetic predisposition. The main consequences of having a musculoskeletal disease are chronic pain and disability. The burden of musculoskeletal conditions is high. The impact of these conditions on the health service and society will continue to rise alongside increasing life expectancy.

Woman with multiple tender plaques with subsequent atrophy and scarring

A 45-year-old woman presented with a several-year history of multiple painful and tender nodular swellings involving her face, breasts, and upper aspects of her arms followed by atrophic scarring of the affected areas (Fig 7). She also had chronic arthralgia, myalgia, and fatigue.19.The most likely diagnosis is (Choose single best response.)a.discoid lupus erythematosusb.lupus profundusc.lupus tumidusd.lupus pernioe.erythema nodosum20.A deep excisional biopsy specimen revealed a lobular panniculitis with a dense infiltrate of lymphocytes. The differential diagnosis includes the following except (Choose single best response.)a.traumatic panniculitisb.lupus panniculitisc.erythema nodosumd.pancreatic panniculitise.erythema induratum of Bazin21.Lupus profundus occurs in what percentage of patients with cutaneous lupus erythematosus? (Choose single best response.)a.1% to 3%b.5% to 10%c.20% to 40%d.40% to 60%e.60% to 80%22.Successful treatment of lupus profundus include the following except (Choose single best response.)a.dapsoneb.hydroxychloroquinec.systemic glucocorticoidsd.azathioprinee.systemic retinoids

Sindbis viruses and other alphaviruses as cause of human arthritic disease

Amongst the arthritis-causing arboviruses, i.e. those spread by insects, the alphavirus group is of special interest. These viruses occasionally cause vast outbreaks, such as O'nyong-nyong in Africa in 1959. In Fennoscandia, Sindbis-related Ockelbo, Pogosta, or Karelian fever viruses have been found to cause significant morbidity. The major symptoms in addition to joint inflammation are fever, fatigue, headache and rash. The joint symptoms may persist for weeks, even months. The diagnosis is based on the clinical picture and serology. The causative viruses are closely related but not identical. It appears that at least in Finland the Pogosta disease is more common than thought, and the symptoms may often be overlooked. Several factors related to the viruses, their hosts, and global environmental changes may affect the spread of these viruses. All over the world arbovirus-caused diseases have increased, because of global changes.

A targeted approach significantly increases the identification rate of patients with undiagnosed haemochromatosis.

To determine the optimal means of identifying patients with undiagnosed haemochromatosis. Case-control study where cases are defined by the presence of specific clinical diagnoses or symptoms. Primary care patients were recruited from three Oxfordshire practices and secondary care patients were recruited from those patients attending specialist clinics in Amiens University Hospital. A total of 569 patients recruited via hospital clinics and 60 primary care patients (recruited from 4022 consultations) presenting with the following haemochromatosis associated conditions, diabetes, arthralgia/chronic fatigue, osteoporosis or arthropathy were studied. The control group, a total of 991 healthy volunteers, were recruited through a Health Appraisal Centre. Patients and controls were included in the study if they or their family members had not previously been diagnosed with hereditary haemochromatosis. Serum ferritin concentration, transferrin saturation (Tsat) and presence of HFE mutations, C282Y and H63D. The check-up in controls consisted of a questionnaire, clinical examination, biochemical tests and screening for the presence of the C282Y and H63D mutations. Patient groups presenting with unstable diabetes or chronic fatigue and arthralgia together with a raised serum ferritin concentration showed an enrichment in the haemochromatosis-associated genotype HH/YY, odds ratio (OR) = 40.1, confidence interval (CI) = 8.0-202.1 and OR = 103, CI = 22.9-469.7, respectively. Patients presenting to hospital clinics with haemochromatosis associated conditions should be screened biochemically for iron overload. Only those with a serum ferritin >300 microg L-1 or Tsat >40% should subsequently go on to be genotyped for HFE mutations. The patients at greatest risk of having undiagnosed haemochromatosis are those presenting with unstable diabetes, or fatigue and/or arthralgia in the absence of any other explanation.