Recurrent Arthralgia Research Articles

Renal involvement in secondary amyloidosis of Muckle-Wells syndrome: marked improvement of renal function and reduction of proteinuria after therapy with human anti-interleukin-1β monoclonal antibody canakinumab

Muckle-Wells syndrome (MWS) is a rare hereditary autoinflammatory disorder characterized by recurrent urticaria-like skin rashes, arthralgias, conjunctivitis, hypoacusia, and risk of reactive AA amyloidosis due to the progressive accumulation of amyloid fibrils in different organs. Its genetic defect lies in mutations in the NLRP3 gene, encoding the cryopyrin protein, and resulting in interleukin (IL)-1β oversecretion. Renal involvement, in terms of proteinuria or renal insufficiency, can be observed in up to 25% of patients. Herein, we describe our experience with two Caucasian patients, father and son, aged 52 and 26 years, respectively, heterozygous for both V198M and R260W NLRP3 mutations who had AA amyloid deposits on renal biopsy. The fully human monoclonal antibody canakinumab, providing selective and prolonged IL-1β blockade, was administered in both patients every 60 days over a period of 18 months. This treatment allowed to obtain amazing results: a rapid disappearance of any clinical symptoms, the stable normalization of serum amyloid-A and, furthermore, a marked improvement of glomerular filtration rate and proteinuria with no adverse events. Our data, though limited to only two patients, emphasize that therapeutic intervention with canakinumab, suppressing both inflammation and IL-1β-mediated manifestations, can contribute to improve kidney function in MWS with overt renal amyloidosis.

AB0679 One third of primary sjÖgren syndrome (PSS) patients with anti-CCP develop erosive rheumatoid arthritis (RA) after a 5-year follow-up

BackgroundRheumatologic manifestations affect 30 to 70% of pSS patients and present as recurrent and transient arthralgia or a real polyarthritis. These manifestations may sometimes be very similar to that of...

How not to miss autoinflammatory diseases masquerading as urticaria

Urticarial skin reactions are one of the most frequent problems seen by allergists and clinical immunologists in daily practice. The most common reason for recurrent wheals is spontaneous urticaria. There are, however, several less common diseases that present with urticarial rash, such as urticarial vasculitis and autoinflammatory disorders. The latter include cryopyrin-associated periodic syndrome and Schnitzler's syndrome, both rare and disabling conditions mediated by increased interleukin-1 secretion. Apart from the urticarial rash, patients are suffering from a variety of systemic symptoms including recurrent fever attacks, arthralgia or arthritis and fatigue. Autoinflammatory diseases are often associated with a diagnostic delay of many years and do not respond to antihistamines and other treatments of urticaria. Also, the chronic inflammation may lead to long-term complications such as amyloidosis. It is therefore important not to miss these diseases when diagnosing and treating patients with chronic recurrent urticarial rash. Here, we present clinical clues and tips that can help to identify autoinflammatory disorders in patients presenting with chronic urticarial rash and discuss their clinical picture and management.

The cell biology of Chikungunya virus infection

Chikungunya virus (CHIKV) infection causes a disease which appears to affect multiple cell types and tissues. The acute phase is manifested by a non-fatal febrile illness, polyarthralgia and maculopapular rashes in adults, but with recurrent arthralgia that may linger for months during convalescence. The issue of cellular and tissue tropism of CHIKV has elicited interest primarily because of this lingering incapacitating chronic joint pain, as well as clear encephalopathy in severe cases among neonates during the re-emergence of the virus in recent epidemics. The principle cell types productively infected by CHIKV are skin fibroblasts, epithelial cells and lymphoid tissues. There is controversy as to whether CHIKV productively infects haematopoietic cells and neurones/glia. CHIKV infection triggers rapid and robust innate immune responses which quickly clears the acute phase infection. However, significant acute as well as chronic infection of less obvious cell types, such as monocytes, neurones/glia or even CNS neural progenitors may conceivably occur. There is therefore a need to ascertain the full range potential of CHIKV tropism, fully understand the cellular responses triggered during the acute the convalescent phases, and explore possible cell types that might be the source of chronic problems associated with CHIKV infection.

Young female with fever, recurrent arthralgias and Raynaud’s phenomenon

Young female with fever, recurrent arthralgias and Raynaud’s phenomenon

Dengue fever evolving into systemic lupus erythematosus and lupus nephritis: a case report

Dengue viremia may be the trigger for immune complex formation in patients who are predisposed to developing autoimmune disease. We report a rare case of dengue virus infection evolving into systemic lupus erythematosus (SLE) and lupus nephritis. To the best of our knowledge this is the first case of dengue fever evolving into lupus nephritis. A 22 year old female presented with having had high grade fever, skin rash, breathlessness, retro-orbital pain, abdominal pain, arthralgias and myalgias for 10 days. She tested positive for dengue immunoglobulin M (IgM). She was given supportive treatment and was subsequently discharged. Four weeks later she developed recurrent fever, arthralgia, rash and anasarca. She was suspected as having SLE with active lupus nephritis. Antinuclear antibody (ANA), and anti double stranded deoxyribonucleic acid (anti dsDNA) titers were positive and complements were low. Renal biopsy showed diffuse proliferative glomerulonephritis grade IV. She was treated with steroids and immunosuppressants to which she responded. Dengue viremia incites antibody production, which if excessive causes deposition of viral antigen-antibody immune complexes. This could possibly lead to renal tubular damage and glomerulonephritis in susceptible individuals. Dengue fever leading to development of glomerulonephritis is rarely seen. Our patient developed dengue fever and after a month presented with manifestations of SLE and lupus nephritis. Both dengue fever and SLE have common manifestations of fever, arthralgia, rash, leucopenia with thrombocytopenia and serositis. Bacterial and viral infections may act as a 'trigger' for starting or relapsing lupus activity in genetically predetermined individuals. In our case it may be possible that dengue virus could have triggered a dysfunctional immune response, resulting in the developing of autoimmunity and SLE with lupus nephritis.

TNFSFR1A R92Q mutation, autoinflammatory symptoms and multiple sclerosis in a cohort from Argentina

Systemic autoinflammatory diseases are genetic disorders characterized by seemingly unprovoked inflammation, without major involvement of the adaptive immune system. Among them it is recognized the TNF receptor associated periodic syndrome (TRAPS) caused by mutations in the TNFRSF1A gene and characterized by symptoms such as recurrent high fevers, rash, abdominal pain, arthralgia and myalgia. Recent studies have recognized the potential role of TNFRSF1A mutations in Multiple Sclerosis (MS). Our aim was to investigate the role of TNFRSF1A R92Q gene mutation in a cohort of 90 Argentinean MS patients, where we determined the frequency of the TNFRSF1A R92Q mutation. We also compared autoinflammatory symptoms, MS clinical characteristics and treatment response and tolerability in R92Q carriers and non-carriers. Also, we used a case-control study design to obtain the genotypes of 78 healthy controls and assess the role of this mutation as a risk factor for MS. We found that five patients (5.5%) carried the R92Q mutation, four reported autoinflammatory symptoms previous to MS onset. We found no differences in MS clinical features, treatment response and tolerability between carriers and non-carriers. R92Q mutation was more frequent in MS patients as compared to controls. This increases the risk to develop MS in about 4.5 times. The TNFRSF1A R92Q mutation is a common finding in Argentinean MS patients. This genetic variant might be a risk factor for MS.

A case of Weber-Christian disease with later development of rheumatoid arthritis

Weber-Christian disease (WCD) is a syndrome characterized by recurrent subcutaneous nodules, fever, occasional lipoatrophy, fatigue, arthralgia, and myalgia. We report a case of WCD associated with rheumatoid arthritis. A 65-year-old woman consulted our outpatient clinic because of bilateral hand swelling. The patient had presented with fever and subcutaneous nodules in her trunk and upper and lower extremities in 1983. At that time, the dermatology department diagnosed this patient as having WCD after biopsy of the nodules demonstrated lobular panniculitis. She has been treated with corticosteroid (5-15 mg/day) since then. The patient continued to have recurrent episodes of transient inflammatory arthritis in the small joints of the fingers and fever, and was initially assessed at our institution in October 2007. Finally, in November 2007, she was diagnosed as having both WCD and rheumatoid arthritis (RA) and treated with corticosteroid (5 mg/day) and methotrexate (MTX) (7.5 mg/week). Thereafter, her clinical symptoms gradually improved. This is the second case of WCD showing the subsequent development of RA, successfully treated with MTX, in the English literature. This case may provide clinical insight into WCD and RA.

Fièvre prolongée associée à une éruption cutanée diffuse révélant une méningococcémie chronique

Chronic meningococcemia is an unusual clinical presentation within the spectrum of infections due to Neisseria meningitidis. We report a 32-year-old man who presented with a 15-day history of fever and maculopapular skin rash, in the absence of meningeal irritation or severe sepsis manifestation. Blood culture identified N. meningitidis. Clinical course was uneventful after antibiotic treatment was initiated. Early diagnosis of chronic meningococcemia is crucial for optimal management of the patient and his/her contacts. Such a diagnosis should be suspected in the presence of the characteristic clinical triad (recurrent fever, skin rash and arthralgia), and this clinical presentation should be distinguished from systemic vasculitis as inadequate prescription of corticosteroids may be deleterious.

Systemic lupus erythematosus complicated by acquired von Willebrand’s syndrome

Haematological abnormalities are common in systemic lupus erythematosus (SLE). In some cases of acquired von Willebrand syndrome (AvWS), von Willebrand disease (vWD) is associated with autoimmune or lymphoproliferative disorders. In this study, we describe a 36-year-old woman with SLE and AvWS. The patient was referred to our hospital because of easy bruisability and recurrent vaginal bleeding. She had no history of bleeding tendency and no family history of bleeding diathesis, but she had a history of recurrent arthralgia, photosensitivity and sicca symptoms. Tests for antinuclear, anti-double stranded DNA, anticardiolipin and anti-beta2-glycoprotein I antibodies were all positive. Analysis of haemostatic parameters showed complete absence of von Willebrand factor ristocetin cofactor (vWF:Rco), von Willebrand antigen (vWF:Ag) and ristocetin-induced platelet aggregation (RIPA). Electrophoretic analysis of plasma showed a complete absence of high-molecular weight vWF multimer. The presence of antibody to vWF was detected by enzyme linked immunosorbent assay (ELISA). Treatment with corticosteroids improved SLE symptoms and corrected bleeding diasthesis. Also, the multimeric patterns of vWF became normalised and anti-vWF antibody disappeared. These findings indicated that this patient had SLE associated with AvWS, which was ameliorated by corticosteroid treatment.

Primär kutane Manifestation einer Wegener-Granulomatose

A 57-year-old man was admitted with hemorrhagic papules and necrotising nodules on both elbows and upper legs. Recurrent arthralgia occurred.The skin biopsy showed a cutaneous necrotising vasculitis. Positive test results for c-ANCA and proteinase 3 antibodies and a slightly increased WBC and a mild proteinuria were noticeable.The diagnosis of an early systemic Wegener's granulomatosis was based on elevated proteinase 3-titres and cutaneous histologic findings as necrotising vasculitis and granulomatous inflammation. Treatment with prednisolone followed by methotrexate resolved the cutaneous symptoms and the arthralgia completely. Three months later the patient developed a progredient methotrexate toxicity caused by a glomerulonephritis.Wegener's granulomatosis should be considered if a cutaneous necrotising vasculitis is diagnosed. A cutaneous manifestation could be an early symptom. Methotrexate could be used for treatment of mild courses of Wegener's disease without renal involvement.

A devilishly interesting case

A 47-year-old woman presented with a two-week history of a sore throat and a “dirty” sensation in her left eye, followed by a week of reduced vision in the same...

Komplikationen im Verlauf eines Muckle-Wells-Syndroms

A 35-year-old woman had since early childhood suffered from recurrent urticaria-like rash, intermittent fever, arthralgia and pancochlear inner-ear deafness. At the age of 17 years she also developed a steroid-resistant nephrotic syndrome, found to be due to renal amyloidosis (type AA). The triad of renal amyloidosis, inner-ear deafness and recurrent urticaria is characteristic of Muckle-Wells syndrome, which has a hereditary basis. Rapidly progressive renal failure necessitated long-term haemodialysis and two renal transplantations. The accompanying immunosuppressive treatment with corticosteroids, azathioprin and, later, cyclophosphamide brought about a remission of the joint and skin abnormalities. After removal of the first donor kidney and termination of immunosuppressive treatment the syndrome recurred with subacute growth of an amyloid goitre as well as amyloidosis of the optic nerve. A few weeks before death a malignant non-Hodgkin lymphoma of the stomach was demonstrated. It was presumably a complication of long-term immunosuppression and not of the Muckle-Wells syndrome. The patient died of the complications of combination chemotherapy. Necropsy revealed generalized amyloidosis.

Morbus Whipple: abdominale Lymphome, Fieberschübe und rezidivierende Arthralgien

A diagnostic laparotomy was performed on a 41-year old woman who, having suffered from recurrent arthralgias for several years and intermittent fever for many months, was found to have extensive enlargement of abdominal lymph-nodes, raising the suspicion of malignant lymphoma. Frozen-tissue biopsy was highly suspicious of Hodgkin's lymphoma, but light- and electron-microscopy revealed Whipple's disease, confirmed in an endoscopically obtained duodenal mucosal biopsy. The arthralgia quickly responded to antibiotic treatment. This case demonstrates the potential difficulties and errors in the diagnosis of Whipple's disease.

Hypermobility disorders in children and adolescents

It is well recognized that many if not most children and adolescents attending paediatric rheumatology clinics will have a non-inflammatory origin for their complaints or disorder. Mechanical causes are frequently identified, and hypermobility or ligamentous laxity of joints is increasingly recognized as an aetiological factor in the presentation. Such conditions include 'growing pains', recurrent lower-limb arthralgia, anterior knee pain syndromes, and back pain. Studies of significant cohorts of such patients have now been published supporting the link of ligamentous laxity to particular symptom complexes. However, much disagreement remains as to the validity of hypermobility as an aetiogical factor. What seems clear is that not all hypermobile individuals will be symptomatic or indeed possibly have any risk for specific musculoskeletal disorders in later life. Screening tools such as the Beighton score are likely to be inadequate in many paediatric populations. Along with increasing recognition of these disorders in childhood and adolescence has been the development of a multidisciplinary management approach, which usually involves predominantly allied health professionals such as podiatrists, physiotherapists and occupational therapists. The challenge remains to interpret symptoms correctly as being related to the hypermobility and to predict why such children become symptomatic. The answer is likely to involve physiological and psychosocial factors. In addition, early identification and modification of risk factors may have major implications for subsequent prevalence of many adult medical disorders such as low back pain, chronic pain syndromes and degenerative osteoarthritis.

Diagnostic challenge of hyper-IgD syndrome in four children with inflammatory gastrointestinal complaints

Objective. Hyper-IgD syndrome (HIDS) is a rare autosomal recessive disease characterized by recurrent fever, lymphadenopathy, diarrhoea, abdominal pain, headache, arthralgia and skin rash. Abdominal symptomatology may mimic inflammatory bowel disease. We report on four patients with HIDS who had been previously investigated for Crohn's disease (CD). The levels of IgD were measured in a series of patients with CD to evaluate the specificity of this assay in the differential diagnosis between the two conditions. Material and methods. Diagnosis of HIDS was based on clinical criteria as well as immunological or genetic data. IgD levels were measured in the four subjects affected by HIDS, in 59 patients with CD and in a group of 160 healthy controls. Result. All patients underwent a variety of gastroenterological investigations because inflammatory bowel disease was suspected. Ultrasonography was pathologic in all the patients, showing enlargement of mesenteric lymph nodes. Abdominal leucocyte scintigraphy displayed diffuse signals of mild to moderate degree. IgD and IgA levels were elevated in three out of four patients. No difference in IgD values was found in CD patients as compared to the control group. Conclusions. Gastrointestinal complaints associated with recurrent fever and mesenteric adenopathy warrant genetic investigation for HIDS, in order to avoid unnecessary invasive investigations and treatment.

Recurrent Arthralgias in a Patient With Previous Mayaro Fever Infection

Mayaro fever is an acute, self-limited, febrile, mosquito-borne viral disease manifested by fever, chills, headache, myalgias, and arthralgias. The virus belongs to the family Togaviridae and the genus Alphavirus. Five other mosquito-borne viruses have been described as causing a similar dengue-like illness. The virus was first isolated in 1954, and the first epidemics were described in 1955 in Brazil and Bolivia. Other cases have been reported in Suriname, Brazil, Peru, French Guiana, and Trinidad. Up to 10 to 15% of febrile illnesses in endemic areas have been attributed to Mayaro virus. The exact pathogenesis and pathophysiology among humans is unknown. Animal models have demonstrated necrosis of skeletal muscle, periosteum, perichondrial tissues, and evidence of meningitis and encephalitis. All previous cases of Mayaro fever describe a self-limited illness. No reports of recurrent symptoms exist in the literature. This report describes a case of recurrent arthralgias in a military service member presenting to the emergency department.

Vasculo-Behcet's Disease Mimicking a Metastatic Neck Mass

This article presents a case of Behcet's Disease (BD) with vascular involvement of the neck, which mimicks a metastatic neck mass in the initial presentation. A 58-year-old man presented with dysphagia, weight loss, bulging on the lateral wall of the left pyriform sinus, and a firm and fixated neck mass suggestive of metastasis. Computed tomography of the neck demonstrated a solid mass, around the bifurcation of the carotid artery together with a pseudoaneurysm of the left external carotid artery. The mass was about four centimeters in diameter and extended to hypopharynx medially. Biopsy from neck mass and hypopharynx revealed no specific pathology. During follow-up the firm and fixated mass changed into a completely pulsatile one in the following three weeks. Reassessment of the patient's past history in detail revealed that he had had recurrent oro-genital ulcers, arthralgia and recurrent skin lesions. The pathergy test was positive. The patient was diagnosed to be BD and treatment consisting of colchicine 1 mg/day, peroral was started. He had a favorable outcome after treatment and was asymptomatic at follow-up of 24 months. It is unusual for BD to present as a neck mass but yet it must be considered in the differential diagnosis of neck masses. The present case report demonstrates how such a mass may mimic metastatic tumoral involvement and cause diagnostic dilemma.

Behçet's disease in childhood

To make Pediatricians aware of the fact that they must investigate Behçet's disease while performing differential diagnosis of recurrent aphthous stomatitis, even though it is a vasculitis of rare occurrence in early life. Between June 1996 and December 2000, we retrospectively evaluated seven patients of our Pediatric Rheumatology Unit. Demographic, clinical, and laboratory data as well as data regarding treatment and follow-up were presented. Five out of seven patients were female (71.4%), four were non-Caucasian (57.1%), the mean age at onset was 8 years and 11 months (variation of 6 months to 13 years and 8 months), the mean period until diagnosis was 2 years and 3 months (variation of 2 months to 8 years) and the mean follow-up period was 4 years and 2 months (three patients without follow-up). The major criteria of diagnosis were: oral ulcers in seven patients (100%), genital ulcers in three patients (42.8%), ophthalmic alterations in four patients (57.1%) cutaneous vasculitis in one patient (14.2%) and positive pathology test in one patient (14.2%). The minor criteria were: arthralgia/arthritis in five patients (71.4%), family history in two patients (28.5%), and sagittal sinus thrombosis in one patient (14.2%). The initial symptoms included recurrent aphthous stomatitis (more than three painful aphthous ulcers episodes in the period of 1 year), genital ulcers, arthralgia, fever and weight loss. The laboratory findings were: mild anemia in 1/6 patients, ESR>25 in 3/6 patients, increased serum gammaglobulin level in 2/4 patients, B5 histocompatibility antigen in 2/7 patients. The treatment included corticosteroids for 5/7 patients (4 oral, 1 intravenous and one local use), thalidomide for 4/7 patients, colchicine for 2/7 patients and dapsone for 1/7 patient. The outcome was favorable in 4/6, and 3/6 patients presented relapse. Our results confirm the importance of considering the diagnosis of Behçet's disease in patients with recurrent oral and genital ulcers.

Chronic fatigue syndrome: probable pathogenesis and possible treatments.

Chronic fatigue syndrome (CFS) belongs in the medically unexplained illnesses. It affects approximately 0.2-0.7% of the population in Western countries. It is characterised by unexplained fatigue, lasting 6 months or more, impairment of neurocognitive functions and quality of sleep, and of somatic symptoms, such as recurrent sore throat, muscle aches, arthralgias, headache and postexertional malaise. No link between infections and CFS has been clearly established but the immune system is activated, there are aberrations in several hypothalamic-pituitary axes and involvement of other parts of the central nervous system. No specific treatment has been found. Cognitive behavioural therapy is established to be of value to improve quality of life. More effective treatment should result, as advances in biomedical as well as psychological research continue.