Relapsing polychondritis in childhood – case report and short review

Relapsing polychondritis (RP) is a disease of unknown etiology and it is characterized by inflammation of the cartilage. While the clinical picture of RP in adults is well described, RP in childhood is poorly documented. We describe a young girl presenting with acute dyspnea, stridor and polyarthritis. The diagnosis of RP was made 2 years after first presentation, when auricular chondritis occurred. Based on a MEDLINE search, reports on RP in childhood were reviewed. The frequency of chondritis and systemic manifestations of RP in children was compared to data in adults and found to be very similar. RP in childhood can be a life-threatening and debilitating disease. Received: 18 March 2000 / Accepted: 16 June 2000     

The autoinflammatory side of recurrent pericarditis: Enlightening the pathogenesis for a more rational treatment

Recurrent pericarditis (RP) is a troublesome and debilitating complication of acute pericarditis. Although the etiopathogenesis of this condition remains unknown, an intricate overlap of autoimmune and autoinflammatory pathways has been hypothesized to explain its beginning and recurrence over time. The majority of cases are defined as “idiopathic”, reflecting our awkwardness to unravel the intimate mechanisms of RP. Given the possible occurrence of anti-nuclear, anti-heart and anti-intercalated disk antibodies as well as the association with peculiar human leukocyte antigen haplotypes, an autoimmune contribution has been claimed to specify the nature of RP. However, the most innovative pathogenic scenario of RP has been conferred to the innate immune system, mainly involving neutrophils and macrophages that produce a large amount of interleukin (IL)-1 via inflammasome activation. The clinical resemblance of RP with autoinflammatory diseases that may be marked by symptomatic serositis, high fevers and strikingly increased inflammatory parameters further suggests a similar inflammasome-mediated pathogenesis. Aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) remain the mainstay of therapy in RP, whereas colchicine is recommended on top of standard anti-inflammatory therapy, due to its role in inhibiting the IL-1 converting enzyme (caspase 1) within the inflammasome as well as the release of additional pro-inflammatory mediators and reactive oxygen species. With regard to treatment of RP refractory to NSAIDs and colchicine, blockade of IL-1 is the most relevant advance achieved in the last decade: the outstanding effect of the short-acting IL-1 receptor antagonist anakinra has been first recognized in the pediatric population, giving a proof of its practical feasibility. Over a more recent time, a growing experience with anakinra deriving from both large and small studies has further confirmed that RP might be regarded as an IL-1-mediated disease. This review aims to provide a contemporary insight into the mechanisms leading to RP as well as into the most recent literature data showing the beneficial approach originating from IL-1 blockade in this intriguing disorder.     

Relapsing polychondritis: a clinical review

OBJECTIVE: This study comprehensively reviews the literature related to relapsing polychondritis (RP). METHODS: A detailed search via MEDLINE (PubMed) was performed using relapsing polychondritis as the key term. Relevant articles were analyzed with a focus on history, epidemiology, etiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prognosis of RP. RESULTS: RP is a rare episodic and progressive inflammatory disease of presumed autoimmune etiology first described in 1923. RP affects cartilage in multiple organs, such as the ear, nose, larynx, trachea, bronchi, and joints. In addition, it can affect proteoglycan-rich tissues, such as the eyes, aorta, heart, and skin. The diagnosis of RP is based on the presence of clinical criteria. A standardized therapeutic protocol for RP has not been established. Nonsteroidal anti-inflammatory drugs, dapsone and/or colchicine, may control disease activity in some patients. In other patients, immunosuppressive drugs and prednisone have been effective. RP is a potentially lethal disease; pulmonary infection, systemic vasculitis, airway collapse, and renal failure are the most common causes of death. Earlier studies indicate survival rates between 70% at 4 years and 55% at 10 years. In a recent study, a survival rate of 94% at 8 years may be due to improved medical and surgical management. CONCLUSIONS: RP is a rare, multisystemic, and potentially fatal disease. The pathogenesis and optimal therapeutic approach to patients with RP is poorly understood.     

Patients with relapsing polychondritis and previous cartilage trauma present more autoimmunity phenomena

Relapsing polychondritis (RP) is an autoimmune disease characterized by inflammation and destruction of all type of body cartilage, and the cartilage trauma may be a trigger of the disease in a susceptible person. We describe the clinical and laboratory findings in a group of 18 patients with RP with (7 cases) or without (11 cases) anteceding cartilage trauma. The mean age was 41 years in the group with cartilage trauma and 55 years in the group without cartilage trauma. For both groups, female gender was predominant. All patients presented with auricular chondritis. Systemic manifestations and autoimmunity were more common in patients with anteceding trauma.     

New onset of immunoglobulin G4-related disease in a patient with relapsing polychondritis

Relapsing polychondritis (RP) is a rare systemic autoimmune disorder characterized by the episodic and progressive deterioration of cartilage inflammation. Approximately 30% patients with RP have concurrent disease. However, there have been no previous reports of RP complicated by immunoglobulin G4-related disease (IgG4-RD). Here we report the case of a 67-year-old male who developed IgG4-RD approximately 20 years after RP diagnosis. The association between IgG4-RD and RP remains unclear.     

Relapsing polychondritis

Relapsing polychondritis (RP) is a rare disease causing inflammation and destruction of cartilage and other connective tissues. Specific laboratory aberrations are lacking. Predominant clinical manifestations include auricular chondritis, polyarthritis, nasal chondritis, ocular inflammation, audiovestibular damage, and respiratory tract chondritis. A relapsing course is characteristic. Airways are involved in 50% of patients and may cause dyspnea, stridor, wheezing, hoarseness, aphonia, and laryneal or tracheal tenderness. Airflow obstruction may result from RP involving the tracheobronchial tree; there is no interstitial or pulmonary vascular component. Collapse or failure of the trachea to dilate during inspiration is a key feature. Fast computed tomographic (CT) scanners can visualize dynamic airway collapse. Randomized, controlled trials of therapy have not been done. Corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs) are used most commonly, but optimal regimens and duration of therapy have not been elucidated. Endobronchial stents or tracheostomy may be required for severe stenoses refractory to medical therapy.     

Hyperbaric oxygen therapy as a complementary treatment for radiation proctitis: Useless or useful? – A literature review

Radiotherapy (RT) is the backbone of multimodality treatment of more than half of cancer cases. Despite new modern RT techniques, late complications may occur such as radiation proctitis (RP). The natural history of RP is unpredictable. Minor symptoms may resolve spontaneously or require conservative treatment. On the other hand, for similar and uncomplicated clinical contexts, symptoms may persist and can even be refractory to the progressive increase in treatment measures. Over the last decades, an enormous therapeutic armamentarium has been considered in RP, including hyperbaric oxygen therapy (HBOT). Currently, the evidence regarding the impact of HBOT on RP and its benefits is conflicting. Additional prospective and randomised studies are necessary to validate HBOT’s effectiveness in the ‘real world’ clinical practice. This article reviewed the relevant literature on pathophysiology, clinical presentation, different classifications and discuss RP management including a proposal for a therapeutic algorithm with a focus on HBOT.     

Evidence that a humoral immune response to autologous cartilage proteoglycan can participate in the induction of cartilage pathology

We examined antiproteoglycan antibodies as an autoimmune response for induction of synovitis. This hypothesis was studied by monitoring humoral antiproteoglycan antibody following IgG induction of experimental immune synovitis, localization in the articular cartilage of an autologous immune response, and loss of proteoglycan from cartilage following intravenous administration of antiproteoglycan monoclonal antibodies. The data support the hypothesis that autoimmunity to cartilage macromolecules may play a role in the etiopathogenesis of arthritis.     

Nailfold video-capillaroscopy in systemic sclerosis

The Raynaud's phenomenon (RP) is the most common and significant clinical condition supporting microvascular analysis as soon as possible. Microvascular involvement is a key feature of RP, and several rheumatic diseases are characterized by the presence of the RP. Nailfold capillary microscopy shows an impressive cost/effectiveness ratio: it is simple, noninvasive and inexpensive.Well-recognized videocapillaroscopic patterns (NVC) have been described mainly in scleroderma (SSc) patients complaining of a secondary RP. The peripheral microvascular damage in SSc is characterized by increasing structural alterations of the capillaries (giant capillaries and microhemorrhages) with progressive decrease of their density. The detection of the scleroderma NCV allows early differentiation between primary RP (functional, not disease associated), and secondary RP (disease associated). Other major NVC patterns have been described in the field of rheumatic diseases. Interestingly, correlations are evident between the NCV and the clinical symptoms, severity of the disease and the laboratory findings. Further clinical and epidemiological studies, as well as a standardized and computerized quantitation of the observed damages are required.     

Primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is an idiopathic, chronic cholestatic liver disease of uncertain etiopathogenesis commonly associated with inflammatory bowel disease (IBD) and is characterized by patchy inflammation of the biliary tree progressing to fibrosis and strictures. The natural history of PSC is highly variable but characteristically follows a progressive clinical course leading to biliary tree strictures, cholestasis, and choledocholithiasis. The course of the disease may be complicated by cholangitis, secondary biliary cirrhosis, liver failure, and cholangiocarcinoma. The diagnosis of PSC is based on typical cholangiographic findings, supported by nonspecific clinical signs and symptoms, cholestatic liver biochemical tests, and liver biopsy. Uncommon and usually clinically obvious secondary causes of sclerosing cholangitis are excluded before establishing the diagnosis of PSC. Therapeutic approaches that show promise include endoscopic therapy and ursodeoxycholic acid. The only accepted therapy for end-stage PSC that can improve long-term outcome is liver transplantation. The diagnosis of cholangiocarcinoma--often difficult and elusive--usually precludes liver transplantation because its prognosis is very poor.     

Relapsing polycondritis associated with microscopic polyangiitis: description of a clinical case

A clinical case of Relapsing Polychondritis (RP) with Microscopic Polyangiitis (MPA) is described in a 66 years old woman. This case represents a rare association of the two pathologies. Polychondritis is a rare inflammatory disease of unknown origin, but immunological mechanisms are essential in the pathogenesis. Histological features are inflammation and destruction of cartilage. The disease is systemic, may have a remitting course. The osteoarticular lesions are sometimes unusual, involving the temporomandibular or cervical articulations, and the renal lesions may be severe. This can be primary or associated with several other diseases. Microscopic Polyangiitis is a systemic disorder characterized by necrotizing vasculitis, affecting the small vessels. Most patient with MPA have Antineutrophil Cytoplasmic Antibodies for Myeloperoxidase (MPO-ANCA). ANCA have become an established tool for the diagnosis of systemic vasculitis. The primary target antigens for ANCA are myeloperoxidase (enzyme present in the secretory granules of neutrophils and monocytes) and antibodies to these antigens are tested by ELISA and IIF (indirect immunofluorescence). We describe a case of histologically confirmed MPA with Relapsing Polychondritis. Clinically she presented livedo reticularis in the lower limbs and pain in the joints. During the follow-up the patient developed asymmetric oligoarticular arthritis. Immunosuppressive drugs like glucocorticoids and cyclofosfamide are the drugs of choice, depending on the stage and severity of the disease.     

Autoimmune hepatitis,one disease with many faces:Etiopathogenetic,clinico-laboratory and histological characteristics

Autoimmune hepatitis(AIH) is an unresolving progressive liver disease of unknown etiology characterized byhypergammaglobulinemia,autoantibodies detection and interface hepatitis.Due to the absence of specific diagnostic markers and the large heterogeneity of its clinical,laboratory and histological features,AIH diagnosis may be potentially difficult.Therefore,in this in-depth review we summarize the substantial progress on etiopathogenesis,clinical,serological and histological phenotypes of AIH.AIH has a global distribution affecting any age,both sexes and all ethnic groups.Clinical manifestations vary from asymptomatic to severe or rarely fulminant hepatitis.Hypergammaglobulinemia with selective elevation of IgG is found in most cases.Autoimmune attack is perpetuated,possibly via molecular mimicry,and favored by the impaired control of T-regulatory cells.Histology(interface hepatitis,emperipolesis and hepatic rosette formation) and autoantibodies detection although not pathognomonic,are still the hallmark for a timely diagnosis.AIH remains a major diagnostic challenge.AIH should be considered in every case in the absence of viral,metabolic,genetic and toxic etiology of chronic or acute hepatitis.Laboratory personnel,hepato-pathologists and clinicians need to become more familiar with disease expressions and the interpretation of liver histology and autoimmune serology to derive maximum benefit for the patient.     

The occurrence of autoantibodies to matrilin 1 reflects a tissue-specific response to cartilage of the respiratory tract in patients with relapsing polychondritis

OBJECTIVE: Relapsing polychondritis (RP) is an inflammatory disease that mainly affects cartilage tissue in the auricle, nose, and lower respiratory tract. When tracheolaryngeal cartilage is involved, the disease is occasionally fatal. Matrilin 1 is a cartilage-specific protein most prominently expressed in tracheal cartilage, but not in joint cartilage. Immunization with the protein in rats and mice induces respiratory distress and nasal destruction, as seen in RP. We investigated the response to matrilin 1 and other cartilage proteins in sera from patients with RP, 4 additional groups of patients with other major connective tissue diseases, and healthy control subjects. METHODS: Sera were analyzed by enzyme-linked immunosorbent assay (ELISA) for antibody responses to matrilin 1, types II, IX, and XI collagen, and cartilage oligomeric matrix protein (COMP). Titers above the mean + 3SD of controls were considered positive. Specificity of matrilin 1 recognition was further investigated by the capacity of high-titer sera to block the binding of a matrilin 1-specific monoclonal antibody in inhibition ELISAs. In vivo reactivity and specificity were tested by injecting sera into neonatal mice, and antibody binding was detected by immunohistochemical staining. RESULTS: Serum antibodies from RP patients bound tracheolaryngeal and nasal cartilage in vivo and inhibited the binding of anti-matrilin 1-specific monoclonal antibodies. Thirteen of the 97 RP patients had increased titers of matrilin 1 antibody. Positive titers correlated with respiratory symptoms in 69% of the cases. Significant responses to type II collagen and COMP were also detected. CONCLUSION: Antibodies to matrilin 1 bind tracheolaryngeal cartilage in vivo and are correlated with an inflammatory attack on tracheolaryngeal cartilage that is often seen in RP.     

Long term anti-tumour necrosis factor alpha monotherapy in rheumatoid arthritis: effect on radiological course and prognostic value of markers of cartilage turnover and endothelial activation

OBJECTIVES: To investigate the effect of prolonged neutralisation of tumour necrosis factor alpha (TNFalpha) on the radiological course in rheumatoid arthritis (RA). To assess whether the radiological course can be predicted by clinical variables or biological markers of cartilage and synovium turnover and of endothelial activation. PATIENTS AND METHODS: Forty seven patients with active RA enrolled at our centre in monotherapy trials with adalimumab (D2E7), a fully human anti-TNFalpha monoclonal antibody, were studied for two years. Radiographs of hands and feet obtained at baseline and after one and two years were scored in chronological order by a single, blinded observer using the modified Sharp method. Radiological course was classified as stable or progressive using the smallest detectable difference as cut off point. The relation between radiological course and serum markers of cartilage and synovium turnover (metalloproteinases (MMP-1 and MMP-3), cartilage oligomeric matrix protein (COMP), human cartilage glycoprotein-39 (HC gp-39)), endothelial activation (soluble E-selectin and intercellular adhesion molecule (ICAM-1)), and integrated measures of disease activity were assessed using univariate and multivariate analysis. RESULTS: Radiological evaluation was performed in 36 patients with paired sets of radiographs at baseline and two years. After two years a total of 15/36 (42%) presented no radiological progression. More patients with stable radiological course were still receiving anti-TNFalpha treatment after two years (13/15 (87%) v 11/21 (52%); p=0.03) and had lower baseline COMP and sICAM-1 levels (p=0.01 and 0.04, respectively) than those in the group with progressive disease. In a logistic regression model the combination of sustained TNF neutralisation and baseline COMP and sICAM-1 levels was predictive for radiological outcome (p=0.03). C reactive protein and disease activity score area under the curve were significantly correlated with changes in radiological scores after two years (r=0.40 and 0.37, p<0.05). Long term TNFalpha neutralisation decreased the levels of COMP, sICAM, MMPs, and HC gp-39, but not sE-selectin. CONCLUSION: The results suggest that long term monotherapy with anti-TNFalpha has a positive effect on radiological outcome and modulates cartilage and synovium turnover as measured by biological markers. Baseline serum sICAM-1 levels and COMP levels may be helpful to identify patients with progressive or non-progressive radiological outcome.     

Relapsing Polychondritis Associated with Miscellaneous Ocular Symptoms and Increased IgA: a Case Report

A male patient had suffered miscellaneous ocular symptoms for 20 years with auricular dysmorphosis and was diagnosed with Relapsing Polychondritis (RP) in the ear, nose, joints, and costal cartilage. The patient lost his vision owing to recurrent ocular symptoms for decades. He presented an increased IgA and was diagnosed with monoclonal gammopathy of undetermined significance (MGUS) and treated by prednisone and cyclophosphamide. His ocular symptoms relieved and serum IgA decreased after six months. In conclusion, RP is a systemic disease with a wide range of clinical symptoms and may lead to serious complications.     

Relapsing polychondritis--case series from South India

Relapsing polychondritis (RP) is a rare recurring inflammatory disorder with variable clinical course. It has been described mainly in Caucasian population. Reports from other ethnic groups are few. We report seven cases of relapsing polychondritis in south Indian population. In between 1995 and 2008, seven patients fulfilling the McAdam-Damiani-Levine criteria for diagnosis of relapsing polychondritis were identified. Records pertaining to these patients were studied and clinical presentation, course, and treatment offered were analyzed retrospectively. The female-to-male ratio in our series was 2.5:1. The age of onset of symptoms ranged from 28 to 54 years, with a mean of 40.2 years. An average of 20 months, ranging from 3 months to 6 years, elapsed before the patient presented to us seeking a diagnosis. Various structural involvement in our series were as follows: pinna in four (57%), nasal cartilage in five (71%), joints in three (43%), eyes in three (43%), laryngotracheal tree in three (43%), inner ear in one (14.3%), skin in one (14.3%), and heart in one (14.3%). Associated autoimmune diseases were present in four (57%) patients in the form of one of the following in each: vasculitis, autoimmune hemolytic anemia, hypothyroidism, and rheumatoid arthritis. All seven patients received prednisolone with three of them requiring additional immunosuppressants. There was no mortality amongst the four patients who had remained on follow-up at the time of this report. Although RP is an uncommon disorder, clinicians should be aware of the manifestations so as to initiate prompt treatment and prevent complications. Our series reports less frequent auricular cartilage and skin involvement and an exceptional case of basal cell carcinoma, although the other manifestations were similar to that seen in Caucasian and other Asian populations.     

Update on juvenile dermatomyositis: new advances in understanding its etiopathogenesis

PURPOSE OF REVIEW: Juvenile dermatomyositis is the most common of the idiopathic inflammatory myopathies in children. It is considered an autoimmune disease of relatively unknown etiology, although environmental exposures and infectious agents are thought to play a role in disease pathogenesis. More recently, data has become available regarding the molecular genetics of children affected with juvenile dermatomyositis and the impact these genes have on disease expression and clinical course. Additionally, features of the immune response, including specific pathways of the humoral and cellular immune systems, have been further described. This article summarizes the most recent advances in understanding the etiopathogenesis of juvenile dermatomyositis. RECENT FINDINGS: This article focuses on advances made in understanding the role that complement, soluble adhesion molecules, thrombospondin-1 levels, and genetics play in the evolution of juvenile dermatomyositis. It also describes microarray technology and gene expression profiling as means of identifying those genes overexpressed in affected children and thus likely involved in disease pathogenesis; microarray technology may also be used to distinguish dermatomyositis from the other inflammatory myopathies, as well as from other myopathies. SUMMARY: In better understanding the pathogenetic mechanisms whereby disease evolves and the means by which genetic profiles influence susceptibility to and expression of disease, immunotherapies to better treat juvenile dermatomyositis may become available in the future.     

Resistive Exercise for Arthritic Cartilage Health (REACH): A randomized double-blind, sham-exercise controlled trial

Background

This article provides the rationale and methodology, of the first randomised controlled trial to our knowledge designed to assess the efficacy of progressive resistance training on cartilage morphology in women with knee osteoarthritis. Development and progression of osteoarthritis is multifactorial, with obesity, quadriceps weakness, joint malalignment, and abnormal mechanical joint forces particularly relevant to this study. Progressive resistance training has been reported to improve pain and disability in osteoarthritic cohorts. However, the disease-modifying potential of progressive resistance training for the articular cartilage degeneration characteristic of osteoarthritis is unknown. Our aim was to investigate the effect of high intensity progressive resistance training on articular cartilage degeneration in women with knee osteoarthritis.

Methods

Our cohort consisted of women over 40 years of age with primary knee osteoarthritis, according to the American College of Rheumatology clinical criteria. Primary outcome was blinded measurement of cartilage morphology via magnetic resonance imaging scan of the tibiofemoral joint. Secondary outcomes included walking endurance, balance, muscle strength, endurance, power, and velocity, body composition, pain, disability, depressive symptoms, and quality of life. Participants were randomized into a supervised progressive resistance training or sham-exercise group. The progressive resistance training group trained muscles around the hip and knee at 80% of their peak strength and progressed 3% per session, 3 days per week for 6 months. The sham-exercise group completed all exercises except hip adduction, but without added resistance or progression. Outcomes were repeated at 3 and 6 months, except for the magnetic resonance imaging scan, which was only repeated at 6 months.

Discussion

Our results will provide an evaluation of the disease-modifying potential of progressive resistance training for osteoarthritis.

Trial Registration

ANZCTR Reference No. 12605000116628     

Transition from primary Raynaud's phenomenon to secondary Raynaud's phenomenon identified by diagnosis of an associated disease: results of ten years of prospective surveillance

OBJECTIVE: To assess the early signs, risk factors, and rate of transition from primary Raynaud's phenomenon (primary RP) to secondary RP. METHODS: A clinical sample of 307 consecutive patients with RP was included in a prospective followup study. After an initial screening, 244 patients were classified as having primary RP, of whom 236 were followed up for a mean +/- SD of 11.2 +/- 3.9 years. Patients classified according to the screening as having suspected secondary RP underwent an extended screening program annually until transition to secondary RP occurred. RESULTS: The initial prevalence of secondary RP was 11%. The annual incidence of transition to suspected secondary RP was 2%, and the annual incidence of transition to secondary RP was 1%. Overall, 46 patients were classified as having suspected secondary RP, and 23 of these later were classified as having secondary RP. Older age at onset of RP (hazard ratio 2.59, 95% confidence interval [95% CI] 1.40-4.80), shorter duration of RP at enrollment (hazard ratio 0.87, 95% CI 0.81-0.94), and abnormal findings on thoracic outlet test (hazard ratio 2.69, 95% CI 1.12-6.48) were associated with an increased risk for transition to secondary RP. Compared with patients with suspected secondary RP, those diagnosed as having secondary RP had a higher number and earlier occurrence of pathologic findings. Furthermore, antinuclear antibodies at a titer of > or = 1:320 and positive findings in specific serologic subsets were associated with a significantly increased risk for developing a connective tissue disease. CONCLUSION: Patients diagnosed initially as having primary RP may actually comprise 1 of 3 groups: those with idiopathic RP, those with a rather benign disease course, and those with a more severe course of the disease.     

SAPHO syndrome complicated with relapsing polychondritis: A case report

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare chronic inflammatory disease. The main clinical manifestation of SAPHO syndrome is an osteoarthropathy with cutaneous involvement. Relapsing polychondritis (RP) characterized by chronic inflammation and cartilage degeneration is a rare systematic autoimmune disease. Here we report a RP case in a SAPHO syndrome patient, in which auricularitis happened 10 years after the diagnosed as SAPHO syndrome. Tofacitinib treatment can alleviate the symptoms.