Relapsing polychondritis | |
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Other names | Atrophic polychondritis, [1] systemic chondromalacia, [1] chronic atrophic polychondritis, Meyenburg-Altherr-Uehlinger syndrome, generalized chondromalacia |
Ear inflammation with sparing of ear lobe in a person with relapsing polychondritis [2] | |
Specialty | Rheumatology, Immunology |
Relapsing polychondritis is a multi-systemic condition characterized by repeated episodes of inflammation and deterioration of cartilage. The often painful disease can cause joint deformity and be life-threatening if the respiratory tract, heart valves, or blood vessels are affected. The exact mechanism is poorly understood, but it is thought to be related to an immune-mediated attack on particular proteins that are abundant in cartilage.
The diagnosis is reached on the basis of the symptoms and supported by investigations such as blood tests and sometimes other investigations. Treatment may involve symptomatic treatment with painkillers or anti-inflammatory medications, and more severe cases may require suppression of the immune system.
Though any cartilage in the body may be affected in persons with relapsing polychondritis, in many cases the disease affects several areas while sparing others. The disease may be variable in its signs and symptoms, resulting in a difficult diagnosis which may leads to delayed recognition for several months, years or decades. [3] Joint symptoms are often one of the first signs of the disease with cartilage inflammation initially absent in nearly half the cases. [3]
There are several other overlapping diseases associated with RP, that should also be taken into account. About one-third of people with RP might be associated with other autoimmune diseases, vasculitides and hematologic disorders. [4] Systemic vasculitis is the most common association with RP, followed by rheumatoid arthritis and systemic lupus erythematosus. [5] The following table displays the main diseases in association with RP.
Cartilage inflammation (technically known as chondritis) that is relapsing is very characteristic of the disease and is required for the diagnosis of RP. [3] These recurrent episodes of inflammation over the course of the disease may result in breakdown and loss of cartilage. [3] The signs and symptoms of cartilage inflammation in various parts of the body will be described first.[ citation needed ]
Inflammation of the cartilage of the ear is a specific symptom of the disease and affects most people. [3] It is present in about 20% of persons with RP at presentation and in 90% at some point. [3] Both ears are often affected but the inflammation may alternate between either ear during a relapse. [3] It is characteristic for the entire outer part of the ear except the earlobe to be swollen, red, or less often purplish, warm and painful to light touch. [3]
The inflammation of the ear usually lasts a few days or more, rarely a few weeks, and then resolves spontaneously and recurs at various intervals. [3] Because of the loss of cartilage, after several flares cauliflower ear deformity may result. [3] The outer part of the ear may be either floppy or hardened by calcifications of the scar tissue that replaces the cartilage. [3] These cauliflower ear deformities occur in about 10% of persons with RP. [3]
The inflammation of the cartilage of the nose involves the bridge of the nose and is often less marked than the ears. [3] Statistics show that this clinical manifestation is present in 15% of persons with RP and occurs at some point in 65% of persons with RP. [3] Nasal obstruction is not a common feature. [3] Atrophy may eventually develop secondarily during the disease, this appears gradual and is not easily noticed. [3] This can result in collapse of the nasal septum with saddle-nose deformity, which is painless but irreversible. [3]
Inflammation occurs in the laryngeal, tracheal and bronchial cartilages. [6] Both of these sites are involved in 10% of persons with RP at presentation and 50% over the course of this autoimmune disease, and is more common among females. [3] The involvement of the laryngotracheobronchial cartilages may be severe and life-threatening; it causes one-third of all deaths among persons with RP. [3] [4] Laryngeal chondritis is manifested as pain above the thyroid gland and, more importantly, as dysphonia with a hoarse voice or transient aphonia. [3] Because this disease is relapsing, recurrent laryngeal inflammation may result in laryngomalacia or permanent laryngeal stenosis with inspiratory dyspnea that may require emergency tracheotomy as a temporary or permanent measure. [3]
Tracheobronchial involvement may or may not be accompanied with laryngeal chondritis and is potentially the most severe manifestation of RP.[ citation needed ]
The symptoms consist of dyspnea, wheezing, a nonproductive cough, and recurrent, sometimes severe, lower respiratory tract infections. [3] [4] Obstructive respiratory failure may develop as the result of either permanent tracheal or bronchial narrowing or chondromalacia with expiratory collapse of the tracheobronchial tree. [3] Endoscopy, intubation, or tracheotomy has been shown to hasten death. [3]
Involvement of the rib cartilages results in costochondritis. [3] Symptoms include chest wall pain or, less often, swelling of the involved cartilage. [3] The involvement of the ribs is seen in 35% of persons with RP but is rarely the first symptom. [3]
Relapsing polychondritis may affect many different organ systems of the body. At first, some people with the disease may have only nonspecific symptoms such as fever, weight loss, and malaise. [7]
The second most common clinical finding of this disease is joint pain with or without arthritis, after chondritis. [3] [6] All synovial joints may be affected. [6] [4]
At presentation, around 33% of people have joint symptoms that involve Polyarthralgia and/or polyarthritis or oligoarthritis that affects various parts of the body and often appears to be episodic, asymmetric, migratory and non-deforming. [4] The most common sites of involvement are the metacarpophalangeal joints, proximal interphalangeal joints and knees. After which is followed by the ankles, wrists, metatarsophalangeal joints and the elbows. [3] Any involvement of the axial skeleton is considered to be very rare. [3] Tests for rheumatoid factor are negative in affected persons with RP, unless there is a co-morbidity with RA. [6]
Less often it has been reported that persons may experience arthralgia, monoarthritis, or chronic polyarthritis that mimics rheumatoid arthritis, leading to a difficult diagnosis for this disease. [3] The appearance of erosions and destruction, however, is exceedingly rare and this may point instead to rheumatoid arthritis as a cause. [3]
Diseases and inflammation of tendons have been reported in small numbers of people with RP. [3] During the course of the disease, around 80% of people develop joint symptoms. [3]
Involvement of the eye is rarely the initial symptom but develops in 60% of persons with RP. [3] [6] [4] [8] [9] The most common forms of ocular involvement are usually mild and often consist of unilateral or bilateral episcleritis and/or scleritis, that is often anterior and could be lingering or relapsing. [3] [4] Scleritis that is necrotizing is found to be exceedingly rare. [3] Less often, conjunctivitis occurs. [3] [4] There are also other ocular manifestations that occur in persons with RP, these include keratoconjunctivitis sicca, peripheral keratitis (rarely with ulcerations), anterior uveitis, retinal vasculitis, proptosis, lid edema, keratoconus, retinopathy, iridocyclitis and ischemic optic neuritis that can lead to blindness. [3] [6] [4] [10] Cataract also is reported in relation to either the disease or to glucocorticoid exposure. [3]
The involvement of the peripheral or central nervous system is relatively rare and only occurs in 3% of persons affected with RP, and is sometimes seen in a relation with concomitant vasculitis. [3] The most common neurological manifestation are palsies of the cranial nerves V and VII. Also hemiplegia, ataxia, myelitis and polyneuropathy have been reported in scientific literature. Very rare neurological manifestations include aseptic meningitis, meningoencephalitis, stroke, focal or generalized seizures and intracranial aneurysm. [3] [4] Magnetic Resonance Imaging of the brain shows multifocal areas of enhancement consistent with cerebral vasculitis in some cases. [6]
The involvement of the kidney can be caused by primary renal parenchymal lesions, or an underlying vasculitis, or another associated autoimmune disease. Actual kidney involvement is quite rare, elevated creatinine levels are reported in approximately 10% of people with RP, and abnormalities in urinalysis in 26%. Involvement of the kidney often indicates a worse prognosis, with a 10-year survival rate of 30%. [3] [6] [4] The most common histopathologic finding is mild mesangial proliferation, that is followed by focal and segmental necrotizing glomerulonephritis with crescents. Other abnormalities that are found include glomerulosclerosis, IgA nephropathy and interstitial nephritis. Immunofluorescence studies most often reveal faint deposits of C3, IgG or IgM in the primarily mesangium. [6]
These symptoms could consist of asthenia, fever, anorexia, and weight loss. They mostly occur during a severe disease flare. [3] [6]
Relapsing polychondritis is an autoimmune disease [11] in which the body's immune system begins to attack and destroy the cartilage tissues in the body. It has been postulated that both cell-mediated immunity and humoral immunity are responsible. [7]
Reasons for disease onset are not known, but there is no evidence of a genetic predisposition to developing relapsing polychondritis. [7] However, there are cases where multiple members of the same family have been diagnosed with this illness. Studies indicate that some genetic contribution to susceptibility is likely. [12]
There is no specific test for relapsing polychondritis. Some people may exhibit abnormal lab results while others may have completely normal labs even during active flares.[ citation needed ]
There are several clinical criteria used to diagnose this disease. McAdam et al. introduced the clinical criteria for RP in 1976. [4] [10] These clinical criteria have later been expanded by Damiani et al. in 1979 and finally Michet et al. modified them in 1986. [4] [13] [14] See the following table for these diagnostic clinical criteria and the number of conditions required for an official diagnosis.
Authors | Criteria | Conditions required |
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McAdam et al. |
| 3 out of 6 criteria |
Damiani et al. |
|
|
Michet et al. |
|
|
Patients presenting with acute episodes often have high levels of inflammatory markers such as erythrocyte sedimentation rate or C-reactive protein, ESR or CRP. Patients often have cartilage-specific antibodies present during acute relapsing polychondritis episodes. Antinuclear antibody reflexive panel, rheumatoid factor, and antiphospholipid antibodies are tests that may assist in the evaluation and diagnosis of autoimmune connective-tissue diseases.[ citation needed ]
FDG positron emission tomography (PET) may be useful to detect the condition early. [15] Other imaging studies including MRI, CT scans, and X-rays may reveal inflammation and/or damaged cartilage facilitating diagnosis.[ citation needed ]
Biopsy of the cartilage tissue (for example, ear) may show tissue inflammation and destruction, and may help with the diagnosis. The Biopsy of cartilage in patients with relapsing polychondritis may demonstrate chondrolysis, chondritis, and perichondritis.[ citation needed ]
It is useful to do a full set of pulmonary function tests, including inspiratory and expiratory flow-volume loops. Patterns consistent with either extrathoracic or intrathoracic obstruction (or both) may occur in this disease. Pulmonary function tests (flow-volume loops) provide a useful noninvasive means of quantifying and following the degree of extrathoracic airway obstruction in relapsing polychondritis. [16]
A differential diagnosis should be taken into account with the following main RP manifestations. [4]
Manifestation of RP | Differential diagnosis |
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Arthritis | Rheumatoid arthritis. |
Auricular chondritis | Infectious perichondritis, injury, insect bites and stings, ear erysipelas, cystic chondromalacia, overexposure to extreme cold temperatures or to sunlight, frostbite of the ear, congenital syphilis. |
Airway/kidney involvement | Granulomatosis with polyangiitis, bronchial asthma. |
Nose cartilage involvement/saddle nose | Granulomatosis with polyangiitis, leishmaniasis, congenital syphilis, leprosy, aspergillosis, paracoccidioidomycosis, cocaine inhalation, systemic lupus erythematosus. |
Subglottic stenosis | Prior endotracheal intubation, amyloidosis, sarcoidosis. |
Vascular involvement | Takayasu's arteritis, polyarteritis nodosa, Behçet's disease, antiphospholipid syndrome. |
Vestibular disease | Posterior circulation infarct, vestibulitis, benign paroxysmal vertigo, Ménière's disease. |
There are no prospective randomized controlled trials studying therapies for relapsing polychondritis. Evidence for efficacy of treatments is based on many case reports and series of small groups of patients. There are case reports that non-steroidal anti-inflammatories are effective for mild disease and that corticosteroids are effective for treatment of severe relapsing polychondritis. There are multiple case reports that dapsone is effective in doses from 25 mg/day to 200 mg/day. [17] Corticosteroid-sparing medications such as azathioprine or methotrexate may be used to minimize steroid doses and limit the side effects of steroids. For severe disease cyclophosphamide is often given in addition to high dose intravenous steroids. [7]
Many individuals have mild symptoms, which recur infrequently, while others may have persistent problems that become debilitating or life-threatening. [18]
Relapsing polychondritis occurs as often in men as in women. In a Mayo Clinic series, the annual incidence was about 3.5 cases per million. The highest incidence is between the ages of 40 and 50 years, but it may occur at any age. [7]
In 1923, Rudolf Jaksch von Wartenhorst first discovered relapsing polychondritis while working in Prague and initially named it Polychondropathia. [19] [7]
His patient was a 32-year-old male brewer who presented with fever, asymmetric polyarthritis, and the ears and nose showed signs of swelling, deformity and were painful. Biopsy of nasal cartilage revealed loss of the cartilage matrix and a hyperplastic mucous membrane. Jaksch von Wartenhorst considered this was an undescribed degenerative disorder of cartilage and named it Polychondropathia. He even took his patient's occupation into consideration, and related the cause to excessive alcohol intake. [7]
Since then, the disease has received many names. The following table shows the history of the nomenclature of relapsing polychondritis. The current name, Relapsing Polychondritis (RP), was introduced by Pearson and his colleagues in 1960 to emphasize the episodic course of the disease. [7] [20]
Suggested name | Author(s) and year |
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Polychondropathia | Rudolf Jaksch von Wartenhorst in 1923 |
Chondromalacia | Von Meyenburg in 1936 and Altherr in 1936 |
Panchondritis | Harders in 1954 |
Polychondritis chronica atrophicans | Bober and Czarniecki in 1955 |
Chronic atrophic polychondritis | Bean, Drevets, and Chapman in 1958 |
Relapsing polychondritis | Pearson, Kline, and Newcomer in 1960 |
Atrophic polychondritis | Rhys Davies and Kelsall in 1961 |
There has been little research on neurological problems related to RP. [3] If these cartilage structures get inflamed, they could press against nerves and cause a variety of problems that is seen in RP like peripheral neuropathy and many more. [3] [4]
Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In some types of arthritis, other organs are also affected. Onset can be gradual or sudden.
Rheumatology is a branch of medicine devoted to the diagnosis and management of disorders whose common feature is inflammation in the bones, muscles, joints, and internal organs. Rheumatology covers more than 100 different complex diseases, collectively known as rheumatic diseases, which includes many forms of arthritis as well as lupus and Sjögren's syndrome. Doctors who have undergone formal training in rheumatology are called rheumatologists.
Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis. Vasculitis is primarily caused by leukocyte migration and resultant damage. Although both occur in vasculitis, inflammation of veins (phlebitis) or arteries (arteritis) on their own are separate entities.
Granulomatosis with polyangiitis (GPA), also known as Wegener's granulomatosis (WG), after the Nazi German physician Friedrich Wegener, is a rare long-term systemic disorder that involves the formation of granulomas and inflammation of blood vessels (vasculitis). It is an autoimmune disease and a form of vasculitis that affects small- and medium-size vessels in many organs but most commonly affects the upper respiratory tract, lungs and kidneys. The signs and symptoms of GPA are highly varied and reflect which organs are supplied by the affected blood vessels. Typical signs and symptoms include nosebleeds, stuffy nose and crustiness of nasal secretions, and inflammation of the uveal layer of the eye. Damage to the heart, lungs and kidneys can be fatal.
Henoch–Schönlein purpura (HSP), also known as IgA vasculitis, is a disease of the skin, mucous membranes, and sometimes other organs that most commonly affects children. In the skin, the disease causes palpable purpura, often with joint pain and abdominal pain. With kidney involvement, there may be a loss of small amounts of blood and protein in the urine, but this usually goes unnoticed; in a small proportion of cases, the kidney involvement proceeds to chronic kidney disease. HSP is often preceded by an infection, such as a throat infection.
Polyarteritis nodosa (PAN) is a systemic necrotizing inflammation of blood vessels (vasculitis) affecting medium-sized muscular arteries, typically involving the arteries of the kidneys and other internal organs but generally sparing the lungs' circulation. Small aneurysms are strung like the beads of a rosary, therefore making this "rosary sign" an important diagnostic feature of the vasculitis. PAN is sometimes associated with infection by the hepatitis B or hepatitis C virus. The condition may be present in infants.
Cryoglobulinemia is a medical condition in which the blood contains large amounts of pathological cold sensitive antibodies called cryoglobulins – proteins that become insoluble at reduced temperatures. This should be contrasted with cold agglutinins, which cause agglutination of red blood cells.
Ear pain, also known as earache or otalgia, is pain in the ear. Primary ear pain is pain that originates from the ear. Secondary ear pain is a type of referred pain, meaning that the source of the pain differs from the location where the pain is felt.
An autoantibody is an antibody produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases are associated with such antibodies.
A connective tissue disease (collagenosis) is any disease that has the connective tissues of the body as a target of pathology. Connective tissue is any type of biological tissue with an extensive extracellular matrix that supports, binds together, and protects organs. These tissues form a framework, or matrix, for the body, and are composed of two major structural protein molecules: collagen and elastin. There are many different types of collagen protein in each of the body's tissues. Elastin has the capability of stretching and returning to its original length—like a spring or rubber band. Elastin is the major component of ligaments and skin. In patients with connective tissue disease, it is common for collagen and elastin to become injured by inflammation (ICT). Many connective tissue diseases feature abnormal immune system activity with inflammation in tissues as a result of an immune system that is directed against one's own body tissues (autoimmunity).
Chondropathy refers to a disease of the cartilage. It is frequently divided into 5 grades, with 0-2 defined as normal and 3-4 defined as diseased.
Felty's syndrome (FS), also called Felty syndrome, is a rare autoimmune disease characterized by the triad of rheumatoid arthritis, enlargement of the spleen and low neutrophil count. The condition is more common in those aged 50–70 years, specifically more prevalent in females than males, and more so in Caucasians than those of African descent. It is a deforming disease that causes many complications for the individual.
Mixed connective tissue disease, commonly abbreviated as MCTD, is an autoimmune disease characterized by the presence of elevated blood levels of a specific autoantibody, now called anti-U1 ribonucleoprotein (RNP) together with a mix of symptoms of systemic lupus erythematosus (SLE), scleroderma, and polymyositis. The idea behind the "mixed" disease is that this specific autoantibody is also present in other autoimmune diseases such as systemic lupus erythematosus, polymyositis, scleroderma, etc. MCTD was characterized as an individual disease in 1972 by Sharp et al., and the term was introduced by Leroy in 1980.
Episcleritis is a benign, self-limiting inflammatory disease affecting part of the eye called the episclera. The episclera is a thin layer of tissue that lies between the conjunctiva and the connective tissue layer that forms the white of the eye (sclera). Episcleritis is a common condition, and is characterized by the abrupt onset of painless eye redness.
Palindromic rheumatism (PR) is a syndrome characterised by recurrent, self-resolving inflammatory attacks in and around the joints, and consists of arthritis or periarticular soft tissue inflammation. The course is often acute onset, with sudden and rapidly developing attacks or flares. There is pain, redness, swelling, and disability of one or multiple joints. The interval between recurrent palindromic attacks and the length of an attack is extremely variable from few hours to days. Attacks may become more frequent with time but there is no joint damage after attacks. It is thought to be an autoimmune disease, possibly an abortive form of rheumatoid arthritis.
Autoimmune Pancreatitis (AIP) is an increasingly recognized type of chronic pancreatitis that can be difficult to distinguish from pancreatic carcinoma but which responds to treatment with corticosteroids, particularly prednisone. Although autoimmune pancreatitis is quite rare, it constitutes an important clinical problem for both patients and their clinicians: the disease commonly presents itself as a tumorous mass which is diagnostically indistinguishable from pancreatic cancer, a disease that is much more common in addition to being very dangerous. Hence, some patients undergo pancreatic surgery, which is associated to substantial mortality and morbidity, out of the fear by patients and clinicians to undertreat a malignancy. However, surgery is not a good treatment for this condition as AIP responds well to immunosuppressive treatment. There are two categories of AIP: Type 1 and Type 2, each with distinct clinical profiles.
Necrotizing vasculitis, also called systemic necrotizing vasculitus, is a category of vasculitis, comprising vasculitides that present with necrosis. Examples include giant cell arteritis, microscopic polyangiitis, and granulomatosis with polyangiitis. ICD-10 uses the variant "necrotizing vasculopathy". ICD-9, while classifying these conditions together, does not use a dedicated phrase, instead calling them "polyarteritis nodosa and allied conditions".
Cryoglobulinemic vasculitis is a form of inflammation affecting the blood vessels caused by the deposition of abnormal proteins called cryoglobulins. These immunoglobulin proteins are soluble at normal body temperatures, but become insoluble below 37 °C (98.6 °F) and subsequently may aggregate within smaller blood vessels. Inflammation within these obstructed blood vessels is due to the deposition of complement proteins which activate inflammatory pathways.
Arthritis of the knee is typically a particularly debilitating form of arthritis. The knee may become affected by almost any form of arthritis.
Red ear syndrome (RES) is a rare disorder of unknown etiology which was originally described in 1994. The defining symptom of red ear syndrome is redness of one or both external ears, accompanied by a burning sensation. A variety of treatments have been tried with limited success.