Relapsing polychondritis is a multi-systemic condition characterized by repeated episodes of

inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...

and deterioration of cartilage. The often painful disease can cause joint deformity and be life-threatening if the respiratory tract,

heart valve A heart valve is a one-way valve that allows blood to flow in one direction through the chambers of the heart. Four valves are usually present in a mammalian heart and together they determine the pathway of blood flow through the heart. A heart ...

s, or

blood vessel The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away ...

s are affected. The exact mechanism is poorly understood, but it is thought to be related to an

immune-mediated An immune disorder is a dysfunction of the immune system. These disorders can be characterized in several different ways: * By the component(s) of the immune system affected * By whether the immune system is overactive or underactive * By whether ...

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 An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It i ...

or anti-inflammatory medications, and more severe cases may require suppression of the immune system.

Signs and symptoms

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. Joint symptoms are often one of the first signs of the disease with cartilage inflammation initially absent in nearly half the cases.

Associated diseases

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. Systemic vasculitis is the most common association with RP, followed by rheumatoid arthritis and systemic lupus erythematosus. The following table displays the main diseases in association with RP.

Cartilage inflammation

Cartilage inflammation (technically known as chondritis) that is relapsing is very characteristic of the disease and is required for the diagnosis of RP. These recurrent episodes of inflammation over the course of the disease may result in

breakdown Breakdown may refer to: Breaking down *Breakdown (vehicle), failure of a motor vehicle in such a way that it cannot be operated *Chemical decomposition, also called chemical breakdown, the breakdown of a substance into simpler components *Decompo ...

and

loss Loss may refer to: Arts, entertainment, and media Music * ''Loss'' (Bass Communion album) (2006) * ''Loss'' (Mull Historical Society album) (2001) *"Loss", a song by God Is an Astronaut from their self-titled album (2008) * Losses "(Lil Tjay son ...

of cartilage. The signs and symptoms of cartilage inflammation in various parts of the body will be described first.

Ear

Inflammation of the cartilage of the

ear An ear is the organ that enables hearing and, in mammals, body balance using the vestibular system. In mammals, the ear is usually described as having three parts—the outer ear, the middle ear and the inner ear. The outer ear consists of ...

is a specific symptom of the disease and affects most people. It is present in about 20% of persons with RP at presentation and in 90% at some point. Both ears are often affected but the inflammation may alternate between either ear during a relapse. 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. 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. Because of the loss of cartilage, after several flares

cauliflower ear Cauliflower ear is an irreversible condition that occurs when the external portion of the ear is hit and develops a blood clot or other collection of fluid under the perichondrium. This separates the cartilage from the overlying perichondrium tha ...

deformity may result. The outer part of the ear may be either floppy or hardened by calcifications of the

scar tissue Scar tissue may refer to: Medicine * Scar, an area of fibrous tissue that replaces normal skin after injury * Granulation tissue, a product of healing in major wounds Film and television * ''Scar Tissue'' (1975 film), or ''Wanted: Babysitter'' ...

that replaces the cartilage. These cauliflower ear deformities occur in about 10% of persons with RP.

Nose

The inflammation of the cartilage of the

nose A nose is a protuberance in vertebrates that houses the nostrils, or nares, which receive and expel air for respiration alongside the mouth. Behind the nose are the olfactory mucosa and the sinuses. Behind the nasal cavity, air next passes ...

involves the bridge of the nose and is often less marked than the ears. 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.

Nasal obstruction Nasal congestion is the blockage of nasal breathing usually due to membranes lining the nose becoming swollen from inflamed blood vessels. Background In about 85% of cases, nasal congestion leads to mouth breathing rather than nasal breathin ...

is not a common feature. Atrophy may eventually develop secondarily during the disease, this appears gradual and is not easily noticed. This can result in collapse of the nasal septum with saddle-nose deformity, which is painless but irreversible.

Respiratory tract

Inflammation occurs in the laryngeal, tracheal and bronchial cartilages. 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. The involvement of the laryngotracheobronchial cartilages may be severe and life-threatening; it causes one-third of all deaths among persons with RP. Laryngeal chondritis is manifested as pain above the

thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thy ...

gland and, more importantly, as

dysphonia A hoarse voice, also known as dysphonia or hoarseness, is when the voice involuntarily sounds breathy, raspy, or strained, or is softer in volume or lower in pitch. A hoarse voice, can be associated with a feeling of unease or scratchiness in the ...

with a hoarse voice or transient aphonia. Because this disease is relapsing, recurrent laryngeal inflammation may result in

laryngomalacia Laryngomalacia (literally, "soft larynx") is the most common cause of chronic stridor in infancy, in which the soft, immature cartilage of the upper larynx collapses inward during inhalation, causing airway obstruction. It can also be seen in o ...

or permanent laryngeal stenosis with inspiratory

dyspnea Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing di ...

that may require emergency

tracheotomy Tracheotomy (, ), or tracheostomy, is a surgical airway management procedure which consists of making an incision (cut) on the anterior aspect (front) of the neck and opening a direct airway through an incision in the trachea (windpipe). The r ...

as a temporary or permanent measure. Tracheobronchial involvement may or may not be accompanied with laryngeal chondritis and is potentially the most severe manifestation of RP. The symptoms consist of dyspnea, wheezing, a nonproductive cough, and recurrent, sometimes severe, lower respiratory tract infections. Obstructive respiratory failure may develop as the result of either permanent tracheal or bronchial narrowing or chondromalacia with expiratory collapse of the tracheobronchial tree. Endoscopy, intubation, or tracheotomy has been shown to hasten death.

Ribs

Involvement of the rib cartilages results in

costochondritis Costochondritis, also known as chest wall pain syndrome or costosternal syndrome, is a benign inflammation of the upper costochondral (rib to cartilage) and sternocostal (cartilage to sternum) joints. 90% of patients are affected in multiple ri ...

. Symptoms include chest wall pain or, less often, swelling of the involved cartilage. The involvement of the ribs is seen in 35% of persons with RP but is rarely the first symptom.

Other manifestations

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.

Joint

The second most common clinical finding of this disease is joint pain with or without arthritis, after chondritis. All synovial joints may be affected. 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. 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. Any involvement of the axial skeleton is considered to be very rare. Tests for rheumatoid factor are negative in affected persons with RP, unless there is a co-morbidity with RA. Less often it has been reported that persons may experience arthralgia, monoarthritis, or chronic polyarthritis that mimics

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are invol ...

, leading to a difficult diagnosis for this disease. The appearance of erosions and destruction, however, is exceedingly rare and this may point instead to

as a cause. Diseases and inflammation of tendons have been reported in small numbers of people with RP. During the course of the disease, around 80% of people develop joint symptoms.

Eye

Involvement of the eye is rarely the initial symptom but develops in 60% of persons with RP. The most common forms of ocular involvement are usually mild and often consist of unilateral or bilateral

episcleritis 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 e ...

and/or

scleritis Scleritis is a serious inflammatory disease that affects the white outer coating of the eye, known as the sclera. The disease is often contracted through association with other diseases of the body, such as granulomatosis with polyangiitis or ...

, that is often anterior and could be lingering or relapsing. Scleritis that is necrotizing is found to be exceedingly rare. Less often,

conjunctivitis Conjunctivitis, also known as pink eye, is inflammation of the outermost layer of the white part of the eye and the inner surface of the eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness, or itchiness may occur. The ...

occurs. There are also other ocular manifestations that occur in persons with RP, these include

keratoconjunctivitis sicca Dry eye syndrome (DES), also known as keratoconjunctivitis sicca (KCS), is the condition of having dry eyes. Other associated symptoms include irritation, redness, discharge, and easily fatigued eyes. Blurred vision may also occur. Symptoms range ...

, peripheral

keratitis Keratitis is a condition in which the eye's cornea, the clear dome on the front surface of the eye, becomes inflamed. The condition is often marked by moderate to intense pain and usually involves any of the following symptoms: pain, impaired e ...

(rarely with ulcerations), anterior uveitis, retinal vasculitis,

proptosis Exophthalmos (also called exophthalmus, exophthalmia, proptosis, or exorbitism) is a bulging of the eye anteriorly out of the orbit. Exophthalmos can be either bilateral (as is often seen in Graves' disease) or unilateral (as is often seen i ...

, lid edema, keratoconus,

retinopathy Retinopathy is any damage to the retina of the eyes, which may cause vision impairment. Retinopathy often refers to retinal vascular disease, or damage to the retina caused by abnormal blood flow. Age-related macular degeneration is technically inc ...

iridocyclitis Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and ...

and ischemic

optic neuritis Optic neuritis describes any condition that causes inflammation of the optic nerve; it may be associated with demyelinating diseases, or infectious or inflammatory processes. It is also known as optic papillitis (when the head of the optic nerv ...

that can lead to blindness.

Cataract A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colors, blurry or double vision, halos around light, trouble ...

also is reported in relation to either the disease or to

glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every verteb ...

exposure.

Neurological

The involvement of the peripheral or

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

is relatively rare and only occurs in 3% of persons affected with RP, and is sometimes seen in a relation with concomitant vasculitis. The most common neurological manifestation are palsies of the

cranial nerves Cranial nerves are the nerves that emerge directly from the brain (including the brainstem), of which there are conventionally considered twelve pairs. Cranial nerves relay information between the brain and parts of the body, primarily to and f ...

V and VII. Also hemiplegia,

ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...

myelitis Myelitis is inflammation of the spinal cord which can disrupt the normal responses from the brain to the rest of the body, and from the rest of the body to the brain. Inflammation in the spinal cord, can cause the myelin and axon to be damaged re ...

and polyneuropathy have been reported in scientific literature. Very rare neurological manifestations include

aseptic meningitis Aseptic meningitis is the inflammation of the meninges, a membrane covering the brain and spinal cord, in patients whose cerebral spinal fluid test result is negative with routine bacterial cultures. Aseptic meningitis is caused by viruses, my ...

meningoencephalitis Meningoencephalitis (; from ; ; and the medical suffix ''-itis'', "inflammation"), also known as herpes meningoencephalitis, is a medical condition that simultaneously resembles both meningitis, which is an infection or inflammation of the menin ...

, stroke, focal or generalized

seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with l ...

and

intracranial aneurysm An intracranial aneurysm, also known as a brain aneurysm, is a cerebrovascular disorder in which weakness in the wall of a cerebral artery or vein causes a localized dilation or ballooning of the blood vessel. Aneurysms in the posterior circula ...

. Magnetic Resonance Imaging of the brain shows multifocal areas of enhancement consistent with

cerebral vasculitis Cerebral vasculitis (sometimes the word angiitis is used instead of "vasculitis") is vasculitis (inflammation of the blood vessel wall) involving the brain and occasionally the spinal cord. It affects all of the vessels: very small blood vessels ( ...

in some cases.

Kidney

The involvement of the kidney can be caused by primary renal parenchymal lesions, or an underlying

vasculitis Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both arteries and veins are affected. Lymphangitis (inflammation of lymphatic vessels) is sometimes considered a type of vasculitis. Vasculitis is primarily caused ...

, or another associated autoimmune disease. Actual kidney involvement is quite rare, elevated

creatinine Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass). Biological relevance Serum creatinine (a blood measurement) is an importa ...

levels are reported in approximately 10% of people with RP, and abnormalities in

urinalysis Urinalysis, a portmanteau of the words ''urine'' and ''analysis'', is a panel of medical tests that includes physical (macroscopic) examination of the urine, chemical evaluation using urine test strips, and microscopic examination. Macroscopic ...

in 26%. Involvement of the kidney often indicates a worse prognosis, with a 10-year survival rate of 30%. The most common histopathologic finding is mild mesangial proliferation, that is followed by focal and segmental necrotizing

glomerulonephritis Glomerulonephritis (GN) is a term used to refer to several kidney diseases (usually affecting both kidneys). Many of the diseases are characterised by inflammation either of the glomeruli or of the small blood vessels in the kidneys, hence the ...

with crescents. Other abnormalities that are found include glomerulosclerosis,

IgA nephropathy IgA nephropathy (IgAN), also known as Berger's disease () (and variations), or synpharyngitic glomerulonephritis, is a disease of the kidney (or nephropathy) and the immune system; specifically it is a form of glomerulonephritis or an inflammati ...

and

interstitial nephritis Interstitial nephritis, also known as tubulointerstitial nephritis, is inflammation of the area of the kidney known as the renal interstitium, which consists of a collection of cells, extracellular matrix, and fluid surrounding the renal tubules ...

. Immunofluorescence studies most often reveal faint deposits of C3, IgG or IgM in the primarily mesangium.

Constitutional symptoms

These symptoms could consist of

asthenia Weakness is a symptom of a number of different conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, i ...

fever Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...

anorexia Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gre ...

, and

weight loss Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat ( adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other co ...

. They mostly occur during a severe disease flare.

Others

* Skin and mucous membranes: 20 to 30% of people with relapsing polychondritis have skin involvement, including aphthous ulcers, genital ulcers, and a number of non-specific skin rashes including

erythema nodosum Erythema nodosum (EN) is an inflammatory condition characterized by inflammation of the fat cells under the skin, resulting in tender red nodules or lumps that are usually seen on both shins. It can be caused by a variety of conditions, and typi ...

livedo reticularis Livedo reticularis is a common skin finding consisting of a mottled reticulated vascular pattern that appears as a lace-like purplish discoloration of the skin. The discoloration is caused by reduction in blood flow through the arterioles that supp ...

, hives, and

erythema multiforme Erythema multiforme (EM) is a skin condition that appears with red patches evolving into target lesions, typically on both hands. It is a type of erythema possibly mediated by deposition of immune complexes (mostly IgM-bound complexes) in th ...

. * Cardiovascular system: Relapsing polychrondritis may cause inflammation of the aorta. It can also cause leaky heart valves (

aortic valve regurgitation Aortic regurgitation (AR), also known as aortic insufficiency (AI), is the leaking of the aortic valve of the heart that causes blood to flow in the reverse direction during ventricular diastole, from the aorta into the left ventricle. As a cons ...

in 4 to 10%,

mitral valve regurgitation Mitral regurgitation (MR), also known as mitral insufficiency or mitral incompetence, is a form of valvular heart disease in which the mitral valve is insufficient and does not close properly when the heart pumps out blood. Section: Valvular Hea ...

in 2%).

Causes

Relapsing polychondritis is an autoimmune disease in which the body's

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splint ...

begins to attack and destroy the cartilage tissues in the body. It has been postulated that both

cell-mediated immunity Cell-mediated immunity or cellular immunity is an immune response that does not involve antibodies. Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in ...

and humoral immunity are responsible. Reasons for disease onset are not known, but there is no evidence of a genetic predisposition to developing relapsing polychondritis. 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.

Diagnosis

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.

Diagnostic criteria

There are several clinical criteria used to diagnose this disease. McAdam ''et al.'' introduced the clinical criteria for RP in 1976. These clinical criteria have later been expanded by Damiani ''et al.'' in 1979 and finally Michet ''et al.'' modified them in 1986. See the following table for these diagnostic clinical criteria and the number of conditions required for an official diagnosis.

Laboratory findings

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.

Imaging studies

FDG positron emission tomography (PET) may be useful to detect the condition early. Other imaging studies including MRI, CT scans, and X-rays may reveal inflammation and/or damaged cartilage facilitating diagnosis.

Special tests

Biopsy

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 Chondrolysis CD Code is the process of breakdown of cartilage. It can occur as a result of trauma (traumatic chondrolysis). Intra-articular infusions of certain local anesthetic agents such as bupivacaine, lidocaine, ropivacaine and levobupivacai ...

chondritis Chondritis is inflammation of cartilage. It takes several forms, osteochondritis, costochondritis, and relapsing polychondritis among them. Costochondritis is notable for feeling like a heart attack. See also * Chondropathy * Chondrolysis * Per ...

, and perichondritis.

Pulmonary function tests

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.

Differential diagnosis

A differential diagnosis should be taken into account with the following main RP manifestations.

Treatment

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. Corticosteroid-sparing medications such as

azathioprine Azathioprine (AZA), sold under the brand name Imuran, among others, is an immunosuppressive medication. It is used in rheumatoid arthritis, granulomatosis with polyangiitis, Crohn's disease, ulcerative colitis, and systemic lupus erythematosus, ...

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.

Prognosis

Many individuals have mild symptoms, which recur infrequently, while others may have persistent problems that become debilitating or life-threatening.

Epidemiology

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.

History

In 1923, Rudolf Jaksch von Wartenhorst first discovered relapsing polychondritis while working in Prague and initially named it ''Polychondropathia''. Vonjakschrudolf

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. 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.

Research

There has been little research on neurological problems related to RP. 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 Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or or ...

and many more.