Systemic features

Fatigue is present during and between flares. Fever could be observed occasionally in severe flares and unexplained prolonged fever may be the presenting symptom of RP.

Ear involvement

The most common and suggestive feature of the disease is chondritis of the pinna of the ear, which is present in up to 90% of patients during the course of the disease . Chondritis can be acute, subacute or chronic and unilateral or bilateral. In the acute presentation, the pinna of the ear (helix, antihelix, tragus, antitragus and external auditory canal) is inflamed, swollen, painful and red. Typically, the inflammation spares the ear lobe, which does not contain cartilage ( Fig. 1 ). The external auditory canal may be obstructed by the inflammatory infiltrate or collapsed, particularly at its opening, leading to conductive hearing loss and/or infectious otitis externa. The inflammation may include surrounding retroauricular soft tissues and could be sometimes associated with lymphadenopathy. Patients cannot press their ear on the telephone handset or the pillow. The inflammation lasts for a couple of days to a few weeks and often spontaneously resolves. Complications include disappearance of the auricular cartilage resulting in drooping of the pinna, which becomes floppy and contorted, namely ‘cauliflower ear’ ( Fig. 2 ). Conversely, the pinna can be thickened and/or rigidified with calcification and deformity of the cartilaginous structure.

Outer ear chondritis . The pinna of the ear is red, hot, and swollen. Inflammation spares the ear lobe, which is not cartilaginous.

‘Cauliflower ear’ . Repeated episodes of chondritis cause a deformity: the normal relief outlines have disappeared and the ear appears thickened. The external auditory canal has collapsed, and its opening can no longer be seen.

The cochlea and/or vestibule may be affected by vasculitis or autoantibodies . This feature is characterised by sudden or less often progressive sensorineural hearing loss and/or vestibular dysfunction (vertigo or dizziness), which may be unilateral or bilateral. Acute hearing losses can reverse with corticosteroids . Serous otitis media and Eustachian tube obstruction are less common . In Michet et al.’s series, hearing loss and vertigo affected 26% and 13% of patients, respectively .

Nose involvement

Nasal chondritis is less symptomatic than auricular chondritis . In the acute form, patients experience pain at the base of the nose, occasionally with a swelling, a sensation of fullness of the nasal bridge and occasionally with local inflammatory signs due to the swelling and tenderness of the distal part of the nasal septum. Patients can have nasal crusting, obstruction, rhinorrhoea or epistaxis . Of note, epistaxis, crusting, ulceration of the nasal mucosa and perforation of the nasal septum are more suggestive of granulomatosis with polyangiitis (Wegener’s disease) than RP.

Nasal chondritis is often combined with ophthalmological or auricular inflammation and may progress rapidly to permanent destruction of the septal cartilage with a characteristic saddle-nose deformity ( Fig. 3 ). This deformity may also occur painlessly and progressively without any acute flares. In Michet et al.’s series, saddle nose affected 29% of patients .

‘Saddle-nose’ deformity . Repeated episodes of chondritis in the nose cause the nasal septum to collapse. This deformity may occasionally develop as a low-grade painless process.

Involvement of the larynx, trachea and major airways

Airway involvement usually involves both the trachea and main bronchi. It may extent to the larynx and intermediary bronchi. Isolated chondritis of the trachea or the larynx can be seen . It is an important cause of mortality, particularly because of the inspiratory collapse of the tracheobronchial tree . Early search for laryngotracheal involvement is therefore mandatory and acute inflammatory episodes must be treated early and intensively. A higher female prevalence of respiratory tract involvement has been reported but is still controversial .

Involvement of the larynx is characterised by dry cough, hoarseness, dysphonia, aphonia, stridor, choking and tenderness over the tracheal or anterior thyroid cartilage responsible for anterior neck pain worsened by palpation of the cartilaginous structures . Inflammation of the mucosa and infiltration of the cartilage structures are sometimes visible on endoscopy above the thyroid and next to the first tracheal rings. The laryngeal involvement can, although rarely, progress to stenosis with respiratory failure and laryngeal dyspnoea. Tracheobronchial disease is more serious and is often difficult to diagnose early as it may be the only chondritis and its symptoms may be late and misleading. These include dry cough, dyspnoea and occasionally wheezing. This feature of the disease may mimic atypical asthma . Respiratory distress and/or sudden tracheal collapse can occur in acute forms .

The lesions consist of cartilaginous and peri-cartilaginous inflammation with a thickening of the tracheobronchial wall leading to the stenosis of the lumen. This inflammation may progress to fibrosis with fixed stenosis for which anti-inflammatory treatment is ineffective. Tracheobronchomalacia may also occur due to progressive destruction of the cartilage with inspiratory collapse of the lumen . Involvement of the large airways is a concern when it is fixed as it is difficult to access for endoscopic or surgical procedures and is also frequently complicated by atelectasis and/or bacterial infection.

Respiratory function test (RFT) is the most sensitive test to determine airway involvement in RP . RFTs should include spirometry, peak expiratory and inspiratory flow-volume loop and airway resistance to assess the obstructive consequences of the disease .

Respiratory involvement should also be investigated by a chest radiograph and specifically by computed tomography (CT) of the respiratory tract and chest ( Fig. 4 ) . The larynx and trachea are most commonly affected. The disease may also involve the airways more distally to the level of subsegmental bronchi. At the early stage of the disease, CT shows smooth anterior and lateral airway wall thickening with sparing of the posterior membranous wall. There is often an increased attenuation of the cartilages (ranging from subtle to frankly calcified). In more advanced disease, thickening of airway walls become circumferential because the posterior (non-cartilaginous) wall of the trachea and main bronchi is thickened. At this stage, focal or diffuse luminal narrowing of the trachea and bronchi may occur resulting from fibrosis following cartilaginous destruction. Loss of cartilaginous support due to cartilaginous inflammation and destruction also results in excessive dynamic expiratory collapsibility (tracheobronchomalacia). Expiratory air trapping is frequently observed involving one lung, lobes, segments or lobules. Laryngotracheal reconstructions in different three-dimensional planes using virtual endoscopy (3D CT) can be used to analyse the patency of the respiratory tract. End of inspiration images are used to assess fixed airway narrowing and those during forced exhalation assess tracheobronchomalacia and air trapping .

Severe tracheal and bronchial involvement in RP . CT scan of the chest in a 34-year-old male patient suffering from RP. Axial (A) and coronal oblique reformatted (B) CT images show thickening and hyperattenuation (calcified) of the anterior and lateral walls of the trachea, main bronchi, right intermediate bronchus and left upper lobar bronchus. Note the sparing of the posterior wall of the airways. On axial images with lung window settings (C), luminal narrowing is visible on the right intermediate bronchus (red arrow) and the lingular bronchus (yellow arrow). On expiratory CT scan (bottom right), gas trapping is present in the left upper lobe (yellow star).

Because of the increased risk of perforation and exacerbation of the inflammation and the small amount of information it provides, bronchoscopy should be carefully considered although it may nevertheless be performed . It can show airway-wall oedema, stenosis and tracheobronchomalacia . An acceptable correlation appears between 3D CT and bronchoscopy findings, except for the diagnosis of tracheobronchomalacia . Cartilage biopsies have been obtained from the trachea or main bronchus . In our experience, this procedure is never essential and we do not recommend it.

Costal chondritis

This is characterised by parasternal pain (costochondral cartilage) and/or pain in the floating ribs, which can be reproduced on pressure. Costochondral chondritis is sometimes accompanied by local swelling. It is highly suggestive of the disease. In severe cases, this chondritis can result in dislocation of the ribs and in pectus deformity .

Musculoskeletal involvement

This is the second most common feature of RP. The involvement may be either oligoarthritis or polyarthritis affecting the small and large joints. It is usually asymmetrical and intermittent. It affects both large and small joints and the parasternal joints (sternomanubrial junction and sternoclavicular joints) . Inflammatory flares may resolve without treatment. The disease is neither erosive nor deforming apart from cases in which the RP is associated with rheumatoid arthritis. RP may present as an axial rheumatic disease although the combination with spondyloarthritis should be considered if spinal radiological changes are present. Arthralgia without true clinical arthritis is very common and other rheumatological features may exist including tendinitis, tenosynovitis, enthesopathy and myalgia.

Ophthalmological involvement

Ophthalmological involvement is reported in 20–60% of patients . It is often contemporaneous with other features of RP although it could precede the development of chondritis by several years. Various types of involvement may occur. The most common are episcleritis, scleritis and conjunctivitis . Published biopsies report polymorph inflammatory infiltrates and vasculitis . Episcleritis is often satellite to visceral involvement and carries a good prognosis. This is generally responsive to simple local anti-inflammatory treatment. Scleritis is the most common ocular manifestation and often progresses in combination with extra-ophthalmological disease particularly auricular or nasal chondritis and audiovestibular damage . All forms of scleritis may occur, ranging from diffuse anterior ( Fig. 5 ) to nodular or necrotising that can, although rarely, progresses to perforation of the eye globe. Severe scleritis leaves the complication of scleromalacia, suggesting the diagnosis retrospectively ( Fig. 6 ). A recent study reported that RP-associated scleritis was often bilateral (92.3%), diffuse (76.9%), recurrent (84.6%), sometimes with decreased vision (46.2%), anterior uveitis (38.5%), necrosis (23.1%), peripheral keratitis (15.4%), optic neuritis (15.4%) and ocular hypertension (30.8%) .

Diffuse scleritis.

Scleromalacia . Scleromalacia is a complication of episodes of severe anterior scleritis.

Other involvements of the eye may be encountered : simple conjunctivitis, conjunctival ‘salmon-patch’ mass, chemosis, eyelid and periorbital oedema, simple keratitis, peripheral ulcerative keratitis, thinning of the cornea, corneal melting, anterior uveitis, retinal vasculitis, chorioretinitis, ischaemic optic neuropathy and orbital inflammatory pseudotumour.

Cardiovascular involvement

Cardiac complications are more prevalent in older and male patients and are the second cause of death in RP . The most common lesion is aortic valve disease due to progressive dilatation of the aortic ring often associated with an ascending thoracic aortic aneurysm . This lesion occurs insidiously in the course of the disease and requires repeated monitoring with echocardiography. Direct inflammatory valve destruction may occur but is rare. Mitral disease is rarely reported. In Michet et al.’s series aortic regurgitation and mitral regurgitation affected 4% and 2% of patients, respectively .

The second most common cardiovascular feature is acquired thoracic aortic aneurysm, which is located and usually limited to the aortic root and the ascending thoracic aorta. This develops in 5–7% of patients . The main mechanism is generally slowly progressive aortitis with inflammation and gradual destruction of the medial layers . This lesion is generally progressive and carries a risk of ruptured aorta. Extension to the major arterial vessels and abdominal aorta is rare.

Other cardiovascular involvements have been described, including pericarditis, atrioventricular conduction block (which can resolve on corticosteroid therapy), arrhythmias, vasculitis of the great vessels with stenotic and thrombotic lesions similar to Takayasu arteritis and aneurysms in vessels other than the aorta .

Skin features

These are more frequent with concomitant myelodysplastic syndrome . Skin lesions affect one-third of the patients : buccal aphthous ulcers, erythema nodosum-like nodules, purpura, papules, sterile pustules, superficial phlebitis, livedo reticularis, skin ulcerations, distal necrosis and neutrophilic dermatoses including erythema elevatum diutinum, Sweet’s syndrome, urticaria and angio-oedema. A biopsy may show leukocytoclastic vasculitis (occasionally necrotic and rarely lymphocytic), small-vessel thromboses, neutrophilic infiltrates or panniculitis.

Nervous system involvement

Involvement of the peripheral or central nervous system (CNS) is uncommon, occurring in approximately 3% of the cases of RP . A recent literature review reported approximately 20 cases of encephalitis or meningoencephalitis in RP . In this review, the male-to-female ratio was 16:3. The neurological symptoms are not different from encephalitis or meningoencephalitis of other causes: headache, confusion, disorientation, memory disturbances, visual disturbances, speech disturbances, cognitive impairment, seizures and wandering. Several cases presented as limbic encephalitis and/or dementia. Cerebrospinal fluid analysis showed a predominantly mononuclear pleocytosis and brain MRI showed bilateral high-signal-intensity lesions on FLAIR (fluid-attenuated inversion recovery) and T2-weighted images of the medial temporal lobe or subcortical and periventricular deep white matter . Histopathological examination shows neurological loss and gliosis with non-specific inflammation of the meninges and both white and grey matters spreading cortically without evidence of vasculitis . The CNS involvement usually improves on high-dose corticosteroid therapy . The peripheral neurological involvement is similar to that observed in the vasculitis: paralysis of the cranial nerve (second, sixth, seventh and eighth cranial nerves being the most frequently affected) and polyneuritis .

Renal involvement

The predominant lesions are mild mesangial expansion and cell proliferation as well as segmental necrotising glomerulonephritis with crescents without or with small deposits of immune complexes . In the series reported by Chang-Miller et al., renal involvement was observed in 22.5% of patients . This is far rarer in our practice. The differential diagnosis of granulomatosis with polyangiitis should be considered. Cases of IgA nephropathy and tubulointerstitial nephritis have been reported .