Overview
- Definition: Recurrent episodic autoimmune inflammation against collagen types II, IX, and XI, involving cartilages and proteoglycan-rich structures, such as the eye, heart, blood vessels, and inner ear
Ocular disease (50–67%): 30% can be the initial presentation of the disease. Most commonly involves the episclera and sclera, but may affect any ocular structure
Auricular chondritis (83–95%): unilateral or bilateral auricular pain and swelling; associated with hearing loss, tinnitus, and vertigo from inner ear involvement
Nonerosive arthritis (52–85%): asymmetric and often migratory polyarthritis lasting weeks to months
Nasal chondritis (33–72%): sudden painful onset with mild epistaxis
Laryngotracheal disease (30–67%): varies from asymptomatic to life-threatening complications; hoarseness, aphonia, wheezing, inspiratory stridor, nonproductive coughing, dyspnea
Skin/mucosal disease (0–83%): nonspecific and range from aphthous ulcers, nodules on the limbs, to purpura and pustules
Cardiovascular disease (6–23%): chest pain, silent MI, arrhythmias, heart block, and syncope from aortitis
Neurological disease (0–10%): due to vasculitis of the peripheral nervous system or CNS; peripheral neuropathy, cranial nerve palsy, hemiplegia, and seizures
- Symptoms
Pain
Redness
Photophobia
Blurry vision
- Laterality
Unilateral or bilateral
- Course
Relapsing and remitting
- Age of onset
40–50s but can occur in childhood
- Gender/race
Slight female preponderance
Equal frequency across races
- Systemic association
HLA-DR4 and HLA-DR6
A third of cases coexist with other autoimmune diseases, including systemic vasculitis of small, medium, and large vessels; rheumatoid arthritis; ankylosing spondylitis; systemic lupus erythematosus; antiphospholipid syndrome; inflammatory bowel diseases; Behçet’s disease (“MAGIC” syndrome: mouth and genital ulcers with inflamed cartilage)
RP can also be seen with myelodysplastic syndrome, typically in older males (Table 10.1)
McAdam/Michet diagnostic criteria of RP with Damiani-Levine modifications
Recurrent bilateral auricular chondritis |
Nonerosive seronegative inflammatory polyarthritis |
Nasal chondritis |
Ocular inflammation |
Respiratory tract chondritis |
Cochlear and/or vestibular dysfunction |
One of the following is required to establish diagnosis: ≥3 of the above criteria ≥1 of the above criteria with positive histologic confirmation Chondritis in ≥2 separate anatomic locations with response to steroids and/or dapsone |
Exam: Ocular
Anterior Segment
Episcleritis (39%)
- Scleritis (14%)
First disease manifestation in 2–3% of RP patients
Stronger marker of systemic inflammation
Diffuse, nodular, or necrotizing
Scleromalacia after repeat scleritis
- Peripheral ulcerative keratitis (PUK)
Like scleritis, presence of PUK calls for more aggressive treatment
Non-granulomatous anterior uveitis
Conjunctivitis (10%)
Posterior Segment
Unusual, but retinal vasculitis, vascular occlusion, exudative RD, and inflammatory or ischemic optic neuropathy have been reported
Exam: Systemic
Auricles: diffusely violaceous and erythematous with sparing of non-cartilaginous ear lobes, +/− sensorineural hearing loss
Joints: nondeforming and nonerosive arthritis which affect mostly the metacarpophalangeal, proximal interphalangeal joints and knees Sternoclavicular, costochondral, and manubriosternal articulations are also typically involved
Nose: saddle-nose deformity (17–29%) and a flat nasal tip, more common in men and younger patients
Large airways: (sub)glottic, laryngeal, or tracheobronchial inflammation with luminal encroachment. Laryngeal collapse during inspiration and/or tracheal collapse during expiration
Skin: urticaria, angioedema, erythema multiforme, livedo reticularis, panniculitis, and erythema nodosum
Imaging
FA: retinal vascular occlusion or peripheral vasculitis
B-scan: sclerochoroidal thickening in areas of posterior scleritis
Laboratory and Radiographic Testing
- Labs
Elevated CRP is most common, but 1 in 10 patients may have normal acute phase reactants during acute disease flare
Serum antibodies to type II collagen: present in 20–50%, but not specific nor sensitive, and only performed in a few laboratories
ANA: present in 20–60%; homogenous or speckled pattern
ANCA: may be present in RP, but granulomatosis with polyangiitis should be strongly considered if ANCA+, especially if it is c-ANCA and associated with anti-PR3 antibodies
- Imaging
Chest radiography: laryngotracheal bronchial wall thickening, airway stenosis, and cartilaginous calcification
Differential Diagnosis
Granulomatosis with polyangiitis
Polyarteritis nodosa
Rheumatoid arthritis
Treatment
- Mild disease with diffuse anterior scleritis and involvement of nasal/auricular cartilages
NSAIDs
Dapsone
- Severe disease with nodular/necrotizing scleritis and involvement of respiratory tract cartilages, inner ear, and vital organs
Corticosteroids
Methotrexate
Azathioprine
Mycophenolate mofetil
Leflunomide
Cyclosporine A
Cyclophosphamide (life-threatening disease with necrotizing scleritis, laryngotracheal involvement, and aortitis)
- Biologics
TNF-alpha inhibitors, mainly infliximab, appear effective in many cases after conventional immunosuppressants failed or were poorly tolerated
Anakinra (anti-IL-1R), tocilizumab (anti-IL-6R), and abatacept (co-stimulatory signaling pathway inhibitor) are effective in fewer reports
Rituximab (anti-CD20) appears ineffective
Plasmapheresis and IVIg used in some cases
Referral/Co-management
Rheumatology
ENT
Pulmonary