Silent tracheobronchial chondritis in a patient with a delayed diagnosis of relapsing polychondritis

Abstract

Relapsing polychondritis is a very rare autoimmune disease characterised by a relapsing inflammation of hyaline, elastic and fibrous cartilaginous tissues. The incidence is estimated to be between 3.5 and 4.5 per million people per year. Clinical signs and symptoms can be very subtle, and if left undiagnosed for a prolonged period, airway involvement can cause fibrosis of the tracheobronchial wall, leading to a fixed tracheobronchial stenosis. Eventually, this can progress to life-threatening tracheobronchomalacia due to irreversible damage and loss of tissue integrity. We report an elderly man who presented with recurrent bilateral ear inflammation and intermittent polyarthritis who was diagnosed with relapsing polychondritis with asymptomatic involvement of his large airways.

Full text

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AfridiF, FroshS. BMJ Case Rep 2017. doi:10.1136/bcr-2017-220172
SUMMARY
Relapsing polychondritis is a very rare autoimmune
disease characterised by a relapsing inflammation of
hyaline, elastic and fibrous cartilaginous tissues. The
incidence is estimated to be between 3.5 and 4.5 per
million people per year. Clinical signs and symptoms can
be very subtle, and if left undiagnosed for a prolonged
period, airway involvement can cause fibrosis of the
tracheobronchial wall, leading to a fixed tracheobronchial
stenosis. Eventually, this can progress to life-threatening
tracheobronchomalacia due to irreversible damage and
loss of tissue integrity. We report an elderly man who
presented with recurrent bilateral ear inflammation
and intermittent polyarthritis who was diagnosed with
relapsing polychondritis with asymptomatic involvement
of his large airways.
BACKGROUND
The first case of relapsing polychondritis (RPC)
was described in 1923 by Jaksch-Wartenhortst, but
the term ‘relapsing polychondritis’ was first used
by Person et al in 1960.1 RPC is a very rare auto-
immune disease with an incidence estimated to be
between 3.5 and 4.5 cases per million people per
year.2 It is characterised by recurrent episodes of
inflammation of the hyaline, elastic and fibrous
cartilaginous tissues involving the cartilage of the
ears, nose, upper and lower airways, larynx, cardio-
vascular system and joints. Recurrent inflammation
can lead to cardiovascular and respiratory compli-
cations with significant morbidity and mortality.
The highly variable presentation combined with
its rarity makes this condition difficult to diagnose,
which can lead to a delay in treatment. The average
time from symptom onset to the diagnosis is esti-
mated to be 3 years.3 During the first occurrences
of symptoms, patients are most likely to present to
primary care providers, rheumatologists, ophthal-
mologists and otolaryngologists.
CASE PRESENTATION
A 72-year-old man with a medical history signifi-
cant for recurrent episcleritis/scleritis, benign pros-
tatic hyperplasia, obesity, obstructive sleep apnoea,
hyperlipidaemia, tobacco use and a remote history of
non-steroidal anti-inflammatory drug (NSAID)-in-
duced gastrointestinal (GI) bleeding presented to
the rheumatology clinic with a 4-month history of
bilateral hand pain associated with swelling and
stiffness of the hand joints. He reported recurrent
episodes of arthralgia and arthritis of the wrists and
ankles, which had been treated with oral corticoste-
roids on several occasions. NSAIDs were avoided by
previous providers given the history of NSAID-in-
duced GI bleeding. Further, he reported multiple
intermittent episodes of bilateral ear pain with
redness and swelling, previously diagnosed and
treated as cellulitis by multiple providers without
response. His most recent course of oral antibiotics
was 2 weeks prior to presentation to our clinic, with
no improvement. Review of systems was significant
for a recent episode of episcleritis in the right eye,
1 week prior to presentation, with complete resolu-
tion. He denied fevers, chills, night sweats, fatigue,
weight loss, hearing loss, tinnitus, vertigo, short-
ness of breath or haemoptysis. Social history was
significant only for a 30 pack-year smoking history.
Family history included rheumatoid arthritis in his
father. Physical exam was remarkable for erythema,
Figure 1 Left: Bilateral erythema and swelling of the antihelices of the ears with sparing of the ear lobes (yellow
arrows). Right: CT chest showing thickening of the tracheal wall extending down to the level of left mainstem bronchus
with sparing of the posterior trachea suggestive of cartilaginous calcification (yellow arrow).
CASE REPORT
Silent tracheobronchial chondritis in a patient with a
delayed diagnosis of relapsingpolychondritis
Faraz Afridi,1 Seema Frosh1,2
Rare disease
To cite: AfridiF, FroshS. BMJ
Case Rep Published Online
First: [please include Day
Month Year]. doi:10.1136/
bcr-2017-220172
1Internal Medicine, University
of Central Florida College of
Medicine, Orlando, Florida, USA
2Rheumatology, Orlando
VA Medical Center, Orlando,
Florida, USA
Correspondence to
Dr Faraz Afridi,
faraz. afridi@ ucf. edu
Accepted 22 June 2017

2AfridiF, FroshS. BMJ Case Rep 2017. doi:10.1136/bcr-2017-220172
Rare disease
swelling and profound tenderness of the bilateral antihelices
of the ears with sparing of the ear lobes (figure 1, left). There
was no redness or excessive tearing of the eyes and hearing was
grossly normal. The remainder of the physical exam, including
the chest and musculoskeletal exam, was unremarkable.
INVESTIGATIONS
Laboratory evaluation including complete blood count and
complete metabolic profile was unremarkable. Rheumatoid
factor, anticyclic citrullinated peptide antibody, antineutrophil
cytoplasmic antibody, human leukocyte antigen-B27 (HLA-
B27), Lyme and viral hepatitis serologies were all negative.
Uric acid was within normal limits. Radiographs of the bilateral
hands, wrists and ankles were unremarkable.
Given the patient’s constellation of steroid-responsive,
non-erosive, seronegative inflammatory polyarthritis, episodic
auricular chondritis and history of recurrent scleritis/episcleritis,
the diagnosis of RPC was made based on meeting three out of six
features of the McAdam’s criteria for RPC (see Discussion). Due
to the potential involvement of cardiac and pulmonary airway
structures in this disease, echocardiogram, pulmonary function
tests (PFTs) and CT scan of the chest were performed. Echo-
cardiogram and PFTs were normal; however, CT of the chest
revealed thickening of the tracheal wall extending down to the
level of left mainstem bronchus with sparing of the posterior
trachea, suggestive of cartilaginous calcification due to chronic
chondritis of the tracheobronchial tree (figure 1, right).
TREATMENT
Prednisone 20 mg per oral daily was initiated at that time, with a
subsequent taper. Given the likely chronic nature of the tracheo-
bronchial tree involvement, recurrent inflammatory arthritis
and episodic auricular swelling, he was transitioned to a steroid-
sparing regimen of methotrexate 12.5 mg per oral weekly.
OUTCOME AND FOLLOW-UP
His symptoms of auricular chondritis and polyarthralgia
improved after a few weeks. At 1-year follow-up, he has not had
any recurrence of these symptoms and continues to deny short-
ness of breath, wheezing, cough or haemoptysis. He follows
closely with rheumatology with regular monitoring of metho-
trexate therapy.
DISCUSSION
RPC is a very rare autoimmune disease characterised by a
relapsing inflammation of the hyaline, elastic and fibrous carti-
laginous tissues.4
Epidemiology
Epidemiological data for this rare entity are poorly documented
and likely underestimated. The incidence is currently estimated
to be between 3.5 and 4.5 cases per million people per year
based on a study in Rochester, Minnesota, and from a recent
study by the US Department of Defense of their beneficiary
population.2 5 6 RPC on average bcr-2017-220172begins at age
50 and affects men and woman equally.4bcr-2017-220172
Pathophysiology
The pathogenesis of RPC is largely unknown, but the main
hypothesis is an autoimmune reaction that initially targets carti-
lage and subsequently affects non-cartilaginous tissues. Many
features of the disease support this autoimmune aetiology. The
inflammatory infiltrates seen in the affected tissues consists of a
collection of lymphocytes (mostly CD4+ T cells), macrophages,
neutrophils and plasma cells. This infiltration of tissues by cellular
components with the addition of inflammatory mediators leads
to a cascade releasing degradative enzymes such as matrix metal-
loproteinase and reactive oxygen metabolites by inflammatory
cells and chondrocytes, which eventually leads to the destruc-
tion of cartilage and proteoglycan-rich tissues.7 The provoking
event that triggers the cascade has been hypothesised to be an
initial damaging event to cartilage, which exposes immunogenic
epitopes of the chondrocytes or extracellular cartilage matrix.7
This hypothesis of cartilage destruction being the inciting event
has been supported by studies showing the development of RPC
following piercing of cartilage of the pinna of the ear and inges-
tion of glucosamine chondroitin supplements.8 Autoantibodies
can also be found in patients with RPC directed against carti-
lage, collagen, matrilin-1 and matrix proteins, but the diagnostic
utility of these autoantibodies is poor in light of them only being
found in approximately 30% of patients with RPC.9 Further-
more, they can also be detected in conditions such as rheumatoid
arthritis, which reduces their specificity.
Clinical presentation
The clinical features of RPC change with severity and duration
of the disease. The most common and characteristic feature
of RPC is auricular inflammation, but other structures may be
involved, including the eyes, nose, heart, lungs and joints.
Systemic involvement
During flares of the disease process, fatigue and fever can be
seen.3
Auricular involvement
The most common feature of RPC is chondritis of the pinna
of the ear, which is present in up to 90% of patients with the
disease.2 During acute episodes, the pinna of the ear, which
contains a large amount of cartilage, becomes swollen, tender
and red, and can often be mistaken as cellulitis as in our
patient’s case. Classically the ear lobe is spared as it contains a
minimal amount of cartilage. There may be associated external
auditory canal obstruction due to the swelling, which can lead
to a conductive hearing loss and/or otitis externa. Chronic
inflammation may cause a ‘cauliflower’ pinna deformity in
which the auricular cartilage is severely damaged to the extent
that it causes the pinna to have a persistent swollen appear-
ance and have a structural deformity.4 In some cases, there
may be cochlear or vestibular involvement, which can result
in progressive sensorineural hearing loss or vertigo, respec-
tively.10
Nasal involvement
Acutely, patients may report pain at the base of the nose, with
swelling and a sensation of fullness at the nasal bridge. There
may be associated nasal obstruction, rhinorrhoea, crusting or
epistaxis.3 Chronic involvement may also lead to permanent
destruction of the septal cartilage causing a septal perforation.
This is the cause of the nasal collapse and the characteristic
saddle nose deformity, which is seen in up to 29% of patients.4
Eye involvement
Ocular involvement can be seen in 20%–60% of patients and
can present as episcleritis, scleritis or conjunctivitis.3 Scleritis is
the most common ocular presentation.

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AfridiF, FroshS. BMJ Case Rep 2017. doi:10.1136/bcr-2017-220172
Figure 2 Diagram showing the cross-section of normal tracheal
airways (top) with normal tracheal cartilage (light blue), fixed airway
stenosis (middle) and tracheal collapse due to tracheobronchomalacia
secondary to relapsing polychondritis (bottom).
Rare disease
Pulmonary involvement
Pulmonary structures extending from the larynx to the bronchi
may be involved, with initial symptoms of a dry cough, hoarse-
ness, dysphonia, aphonia, stridor, choking or anterior neck pain.
When there is larynx involvement causing laryngeal chondritis, it
can manifest initially as pain above the thyroid gland, dysphonia
or aphonia. Ongoing laryngeal inflammation may result in irre-
versible laryngeal stenosis with inspiratory dyspnoea, which
may require an emergency tracheotomy.8 With tracheobronchial
involvement, inflammation and destruction of the cartilaginous
structures cause fibrosis of the tracheobronchial wall, which
results in luminal narrowing of the tracheobronchial tree. This
represents fixed tracheobronchial stenosis, which is the start of
the life-threatening nature of airway involvement seen in RPC.
Eventually, this cartilaginous destruction causes dynamic expi-
ratory collapsibility of the tracheobronchial tree, referred to as
tracheobronchomalacia (figure 2). This can eventually progress
to respiratory failure due to the irreversible expiratory collapse
of the tracheobronchial tree, and this represents a significant
cause of mortality. These respiratory complications, mostly
tracheal collapse, are the leading cause of mortality.11 Further-
more, anti-inflammatory treatment is ineffective at this stage.
Due to the severity of this process, any patient diagnosed with
RPC should have mandatory imaging to evaluate for laryngeal
and tracheobronchial tree involvement so that early treatment
can be initiated. Work-up includes PFTs and chest CT imaging.12
If tracheobronchial involvement is present, PFTs may show either
an obstructive, restrictive or mixed ventilatory defect with low
maximum forced expiratory flow.13 CT chest may show smooth
anterior and lateral airway wall thickening, with increased atten-
uation of the cartilage with sparing of the posterior membrane
wall.14 Chronic involvement may be demonstrated by calcifica-
tion of these structures.
Cardiovascular involvement
Cardiovascular involvement is the second most common cause
of death in RPC, mainly from the associated vasculitis and
valvular heart disease.11 15 Vasculitis can present in RPC, which
affects any vessel size, and the clinical presentation can range
from cutaneous leucocytoclastic vasculitis to large vessel vascu-
litis with aneurysmal involvement.11 The prevailing presenting
feature is aortic valve disease secondary to progressive dilata-
tion of the aortic ring with an associated ascending thoracic
aortic aneurysm. The mechanism involves aortitis with progres-
sive destruction of the tunica media, which itself increases the
risk of aortic rupture.15 Considering this serious complication,
repeated monitoring with two-dimensional echocardiography is
warranted in all patients diagnosed with RPC.16
Musculoskeletal involvement
Musculoskeletal involvement represents the second most
common feature of RPC, in the form of non-erosive, non-de-
forming oligoarthritis or polyarthritis affecting both small
and large joints. Characteristically, the arthritis is asymmetric
and intermittent, with flare-ups often spontaneously resolving
without treatment.4 Costochondral cartilage can also be affected,
which presents as parasternal and rib pain that is reproducible
on palpation. In severe cases, dislocation of the ribs and pectus
deformity can be seen.4
Diagnosis
The diagnosis of RPC is based on an empiric diagnostic criterion
that encompasses clinical features, radiographic evidence and
occasionally biopsy of the affected cartilaginous structures. Labo-
ratory blood testing is generally non-specific. Anticartilage and
anticollagen (type II) antibodies have poor sensitivity and spec-
ificity and are only tested by a limited number of laboratories.
Acute phase reactants, in particular serum C reactive protein,
can be normal during acute flares in over 10% of patients and
therefore are not routinely checked.4
The original diagnostic criteria was the McAdam’s criteria,
introduced in 1976 which is primarily based on clinical
features at a particular given time and requires three out of
six features to make a diagnosis of RPC (figure 3, left).11
However, due to the to the variability of clinical manifesta-
tions occurring at a given point in time, Damiani’s criteria has
frequently been used. It includes histological features and ther-
apeutic responses, which can confirm the diagnosis of RPC
with any single feature, in addition to that met by McAdam’s
criteria (figure 3, middle). The latest criteria, which is the
Michet’s criteria, avoids the need for histological biopsy and is
used presently. This criterion requires the presence of inflam-
mation in at least two out of the following three cartilages:
auricular, nasal or laryngotracheal cartilages. Additionally,
criteria can be met if one of the above cartilages are affected,
but with two other signs which include ocular inflammation,

4AfridiF, FroshS. BMJ Case Rep 2017. doi:10.1136/bcr-2017-220172
Learning points
►Relapsing polychondritis(RPC) is a rare destructive
autoimmune disorder of the cartilaginous structures with
an incidence estimated to be between 3.5 and 4.5 cases per
million people per year.
►The diagnosis of RPC is established by the combination of
clinical features, radiographic evidence and occasionally
biopsy of the affected cartilaginous structures as per
McAdam’s, Damiani’s and Michet’s criteria.
►There is a crucial need for functional and anatomic
assessment of the upper and lower airways in seemingly
asymptomatic patients.
►If left undiagnosed for a prolonged period of time,
airway involvement can cause a fixed tracheobronchial
stenosis, which can ultimately lead to life-threatening
tracheobronchomalacia due to irreversible damage and loss
of tissue integrity.
►Rapid recognition and treatment of RPC by primary
providers may ultimately prevent misdiagnosis and help
prevent delays in treatment, which could otherwise lead to
irreversible damage or death.
Figure 3 Left: McAdam’s criteria for the diagnosis of relapsing polychondritis, which requires meeting any three out of six clinical features. Middle:
Damiani’s criteria for the diagnosis of relapsing polychondritis, which can diagnose relapsing polychondritis based on a single histological feature,
therapeutic response or meeting McAdam’s criteria. Right: Michet’s criteria, which requires the presence of inflammation in at least two out ofthree
specific cartilage sites or one cartilage site with two other specific signs.
Rare disease
vestibular dysfunction, hearing loss or seronegative inflamma-
tory arthritis (figure 3, right).7
Treatment
Considering the rarity of RPC, there are few clinical trials that
compare the treatment modalities of this condition. The phar-
macological approach is based on a collection of case reports
and case series. Despite the improvement of clinical features seen
in RPC, no treatment modality has been proven to change the
natural course of the disease.17
Treatment is tailored to disease severity and extent of involve-
ment of the disease. The assessment of severity can be quan-
tified by a disease activity scoring system, which has recently
been developed for RPC: the Relapsing Polychondritis Disease
Activity Index (RPDAI).18 The scoring system is comprised of
27 items with individual scores ranging from 1 to 24, with a
maximum RPDAI score of 265. In general, patients with local-
ised nasal, auricular or articular chondritis without visceral
involvement can be treated with NSAIDs, colchicine or dapsone,
although efficacy is variable.15 Glucocorticoids are often used
during acute flares. In patients with visceral involvement
including the airways, heart or eyes, oral glucocorticoids are
the initial treatment of choice. However, manifestations such as
severe laryngeal or tracheobronchial chondritis often warrant
intravenous methylprednisolone bolus therapy (15 mg/kg/day)
combined with a steroid-sparing immunomodulating agent as
initial therapy.17 Frequently used immunomodulatory treatments
include cyclophosphamide, methotrexate, azathioprine and
ciclosporin. More recently, biological agents (in particular inflix-
imab) have been reviewed in the treatment of RPC; however,
the results have been variable.19
Surgery is sometimes warranted in selected patients due to
complications of visceral involvement including airway collapse
and intractable heart failure due to valvular involvement or an
aortic aneurysm formation.17
Prognosis
With increasing recognition and a better understanding of
this rare disease, improvements in the outcomes of patients
with RPC have been recognised. Survival rates have been
estimated to have increased from 70% at 5 years to 91%
at 10 years in the last decade according to a recent review
in 2014.16 The main causes of mortality are airway collapse
with respiratory failure and infectious complications of
the treatment itself.
CONCLUSION
RPC is a rare autoimmune disorder and if left undiagnosed
for a prolonged period, untreated airway involvement can
cause fibrosis of the tracheobronchial wall, leading to a fixed
tracheobronchial stenosis. Eventually this can progress to
life-threatening tracheobronchomalacia due to irreversible
damage and loss of tissue integrity. These respiratory compli-
cations, mostly tracheal collapse, are the leading cause of
mortality seen in RPC. The diagnosis of RPC is established by
the combination of clinical findings, supportive laboratory
data, and imaging as per McAdam’s, Damiani’s and Michet’s
criteria. We would like to highlight the importance of early
recognition of RPC by primary care providers so that early
specialist referrals can be made. This can allow the functional
and anatomic assessments of the upper and lower airways to
be made and earlier treatment to be initiated in seemingly
asymptomatic patients.
Contributors FA developed the design of the case report, collected data regarding
the patient, analysed the data, drafted the article and approved the final version to
be published. SF collected data regarding the patient, analysed the data, revised the
manuscript critically for important intellectual content and approved the version of
the manuscript to be published.
Competing interests None declared.

5
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