Subglottic Stenosis in Granulomatosis With
Polyangiitis: The Role of Laryngotracheal
Resection
Christina L. Costantino, MD, John L. Niles, MD, Cameron D. Wright, MD,
Douglas J. Mathisen, MD, and Ashok Muniappan, MD
Division of Thoracic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston; and Division of Nephrology,
Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
Background. Granulomatosis with polyangiitis (GPA)
is associated with development of subglottic stenosis in
about one-fourth of all patients. Although endoscopic
management is the primary treatment method for
tracheobronchial stenosis, some patients have refractory
disease, and tracheostomy is required. It is unclear if
laryngotracheal resection and reconstruction (LTRR) can
be safely performed in patients with GPA.
Methods. A retrospective review was performed of 11
patients with GPA undergoing LTRR.
Results. Eleven female patients with GPA and a me-
dian age of 47 years underwent LTRR. Six patients were
diagnosed with GPA after LTRR and had not received
any induction immunosuppression regimen. Five pa-
tients had received induction immunosuppression
regimen and were in clinical remission before LTRR.
LTRR was performed with a protective tracheostomy in 3
patients, which was eventually removed in all. There
G ranulomatosis with polyangiitis (GPA, formerly
Wegener’s granulomatosis) is a systemic disorder
characterized by necrotizing vasculitis of small arteries,
necrotizing granulomatous inflammation of the upper
and lower respiratory tracts, and necrotizing glomerulo-
nephritis. GPA is a member of a family of small vessel
vasculitides referred to as antineutrophil cytoplasmic
antibody (ANCA)-associated vasculitis [1]. Limited GPA
is found in approximately one-fourth of GPA patients and
refers to disease that is restricted to the airways, but it can
also be associated with ocular and sinus involvement. The
term “limited” is a misnomer because disease severity
can be considerable. Approximately 15% to 25% of all
GPA patients will experience subglottic stenosis (SGS) [2].
Pathologic assessment of airway disease often reveals
nonspecific fibrosis and infiltration by neutrophils and
epitheliod histiocytes without overt vasculitis.
Accepted for publication July 17, 2017.
Presented at the Poster Session of the Fifty-third Annual Meeting of The
Society of Thoracic Surgeons, Houston, TX, Jan 21–25, 2017.
Address correspondence to Dr Muniappan, 55 Fruit St, Blake 1570, Boston,
MA 02114; email: amuniappan@partners.org.
Ó 2018 by The Society of Thoracic Surgeons
Published by Elsevier Inc.
GENERAL THORACIC
were no major complications and no postoperative
deaths. One patient (9%) failed surgical management and
had replacement of a permanent tracheostomy 4 months
after LTRR. Six patients (55%) required additional
tracheal dilations after LTRR. Ten patients (91%) had
durable control of symptoms and freedom from trache-
ostomy with a median follow-up of 9.7 years. Two pa-
tients (18%) experienced subsequent lower airway
stenoses.
Conclusions. Surgical treatment of subglottic stenosis
in highly selected patients with GPA is effective and
associated with minimal morbidity. Although long-term
outcomes are encouraging, additional procedures may
be necessary, and patients are at risk of experiencing
lower airway disease.
(Ann Thorac Surg 2018;105:249–53)
Ó 2018 by The Society of Thoracic Surgeons
GPA was almost always fatal before the advent of
immunosuppression regimens that lead to remission in
most patients. Different regimens are chosen for inducing
and maintaining remission [3]. Airway complications
such as symptomatic SGS are typically treated with
bronchoscopic techniques, and they include dilation,
laser debridement, and corticosteroid injection. Patients
with refractory SGS require tracheostomy placement.
Surgical resection, generally laryngotracheal resection
and reconstruction (LTRR), of SGS in patients with GPA
is rarely performed because of the concern for anasto-
motic complications and questionable long-term efficacy.
The aim of this study is to characterize patient selection,
immunosuppressive management, and outcomes associ-
ated with LTRR in patients with GPA.
Patients and Methods
Patients
This study was approved by the Institutional Review
Board of the Massachusetts General Hospital (MGH),
who determined that patient consent was unnecessary.
The study population consisted of all patients undergoing
tracheal operation at MGH from January 1988 through
0003-4975/$36.00
http://dx.doi.org/10.1016/j.athoracsur.2017.07.026
 250 COSTANTINO ET AL Ann Thorac Surg
LARYNGOTRACHEAL RESECTION AND GPA 2018;105:249–53

December 2016. Patients were included in this study if
they underwent tracheal resection for SGS and had a
diagnosis of GPA. Six patients, all from 1988 to 2001, were
diagnosed with GPA when ANCA testing was found to be
positive after LTRR was performed. Five patients, all from
2002 and onward, had a preoperative diagnosis of GPA.
complications and efficacy of surgical management.
Long-term follow-up was achieved by reviewing the most
recent clinical note or contacting the patient to determine
subsequent need for immunosuppression regimen,
additional airway interventions, and quality of breathing.

GPA Diagnosis Results

All patients met the Chapel Hill Consensus Guidelines Patient Characteristics
for ANCA-associated vasculitis based on ANCA serologic
There were 11 patients with GPA who underwent LTRR
or clinicopathologic findings [1]. Serologic testing of
at our institution in the period from 1988 to 2016 (Table 1).
ANCA antibody consisted of both indirect immunofluo-
GENERAL THORACIC

The median age at onset of airway symptoms was 35

rescence detection of cytoplasmic staining (C-ANCA) and
enzyme-linked immunosorbent assay (ELISA) quantifi-
cation of the titers of anti-proteinase 3 (PR3) and anti-
myeloperoxidase (MPO) antibodies [4].
Surgical Management
All patients underwent a single-stage LTRR using a
technique previously described by our group for man-
agement of idiopathic laryngotracheal stenosis [5]. The
standard procedure involved removal of the anterior and
about one-half of the lateral cricoid cartilage in addition
to resection of the involved proximal trachea to enlarge
the subglottic lumen. Lateral heavy polyglactin 910 (2-0)
stay sutures were placed, followed by interrupted
circumferential fine polyglactin 910 (4-0) sutures, after
which time the airway was approximated and the sutures
were sequentially tied. The anastomosis was buttressed
with strap muscle or thyroid gland. A protective trache-
ostomy was performed at the time of LTRR in a minority
of patients (3 of 11 patients) when there was concern
about edema at the level of the anastomosis or glottis. All
patients underwent routine surveillance bronchoscopy
approximately 1 week after the operation.
Outcomes and Follow-Up
A retrospective electronic and paper chart review of all
patients was performed to determine postoperative
years (range: 17 to 47 years), and the median age at
operation was 47 (range: 27 to 63 years). All patients were
women. The primary symptoms related to upper airway
disease were dyspnea on exertion (n ¼ 6, 55%) and stridor
(n ¼ 5, 45%).
Six patients (55%) were diagnosed with GPA after un-
dergoing LTRR for a presumed diagnosis of idiopathic
laryngotracheal stenosis. Five of these patients had posi-
tive ANCA antibody levels identified after operation. All
tracheal resection specimens exhibited nonspecific
fibrosis or inflammation and were free of granulomatous
or vasculitic changes. A sixth patient did not have any
ANCA testing available but underwent sleeve resection
for left main-stem stenosis 1 year after LTRR. The path-
ologic specimen revealed changes consistent with the
healed phase of GPA. Five other patients (45%) had a
diagnosis of GPA before undergoing LTRR. They were all
considered to be in clinical remission before LTRR and
had been weaned completely from immunosuppressive
drugs before operation. All patients with previous history
of GPA had negative ANCA levels just before operation.
All but one patient in this series had limited GPA with a
primary clinical feature of SGS. The exception was a pa-
tient who had undergone kidney transplantation for GPA
glomerulonephritis and then experienced SGS. Of the 10
patients with limited GPA, 5 patients had additional
involvement of sinus, eye, or lung.

Table 1. Characteristics of 11 Patients With Granulomatous Polyangiitis Undergoing Surgical Treatment of Subglottic Stenosis at
Massachusetts General Hospital
Preoperative Age at Onset Age at
Diagnosis of Airway Operation,
Patient of GPA ANCA Other Organs Prior Interventions Symptoms, Years Years

1 No Positive Nasal septum, eye, joints Dilations, steroid injection 22 46

2 No Positive Lung Tracheal dilations Unknown 63
3 No Positive None None 43 45
4 No Positive None None 46 49
5 No Unknown None Laser debridement, tracheostomy 29 36
6 No Positive Sinus, joints Dilations 47 49
7 Yes Unknown None Dilations 35 50
8 Yes Unknown Lung, sinus, nasal septum Dilations, T-tube, stents 17 27
9 Yes Negative Kidney, sinus, joints Laser debridement, T-tube 27 47
10 Yes Positive Eye Dilations, tracheostomy 35 42
11 Yes Positive None Dilations 39 49

ANCA ¼ anti-neutrophil cytoplasmic antibody; GPA ¼ granulomatous polyangiitis; T-tube ¼ tracheal T-tube.
Ann Thorac Surg COSTANTINO ET AL 251
2018;105:249–53 LARYNGOTRACHEAL RESECTION AND GPA

Most patients (n ¼ 9, 82%) had undergone bronchoscopic
tracheal interventions before LTRR. Interventions included
tracheal dilation (n ¼ 7 patients, 64%), steroid injection (n ¼
1, 9%), laser debridement (n ¼ 2, 18%), and tracheal stenting
(n ¼ 1, 9%). Most patients had multiple interventions, and 4
patients (36%) had undergone more than 15 dilations before
LTRR. Three patients (27%) had prior tracheostomies, one of
which was in place at the time of LTRR.
Operative Management
All patients underwent LTRR to correct SGS and any
stricture related to prior tracheal interventions. A single-
severe GPA (eye enucleation, SGS leading to tracheos-
tomy) that was refractory to induction immunosuppres-
sion regimen with cyclophosphamide and abatacept but
ultimately responded to rituximab. She was decannulated
before operation, and the ANCA antibody titer resolved
after rituximab treatment. She was the only patient with a
history of PR3 antibody, whereas all other patients had
MPO antibodies. Her SGS recurred without an obvious
anastomotic complication and despite perioperative
immunosuppression regimen, including rituximab.
Additional tracheal dilations were necessary for 6 pa-
tients (55%) after LTRR. The median number of dilations

stage laryngotracheal resection with primary anastomosis
was used in all patients, and 3 patients (27%) had a pro-
tective tracheostomy placed distal to the anastomosis
to manage anticipated airway and laryngeal edema
(Table 2). All patients were decannulated before
discharge, one with a tracheal button in place that was
subsequently removed as an outpatient.
Complications
There were no major postoperative complications and no
postoperative deaths (Table 2). Two patients were re-
intubated to manage transient airway swelling and were
promptly extubated. One patient required tube thor-
acostomy for pneumothorax. One patient required
bronchoscopy and debridement of anastomotic granula-
tion tissue. Another patient was re-admitted for a wound
infection that required incision and drainage.
Long-Term Outcomes
The median follow-up was 10.9 years (range: 4 months to
28 years) after LTRR (Table 2). Ten of 11 patients (91%)
were considered to have a good airway outcome, with
control of symptoms related to their prior SGS and
avoidance of tracheostomy. One patient (9%) was
considered an operative failure, because a tracheostomy
tube was replaced 2 months after LTRR. She remained
cannulated 8 months later. This patient had relatively
GENERAL THORACIC
in these 6 patients was two (range: 1 to 8 dilations). One
patient presented with left main-stem bronchial
obstruction 1 year after LTRR and underwent successful
sleeve reconstruction. This patient was free from recur-
rent tracheal stenosis. Four patients (36%) had no further
airway interventions after LTRR. Two of these 4 patients
had a positive ANCA antibody test after LTRR and did
not receive any immunosuppressive drugs. One patient
died 16 years after LTRR with progressive pulmonary and
lower airway GPA. This patient required multiple
tracheal dilations for 2 years after LTRR but did not have
recurrent SGS before death.
Seven patients (64%) received immunosuppression
regimen after LTRR. Immunosuppression regimens
included prednisone, adalimumab, azathioprine, tacroli-
mus, and rituximab. Rituximab was used to manage
suspected recrudescence of GPA in 2 patients and to
prevent reactivation of GPA in 1 patient. One patient
received tacrolimus after undergoing a second renal
transplantation.
Comment
In an earlier review of our experience with LTRR, we
concluded that open surgical treatment of SGS in patients
with rheumatologic disease such as GPA should be
avoided [5]. The primary concerns were disease relapse,

Table 2. Outcomes Associated With Laryngotracheal Resection in Patients With Granulomatous Polyangiitis
Postoperative
Follow-Up Status of Immunosuppression
Patient Operation Complications Period (Years) Delayed Interventions Airway Regimen

1 LTRR Reintubation 27.9 Dilations (n ¼ 8) Good Adalimumab, methotrexate

2 LTRR None 16 Dilations (n ¼ 4) Gooda Prednisone
3 LTRR Wound infection 18.5 None Good None
4 LTRRb Anastomotic granulation 21.8 None Good None
5 LTRRb Pneumothorax 1 LMSB sleeve resection Good None
6 LTRR Reintubation 15.9 Dilations (n ¼ 2) Good Rituximab
7 LTRR None 10.9 Dilations (unknown number) Good Unknown
8 LTRR Vocal cord paresis 9.7 None Good Azathioprine
9 LTRR None 8.8 Dilation (n ¼ 1) Good Tacrolimus, prednisone
10 LTRRb None 0.9 Dilation (n ¼ 1) Failure Rituximab, azathioprine
11 LTRR None 0.3 None Good Rituximab
a b
Deceased with left main-stem bronchial stenosis and pulmonary disease. Protective tracheostomy.
LMSB ¼ left main-stem bronchus; LTRR ¼ laryngotracheal resection and reconstruction.
 252 COSTANTINO ET AL Ann Thorac Surg
LARYNGOTRACHEAL RESECTION AND GPA 2018;105:249–53

anastomotic complications, and the need for immuno-
suppressive drugs that could impair healing. The
cornerstone of management of SGS developing in pa-
tients with GPA remains bronchoscopic intervention,
whereas refractory disease might require tracheostomy.
Although clinical remission rates and overall outcomes
are markedly improved with newer immunosuppression
regimens, SGS may prove refractory to pharmacologic
management alone [3, 6, 7].
In a highly selected group of patients with GPA and
SGS, 91% of patients achieved a good airway outcome
after LTRR and avoided tracheostomy during long-term
GENERAL THORACIC
renal involvement, must be thoroughly investigated. Two
patients in our early experience with LTRR had positive
ANCA tests shortly after operation and have had excel-
lent long-term outcomes (18 and 21 years of follow-up)
without any immunosuppression regimen. We consider
these patients to be the exception to the rule and have
adhered to the standard that all patients with GPA un-
dergoing LTRR must have negative ANCA testing at the
time of operation. There is likely a role for serial moni-
toring of ANCA antibody levels with PR3 and MPO
ELISA to guide maintenance immunosuppression
regimen, as explained by Han and colleagues [13]. It re-

follow-up. Four patients (36%) required no further dila- mains to be seen if this contemporary strategy for man-
tion or airway intervention and had an excellent outcome. aging postoperative immunosuppression regimen will
Seven patients (64%) required additional bronchoscopic improve long-term outcomes.
airway intervention, only one (9%) of which did not Because ANCA levels do not absolutely correlate with
resolve or stabilize, necessitating a tracheostomy. These disease activity in GPA, bronchoscopic examination to
outcomes were achieved without major complications rule out active inflammation is recommended before
and with no postoperative deaths. LTRR. In our experience, all patients were free of bron-
One of the earliest reports suggesting that LTRR could choscopic signs of inflammation such as airway edema
be safely performed in patients with GPA was by Her- and hyperemia (Fig 1). In our 1 patient who was an
ridge and colleagues [8], who described their experience operative failure, there was an early recurrence of SGS
with 3 patients. Although long-term follow-up was only that necessitated a tracheostomy and was likely related to
available for one of the patients, the investigators reactivation of her GPA. Her ANCA/PR3 levels rose
concluded that the operation could be performed safely several weeks after LTRR and did not decline with
as long as patients were in remission and received peri- resumption of rituximab. PR3 antibody was only detected
operative immunosuppression regimen. A more recent in this 1 patient, whereas all other patients had MPO
report by Wester and colleagues [9], who had a series of 8 antibody. Han and colleagues [13] noted that the presence
GPA patients undergoing open surgical management, of PR3 antibody is associated with increased risk of
observed that 75% of these patients required additional relapse and disease severity. An intriguing report on the
tracheal dilation and only 1 patient (13%) required per- utility of magnetic resonance imaging in assessing for
manent tracheostomy, which is similar to our observed granulomatous involvement of the airway and
rates of 55% and 9%, respectively. These rates are clearly
higher than observed for patients undergoing LTRR for
idiopathic laryngotracheal stenosis and suggests that
even with GPA remission and maintenance immuno-
suppression regimen, there is likely a chronic phase of
the disease that affects long-term outcomes.
In addition to concern about recurrent SGS, a small
proportion of GPA patients appear to be also susceptible
to lower airway stenosis. In our experience, 2 patients
(18%) went on to experience left main-stem stenosis 1 and
9 years after LTRR, respectively. Guardiani and col-
leagues [10] also noted that 18% of their patients with
GPA and SGS experienced lower airway disease. The risk
of developing lower airway disease in GPA patients after
LTRR mandates long-term clinical follow-up to ensure
early diagnosis and effective management. Although
bronchoscopic management of lower airway stenosis is
the mainstay of treatment, on occasion sleeve resection
may be successfully performed, as in our experience with
1 patient and the report by Soo and colleagues [11].
The precise role of ANCA antibody testing in man-
agement of SGS in GPA has yet to be defined. Patients
who experience SGS seem to represent a distinct subset
of all patients with GPA and are known to have a higher
incidence of negative ANCA testing [12]. A high index of
suspicion needs to be maintained in patients undergoing Fig 1. Bronchoscopic image of subglottic stenosis in patient with
evaluation for SGS, and clinical manifestations of rheu- granulomatosis with polyangiitis before laryngotracheal resection.
matologic disease, such as sinus, ocular, pulmonary, or The stenosis is mature and free of inflammation.
Ann Thorac Surg
2018;105:249–53
inflammation suggests that imaging might also have a
role in assessing a patient’s suitability for LTRR [14].
Although this is the largest report of GPA patients un-
dergoing LTRR to date, the relatively small number of
patients and large time span in which care was delivered
prevent more rigorous assessment of patient variables that
may affect outcomes. The disparate immunosuppression
regimens used in the study period also makes it difficult to
draw conclusions about ideal medical management of GPA
patients with SGS. Nonetheless, we conclude that there are
some patients who might benefit from LTRR when bron-
choscopic interventions become more frequent or when
tracheostomy is threatened. The ideal patient has limited
GPA with airway disease confined to a short segment of the
subglottic trachea, evidence of clinical remission for at least
6 months after induction immunosuppression regimen,
negative ANCA antibody testing, minimal or no steroid
requirement just before operation, and a bronchoscopic
examination revealing no active airway inflammation. Pa-
tients should be fully informed about the risk of recurrence,
need for future airway dilations, and the possibility of
subsequent lower airway disease. Although there is no
difference in LTRR technique performed for patients with
GPA and idiopathic SGS, the need for protective trache-
ostomy is more likely in GPA patients. Long-term control
of the disease requires careful surveillance of clinical var-
iables and ANCA levels as well as a lower threshold to
escalate immunosuppression regimen. We have demon-
strated that there are reasonable long-term outcomes,
including freedom from tracheostomy, in a highly selected
group of GPA patients undergoing LTRR.
References
1. Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised Interna-
tional Chapel Hill Consensus Conference Nomenclature of
Vasculitides. Arthritis Rheum 2013;65:1–11.
COSTANTINO ET AL 253
LARYNGOTRACHEAL RESECTION AND GPA
2. Langford CA, Sneller MC, Hallahan CW, et al. Clinical fea-
tures and therapeutic management of subglottic stenosis in
patients with Wegener’s granulomatosis. Arthritis Rheum
1996;39:1754–60.
3. Wojciechowska J, Krajewski W, Krajewski P, Krecicki T.
Granulomatosis with polyangiitis in otolaryngologist prac-
tice: a review of current knowledge. Clin Exp Otorhinolar-
yngol 2016;9:8–13.
4. Niles JL. Antineutrophil cytoplasmic antibodies in the clas-
sification of vasculitis. Annu Rev Med 1996;47:303–13.
5. Ashiku SK, Kuzucu A, Grillo HC, et al. Idiopathic laryngo-
tracheal stenosis: effective definitive treatment with lar-
yngotracheal resection. J Thorac Cardiovasc Surg 2004;127:
99–107.
6. Girard C, Charles P, Terrier B, et al. Tracheobronchial
GENERAL THORACIC
stenoses in granulomatosis with polyangiitis (Wegener’s):
a report on 26 cases. Medicine (Baltimore) 2015;
94:e1088.
7. Rhee EP, Laliberte KA, Niles JL. Rituximab as maintenance
therapy for anti-neutrophil cytoplasmic antibody-associated
vasculitis. Clin J Am Soc Nephrol 2010;5:1394–400.
8. Herridge MS, Pearson FG, Downey GP. Subglottic stenosis
complicating Wegener’s granulomatosis: surgical repair as a
viable treatment option. J Thorac Cardiovasc Surg 1996;111:
961–6.
9. Wester JL, Clayburgh DR, Stott WJ, Schindler JS,
Andersen PE, Gross ND. Airway Reconstruction in Wege-
ner’s granulomatosis-associated laryngotracheal stenosis.
Laryngoscope 2011;121:2566–71.
10. Guardiani E, Moghaddas HS, Lesser J, et al. Multilevel
airway stenosis in patients with granulomatosis with poly-
angiitis (Wegener’s). Am J Otolaryngol 2015;36:361–3.
11. Soo A, Aziz R, Buckley M, Young V. Bronchoplastic pro-
cedure for an unusual indication–Wegener’s granulomatosis.
Interact Cardiovasc Thorac Surg 2009;9:530–1.
12. Hoffman GS, Kerr GS, Leavitt RY, et al. Wegener gran-
ulomatosis: an analysis of 158 patients. Ann Intern Med
1992;116:488–98.
13. Han WK, Choi HK, Roth RM, McCluskey RT, Niles JL. Serial
ANCA titers: useful tool for prevention of relapses in ANCA-
associated vasculitis. Kidney Int 2003;63:1079–85.
14. Klink T, Holle J, Laudien M, et al. Magnetic resonance im-
aging in patients with granulomatosis with polyangiitis
(Wegener’s) and subglottic stenosis. MAGMA 2013;26:
281–90.