TITLE: Subglottic Stenosis in Wegener’s Granulomat=
osis
SOURCE: Grand Rounds Presentation, UTMB, Dept. of Otolaryngology
DATE: May 21, 2008
RESIDENT PHYSICIAN: Chad Simon, MD
FACULTY PHYSICIAN: Susan McCammon, MD
DISCUSSANT’S REMARKS: Francis B. Quinn, Jr., MD
SERIES EDITORS: Francis B. Quinn, Jr., MD
"This
material was prepared by resident physicians in partial fulfillment of
educational requirements established for the Postgraduate Training Program =
of
the UTMB Department of Otolaryngology/Head and Neck Surgery and was not
intended for clinical use in its present form. It was prepared for the purp=
ose
of stimulating group discussion in a conference setting. No warranties,
either express or implied, are made with respect to its accuracy, completen=
ess,
or timeliness. The material does not necessarily reflect the current or past
opinions of members of the UTMB faculty and should not be used for purposes=
of
diagnosis or treatment without consulting appropriate literature sources and
informed professional opinion."
In 1931, Heinz Klinger of the
Wegener joined the Nazi Party in 1932. As a high
ranking military doctor he spent some of WWII in a medical office near a Je=
wish
ghetto in
Wegener’s Granulomatosis (WG) is a necroti= zing granulomatous vasculitis of autoimmune origin. = The disease has a predilection for the upper and lower respiratory tracts and the kidneys. In the sinonasal tract, the vasculitis can cause sinusitis, nasal crusting, epistaxis, septa= l perforation and saddle-nose deformity. In the lungs, the disease may lead t= o pneumonitis and hemoptysis. In the kidneys, a crescentic = glomerulonephritis develops, eventually leading to renal failure. Other manifestations include skin lesions, arthritides,<= span style=3D'mso-spacerun:yes'> conjunctivitis, and other n= on-specific systemic inflammatory problems. Subglottic stenosis is a potentially life-threatening manifestation of Wegener’s granulomatosis. This narrowing of the upper airway at the level of the cric= oid cartilage and/or upper tracheal rings presents a management dilemma.
Subglottic stenosis (SGS) is reported to occur in 16-23% of patients with Wegener’s Granulomatosis. (Langford) It has b= een reported to occur more often in females. (Shokkenbroek= , Gluth) The median age at diagnosis is 26. (Lang= ford) and is more likely to occur in patients diagnosed with Wegener’s before a= ge 20. (Langford) Patients with WG and SGS tend to have more sinus involvement= and saddlenose deformity than other WG patients. On= the contrary, SGS patients tend to have less lung and kidney involvement. (Langford)
The pathogenesis is unclear. Subglottic stenosis= can progress in the absence of systemic disease. Few patients have WG exacerbat= ions around the time of diagnosis with SGS. In series where patients were follow= ed, need for repeat procedures was not related to re= peated systemic disease flares. It is postulated that during flares of systemic disease, subclinical subglottic involvement occurs, which subsequently heals with circumferential scarring. (Shokkenbroek) S= ome authors speculate that the subglottis is vulner= able because it is a watershed area of the microcirculation. This watershed area= is the junction of 2 separate embryological growth centers. (Eliachar) Exposur= e of respiratory epithelium to gastric contents during LPR episodes is also beli= eved to play a role. (Gluth) Initial granulomatous inflammation is followed by circumferential scarring and airway narrowing.<= /p>
Dyspnea on exertion =
is the
most common presenting symptom. (79-82%)(Gluth, Langford) Other symptoms include voice change,=
stridor, or cough. Patients may have a known diagnosi=
s of
WG (50%), have other symptoms of systemic disease, or present as a new pati=
ent
with airway complaints. If the diagnosis of WG is not established, an anti-=
cytoplasmic antibody assay should be performed. It ha=
s been
suggested that ANCA titers be performed on nearly all patients with SGS. (<=
span
class=3DSpellE>Gluth) A positive C-ANCA assay is reported to be 91%
sensitive and 99% specific for active Wegener’s granulomatosis.
However, a series of patients with SGS and presumed WG showed that only 57%
initially showed a positive ANCA assay. 85% of the cohort eventually became
positive at a later date. (Alaani) This emphasizes the fact that SGS can be
present in the absence of active disease. It also suggests that ANCA assay =
be
repeated serially if there is diagnostic uncertainty. The presence of ANCA =
in
serum can be detected by indirect immunofluorescence
or by radioimmunoassay. Indirect immunofluorescence
reveals a pattern of staining that can be more specific for a particular
disease. The “cytoplasmic” pattern
(c-ANCA) is associated with ANCA reacting with a 29
·
Gr=
ade I
- Obstruction of 0-50% of the lumen obstruction
·
Gr=
ade II
- Obstruction of 51-70% of the lumen
·
Gr=
ade
III - Obstruction of 71-99% of the lumen
·
Gr=
ade IV
- Obstruction of 100% of the lumen (ie, no dete=
ctable
lumen)
Histological proof of WG is obtained by finding = vasculitis, necrotizing granulom= ata and giant cells in biopsy material. But, in general, biopsies of the subglo= ttic lesion are not sensitive for the detection of WG. Only 5-15% of subglottic biopsies performed on patients with positive ANCA titers and SGS return cha= nges consistent with WG. (Gluth, Langford) In contra= st, nasal biopsies on a similar cohort of patients yielded 82% sensitivity for = WG. (Gluth) Pulmonary function tests are abnormal i= n 60% of patients with subglottic stenosis. (Langford) Flattening occurs in the flow-volume loop in both the inspiratory and expiratory portions, giving it a box-like appearance. However, PFTs may not detect less severe = stenoses and should never be used for primary diagnosis. An abnormal flow-volume loo= p is correlated with need for surgical intervention. (Langford)
Treatment of subglottic stenosis should be consi= dered based on the presence of symptoms combined with objective evidence of trach= eal narrowing. Other parameters, such as active systemic disease or a change in ANCA titers should never be used as consideration for procedures. Treatment options include immunosuppression, tracheostomy, endoscopic dilation, intralesional steroids, laser procedures, cold knife lysis, o= pen surgical procedures, and airway stents.
Drugs such as corticosteroid= s, cyclophosphamide, and azothiopri= ne has revolutionized the treatment of WG, with a dramatic reduction in mortality. However, subglottic lesions are generally unresponsive to system= ic agents. 49% of SGS cases are diagnosed while a patient is on active therapy. (Langford) Success rates of medical therapy in relieving the obstruction va= ry from 22%-26%. (Gluth, Langford)
Life-threatening airway obstruction may require = tracheostomy as a temporizing or permanent measure. <= span class=3DSpellE>Tracheostomy is necessary in 8 - 60% of cases. (Langf= ord, Schokkenbroek, Gluth, Ala= ani) Often, success of other therapies is measured by decannulatio= n of the tracheostoma.
Endoscopic procedures have been variably success=
ful at
managing this airway lesion. Dilation tracheoscopy
can be performed using a
Traditional dilation techniques, combined with <= span class=3DSpellE>intralesional steroid injection have been reported. U= nder suspension laryngoscopy and spontaneous ventila= tion, graduated dilators are used to dilate the trachea. Next, methylprednisolone injections are performed in a a 4-quadrant, submucosal pattern. Perioperative, systemic steroids are also used. 20 patients received this treatment and we= re followed for a median of 35 months. The median number of treatments required was 3. Six patients required only 1 procedure. One patient required 22 procedures.. All patients who began therapy with= a tracheostomy were eventually dec= annulated. No patients required a new tracheostomy.
In another series, 21 patients with WG and signi= ficant SGS were studied. These patients were treated with int= ralesional steroid injection combined with mechanical dilation and cold-knife lysis of the lesion. Under suspension laryngoscopy and jet ventilation, methylprenisolone was inje= cted submucosally in 4 quadrants. Lys= is of the stenotic ring was then performed by maki= ng radial incisions with a laryngeal microsickle k= nife. The stenosis was then serially dilated with Maloney bougie= s or a Foley catheter. Topical mitomycin C was va= riably used. (Hoffman) Patients with prior procedures (mostly laser) averaged more procedures to obtain adequate airway patency and with a shorter interval between procedures. The authors comment that, subjectively, lesions seen in= patients who had undergone prior laser procedures were severe, extensive, and thickly fibrotic. No new tracheotomies were necessary in either group. (Hoffman) The most difficult lesions were found in the 6 patients with prior tracheotomie= s, presenting with multilevel stenoses, cicatrix formation, vocal cord fixation and arytenoid da= mage. In these patients, widening of the subglottic region alone was not sufficient.= 4 of the 6 patients achieved decannulation by mea= ns of various laryngotracheoplastic techniques which = were not specified. The authors comment that laser procedures cause extensive scarring and thus patients are more difficult to manage afterward. However, these patients may represent a cohort with more severe disease, who would be more difficult to manage anyway. There is no way to differentiate whether t= he scarring is from prior laser procedure, or from more extensive inflammation= in the airway .
Although abhorred by other authors, laser treatm= ent of SGS has been performed and reported on. For lesions close to the vocal cord= s, in 2 patients, CO2 laser was used with microsuspension= laryngoscopy to resect the stenosis. For lesions far from the cords (>1 cm), in 3 patients, Nd:YAG laser was used with= through a fiberoptic bronchoscope, under local anesthes= ia. (Shvero) 4 out of these 5 patients are reported to have favorable outcomes or decannulation during their follow up period of 6-60 months. However, all patients required multiple treatments (2-18) In addition, one patient required placement of a subglott= ic stent. (Shvero)
Open surgical procedures hav= e been performed with success= . Most commonly performed is the laryngotracheal reconstruction with costal cartilage graft (LTR). It is recommended to defer LTR until a patient is in a quiescent phase of the systemic disease. This should be monitored by serum ANCA titers, CRP, and ESR. It is also recommen= ded that surgery be deferred until a patient is not actively taking steroids or other immunosuppressant medications. (Gluth) A = small series of Wegener’s patients who received laryng= otracheal reconstruction for SGS shows excellent results. 6 of 6 patients were decannulated from their tracheos= tomy after the LTR. There were no cases of graft failure even in 3 of the patien= ts in whom reactivation of systemic WG occurred. 1 complication of graft displacement occurred. (Gluth)
The use of airway stents to<= span style=3D'mso-spacerun:yes'> maintain airway patency in = SGS and WG is controversial. Some authors have advocated deployment of a Nitinol (nickel-titanium alloy) expandable stent into= the subglottic airway when all other therapies fail. Similar stents have been u= sed with success in the distal tracheobronchial tre= e. A case report exists in the literature. A patient was followed for 48 months after deployment of a nitinol stent. She had a = patent airway, no complications, and no ingrowth of granulation tissue. (Watters) Other authors argue that the long-term safety= and efficacy of these stents has not been well established. They argue that the= se devices are associated with stent fracture, migration, increased granulation tissue, and even death. Stents in the subglottis also undergo movement with swallowing and saliva exposure. These factors preclude early mucosalization of the stent, as occurs in= more distal portions of the airway. The foreign body reaction, it is argued, cau= ses more granulation tissue ingrowth. (Mair- anecdotal) The argument against stents is furth= er supported by the fact that an emergency trachotomy in the setting of a subglottic metal stent is very difficult to perform.
Based on the published research, the following treatment plan should be followed. If the airway is tenuous, perform emerge= nt tracheotomy. If patient is stable, perform PFTs= , CT scan, and fiberoptic endoscopy. 1st line therapy should be endoscopic dilation. With subsequent dilations, cold-knife lysis, and intralesional = steroids should be added. Patient should be followed every 3 months with repeat fiberoptic exams and PFTs= . Serial ANCA titers are not necessary from an ENT standpoint, since they correlate poorly with SGS progression. Endoscopic procedures should be repeated as necessary. If endoscopic procedures must be performed at an increasingly mo= re frequent interval, consideration should be given to open laryngotracheal reconstruction. Subglottic stents should be avoided if at all possible.
Discussant’s Remarks: Francis B. Quinn, Jr., MD, FACS
Idiopathic Midline Destructive Disease
Today’s Grand Rounds is a fine discussion = of the incidence and treatment of subglottic stenosis occurring in patients who suffer from idiopa= thic midline destructive disease. = One may infer or doubt a causative relationship based on data regarding the abs= ence of granulomatous histology in the stenosis itself, or by the association of positive C-ANCA titers in cases of stenosis occurring in the absence of clinical midline destructive disease.
The taxonomy of idiopathic midline destructive d= isease has not benefited from the attempts to identify and classify its variants, based on etiology (autoimmune, infectious, neoplastic<= /span>), histology, clinical manifestations, responses to therapy (microbial, corticosteroid, chemotherapeutic, ionizing radiation) and natural history (remittent, inexorable progression, lethal).
A brief walk through the medical literature yiel=
ds a
collection of terms including polymorphic reticulosis<=
/span>,
lethal midline granuloma, malignant midline
While the eponymic “Wegener’s granulomatosis” se= rves the vulgate, the inclusive “idiopathic midline destructive disease= 221; will point to the disorder as a challenge to the therapist and not merely a diagnostic dead end with ineluctably hopeless prognosis.
The term “idiopathic midline destructive d= isease” can be considered as a collection of vectors in which every manifestation of the disease (clinical, histologic, course, etc.= ) is represented by data types appropriate to that manifestation (continuous, discrete, Boolean, or null). = The individual patient can be mapped onto the N-space such that cluster analysis leads to a rational nosology permitting an enlightened pathophysiologic understanding of t= his (group of) disease(s).
Bibliography
Alaani et al. We= gener's granulomatosis and subglottic stenosis: management of the airway. J Laryngol Otol. 2004 Oct;118(10):786-90.
Eliachar et al. <= span class=3DGramE>New approaches to the management of subglottic stenosis in We= gener's granulomatosis. Cleve Clin J Med. 2002;69= Suppl 2:SII149-51.
Gluth et al. Sub= glottic stenosis associated with Wegener's granulomatosis. Lary= ngoscope. 2003 Aug;113(8):1304-7.
Hoffman et al. Treatment= of subglottic stenosis, due to Wegener's granulomatosis, with intralesional corticosteroids and dilation. J Rheumatol. 2003 May;30(5):1017-21.
Langford et al. Clinical features and therap= eutic management of subglottic stenosis in patients with Wegener's granulomatosis= . Arthritis Rheum. 1996 Oct;39(10):1754-60.
Sho= kkenbroek et al. Dilatation tracheoscopy f= or laryngeal and tracheal stenosis in patients with Wegener's granulomatosis.<= /span> Eur Arch Otorhinolaryngol. 2008 May= ;265(5):549-55. Epub 2007 Nov 14.
Shvero et al. En= doscopic laser surgery for subglottic stenosis in Wegener's granulomatosis. Yonsei Med J. 2007 Oct 31;48(5):748-53.
Watters et al. Su= bglottic stenosis in Wegener's granulomatosis and the nitinol stent. Laryngoscope. 2003 Dec;113(12):2222-4.