Pulmonary disease in small-vessel vasculitis

TREATMENT STRATEGIES

Medications

Although many patients with GPA are surgical candidates because of dyspnea related to fixed endobronchial or endotracheal obstructions, any surgical treatment carries the risk of inciting further flares. Treatment should focus first on mitigating the systemic inflammatory disorder with pharmacologic intervention. Standard pharmacologic therapy includes corticosteroids, azathioprine, cyclophosphamide, and rituximab. Patients with subglottic stenosis are frequently unresponsive to standard immunosuppressive therapy (glucocorticoids in combination with a cytotoxic agent).¹

Surgical reconstruction

When medication falls short and surgery is needed to reverse strictures, a number of tools are at our disposal. Some involve heat, such as laser, cauterization, and argon plasma coagulation. In argon plasma coagulation, a jet of ionized argon gas (plasma) is directed through a probe passed through an endoscope. Other techniques rely on cold: cryoprobes, microdebriders, and rigid scissors. In general, freeze therapies cause less scarring than heat therapy. With any surgical technique, there is risk of scars that will contract and cause structural collapse, resulting in restenosis.

Dilation

The high rate of stenosis relapse has spurred interest in alternatives to surgical treatment. One of these, dilation via endoscopy, also may mitigate the wound healing process. Other techniques for clearing the obstructed area include rigid bronchoscopy, the use of bougies (increasingly larger dilators), and balloon dilation. Balloon dilation has some advantages over the other techniques. It permits maximal radial direction and pressure, causes less damage to trachea wall mucosa, and achieves better overall results; however, the procedure usually needs to be repeated.⁵ It must be done quickly, and it requires flawless communication between the otolaryngologist or pulmonologist and anesthesiologist in order to stabilize the airway below the vocal cords.

Intratracheal dilation-injection therapy

Dilation can be augmented with glucocorticoid injections. In 1991, researchers at the National Institutes of Health utilized a combination dilation-injection therapy for 20 patients who had GPA and subglottic stenosis.¹ Patients were first treated with mercury-filled dilators coated with 1% triamcinolone cream. Methylprednisolone acetate was then injected into the stenotic area. None of the patients treated with intratracheal dilation-injection therapy required a tracheostomy and six who already had tracheostomies were decannulated. In contrast, 56% of patients who received standard immunosuppressive therapy and no intratracheal dilation-injection therapy required tracheostomy. Intratracheal dilation-injection therapy is considered a safe and effective treatment of GPA-associated subglottic stenosis and, in the absence of major organ disease activity, could be used without systemic immunosuppressive agents.

Mitomycin-C is a controversial alternative to corticosteroids during dilation. Mitomycin-C is an alkylating agent that inhibits fibroblast proliferation and extracellular matrix protein synthesis, with the potential for reduced scarring. In a recent trial of 26 patients, two doses given 3 to 4 weeks apart reduced the rate of stenosis for 2 to 3 years compared with a single dose.⁶ Restenosis occurred in both groups, however, and after 5 years, the relapse rates were the same.

Nd:YAG laser photoresection versus endobronchial electrosurgery

One of the most effective therapies for treating obstructive lesions is Nd:YAG laser photoresection (LPR) in which a laser that utilizes the crystal neodymium-doped yttrium aluminum garnet (Nd:Y₃Al₅O₁₂) is paired with a flexible bronchoscope. The procedure can produce favorable outcomes,⁷ but it has not gained favor because of perceptions that the lasers require rigid bronchoscopy, expensive equipment, and special training. There are also concerns about complications.

The lower-cost endobronchial electrosurgery (EBES) also failed to gain acceptance because of cumbersome delivery systems and complications associated with power units. Recently, engineers have spawned a new generation of electrosurgical devices, prompting renewed interest in EBES.

A recent study compared LPR and EBES in patients who represented 118 evaluations for LPR.⁸ Forty percent were considered amenable to EBES and so did not go on to receive the more costly LPR. Of those, 89% achieved success in alleviating the obstruction. The authors concluded that EBES can potentially eliminate the need for LPR in 36% of procedures, and that it could achieve significant savings in cost and time. We use these ablative therapies only in dire circumstances; we use non–heat-based therapies, including repeated dilation, prior to considering use of other therapies.

Cryotherapy

Cryotherapy spray was initially thought to have great therapeutic potential, but the high pressures of the spray caused complications. This modality remains under investigation, however. Some probe-based cryotherapy techniques have been effective anecdotally. These use a metal-tipped probe attached to a cryogen; the Joule-Thompson effect causes delayed tissue destruction.

Stents

A small number of case reports note patient improvement after stenting.^9,10 We use stents in rare circumstances, but because complications are frequent and sometimes severe, we consider stenting a last-resort option. In 2005, the US Food and Drug Administration mandated a Black Box warning against the use of metallic stents in patients who have benign tracheal strictures.

Multimodality therapies

In general, when intervention is required to salvage airways, a combination of dilation and steroid injection with or without topical mitomycin-C is standard. We try to avoid use of thermal therapy with laser or electrocautery because of the risk of exuberant inflammation and restenosis from thermal injury. No specific standard of care exists in these cases; reliance on clinical judgment is critical because of the presentation and variety of airway lesions. Further, no large-scale randomized trials exist to guide therapy, so it is best to work with a multidisciplinary team whose members have experience in managing these complex patients.

CONCLUSION

The differential diagnosis of pulmonary manifestations of small-vessel vasculitis is complex. Several diagnoses can mimic various forms of pulmonary vasculitis, and the manifestations and symptoms often overlap with other organ systems.

Imaging is useful for analysis of common patterns of small and midsize vasculitis, although the results may be confounded by disorders that mimic pulmonary vasculitis. To enhance diagnostic accuracy, laboratory and clinical findings should be considered along with images. Ideally, treatment will be minimally destructive and mucosa-sparing. Dilation therapies can be augmented with corticosteroid injections or, possibly, mitomycin-C.