Idiopathic Nonspecific Interstitial Pneumonia (NSIP) is a relatively new diagnosis only recently validated as a distinct clinical entity. Although immunosuppressive medications are the cornerstone of treatment, there is no consensus with regard to the best regimen. Below we present a case of idiopathic NSIP inadvertently treated with triple immunosuppression in the setting of a single lung transplantation resulting in significant resolution of radiographic native lung infiltrates.
We report the case of a 30 year old female sculptor who presented with subacute onset dyspnea preventing her from climbing a single flight of stairs without stopping to rest. Her initial examination revealed clubbing and bibasilar crackles. She required 2 liters per minute (lpm) of supplemental oxygen in order to maintain a resting room air oxygen saturation (SaO2) above 88%. Spirometry was normal but the diffusion capacity for carbon monoxide was 20% predicted. SaO2 nadir during six minute walk test was 90% on 4lpm of oxygen. High resolution computed tomography revealed bilateral predominately lower lobe ground glass opacities with reticular abnormalities. Surgical lung biopsy led to a diagnosis of fibrotic NSIP based on radiographic, clinical, and pathologic correlation. A thorough evaluation for underlying connective tissue disease (CTD) was unrevealing. Her disease progressed despite treatment with azathioprine and prednisone. Given the lack of response to therapy and rapid progression, the patient underwent single lung transplantation approximately one year after symptom onset. Post-transplant medications included a tapering dose of prednisone, tacrolimus, and azathioprine. Her postoperative course was marked by several episodes of acute rejection, one episode of pneumonia, and spontaneous hydropneumothorax resulting in a trapped, fibrotic, and poorly functional allograft. Nuclear medicine imaging revealed 13% ventilation and 10% allograft perfusion. Despite these complications, continued clinical improvement was noted, ascribed to improvement in native lung pneumonitis. This was supported by an almost complete clearing of radiographic infiltrates. Eighteen months post transplant, the patient has minimal dyspnea and is able to complete a six minute walk test without requiring supplemental oxygen.
NSIP was first described in 1994 but not established as a specific histopathologic entity until 2002. Along with this recognition, a strong association with CTD was acknowledged. However, a significant portion of NSIP patients do not meet criteria for underlying CTD. It was suggested that in these cases NSIP was either the initial presentation of a yet to be diagnosed underlying CTD, a pathologic presentation of another entity (i.e. drug reaction), or a distinct single organ autoimmune process. Idiopathic NSIP was identified as a distinct clinical diagnosis by the ATS in 2008. Typically, treatment of CTD associated interstitial lung disease is aimed at the underlying process. Similarly, both cellular and mixed idiopathic NSIP is treated with immunosuppressive medications. In case series and uncontrolled trials, a clear improvement is reported among cellular NSIP patients treated with prednisone and a single cytoxic agent. Conversely, fibrotic NSIP behaves more like idiopathic pulmonary fibrosis (IPF) and immunosuppressive regimens tend to be ineffective in this subgroup. To our knowledge, successful treatment with a triple immunosuppressive approach has not been described. Given its varied histopathologic manifestations and known ties with autoimmune etiologies, NSIP may be a final common pathway of various autoimmune processes. As such, empiric multiple agent immunosuppressive therapy may have a therapeutic value in a certain refractory NSIP subset.
Cellular and mixed NSIP is distinguished from Idiopathic Pulmonary Fibrosis/Usual Interstitial Pneumonia by a favorable prognosis and response to therapy. As such, targeted therapeutic regimens need to be developed and tested. In the fibrotic subset, progression despite treatment with glucocorticoids and a single cytoxic agent is common. In this setting, treatment with triple immunosuppression may be beneficial.
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