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Polymyositis Associated With Severe Interstitial Lung Disease: Remission After Three Doses of IV Immunoglobulin FREE TO VIEW

Catherine J. Bakewell, MD; Ganesh Raghu, MD
Author and Funding Information

From the Division of Rheumatology (Dr Bakewell) and the Division of Pulmonary and Critical Care Medicine (Dr Raghu), University of Washington Medical Center, Seattle, WA.

Correspondence to: Catherine J. Bakewell, MD, Division of Rheumatology, Box 356428, University of Washington Medical Center, Seattle, WA 98195; e-mail: bakewell@uw.edu


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2011 American College of Chest Physicians


Chest. 2011;139(2):441-443. doi:10.1378/chest.10-0360
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Interstitial lung disease associated with polymyositis/dermatomyositis (ILD-PM/DM) often confers a poor prognosis, and optimal treatment of this condition is not well defined. This report describes a 63-year-old man with severe ILD-PM/DM who presented with 5 months of progressive dyspnea and weakness. He had an initial carbon-monoxide-diffusing capacity of 35% predicted and a creatine kinase level of 2,112 U/L. After three monthly doses of immunoglobulin at 2 gm/kg IV, he has sustained clinical remission for > 2 years. IV immunoglobulin has not previously been studied as a first-line agent for rheumatologic diseases, and it is currently used as a salvage therapy. However, if IV immunoglobulin is capable of inducing sustained remission after brief use as a treatment, as demonstrated in this patient, especially in the setting of significant pulmonary involvement, then it merits further consideration for investigation as a first-line therapeutic agent.

Figures in this Article

A 63-year-old man presented with 5 months of progressive exertional dyspnea. He had weakness and pain involving his proximal musculature as well as generalized arthralgias. A chest radiograph (Fig 1) and a high-resolution CT (HRCT) scan of his chest (Fig 2) demonstrated diffuse abnormalities consistent with interstitial lung disease (ILD). A BAL cellular profile revealed the following: lymphocytes were 65% of the visualized cells, neutrophils were 6%, macrophages were 12%, and eosinophils were 16%. There were no ciliated epithelial cells. The CD4 to CD8 ratio was 0.1:1. Examination of transbronchial lung biopsy specimens revealed histologic features of inflammation with organizing pneumonia and without evidence of infection (Fig 3). Pulmonary function tests (PFTs) revealed a severely decreased carbon-monoxide-diffusing capacity (Dlco) at 35% of predicted, preserved lung volumes, and no evidence of airflow obstruction.

Figure Jump LinkFigure 1. Postero-anterior chest radiograph at initial presentation demonstrating irregular streaky opacities consistent with interstitial fibrosis at the lung bases bilaterally.Grahic Jump Location
Figure Jump LinkFigure 2. A, Initial high-resolution CT (HRCT) scan of the chest demonstrating interstitial pneumonia with ground glass opacification, mild intralobular septal thickening, and subtle honeycombing, with subpleural sparing consistent with features of nonspecific interstitial pneumonia. B, HRCT scan 20 months later demonstrates complete resolution of previously noted changes.Grahic Jump Location
Figure Jump LinkFigure 3. Histopathologic examination of transbronchial lung biopsy specimen. A, Plugs of granulation tissue characteristic of organizing pneumonia. A mechanically crushed inflammatory infiltrate is also present (hematoxylin and eosin stain, original magnification × 10). B, Mostly compressed alveolar lung tissue with mild lymphocytic inflammation in the top of the image (hematoxylin and eosin stain, original magnification × 20). Together the images show cellular (lymphocytic) interstitial pneumonitis with organizing pneumonia.Grahic Jump Location

He had an elevated creatine kinase (CK) level of 2,112 U/L and an aldolase level of 31 U/L as well as markers of inflammation (Table 1). Serologic test results were negative, including tests for antinuclear antibodies and anti-Jo-1. MRI of the thighs revealed an abnormal T2 signal within the bilateral brachius femoris muscles, vastus lateralis muscles, and biceps femoris muscles, with no evidence of muscle atrophy. MRI of the shoulders demonstrated a similar increase in the T2 signal in the deltoid and biceps muscles. Examination of a biopsy specimen from the right thigh muscle demonstrated fiber necrosis and regeneration. Immunoperoxidase studies demonstrated a predominance of CD8-positive T lymphocytes, consistent with a diagnosis of polymyositis.

Table Graphic Jump Location
Table 1 —Clinical Course

The table presents the initial to final-testing results. Oxygen saturation was measured while breathing air at sea level, and 6-min walk tests were performed on level ground. CRP had returned to normal values by 5 months, and all indices with the exception of Dlco returned to normal over the course of 2 years. The Dlco, corrected to hemoglobin, remains mildly reduced. CK = creatine kinase; CRP = C-reactive protein; Dlco adjusted = carbon monoxide diffusing capacity adjusted for hemoglobin; RV = cresidual volume; TLC = total lung capacity.

a 

Normal values are < 285.

b 

Normal values are < 15.

c 

Normal values are < 10.

For the severe interstitial pneumonia/pulmonary fibrosis attributed to polymyositis, the patient was started on prednisone, 60 mg daily. After 2 weeks, he had no significant clinical or subjective improvement in his pulmonary status; rather, he felt worse, and he was hospitalized with herpes zoster infection involving his right eye and treated with IV acyclovir. Because of the manifested herpes zoster infection following oral prednisone treatment, the patient declined further corticosteroids and conventional immunosuppressive therapy. He received three infusions of IV immunoglobulin at a dosage of 2 gm/kg monthly for 3 months. Following his last infusion, he clinically improved; his studies demonstrated significant improvement (CK, 327; aldolase level, 10; sedimentation rate, 30; and Dlco, 13.3, or 44% of predicted). The patient declined further treatment and maintenance therapy with immune-modulating agents, including IV immunoglobulin. He was monitored closely at regular intervals, with no evidence of recurrence by objective measurements. At 2 years since his presentation, his room air saturation was 98%, with no desaturation after 6 min of ambulation. His last PFTs demonstrated a Dlco of 16.5, or 55% of predicted (Table 1). He has no functional limitations. His muscle enzymes and inflammatory markers remain normal. An HRCT scan of his chest demonstrated complete resolution of the fibrotic changes and interstitial pneumonia (Fig 2).

ILD associated with polymyositis/dermatomyositis (ILD-PM/DM) often confers a poor prognosis and can be fatal despite aggressive treatment with corticosteroids and other immunosuppressive agents such as cyclosporine A and cyclophosphamide.1 This case report depicts a unique approach to the treatment of ILD-PM/DM. While there have been no randomized, controlled clinical trials to determine an efficacious regimen for ILD-PM/DM, current recommendations include the initiation of corticosteroids along with a steroid-sparing agent such as azathoiprine. Second-line agents include tacrolimus and cyclophosphamide, both of which have been used successfully in the treatment of moderate to severe myositis associated with ILD.2 IV immunoglobulin has been successfully employed in cases of polymyositis/dermatomyositis that were treatment resistant, but its mechanism of action remains unknown. In a double-blind, placebo-controlled trial, patients with dermatomyositis who were treatment resistant were given IV immunoglobulin at a monthly dosage of 2 gm/kg for 3 months. Nine out of 12 patients had marked improvement in their symptoms, two had mild improvement, and only one patient was unresponsive to this therapy.3 Another study of 35 patients with polymyositis who had failed multiple other therapies demonstrated significant clinical improvement in 25 patients when treated with IV immunoglobulin at a dosage of 1 gm/kg/d for 2 days monthly for 4 to 6 months. Twelve of 25 patients remained in full remission for a mean follow-up period of > 4 years following their initial course of IV immunoglobulin, resulting in the stoppage of medication in five patients and the use of low doses of steroids in seven patients.4 Only one small retrospective study has examined the efficacy of IV immunoglobulin in ILD-PM/DM. Of five patients hospitalized with refractory ILD-PM/DM and treated with 0.4 gm/kg of IV immunoglobulin for 5 days consecutively as a salvage therapy, only two of the five patients survived. There were no treatment-related adverse events.5 These patients were late in their disease course, and the natural history of polymyositis/dermatomyositis may mirror that of rheumatoid arthritis, in which early, aggressive intervention is associated with better outcome.

The histologic examination of the lung biopsy specimen demonstrated dominant inflammation with features of organizing pneumonia and little evidence of fibrosis. It must, however, be noted that the tissue sample was from transbronchial lung biopsies; the intensity and extent of fibrosis and inflammation can therefore be an underestimate of the overall pathologic condition, and thus should be interpreted with caution. The abnormalities seen on the HRCT scan were consistent with nonspecific interstitial pneumonia. The noted reversibility in the abnormal parenchymal changes suggests that the overall pathologic condition was dominated by an inflammatory component rather than dense fibrosis. It is very unlikely that poor ventilatory function, ineffective draining of the lower airways, or aspiration were playing a role in this patient’s pulmonary decline, given his preservation of lung volumes and the absence of obstructive airflow disease in his PFT results. There was no evidence of bronchiectasis or atelectasis on his HRCT scan of the chest, and he did not have productive cough. Thus, it seems very unlikely that his improvement could have been attributed to improved ventilation. The patient did not have overt symptoms of aspiration. Acknowledging that physiologically abnormal gastroesophagial reflux has been documented in patients with idiopathic pulmonary fibrosis without overt symptoms of abnormal gastroesophagial reflux, silent microaspiration is a possibility.6,7

IV immunoglobulin has not previously been studied as a first-line agent for rheumatologic diseases and is currently used as a salvage therapy. However, if IV immunoglobulin is capable of inducing sustained remission after brief treatment, as demonstrated in this patient, especially in the setting of significant pulmonary involvement, then it merits further consideration for investigation as a first-line therapy.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Other contributions: We are indebted to our patient for allowing us to report his clinical course. We acknowledge Dr Aashiyana Koreishi and Dr Rodney Schmidt (Department of Pathology, University of Washington Medical Center, Seattle, Washington) for their interpretations and photomicrographs of pathology specimens.

CK

creatine kinase

Dlco

carbon-monoxide-diffusing capacity

HRCT

high-resolution CT

ILD

interstitial lung disease

ILD-PM/DM

interstitial lung disease associated with polymyositis/dermatomyositis

PFT

pulmonary function test

Nawata Y, Kurasawa K, Takabayashi K, et al. Corticosteroid resistant interstitial pneumonitis in dermatomyositis/polymyositis: prediction and treatment with cyclosporine. J Rheumatol. 1999;267:1527-1533. [PubMed]
 
Yamasaki Y, Yamada H, Yamasaki M, et al. Intravenous cyclophosphamide therapy for progressive interstitial pneumonia in patients with polymyositis/dermatomyositis. Rheumatology (Oxford). 2007;461:124-130. [CrossRef] [PubMed]
 
Dalakas MC, Illa I, Dambrosia JM, et al. A controlled trial of high-dose intravenous immune globulin infusions as treatment for dermatomyositis. N Engl J Med. 1993;32927:1993-2000. [CrossRef] [PubMed]
 
Cherin P, Pelletier S, Teixeira A, et al. Results and long-term followup of intravenous immunoglobulin infusions in chronic, refractory polymyositis: an open study with thirty-five adult patients. Arthritis Rheum. 2002;462:467-474. [CrossRef] [PubMed]
 
Suzuki Y, Hayakawa H, Miwa S, et al. Intravenous immunoglobulin therapy for refractory interstitial lung disease associated with polymyositis/dermatomyositis. Lung. 2009;1873:201-206. [CrossRef] [PubMed]
 
Raghu G, Freudenberger TD, Yang S, et al. High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis. Eur Respir J. 2006;271:136-142. [CrossRef] [PubMed]
 
Tobin RW, Pope CE II, Pellegrini CA, Emond MJ, Sillery J, Raghu G. Increased prevalence of gastroesophageal reflux in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 1998;1586:1804-1808. [PubMed]
 

Figures

Figure Jump LinkFigure 1. Postero-anterior chest radiograph at initial presentation demonstrating irregular streaky opacities consistent with interstitial fibrosis at the lung bases bilaterally.Grahic Jump Location
Figure Jump LinkFigure 2. A, Initial high-resolution CT (HRCT) scan of the chest demonstrating interstitial pneumonia with ground glass opacification, mild intralobular septal thickening, and subtle honeycombing, with subpleural sparing consistent with features of nonspecific interstitial pneumonia. B, HRCT scan 20 months later demonstrates complete resolution of previously noted changes.Grahic Jump Location
Figure Jump LinkFigure 3. Histopathologic examination of transbronchial lung biopsy specimen. A, Plugs of granulation tissue characteristic of organizing pneumonia. A mechanically crushed inflammatory infiltrate is also present (hematoxylin and eosin stain, original magnification × 10). B, Mostly compressed alveolar lung tissue with mild lymphocytic inflammation in the top of the image (hematoxylin and eosin stain, original magnification × 20). Together the images show cellular (lymphocytic) interstitial pneumonitis with organizing pneumonia.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Clinical Course

The table presents the initial to final-testing results. Oxygen saturation was measured while breathing air at sea level, and 6-min walk tests were performed on level ground. CRP had returned to normal values by 5 months, and all indices with the exception of Dlco returned to normal over the course of 2 years. The Dlco, corrected to hemoglobin, remains mildly reduced. CK = creatine kinase; CRP = C-reactive protein; Dlco adjusted = carbon monoxide diffusing capacity adjusted for hemoglobin; RV = cresidual volume; TLC = total lung capacity.

a 

Normal values are < 285.

b 

Normal values are < 15.

c 

Normal values are < 10.

References

Nawata Y, Kurasawa K, Takabayashi K, et al. Corticosteroid resistant interstitial pneumonitis in dermatomyositis/polymyositis: prediction and treatment with cyclosporine. J Rheumatol. 1999;267:1527-1533. [PubMed]
 
Yamasaki Y, Yamada H, Yamasaki M, et al. Intravenous cyclophosphamide therapy for progressive interstitial pneumonia in patients with polymyositis/dermatomyositis. Rheumatology (Oxford). 2007;461:124-130. [CrossRef] [PubMed]
 
Dalakas MC, Illa I, Dambrosia JM, et al. A controlled trial of high-dose intravenous immune globulin infusions as treatment for dermatomyositis. N Engl J Med. 1993;32927:1993-2000. [CrossRef] [PubMed]
 
Cherin P, Pelletier S, Teixeira A, et al. Results and long-term followup of intravenous immunoglobulin infusions in chronic, refractory polymyositis: an open study with thirty-five adult patients. Arthritis Rheum. 2002;462:467-474. [CrossRef] [PubMed]
 
Suzuki Y, Hayakawa H, Miwa S, et al. Intravenous immunoglobulin therapy for refractory interstitial lung disease associated with polymyositis/dermatomyositis. Lung. 2009;1873:201-206. [CrossRef] [PubMed]
 
Raghu G, Freudenberger TD, Yang S, et al. High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis. Eur Respir J. 2006;271:136-142. [CrossRef] [PubMed]
 
Tobin RW, Pope CE II, Pellegrini CA, Emond MJ, Sillery J, Raghu G. Increased prevalence of gastroesophageal reflux in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 1998;1586:1804-1808. [PubMed]
 
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