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Clinically amyopathic dermatomyositis complicated by pleural effusion: case report, literature review, and proposed mechanism.

Dermatomyositis is a rare disease with an overall incidence of 9.63 per 1 million persons. Clinically amyopathic dermatomyositis (CADM) represents an estimated 20% of all cases of dermatomyositis according to a USA population-based study. (1) Case reports from Eastern Asia have shown a relatively high incidence of rapidly progressive and often fatal interstitial lung disease (ILD) in patients with CADM. (2) In contrast to the frequent ILD involvement in patients with CADM, development of pleural effusion is uncommon. Clinically important pleural disease has not been reported in patients with CADM.

An immune mechanism appears to be an important cause of pleural effusions in this case, given the positive response to immunosuppression and meticulous workup for other etiologies. In review of the literature, autoimmunity associated with underlying connective tissue disease (CTD) and ILD has been postulated as an important cause of pleural effusion in PM-DM, given the similar histological patterns and early-onset of ILD in both PM-DM and rheumatoid arthritis (RA). Optimal intervention is unknown; however, most patients respond to corticosteroid therapy.

Case Report

A 24-year-old Hispanic male with history of right index digital gangrene and multiple episodes of skin infections presented with fever, chills, and a chronic non-healing wound of the left leg. He was admitted and treated for infection of the leg. However, on hospital day 2, he developed dyspnea and respiratory failure with bilateral pleural effusions.

The patient had characteristic dermatomyositic skin lesions that included facial erythema, eyelid edema with heliotrope patches, positive Gottron's papules, mechanic's hands, holster sign, scaly erythema of knees, scalp, fingers, and plantar feet. In addition to these findings, he had calcinosis cutis on elbows, knees, hips, and fingers, as well as photosensitivity.

The patient was never diagnosed or treated with dermatomyositis prior to this evaluation. He was previously treated as presumed thromboangiitis obliterans based on the ischemic digit and history of heavy smoking. He was an immigrant from Mexico with limited access to medical care in the USA. At the time of this evaluation, he presented with characteristic skin findings and subjective weakness suggestive of dermatomyositis. Upon further interview, he mentioned having symptoms suggestive of Raynaud's disease since the age of 16 before developing the ischemic digit but was not evaluated. He denied previous treatment with immunosuppressive agents, such as systemic steroids or steroid-sparing agents.

The patient had minimal muscle weakness on physical exam. Serum creatine kinase and aldolase levels were normal. The anti-Jo-1 antibody was negative, as well as antinuclear (ANA) antibodies, SSA, SSB, double-stranded DNA, anti-Smith, anti-U1-RNP, scleroderma SCL-70, centromere, anti-PM/SCL, anti-SRP antibodies, rheumatoid factor, and cyclic citrullinated peptide IgG. Studies for HIV, tuberculosis, hepatitis B or C infections were negative, and pleural fluid, sputum, urine, and blood cultures were not rewarding. However, the serum Coccidioides IgM and IgG by EIA were both positive, as well as Coccidioides immunodiffusion for antibodies, but Coccidioides antibody complement fixation and pleural fluid Coccidioides antigen were negative. The skin biopsies were consistent with dermatomyositis. Direct immunofluorescence (DIF) was negative for systemic lupus erythematosus.

The admission chest x-ray revealed a small right-sided pleural effusion, but over two days, the chest radiograph and CT angiogram revealed a massive right and a small left pleural effusion, as well as dense consolidations bilaterally, and two mass-like opacities within upper lungs.

Pleural fluid was obtained which revealed a sterile exudative process with pH: 7.0, glucose 64 mg/dL, total nucleated cell count 7073 [mm.sup.3], with 27% lymphocytes, 43% neutrophils, and 30% mononuclear cells. The pleural fluid protein to serum protein ratio was 0.55, and lactate dehydrogenase ratio was 0.71. C-reactive protein was 134 mg/L (normal, 0 to 3 mg/L). A needle biopsy of a right upper lobe lung mass showed no evidence of granulomas, organisms, or malignancy but did reveal fibrous exudate with focal early organization, mild interstitial fibrosis, and nonspecific interstitial septal thickening with areas of mild cellularity (Fig. 1).

An echocardiogram demonstrated a left ventricular ejection fraction of 45% to 54%, normal left ventricle wall thickness without regional wall motion abnormalities, and mild pulmonary hypertension with an estimated pulmonary artery pressure of 43 mmHg. MRI of bilateral thighs did not show evidence of active myositis.

A diagnosis of clinically amyopathic dermatomyositis (CADM) was made. A right thoracostomy tube was placed for the massive pleural effusion. Staphylococcus aureus was isolated from the leg wound and treated with clindamycin. The pulmonary consolidations were thought to be due to aspiration or Coccidioides pneumonia with underlying dermatomyositis-associated interstitial lung disease. Vancomycin, piperacillin-tazobactam, and fluconazole were given. However, despite antimicrobial therapy, the thoracostomy tube drained more than 600 ml serous fluid per day for more than 1 week, and no evidence of other causes of the effusion were identified. Immunosuppressive therapy was initiated on day 9 with immunoglobulin, and intravenous methylprednisolone for 4 days, followed by oral prednisone 80 mg daily.

The pleural effusion improved rapidly, and the chest tube was discontinued after 4 days of immunosuppressive therapy. A chest x-ray on discharge showed minimal right subpulmonic effusion. As an outpatient, the patient was maintained on prednisone 60 mg daily and hydroxychloroquine 200 mg twice a day. Additional therapy included immunoglobulin 1 g/kg once monthly for a total of 5 months, mycophenolate 2 g/day, and prednisone at a slow tapering dose. There has been no recurrence of pleural effusion in 18 months.


It was recognized that patients with connective tissue diseases (CTDs) have associated pleuropulmonary abnormalities. At postmortem examination and thoracotomy, pleural lesions are commonly observed in connective tissue diseases (CTDs). (3) However, pleural effusions rarely are clinical problems except in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), with an incidence of 20% and 50%, respectively. (4) Although studies using High Resolution Computed Tomography (HRCT) demonstrate the common occurrence of pleural irregularities in patients with polymyositis-dermatomyositis (PM-DM), pleural effusions rarely occur. (3,5)

Five cases of clinically important pleural effusions in patients with PM-DM have been reported. (6) These cases are summarized in Table 1. This patient shares similarities with four of the patients from the literature in that pleural effusion was found in association with underlying interstitial lung disease (ILD) and autoimmune process secondary to PM-DM. The histopathology of ILD in PM-DM have shown several patterns, including bronchiolitis obliterans with organizing pneumonia, diffuse alveolar damage (DAD), nonspecific interstitial pneumonia (NSIP), and usual interstitial pneumonia (UIP). (10) These four subtypes are also common histological patterns of RA-associated ILD. (11) Interstitial lung disease is a common and early manifestation in many connective tissue diseases (CTDs), especially in patients with PM-DM (12) and rheumatoid arthritis. (11)

Both CD4+ T cells and the autoreactive B cells are known to produce pathogenic autoantibodies in systemic CTDs. Hakala and associates have reported a strong association of HLA-B8 antigen with the presence of pleural effusion in RA patients. (13) Introduction of antigens intrapleurally to previously sensitized mice produces granulomatous pleuritis with formation of RA cells in the effusion, suggesting an immune process initiating the pleuropulmonary pathology in RA. (14) Furthermore, Halla and associates have demonstrated that the pleura and pleural fluid mononuclear cells from patients with rheumatoid pleuritis synthesize IgG and IgM rheumatoid factor. (15) Their observations support the concept that local immune injury is responsible for pleuritis and pleural effusion formation in RA.

Overt clinical pleural effusion is exceedingly rare in PMDM. Pleural effusion in PM-DM has not been reported as an isolated finding but only in association with interstitial lung disease. The role of autoimmunity associated with underlying interstitial lung disease (ILD) and CTD itself has been postulated as an important cause of pleural effusion in PM-DM, given the similar histological patterns and early-onset of ILD in both PM-DM and RA. With the frequency of aspiration pneumonia and respiratory muscle weakness leading to atelectasis, it is difficult to be certain about the etiology of pleural effusion in PM-DM. Other causes, such as pulmonary infections, congestive heart failure, hypothyroidism, malignancy, and renal insufficiency, always need to be excluded or treated before initiating immunosuppressive therapy.

In the present case, studies for an infectious etiology were negative except the positive serum Coccidioides IgM/ IgG by EIA and immunodiffusion. Both serum antibody complement fixation and pleural fluid antigen detection tests for Coccidioides were negative, and the lung biopsy did not show evidence of granuloma with Coccidioides spherules. Accordingly, we cannot exclude the possibility of Coccidioides infection in this case, and the patient received fluconazole. However, we believe it was unlikely that the pleural effusion was caused by pulmonary coccidioidomycosis given the rapid onset, negative antibody complement fixation, fluid antigen detection, lung biopsy, and the absence of eosinophils found on pleural fluid analysis. Additionally, this patient did not have a clinical picture suggesting heart failure; the bilateral pleural effusion was exudative with no cardiomegaly on chest x-ray, and the echocardiogram did not show evidence of congestive heart failure.

The pleural effusion responded rapidly to immunosuppressive treatment instead of diuretics, suggesting an autoimmune rather than cardiac etiology. Finally, a needle biopsy of the lung mass showed no evidence of malignancy but did demonstrate interstitial fibrosis and nonspecific interstitial septal thickening with areas of mild cellularity.


Overt clinical pleural effusion in patients with PM-DM has seldom been reported. We describe a patient with clinically amyopathic dermatomyositis (CADM) in whom massive pleural effusion developed in association with interstitial lung disease. Clinical and radiographic responses to immunosuppressive treatment were excellent. We suggest that for patients with PM-DM complicated with massive pleural effusion, immune-mediated lung and pleural involvement appears to be the most important cause. However, other etiologies, such as infections, must be considered. Management should be individualized and may include not only immunosuppressive therapies but antimicrobial and potentially other agents.

Disclosure Statement

None of the authors have a financial or proprietary interest in the subject matter or materials discussed, including, but not limited to, employment, consultancies, stock ownership, honoraria, and paid expert testimony.

Ying Wu, M.D., Department of Internal Medicine, Maricopa Medical Center, Phoenix, Arizona. Sheetal Chhaya, D.O., and Bert Hurowitz, M.D., Department of Internal Medicine, Section of Rheumatology, Maricopa Medical Center, Phoenix, Arizona. Thomas Ardiles, M.D., Department of Internal Medicine, Maricopa Medical Center, and College of Medicine, University of Arizona, Phoenix, Arizona. Richard Carlson, M.D., Ph.D., Department of Internal Medicine, Section of Pulmonary and Critical Care Medicine, Maricopa Medical Center, and College of Medicine, University of Arizona, Phoenix, Arizona, and Mayo Clinic, Scottsdale, Arizona.

Correspondence: Richard Carlson, M.D., Ph.D, Maricopa Medical Center, 2601 Roosevelt Street, Phoenix, Arizona 85008;


(1.) Bendewald MJ, Wetter DA, Li X, Davis MD. Incidence of dermatomyositis and clinically amyopathic dermatomyositis: a population-based study in Olmsted County, Minnesota. Arch Dermatol. 2010 Jan; 146(1):26-30.

(2.) Mukae H, Ishimoto H, Sakamoto N, et al. Clinical differences between interstitial lung disease associated with clinically amyopathic dermatomyositis and classic dermatomyositis. Chest. 2009 Nov; 136(5):1341-7.

(3.) Highland KB, Heffner JE. Pleural effusion in interstitial lung disease. Curr Opin Pulm Med. 2004 Sep; 10(5):390-6.

(4.) Bouros D, Pneumatikos I, Tzouvelekis A. Pleural involvement in systemic autoimmune disorders. Respiration. 2008; 75(4):361-71.

(5.) Mino M, Noma S, Taguchi Y, et al. Pulmonary involvement in polymyositis and dermatomyositis: sequential evaluation with CT. AJR Am J Roentgenol. 1997 Jul; 169(1):83-7.

(6.) Roach DG, Salter WM. Polymyositis with pulmonary infiltrate and pleural effusion. Minn Med. 1980 Apr; 63(4):277-9, 281.

(7.) Miyata M, Fukaya E, Takagi T, et al. Two patients with polymyositis or dermatomyositis complicated with massive pleural effusion. Intern Med. 1998 Dec; 37(12):1058-63.

(8.) Mogulkoc N, Kabasakal Y, Ekren PK, Bishop PW. An unusual presentation of anti-Jo-1 syndrome, mimicking lung metastases, with massive pleural and pericardial effusions. J Clin Rheumatol. 2006 Apr; 12(2):90-2.

(9.) Sugie K, Tonomura Y, Ueno S. Characterization of dermatomyositis with coexistence of anti-Jo-1 and anti-SRP antibodies. Intern Med. 2012; 51(7):799-802.

(10.) Tazelaar HD, Viggiano RW, Pickersgill J, Colby TV Interstitial lung disease in polymyositis and dermatomyositis. Clinical features and prognosis as correlated with histologic findings. Am Rev Respir Dis. 1990 Mar; 141(3):727-33.

(11.) Lake F, Proudman S. Rheumatoid arthritis and lung disease: from mechanisms to a practical approach. Semin Respir Crit Care Med. 2014 Apr; 35(2):222-38.

(12.) Fathi M, Dastmalchi M, Rasmussen E, et al. Interstitial lung disease, a common manifestation of newly diagnosed polymyositis and dermatomyositis. Ann Rheum Dis. 2004 Mar; 63(3); 297-301.

(13.) Hakala M, Tiilikainen A, Hameenkorpi R, et al. Rheumatoid arthritis with pleural effusion includes a subgroup with autoimmune features and HLA-B8, Dw3 association. Scand J Rheumatol. 1986; 15(3):290-6.

(14.) Faarup P, Faurschou P. Rheumatoid arthritis cells in experimental pleuritis in mice. Acta Pathol Microbiol Immunol Scand A. 1985 Sep; 955):209-14.

(15.) Halla JT, Koopman WJ, Schrohenloher RE, et al. Local synthesis of IgM and IgM rheumatoid factor in rheumatoid pleuritis. J Rheumatol. 1983 Apr; 10(2):204-9.

Caption: Figure 1 Biopsy of right upper lobe lung mass showing fibrous exudate with focal early organization, mild interstitial fibrosis, and nonspecific interstitial septal thickening with areas of mild cellularity. To view this figure in color, see

Table 1 Summary of Published Cases of Pleural Effusion in

Age      Sex   Diagnosis   Serology              Lung Imaging/

67 (6)   F     PM          ANA (-); Elevated     Parenchymal
                             CK                    Infiltrate,
50 (7)   F     PM          Anti-Jo-1 (-),        Interstitial
                             Anti-SSA (+),         Edema
                             Elevated CK

34 (7)   M     DM          Anti-Jo-1(+),         Interstitial
                             Elevated              Pneumonia
43 (8)   F     Anti-Jo-1   Anti-Jo-1(+),         Interstitial
               Syndrome      Elevated              Fibrosis

61 (9)   M     DM          ANA(+), Anti-Jo-1     Interstitial
                             (+), Anti-SRP(+),     Lung Disease
                             Elevated CK
24       M     CADM        ANA (-)               Interstitial
                             Anti-Jo-1(-),         Fibrosis,
                             Anti-SRP(-),          Nonspecific
                             Aldolase/CK nl        Interstitial

Age      Treatment             Outcome

67 (6)   Thoracentesis,        Resolved
50 (7)   Thyroid               Resolved

34 (7)   Steroids,             Died of
           Cyclosporine          Respiratory
43 (8)   Pericardiocentesis,   Resolved
61 (9)   Thoracentesis,        Died

24       Thoracentesis,        Resolved

Age      Propable Pathogenesis     Effusion Type

67 (6)   Local immune pleuritis    Unknown

50 (7)   Combined process of       Transudative
           pleural inflammation,
           cardiomyopathy, and
34 (7)   Local immune pleuritis    Exudative

43 (8)   Local immune pleuritis    Exudative

61 (9)   Local Immune pleuritis    Exudative

24       Local immune pleuritis    Exudative


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Author:Wu, Ying; Chhaya, Sheetal; Hurowitz, Bert; Ardiles, Thomas; Carlson, Richard
Publication:Bulletin of the NYU Hospital for Joint Diseases
Article Type:Case study
Date:Jul 1, 2015
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