Rapidly Progressive Interstitial Lung Disease in a

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1 CASE REPORT Rapidly Progressive Interstitial Lung Disease in a Dermatomyositis Patient with High Levels of Creatine Phosphokinase, Severe Muscle Symptomsand Positive Anti-Jo-1 Antibody Kosuke Kashiwabara and Kosuke Ota Abstract It has been reported that there is a subgroup of dermatomyositis (DM) patients with rapidly progressive interstitial lung disease (ILD) who have mild muscle symptoms, slightly increased levels of muscle enzymes, and absence of anti-jo- 1 antibody. A 51-year-old womanwith DMwas intubated requiring mechanical ventilation because of a rapidly progressing ILD in spite of the absence of the typical poor prognostic factors. A high dose or pulse therapy of corticosteroids was not effective, but additional treatment of cyclosporine gradually improved her respiratory condition. It is not clear whya rapidly progressive ILD occurred in this case lacking poor prognostic factors. However, if corticosteroid treatment is not effective, additional administration of cyclosporine in the early period of rapidly progressive ILD may rescue deteriorating cases. (Intrenal Medicine 41: , 2002) Key words: poor prognostic factors, bronchiolitis obliterans organizing pneumonia (BOOP), bronchoalveolar lavage fluid (BALF), corticosteroid, cyclosporine Introduction Dermatomyositis (DM) and polymyositis (PM) are inflammatory conditions of presumed autoimmune etiology in which the skeletal muscle is damaged by lymphocytic infiltration. The term DMis applied when polymyositis is associated with a characteristic skin rash or the classic lilac-colored rash (heliotrope) (1-4). A poor prognosis is seen in DMpatients with significant dysphagia, associated cancer or connective tissue diseases (1). In addition, it has been reported that there is a subgroup of DMpatients with rapidly progressive interstitial lung disease (ILD) who have mild muscle symptoms (2), slightly increased levels of muscle enzymes (5), and the absence of antibody to histidyl trnasynthetase, known as anti- Jo-1 antibody (6, 7). The present report describes a case of DM who had a rapidly progressive ILD requiring mechanical ventilation in spite of the presence of severe musclesymptoms, high levels of creatine phosphokinase (CPK) and anti-jo-1 antibody. Case Report A 5 1-year-old non-smoking womanconsulted our hospital because a chest roentgenogramtaken on a medical examination showed an abnormal lung shadow (Fig. 1A) in June A computed tomogram (CT) of the chest revealed asymptomatic air space consolidations with ground glass opacities in both lower lung fields (Fig. IB). She refused a transbronchial lung biopsy examination because she did not have any respiratory symptoms. She was admitted to our hospital on July 5, 2001 because of low grade fever, general fatigue with severe muscle pain and heliotrope rash with periorbital edema. On admission, her temperature was 37.5 C, heart rate 85 beat/min, respiratory rate 16/min, and blood pressure 94/62 mmhg. Laboratory data revealed a white blood cell count of 8,100/mm3, red blood cell count 425xlO4/jil, hemoglobin 12.3 g/dl, platelet count 14.8xlO4/jil, aspartate aminotransferase 354 U//, alanine aminotransferase 192 U//, lactate dehydrogenase 1,081 U//, alkaline phosphatase 186 U//, CPK 10,941 IU//, blood urea nitrogen 14.6 mg/dl, creatinine 0.64 mg/dl and CRP 1.7 mg/dl. Serum antibodies to anti RNP, anti Scl-70, anticentromere, and PR3-ANCAand MPO-ANCA were negative. The antinuclear antibody titer was 1: 640 and serum levels of anti Jo-1 antibody and KL-6 were 500 U/ml and 1,840 U/ml, respectively. Electromyogramand muscle biopsy examinations were not done. She complained of exertional dyspnea and weakness of the From the Respiratory Department, Taragi Municipal Hospital, Kumamoto Received for publication December 6, 2001 ; Accepted for publication February 27, 2002 Reprint requests should be addressed to Dr. Kosuke Kashiwabara, the Respiratory Department, Taragi Municipal Hospital, Taragi, Taragi-machi, Kumagun, Kumamoto

2 Severe ILD in DMLacking Poor Prognostic Factors ganizing though a material, revealed pneumonia (BOOP)-type DM-associated ILD. Altransbronchial lung biopsy failed to obtain diagnostic an analysis of bronchoalveolar lavage fluid (BALF) a large number of cells (10.3xl05 cell/ml) and in- creased percentages of neutrophils (23%) and lymphocytes (74%) with a decreased value of CD4/CD8 ratio (0.85) and B A right proximal limb muscles on July 10. DMwas diagnosed on the basis of the heliotrope rash, increased levels of CPKand muscle pain with systemic inflammatory reaction in addition to positive anti-jo-1 antibody using the diagnostic criteria by Bohan and Peter (8). The air space consolidations with ground glass opacities were diagnosed as bronchiolitis obliterans or- with ground glass opacities in B A Figure 1. Chest roentgenogram (A) and CT (B) revealed asymptomatic air-space consolidations both lower lung fields (June 15, 2001). Figure 2. Chest roentgenogram (A) and CT (B) showed that the consolidations expanded to the upper and middle lung fields and involved mainly the posterior area of the lung (July 10, 2001). Internal Medicine Vol. 41, No. 7 (July 2002) 585

3 Kashiwabara and Ota supported the radiologic diagnosis. In July 10, as a chest roentgenogramand CTshowed that the consolidations expanded to the middle lung fields and involved mainly the posterior side of the lung (Fig. 2), she was given 50 mg prednisolone per day. However she was given 1,000 mg methylprednisolone pulse Figure 3. Chest roentgenogram before intubation showed the consolidations did not improve after methylprednisolone pulse therapy (July 15, 2001). therapy on July 15 because of a rapidly progressing ILD (Fig. 3) with severe hypoxemia (arterial blood gas analysis on room air: ph 7.50, PaO Torr, PaCO Torr, HCCV 26.7 mmol//) and was intubated requiring mechanical ventilation onjuly 18. On July 20, she was given 100 mg cyclosporine per day as well as a second 1,000 mgmethylprednisolone pulse therapy because there was no improvement of DM-associated ILD. But the trough level of cyclosporine was 52 ng/ml and the ratio of PaO2 to inspired oxygen concentration (PaO2/FiO2) (9) decreased in spite of improved levels of LDHand CPK. After increasing the dose of cyclosporine (200 mg/day) and the third administration of 1,000 mg methylprednisolone on July 25, the trough level increased to 96 ng/ml and the PaO2/FiO2 ratio improved gradually. She was extubated on August 1. Chest CT showed that the consolidation had improved one month after the administration of 50 mg prednisolone and 200 mg cyclosporine per day (Fig. 4). After tapering of the prednisolone dose (5 mgper two weeks), she was discharged on October 5 with administration of 30 mg prednisolone and 200 mg cyclosporine per day. Discussion Pulmonary complications are important determinants of the clinical course of polymyositis and dermatomyositis (PM/DM) and commonlyoccur through four processes: aspiration pneumonia secondary to bulbar weakness, ventilatory insufficiency caused by muscle weakness of the chest wall and diaphragm, secondary infection, and ILD. ILD has been reported to be found in 5% to 9% of patients with PM/DM(10, ll), but in Japan, it has been emphasized that PM/DMwith ILD occurs muchmore Figure 4. Chest roentgenogram (A) and CT (B) showed the consolidation had improved one month after administrations of 50 mg prednisolone and 200 mg cyclosporine per day (August 27, 2001). 586

4 Severe ILD in DMLacking Poor Prognostic Factors frequently than has been previously reported (46%-8 1%) (7). Three major histopathological types of a PM/DM-associated ILD have been identified: BOOP, usual interstitial pneumonia (UIP) and diffuse alveolar damage (DAD) (12). In the present study, although a transbronchial lung biopsy failed to obtain diagnostic material, the consolidations with ground glass opacities were diagnosed as BOOP(13) because an analysis ofbalf showed an increased percentage of lymphocytes (74%) with a decreased value of CD4/CD8ratio. Tazelaar et al ( 12) reported that patients with BOOPhave a more favorable prognosis than patients with UIP and that patients with DADhave the worst prognosis. It has been reported that there is a subgroup of DMpatients with a rapidly progressive ILD whohave mild muscle symptoms, slightly increased levels of muscle enzymes, and the absence of anti-jo-1 antibody. Amyopathic dermatomyositis (ADM) was first described by Pearson (14) and is a disease which only has the cutaneous manifestations of DMwithout any clinical evidence of underlying inflammatory muscle disease. Euwer and Sontheimer (15) discussed that the diagnostic criteria set forth for DMby Bohan and Peter (I: polymyositis, II: dermatomyositis, III: myositis with malignancy, IV: childhood myositis, V: myositis with overlap syndromes) (8) should be altered to include a sixth diagnostic category, ADM.The rapidly progressive ILD has occurred in many DMpatients with mild muscle symptoms (2, 6) or slightly increased CPK levels (5, 7), but it is not clear whether or not all of such patients correspond to ADM. Anti-Jo-1 antibody is found in about 20% in PM/DMpatients and other types of antisynthetase antibodies, such as anti- PL-12, anti-oj, are also found (16). It has been reported that those autoantibodies are markers for PMpatients with ILD ( 1-4). In Japan, however, there are some reports in which a rapidly progressive ILD was related to DMpatients without anti- Jo-1 antibody (6, 7, 17, 18). Takizawa and Ito (19) reported that these patients often showed intractable respiratory failure even if when treated with a high dose or pulse therapy of corticosteroids and survive less than one year after onset. To the best of our knowledge, there has been no report in other countries that rapidly progressive ILD occurs frequently in DMpatients without anti-jo-1 antibody. One reason maybe that the incidence of ILD in PM/DMpatients is lower in the other countries than in Japan (7, 10, ll). Although the response to corticosteroid and other immunosuppressive agents is variable in PM/DM-associated ILD (2), it has been suggested that the presence of active inflammation in lung biopsy, especially BOOP, is predictive of a good therapeutic response (4, 20). In addition, ILD with anti-synthetase antibodies has been reported to be generally responsive to therapy (21). In the present case, however, the BOOPtype ILD progressed rapidly and she required intubation and mechanical ventilation in spite of the absence of the above-mentioned poor prognostic factors. Because she finally survived severe respiratory failure after treatments with both corticosteroid and cyclosporine, the question arises whether the disease was a poor prognostic ILD. Maeda et al (22) suggested that cyclosporine treatment rescues worsening cases of PM/DM-associatedILD. In the present case, the ILD also improved gradually after increasing the dose of cyclosporine in addition to the third pulse therapy of corticosteroids, then werecognized that cyclosporine treatment can rescue a deteriorating case with poor prognostic ILD. It is not clear whyrapidly progressive ILDoccurred in this case which lacked the poor prognostic factors, but the incidence of respiratory failure in PM/DMpatients may be higher than previously reported. A high dose or pulse therapy of corticosteroids may be initially selected on the basis of the presence of poor prognostic factors, but it is important to add administration of cyclosporine in the early period of a rapidly progressive ILD whenother treatments are not effective. Acknowledgements: The authors are indebted to Prof. J. Patrick Barron of the International Medical Communications Center of Tokyo Medical University for his review of this manuscript. References 1) Tandan R. Dermatomyositis and polymyositis. in: Harrison's Principles of Internal Medicine. 14th ed. Fauci AS, Braunwald E, Isselbacher KL, et al, Eds. McGraw-Hill, New York, 1998: ) Saag KG, Kline JN, Hunninghake GW. Idiopathic inflammatory myopathy, Interstitial lung diseases, in: Textbook of Pulmonary Diseases. 6th ed. Baum GL, Crapo JD, Celli BR, Karlinsky JB, Eds. Lippincott-Raven, New York, 1998: ) Dermatomyositis and polymyositis [editorial], in: Fraser and Pare's Diagnosis of Diseases of the Chest. 4th ed. Fraser RS, Miiller NL, Calmon N, Pare PD, Eds. W.B. Saunders Company, Philadelphia, 1999: ) King Jr TE. Polymyositis and dermatomyositis. Connective tissue disease, in: Interstitial Lung Disease. 3rd ed. Schwarz MI, King TE, Eds. B. C. Decker Inc., Hamilton, 1998: ) Fudman EJ, Schnitzer TJ. Dermatomyositis without creatine kinase elevation. Apoor prognostic sign. AmJ Med80: , ) Takizawa H, Suzuki N, YanagawaT, et al. Outcomein patients with interstitial lung disease and polymyositis-dermatomyositis: Subgroup with poor prognosis. Nihon Kyobu Shikkann Gakkai Zasshi 34: , 1996 (Abstract in English). 7) Takizawa H, Shiga J, Moroi Y, Miyachi S, Nishiwaki M, Miyamoto T. Interstitial lung disease in dermatomyositis: clinicopathological study. J Rheumatol 14: , ) Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med 292: , ) Kollef MH. Critical care, in: The Washington Manual of Medical Therapeutics. 30 th ed. Ahya SN, Flood K, Paranjothi S, Eds. Lippincott Williams & Wilkins, Philadelphia, 2001 : ) Frazier AR, Miller RD. Interstitial pneumonitis in association with polymyositis and dermatomyositis. Chest 65: , ) Salmeron G, Greenberg SD, Lidsky MD. Polymyositis and diffuse interstitial lung disease. A review of the pulmonary histopathologic findings. Arch Intern Med 141: , ) Tazelaar HD, Viggiano RW, Pickersgill J, Colby TV. Interstitial lung disease in polymyositis and dermatomyositis. Clinical features and prognosis as correlated with histologic findings. AmRev Respir Dis 141: , ) Collagen-vascular disease [editorial]. Diseases characterized primarily by linear and reticular opacities, in: High-resolution CT of the lung. 3rd ed. Webb WR, Miiller NL, Naidich DP, Eds. Lippincott Williams & Wilkins Inc., Philadelphia, 1998: ) Pearson CM. Polymyositis and dermatomyositis. in: Arthritis and Allied 587

5 Kashiwabara and Ota Conditions. A Textbook JL, Eds. Lea & Febiger, of Rheumatology. 9th Philadelphia, 1979: ed. McCarty DJ, Hollander 15) Euwer RL, Sontheimer RD. Amyopathic Invest Dermatol 100: 124S-127S, dermatomyositis: a review. J 16) Wasicek CA, Reichilin M, Montes M, Raghu G. Polymyositis and interstitial disease in a patient with anti-jo-1 prototype. AmJ Med 76: , ) Hidano A, Torikai S, Uemura T, Shimizu S. Malignancy and interstitial pneumonitis as fatal complications in dermatomyositis. J Dermatol 19: , ) Shinohara T, Hidaka T, Matsuki Y, et al. Rapidly progressive interstitial lung disease associated with dermatomyositis responding to intravenous cyclophosphamide pulse therapy. Internal Med 36: , 1997 (see comments). 1 9) Takizawa H, Ito K. Cyclophosphamide pulse therapy for rapidly progressive interstitial pneumonia in dermatomyositis. A new possibility for rescue? Internal Med 36: , 1997 (editorial; comment). 20) Schwarz MI, Matthay RA, Sahn SA, Stan ford RE, Marmorstein BL, Scheinhorn DJ. Interstitial lung disease in polymyositis and dermatomyositis: analysis of six cases and review of the literature. Medicine (Baltimore) 55: , ) Friedman AW, Targoff IN, Arnett FC. Interstitial lung disease with autoantibodies against aminoacyl-trnasynthetases in the absence of clinically apparent myositis. Semin Arthritis Rheum 26: , ) Maeda K, Kimura R, Komuta K, Igarashi T. Cyclosporine treatment for polymyositis/dermatomyositis: is it possible to rescue the deteriorating cases with interstitial pneumonitis? Scand J Rheumatol 26: 24-29,