International Journal of Rheumatic Diseases 2014
APLAR GRAND ROUNDS CASE
Pulmonary manifestation as initial presentation for systemic lupus erythematosus Chiew Gek KHOR, Sow Lai KAN and Bee Eng TAN Rheumatology Unit, Department of Internal Medicine, Penang General Hospital, Georgetown, Malaysia
Abstract We report a 29-year-old Malay man who had pulmonary manifestations as an initial presentation for systemic lupus erythematosus. He had prolonged hospitalization and was treated with intensive care therapy with immunosuppressants. Key words: plasmapheresis, pneumonitis, pulmonary hemorrhage, systemic lupus erythematosus.
INTRODUCTION Systemic lupus erythematosus (SLE) is a multisystem, autoimmune connective tissue disease and more common early manifestations include arthritis, cutaneous lupus, cytopneia and glomerulonephritis.1–3 Pulmonary and pleural involvement have been reported in 3–17% at the time of diagnosis and 7–36% over the course of the SLE.4 In addition, Font et al. and Orens et al. found pulmonary involvement in only 4–6% in SLE patients.5,6Acute pneumonitis and pulmonary hemorrhage are uncommon pulmonary manifestation of SLE. The reported mortality rate is as high as 50%.7,8 We describe a case of a young Malay man who presented with these conditions as his initial SLE disease manifestations.
CASE REPORT A 29 year-old Malay man presented with intermittent fever, productive cough with yellowish sputum, pleuritic chest pain for 1 month, progressive breathlessness and one episode of hemoptysis 4 days prior to admission. He gave a history of weight loss and loss of appetite for 1 year and polyarthritis, oral ulcer and alopecia for 1 month. His sister had passed away at a young Correspondence: Dr Chiew Gek Khor, Rheumatology Unit, Department of Internal medicine, Hospital Pulau Pinang, Jalan Residensi, 10990 Georgetown, Pulau Pinang, Malaysia. Email: [email protected]
age due to febrile illness suggestive of connective tissue disease. Physical examination on admission revealed blood pressure of 122/79 mmHg, with low-grade fever. He was hypoxic on air and with high-flow mask oxygen, his saturation was 95%. There were generalized crepitations over both lungs and bilateral pedal edema. However, cardiovascular and abdominal examination revealed no abnormalities. There were no cutaneous vasculitic lesions or rash. His laboratory investigation results showed: hemoglobin 8.8 g/dL (mean corpuscular volume: 92.4); total white cell count 11.4 9 1000/lL; lymphocytes 0.6 9 1000/lL; platelet count 168 9 1000/lL; Coomb test direct 4+, indirect 2+; C-reactive protein 166.6 mg/L (normal < 5 mg/L); erythrocyte sedimentation rate (ESR) 8 mm/h; hepatitis B surface antigen, hepatitis C virus antibodies, human immunodeficiency virus and VDRL (syphilis test) were all non-reactive, serum creatinine 143 lmol/L; albumin 23 g/L; globulin 51 g/L; alanine aminotransferase 60U/L, aspartate aminotransferase 83 U/L; C3 0.33 g/L (0.82–1.85 g/L), C4 0.036 g/L (0.15–0.53 g/L); urine microscopic protein 4+; red blood cell 5+; antinuclear antibodies (ANA) positive 1 : 640 homogenous; lupus anticoagulant strongly positive; anti-double-stranded DNA negative; antiextractable nuclear antibody, antineutrophil cytoplasmic antibodies (c-ANCA), anti-glomerular basement membrane antibody negative; arterial blood gas on high-flow mask oxygen pH7.3, partial pressure carbon
© 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd
C. G. Khor et al.
days. Unfortunately, on day 2 post-extubation, he developed respiratory distress. He subsequently was reintubated. The ventilator setting remained high using high-frequency oscillatory ventilation (HFOV) after reintubation. Copious blood during endotracheal tube (ETT) suction and increasing pulmonary infiltrates were noted 7 days after reintubation (Fig. 3). He remained anemic despite treatment for AIHA. In view of clinically high probability of pulmonary hemorrhage, plasmapheresis was commenced for three consecutive days. His prolonged ventilation was complicated by a multidrug-resistant organism (MRO) infection, which was treated accordingly with i.v. antimicrobials, including
Figure 1 Chest X-ray showing bilateral lung infiltrates (before intravenous methylprednisolone).
dioxide (pCO2) 56 mmHg, pO2 67 mmHg, HCO3 27.6; blood culture and sputum culture negative. A portable supine chest radiograph showed bilateral lung infiltrates (Fig. 1). Echocardiography was done showing normal ejection fraction with normal chamber sizes. There was no pericardial effusion seen. He was admitted to the intensive care unit (ICU), intubated and ventilated. A diagnosis of SLE (polyarthritis, oral ulcer, ANA positive, autoimmune hemolytic anemia [AIHA] with lymphopenia) with pneumonia (differential diagnosis of acute lupus pneumonitis) was made. Intravenous meropenem 1 g 8-hourly, azithromycin 500 mg daily and fluconazole 400 mg daily were initiated to cover for possible pneumonia. In addition, intravenous hydrocortisone 100 mg 8-hourly was given for possible lupus-related lung disease. Despite 3 days of maximum treatment, his condition continued to deteriorate and required a high ventilator setting. After a normal finding on bronchoscopy examination, a diagnosis of acute lupus pneumonitis was made. High-dose intravenous methylprednisolone 1 g daily (for 3 days) was therefore initiated, followed by intravenous (i.v.) hydrocortisone 100 mg 8-hourly. His lung ventilation and serial chest radiographs showed improvement after intravenous methylprednisolone (Fig. 2). He was successfully extubated shortly after completion of i.v. methylprednisolone. Despite his respiratory improvement, his hemoglobin was noted to be on a downward trend. Diagnosis of AIHA was made after excluding active bleeding. Intravenous immunoglobulin (0.4 g/kg/day) was given for five consecutive
2
Figure 2 Chest X-ray (after intravenous methylprednisolone).
Figure 3 Chest X-ray showing when patient developed copious bloody secretion from endotracheal tube.
International Journal of Rheumatic Diseases 2014
Pulmonary manifestation in SLE
underlying chest infection. Pulse i.v. cyclophosphamide was initiated after resolution of infection. With the above intensive treatment, he was taken off the ventilator and discharged after 60 days in ICU and 10 days of general ward stay. His chest radiography on follow-up showed significant improvement (Fig. 5).
DISCUSSION
Figure 4 High-resolution computed tomography scan showing reticular shadowing with subdural blebs in keeping with fibrosis. Also, there are generalized ground glass opacities of the lungs plus bilateral pleural effusion.
Figure 5 Chest X-ray upon discharge.
polymycin B, vancomycin, carbapenems,tigecycline and an antifungal (caspofungin). His condition was also complicated with acute renal failure requiring hemodialysis. High-resolution computed tomography (HRCT) of the thorax (Fig. 4) showed bilateral pleural effusion, reticular shadowing in keeping with fibrosis and generalized ground glass opacities of the lungs. Hence, the diagnosis of pneumonitis with pulmonary fibrosis was confirmed. He was given a repeat dose of i.v. immunoglobulin (0.4 g/kg/day for 5 days) 2 weeks after the first course in view of persistent lung disease and
International Journal of Rheumatic Diseases 2014
Systemic lupus erythematosus is diagnosed more often in women with a ratio of 9 : 1. The majority of patients develop pulmonary hemorrhage after diagnosis of SLE is established and usually in young women.9 In this case, we report a 29-year-old man who had pulmonary manifestation as his initial SLE presentation. He had acute pneumonitis and pulmonary hemorrhage. He survived after intensive management and ventilator support. Acute lupus pneumonitis is one of the most serious complications of SLE and occurs in 1–12% of patients.10,11 The most immediate concern for patients with suspected lupus pneumonitis is to exclude the presence of a pulmonary infection, because these two conditions may have similar presentations but requiring different treatments. Although acute lupus pneumonitis has high mortality despite glucocorticoids, high-dose systemic corticosteroids (prednisone 1–1.5 mg/kg/day in divided doses) remains the mainstay of treatment.12 Pulmonary hemorrhage is a rare but potentially fatal complication of SLE.13 Highdose corticosteroids with cyclosphosphamide greatly improves the prognosis.9 Erickson et al. reported 7/11 patients who failed high-dose corticosteroids and cyclophosphamide treatment (64%) survived after treatment with plasmapheresis.14 In summary, diagnosis of SLE with pulmonary manifestation must be suspected in young patients presenting with respiratory distress and failing to respond to conventional treatment. Infection, which usually sets in after prolonged hospitalization, mechanical ventilation and intensive immunosuppressants, needs to be recognized and treated adequately with antimicrobials.
REFERENCES 1 Cervera R, Khamashta MA, Font J et al. (2003) Morbidity and mortality in systemic lupus erythematosus during a 10year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore) 82, 299. 2 Alarcon GS, McGwin G Jr, Petri M, Reveile JD, RamseyGoldman R, Kimberly RP (2002) Baseline characteristics of a multiethnic lupus cohort: PROFILE. Lupus 11, 95–101.
3
C. G. Khor et al.
3 Wang F, Wang CL, Tan CT, Manivasagar M (1997) Systemic lupus erythematosus in Malaysia: a study of 539 patients and comparison of prevalence and disease expression in different racial and gender groups. Lupus 6, 248–53. 4 Cervera R, Khamashta MA, Font J et al. (1993) Systemic lupus erythematosus: clinical and immunologic patterns of disease expression in a cohort of 1,000 patients. The European Working Party on systemic lupus erythematosus. Medicine (Baltimore) 72, 113–24. 5 Font J, Cervera R, Ramos-Casals M et al. (2004) Clusters of clinical and immunologic features in systemic lupus erythematosus: analysis of 600 patients from a single center. Semin Arthritis Rheum 33, 217–30. 6 Orens JB, Martinez FJ, Lynch JP III (1994) Pleuropulmonary manifestations of systemic lupus erythematosus. Rheum Dis Clin North Am 20, 159–93. 7 Mintz G, Galindo LF, Fernandez-Diez J, Jimenez FJ, RoblesSaavedra E, Enriqyez-Casillas RD (1978) Acutemassive pulmonary hemorrhage in systemic lupus erythematosus. J Rheumatol 5, 39–50.
4
8 Zamora MR, Warner ML, Tuder R (1997) Diffuse alveolar hemorrhage and systemic lupus erythematosus. Clinical presentation, histology, survival and outcome. Medicine (Baltimore) 76 (3), 192–202. 9 Schwab EP, Schumacher HR Jr, Freundlich B, Callegari PE (1993) Pulmonary alveolar hemorrhage in systemic lupus erythematosus. Semin Arthritis Rheum 23, 8–15. 10 Wiedemann HP, Matthay RA (1992) Pulmonary manifestations of systemic lupus erythematosus. J Thorac Imaging 7, 1–18. 11 Cheema GS, Ouismorio FP Jr (2000) Interstitial lung disease in systemic lupus erythematosus. Curr Opin Pulm Med 6, 424–9. 12 Wiedemann HP, Matthay RA (1989) Pulmonary manifestations of the collagen vascular diseases. Clin Chest Med 10 (4), 677–722. 13 Badsha H, Teh CL, Kong KO, Lian TY, Chng HH (2004) Pulmonary hemorrhage in systemic lupus erythematosus. Semin Arthritis Rheum 33 (6), 414–21. 14 Erickson RW, Franklin WA, Emlen W (1994) Treatment of hemorrhagic lupus pneumonitis with plasmapheresis. Semin Arthritis Rheum 24, 114–23.
International Journal of Rheumatic Diseases 2014
APLAR GRAND ROUNDS CASE
Pulmonary manifestation as initial presentation for systemic lupus erythematosus Chiew Gek KHOR, Sow Lai KAN and Bee Eng TAN Rheumatology Unit, Department of Internal Medicine, Penang General Hospital, Georgetown, Malaysia
Abstract We report a 29-year-old Malay man who had pulmonary manifestations as an initial presentation for systemic lupus erythematosus. He had prolonged hospitalization and was treated with intensive care therapy with immunosuppressants. Key words: plasmapheresis, pneumonitis, pulmonary hemorrhage, systemic lupus erythematosus.
INTRODUCTION Systemic lupus erythematosus (SLE) is a multisystem, autoimmune connective tissue disease and more common early manifestations include arthritis, cutaneous lupus, cytopneia and glomerulonephritis.1–3 Pulmonary and pleural involvement have been reported in 3–17% at the time of diagnosis and 7–36% over the course of the SLE.4 In addition, Font et al. and Orens et al. found pulmonary involvement in only 4–6% in SLE patients.5,6Acute pneumonitis and pulmonary hemorrhage are uncommon pulmonary manifestation of SLE. The reported mortality rate is as high as 50%.7,8 We describe a case of a young Malay man who presented with these conditions as his initial SLE disease manifestations.
CASE REPORT A 29 year-old Malay man presented with intermittent fever, productive cough with yellowish sputum, pleuritic chest pain for 1 month, progressive breathlessness and one episode of hemoptysis 4 days prior to admission. He gave a history of weight loss and loss of appetite for 1 year and polyarthritis, oral ulcer and alopecia for 1 month. His sister had passed away at a young Correspondence: Dr Chiew Gek Khor, Rheumatology Unit, Department of Internal medicine, Hospital Pulau Pinang, Jalan Residensi, 10990 Georgetown, Pulau Pinang, Malaysia. Email: [email protected]
age due to febrile illness suggestive of connective tissue disease. Physical examination on admission revealed blood pressure of 122/79 mmHg, with low-grade fever. He was hypoxic on air and with high-flow mask oxygen, his saturation was 95%. There were generalized crepitations over both lungs and bilateral pedal edema. However, cardiovascular and abdominal examination revealed no abnormalities. There were no cutaneous vasculitic lesions or rash. His laboratory investigation results showed: hemoglobin 8.8 g/dL (mean corpuscular volume: 92.4); total white cell count 11.4 9 1000/lL; lymphocytes 0.6 9 1000/lL; platelet count 168 9 1000/lL; Coomb test direct 4+, indirect 2+; C-reactive protein 166.6 mg/L (normal < 5 mg/L); erythrocyte sedimentation rate (ESR) 8 mm/h; hepatitis B surface antigen, hepatitis C virus antibodies, human immunodeficiency virus and VDRL (syphilis test) were all non-reactive, serum creatinine 143 lmol/L; albumin 23 g/L; globulin 51 g/L; alanine aminotransferase 60U/L, aspartate aminotransferase 83 U/L; C3 0.33 g/L (0.82–1.85 g/L), C4 0.036 g/L (0.15–0.53 g/L); urine microscopic protein 4+; red blood cell 5+; antinuclear antibodies (ANA) positive 1 : 640 homogenous; lupus anticoagulant strongly positive; anti-double-stranded DNA negative; antiextractable nuclear antibody, antineutrophil cytoplasmic antibodies (c-ANCA), anti-glomerular basement membrane antibody negative; arterial blood gas on high-flow mask oxygen pH7.3, partial pressure carbon
© 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd
C. G. Khor et al.
days. Unfortunately, on day 2 post-extubation, he developed respiratory distress. He subsequently was reintubated. The ventilator setting remained high using high-frequency oscillatory ventilation (HFOV) after reintubation. Copious blood during endotracheal tube (ETT) suction and increasing pulmonary infiltrates were noted 7 days after reintubation (Fig. 3). He remained anemic despite treatment for AIHA. In view of clinically high probability of pulmonary hemorrhage, plasmapheresis was commenced for three consecutive days. His prolonged ventilation was complicated by a multidrug-resistant organism (MRO) infection, which was treated accordingly with i.v. antimicrobials, including
Figure 1 Chest X-ray showing bilateral lung infiltrates (before intravenous methylprednisolone).
dioxide (pCO2) 56 mmHg, pO2 67 mmHg, HCO3 27.6; blood culture and sputum culture negative. A portable supine chest radiograph showed bilateral lung infiltrates (Fig. 1). Echocardiography was done showing normal ejection fraction with normal chamber sizes. There was no pericardial effusion seen. He was admitted to the intensive care unit (ICU), intubated and ventilated. A diagnosis of SLE (polyarthritis, oral ulcer, ANA positive, autoimmune hemolytic anemia [AIHA] with lymphopenia) with pneumonia (differential diagnosis of acute lupus pneumonitis) was made. Intravenous meropenem 1 g 8-hourly, azithromycin 500 mg daily and fluconazole 400 mg daily were initiated to cover for possible pneumonia. In addition, intravenous hydrocortisone 100 mg 8-hourly was given for possible lupus-related lung disease. Despite 3 days of maximum treatment, his condition continued to deteriorate and required a high ventilator setting. After a normal finding on bronchoscopy examination, a diagnosis of acute lupus pneumonitis was made. High-dose intravenous methylprednisolone 1 g daily (for 3 days) was therefore initiated, followed by intravenous (i.v.) hydrocortisone 100 mg 8-hourly. His lung ventilation and serial chest radiographs showed improvement after intravenous methylprednisolone (Fig. 2). He was successfully extubated shortly after completion of i.v. methylprednisolone. Despite his respiratory improvement, his hemoglobin was noted to be on a downward trend. Diagnosis of AIHA was made after excluding active bleeding. Intravenous immunoglobulin (0.4 g/kg/day) was given for five consecutive
2
Figure 2 Chest X-ray (after intravenous methylprednisolone).
Figure 3 Chest X-ray showing when patient developed copious bloody secretion from endotracheal tube.
International Journal of Rheumatic Diseases 2014
Pulmonary manifestation in SLE
underlying chest infection. Pulse i.v. cyclophosphamide was initiated after resolution of infection. With the above intensive treatment, he was taken off the ventilator and discharged after 60 days in ICU and 10 days of general ward stay. His chest radiography on follow-up showed significant improvement (Fig. 5).
DISCUSSION
Figure 4 High-resolution computed tomography scan showing reticular shadowing with subdural blebs in keeping with fibrosis. Also, there are generalized ground glass opacities of the lungs plus bilateral pleural effusion.
Figure 5 Chest X-ray upon discharge.
polymycin B, vancomycin, carbapenems,tigecycline and an antifungal (caspofungin). His condition was also complicated with acute renal failure requiring hemodialysis. High-resolution computed tomography (HRCT) of the thorax (Fig. 4) showed bilateral pleural effusion, reticular shadowing in keeping with fibrosis and generalized ground glass opacities of the lungs. Hence, the diagnosis of pneumonitis with pulmonary fibrosis was confirmed. He was given a repeat dose of i.v. immunoglobulin (0.4 g/kg/day for 5 days) 2 weeks after the first course in view of persistent lung disease and
International Journal of Rheumatic Diseases 2014
Systemic lupus erythematosus is diagnosed more often in women with a ratio of 9 : 1. The majority of patients develop pulmonary hemorrhage after diagnosis of SLE is established and usually in young women.9 In this case, we report a 29-year-old man who had pulmonary manifestation as his initial SLE presentation. He had acute pneumonitis and pulmonary hemorrhage. He survived after intensive management and ventilator support. Acute lupus pneumonitis is one of the most serious complications of SLE and occurs in 1–12% of patients.10,11 The most immediate concern for patients with suspected lupus pneumonitis is to exclude the presence of a pulmonary infection, because these two conditions may have similar presentations but requiring different treatments. Although acute lupus pneumonitis has high mortality despite glucocorticoids, high-dose systemic corticosteroids (prednisone 1–1.5 mg/kg/day in divided doses) remains the mainstay of treatment.12 Pulmonary hemorrhage is a rare but potentially fatal complication of SLE.13 Highdose corticosteroids with cyclosphosphamide greatly improves the prognosis.9 Erickson et al. reported 7/11 patients who failed high-dose corticosteroids and cyclophosphamide treatment (64%) survived after treatment with plasmapheresis.14 In summary, diagnosis of SLE with pulmonary manifestation must be suspected in young patients presenting with respiratory distress and failing to respond to conventional treatment. Infection, which usually sets in after prolonged hospitalization, mechanical ventilation and intensive immunosuppressants, needs to be recognized and treated adequately with antimicrobials.
REFERENCES 1 Cervera R, Khamashta MA, Font J et al. (2003) Morbidity and mortality in systemic lupus erythematosus during a 10year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore) 82, 299. 2 Alarcon GS, McGwin G Jr, Petri M, Reveile JD, RamseyGoldman R, Kimberly RP (2002) Baseline characteristics of a multiethnic lupus cohort: PROFILE. Lupus 11, 95–101.
3
C. G. Khor et al.
3 Wang F, Wang CL, Tan CT, Manivasagar M (1997) Systemic lupus erythematosus in Malaysia: a study of 539 patients and comparison of prevalence and disease expression in different racial and gender groups. Lupus 6, 248–53. 4 Cervera R, Khamashta MA, Font J et al. (1993) Systemic lupus erythematosus: clinical and immunologic patterns of disease expression in a cohort of 1,000 patients. The European Working Party on systemic lupus erythematosus. Medicine (Baltimore) 72, 113–24. 5 Font J, Cervera R, Ramos-Casals M et al. (2004) Clusters of clinical and immunologic features in systemic lupus erythematosus: analysis of 600 patients from a single center. Semin Arthritis Rheum 33, 217–30. 6 Orens JB, Martinez FJ, Lynch JP III (1994) Pleuropulmonary manifestations of systemic lupus erythematosus. Rheum Dis Clin North Am 20, 159–93. 7 Mintz G, Galindo LF, Fernandez-Diez J, Jimenez FJ, RoblesSaavedra E, Enriqyez-Casillas RD (1978) Acutemassive pulmonary hemorrhage in systemic lupus erythematosus. J Rheumatol 5, 39–50.
4
8 Zamora MR, Warner ML, Tuder R (1997) Diffuse alveolar hemorrhage and systemic lupus erythematosus. Clinical presentation, histology, survival and outcome. Medicine (Baltimore) 76 (3), 192–202. 9 Schwab EP, Schumacher HR Jr, Freundlich B, Callegari PE (1993) Pulmonary alveolar hemorrhage in systemic lupus erythematosus. Semin Arthritis Rheum 23, 8–15. 10 Wiedemann HP, Matthay RA (1992) Pulmonary manifestations of systemic lupus erythematosus. J Thorac Imaging 7, 1–18. 11 Cheema GS, Ouismorio FP Jr (2000) Interstitial lung disease in systemic lupus erythematosus. Curr Opin Pulm Med 6, 424–9. 12 Wiedemann HP, Matthay RA (1989) Pulmonary manifestations of the collagen vascular diseases. Clin Chest Med 10 (4), 677–722. 13 Badsha H, Teh CL, Kong KO, Lian TY, Chng HH (2004) Pulmonary hemorrhage in systemic lupus erythematosus. Semin Arthritis Rheum 33 (6), 414–21. 14 Erickson RW, Franklin WA, Emlen W (1994) Treatment of hemorrhagic lupus pneumonitis with plasmapheresis. Semin Arthritis Rheum 24, 114–23.
International Journal of Rheumatic Diseases 2014
