|Year : 2015 | Volume
| Issue : 1 | Page : 84-87
First presentation of systemic lupus erythematosus as interstitial lung disease: A unique scenario
Subrata Chakrabarti, Koushik Pan
Department of General Medicine, IPGMER, Kolkata, West Bengal, India
|Date of Web Publication||20-Jan-2015|
IPGMER, AJC Bose Road, Kolkata - 700 020
Interstitial lung disease (ILD) is regarded as an unusual manifestation of systemic lupus erythematosus (SLE). ILD in SLE patients usually develop in long-standing disease course and follows a chronic course. Isolated presentation of ILD in SLE without another involvement is quite striking. We report such a unique case where patient's first presentation in SLE was ILD.
يعتبر مرض الرئة ألخلالي مظهر غير عادي لمرضى الذئبة ألحمامي الجهازي. يتطور هذا المرض عند المرضى عادة إلى مرض مزمن لفترة طويلة. ويعتبر ظهور مرض الرئة ألخلالي كحالة منعزلة وبدون تدخل أمرًا غريبا. يعرض الباحثون حالة فريدة لمرض الذئبة ألحمامي الجهازي كان ظهورها لأول مرة بمرض الرئة ألخلالي.
Keywords: Interstitial lung disease, systemic lupus erythematosus, presentation
|How to cite this article:|
Chakrabarti S, Pan K. First presentation of systemic lupus erythematosus as interstitial lung disease: A unique scenario. Saudi J Med Med Sci 2015;3:84-7
|How to cite this URL:|
Chakrabarti S, Pan K. First presentation of systemic lupus erythematosus as interstitial lung disease: A unique scenario. Saudi J Med Med Sci [serial online] 2015 [cited 2020 Apr 6];3:84-7. Available from: http://www.sjmms.net/text.asp?2015/3/1/84/149696
| Introduction|| |
Systemic lupus erythematosus (SLE) is a multisystem connective tissue disorder with diverse clinical presentations. The disease has a wide spectrum of organ involvement with cutaneous, muskuloskeletal, renal, neurological, hematological and pulmonary manifestations. Interstitial lung disease (ILD) is not so common in SLE and even much rarer to be the initial manifestation of SLE without other organ involvement. We describe a patient of SLE who presented with ILD as the only manifestation.
| Case report|| |
A 40-year-old male non-diabetic and non-hypertensive presented to the outpatient department of SSKM Hospital with history of dry cough for the last 6 months along with exertional dyspnea for the last 2 months. He did not have any history of chest pain, palpitations, paroxysmal nocturnal dyspnea, orthopnea, bipedal edema and syncope. However, there was a history of inflammatory arthralgia involving both large and small joints of all four limbs for the last 6 months. There was no history of fever, rash, photosensitivity or oral ulceration. No history of skin tightening, dysphagia, dryness of eyes or mouth was documented. He was non-alcoholic and non-smoker. He had no travel history in the recent past or contact with patients suffering from active pulmonary tuberculosis. Patient had no significant occupational exposure to respiratory irritants, he was a school teacher by profession. He denied significant passive smoke exposure or use of illicit drugs. He was not being treated with any drug having established pulmonary toxicity. Also, he had no family history of lung disease. Possibilities considered at that time included ILD on a background of connective tissue disorder, pulmonary arterial hypertension, heart disease, pulmonary tuberculosis, sarcoidosis and occupational lung disease.
On general examination, he was pale, tachycardic with high volume, collapsing pulse (blood pressure 122/54 mm/hg) was noted. Respiratory system examination revealed bilateral end-inspiratory coarse crackles, mainly at lung bases. Oxygen saturation (SpO 2 ) in room air was 95%. Musculoskeletal examination revealed tenderness, swelling, restriction of motion in the wrist, elbow, proximal interphalangeal and knee joints bilaterally. Skin tightening was absent and Schirmer test showed no abnormality. Other system examination including the cardiovascular system (no evidence of pulmonary hypertension like loud or palpable P2, right ventricular enlargement) was normal.
Routine investigations revealed normocytic, normochromic anemia: Hb 10.2 g/dL, total leucocyte count 6300/cmm, platelet count 270,000/cmm. Reticulocyte production index was normal ruling out presence of hemolysis. Direct Coombs' test was negative. Liver and renal function tests, serum electrolytes, urine routine examination were normal. Chest x-ray revealed diffuse reticulonodular shadows in both lung fields. No hilar lymphadenopathy was noted [Figure 1]. Antinuclear antibody (ANA) by Hep 2 method was strongly positive (4+, 1:100 dilution); anti-Ds DNA was also positive in high titers 552 U/mL (normal <100 IU/mL); anti-Smith antibody was positive. Anticardiolipin, antiphospholipid, anti-Ro, anti-RNP, anti-Jo1 and anti-Scl 70 antibodies were negative. Blood for C3 and C4 showed diminished values; C3 level was 36 mg/dL (normal range: 90-180 mg/dL); C4 level was 14 mg/dL (normal range: 10-40 mg/dL) respectively. Angiotensin converting enzyme level was found to be normal and Mantoux test was negative. Ultrasonography of whole abdomen and pelvis was normal. Pulmonary function test showed restrictive pattern of lung disease with a forced expiratory volume in 1s (FEV1) 2.63 L (<80% predicted), Forced Vital Capacity (FVC) 3.15 L (<80% predicted) and FEV1/FVC ratio 84% (normal ≥80%). There was no evidence of obstruction. Diffusing capacity for carbon monoxide (DL CO ) was diminished (<80% predicted). On a 6-minute walk test, he could walk only 360 meters with drop in SpO 2 from 94% to 82% at end of 6 minutes. High resolution computed tomography (HRCT) of the thorax revealed diffuse bilateral ground glass opacification, interlobular septal thickening, bronchiectatic changes and honeycombing pattern in both lung fields, suggestive of ILD-predominantly nonspecific interstitial pneumonitis (NSIP) pattern with some atypical features (honeycombing) [Figure 2]. Thoracoscopic lung biopsy confirmed the histopathological variety as NSIP. Bronchoalveolar lavage (BAL) fluid analysis excluded any infectious, granulomatous or malignant pathology. Transthoracic echocardiography with Doppler imaging ruled out significant pulmonary arterial hypertension as the cause of dyspnea and cough in this patient. Normal sized left and right ventricles with normal systolic and diastolic function were noted.
|Figure 2: Bilateral diffuse bilateral ground glass opacification, nodular markings, interlobular septal thickening, bronchiectatic changes and honeycombing pattern suggestive of interstitial lung disease.|
Click here to view
A final diagnosis of SLE (with ILD-NSIP subtype as the only major organ involvement) according to SLICC criteria; which requires at least four criteria with at least one clinical and one immunologic criterion or biopsy proven lupus nephritis with ANA or Ds DNA positivity was made as the patient had fulfilled one clinical criteria (arthritis) and four immunologic criteria (ANA positivity, anti-Ds DNA positivity, anti-Smith antibody positivity and diminished complement titer). The patient was started on hydroxychloroquine sulfate and immunosuppression with corticosteroids and cyclophosphamide with advice for regular follow-up.
| Discussion|| |
Pulmonary involvement is common in SLE, occurring in up to 50% of patients. It is usually seen in cases of long standing SLE; however in only 2-3% it is the initial manifestation. The prevalence and severity of ILD appears to be lower in SLE than in the other connective tissue diseases.  Lung disorders are classified as primary (due to lupus) and secondary (due to other causes).  Pulmonary involvement can affect the pleura, airway, pulmonary vasculature, and parenchyma.  Pleurisy or pleural effusion is the most common pulmonary manifestation of SLE occurring in 30-60% cases. , Pleural effusion, ILD, pulmonary embolism, pulmonary vasculitis, pulmonary hypertension, pulmonary embolism, bronchiolitis obliterans with organizing pneumonia (BOOP), shrinking lung syndrome, diffuse alveolar hemorrhages, acute respiratory distress syndrome, opportunistic pulmonary infections and toxicity due to immunosuppressive drugs are the other pulmonary complications of SLE. Among secondary lung disorders, those due to infections are most common. 
The presence of ILD is rare in SLE occurring in 3-13% cases.  The onset is usually insidious, but it may be preceded by episode of acute pneumonitis. The presence of anti-Ro (anti SS-A) antibodies may be a risk factor for SLE-associated chronic ILD. ILD in SLE usually follows a benign course with a sub-acute to chronic presentation.  Patients present with chronic non-productive cough, dyspnea, recurrent pleuritic chest pain and decreased exercise tolerance. Asymptomatic involvement is more common and abnormalities in pulmonary function tests are seen in the majority of patients with SLE in some studies.  Decreased diffusing capacity of carbon monoxide (DLCO) along with abnormal chest x-rays may be detected in asymptomatic patients.  Pulmonary abnormalities do not correlate with immune parameters. The presence of lupus is suggested by the characteristic extrapulmonary and serological manifestations. Besides, restrictive abnormalities in pulmonary function tests (PFT), there is decreased DLCO and oxygen desaturation with exercise.
HRCT may be extremely helpful in diagnosis, and two patterns are frequently seen ground-glass appearance (consistent with biopsy showing cellular infiltrate pattern of NSIP) or reticular appearance usually with honeycombing (consistent with biopsy showing fibrotic pattern of usual interstitial pneumonia [UIP]). NSIP is the most commonly observed histopathological pattern of ILD in SLE.  In fact, NSIP is the most common histologic abnormality in those with collagen vascular disease and coexistent lung abnormalities.  Besides UIP and NSIP, other patterns seen include lymphocytic interstitial pneumonitis, cryptogenic organizing pneumonia, BOOP. However, Esmaeilbeigi et al. reported a case of SLE with desquamative interstitial pneumonia, a rare form of ILD.  An accurate diagnosis of the histopathological subtype of ILD is important to guide prognosis and management. Although UIP and NSIP may be both responsive to corticosteroids, the prognosis in patients with NSIP is slightly better than UIP. Moreover, histopathological subtypes may have a similar appearance on chest HRCT-UIP which typically presents with honeycombing, can present with ground-glass opacities and cystic nodules that suggest NSIP. Conversely NSIP in advanced stages may have significant honeycombing as in the index case.  Lung biopsy should only be done if the diagnosis is still in doubt despite the less invasive testing. The index patient underwent biopsy due to prominent honeycombing. In fact, surgical lung biopsy is the most sensitive method for exact subtyping of the ILD; but this procedure is invasive and so performed in <15% of patients. BAL can also be useful, especially to exclude infection, malignancy and granulomatous disease (specially tuberculosis and sarcoidosis).  Corticosteroids either alone or in combination with an additional immunomodulator is the mainstay of treatment. However, patients with established pulmonary fibrosis are unlikely to benefit from immunosuppressive therapy. In the case of progressive or severe disease but without features of irreversibility (lung fibrosis), high-dose steroid therapy is initiated along with intravenous/oral cyclophosphamide with a gradual transition to azathioprine or mycophenolate mofetil. Immunosuppressants like azathioprine or mycophenolate mofetil may also be used in corticosteroid ineffectiveness or dependence. , Trials for the use of investigational agents such as Pirfenidone in treatment of fibrotic lung disease are underway. 
Interstitial lung disease, as a presenting feature of SLE without any other significant systemic involvement is a unique presentation and this case reports such example. Kumar et al. reported a similar case in which, a 40-year-old Asian female patient presented with progressive dyspnea and was diagnosed as a case of ILD due to SLE. 
| Conclusion|| |
The highlighting point of this case is physicians and rheumatologists should bear in mind that ILD may be the initial manifestation of SLE. SLE should be a diagnostic consideration in patient with ILD, male or female, with or without other system involvement as with early diagnosis, suitable treatment is available but with late diagnosis, disease is usually irreversible and without possibility of any treatment, except palliation and obviously prognosis is dismal with shortening of lifespan.
| References|| |
Dubois EL, Tuffanelli DL. Clinical manifestations of systemic lupus erythematosus. Computer analysis of 520 cases. JAMA 1964;190:104-11.
Castelino FV, Varga J. Interstitial lung disease in connective tissue diseases: Evolving concepts of pathogenesis and management. Arthritis Res Ther 2010;12:213.
Pego-Reigosa JM, Medeiros DA, Isenberg DA. Respiratory manifestations of systemic lupus erythematosus: Old and new concepts. Best Pract Res Clin Rheumatol 2009;23:469-80.
Fekih L, Boussoffara L, Chaouachi S, Fenniche S, Abdelghaffar H, Akrout I, et al.
Thoracic manifestations of systemic lupus erythematosus. Tunis Med 2011;89:269-73.
Keane MP, Lynch JP 3 rd
. Pleuropulmonary manifestations of systemic lupus erythematosus. Thorax 2000;55:159-66.
Kakati S, Doley B, Pal S, Deka UJ. Pulmonary manifestations in systemic lupus erythematosus (SLE) with special reference to HR CT. J Assoc Physicians India 2007;55:839-41.
Hedgpeth MT, Boulware DW. Interstitial pneumonitis in antinuclear antibody-negative systemic lupus erythematosus: A new clinical manifestation and possible association with anti-Ro (SS-A) antibodies. Arthritis Rheum 1988;31:545-8.
Weinrib L, Sharma OP, Quismorio FP Jr. A long-term study of interstitial lung disease in systemic lupus erythematosus. Semin Arthritis Rheum 1990;20:48-56.
Beresford MW, Cleary AG, Sills JA, Couriel J, Davidson JE. Cardio-pulmonary involvement in juvenile systemic lupus erythematosus. Lupus 2005;14:152-8.
Fenlon HM, Doran M, Sant SM, Breatnach E. High-resolution chest CT in systemic lupus erythematosus. AJR Am J Roentgenol 1996;166:301-7.
Sant SM, Doran M, Fenelon HM, Breatnach ES. Pleuropulmonary abnormalities in patients with systemic lupus erythematosus: Assessment with high resolution computed tomography, chest radiography and pulmonary function tests. Clin Exp Rheumatol 1997;15:507-13.
Esmaeilbeigi F, Juvet S, Hwang D, Mittoo S. Desquamative interstitial pneumonitis in a patient with systemic lupus erythematosus. Can Respir J 2012;19:50-2.
Cheema GS, Quismorio FP Jr. Interstitial lung disease in systemic lupus erythematosus. Curr Opin Pulm Med 2000;6:424-9.
Ciftçi E, Yalçinkaya F, Ince E, Ekim M, Ileri M, Orgerin Z, et al.
Pulmonary involvement in childhood-onset systemic lupus erythematosus: A report of five cases. Rheumatology (Oxford) 2004;43:587-91.
Swigris JJ, Olson AL, Fischer A, Lynch DA, Cosgrove GP, Frankel SK, et al.
Mycophenolate mofetil is safe, well tolerated, and preserves lung function in patients with connective tissue disease-related interstitial lung disease. Chest 2006;130:30-6.
Azuma A, Nukiwa T, Tsuboi E, Suga M, Abe S, Nakata K, et al.
Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2005;171:1040-7.
Kumar A, Khan U, Shrestha B, Thapa S, Rizvi N. Interstitial lung disease as initial manifestation of systemic lupus erythematosus. J Nepal Health Res Counc 2013;11:83-5.
[Figure 1], [Figure 2]