Case CommuniCations IMAJ • VOL 17 • OctOber 2015 Pulmonary granulomatous inflammation in systemic lupus erythematosus Lone Sølling Avnon MD1, Alexander Smoliakov MD2, Igor Sinelko MD3 and Mahmoud Abu-Shakra MD4 1Pulmonary Clinic, 2Department of Radiology and Imaging, 3Pathology Institute and 4Rheumatic Diseases Unit, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel the primary diagnosis of granulomatous KeY wOrDs: granulomatous inflammation (GI), disease of the lungs [1]. PATIENT DescriPtiOns systemic lupus erythematosus (SLE), Primary involvement of the lung paren- Patient 1 sarcoidosis chyma in systemic lupus erythematosus A 23 year old single woman, born in IMAJ 2015; 17: 650–652 (SLE) is quite rare [2], and a new pulmo- Israel, presented with irritating dry cough nary infiltrate is more frequently the result of 4 months duration. The cough did not of common and opportunistic infections. disturb her at night, but for 6 weeks before Granulomatous disease in the lungs of her assessment she began to suffer from patients with SLE is very rare. While a night-time sweating. The chest X-ray was ranulomatous inflammation (GI) in literature search identified only a single normal but high resolution chest com- g the lung can be associated with infec- case report of a patient with acute lupus puted tomography (CT) showed a fine tion (mycobacterial) or immunological pneumonitis who presented with a miliary bilateral micronodular pattern [Figure conditions (granulomatosis with angiitis), pattern on chest and lung histopathology 1A]. or it may be idiopathic (sarcoidosis) [1]. of bronchocentric granulomatosis [3], the Five years earlier, at age 17, she had The pathological features (presence of development of sarcoidosis among patients been diagnosed with SLE based on skin necrosis, cohesiveness and coalescence of with SLE has been reported. rash, arthritis, peritonitis, positive anti- granulomas, fibrosis and type of inflam- We report here two patients with SLE nuclear antibodies (ANA), positive anti- matory infiltrate), microbiological data on treatment with low dose steroids who DNA, and high titers of anticardiolipin (fungal and mycobacterial cultures) and presented with pulmonary findings proven antibodies. She was started on prednisone, radiological characteristics of the granu- in transbronchial biopsies to be non-nec- aspirin and hydroxyl-chloroquine. One loma are essential measures to determine rotizing epithelioid GI. year later she presented with nephritis, Figure 1. Patient 1: [a] Chest CT showing a fine micronodular pattern bilaterally more in the middle lung fields, both centrally and peripherally. [B] Transbronchial biopsy shows non-necrotizing GI with central multinucleated cells a B 650 IMAJ • VOL 17 • OctOber 2015 Case CommuniCations and renal biopsy revealed diffuse prolifer- findings. At her last assessment at the granulomata with many multinucleated ative glomerulonephritis. She was treated clinic her clinical condition is stable. giant cells. The culture for Mycobacterium with intravenous cyclophosphamide every was sterile. He attends our follow-up clinic other week, enalapril and high dose of Patient 2 and is not on any additional treatment prednisone. After 3 months on this thera- A 65 year old man with SLE presented with apart from his maintenance regimen of peutic regimen the cyclophosphamide was fever, cough, and weight loss of 4 kg over 2 prednisone 5 mg/day. He is clinically replaced by azathioprine and prednisone months. He was born in South America and stable and his chest CT has not changed. was gradually reduced to 5 mg/day. For 30 immigrated to Israel in 1980. He is retired months she continued this regimen with but previously worked in a factory without normalization of the renal function until chemical exposures. He is a non-smoker. cOmment her present complaints. The chest X-ray showed a right middle We present two patients with SLE who sub- She worked as a bank teller and was not lobe infiltrate. He was treated with anti- sequently developed a pulmonary granu- subject to any environmental exposures; biotics. Six weeks later he was examined lomatous inflammation (GI) while treated however, she smoked 6–10 cigarettes a day. in the pulmonary clinic at which time with low dose systemic steroids; the first The physical examination did not reveal the cough had resolved. He denied fever, patient also received azathioprine. skin rash, lymphadenopathy or clubbing. fatigue and excessive sweating, and felt The pathogenesis of GI in both cases is The lung, heart and abdomen examina- well, but the chest X-ray showed that the unknown. Pulmonary infections contribute tion was normal. Laboratory tests showed infiltrate had not resolved. significantly to the morbidity and mortality a hemoglobin level of 12.2 g/dl. The white At the age of 46 he had been diagnosed of patients with SLE [2]. In a large European blood cell count (WBC) was 5100/ml with SLE based on acute lupus rash, arthri- study, 11.7% of patients with SLE devel- with 79% neutrophils. Platelet count was tis, positive ANA, positive anti-DNA, low oped major lower respiratory tract infec- 375,000/ml. Serum electrolytes, kidney and complement levels and leukopenia. His tion during a mean follow-up of 10 years. liver functions tests were normal. Globulin kidney functions were normal. He was Mycobacterial and fungal infections were level was 2.9 g/dl and lactate dehydrogenase treated with systemic steroids. At age 52 excluded in our cases. The histopathological (LDH) was slightly elevated 495 U/L (nor- he presented with renal failure (creatinine report and cultures from the BAL did not mal range 150–480 IU/L). Pulmonary func- 2.2 mg/dl). A kidney biopsy was not per- identify microbial agents. tion tests revealed a moderate restrictive formed. An increase in the systemic steroid Non-infectious causes of pulmonary ventilatory defect with a reduction in mon- dosage resulted in normalization of his kid- GI include, among others, hypersensitiv- oxide diffusion capacity (DLco). Forced ney function and he continued on 5 mg/ ity pneumonitis, vasculitis, berylliosis vital capacity (FVC) was 2.23 L (61%), slow day prednisone until his referral. and, most frequently, sarcoidosis [1]. In vital capacity (SVC) 2.19 L (61%), total lung The physical examination showed tem- both our patients the pathologist noted the capacity (TLC) 2.65 L (68%), monoxide dif- perature of 36.6°C, breath rate 14/minute, presence of well-formed GI consistent with fusing capacity (DLco) 46%, percentage blood pressure 150/80 mmHg and regular sarcoidosis [Figure 1B]. The occurrence of predicted for gender, age and height. pulse of 66/min. The skin examination sarcoidosis in patients with SLE has been A bronchoscopy was performed, reveal- demonstrated vitiligo. There were no pal- reported from two centers [4]. In the first ing normal airways without secretions. pable lymph nodes. Examination of the study sarcoidosis was diagnosed in 1 of Bronchoalveolar lavage (BAL) showed lungs, heart and abdomen was normal. 144 SLE patients (0.7%), and in the second 320 cells/ml; 12% were neutrophils, 10% Laboratory tests demonstrated hemo- study in 3 of 300 SLE patients (1%). This lymphocytes, and 78% macrophages. globin 15.3 g/dl, WBC count 6930 cells/ prevalence is higher than that of sarcoidosis The transbronchial biopsy showed non- ml with 81.3% neutrophils, and platelet in the general population, which in Israel necrotizing granulomatous inflammation count 192,000 cells/ml. He had normal has been reported to be 0.8/100,000 and in with giant multinucleated cells [Figure 1B]. electrolytes, kidney and liver functions. Europe and the United States 7–50/100,000 There was no evidence ofMycobacterium , The globulin level was 3.3 g/dl. Pulmonary [5]. Of 34 Israeli patients with sarcoidosis, fungi or Pneumocystis jirovecii in the spe- function tests were normal with a slightly 10 had a positive antinuclear antibody cial stains or in the cultures. reduced DLco, 65%. and 2 had positive antibodies to double- Within a few weeks of increasing the The chest CT scan showed an infiltrate stranded dsDNA, but none of these patients dose of systemic steroids to 30 mg/day the with air bronchogram in the right middle had clinical evidence of SLE, nor did they cough and night-time sweating resolved, lobe and a slight bilateral reticular nodular develop it over time [5]. In the European as did the restrictive ventilator defect, and pattern without lymphadenopathy. This report, of 1000 SLE patients none was DLco increased to 69%. Eighteen months did not resolve after 3 months of follow- reported to suffer concomitant sarcoidosis. later a repeat high resolution chest CT up. Bronchoscopy with transbronchial During the period 1979–2007, 19 pa- showed no evidence of the radiological biopsy showed multiple non-necrotizing tients (mean age 46 years, range 20–82) 651 Case CommuniCations IMAJ • VOL 17 • OctOber 2015 were reported with a concomitant diag- with pulmonary GI associated with SLE, histopathological features of the GI were nosis of SLE and sarcoidosis; only one was five had bilateral hilar adenopathy and consistent with sarcoidosis, our patients male. Ten patients were initially diagnosed two had mediastinal lymphadenopathy. did not have classic features of sarcoidosis with SLE and subsequently with sarcoid- Acute lupus pneumonitis and acute characterized by multisystem involve- osis, 5 patients were diagnosed with both alveolar hemorrhage are recognized but ment. The combination of pulmonary GI conditions simultaneously, while 4 were rare complications of SLE [2]. A recent with SLE should perhaps be considered yet first diagnosed with sarcoidosis and subse- case report suggested a new and separate another overlap syndrome, which appears quently developed SLE. The development entity of SLE-associated acute granulo- to occur in up to 1% of SLE patients. of the second condition was reported to matous pneumonitis [3]. The chest CT be associated with a reduction in the dos- scan of their patient showed very similar correspondence age of systemic steroids in 9 of 14 patients.