British Journal of Radiology (2004) 77, 1042-1045
© 2004 British Institute of Radiology
doi: 10.1259/bjr/29049682
The CT halo: a new sign in active pulmonary sarcoidosis
K Marten, MD
E J Rummeny, MD
and
C Engelke, MD
Department of Radiology, Klinikum rechts der Isar der TU München, Ismaningerstr. 22, 81675 München, Germany
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Abstract
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A case of pulmonary sarcoidosis is presented characterized by multiple coalescent nodules and peripheral ground glass halos, which were fully reversible under repeat systemic glucocorticoid treatment. The differential diagnostic aspects of the pulmonary CT halo sign and its potential for indicating active reversible disease in patients with sarcoidosis is discussed.
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Introduction
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Sarcoidosis is a multisystem disorder of unknown cause characterized by the presence of non-caseating granulomatous inflammation that can affect various sites of the body. Although a self-limiting or treatment responsive process in most individuals, development of extensive pulmonary fibrosis may occur in up to about 20% of cases and lead to progressive worsening of lung function with respiratory failure or development of secondary pulmonary hypertension [1–3]. There is controversy about the possible influence of early pulmonary pathology on the natural history of pulmonary sarcoidosis and substantial effort has been dedicated to identifying patients at risk for a severe course employing immunological and biochemical markers and imaging. However, familiar diagnostic tests such as bronchoalveolar lavage (BAL) fluid cell count [4] and pulmonary gallium scintigraphy [5] are only moderately accurate for diagnosis of active disease, while pulmonary function tests, chest radiography or gas exchange studies on exercise do not allow for a differentiation of inflammatory from fibrotic components [6, 7]. Based on the hypothesis that reversible lesions are generally inflammatory and irreversible lesions are fibrotic, CT has been shown to be a valuable tool for assessment of lesion reversibility [8]. Brauner and co-workers demonstrated that nodules, irregularly marginated nodules, or alveolar or pseudoalveolar consolidations found in clinically active sarcoidosis always disappeared with clinical remission, whereas septal or non-septal lines and lung distortion remained unchanged [8]. Similarly, nodular patterns in sarcoidosis short-duration ground-glass opacities are usually reversible and were proposed to be indicative of alveolitis [8–11].
The high resolution CT finding of a pulmonary nodule or mass lesion surrounded by a rim of ground glass attenuation, referred to as the pulmonary CT halo sign [8] is commonly regarded as indicating an active, and (in benign disease) reversible pathological process. The CT halo sign is known to occur with a variety of pathologies but to the best of our knowledge, has not been reported in patients with sarcoidosis. We report a case of pulmonary sarcoidosis characterized by multiple coalescent pulmonary nodules on high resolution CT, and occurrence of ground glass halos with relapsing disease activity which resolved with systemic glucocorticoid therapy. This may be a new sign in active and potentially reversible pulmonary sarcoidosis.
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Case report
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A 30-year-old Caucasian woman presented to our centre with weight loss of 4 kg within 3 months and productive cough. She had a past medical history of ventricular fibrillations, which required the implantation of a cardiac defibrillator. On admission there was no clinical evidence of infection. The patient's laboratory investigations, including routine blood cell counts and electrolyte tests revealed erythrocyte sedimentation rate, c-reactive protein and serum angiotensin converting enzyme levels within normal limits. Liver function tests were unremarkable. Pulmonary function tests demonstrated normal forced expiratory volume in 1 s (FEV1), FEV1 in % of maximum vital capacity, and vital capacity values of 2.51 l (77% of predicted), 76.3% (92% of predicted), and 3.29 l (87% of predicted), respectively. There was no evidence of an obstructive or restrictive ventilation, or a diffusing disorder. The arterial blood gas analysis was normal.
The patient's chest radiograph revealed bilateral pulmonary focal round consolidations and nodular shadows but no mediastinal or hilar lymphadenopathy. A subsequent contrast-enhanced CT scan confirmed bilateral pulmonary nodules of 1–3 cm in size in an angiocentric distribution that were composed of multiple 1–2 mm coalescent nodular lesions visible in the nodule peripheries (Figure 1
a–c, g). The remainder of the pulmonary parenchyma was normal. In addition, there was evidence of right hilar lymphadenopathy. The patient underwent CT-guided transthoracic core biopsy of the largest (3 cm) of the coalescent nodular lesions in the anterior right upper lobe segment (Figure 1a–c), which revealed non-caseating granulomas with Langerhans' giant cells, suggestive of sarcoidosis. Tuberculosis was subsequently excluded by sputum cultures for Mycobacterium tuberculosis, and polymerase chain reactions for Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium intracellulare, which were negative. The sputum contained Langerhans' giant cells and the diagnosis of sarcoidosis was made. Concomitant myocardial involvement was suspected and the patient underwent additional cardiac 13N ammonia and 18FDG PET scans as well as a body 18FDG PET scan, which revealed pronounced left ventricular and septal myocardial tracer uptakes, commensurate with sarcoid involvement of the heart. The bilateral pulmonary nodules displayed increased 18FDG tracer activity.
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Figure 1. 30-year-old woman with pulmonary nodular and cardiac sarcoidosis. (a) Chest CT at the time of diagnosis displaying a 3 cm right upper lobe mass. Adjacent sections show that the pulmonary nodule is composed of innumerable coalescing micronodules (arrowheads), referred to as the "sarcoid galaxy sign" (b, c). This lesion was chosen for transthoracic biopsy. Follow-up CT scans after first course of steroid therapy 2 months later (d), showing size reduction of the nodule and no evidence of ground glass opacitiy. After 5 months, there occurred a large perifocal ground glass halo with relapsing clinical disease activity (e) and final follow-up 6 months after termination of second course of steroid therapy displaying a residual scar-like shaped density without any ground glass attenuation (f). Initial and follow-up CT scans showing the evolution of lingular, middle lobe and right lower lobe angiocentric nodules before therapy (g, arrowheads), their residua after first steroid therapy course with 60 mg day–1 prednisolone 2 months later (h, arrowheads), ground glass halos with relapsing sarcoid activity after steroid dose reduction to 10 mg day–1 prednisolone after 5 months (i, arrows) and final resolution and minimal scar-like residua 6 months after termination of second steroid course (j, arrowheads). Note that the ground glass halos have completely resolved.
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After oral glucocorticoid therapy was initiated with a daily prednisolone equivalent dose of 60 mg the clinical symptoms resolved and the patient was discharged. On follow-up high resolution CT after 2 months the pulmonary nodules had disappeared or reduced size significantly assuming irregular shapes (Figure 1
d, h). This treatment success prompted a tapering of the steroid dose to 10 mg day–1. However, the clinical symptoms recurred 5 months after initial presentation with chest pain and non-productive cough. On repeat CT recurrence of the bilateral pulmonary nodules in identical locations as on the initial scan was observed (Figure 1e, i). All nodules displayed an about 1 cm-wide peripheral halo of ground glass attenuation.
The steroid dose was increased to 20 mg day–1, with immediate cessation of clinical symptoms and a radiological response at follow-up CT showing complete resolution of perinodular ground glass opacities and disappearance of the majority of pulmonary nodules. Subsequently, the steroid dose was tapered to 5 mg day–1, without any further recurrence of symptoms. 6 months after termination of steroid therapy a final follow-up CT scan displayed a scar-like appearance of few nodular residua, and no other pulmonary or mediastinal abnormalities were present (Figure 1f, j). Currently the patient is well without clinical or laboratory evidence of active sarcoidosis.
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Discussion
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The high resolution CT finding of a halo sign is found with a variety of underlying disorders. In immunocompromised patients, it is associated with invasive pulmonary aspergillosis [12]. Other diseases known to cause perinodular ground glass halos in this patient group include atypical pneumonias [1], pulmonary Kaposi's sarcoma and lymphoproliferative disorders [13]. In immunocompetent patients pathologies that are associated with a solitary pulmonary CT halo include tuberculoma, non-Hodgkin's lymphoma, or bronchoalveolar carcinoma, whereas multiple such lesions can occur with metastatic disease of highly vascularized locally invasive neoplasia such as angiosarcoma, teratoma or malignant melanoma and with benign disease including Wegener's granulomatosis, cryptogenic organizing pneumonia [13], drug-induced lung disease [14] and infectious eosinophilic pneumonitis [15]. Although the rim of ground glass opacity was demonstrated in a variety of diseases to represent coagulation necrosis or haemorrhage surrounding a central nodule, in neutropenic patients the pulmonary CT halo sign has been claimed sufficiently characteristic for early invasive pulmonary aspergillosis to warrant antimycotic therapy without further diagnostic procedures [12, 16]. However, some investigators found low positive predictive values (53–58%) for this diagnosis [17]. Nevertheless, in general the halo sign can be considered suggestive of an active disease process [1, 12].
Our patient with active pulmonary sarcoidosis showed a clear evolution of CT findings through the course of the disease. The major initial features were bilateral coalescent angiocentric pulmonary nodules with tiny peripheral satellite lesions, which had previously been referred to as the "sarcoid galaxy sign", reflecting numerous confluent granulomatous lesions [18]. In conformity with remission of clinical symptoms, these lesions responded to steroid administration. When steroid doses were tapered, nodule residua increased in size displaying multiple CT halo signs which, to our best knowledge, have not been reported in sarcoidosis. Interestingly, in keeping with the patient's clinical symptoms the halos and the majority of nodules disappeared simultaneously upon repeat increase of glucocorticoid dose.
As opposed to the CT halo sign, the appearance of diffuse ground glass opacity (GGO) in pulmonary sarcoidosis has been repeatedly investigated [8, 9, 19]. Although its incidence may have been overestimated in studies using 10 mm collimation it is relatively frequent (stage I: 9%, stages II, III 20–30%) in radiographically positive disease stages [19–22]. Similarly to nodular patterns in sarcoidosis short-duration GGO is usually reversible and thought to be indicative of alveolitis [8–11]. Alveolitis was investigated by Takemura and co-workers, who correlated an increased percentage of T-lymphocytes in BAL fluid with the degree of inflammation [23]. Swelling and bleb formation of the endothelium of alveolar capillaries and changes in the capillary basement membrane were significantly increased in sarcoid alveolitis as compared with hypersensitivity pneumonitis. However, changes of the alveolar epithelium were non-significant, suggesting a pathogenetic role of a minimal capillaritis or granulomatous vasculitis, which was found in patients with only minimal parenchymal disease distant from the involved vessels [24]. In an isolated case report with histological correlation GGO areas corresponded to lesions of such "alveolar septal" inflammation that could be attributed to varying degrees of reversible capillaritis, alveolitis and microgranuloma formation [25]. On the other hand, chronically stable GGO is more likely to represent minimal fibrosis [19]. The reversibility of short-duration GGO areas in stage II disease has also been demonstrated in studies by Krychniak and Brauner [8, 26]. Areas of ground-glass attenuation disappeared in 69% upon clinical remission, but persisted in long-standing disease [8]. Given the rapidly changing HRCT features in our patient, it is reasonable to assume that in sarcoidosis the appearance of the CT halo sign and of diffuse GGO share similar pathological features.
In conclusion, we describe a new sign in pulmonary sarcoidosis, which in our patient was indicative of active reversible disease. Although further studies with radiological-pathological correlations are required to elucidate this issue, the CT halo sign may serve as a valuable adjunct for radiological assessment of activity and potential reversibility of pulmonary sarcoidosis.
Received for publication November 14, 2003.
Revision received May 5, 2004.
Accepted for publication June 16, 2004.
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Abstract
Introduction
