Loading...
 

January - March 2018: 
Volume 31, Issue 1

Click on the image to download the Issue in PDF format.

ARCHIVE

Pneumon 2018, 31(1):44-48
Reversed halo sign in community acquired pneumonia. A case report
Authors Information
1Pneumonology Department of General Hospital of Serres, Greece
Abstract

Reversed halo sign (RHS) is defined as central annular ground-glass opacity surrounded by a ring of denser consolidation at least 2mm thickness. It was first described by Voludaki et al. in a case report of two COP cases and later concluded that it was specific to cryptogenic organizing pneumonia. Since then, the RHS was associated with a wide range of pulmonary diseases: pulmonary fungal infections, tuberculosis, community – acquired pneumonia, sarcoidosis, pulmonary neoplasms, Wegener granulomatosis, pulmonary infraction and other diseases. We report a patient case of community-acquired pneumonia with of RHS on HRCT, and we review the literature on this radiological sign. We present a 70 years-old male, who was admitted to emergency department with lower tract respiratory infection symptoms, HRCT was performed and revealed multiple round ground-glass opacities fringed with peripheral consolidation in both lungs. The patient was diagnosed with community-acquired pneumonia and treated successfully with respiratory quinolone. Unfortunately, the infectious agent was not determined, as well as bronchoscopy with BAL was not helpful for diagnosis. At follow up, in 21 days and 4 months, the patient remained asymptomatic, and chest CT revealed a clear improvement. Finally, reversed halo sign has been reported in a wide range of conditions, and investigation of its aetiological factors is required.

Full text

Introduction

Reversed halo sign, also known as atoll sign, is defined as central ground-glass opacity surrounded by denser consolidation of crescentinc or ring shape of at least 2mm thickness. It was first described on high-resolution CT (HRCT) as being specific for cryptogenic organizing pneumonia (COP). Since then, the reversed halo sign was associated with a wide range of pulmonary diseases: pulmonary fungal infections, pneumonocystis pneumonia, tuberculosis, community – acquired pneumonia, lymphomatoid granulomatosis, Wegener granulomatosis, lipoid pneumonia, sarcoidosis, pulmonary neoplasms, pulmonary infraction and following radiation and radiofrequency therapy of pulmonary malignancies.

Case Presentation

We are reporting a 70 years-old male patient who was admitted to our hospital with a one-week history of fever and non-productive cough. The patient also complained for anorexia and weight loss. He was treated with antibiotics (Amoxicillin/Clavulanic Acid Tb 875/125mg 1x2 + Clarithromycin Tb 500mg 1x2) five days before his admission by his general practitioner. Due to the persistence of fever he was referred to our clinic. His past medical history was unremarkable for any chronic medical illness. He was a smoker of 50 pack/years and denied ethanol, drug abuse and recent travel. No drug allergies were noted.

At presentation the patient’s body temperature was 37.8°C, blood pressure was 120/75 mm Hg and percutaneous oxygen saturation was 97% in room air. His heart rate was 100 to 110 beats per minute with a sinus rhythm revealed on ECG. Respiratory rate was 18 to 20 breaths per minute. His heart sounds were normal with no murmurs or extra sounds. Auscultation revealed coarse crackles over the posterior right lung. There was no clubbing, cervical or axillary lymphadenopathy, skin lesions or joint swelling. Physical examinations of the rest systems did not provide any significant information.

The patient’s white blood count was 5,760 cells/mm3 (lymphocytes = 20%, neutrophils = 69%, and atypical = 8%). CRP level was 8.4 mg/L.

At presentation the chest X-ray showed a consolidative pattern in the right middle and lower lung fields. Chest computed tomography (CT) revealed multiple round ground-glass opacities fringed with consolidation in both lungs, namely the “reversed halo sign” (Figure 1).

Figure 1. Multiple round ground-glass opacities fringed with consolidation in both lungs.
 

Afterwards bronchoscopy with BAL was done and didn’t reveal any remarkable endoscopic findings (bronchoalveolar lavage fluid (BALF) cell analysis: alveolar macrophages 84%, CD4+ 5%, CD8+ 3%, CD4+/CD8+ =1.6, neutrophils 5%, squamous epithelial cells 3%). Tests for antinuclear antibody (ANA) and anti neutrophil cytoplasmic antibody (ANCA) were negative. The Legionella and Pneumonococcal antigen urine testing were negative. Blood cultures were negative. Sputum cultures were not performed, since the patient had no expectoration.

The patient was diagnosed with community – acquired pneumonia and treated successfully with Moxifloxacin i.v. (400mg/d), without receiving corticosteroids. The symptoms were improved dramatically and he became afebrile within the fourth day. At follow up the patient remained afebrile. Computed tomography of the chest (after 21 days and 4 months) revealed a clear improvement (Figure 2, Figure 3).

Figure 2. After 21 days
 


Figure 3. After 4 month
 

Review

The reversed halo sign was first described and associated with COP1, but it is not specific to this disease. A wide spectrum of conditions can manifest with the reversed halo sign on chest HRCT2.

The reversed halo sign (RHS) is characterized by a focal area of ground-glass opacity surrounded by a more or less complete ring of consolidation on high-resolution CT (HRCT)3.

Sometimes RHS can have specific morphological findings helpful in differential diagnosis as RHS with thickened rim and reticulation or “bird nest sign” and RHS with micronodules. The reticular RHS is linked with invasive fungal disease. RHS with micronodules is related to active granulomatous disease, mainly tuberculosis4, but also paracoccidioidomycosis (PCM) or cryptococcosis and non-infectious granulomatous diseases such as sarcoidosis5.

The presence of RHS on HRCT can be useful to narrow the differential diagnosis. Analyzing the patient’s clinical history and additional CT findings is helpful for the final decision and treatment.

There is a spectrum of infectious, neoplastic, non-infectious/non-neoplastic diseases that may appear as RHS on HRCT. Various clinical situations that can guide the clinicians were described.

Clinical signs and symptoms of pulmonary infection

In immunosuppressed patients opportunistic fungal diseases should be included in the differential diagnosis5. Opportunistic invasive fungal pneumonias (IFPs) have high morbidity and mortality. The most common IFP is an invasive pulmonary aspergilosis (IPA). Other angioinvasive moulds, such as Zygomycetes species are encountered in immunosuppressed patients7,8. In cases of IFP, the RHS is an early sign that results from pulmonary infarct. Other findings include nodules and pleural effusion9.

The RHS has been described in up to 10% of patients with PCM10. PCM is frequent mycosis in Latin America. The HRCT findings of patients with pulmoparacoccidioidomycosis include ground-glass areas, small centrolobular nodules, cavitated nodules, and areas of emphysema10.

In patients from areas with high rates of Mycobacterium tuberculosis infection (TB), pulmonary tuberculosis should always be included in the differential diagnosis. Additional CT findings can help the radiologist: centrilobular nodules and tree-in-bud opacities, as well as subcarinal and hilar lymphadenopathy, areas of consolidation with cavitation11,12. It is remarkable that areas of consolidation have usually upper lobe distribution in these cases.

Pneumocystic Jiroveci Pneumonia (PJP) is the most common opportunistic infection in HIV-positive patients. The RHS has been described in AIDS patients with pneumocystis pneumonia13,6.

The RHS has been reported in cases of bacterial, pneumococcal14, psittacosis or legionella pneumonias. Since infection can cause organizing pneumonia, it is possible that in some of the reported cases of bacterial pneumonia the RHS was a part of secondary organizing pneumonia, provoked by the inflammatory damage.

Known primary neoplasm

The RHS has been described as an early secondary finding of radiofrequency ablation (RFA) of pulmonary nodules. The central GGO area is corresponded to an area of coagulative necrosis of the nodule, whereas peripheral consolidation is corresponded to fibrotic tissue15.

Radiation-induced lung disease (RILD) is common following radiation therapy of the thorax. The RHS may be seen during the acute phase of RILD, in the first 4-12 weeks after treatment. It is probably related to inflammatory process or pulmonary necrosis related to radiation, or secondary organizing pneumonia triggered by radiation injury of the lung2.

In patients under chemotherapy, multiple RHS lesions may correlate with non-specific interstitial pneumonia (NSIP) or organizing pneumonia linked with drug-induced toxicity7.

In patients with a known primary malignancy RHS lesions may appear as atypical presentation of metastatic disease. The presence of new RHS lesions in these patients should be examined for lung metastatic progression7.

Patients with vascular or thromboembolic disease

Patients with pulmonary embolism (PE) may present RHS on CT in case of pulmonary infarction. The RHS in patients with pulmonary infarction translates central coagulative necrosis with peripheral rim of collagen tissue produced by fibroblasts16,17.

The RHS has been described in patient with Wegener’s granulomatosis, in association with lung nodules, ground-glass opacities and cavitary lesions. RHS in this condition represent an intermediate stage that preceded cavitation18.

Asymptomatic patient or with subacute clinical symptoms

RHS has been described as an atypical manifestation in sarcoidosis. Sarcoidosis is a granulomatous disease. In 90% of cases lungs and intrathoracic lymph nodes are affected. RHS in sarcoidosis can represent either non-caseating granulomatous inflammation or secondary organizing pneumonia7.

Cryptogenic organizing pneumonia (COP) is the most common lung disease described in immunocompetent patients with the RHS1. This sign can also be seen in cases of secondary organizing pneumonia. Histopathologically, the central ground-glass opacity of the RHS corresponds to alveolar septal inflammation; the peripheral consolidation represents organizing pneumonia within the alveolar ducts6.

Non-specific interstitial pneumonia (NSIP) is an interstitial lung disease that may be idiopathic, but is more commonly associated with collagen vascular disease, hypersensitivity pneumonitis or drug toxicity7. The RHS correlates with interstitial inflammation that predominates in the middle and lower lung. HRCT in patient with NSIP reveal also reticular pattern, areas of consolidation and traction bronchiectasis.

The RHS has been described by Kanaji et al in case of exogenous lipoid pneumonia after inhaling spray paint. In this case RHS represented organizing pneumonia resulting from lipoid pneumonia19.

Pulmonary adenocarcinoma may present as an area of consolidation, a single node or as multiple nodules. The RHS is an uncommon presentation of lung adenocarcinoma7.

Lymphomatoid granulomatosis (LG) is associated with Epstein-Barr virus (EBV) which mainly affects the lungs. In this case, the RHS corresponds to area of aerated parenchyma with a peripheral ring of lymphomatoid vascular invasion2.

Conclusion

A wide variety of diseases, infectious and noninfectious, may present with the reversed halo sign on chest CT. The two most commonly associated diseases are the organizing pneumonia and invasive fungal pneumonia. The patient’s history and clinical data in combination with the additional radiological findings should help to narrow the differential diagnosis. Although a biopsy is needed in many diseases with RHS on HRCT, it can be avoided in certain scenarios.

In the clinical case reported above, the RHS on chest CT was related with inflammatory process, provoked by infection. The diagnosis of CAP was based on clinical presentation, laboratory tests (acute phase protein), and clinical improvement after treatment with antibiotics only. Unfortunately, the infectious agent was not determined, as well as bronchoscopy with BAL was not helpful, since it was performed in the convalescent phase. Nevertheless, we assume that the causative agent provoked organizing pneumonia and persistent inflammation in lung parenchyma, causing prolonged symptoms.

References

1. Voludaki AE, Bouros DE, Froudarakis ME, Datseris GE, Apostolaki EG, Gourtfoyiannis NC. Crescentic and ring-shaped opacities. CT features in two cases of bronchiolitis obliterans organizing pneumonia (BOOP). Acta Radiologica 1996; 37:889-92.

2. Del Rio B, Esteba Bech de Careda L, Ferrer M, et al. Interpreting the reversed halo sign: Differential characteristics and key clues. Electronic Presentation Online System: ECR 2017/C-2304.

3. Hansell DM, Bankier AA, MacMahon H, McLoud TC, Muller NL, Remy J. Fleischner society: Glossary of terms for thoracic imaging. Radiology 2008; 246:697-722.

4. Marchiori E, Zanetti G, Goboy MCB. Can morphologic characteristics of the reversed halo sign narrow the differential diagnosis of pulmonary infections? American Journal of Roentgenology 2014; 203:557-8.

5. Marchiori E, Zanetti G, Escuissato DL, et al. The reversed halo sign: High-resolution CT scan findings in 79 patients. Chest 2012; 5:1260-66.

6. Marchiori E, Zanetti G, Meirelles GS, Escuissato DL, Souza AS, Hochhegger B. The reversed halo sign on high-resolution CT in infectious and noninfectious pulmonary diseases. American Journal of Roentgenology 2011; 197:69-75.

7. Goboy MC, Viswanathan C, Marchiori E, et al. The reversed halo sign: Update and differential diagnosis. The British Journal of Radiology 2012; 85:1226-35.

8. Chamilos G, Marom EM, Lewis RE, Lionakis MS, Kontoyannis DP. Predictors of pulmonary zygomycosis versus invasive pulmonary aspergolosis in patients with cancer. Clinical Infectious Diseases 2005; 42:60-66.

9. Marom EM, Kontoyiannis DP. Imaging studies for diagnosing invasive fungal pneumonia in immunocompromised patients. Current Opinion in Infectious Diseases 2011; 24:309-14.

10. Gasparetto EL, Escuissato DL, Davaus T, et al. Reversed halo sign in pulmonary paracoccidioidomycosis. American Journal of Roentgenology 2005; 184:1932-4.

11. Ahuja A, Gothi D, Joshi JM. A 15-year-old boy with “Reversed Halo”. The Indian Journal of Chest Diseases and Allied Sciences 2007; 49:99-101.

12. Marchiori E, Grando RD, Simoes Dos Santos CE, et al. Pulmonary tuberculosis associated with the reversed halo sign on high-resolution CT. British Journal of Radiology 2010; 83:58-60.

13. Otera H, Tada K, Sakurai T, Hashimoto K, Ikeda A. Reversed Halo sign in pneumocystis pneumonia: a case report. BMC Medical Imaging 2010; 14: 481-6.

14. Tzilas V, Provata A, Koti A, Tzouda V, Tsoukalas G. The “Reversed Halo” Sign in pneumonococcal pneumonia: a review with a case report. European Review for Medical and Pharmacological Sciences 2010; 14:481-6.

15. Mango VL, Naidich DP, Goboy MC. Reversed halo sign after radiofrequency ablation of a lung nodule. Journal of Thoracic Imaging 2011; 26:150-52.

16. Casullo J, Semionov A. Reversed halo sign in acute pulmonary embolism and infarction. Acta Radiologica 2013; 54:505-10.

17. Tzilas V, Bouros D. Reversed halo sign in pulmonary infarction. Pneumon 2015, 27:188.

18. Agarwal R, Gupta D. Another couse of reversed halo sign: Wegener’s granulomatosis. British Journal of Radiology 2007; 80:849-50.

19. Kanajia N, Ishikawab SS, Kushidac HY. Lipoid pneumonia showing multiple pulmonary nodules and reversed halo sign. Respiratory Medicine Extra 2007; 3:98-101.