Sarcoidosis Presenting as a Giant Pulmonary Bulla With Concurrent COVID-19 Infection

Abstract

Sarcoidosis is a systemic granulomatous disease that predominantly affects the lungs. However, its presentation as a giant pulmonary bulla is exceptionally rare. Its association with COVID-19 has raised new concerns regarding disease exacerbation and misdiagnosis. We report a case of a 38-year-old man who developed a large left lower lobe bulla in the context of recent COVID-19 infection. Initial misinterpretation of the bulla as loculated pneumothorax nearly led to an unnecessary chest tube placement. A subsequent thoracotomy with lobectomy revealed nonnecrotizing granulomas, confirming sarcoidosis. The patient showed spontaneous remission without requiring treatment. This case highlights the importance of multidisciplinary discussions in atypical lung presentations to prevent mismanagement.

Introduction

Sarcoidosis is a granulomatous inflammatory disease of unknown etiology that primarily affects the lungs and lymphatic system but can involve multiple organs. It is characterized by the formation of nonnecrotizing granulomas, which may lead to fibrosis and organ dysfunction. The pulmonary manifestations of sarcoidosis commonly include bilateral hilar lymphadenopathy and reticulonodular infiltrates in a perilymphatic distribution; however, cystic or bullous lung disease is a rare and poorly understood presentation. ¹

In this report, we present a rare case of sarcoidosis manifesting as a giant pulmonary bulla in the context of COVID-19 infection, emphasizing the diagnostic challenges, and the importance of a thorough clinical and histopathological evaluation.

Case Presentation

A 38-year-old Caucasian man presented to the emergency department with progressive shortness of breath and chest discomfort. One week prior, he experienced low-grade fever, cough, rhinorrhea, and myalgia and was diagnosed with COVID-19. His symptoms initially improved with symptomatic management, but he later developed worsening dyspnea, prompting an emergency evaluation. The patient had no history of smoking, recreational drug use, or significant occupational exposures.

Chest X-ray revealed bilateral patchy lung infiltrates, while a computed tomography (CT) chest angiogram demonstrated a large 7 cm left lower lobe bulla, bilateral ground-glass infiltrates, and mild hilar and subcarinal adenopathy (Figure 1). Initially, the bulla was suspected to represent loculated pneumothorax, leading to consideration of chest tube placement. However, multidisciplinary discussion involving thoracic surgery, pulmonology, and radiology clarified that the lesion was a giant bulla rather than pneumothorax, and chest tube intervention was avoided. He was discharged with 10-day course of prednisone for presumed COVID-related inflammatory changes and scheduled for outpatient follow-up.

Figure 1.

CT of chest (A, B: axial; C: coronal; F: sagittal) showing large left lower lobe bulla occupying 40% to 50% of left hemithorax. Mediastinal window settings of CT of chest (D, E) showing hilar (yellow arrows) and subcarinal lymphadenopathy (blue arrow). CT, computed tomography.

Four weeks later, his symptoms persisted, and pulmonary function testing revealed a moderately severe restrictive ventilatory defect with reduced diffusing capacity (Table 1). A left thoracotomy with left lower lobectomy and mediastinal lymph node dissection was performed. Histopathological analysis confirmed nonnecrotizing granulomas without evidence of fungal or mycobacterial infection (Figure 2). Serum angiotensin-converting enzyme (ACE), antinuclear antibody, antineutrophil cytoplasmic antibody, and alpha-1 antitrypsin levels were within normal limits.

Table 1.

Pulmonary Function Test Results.

Variables	Prelobectomy			Postlobectomy
	Actual	Predicted	% Predicted	Actual	Predicted	% Predicted
FEV1 (L)	3.55	5.67	62	4.60	5.46	84
FVC (L)	2.82	4.52	62	3.46	4.14	84
FEV1/FVC	80	80	NA	75	75	NA
TLC (L)	4.38	7.33	59	5.90	7.46	81
DLCOc (mL/min/L)	21.12	35.03	60	34.4	31.7	108

Abbreviations: DLCOc, diffusing capacity corrected for hemoglobin; FEV1, forced expiratory volume at 1 second; FVC, forced vital capacity; L, liter; NA, not applicable; TLC, total lung capacity.

Figure 2.

Histopathology images from lung: (A) shows part of a large noncaseating granuloma, with adjacent submucosal glands and bronchial cartilage, (B) shows a higher magnification of the noncaseating granulomatous inflammation in the lung, with multinucleated giant cells. Multiple well circumscribed granulomas may coalesce to form large nodules. Histopathology images from left hilar node: (C) showing noncaseating granulomas, coalescing to form large nodules, (D) showing noncaseating granulomas with multinucleated giant cells.

At follow-up, the patient reported resolution of dyspnea and chest discomfort. Repeat pulmonary function tests showed normalization of lung volumes and gas exchange (Table 1). A CT scan performed a year later demonstrated regression of hilar and subcarinal adenopathy (Figure 3). Given his asymptomatic status, no additional therapy for sarcoidosis was initiated, and he remained in spontaneous remission.

Figure 3.

Computed tomography of chest (A, B: lung windows; C, D: mediastinal windows) showing decrease in size of hilar (yellow arrows) and subcarinal (blue arrow) lymph nodes.

Discussion

Sarcoidosis is a systemic granulomatous disease of unknown etiology that primarily affects the lungs and intrathoracic lymph nodes, although it can involve multiple organ systems. The disease is characterized by the presence of nonnecrotizing granulomas, which are clusters of immune cells that form in response to persistent antigenic stimulation. Pulmonary sarcoidosis commonly presents with bilateral, symmetric hilar, and mediastinal lymphadenopathy, and micronodules in a perilymphatic distribution, perihilar patchy infiltrates, and fibrosis. However, atypical presentations including cysts, bullae, solitary nodules, and ground glass infiltrates have been described. ¹

Sarcoidosis presenting as a giant bulla is exceptionally rare, with only a few cases documented in the literature. The estimated prevalence of bullous sarcoidosis remains unknown due to the limited number of reported cases. However, it is believed that <1% of sarcoidosis patients develop significant bullous changes in the lungs. ² A giant bulla is defined as an air-filled space within the lung parenchyma that occupies over 30% of a hemithorax. ³ The formation of giant bullae is thought to result from granulomatous inflammation leading to airway obstruction, air trapping, and alveolar destruction. Other contributing mechanisms include fibrosis-related lung remodeling and local parenchymal destruction secondary to chronic inflammation.^4,5

Diagnosing bullous sarcoidosis can be particularly challenging, primarily due to a lack of immediate suspicion. Bullous changes are often attributed to conditions such as cigarette or marijuana smoking, intravenous drug use, emphysema, alpha-1 antitrypsin deficiency, Marfan syndrome, and Ehlers–Danlos syndrome. ³ The challenge is further compounded when patients have concurrent pathologies that could also contribute to bullae formation. For example, giant bullae have been reported in cases of COVID-19 infection.^6,7

In our patient, COVID-19 was diagnosed approximately a week before their presentation to the emergency department. While it is unclear whether COVID-19 may have accelerated bulla formation, we believe it was not the sole cause for several reasons. First, histopathology revealed nonnecrotizing granulomas within the lung parenchyma rather than being limited to lymph nodes. Second, the short interval between COVID-19 symptom onset and bulla identification raises doubts about a direct causal link. Lastly, COVID-19-associated bullae typically develop in the context of more severe lung infiltrates and fibrotic changes.^6,7

Several studies have explored the association between sarcoidosis and COVID-19, primarily focusing on the management challenges posed by the immunosuppressive treatment often required for sarcoidosis. Interestingly, emerging evidence suggests a possible link between SARS-CoV-2 infection and the development of new-onset sarcoidosis or sarcoid-like immune reactions. Case reports have described patients developing noncaseating granulomas post-COVID-19, raising the hypothesis that SARS-CoV-2 may act as a triggering antigen in genetically predisposed individuals. This may be mediated through mechanisms involving ACE and ACE-2 dysregulation, immune hyperactivation, and granuloma formation, suggesting that sarcoidosis could, in some cases, represent a delayed immune response following COVID-19 infection.^8,9

Additionally, giant bullae can be mistaken for pneumothorax, leading to potential mismanagement. In this case, initial imaging misidentified the bulla as a loculated pneumothorax related to COVID-19 infection. Loculated pneumothorax has been reported in the literature following COVID-19.^10,11 Differentiating between a pneumothorax pleural line and a bulla wall can be difficult, but the double-wall sign serves as a crucial diagnostic clue. This sign appears when air outlines both sides of the bulla wall, running parallel to the chest wall. ¹² Its absence argues against pneumothorax and helps prevent unnecessary chest tube placement, which could lead to complications such as bronchopleural fistula. This highlights the importance of multidisciplinary collaboration in diagnosing complex pulmonary conditions.

Maintaining a high index of suspicion for sarcoidosis is essential in patients presenting with giant bullae. Histopathological evaluation is particularly important when bullous changes remain unexplained, or when underlying risk factors and concurrent conditions fail to fully account for the presentation. The presence of nonnecrotizing granulomas in biopsy samples is critical for confirming sarcoidosis while ruling out infectious causes like tuberculosis and fungal infections. Notably, granulomatous changes have often been sparse along the walls of resected bullae, underscoring the need to biopsy relatively unaffected lung tissue when pursuing a definitive histological diagnosis. ¹³

The optimal management of giant bullae in sarcoidosis remains unclear. Currently, there are no reported benefits of corticosteroid therapy in treating bullae associated with sarcoidosis. Management needs to be tailored to the severity of symptoms and the extent of pulmonary involvement. While asymptomatic patients may require only monitoring, those with significant dyspnea, respiratory failure, or infected bullae need surgical intervention in the form of bullectomy or lobectomy. In our case, the patient underwent lobectomy due to persistent symptoms and presence of significant restrictive defect on pulmonary function test, which led to spontaneous remission without further pharmacologic therapy.

Conclusion

Giant pulmonary bulla as a manifestation of sarcoidosis is a rare but important diagnostic consideration. Misinterpretation as pneumothorax can lead to unnecessary procedures and potential complications. This case underscores the importance of recognizing sarcoidosis-related bullous lung disease and highlights the role of a multidisciplinary approach in achieving accurate diagnosis and management. Long-term follow-up is essential, as disease progression and recurrence remain possibilities despite initial remission.