Nodular reverse halo sign in a hemodialysis patient with polycystic kidney disease and pulmonary tuberculosis

Abstract

A 56-year-old man with polycystic kidney disease (PKD) and end-stage renal disease (ESRD) on long-term hemodialysis presented with decreased appetite, malaise, cough and fever. Chest CT revealed a nodular reverse halo sign (NRHS), a rare but relatively specific feature associated with pulmonary tuberculosis (TB). Although conventional sputum smears were negative for acid-fast bacilli, Mycobacterium tuberculosis was identified in bronchoalveolar lavage fluid through Xpert MTB/RIF testing and targeted next-generation sequencing. This case highlights: (1) NRHS as a significant radiologic indicator of TB, even in immunocompromised patients; (2) the need for advanced diagnostic tools when conventional tests are inconclusive; and (3) the impact of economic barriers in resource-limited settings, which can delay treatment and contribute to poor outcomes. Timely TB screening and accessible treatment are essential for high-risk populations, particularly those undergoing hemodialysis.

Introduction

The reversed-halo sign (RHS) is defined as a focal, circular area of ground-glass attenuation on chest CT surrounded by partially or completely solid margins. Initially described in association with cryptogenic organizing pneumonia [1], RHS has since been identified in a range of infectious (e.g., mucormycosis, aspergillosis) and non-infectious conditions. When nodular components are present within the halo, the pattern is referred to as the nodular reverse halo sign (NRHS), a radiologic feature most commonly linked to granulomatous infections, particularly pulmonary tuberculosis (TB). Identification of NRHS can help refine the differential diagnosis of RHS. Although NRHS is relatively uncommon, early recognition is critical, especially in immunocompromised patients, as it can facilitate prompt diagnosis and treatment of TB.

Case presentation

A 56-year-old man with a medical history of polycystic kidney disease (PKD) and end-stage renal disease (ESRD) had been receiving government-subsidized hemodialysis three times weekly for the past 11 years. He presented to a community hospital with a five-day history of decreased appetite, malaise, and dry cough. Chest radiographs revealed bilateral pulmonary infiltrates, leading to a diagnosis of severe community-acquired pneumonia. Despite receiving intravenous piperacillin for 10 days, his condition failed to improve. Instead, he developed a high-grade fever, with a peak temperature of 40 °C occurring four days before presentation. Due to persistent symptoms and lack of treatment response, he was referred to Xichong County People's Hospital for further evaluation and management.

On admission, his axillary temperature was 37.7 °C, and fine moist rales were heard in both upper lung fields. Laboratory investigations revealed a white blood cell count was 11.43 × 10⁹/L (reference 3.5–9.5 × 10⁹/L) with 87.2 % neutrophils. C-reactive protein was 82 mg/L (reference <6 mg/L), erythrocyte sedimentation rate was 44 mm/h (reference <15 mm/h) and procalcitonin was 3.12 ng/ml (reference <0.06 ng/ml). Chest CT demonstrated nodules, consolidations, and ground-glass opacities predominantly in the upper lobes, arranged along bronchovascular bundles and forming multiple NRHS. A small cavitary lesion in the right upper lung and calcifications in both pulmonary and mediastinal lymph nodes were also noted (Fig. 1A–C). Abdominal CT revealed multiple renal cysts of varying size in both kidneys with calcified cyst walls, as well as multiple hepatic cysts and splenomegaly, consistent with a diagnosis of PKD (Fig. 1D).

Fig. 1.

Chest and abdominal CT images obtained at the time of patient presentation. A) Axial chest CT demonstrates multiple nodules, areas of consolidation, and ground-glass opacities in the bilateral upper lobes, forming nodular reverse halo signs (NRHS). B) Axial chest CT shows NRHS in both upper lungs, along with calcifications and a small cavitary lesion in the right upper lobe (arrow). C) Axial chest CT reveals NRHS distributed along the bronchovascular bundles, accompanied by intrapulmonary and mediastinal lymph node calcifications. D) Coronal chest and abdominal CT reconstruction shows mediastinal lymph node calcifications, multiple renal cysts with calcified walls, hepatic cysts, and splenomegaly.

Further immunological tests, including a gamma interferon release assay and an ESAT-6/CFP-10 skin test, were positive. However, multiple sputum smears were negative for acid-fast bacilli. Tests for fungal pathogens (including fungal smear, serum β-D-glucan, galactomannan, and cryptococcal capsular polysaccharide antigen) were all negative. Due to a high clinical suspicion for pulmonary TB, electronic bronchoscopy was performed. Bronchoalveolar lavage fluid was analyzed by Xpert MTB/RIF and targeted second-generation sequencing (tNGS), confirming the presence of rifampicin-sensitive Mycobacterium tuberculosis. tNGS also detected high sequence counts of Enterococcus faecalis, but no fungal or viral organisms. Based on these findings, a definitive diagnosis of pulmonary TB was established. The patient was advised to begin anti-TB therapy at a specialist infectious disease center, alongside ongoing dialysis. Unfortunately, due to financial constraints, he abandoned further treatment and died one week after discharge.

Discussion

NRHS is characterized by micronodules within the wall and center of the reversed halo. These micronodules typically represent granulomas on histology, making NRHS a relatively specific indicator of active granulomatous disease, particularly pulmonary TB [2]. However, NRHS can also be observed in other conditions such as sarcoidosis, paracoccidioidomycosis, and cryptococcosis [3]. Sarcoidosis typically presents with symmetric hilar or mediastinal lymphadenopathy and multiple small nodules along lymphatic routes. In contrast, paracoccidioidomycosis and cryptococcosis often require correlation with clinical context, epidemiological background, and laboratory findings due to their varied imaging features. In this case, the presence of NRHS alongside polymorphic pulmonary findings—including nodules, consolidations, cavitation, and calcifications—supported the diagnosis of pulmonary TB. Given the low sensitivity of sputum smear microscopy, a negative result does not exclude TB. Molecular diagnostic methods based on lower respiratory tract specimens, such as bronchoalveolar lavage fluid, can substantially improve detection rates, as demonstrated here. Although NRHS has primarily been reported in immunocompetent individuals [4], [5], this case highlights its occurrence in an immunocompromised patient with ESRD on long-term dialysis. Patients on maintenance hemodialysis frequently develop uremia-associated immune dysfunction, including impaired cellular and humoral immunity and a chronic inflammatory state, which increases their susceptibility to infections such as TB [6]. Despite an accurate and timely diagnosis, the patient's death may have resulted from rapid renal deterioration compounded by infection, exacerbated by limited access to dialysis for infectious disease patients and financial hardship. TB alone rarely causes death within such a short timeframe, suggesting systemic complications and inadequate supportive care may have contributed.

A key limitation of this case is the presence of mixed infections and the inability to definitively determine the patient’s ultimate cause of death. Nevertheless, the diagnosis of TB was well supported by clinical, radiological, and molecular findings. This case emphasizes the need for early TB screening and preventive therapy in high-risk groups, particularly those with ESRD undergoing dialysis. In resource-limited settings, improving access to diagnostic tools, treatment, and dialysis resources is critical for improving outcomes in these vulnerable populations [7].

Author Agreement Statement

We the declare that this manuscript is original, has not been published before and is not currently being considered for publication elsewhere. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We understand that the Corresponding Author is the sole contact for the Editorial process. He/she is responsible for communicating with the other authors about progress, submissions of revisions and final approval of proofs.

CRediT authorship contribution statement

Guo Li: Writing – review & editing, Writing – original draft, Data curation, Conceptualization. Shan Yuan: Writing – review & editing, Writing – original draft, Data curation, Conceptualization. Peng Wang: Writing – review & editing, Data curation. Min Pang: Writing – review & editing, Data curation. Xianqiong Pang: Writing – review & editing, Data curation.

Consent

Written informed consent was obtained from the patient's son for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Ethical approval

This study was conducted in accordance with the principles of the Declaration of Helsinki. Ethics committee approval is not required for case reports at our institution.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.