Good's Syndrome Presenting With Weaning Failure From Ventilation and Myasthenia Gravis in a Post‐Thymectomy Patient

ABSTRACT

Good's syndrome is a rare adult‐onset immunodeficiency associated with thymoma, hypogammaglobulinemia, and cellular immune dysfunction. We report a man in his 50s with a prior thymectomy who presented with recurrent pneumonia, chronic diarrhoea, and failure to wean from non‐invasive ventilation. Flow cytometry revealed absent B cells and an inverted CD4/CD8 ratio, confirming Good's syndrome. He also developed myasthenia gravis, which contributed to ventilatory failure but improved with pyridostigmine. The patient responded well to monthly intravenous immunoglobulin therapy and remained clinically stable at follow‐up. This case emphasises the importance of suspecting Good's syndrome in patients with thymoma and unexplained infections, as early recognition and timely immunoglobulin replacement are essential for improving outcomes.

This case highlights the importance of long‐term vigilance in patients with thymoma, even after apparently successful resection, as Good's syndrome may manifest years later. Clinicians should maintain a high index of suspicion for Good's syndrome in any thymectomized patient presenting with unexplained infections, diarrhoea, or autoimmune complications, as early diagnosis and timely initiation of IVIg are critical to improving outcomes.

1. Introduction

Good's syndrome is an adult‐onset immunodeficiency first described in 1955, defined by the coexistence of thymoma with hypogammaglobulinemia and cellular immune dysfunction [1]. It typically presents in the fourth or fifth decade of life with recurrent bacterial infections, chronic diarrhoea, or autoimmune disorders [2]. Despite being recognised for decades, Good's syndrome remains underdiagnosed due to its rarity and heterogeneous manifestations, with most reports limited to case series or single cases [2, 3]. We report a patient with thymoma who developed recurrent pneumonia, myasthenia gravis, and persistent diarrhoea, ultimately diagnosed with Good's syndrome.

2. Case Report

A man in his 50s was referred with persistent pneumonia and failure to wean from mechanical ventilation. His history included resection of a type AB thymoma (stage pT1a) 4 years earlier, and two episodes of COVID‐19 pneumonia, the latter complicated by post‐infectious lung fibrosis. He reported chronic diarrhoea, weight loss, and incomplete recovery following his last admission.

On presentation, he was febrile (101°F), tachypneic (respiratory rate 34/min), and tachycardic (heart rate 112/min), requiring non‐invasive ventilation (NIV); fraction of inspired oxygen of 70%, saturation of peripheral oxygen of 93%. Examination revealed pallor, bilateral basal crepitations, and bilateral ptosis with fatigable weakness. Laboratory tests showed anaemia (haemoglobin 7.9 g/dL), neutrophilic leukocytosis, hypokalemia, and elevated C‐Reactive Protein of 187 mg/L. Chest radiograph demonstrated bilateral infiltrates with basal consolidation (Figure 1A). Chest computed tomography (CT) confirmed bilateral infiltrates and dense consolidation (Figure 2).

FIGURE 1.

(a) Chest radiograph at presentation demonstrating diffuse bilateral infiltrates. (b) Follow‐up chest radiograph at 4‐month follow‐up after initiation of intravenous immunoglobulin therapy, showing near‐complete resolution of lung changes.

FIGURE 2.

Computed tomography of the thorax in lung window at presentation demonstrating bilateral patchy infiltrates and dense basal consolidation.

Given fluctuating ptosis and dysarthria, myasthenia gravis was suspected. Anti–acetylcholine receptor (AChR) antibody was < 0.25 nmol/L (negative), and anti–muscle‐specific kinase (MuSK) antibody was also negative. Despite this, a neostigmine challenge test was positive, and pyridostigmine therapy (60 mg three times daily) led to rapid improvement, allowing successful weaning from NIV within 48 h.

Serological testing for HIV, hepatitis B surface antigen, hepatitis C virus, antinuclear antibody, antineutrophil cytoplasmic antibodies, and myositis panel was all negative, excluding secondary immunodeficiency and autoimmune causes.

Further evaluation revealed hypogammaglobulinemia (IgG 30 g/L, IgA 5.0 g/L, IgM 5.0 g/L). Flow cytometry demonstrated absent B lymphocytes, decreased CD4⁺ T lymphocytes, and an inverted CD4/CD8 ratio (Table 1), confirming Good's syndrome. He was started on intravenous immunoglobulin (IVIg) at a dose of 25 g, administered over 3 days, followed by monthly maintenance infusions, along with prophylactic sulfamethoxazole‐trimethoprim.

TABLE 1.

Flow cytometry report.

Subset/test	Results	Reference range (above 12 years)
WBC count	8540 cells/μL	4400–8100 cells/μL
Lymphocyte %	10.1%	—
Absolute lymphocyte count	863 cells/μL	1400–3300 cells/μL
T lymphocyte CD3+ (% of lymphocytes)	86.0%	56%–84%
Absolute CD3+ count	742 cells/μL	1000–2200 cells/μL
T lymphocyte CD4+ (% of lymphocytes)	31.5%	31%–52%
Absolute CD4+ count	272 cells/μL	530–1300 cells/μL
T lymphocyte CD8+ (% of lymphocytes)	50.2%	18%–35%
Absolute CD8+ count	433 cells/μL	330–920 cells/μL
B lymphocyte CD19+ (% of lymphocytes)	0.0%	6%–23%
Absolute CD19+ count	0 cells/μL	110–570 cells/μL
NK cells CD56+/CD16+ (% of lymphocytes)	13.3%	3%–22%
Absolute NK CD56+/CD16+ count	115 cells/μL	70–480 cells/μL
AChR	< 0.25 nmol/L	< 0.5 nmol/L (Negative)
MuSK	Negative	Negative

Abbreviations: AChR, anti–acetylcholine receptor; MuSK, anti–muscle‐specific kinase.

At 4‐month follow‐up, he remained free of infections, had gained weight, and the chest radiograph showed near‐complete resolution of lung changes (Figure 1).

3. Discussion

Unlike other primary antibody deficiencies such as common variable immunodeficiency, X‐linked agammaglobulinemia, and Good's syndrome is distinguished by the coexistence of humoral and cellular immune defects, which underlies its poorer prognosis [1, 2, 3]. Affected patients are at risk not only for recurrent bacterial infections but also for opportunistic pathogens and diverse autoimmune manifestations. Consequently, morbidity and mortality are often driven by infections, autoimmune cytopenias, and hematologic complications, with delays in diagnosis contributing significantly to adverse outcomes [3].

The pathogenesis of Good's syndrome is incompletely understood. Although the presence of thymoma is a consistent feature, it does not fully explain the immune dysfunction. Studies suggest that bone marrow defects, impaired lymphopoiesis, and altered T‐cell maturation may all contribute. The clinical presentation is heterogeneous, ranging from an incidental mediastinal mass discovered on imaging to recurrent respiratory infections, chronic diarrhea, and manifestations of autoimmunity. In some cases, thymoma is diagnosed in the course of evaluating myasthenia gravis, further complicating the clinical picture [2, 3, 4].

Our patient illustrates several important aspects of Good's syndrome. He developed recurrent respiratory infections and persistent diarrhoea several years after thymectomy, which underscores that Good's syndrome may manifest long after surgical excision of thymoma. Opportunistic infections such as cytomegalovirus and bacterial pathogens like Enterococcus were isolated, reflecting profound cellular immune dysfunction. In addition, he developed neuromuscular weakness due to myasthenia gravis, confirmed clinically by a positive neostigmine test despite being antibody‐negative for both AChR and MuSK antibodies. The coexistence of Good's syndrome and seronegative myasthenia gravis complicated his course by contributing to ventilatory failure and delayed weaning, highlighting the need to consider overlapping pathologies in patients with thymoma and respiratory compromise.

Autoimmune manifestations are well described in Good's syndrome, including pure red cell aplasia, autoimmune haemolytic anaemia, thyroiditis, lichen planus, and myasthenia gravis [5]. Our patient demonstrated several such features, reinforcing the concept that Good's syndrome represents a state of broad immune dysregulation rather than a purely antibody‐deficient condition.

From a therapeutic perspective, IVIg remains the cornerstone of management, restoring humoral immunity and reducing susceptibility to infections. In our case, the patient was initiated on IVIg at a dose of 25 g administered over 3 days, followed by monthly maintenance infusions. He showed marked clinical improvement with resolution of infections, weight gain, and radiographic clearing of lung infiltrates. Importantly, thymectomy and immunosuppression do not reverse the underlying immunodeficiency, and most patients require lifelong IVIg replacement. Adjunctive measures such as antimicrobial prophylaxis and appropriate vaccination strategies are also recommended.

In summary, this case highlights the importance of long‐term vigilance in patients with thymoma, even after apparently successful resection, as Good's syndrome may manifest years later. The combination of delayed Good's syndrome diagnosis, unusual infectious pathogens, and sero‐negative myasthenia gravis leading to ventilatory failure makes this case particularly instructive. Clinicians should maintain a high index of suspicion for Good's syndrome in any thymectomized patient presenting with unexplained infections, diarrhoea, or autoimmune complications, as early diagnosis and timely initiation of IVIg are critical to improving outcomes.

Author Contributions

Asmita Anilkumar Mehta, Aditya Ashok and Suchitra Sivadas: conceive/design. George Justin Mothi, Aditya Ashok and Suchitra Sivadas: clinical Ix. Asmita Anilkumar Mehta and Lakshmi Priya Valathara Pradeep: writing and editing.

Consent

The authors declare that written informed consent was obtained for the publication of this manuscript and accompanying images using the form provided by the Journal.

Conflicts of Interest

The authors declare no conflicts of interest.

Mehta A. A., Ashok A., Valathara Pradeep L. P., Sivadas S., and Mothi G. J., “Good's Syndrome Presenting With Weaning Failure From Ventilation and Myasthenia Gravis in a Post‐Thymectomy Patient,” Respirology Case Reports 13, no. 11 (2025): e70389, 10.1002/rcr2.70389.

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.