Case presentation

A 57-year-old woman with no significant past medical history was referred to our pulmonology department for recurrent lower respiratory tract infections evolving over the preceding year. She presented with a chronic productive cough associated with mucoid sputum, recurrent episodes of purulent expectoration, and intermittent fever. Several courses of antibiotics resulted in only partial and transient clinical improvement. She denied weight loss, arthralgia, ocular symptoms, skin lesions, or other systemic manifestations.

An initial chest computed tomography (CT) scan performed in 2024 revealed a right-sided pneumonic consolidation associated with centrilobular tree-in-bud micronodules (Figure 1).

Figure 1: Initial chest computed tomography scan (2024)Right-sided pneumonic consolidation associated with centrilobular tree-in-bud micronodules (red arrow)

A follow-up chest CT performed one year later showed complete resolution of the tree-in-bud micronodules on the lung parenchymal window (Figure 2). However, persistent mediastinal lymphadenopathy was observed on the mediastinal window (Figure 3), prompting further investigations.

Figure 2: Follow-up chest computed tomography (CT) scan (2025, lung window)Complete resolution of the tree-in-bud micronodules following antibiotic therapy, with the appearance of two small nodules in the right upper lobe

Figure 3: Follow-up chest computed tomography (CT) scan (2025, mediastinal window)Persistent mediastinal lymphadenopathy (white arrow)

An excisional biopsy of an axillary lymph node demonstrated reactive follicular hyperplasia without evidence of malignancy or granulomatous inflammation (Figure 4). Xpert MTB/RIF performed on the biopsy specimen was negative.

Figure 4: Histopathological examination of the excised axillary lymph nodeA. Hematoxylin and eosin (H&E, ×5) stain showing lymph node parenchyma with cortical reactive lymphoid follicles containing prominent germinal centers, associated with sinus histiocytosis. B. Higher-power view (H&E, ×10) highlighting sinus histiocytosis.

Routine laboratory investigations, including complete blood count, liver and renal function tests, serum angiotensin-converting enzyme level, and calcium-phosphate metabolism, were all within normal limits (Table 1).

Parameter | Patient value | Reference range
Hemoglobin | 13.4 g/dL | 12.0-16.0 g/dL
White blood cell count | 6.8 × 10⁹/L | 4.0-10.0 × 10⁹/L
Platelet count | 278 × 10⁹/L | 150-400 × 10⁹/L
Serum creatinine | 8.1 mg/L | 6.0-12.0 mg/L
Serum angiotensin-converting enzyme (ACE) | 42 U/L | 8-52 U/L
Serum calcium | 2.32 mmol/L | 2.15-2.55 mmol/L
Serum phosphate | 1.18 mmol/L | 0.80-1.50 mmol/L

Flexible bronchoscopy revealed no endobronchial abnormalities. Histopathological examination of bronchial biopsies showed non-specific chronic inflammatory changes. Bronchoalveolar lavage was negative for Mycobacterium tuberculosis by Xpert MTB/RIF and culture, as well as for fungal, parasitological, and slow-growing bacterial investigations.

Further investigations, including minor salivary gland biopsy, ophthalmological examination, transthoracic echocardiography, pulmonary function tests, and bone marrow biopsy, failed to identify an alternative diagnosis. The salivary gland biopsy demonstrated non-specific chronic sialadenitis (Figure 5), whereas bone marrow examination showed reactive lymphoid infiltration without evidence of hematological malignancy.

Figure 5: Histopathological examination of the minor salivary gland biopsyHematoxylin and eosin (H&E, ×5) stain showing minor salivary gland tissue with fibrous stroma containing scattered lymphocytic inflammatory cells.

Given the persistence of recurrent respiratory infections associated with unexplained lymphadenopathy despite an extensive negative diagnostic work-up, an underlying primary immunodeficiency was suspected. Serum protein electrophoresis revealed marked hypogammaglobulinemia (γ-globulin fraction: 6 g/L; reference range: 8-13 g/L). Quantitative immunoglobulin testing demonstrated profoundly decreased serum IgG levels (0.98 g/L; reference range: 7-16 g/L) with complete IgA deficiency (0 g/L; reference range: 0.7-4.0 g/L). Immunophenotyping showed normal T- and B-cell subsets. These findings were consistent with the diagnosis of CVID (Table 2).

Parameter | Patient value | Reference range
Serum protein electrophoresis | Hypogammaglobulinemia (γ-globulin fraction: 6 g/L) | 8-13 g/L*
Serum IgG | 0.98 g/L | 7.0-16.0 g/L
Serum IgA | 0 g/L | 0.70-4.00 g/L

After secondary causes of hypogammaglobulinemia had been excluded, the diagnosis of CVID was established. The patient was subsequently referred to the Internal Medicine Department for immunoglobulin replacement therapy and long-term follow-up.