D2.125 - When Severe Asthma Isn’t Asthma: A Case of Humoral Immunodeficiency With Suspicion of Lymphoproliferative Disease

Asthma is one of the most prevalent chronic respiratory conditions worldwide, but the presence of atypical features should always raise the suspicion of alternative diagnoses. Severe or refractory asthma may in rare cases be the first clinical manifestation of an underlying immunological disorder. We present the case of a 36-year-old male with a long-standing history of asthma since childhood, referred to our clinic for qualification for biological therapy.

A 36-year-old male with a history of asthma since childhood was referred for evaluation and qualification for biological therapy. The disease, diagnosed in 2002, worsened after 2021, with recurrent respiratory infections and dyspnea since adolescence. Documented exacerbations occurred in October 2024, January 2025, and June 2025. No allergic comorbidities were reported. In 2024, the patient underwent alloplasty of the left hip joint due to sterile osteonecrosis. Clinically, the patient was stable without dyspnea. Physical examination showed no significant abnormalities.

On admission, spirometry revealed mild obstruction (FEV1 70%,FVC 89%, FEV1/FVC 65%). Peak expiratory flow monitoring showed no daily variability. Chest and abdominal CT revealed mediastinal and subphrenic lymphadenopathy (up to 20×15 mm), splenomegaly, and mosaic perfusion. Laboratory studies showed severe microcytic anemia (Hgb 7.8 g/dL), iron deficiency, and fecal occult blood positivity. Allergen-specific IgE and skin prick tests were negative, and total IgE was low. Gastroscopy confirmed gastroesophageal reflux disease (LA C) and diaphragmatic hernia. Immunological evaluation revealed profound hypogammaglobulinemia (IgG 3.2 g/L) with preserved IgA and IgM. Flow cytometry showed B lymphocytes lacking CD19 surface expression, indicating a humoral immunodeficiency.

The patient’s long-standing diagnosis of severe asthma was challenged by the absence of atopy, mild current airway obstruction, and additional systemic findings including lymphadenopathy, splenomegaly, hypogammaglobulinemia, and anemia. Together, these features strongly suggested primary antibody deficiency, and raised concern for an underlying lymphoproliferative disease. Although asthma was part a of the clinical picture, it no longer explained the full extent of the patient’s symptoms.

This case illustrates how chronic respiratory symptoms initially attributed to severe asthma may, in fact, be the consequence of underlying immunological and hematological disorders. A comprehensive diagnostic approach, integrating pulmonary, immunological, and hematological findings, is essential to avoid misdiagnosis and to implement targeted treatment strategies at an early stage.