Challenges in recognition and reporting of infections in immune deficiency

Our immune system protects us from infections caused by bacteria, viruses, and fungi. When the immune system does not work properly - either because of innate diseases or because of medication that suppresses immune activity - people become more vulnerable to infections. This thesis studies such infections in rheumatoid arthritis (RA) patients who use biological medicines that intentionally suppress parts of the immune system, and those with primary antibody deficiencies (PAD) as prototypes of secondary and primary immunodeficiencies, in whom the immune system is naturally weakened. In RA, the use of biologicals greatly improves disease control but increases the risk of infections. In antibody deficiencies, infections are a direct consequence of the disorder and often point to the diagnosis itself. In both cases, infections can seriously affect quality of life, cause long-term organ damage, or even lead to premature death. They can also lead to interruptions in treatment or delays in diagnosis.

A large overview of published studies showed that mild or “non-serious” infections, such as colds, sinus infections or skin infections, occur far more often than severe infections that require hospitalisation, but receive much less attention in research and medical practice. To better understand how these mild infections affect patients, a separate study was performed among RA patients using biologicals. It showed that nearly one in four patients experienced infections, mainly of the airways and skin. These infections often lasted a long time or recurred and caused considerable discomfort, even though most patients did not consult their doctor for them. Another part of the research investigated how reliable COVID-19 laboratory tests are in people with a weakened immune system. It showed that test results can be harder to interpret in such patients, because their immune system responds differently. Doctors should therefore always interpret test results in the context of a patient’s immune status. This thesis also describes a rare but serious case of a patient with RA treated with rituximab who developed progressive multifocal leukoencephalopathy (PML). There was some delay in diagnosis due to both caregiver and patient-related reasons, and this delay is also apparent in all other described cases of PML in biological use in the medical literature to date. This case and others like it underline the importance of awareness among doctors and patients that serious infections can occur even in groups not traditionally considered “at risk”. Finally, the research examined patients with antibody deficiencies before they were diagnosed. Many had suffered from recurrent respiratory infections caused by specific bacteria, but in most cases no germ was ever identified, probably often because cultures were not performed. Certain infection patterns, such as repeated lung infections with encapsulated bacteria, were found to predict lung damage at diagnosis. Recognising such patterns earlier could help achieve faster diagnosis and better care.

Together, these studies show that infections in people with impaired immunity deserve much greater attention, especially the recurring mild infections that are often underestimated. Greater awareness among healthcare professionals, consistent testing and documentation of infections, and earlier recognition of suspicious infection patterns can lead to earlier diagnosis, more effective treatment, and ultimately a better quality of life for people with immune deficiencies.