A case report published in the Journal of Neurology describes a patient with multiple sclerosis who developed severe invasive pneumococcal pneumonia after an influenza A infection while being treated with dimethyl fumarate, a widely used oral disease-modifying therapy. The report, authored by an intensive care team at Mont-Godinne University Hospital in Belgium, uses the single clinical course to argue for two practical safeguards that clinicians sometimes overlook: a systematic assessment of vaccination status before and during immunotherapy, and disciplined hematologic monitoring throughout treatment. Although the article takes the form of a letter to the editors, its message reaches well beyond one hospital ward, touching on how viral infections can pave the way for bacterial superinfections in patients whose immune systems are pharmacologically dampened.
Dimethyl fumarate has been a mainstay of therapy for relapsing-remitting multiple sclerosis for years, valued for its combination of efficacy, oral administration, and a generally favorable long-term safety profile. The drug exerts immunomodulatory effects through several mechanisms, including activation of the nuclear factor erythroid 2-related factor 2 pathway and a characteristic reduction in circulating lymphocytes. That lymphocyte decline is usually mild to moderate and reversible, but it is precisely the reason that treatment guidelines mandate regular white blood cell counting. The Belgian authors emphasize that patient-specific factors can modulate the leukocyte response to the drug, a point supported by prior research showing that baseline counts, body characteristics, and other variables influence how far lymphocytes fall in individual patients.
The clinical sequence at the heart of the report follows a pattern that respiratory physicians know well: influenza first, bacterial pneumonia second. Influenza A damages the respiratory epithelium, disrupts mucociliary clearance, and creates conditions in which colonizing bacteria such as Streptococcus pneumoniae can invade the lower airways. In an immunocompetent host this secondary bacterial pneumonia can still become life-threatening; in a patient with drug-induced lymphopenia the barrier to invasion is substantially lower. The patient in this report progressed to severe, invasive disease requiring intensive care, illustrating how a common seasonal virus and an opportunistic bacterium can combine catastrophically when immune defenses are compromised.
Severe pneumococcal pneumonia of this kind is not merely a chest infection that responds slowly to antibiotics. Community-acquired pneumonia that deteriorates into acute respiratory distress syndrome carries substantial mortality even in modern intensive care units, and studies of mechanically ventilated patients with pneumonia have documented how frequently this syndrome complicates the course. The global definition of acute respiratory distress syndrome was updated in 2024 to improve recognition of this entity, which involves diffuse lung inflammation, impaired oxygenation, and bilateral radiographic opacities. The Belgian team situates their case within this framework, noting that the combination of viral priming, bacterial invasion, and impaired cellular immunity created the conditions for profound respiratory failure.
The first of the report’s two central lessons concerns vaccination. People with multiple sclerosis are not inherently excluded from standard vaccine recommendations; on the contrary, the ECTRIMS/EAN consensus published in 2023 provides detailed guidance on immunization in this population, urging clinicians to complete recommended vaccines before starting highly active immunotherapies and to maintain coverage thereafter. Evidence indicates that immune responses to vaccines are generally maintained in patients treated with dimethyl fumarate, and a prospective single-center study in 2024 found that seasonal influenza and pneumococcal polysaccharide vaccines remain immunogenic in patients on various disease-modifying therapies. Yet a multicenter cross-sectional study published in 2025 documented that vaccination coverage among patients with multiple sclerosis remains incomplete and variable, with determinants ranging from disease characteristics to health system factors. The case therefore functions as a concrete reminder that every patient starting or continuing immunotherapy should have a documented vaccination history, with influenza and pneumococcal vaccines addressed explicitly.
The second lesson concerns hematologic monitoring. Treatment labels and consensus recommendations call for lymphocyte counting before initiation, at three and six months, and periodically thereafter, with dose adjustment or interruption when counts fall below defined thresholds. The Common Terminology Criteria for Adverse Events provides the grading framework used to classify the severity of leukopenia and lymphopenia, and the authors apply this vocabulary to describe the degree of immune suppression in their patient. Research into interventions to increase leukocyte testing during dimethyl fumarate treatment has shown that adherence to monitoring schedules is imperfect in real-world practice, and that structured interventions can improve testing rates. The report argues that the effort required for a simple blood test is small compared with the cost of missing a progressive lymphopenia that leaves a patient vulnerable to invasive bacterial disease.
The interplay between the two lessons deserves emphasis. Vaccination reduces the probability of the triggering infections, while monitoring detects the immune vulnerability that turns those infections into emergencies. Neither measure alone is sufficient. A fully vaccinated patient can still encounter a pneumococcal serotype not covered by the vaccine or an influenza strain drifted beyond the seasonal match, and a patient with normal lymphocyte counts can still suffer severe pneumonia. But the two safeguards together shrink the risk in complementary ways: vaccination lowers exposure to the pathogens most likely to cause invasive disease, and monitoring ensures that the pharmacologically induced component of susceptibility is caught and corrected before a routine viral illness escalates. German consensus recommendations on vaccination strategies in neurological autoimmune diseases similarly stress the need to evaluate both cellular and humoral vaccine responses under immunotherapy, reflecting the same integrated logic.
For neurologists, the case underscores a division of labor that can fail in fragmented health systems. Disease-modifying therapy is typically prescribed and monitored by a neurologist, while vaccinations may be administered by general practitioners, and acute infections present first to emergency departments. When no single actor owns the whole picture, vaccination assessment can fall through the cracks, and abnormal blood counts can be reviewed without connecting them to infection risk. The authors’ experience suggests that a simple checklist at each follow-up visit, covering current lymphocyte trajectory and vaccination status against influenza and pneumococcal disease, could close many of these gaps. The intensive care perspective adds weight to the argument: the clinicians writing this report encountered the end result of the missed safeguards, not the manageable outpatient problem that earlier intervention might have preserved.
It is worth stating clearly what the case does and does not show. A single report cannot establish that dimethyl fumarate caused the severe outcome, nor can it quantify the absolute risk of invasive pneumococcal disease among patients on the drug, which appears low given the large numbers treated worldwide. Network meta-analytic evidence supports the overall efficacy and acceptable safety of immunomodulators for relapsing-remitting multiple sclerosis, and dimethyl fumarate remains an appropriate choice for many patients. The value of the report lies in its illustration of a known mechanism, viral-bacterial synergy in the lung, meeting a known vulnerability, drug-associated lymphopenia, in a setting where both were potentially modifiable. Rare severe infections are precisely the kind of outcome that routine precautions are designed to prevent, and their occurrence signals a need to audit whether those precautions were actually in place.
The broader takeaway for patients is equally direct. Anyone living with multiple sclerosis and taking an immunomodulatory therapy should know their vaccination record, ask whether influenza and pneumococcal vaccines are up to date, and confirm that blood counts are being checked on the recommended schedule. Anyone prescribing such therapy should treat the vaccination assessment and the lymphocyte count as inseparable parts of the same safety routine. The Belgian case ended in an intensive care unit, but its authors frame it not as a reason to abandon an effective drug rather as evidence that the infrastructure around the drug, the vaccines given and the blood drawn, matters as much as the prescription itself. In an era of increasingly powerful immunotherapies for neurological disease, that infrastructure is where preventable harm is most often caught, or missed.
Subject of Research: Severe pneumococcal pneumonia following influenza A in a multiple sclerosis patient treated with dimethyl fumarate
Article Title: Severe invasive pneumococcal pneumonia following influenza A in a patient with multiple sclerosis treated with dimethyl fumarate: the importance of vaccination assessment and hematologic monitoring
Article References: Severe invasive pneumococcal pneumonia following influenza A in a patient with multiple sclerosis treated with dimethyl fumarate: the importance of vaccination assessment and hematologic monitoring. (n.d.). https://doi.org/10.1007/s00415-026-14118-z
Image Credits: AI Generated
DOI: 10.1007/s00415-026-14118-z
Keywords: multiple sclerosis, dimethyl fumarate, influenza A, pneumococcal pneumonia, lymphopenia, vaccination, hematologic monitoring, immunotherapy, Streptococcus pneumoniae, acute respiratory distress syndrome, disease-modifying therapy, intensive care
News Source: Kristina Jarvis. (October 8, 2026). Flu Followed by Pneumococcal Pneumonia: A Multiple Sclerosis Case Exposes Gaps in Vaccine and Blood Monitoring. Scienmag.
