Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) is a rare immune-mediated disorder with a heterogeneous pathophysiology (1) and presentation. A number of CIDP variants have been identified, including asymmetrical (also known as MADSAM), focal, distal, sensory and motor CIDP. The disease is typically characterized by progressive symmetrical weakness and sensory symptoms in arms and legs which develop over a period of more than 8 weeks. More rapid onset of acute symptoms within 4 weeks has also been observed in up to 13% of patients (2). Traditional first-line treatment options such as intravenous immunoglobulin and corticosteroids aim to alleviate these symptoms and, ideally, induce and maintain long-term remission. However, many patients continue to experience symptoms despite treatment (3, 4), and some do not respond to treatment at all (5). The prevalence of CIDP has been observed to increase with age, is higher in men and ranges between 0.7 to 10.3 cases per 100,000 people (6). This considerable variation in prevalence rates may be explained by the level of neuromuscular expertise involved, as well as the differences between countries or regions (7). The use of different diagnostic criteria has also been implicated herein (8).

The diagnosis of CIDP is typically made using a combination of clinical and electrodiagnostic criteria, potentially supported by ultrasound or magnetic resonance imaging results, cerebrospinal fluid, nerve biopsy or antibody testing (2). However, several factors can complicate the diagnostic process. Firstly, the disease presents heterogeneously, and no reliable biomarkers have yet been identified (9, 10). Secondly, while there is consensus in theory, existing guidelines may be underutilized in practice due to lack of awareness (11) or practical constraints. Thirdly, diagnostic test results have been known to be misinterpreted (12, 13). And finally, mimics – diseases which present similarly to CIDP and its variants – can cause confusion during the diagnostic process (14–16). All of these aspects can prevent patients from receiving an early diagnosis and proper therapies, which are crucial to prevent axonal loss and resulting disability (17–19).

Another consequence of the aforementioned confounding factors is that both over- and underdiagnosis are a common problem (20). Cornblath et al. (21) estimated that up to one-third of patients in the US with a diagnosis of CIDP do not have the disease. In a Dutch sample of 96 patients, 32% had a referral diagnosis of CIDP that was later revised (22). Patients erroneously diagnosed with CIDP may be treated for long periods of time without clear therapeutic effect, potentially posing a substantial cost to not just the patients, but also to the health care system (23). Simultaneously, many patients with CIDP initially receive a different diagnosis: a Dutch and a British study found this to be the case for 20% and 68% of patients in their respective samples (22, 24). An incorrect diagnosis can contribute to a substantial diagnostic delay and ineffective treatment (25). Bunschoten et al. (4) reported that the time between symptom onset and correct CIDP diagnosis was highly variable, with a median duration of 5 months (interquartile range: 2–12 months), and that it took more than a year for a quarter of CIDP patients to receive their diagnosis. According to Chaudhary et al. (24), patients (n = 27) that had been referred with a non-CIDP or Guillain-Barré syndrome (GBS) diagnosis experienced a mean delay of 21.3 months (range 2–123 months) before finally being diagnosed with CIDP.

Beyond the studies previously mentioned, there has been little real-world research into CIDP patients’ journey to diagnosis and what patient characteristics might potentially influence it. This study seeks to further elucidate this aspect of CIDP through a secondary analysis of patients’ demographics, comorbidities, symptomatology, disease severity, Inflammatory Neuropathy Cause and Treatment (INCAT) score, experience with (mis)diagnosis, and diagnostic tests, as reported by their physician. We will also look at the association between a number of variables (age category, sex, disease severity at symptom onset, Body Mass Index (BMI) and CIDP type) and misdiagnosis, as well as time to diagnosis.

We sought to contribute to the limited evidence on diagnosis of CIDP in the published literature through a description of a large real-world sample of CIDP patients and their experience in in getting diagnosed with CIDP. This study illustrated that CIDP patients’ journey to diagnosis can be lengthy and laborious. Median time from symptom onset to first consultation was 3.0 months (maximal value: 267 months) and median time from first consultation to diagnosis was also 3.0 months, (maximal value: 155 months). It should be noted that the latter maximum value suggests very mild disease, making it difficult to determine if the symptoms for that entire period were indeed related to CIDP. In addition, patients underwent 19.6 diagnostic procedures on average before receiving a confirmatory diagnosis of CIDP. The most frequently used diagnostic tests in our sample correspond to the EAN/PNS guidelines’ strongly advised investigations and investigations to be performed if indicated (2).

The majority of patients in our sample were prescribed treatment at the time of survey, with immunoglobulin and corticosteroids being administered most often. The rates at which these treatments were prescribed differed between countries. One of the reasons for this could be local healthcare systems related to the prescription of immunoglobulin, which can impact clinical practice. As the EAN/PNS provide overarching recommendations regarding treatment but do not mandate a single preferred approach, differences in usage rates naturally occur.

Half of our sample had at least one comorbidity, with anxiety and depression being the top 2 reported comorbidities in almost every country, though proportions varied substantially. The differences between countries may be culture-bound, as a lack of emotional wellbeing may not be considered as a comorbidity in some countries or practices. Concurrent diabetes was reported third most often. A fifth of patients with concurrent diabetes in our sample were diagnosed with diabetes after having been diagnosed with CIDP. However, some may have simply had undiagnosed diabetes prior to the onset of CIDP. The rate of diabetes in our cohort was lower than in recent literature from the UK, Serbia and Italy (32, 33). These studies suggest a two-fold risk of diabetes in subjects with CIDP, which is supported by reported rates in cohorts and epidemiological studies from other countries (34, 35). Compared to the study by Doneddu et al. (32), the mean age and the proportion of patients having at least one comorbidity were lower in our cohort (54 years old and 50% vs. 58 years old and 75% in theirs, respectively), which may explain the lower rate of diabetes.

Over a third of patients in our sample were misdiagnosed at least once, though some of these misdiagnoses could represent an initial attempt by a general healthcare practitioner rather than a specialist. GBS represented over a third of misdiagnoses. It can be debated if GBS is a true misdiagnosis, as acute-onset CIDP presents in a similar way to GBS and the diagnosis only becomes apparent with time, demonstrating continuing progression or successive relapses. No statistically significant associations were observed between patient characteristics (age category, sex, disease severity at onset, BMI and CIDP subtype) and the likelihood of misdiagnosis. However, regression analysis indicated that patients who presented with mild symptoms at onset, had variant CIDP or had initially been misdiagnosed on average took longer to receive a diagnosis of CIDP. Previous literature has highlighted that CIDP variants are more challenging to diagnose and have a higher probability of initial misdiagnosis (4, 12, 14, 16, 22). Our findings are consistent with this, with patients that suffered from variant CIDP having a longer time to diagnosis. However, while the proportion of misdiagnoses was higher in patients with variant CIDP (41%) than typical CIDP (35%), this difference was not statistically significant.

The consequences of delayed diagnosis are multiple. In the short-term, patients are delayed in receiving symptom-alleviating immunomodulatory treatment. In the long-term, their physical and mental health, as well as their quality of life, are likely to suffer major consequences, with patients potentially sustaining permanent nerve damage if they are not treated. A recent multicenter study of 144 subjects from Korea and the UK demonstrated poorer outcomes when treatment was commenced over a year after symptom onset as compared to within a year (36). These findings are in keeping with the occurrence of irreversible axonal loss with delayed diagnosis and treatment.

Our study has a number of limitations: first and foremost, it solely utilized physician-reported data, preventing us from capturing the patient’s perspective. Patients included in the DSP sample may not be truly representative of the overall population of CIDP patients, as patients who consult with health care providers more frequently are more likely to be included. In addition, only patients aged 18 and older were included, preventing the capture of diagnostic data for minors with CIDP, a demographic for which little real-world data has been collected thus far. The quality of the data is also dependent on the reporting accuracy of information by physicians which may be subject to recall bias. Additionally, information on misdiagnosis was not available for all patients. Furthermore, this survey captured point-in-time data which, by its very nature, is unable to capture the complete burden associated with a progressive and relapsing/remitting disease such as CIDP. Finally, according to the European Academy of Neurology and Peripheral Nerve Society guidelines, autoimmune nodopathies should not be classified as CIDP, because they show a different clinical manifestation and respond poorly to intravenous immunoglobulin (2). Different studies have shown that Rituximab is effective in patients with an autoimmune nodopathy (37, 38). Nevertheless, nodal and antinodal antibodies can be found in 10–15% of patients diagnosed with CIDP (16). No distinction was made between CIDP and autoimmune nodopathies in the DSP. Despite these limitations, real-world data on CIDP patients’ diagnostic experience is valuable due to its scarcity, especially for large samples. To our knowledge, this is the largest real-world study describing this aspect of the disorder to date.

From our analysis, we conclude that the journey to diagnosis for patients suffering from CIDP is a difficult one: median time to diagnosis in our sample was 7 months and a third of patients were at some point misdiagnosed. The heterogeneous presentation of CIDP, including its variant forms, further complicates timely diagnosis. Mild symptoms at onset, having variant CIDP and having been misdiagnosed were found to be associated with a longer time to diagnosis. In view of recently reported poorer outcomes with delayed treatment, there is a clear need for optimization of the diagnostic process, and for further research into the factors that contribute to delays.