Dengue-induced Guillain–Barre syndrome: a case series

Dengue fever is an infection caused by the dengue virus, which is a single stranded RNA virus belonging to the Flaviviridae family. While most cases of dengue fever present with mild symptoms, such as fever, headache, and joint pain, a small percentage of patients can develop more severe manifestations. Neurological complications are reported to occur in less than 5% with dengue fever [1]. These may include encephalitis, aseptic meningitis, intracranial haemorrhage, myelitis, mononeuropathies, polyneuropathies, brachial plexopathies, and Guillain–Barre syndrome (GBS). GBS is a post infectious ascending, polyradiculoneuropathy accompanied by areflexia, motor paralysis, and elevated cerebrospinal fluid (CSF) total protein without raised cell counts [2].

Although the precise mechanism through which the dengue virus triggers GBS is not completely understood, it is hypothesized that the virus may induce the production of antibodies that attack peripheral nerves, resulting in limb weakness and paralysis [3]. Substances with pro-inflammatory properties that are involved in the immune response to dengue virus (DENV), such as tumor necrosis factor (TNF), interleukins, and complements, may play a significant role in the development of GBS [4].

In Asian countries, the axonal variant of GBS is frequently observed, while the demyelinating variant is more prevalent in Western countries [5]. Limited reports exist in literature documenting GBS cases in adults with dengue fever [6, 7]. In all reported cases, onset of GBS symptoms occurred after recovery from the initial dengue infection. The specific variants of dengue that can cause GBS are unknown.

Herein, we report four cases of GBS variants associated with dengue virus and their outcomes.

The dengue virus, commonly referred to as DENV, has four serotypes: DENV1, DENV2, DENV3, and DENV4. Each of these serotypes can result in a wide range of illness, ranging from subclinical infection to mild, self-limiting dengue fever, as well as severe and potentially fatal conditions such as dengue haemorrhagic fever/dengue shock syndrome [8]. All the patients described in our case series were male, with ages ranging from 21 to 69 years They all presented within three weeks of contracting dengue fever, which was confirmed by either NS1 antigen or IgM serology testing. Given the endemic nature of dengue in our region, we routinely screen patients for dengue with high grade fever, with or without a low platelet count. One patient was diagnosed with AIDP, another with AMAN, and two with AMSAN based on electrophysiological testing. Table 1 provides a summary of the cases.

Lumbar puncture was not performed in any of these patients. Notably, the patient diagnosed with AIDP also had a myopathy, which is a unique finding as there have been no reports of both conditions coexisting after dengue. It is to be noted that the myopathy was non-irritable, accompanied by a normal CPK level, suggesting a non-inflammatory cause. This could be due to a latent underlying myopathy or possibly related to dengue fever. It is worth considering that the study might have been conducted prematurely in the course of the disease, or this myopathy might stem from an existing underlying incidental myopathy. Unfortunately, this patient left the hospital against medical advice without receiving any treatment, and as a result, the outcome of illness is unknown. Two of the patients with AMAN and AMSAN variant showed improvement after receiving plasmapheresis and IVIG treatment respectively (the decision to receive IVIG or plasmapheresis was based on patient’s preference). However, one patient with AMSAN experienced respiratory failure due to hospital-acquired pneumonia and required intubation. He had a cardiac arrest and ultimately passed away.

In a review by Garg et al., which included 29 patients with dengue fever associated GBS, it was reported that most patients had a low platelet count at the time of developing weakness, indicating that GBS was a manifestation of acute dengue fever [1]. On the contrary, our patients had a normal platelet count, suggesting that the acute neuropathy came in the aftermath of acute viremia and not during it. This suggests that the relationship between dengue fever, GBS, and platelet counts may not be straightforward and requires further investigation. It should be noted that variants of dengue are not tested for routinely; therefore, it is not clear if a certain variant of dengue is associated more with the development of GBS.

The outlook of GBS is favorable. A study conducted on ten patients in Brazil with GBS following dengue fever revealed that all patients achieved full recovery after receiving IVIG treatment, and most of them showed recovery within 3 months. AMSAN variant was identified in all these cases [9]. In our series, patient with AMSAN variant had a more severe phenotype and lack of response to appropriate treatment. While the prognosis of GBS is typically good, patients with severe disease may have a mortality rate of around 10%, particularly when they experience complications from extended mechanical ventilation [10]. Three of our patients at 3 months follow up were ambulatory.

Overall, our case series adds to the growing body of evidence that dengue fever can trigger GBS, with various clinical variants observed. The absence of low platelet counts (Refer to Table 1 for laboratory details) in our patient raises questions about the underlying mechanisms of this association and highlights the need for further studies. It is also important to note that while most of the patients recover from illness, some of them may have a poor prognosis despite timely intervention. Therefore, a multidisciplinary approach and close monitoring of patients with dengue associated GBS are crucial for achieving the best possible outcomes.

Dengue fever is a significant public health concern worldwide, particularly in endemic areas. While uncommon, GBS should be considered as a potential diagnosis in patients who experience weakness following dengue infection. In developing nations where such cases may be under-reported, recognizing this condition is crucial in reducing its associated morbidity and mortality.