Lyme disease, also known as Lyme borreliosis, is the most common tick-borne bacterial infection worldwide. The disease is caused by members of the Borrelia burgdorferi sensu lato complex, which can affect multiple organ systems, including the skin, joints, nervous system, and vascular system. The clinical presentation is extremely variable, especially in the late stages, when the infection can have lasting immunological and vascular consequences.
Raynaud’s syndrome is a functional circulatory disorder in which cold or emotional stress causes the peripheral small vessels – most commonly the arteries and arterioles of the fingers and toes – to temporarily constrict. As a result, the affected areas turn pale, then blue, and finally red after warming up. The phenomenon can be primary (idiopathic), but often appears in a secondary form when there is an underlying disease, such as an autoimmune, connective tissue, vascular, or infectious condition that triggers it.
According to a summary by the Global Lyme Alliance, a growing number of clinical observations suggest that Lyme disease may be associated with Raynaud-type symptoms in some patients. Although Lyme infection is not one of the classic causes of Raynaud’s, there may be a biologically plausible link between the two conditions, especially in cases of chronic or late-stage infection. Raynaud’s phenomenon associated with Lyme disease often occurs in an atypical form: it is not always symmetrical, develops at an older age, and may be associated with other neurological or circulatory complaints, which is more indicative of secondary Raynaud’s.
From a pathophysiological point of view, an excessive vasoconstrictive response of the sympathetic nervous system plays a key role in the development of Raynaud’s syndrome, which occurs primarily through α-adrenergic receptors located on the smooth muscle cells of the vessel walls. In a healthy body, this vasoconstrictive response is counterbalanced by effective vasodilatory mechanisms, such as nitric oxide produced by the endothelium. However, if the vessel wall is inflamed, structurally damaged or affected by endothelial dysfunction, vasoconstriction may become excessive and prolonged.
Lyme disease can activate several mechanisms that shift this balance in an unfavourable direction. Borrelia spirochetes are able to adhere to endothelial cells and move in the intercellular space, which can result in local inflammation, microcirculatory disturbance and endothelial dysfunction. In addition, the infection can also affect the functioning of the autonomic nervous system, which can increase vasospastic tendency and make blood vessels more sensitive to cold stimuli.
The immunological consequences of the infection are also significant. In chronic or late-stage Lyme disease, autoimmune processes, immune complex formation and cryoglobulinaemia may also develop. Cryoglobulins and immune complexes precipitated by cold, deposited in the peripheral capillaries, impair microcirculation, increase ischaemic episodes and may contribute to the onset or worsening of Raynaud’s symptoms. These mechanisms are consistent with the clinical observation that cold exposure can cause particularly pronounced Raynaud’s symptoms in patients with Lyme disease.
As early as the 1990s, Hungarian researchers reported cases of Lyme disease in which Raynaud-type symptoms appeared and were alleviated by antibiotic treatment. Since then, several case studies and smaller observations have confirmed this association. For example, a 2022 publication described atypical Raynaud’s syndrome, skin changes and cryoglobulinaemia in a patient with late-stage borreliosis, which were associated with peripheral circulatory disorders. In these cases, the cold clearly provoked the symptoms.
From a clinical point of view, this means that in patients who have had Lyme disease and report finger blanching, numbness, pain or bluish discolouration when exposed to cold, it is reasonable to consider the possibility of secondary Raynaud’s syndrome. According to reports from the Global Lyme Alliance, in some cases, targeted antibiotic treatment has alleviated not only the infectious symptoms but also the Raynaud phenomenon, suggesting a causal role for the infection.
The basis of treatment remains adequate antibiotic therapy for the underlying disease, i.e. Lyme disease. In addition, it is extremely important to avoid exposure to cold, to protect the extremities adequately, and to address lifestyle factors, including quitting smoking, reducing caffeine intake, and reducing stress. In more severe cases, the use of vasodilator drugs, such as calcium channel blockers, may also be considered, but their effectiveness depends largely on whether the underlying infectious and inflammatory processes can be controlled. A multidisciplinary approach – involving collaboration between an infectious disease specialist, a rheumatologist and an angiologist – may be particularly warranted.
Another aspect that may be worth considering is Lyme disease co-infections, e.g. Bartonella, Babesia. These, in combination with Lyme disease or on their own, can further exacerbate vascular and endothelial involvement, thereby intensifying symptoms.
In summary, although the link between Lyme disease and Raynaud’s syndrome is currently supported primarily by case studies and minor observations, vascular, immunological and autonomic nervous system involvement is well documented in borreliosis. Cold as a provoking factor fits logically into this pathophysiological framework. Therefore, in the differential diagnosis of Raynaud’s phenomenon, especially in atypical, late-onset or therapy-resistant cases, it may be justified to consider an infectious background, such as Lyme disease.
https://www.sciencedirect.com/science/article/abs/pii/0140673690910418?dgcid=api_sd_search-api-endpoint
https://link.springer.com/article/10.1007/s00296-024-05580-x
Zajkowska A. et al. Atypical Raynaud’s syndrome and skin changes in late Lyme disease with cryoglobulinemia. ResearchGate, 2022.
https://www.nejm.org/doi/10.1056/NEJMra1507638
https://academic.oup.com/rheumatology/article-abstract/44/5/587/2899267
https://www.globallymealliance.org/blog/raynauds-syndrome-and-lyme-disease
https://www.sciencedirect.com/science/article/abs/pii/0140673690910418
(C) Lyme Borreliosis Foundation
