Borreliosis: A multifaceted disease

Lyme disease is often disguised and may occur long after the tick has left its host. In tick-borne Lyme disease, the bacteria are transmitted by vectors and may lead to various symptoms and skin manifestations.

Lyme disease can be caused by various Borrelia species, leading to neurological symptoms or possibly affecting the joints. Dr Markus Starink (Amsterdam University Medical Centre, the Netherlands) pointed out that these bacteria all depend on vectors for transmission to humans [1]. They are known to cause tick-borne illnesses and are transmitted by the Ixodes ricinus in Europe or the Ixodes scapularis in the USA.

In the early stages of Lyme borreliosis (i.e. days to weeks after an infectious tick bite), the Lyme disease is localised, and one may notice erythema migrans. Erythema migrans is the most prominent manifestation of Lyme disease, occurring in 77-89% of cases. It is an erythematous macule or papule/plaque, spreading centrifugally within days to months -on average 2-3 weeks- after the initial tick bite. Recently, more homogeneous patterns are seen, such as an erythematous macule and, less often, of an annular shape. The lesions are usually asymptomatic and vary in size upon presentation (>5 cm). In adults, erythema migrans is predominantly found in or around the flexor side of the great joints, mostly inguinal/legs. In children, preferred sites are the head and the neck. The lesions usually disappear after several weeks or months (4 weeks on average). Atypical manifestations may be evident in skin folds, where the shape of the erythematous region is no longer circular but is rather an incomplete ring related to local haemorrhage. Within weeks to months, early disseminated disease manifests as borrelial lymphocytoma and multiple erythema migrans.

Borrelial lymphocytoma occurs in 2-3% of the infections and more often in children, often at the earlobe and scrotum, than in adults, often at the areola. Smooth, asymptomatic, blue-red nodules and plaques, 1 to several centimetres in size may be detected in the vicinity of the original tick bite. If left untreated, these lesions can persist for months. In 50% of the cases, they may be detected together with or directly after the resolution of erythema migrans.

Early signs of neuroborreliosis may present as radiculitis, meningitis, and peripheral facial paresis. Further manifestations include Lyme-arthritis, carditis, uveitis, hepatitis, myositis, and orchitis. Late stages of the illness (>1 year) are characterised by acrodermatitis chronica atrophicans, chronic neuroborreliosis, and chronic arthritis. Acrodermatitis chronica atrophicans typically occurs 6 months to 10 years after infection in 1-3% of all cases. In 70% of those cases, one or both (lower) legs are affected. In starts with red/purple "inflammatory" colouration, which is slowly progressive and reversible after treatment. Later, red/blue atrophy is observed, and sometimes localised scleroderma or lichen sclerosus-like changes, or fibrous plaques. Acrodermatitis chronica atrophicans is often accompanied by irreversible treatment-resistant symptoms, including peripheral neuropathy (in 60% of the cases), hyperalgesia (50%), joint involvement, muscle weakness and cramp, headache, and tiredness.

Dr Starink advised not to rule out Lyme disease in people with no history of a tick bite because some tick bites go unnoticed or transmission might have occurred long before skin manifestations have become apparent. Checking for Lyme disease is based on serology, PCR (sensitivity up to 90% in skin), culture (sensitivity 40-80%), and histology. Serology will still render negative results in early stages of the disease and may not be helpful in the erythema migrans phase. Antibody titers, such as IgG, remain positive after successful treatment and are, therefore, not suitable for follow-up. The treating physician should also consider that PCR results may remain positive after treatment. Regarding borrelial lymphocytoma, serology is positive in 70-90% of the cases and PCR sensitivity is up to 90%. For acrodermatitis chronica atrophicans, sensitivity is 75% for PCR and 98% for serology (high IgG).

Therapeutic options differ per country

When it comes to treatment, the Dr Starink advised the audience to stick to regional guidelines as national recommendations may vary tremendously.

Prophylactic treatment after a bite generally consists of one 200-mg doxycycline dose. Data from the USA has indicated that it might prevent erythema migrans, but there is no data available on later stages of the illness.

For primary erythema migrans, doxycycline (100 mg twice daily for 10-14 days) is typically prescribed. In case of allergies, pregnancies, or in children, amoxicillin or azithromycin may both serve as alternatives. Disseminated/multiple erythema migrans, borrelial lymphocytoma, and acrodermatitis chronica atrophicans can be treated with doxycycline or, alternatively, ceftriaxone. In Germany and in the UK, amoxicillin is recommended for acrodermatitis chronica atrophicans. However, not all patients will notice a marked improvement after treatment because of irreversible skin changes. For this group, recent studies showed no improvement after prolonged treatment or re-treatment.

"Tick"-home message

Recognising Lyme borreliosis and treating it as early as possible can prevent chronic and disabling disease. Dr Starink stressed that erythema migrans does not only present as a ring and should be considered when detecting any kind of centrifugally spreading erythema. Further, there is no indication for serology in erythema migrans. Acrodermatitis chronica atrophicans may be suspected in patients presenting with red/purple/blue discoloration on one or more extremities. Lastly, Dr Starink strongly advised his listeners to consult their local guidelines for adequate treatment.

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   1. Starink M. Borreliosis: How to diagnose and treat. D1T04.3D, EADV 2020 Virtual Congress, 29-31 Oct.