Dermatological manifestations of Lyme borreliosis 
DERMATOLOGICAL MANIFESTATIONS 
OF LYME BORRELIOSIS 
G. Trevisan, P. Cattonar, C. Nobile, 
V. Perkan and G. Stinco 
ABSTRACT 
Lyme Borreliosis is a multisystemic infection involving skin, joints, the neivous system, the heart and eyes. 
As of yet four different genospecies of Borrelia burgdoiferi have been identified: Borrelia burgdoiferi sensu 
stricto, Borrelia garinii, Borrelia afzelii, and Borrelia japonica. Different strains of borreliae have been associated 
with different clinical manifestations of Lyme Borreliosis. Lyme Borreliosis is classically described as having 
three clinical stages or, similar to syphilis, an early phase and a late one. The early infection corresponds 
to the first stage, the late infection includes the second and the third stages. Skin manifestations of Lyme 
Borreliosis could be classified into five categories. The first one is characterized by skin manifestations proven 
to be caused by Borrelia burgdorferi infection, including erythema migrans, lymphadenosis benigna cutis and 
acrodermatitis chronica atrophicans. The second category covers controversial Lyme Borreliosis manifestations, 
such as lichen sclerosus et athrophicus, morphea, scleroderma, Scleredema of Buschke, atrophoderma of 
Pasini and Pierini, Parry-Romberg syndrome (facial hemiatrophy) and Shulman's fasciitis. The third category 
encompasses granuloma annulare, atypical persistent pityriasis rosea and pityriasis lichenoides which are skin 
lesions occasionally related to Lyme Borreliosis. Urticaria, erythema nodosum and papular acrodermatitis 
(Giannotti Crosti syndrome) have been classified as reactive Lyme Borreliosis skin manifestations. The last 
category of diseases includes exceptional skin manifestations during Lyme Borreliosis such as nodular 
panniculitis (Weber-Christian), B-cell cutaneous lymphoma and juvenile chronic myeloid leukemia. 
KEY WORDS 
Lyme borreliosis, skin manifestations, Borrelia burgdorferi 
INTRODUCTION 
In recent years there have been numerous and 
important advances in the field of Lyme Borreliosis 
(LB). However, many questions concerning this disease 
still remain unanswered. The spirochetal behaviour 
acta dermatovenerologica A.P.A. Vol 5, 96, No 3-4 
is not clear after Borrelia burgdorferi (Bb) bas infected 
the human body. These organisms can produce 
pathognomonic lesions, skin manifestations mimicking 
other diseases or clinical pictures that can also be 
induced by other causative agents. 
101 
Dermatological manifestations of Lyme borreliosis 
Fig. 1: Ixodes ricinus 
Fig. 2. E,ythema (chronicum) migrans 
Fig. 3. Lymphadenosis benigna cutis of areola mammae 
102 
We have also become aware of 
the complexity of this disease since 
genetic studies were able to identify 
different species of Bb sensu lato 
responsible for human infections: 
Bb sensu stricto, B. garinii and B. 
afzelii (1). In Japan a new species 
was recently described, B. japonica, 
which does not appear to be a 
human pathogen (2). In the future 
additional species of Bb will most 
likely be recognized. The Bb 
infection is mostly transmitted by a 
hard tick of the genus Ixodes (Fig. 
1). Different Bb strains appear to 
have a distinct organotropism and 
can induce various clinical mani-
festations. A possible follicular hair 
tropism of Bb may explain the 
erythema migrans (ECM) with hair 
loss. B . afzelii has been found in 
patients with acrodermatitis chronica 
atrophicans (ACA), whereas Bb 
sensu stricto has been found in 
patients with arthritis and B. garinii 
in patients with neuroborreliosis (3). 
The presence of an infected tick, 
a persistent attachment to the skin 
for about one or two days and the 
appearance of an enlarging erythema 
after an incubation period of at 
least 4 - 5 days indicate the diagnosis 
of LB. Therefore, the clinical diag-
nosis of LB is confirmed when the 
vector is identified and ECM appe-
ars. On the other hand, a tick bite 
can often go unnoticed because skin 
reaction can be limited and asymp-
tomatic. Sometimes a papule, an 
angiomatoid patch, a pseudo-lympho-
matous or granulomatous nodule 
or a persistent oedematous-papular 
dermatitis appear on the tick bite 
site (4). These unspecific lesions 
indicate a chemical reaction to the 
anticoagulant saliva introduced by 
the tick and are not Bb infection-
correlated. 
LB skin manifestations could be 
classified into the following cate-
gories: i) proven LB skin mani-
festations, ii) controversial LB skin 
manifestations, iii) skin manifestations 
acta dermatovenerologica A .P.A. Vol 5, 96, No 3-4 
Dermatological manifestations of Lyme borreliosis 
Fig. 4. Spirochetal-like organisms in the epidermis of 
lymphadenosis benigna cutis (Warthin-Stany stain) 
Fig. 5. Acrodermatitis chronica atrophicans 
acta dermatovenerologica A.P.A. Vol 5, 96, No 3-4 
occasionally related to LB, iv) reactive LB skin 
manifestations, v) exceptional skin manifestations 
during LB. 
PROVEN L YME BORRELIOSIS SKIN 
MANIFESTATIONS 
These consist of erythema (chronicum) migrans, 
lymphadenosis benigna cutis (LABC) and acro-
dermatitis chronica atrophicans. 
The old abbreviation ECM is still used, because 
EM alone may be confused with another skin disease, 
erythema multiforme. ECM is the most common 
and typical manifestation of LB (Fig. 2). It is an 
annular-shaped erythema rapidly extending centrifugally 
with a diameter of at least 5 cm and, over a period 
of 3 - 4 months, ECM can even reach a size of 50 
cm (5). ECM appears about 4 - 30 days after a tick 
bite, usually at the same site. ECM is the only skin 
manifestation in the first stage of LB. It occurs as 
the first lesion in about 50% of LB cases (5). All 
of the Bb species are able to cause ECM. Any site 
on the human body can be affected. In children 
ECM is more often localized on the head because 
Fig. 6. Lichen sclerosus et atrophicus 
103 
Dermatological manifestations of Lyme borreliosis 
of their small stature (6). There is considerable 
variation in the appearance of this lesion, including 
erysipeloid, purpuric, nodular and atrophic aspects 
(7,8). Hair loss on the site of ECM is also 
reported (9). Atypical ECM may be induced by 
different Bb, certain individual host reactivity, 
immunological mechanisms or lengthy Bb persistence 
in the skin. 
This early skin lesion is sometimes associated 
with constitutional signs and symptoms including 
fever, chills, lymphadenopathy, headache, and 
myoarticular pain (7) . 
Untreated ECM can resolve spontaneously, but 
sometimes it persists longer, producing a central 
atrophy (10). 
The criteria for the clinical diagnosis of ECM 
are the presence of an annular-shaped erythema 
with more than 5 cm of diameter and its appearance 
at least 4 - 5 days after a tick bite. These criteria 
are particularly important in case of atypical ECM. 
In cases when the diagnosis is uncertain, spirochetal 
organisms may be detected in involved skin by 
silver stain (Warthin-Starry), uranil stain (Steiner-
Steiner), monoclonal antibodies, cultivation in BSK 
medium or by polymerase chain reaction. Positive 
culture results are able to confirm the clinical 
diagnosis, but false negative results are frequent. 
Serological assays often produce negative results 
during the first few weeks of the illness, therefore 
it is not an important criterion for diagnosis. 
Multiple annular erythemas (MAE) are a con-
sequence of the rapid blood dissemination of Bb. 
This justifies their classification at the early second 
stage, rather than at the first stage. MAE lesions 
are similar to ECM, but there is no evidence of 
a tick bite. MAE are more frequently observed in 
children (6) . 
In rare cases Bb infection may lead to roseolar 
manifestations. In one case we were able to cultivate 
Bb from the affected skin (11) which was later 
identified as B. garinii. 
LABC is the typical second stage manifestation 
of LB (Fig. 3). There is a plain form (Jessner-
Kanof type) and a nodular form (Spiegler-Fendt 
type ). The Jessner-Kanof lymphocytoma consists of 
a port wine-like patch of more than 10 cm in 
diameter (12). 
T-lymphocytic infiltration is present in histological 
samples. The Spiegler-Fendt lymphocytoma may 
appear in a solitary or disseminated form. Solitary 
lesions are often localized on the ear lobe or on 
104 
Fig. 7. Morphea 
Fig. 8. Granuloma annulare 
acta dermatovenerologica A.P.A. Vol 5, 96, No 3-4 
Dermatological manifestations of Lyme borreliosis 
areola mammae (13), whereas ctisseminated lesions 
are localized on the back. The infiltrate consists 
mainly of B-lymphocytes. 
Warthin-Starry stained biopsy specimens of LABC 
examined by light microscopy demonstrate spirochetes 
in the epidermis where these organisms cannot be 
confused with other cutaneous structures (14) (Fig. 4). 
Sometimes LABC is caused by Bb infection (borrelial 
lymphocytoma), but it can also have a different 
etiology. 
LABC resolves spontaneously within months to 
years but is cured more rapidly with antibiotics (10). 
ACA is a typical late skin manifestation of LB 
(Fig. 5). It is caused only by B. afzelii; in the USA 
only few cases have been reported (15), probably 
because B. afzelii is not present in this country. 
ACA is a chronic progressive dermatitis, characte-
rized by an early inflammatory and a late atrophic 
stage (16). The inflammatory stage begins on one 
extremity, most common at an acral site, such as 
the hand or foot, with bluish-red discoloration and 
doughy swelling. 
The atrophic stage involves not only the skin but 
also the subcutaneous tissue and the muscle under-
neath. The atrophy appears as extremely thin, 
transparent skin ( cigarette paper-like) with clearly 
visible veins and a loss of hair follicles and sebaceous 
glands. 
Sometimes fibrous nodules may occur adjacent to 
the joints. In these lesions it is possible to identify 
Bb by staining techniques or culture (17). Pain, 
pruritus, hyperesthesias or paresthesias are usually 
associated with it. 
In our regions the observation of cases of in-
flammatory ACA is frequent, whereas atrophic ACA 
Table l. Controversial skin manifestations of Lyme 
Borreliosis. 
Lichen sclerosus et atrophicus 
Morphea 
Scleroderma with generalized plaque lesions 
Linear scleroderma 
Atrophoderma of Pasini and Pierini 
Parry-Romberg syndrome (facial hemiatrophy) 
Shulman's syndrome ( eosinophilic fasciitis) 
Scleredema of Buschke 
acta dermatovenerologica A.P.A. Vol 5, 96, No 3-4 
is very rare (18). The cause is unknown. It is 
conceivable that either a different strain of B. afzelii 
is present in Italy, climatic conditions or the Italian 
immunogenetic type is responsible for that fact. 
CONTROVERSIAL LYME 
BORRELIOSIS SKIN 
MANIFESTATIONS 
The possible relationship between LB and sclero-
atrophic skin manifestations has been suggested by 
some clinical, immunological and microbiological 
evidence. However, numerous authors were not able 
to demonstrate Bb infection in such patients and 
have cast doubts on an etiological role of Bb in 
scleroatrophic skin lesions. Bb may be an etiological 
agent of lichen sclerosus et atrophicus (LSA) (Fig. 
6), although this affection must be considered a 
multifactorial disease. LSA related to Bb infection 
has been first reported by Asbrink (19) who noticed 
the frequent association between LSA and ACA. 
Aberer et al. demonstrated the presence of Bb in 
LSA (20). Further evidence for Bb infection in 
morphea and LSA has been recently shown by 
PCR. We observed a specific amplification in three 
children living in Trieste (Friuli-Venezia Giulia), an 
Italian area endemic for LB. However, we were not 
able to detect Bb-specific DNA in four patients 
with LSA living in a non-endemic area (Milan) (21) 
(Table 1). 
Since 1985 when Aberer et al. claimed that morphea 
(Fig. 7) might be a late manifestation of LB (22), 
numerous conflicting reports have followed and this 
hypothesis is still debatable (23-26). In some cases 
morphea might be caused by B. afzelii. 
The possible relationship between Bb infection 
and LSA or morphea, respectively, is suggested by 
the following evidence: i) clinical and histological 
similarities between morphea, LSA and ACA and 
the coexistence of ACA, LSA and/or morphea in 
the same patient, ii) the presence of antibodies 
against Bb in some patients with LSA and morphea, 
iii) the identification of borrelial organisms or genoma 
in histologic sections, iv) a response to antimicrobial 
therapy in many cases of LSA and morphea. 
SKIN MANIFESTATIONS OCCASIONALL Y 
RELATED TO LYME BORRELIOSIS 
Granuloma annulare (GA), atypical persistent 
pityriasis rosea and pityriasis lichenoides are skin 
105 
Dennatological manifestations of Lyme borreliosis 
lesions occasionally related to LB. The association 
between GA (Fig. 8) and Bb infection has been 
reported by Strle et al. (27). The correlation has 
been suggested by serological evidence or by iden-
tification of spirochetal organisms in the affected 
skin by silver staining. Based on our experience, 
GA is rarely related to LB. We could detect Bb in 
affected skin by PCR in only three patients with an 
unusual clinical course. 
An atypical persistent pityriasis rosea, lasting longer 
than 4 - 5 months, could also be suspected to be 
related to LB (28). 
We are presently studying some children who 
developed papular dermatitis with perifolliculitis, 
mimicking pityriasis lichenoides. In one case we 
were able to cultivate Borrelia sp. from the affected 
skin (BSK medium) (29). 
Further studies are necessary to define the clinical 
aspects of this form of dermatitis to confirm the 
correlation to LB. 
REACTIVE L YME BORRELIOSIS 
SKIN MANIFESTATIONS 
Reactive LB skin manifestations are nonspecific 
lesions that usually also occur during other infectious 
diseases. They are immunologic responses to spiro-
chetal antigens. None of these manifestations has 
been found to contain spirochetes. 
Diffuse urticaria is more frequent in early LB, 
whereas the localized form is more frequent in late 
LB; the last one usually occurs in the skin adjacent 
to the affected joints during articular attacks (30,31). 
Erythema nodosum has also been observed during 
LB. 
We have recently reported two children who deve-
loped papular acrodermatitis (Gianotti-Crosti syndrome) 
after Bb infection. 
EXCEITIONAL SKIN MANIFESTATIONS 
DURING LYME BORRELIOSIS 
Nodular panniculitis (Weber-Christian), B-cell 
cutaneous lymphoma and juvenile chronic myeloid 
leukemia are exceptional skin manifestations during 
LB. 
Two patients suffering from nodular panniculitis 
associated with Bb infection have been reported 
(32). In one case Bb was repeatedly isolated from 
the skin and subcutaneous tissue even after antibiotic 
treatment. 
The correlation between LB and cutaneous B-cell 
lymphoma is still debated. The evolution from borrelial 
lymphocytoma to malignancy has been suggested 
(33), nevertheless this hypothesis needs to be further 
investigated. 
Only one case of association between LB and 
juvenile chronic myeloid leukemia was described 
(34). 
CONCLUSION 
The subject of cutaneous LB manifestations is not 
fully understood up to now. Further studies may 
reveal that some other skin disorders of actually 
unknown etiology are induced by Bb infection. 
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AUTHORS' ADDRESSES 
Giusto Trevisan, MD, professor, Institute of Dermatology, University of Trieste, Ospedale di Cattinara, 
Strada per Fiume, I-34149 Trieste, Italy 
Patrizia Cattonar, MD, same address 
Carla Nobile, MD, same address 
Valentina Perkan, MD, same address 
Giuseppe Stinco, MD, Department of Dermatology, Palmanova Hospital, Palmanova, Italy 
acta dermatovenerologica A.P.A. Vol 5, 96, No 3-4 107