Lyme Borreliosis (LB) is a complex multisystemic infection that involves the skin, joints, nervous system, eyes, and heart, caused by spirochetes of the
Every case history of each patient addressing to the regional reference centre for Lyme disease in San Daniele del Friuli from June 2004 to June 2010 has been retrospectively recorded and analysed. The medical records of patients that resulted seropositive for
Out of the 2000 analysed case histories, 705 met the inclusion criteria and were recruited in this survey. All of the subjects were resident in Friuli Venezia Giulia.
The ELISA (Enzyme-Linked Immunosorbent Assay) IgM/IgG and Western blot (IgM/IgG immunoblots if early disease was suspected; IgG Western blot alone if late disease was suspected) were performed to define seropositive patients, using the same kit in the same laboratory. Other laboratory and instrumental tests, such as tissue biopsy, culture, polymerase chain reaction (PCR), cerebrospinal fluid examination, sinovial liquid examination, haemochrome, liver function tests, ECG, X-rays, electromyography, and magnetic resonance, have been taken into account, particularly for the doubtful cases.
Seven hundred and five medical records fulfilled the inclusion criteria, and thus were recorded and analysed in this study, including 363 males and 342 females, with a male to female ratio of 1.06. The mean age of the whole survey was 44.7 years, ranging from 4 to 86 years; 67 were under 16 years; 382 were between 16 and 60 years; 256 were over 60 years.
The clinical manifestations observed in the 705 patients seropositive for
The clinical manifestations observed in the 705 patients seropositive for
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Clinical features | Number of patients |
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Skin | 536 |
Musculoskeletal | 511 |
Nervous system | 460 |
Psychae | 37 |
Eye | 71 |
Heart | 57 |
Liver | 41 |
Flu-like | 119 |
There have been 536 (76.03%) cutaneous forms of LB recorded. EM was the most common manifestation and it has been detected in 437 patients (61.99%). There was neither gender difference (M : F = 215 : 222) nor age difference. EM has been found during the visit in 319 patients and it was reported by 118 subjects as an history fact. It appeared from 3 to 25 days after the tick bite (average: after 12 days). Other classical cutaneous manifestations of LB included 58 cases of multiple EM (8.23%), 7 LABC (1%), and 18 ACA (2.55%). Atypical cutaneous manifestations, that is, clinical features not surely linked to LB, were 16 (2.27%), in details: 8 cases of morphoea, 2 Raynaud’s phenomenon, 1 lichen sclerosus and atrophicus, 1 pityriasis lichenoides, 1 Gilbert’s pityriasis rosea, 1 urticaria, 1 anetoderma, and 1 erythema nodosum.
The musculoskeletal system was involved in 511 patients (72.48%): 262 out of 511 presented arthralgias or acute arthritis; they were 119 men and 143 women; 88 had a single episode whereas 174 suffered from several attacks. The evolution to chronic arthritis was seen in 22 cases (8% among the patients with arthralgias/acute arthritis). Muscular hypotonia and/or hypotrophy was observed in 41 patients (5.81%).
Four hundred and sixty patients presented a neurological involvement. Two patients reported Bannwarth’s syndrome, 3 acute encephalopathy and 1 chronic encephalopathy. Two hundred and ninety-three patients (41.56%), 127 males and 166 females, reported cephalea, dizziness, memory and concentration problems, irritability, emotional lability, and sleepiness. As far as the peripheral nervous system is concerned, 161 patients (22.84%) reported paresthesias (115 cases), sensitiveness disorders (47 patients), and motion functionality disorders (19 cases). Out of these 161 patients, 74 suffered from neuritis, polyneuritis, meningoradiculitis and peripheral nerves paralysis, in particular there were 12 cases of the seventh cranial nerve paralysis.
Flu-like symptoms such as fever, arthromyalgia and headache preceded or accompanied or were the only clinical feature in 119 (16.88%) patients. Fever was the only symptom in 11 patients (1.56%) while in 165 (23.4%) cases was accompanied by other manifestations. A reactive regional or generalized lymphadenopathy was recorded in 75 patients (10.64%).
Psychiatric symptoms have been observed in 37 patients (5.25%), 22 men and 15 women. There were 21 cases of anxiety, 10 cases of depression and 6 complex syndromes characterised by panic attacks and phobias.
An intrinsic ocular disease or a disturb deriving from the neuromuscular involvement of the eye has been observed in 71 patients (10.07%), 25 males and 46 females: 28 cases of conjunctivitis, 7 cases of photophobia, 13 cases of visual impairment, 11 of bulbar pain, 4 of diplopia, 1 case of hemianopsia, 1 of orbital muscle tremor, 3 cases of lacrimation and burning and 3 of orbital oedema.
In 57 subjects (8.08%), 26 men and 31 women, there was an involvement of the cardio-vascular system: 14 patients suffered from tachycardia, 3 from bradycardia, and 13 from palpitations. Twenty-four patients presented with the acute onset of varying degrees of intermittent atrioventricular heart block, symptomatic or detected by the ECG. A case of complete atrioventricular block required the implant of a pacemaker. One patient referred angina and 2 patients suffered from a myocarditis.
An involvement of the liver was observed in 41 patients of this survey (5.81) who reported specific alterations of the cytonecrosis enzymes.
With the purpose of better investigating the severity spectrum of LB, an analysis of the summation of the number of symptoms per patient was made. Two hundred and forty-eight (35.1%) patients reported only 1 manifestation. Two different symptoms were observed in 251 (35.6%) patients, 3 clinical features were recorded in 120 (17.0%) subjects, and more than three clinical manifestations assignable to LB were reported for 86 (12.1%) cases.
Friuli Venezia Giulia is one of the endemic regions for LB in Italy because of the wide spread of piedmont zones which are full of underbrushes. Here the climatic, geographical, and faunistic conditions can foster the proliferation of the hard tick
People living in Friuli Venezia Giulia may get in contact with the ticks over and over because the suspension of agricultural activities has caused the wide spread of woody areas.
In this study the seropositivity for
Since the relatively high prevalence of antibodies against
The manifestations of LB recorded in this study are similar to the ones of other endemic areas in Europe, presenting a widespread clinical expressivity, even if there are some peculiar features which are different from those reported in Northern Europe and mostly in the USA, proving the existence of several genospecies of
A solitary EM lesion is the most frequent presentation of LB and EM was found to be the most common manifestation in the population analysed. Its clinical characteristics resulted similar to those reported in the Literature [
Erythema migrans.
In the USA, EM is often accompanied by flu-like symptoms such as fever, malaise, fatigue, headache, myalgia, or arthralgia, whether in Europe it more frequently represents an indolent and localised lesion [
Multiple erythema.
Data gathered about the other cutaneous features are consistent with those found in literature. LABC is the typical subacute cutaneous manifestation of early disseminated LB (Figure
Lymphadenosis benigna cutis.
ACA is the typical cutaneous feature of late LB in Europe (Figure
Acrodermatitis chronica atrophicans.
In this survey, we reported 16 patients presenting skin manifestations considered as atypical forms of LB such as lichen sclerosus and atrophicus, morphoea, and anetoderma [
In untreated LB the joint manifestations can arise months to years after the tick bite, usually in the form of a chronic mono or asymmetrical oligoarthritis. In our series the musculoskeletal involvement appears to be frequent. A not very painful arthritis characterized by brief attacks of joint swelling (Figure
Articular involvement in Lyme borreliosis.
Manifestations of acute peripheral nervous system involvement in LB include cranial neuropathy (peripheral 7th nerve palsy), eventually associated with radiculopathy (“Garin-Boujadoux-Bannwarth” syndrome) or radiculoneuritis (acute onset of severe localised radicular pain and/or motor weakness with or without sensory loss) [
Our data demonstrated that the nervous system has been involved in 65.24% of the analysed population, also presenting severe forms, according to the data recorded in Europe. In Europe, the frequency of neuroborreliosis seems higher, potentially due to the greater neurotropism of
There is much controversy about whether
Ocular involvement in LB, possible at every stage of the disease, is most frequently reported in European patients in the late phases of the disease [
As reported in literature, the cardiac manifestations tend to appear one week to seven months after the tick bite (median, 21 days). Borrelial carditis is a relatively rare complication in Europe, occurring in about 1% of all cases (in contrast to 4–10% of North America) [
Fever was detected in about 25% of the medical records analysed. In Europe the borrelial infection tends to remain localized for a long time without developing severe systemic symptoms and fever is often described during the prodromic phase. Otherwise in Northern America, flu-like symptoms, including fever, may accompany the early cutaneous lesions or can be the first manifestation of the disease. Such differences may be likely caused by the higher capacity of haematic dissemination of
In 5.81% of the patients, laboratory tests showed a high value of liver cyte-necrosis enzymes. Hepatic involvement is not usually a typical characteristic of LB, even if in literature sporadic cases of hepatitis are described [
This survey provides a detailed picture of the various clinical features described during the different stages of
The main limit of the study is that it has been performed on a sample of seropositive patients that could mean a mixture of patients with active
The authors declare that there is no conflict of interests regarding the publication of this paper.