Clnical study s Lyme borreliosis skin, atypical manifestations, LB atypical skin man/f'estations Atypical dermatowgical manif estations oj Lyme borreliosis G. Trevisan SUMMARY Lyme borreliosis {LB) is a multisystemic infectious disease involving the skin, joints, nervous system, heart, and eyes. Today at least three subtypes pathogenic far humans have been identified: Borrelia burgdorferi sensu stricto, Borrelia garini, Borrelia afzelii. Different genospecies strains of Borrelia have been associated with different clinical manifestations. LB is classically described as having three clinical stages or, similarly 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. LB skin manifestations could be divided into five classes. Erythema migrans, lymphadenosis benigna cutis, and acrodermatitis chronica atrophicans are praven ski.n manifestations of LB. Lichen sclerosus et athrophicus, morphea, sclero- derma, scleredema Buschke, atrophodermia of Pierini and Pasini, Parry-Romberg progressive facial hemiatrophy, and Shulman fasciitis are controversial LB manifestations. Granuloma annulare, atypical persistent pityriasis rosea, and pityriasis lichenoides are skin lesions occasionally related to LB. Urti- caria, erythema nodosum, and papular acrodermatitis (Giannotti Crosti disease) are reactive LB skin manifestations. Nodular panniculitis (Pfeifer-Weber-Christian), B-cell cutaneous lymphoma, and juvenile chronic myeloid leukemia are exceptional skin manifestations of LB. In the last years, there have been numerous ancl important advances of many aspects ofLyme borreliosis (LB). However, it appears that many questions concern- ing this disease remain unanswerecl. It is not clear, how spirochetes bebave when they enter into the human body. They can procluce pathognomonic lesions, skin manifestations mimicking other diseases, or clinical pic- h1res that can be inducecl also by other etiologic agents . We became aware of the complexity of this disease since genetic studies can identify different species of Borrelia hurgdorferi (Bb) sensu lato responsible for human infections: Eh sensu stricto, B. garinii and B. afzelii. In.Japan a new species was recently describecl, B. Japonica, which does not appear to be a human pathogen. In future , additional species of Borrelia will probably be identified. The recurrent fever also is caused by severa! species of Borrelia, and the vectors are dif- ferent ticks (B. recurrentistransmitted by Pedicuh1s sp. in epidemic relapsing fever, B. caucasica, B.crocidurae, B. duttonii, B.hermisii, B. hispanica, B. mazzottii, B . Acta Dermatoven APA Vol 10, 2001, No 4 ------------------------- ----- ---- 149 LB atypical skin manifestations parlwri, B.persica, B. turicatae, B. venezuelensistrans- mitted by Ornithodoros sp. in endemic relapsing fever). Diagnosis of LB is certain, when the infection is trans- mittecl by a harcl tick of genus Ixocles, ancl erythema chronicum migrans (ECM) appears. Different Bb species and strains can have different organ tropisms and can incluce different clinical mani- festations. B. afzelii has been founcl in patients with acroclermatitis ' clu·onica atrophicans (ACA), while Bb sensu stricto in patients with arthritis ancl B. garinii in patients with neuroborreliosis. A possible Bb follicular hair tropism can explain the ECM with hair loss. Atypical LB skin manifestations coulcl be orclerecl in the following classes: 1.- Controversial LB skin manifestations 2.- Skin manifestations occasionally related to LB 3.- Reactive LB skin manifestations 4.- Exceptional skin manifestations cluring LB. Skin lesions that appear immediately after tick-bite should also be mentioned: they can be miki and tran- sient reactions, or, sometimes, eclematous papular der- matitis of some centimeters of cliameter, exceptionally with tissue necrosis. Bb infection requires certain preconditions: - Infected tick - Attachment of the tick to the skin - Appearance of enlarging erythema after an incuba- tion period of at least 4-5 days During the visit the tick can be observed on the skin, or sometimes the patient shows a cletached tick in a little box. In :meh cases the tick bite is certain, while in all other cases the tick bite may be only supposed. 1. Controversial manifestations ofLB Essentially the following atrophic ancl sclerosing (sclerodermatous) disorders can be included: - Lichen sclerosus et atrophicus (LSA) - Morphea - Scleroderma with generalized plaque lesions - Linear scleroderma - Atrophoc!erma profundum (Pierini-P;isini) - Pany -Romberg progressive facial hemiatrophy - Shulman's sync!rome (Eosinophilic fasciitis) - Buschke disease Lichen sclerosus et atrophicus (LSA) has been re- lated to Borrelia infection by Asbrink who noticed the frequent association between LSA and ACA. Aberer clemonstrated the presence ofBorrelia in LSA. It is char- acterized by sclerotic atrophic patches, sometimes confluent, and often located on genitals. In 3 children affected by LSA living in endemic areas, borrelial DNA was founcl in the involved skin, by PCR (2). No specific DNA was founcl in 4 cases affected by LSA living in non endemic area. The same authors confirmed the rela- tion of morphea to Borrelia infection, while others main- tain that there is no such correlation. Probably morphea can be causecl sometimes by Borrelia afzelii (1) . The possible relationship between LB and LSA or mor- phea is suggested by the following evidence: - Clinical and histological similarities between morphea, LSAanclACA. - The presence of antibodies against Borrelia burg- do1:f'eri in some patients with LSA and/ or morphea. - Identification of borrelial organisms in histological sec- tions. -The coexistence of ACA, LSA and/ or morphea in the same patient. - A response to antimicrobial therapy in many cases of LSA ancl morphea. 2. Skin manifestations occasionally related to LB Granuloma annulare (GA) has been described in association with LB. In some cases the author was able to fine! positive serological tests or spirochetal bodies in the affectecl skin by silver stain. In his experience the GA is very seldom related to LB. In 3 patients he cle- tected Borrelia in the affectecl skin by PCR, but in these cases clinical evolution has been unusual and the treat- ment by nimesulide hasn't been effective. Atypical persistent pityriasis rosea, lasting longer . than 4-5 months , coulcl be' suspected of being related to LB, The author is studying some children who clevel- oped a papular dermatitis with perifolliculitis , mimick- ing pityriasis lichenoides (2). In one case he was able to isolate Borrelia sp. in BSK from the involved skin. Further studies are necessary to confirm the relation- ship with Lyme clisease (3). 3. Reactive skin manifestations oj LB Such manifestations can be observed also in other infectious diseases: - urticaria, - e1ythema nodosum and Clnical study 150 - - --- ---------- - ----------- --------Acta Dermatoven APA Vol 10, 2001, No 4 Clnical study - papular acroclermatitis Two varieties of urticaria can be distinguishecl: - cliffuse -localized The first form appears usually in early LB, whereas the localizecl form is more freguent in late LB. The lo- calizecl form often involves the skin adjacent to the af- fected joints. Erythema nodosum has also been observecl during active LB. Recently, the author has reported two chil- dren w ho have developecl papular acrodermatitis (Gianotti-Crosti disease) after borrelial infection. R E. I7 E ·R E NT (~ J:;' s·, '.J . . · . .:..i . • ,.J .!. . .i . . .'..f l.... LB atypical skin manifes tations 4. Exceptional skin mani- festations described during LB Hassler ( 4) has reportecl an association between LB and involvement of subcutaneous tissue (~/ef/er-We- ber Christian disease) and he bas been able to demon- strate the presence ofBorrelia in the affected skin even after severa! antibiotic treatments. There is also the prob- lem of a possible correlation between LB and cutane- ous B-cell (or T-cell) lymphomas. Evolution ofborrelial lymphadenosis benigna cutis (LABC) towards malig- nancy bas been supposed, but this hypothesis needs further investigations. l. Trevisan G, Rees D, Stinco G. Borrelia burgdorferi and Localized Scleroderma. Ciin. Dermatol. 1994; 12: 475-9. AUTHOR'S ADDRESS 2. Menni S, Pistritto G, Gelmetti C, Stanta G, Trevisan G. Eruzione a lipo pitiriasi lichenoide con perifollicoliti in corso di borreliosi di Lyme. Eur. J. Pediat. Dermatol. 1994; 4: 77-80. 3. Trevisan G, Cinco M. Lyme Borreliosis in Childood. Eur. J. Pediat. Dermatol. 1992; 2: 81-112. 4. Hassler D, Zorn J, Zoller L et al. Nodulare Pannikulitis: eine Verlaufsform der Lyme -Borreliose ? Hautarzt 1992; 43: 134-8. Giusto Trevisan, MD, professor and chairman, Institute oj Dermatology, University oJTrieste, Ospedale di Cattinara, Stradaper Fiume, I-34149 Trieste, Italy Acta Dermatoven APA Vol 10, 2001, No 4 ---- - -------------- ----- ---------- JJ J