CLINICAL REPORT
355 ActaDV ActaDV Advances in dermatology and venereology Acta Dermato-Venereologica
Granuloma Annulare and Morphea : Correlation with Borrelia burgdorferi Infections and Chlamydia-related Bacteria
Lauri TOLKKI 1 # , Kati HOKYNAR 2 # , Seppo MERI 3 , Jaana PANELIUS 1 , Mirja PUOLAKKAINEN 2 and Annamari RANKI 1
1
Department of Dermatology , Allergology and Venereal Diseases , University of Helsinki and Center of Inflammation , Helsinki University Central Hospital , 2 Department of Virology , and 3 Department of Bacteriology and Immunology , University of Helsinki , Helsinki , Finland
#
These authors contributed equally to this paper .
A retrospective study of 109 skin biopsies with granuloma annulare ( GA ) or morphea histology from patients with suspected tick bite was performed . Biopsies were tested for cutaneous Borrelia burgdorferi DNA using PCR . The same biopsies were analysed for tick-borne novel agents , Chlamydia-related bacteria ( members of the Chlamydiales order ), using a PCRbased method . Borrelia DNA was detected in 7 / 73 ( 9.6 %) biopsies with GA and in 1 / 36 ( 2.8 %) biopsies with morphea , while Chlamydiales DNA was found in 53 / 73 ( 72.6 %) biopsies with GA and 25 / 34 ( 73.4 %) biopsies with morphea . All Borrelia DNA-positive GA samples were also positive for Chlamydiales DNA . The Chlamydiales sequences detected in GA were heterogeneous and contained Waddliaceae and Rhabdochlamydiaceae bacteria , which are also present in Ixodes ricinus ticks , while the Chlamydiales sequences detected in morphea closely resembled those found in healthy skin . In conclusion , tick-mediated infections can trigger GA in some cases , while correlation of either Borrelia or Chlamydiales with morphea is unlikely .
Key words : granuloma annulare ; morphea ; Borrelia burgdorferi ; chlamydia-related bacteria .
Accepted Oct 31 , 2017 ; Epub ahead of print Nov 7 , 2017 Acta Derm Venereol 2018 ; 98 : 355 – 360 .
Corr : Lauri Tolkki , Center of Inflammation , Department of Dermatology , Allergology and Venereal Diseases , Helsinki University Central Hospital , PO Box 160 , FIN-00029 Helsinki , Finland . E-mail : Lauri . Tolkki @ hus . fi
Granuloma annulare ( GA ) and morphea ( localized scleroderma ) are skin reactions with unknown aetiology ( 1 – 5 ). One of the possible causative agents is Borrelia burgdorferi sensu lato , a spirochete transmitted to humans via tick bites . Although the causal connections between B . burgdorferi and GA and morphea have been explored in several studies using various methods , including indirect serological methods and direct detection by PCR , there is no firm evidence of a causative role ( 6 – 11 ).
In addition to B . burgdorferi sensu lato , ticks are known to serve as vectors for a number of other animal and human pathogens , such as Babesia microti , which causes babesiosis , Anaplasma phagocytophilum , which causes human granulocytic anaplasmosis , species of the spotted fever group of Rickettsiae , and Flavivirus , which causes tick-borne encephalitis ( TBE ) ( 12 – 15 ).
Recently , Ixodes ricinus ticks have also been shown to carry another group of potential human pathogens ,
Chlamydia-related bacteria ( 16 – 19 ). They share the characteristic features of the order Chlamydiales : strict intracellular lifestyle , biphasic developmental cycle and a large core-set of genes . The traditional members of the order are the established human pathogens Chlamydia trachomatis and Chlamydia pneumoniae ( genus Chlamydia , family Chlamydiaceae ). During the last 20 years , an increasing number of novel chlamydial species have been described and , currently , 8 additional families are recognized as belonging to the Chlamydiales order . These new families : Parachlamydiaceae , Waddliaceae , Simkaniaceae , Rhabdochlamydiaceae , Criblamydiaceae , Piscichlamydiaceae , Clavichlamydiaceae and Parilichlamydiaceae are collectively called Chlamydiarelated bacteria . They were originally detected in various types of environmental samples ( e . g . soil and water from various sources ), but subsequently also in animals , including arthropods , and humans . Many of them have pathogenic potential ( 20 , 21 ), and their reservoirs , vectors and transmission routes have been widely investigated , but have mainly remained obscure .
In this study , 109 patient skin biopsies with histologically confirmed GA and localized scleroderma ( morphea ) were analysed retrospectively . The samples had been studied for the presence of B . burgdorferi , either because of a clinical suspicion of borreliosis or because of abundant plasma cells in the biopsy . In order to determine whether certain types of Chlamydia-related bacteria could play a role in the pathogenesis of these conditions , the occurrence and type ( s ) of Chlamydiales in the biopsies was examined , and the results compared with our previously published data on healthy skin and ticks ( 17 ). We recently reported the occurrence of Chlamydiales in up to 40 % of Finnish ticks and , furthermore , in human skin biopsies . Chlamydiales DNA was found in human skin samples , with a prevalence of 49 % in healthy skin ( 19 / 39 , 49 %) and 85 % in skin samples from subjects positive for B . burgdorferii PCR . This suggests that ticks could indeed serve as vectors for transmission of Chlamydia-related bacteria .
MATERIALS AND METHODS Patients
Data for all patients whose skin biopsies had a histology of GA or morphea and were submitted to B . burgdorferi DNA analysis
This is an open access article under the CC BY-NC license . www . medicaljournals . se / acta Journal Compilation © 2018 Acta Dermato-Venereologica . doi : 10.2340 / 00015555-2831 Acta Derm Venereol 2018 ; 98 : 355 – 360